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• February 03, 2012
• 17:21

  Editors' Notes

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages ix
  
  [No author name available]
  
• 17:21

  Infection-Induced Hematopoiesis: A Zebrafish Perspective

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 105-106
  
  Philippe Herbomel
  
  In response to infection, the bone marrow adjusts production of leukocyte cell types to fight off disease. In this issue ofCell Stem Cell,use the zebrafish model to show that nitric oxide (NO) production drives expansion of hematopoietic progenitors to produce more granulocytes.
  
• 17:21

  Stem-Cell-like Qualities of Immune Memory; CD4T Cells Join the Party

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 107-108
  
  C. John Luckey, Casey T. Weaver
  
  Similar to hematopoietic stem cells, memory lymphocytes self-renew, while their clonally expanded effector progeny differentiate to fight infection and tumors. Recently,report inImmunitythat a subset of Th17 effector cells function as memory cells and retain stem cell properties.
  
• 17:21

  Common Signaling Networks Characterize Leukemia-Initiating Cells in Acute Myeloid Leukemia

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 109-110
  
  Kenichi Miharada, Stefan Karlsson
  
  Identification and characterization of leukemia-initiating cells (LICs) is important to understand leukemogenesis and develop novel therapies for leukemia. In this issue ofCell Stem Cell,demonstrate that common active signaling pathways in LICs may be targeted to treat acute myeloid leukemia.
  
• 17:21

  Periostin: A Bridge between Cancer Stem Cells and Their Metastatic Niche

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 111-112
  
  Zhe Wang, Gaoliang Ouyang
  
  Only a minority of cancer cells have the potential to initiate metastatic growth, but the factors that limit metastatic colonization remain mostly unknown.recently demonstrated that stromal periostin is crucial for metastatic colonization by regulating the interactions between breast cancer stem cells and their metastatic niche.
  
• 17:21

  Engineering Stem Cell Expansion

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 113-114
  
  Irwin D. Bernstein, Colleen Delaney
  
  In this issue ofCell Stem Cell,develop a culture method that overcomes current limitations in ex vivo hematopoietic stem/progenitor cell expansion by continuously diluting inhibitory signaling factors and maintaining stem cell density. This approach enhances the generation of precursors with potential therapeutic utility.
  
• 17:21

  The Potential of Stem Cells as an In Vitro Source of Red Blood Cells for Transfusion

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 115-119
  
  Anna Rita Migliaccio, Carolyn Whitsett, Thalia Papayannopoulou, Michel Sadelain
  
  Recent advances have increased excitement about the potential for therapeutic production of red blood cells (RBCs) in vitro. However, generation of RBCs in the large numbers required for transfusion remains a significant challenge. In this article, we summarize recent progress in producing RBCs from various cell sources, and discuss the hurdles that remain for translation into the clinical arena.
  
• 17:21

  Hematopoiesis: A Human Perspective

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 120-136
  
  Sergei Doulatov, Faiyaz Notta, Elisa Laurenti, John E. Dick
  
  Despite its complexity, blood is probably the best understood developmental system, largely due to seminal experimentation in the mouse. Clinically, hematopoietic stem cell (HSC) transplantation represents the most widely deployed regenerative therapy, but human HSCs have only been characterized relatively recently. The discovery that immune-deficient mice could be engrafted with human cells provided a powerful approach for studying HSCs. We highlight 2 decades of studies focusing on isolation and molecular regulation of human HSCs, therapeutic applications, and early lineage commitment steps, and compare mouse and humanized models to identify both conserved and species-specific mechanisms that will aid future preclinical research.
  
• 17:21

  Hematopoietic-Stem-Cell-Based Gene Therapy for HIV Disease

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 137-147
  
  Hans-Peter Kiem, Keith R. Jerome, Steven G. Deeks, Joseph M. McCune
  
  Although combination antiretroviral therapy can dramatically reduce the circulating viral load in those infected with HIV, replication-competent virus persists. To eliminate the need for indefinite treatment, there is growing interest in creating a functional HIV-resistant immune system through the use of gene-modified hematopoietic stem cells (HSCs). Proof of concept for this approach has been provided in the instance of an HIV-infected adult transplanted with allogeneic stem cells from a donor lacking the HIV coreceptor, CCR5. Here, we review this and other strategies for HSC-based gene therapy for HIV disease.
  
• 17:21

  Advancing Stem Cell Biology toward Stem Cell Therapeutics

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 149-150
  
  David Scadden, Alok Srivastava
  
  Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of disease-specific articles, outlining the challenges surrounding the clinical translation of stem cell therapeutics.
  
• 17:21

  Clinical Translation of Stem Cells in Neurodegenerative Disorders

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 151-155
  
  Olle Lindvall, Roger A. Barker, Oliver Brüstle, Ole Isacson, Clive N. Svendsen
  
  Stem cells and their derivatives show tremendous potential for treating many disorders, including neurodegenerative diseases. We discuss here the challenges and potential for the translation of stem-cell-based approaches into treatments for Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.
  
• 17:21

  Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 157-170
  
  Emily Brookes, Inês de Santiago, Daniel Hebenstreit, Kelly J. Morris, Tom Carroll, ...
  
  Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5pS7pS2p) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5pS7pS2p); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.
  
  Graphical Abstract
  
  Highlights► A unique RNAPII variant (S5pS7pS2p) binds PRC targets genome-wide in ESCs ► RNAPII-S5p and PRC coincide in time and localization, and show proportional abundance ► Novel, active PRC-target genes identified in ESCs include metabolic genes ► Active PRC targets switch between on/off (active/PRC) states in the ESC population
  
  
• 17:21

  BMP4 Signaling Acts via Dual-Specificity Phosphatase 9 to Control ERK Activity in Mouse Embryonic Stem Cells

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 171-182
  
  Zhongwei Li, Teng Fei, Jianping Zhang, Gaoyang Zhu, Lu Wang, ...
  
  Extrinsic BMP and LIF signaling collaboratively maintain mouse embryonic stem cell (ESC) pluripotency, whereas appropriate ERK activity is essential for ESC fate commitment. However, how the extrinsic signals restrain appropriate ERK activity remains elusive. Here, we show that, whereas LIF sustains relatively high ERK activity, BMP4 can steadily attenuate ERK activity by upregulating ERK-specific dual-specificity phosphatase 9 (DUSP9). This upregulation requires Smad1/5 and Smad4 and specifically occurs to DUSP9, but not other DUSPs, and only in ESCs. Through DUSP9-mediated inhibition of ERK activity, BMP signaling reinforces the self-renewal status of mouse ESCs together with LIF. Upon LIF withdrawal, ESCs spontaneously undergo neural differentiation, during which process DUSP9 can partially mediate BMP inhibition on neural commitment. Collectively, our findings identify DUSP9 as a critical mediator of BMP signaling to control appropriate ERK activity critical for ESC fate determination.
  
  Graphical Abstract
  
  Highlights► BMP4 upregulates dual-specificity phosphatase 9 (DUSP9) in mouse embryonic stem cells ► DUSP9 upregulation requires Smad1/5 and Smad4 ► DUSP9 lowers ERK activity to maintain self renewal in the presence of LIF and BMP4 ► Without LIF, DUSP9 mediates BMP inhibition on neural commitment
  
  
• 17:21

  A Mammary Stem Cell Population Identified and Characterized in Late Embryogenesis Reveals Similarities to Human Breast Cancer

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 183-197
  
  Benjamin T. Spike, Dannielle D. Engle, Jennifer C. Lin, Samantha K. Cheung, Justin La, ...
  
  Gene expression signatures relating mammary stem cell populations to breast cancers have focused on adult tissue. Here, we identify, isolate, and characterize the fetal mammary stem cell (fMaSC) state since the invasive and proliferative processes of mammogenesis resemble phases of cancer progression. fMaSC frequency peaks late in embryogenesis, enabling more extensive stem cell purification than achieved with adult tissue. fMaSCs are self-renewing, multipotent, and coexpress multiple mammary lineage markers. Gene expression, transplantation, and in vitro analyses reveal putative autocrine and paracrine regulatory mechanisms, including ErbB and FGF signaling pathways impinging on fMaSC growth. Expression profiles from fMaSCs and associated stroma exhibit significant similarities to basal-like and Her2intrinsic breast cancer subtypes. Our results reveal links between development and cancer and provide resources to identify new candidates for diagnosis, prognosis, and therapy.
  
  Graphical Abstract
  
  Highlights► Fetal mammary stem cells (fMaSC) increase sharply late in embryogenesis ► fMaSCs coexpress markers of multiple mammary lineages and are multipotent ► We elucidate growth factors and stromal interactions governing fMaSC function ► Expression profiles link fMaSCs and fetal stroma to human breast cancers
  
  
• 17:21

  Infection-Responsive Expansion of the Hematopoietic Stem and Progenitor Cell Compartment in Zebrafish Is Dependent upon Inducible Nitric Oxide

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 198-209
  
  Christopher J. Hall, Maria Vega Flores, Stefan H. Oehlers, Leslie E. Sanderson, Enid Y. Lam, ...
  
  Hematopoietic stem cells (HSCs) are rare multipotent cells that contribute to all blood lineages. During inflammatory stress, hematopoietic stem and progenitor cells (HSPCs) can be stimulated to proliferate and differentiate into the required immune cell lineages. Manipulating signaling pathways that alter HSPC capacity holds great promise in the treatment of hematological malignancies. To date, signaling pathways that influence HSPC capacity, in response to hematopoietic stress, remain largely unknown. Using a zebrafish model of demand-driven granulopoiesis to explore the HSPC response to infection, we present data supporting a model where the zebrafish ortholog of the cytokine-inducible form of nitric oxide synthase (iNOS/NOS2) Nos2a acts downstream of the transcription factor C/ebpβ to control expansion of HSPCs following infection. These results provide new insights into the reactive capacity of HSPCs and how the blood system is “fine-tuned” in response to inflammatory stress.
  
  Graphical Abstract
  
  Highlights► Infection induces a reactive expansion of the zebrafish HSPC compartment ► HSPCs express genes encoding C/ebpβ and Nos2a in response to infection ► C/ebpβ is required for Nos2a expression within HSPCs following infection ► Reactive expansion of the HSPC compartment following infection is dependent on Nos2a
  
  
• 17:21

  Decoupling of Tumor-Initiating Activity from Stable Immunophenotype in HoxA9-Meis1-Driven AML

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 210-217
  
  Kenneth D. Gibbs, Astraea Jager, Oliver Crespo, Yury Goltsev, Angelica Trejo, ...
  
  Increasing evidence suggests tumors are maintained by cancer stem cells; however, their nature remains controversial. In a HoxA9-Meis1 (H9M) model of acute myeloid leukemia (AML), we found that tumor-initiating activity existed in three, immunophenotypically distinct compartments, corresponding to disparate lineages on the normal hematopoietic hierarchy—stem/progenitor cells (Linkit) and committed progenitors of the myeloid (Gr1kit) and lymphoid lineages (Lymkit). These distinct tumor-initiating cells (TICs) clonally recapitulated the immunophenotypic spectrum of the original tumor in vivo (including cells with a less-differentiated immunophenotype) and shared signaling networks, such that in vivo pharmacologic targeting of conserved TIC survival pathways (DNA methyltransferase and MEK phosphorylation) significantly increased survival. Collectively, H9M AML is organized as an atypical hierarchy that defies the strict lineage marker boundaries and unidirectional differentiation of normal hematopoiesis. Moreover, this suggests that in certain malignancies tumor-initiation activity (or “cancer stemness”) can represent a cellular state that exists independently of distinct immunophenotypic definition.
  
  Graphical Abstract
  
  Highlights► In H9M AML, tumor-initiating activity (TIA) and lineage differentiation are separate ► TIA exists in three compartments, corresponding to distinct hematopoietic lineages ► Such tumor-initiating cells (TIC) share signaling networks and survival pathways ► Targeting pathways conserved between TIC in vivo significantly increases survival
  
  
• 17:21

  Rapid Expansion of Human Hematopoietic Stem Cells by Automated Control of Inhibitory Feedback Signaling

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages 218-229
  
  Elizabeth Csaszar, Daniel C. Kirouac, Mei Yu, WeiJia Wang, Wenlian Qiao, ...
  
  Clinical hematopoietic transplantation outcomes are strongly correlated with the numbers of cells infused. Anticipated novel therapeutic implementations of hematopoietic stem cells (HSCs) and their derivatives further increase interest in strategies to expand HSCs ex vivo. A fundamental limitation in all HSC-driven culture systems is the rapid generation of differentiating cells and their secreted inhibitory feedback signals. Herein we describe an integrated computational and experimental strategy that enables a tunable reduction in the global levels and impact of paracrine signaling factors in an automated closed-system process by employing a controlled fed-batch media dilution approach. Application of this system to human cord blood cells yielded a rapid (12-day) 11-fold increase of HSCs with self-renewing, multilineage repopulating ability. These results highlight the marked improvements that control of feedback signaling can offer primary stem cell culture and demonstrate a clinically relevant rapid and relatively low culture volume strategy for ex vivo HSC expansion.
  
  Graphical Abstract
  
  Highlights► Simulations yield a strategy to control non-stem-cell-autonomous feedback signaling ► Fed-batch media dilution enables rapid 11-fold expansion of human blood stem cells ► Enhanced expansion because of global reductions in inhibitory factor concentrations ► Expansion strategy is integrated into an automated clinically relevant bioreactor
  
  
• 16:30

  Decreased colonization of chicks bySalmonella entericaserovar Gallinarum expressing mannose-sensitive FimH adhesin fromSalmonella entericaserovar Enteritidis

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 2 February 2012
  
  Marta Kuźmińska-Bajor, Maciej Kuczkowski, Krzysztof Grzymajło, Łukasz Wojciech, Maryana Sabat, ...
  
  To investigate the role of non-hemagglutinating type 1 fimbriae in the pathogenesis ofSalmonellaGallinarum, the isogenic mutant elaborating type 1 fimbriae with mannose-sensitive (MS) variant of the FimH adhesin fromSalmonellaEnteritidis and the mutant strain with no FimH expression were constructed. Their binding to chicken leukocytesin vitroand invasiveness in 1-day-old chicks were studied. Our results demonstrated thatS. Gallinarum type 1 fimbriae with an endogenous variant of the FimH adhesin mediated mannose-resistant (MR) binding to avian leukocytes and did not bind to human epithelial cells. However, after allelic replacement of the FimH, mutated fimbriae withS. Enteritidis variant of the FimH adhesin bound to both cell types in a mannose-dependent manner. In chick model,S. Gallinarum expressing wild-type FimH variant colonized caecal tonsils and bursa of Fabricius more effectively and invaded the spleen and liver in greater numbers thanS. GallinarumfimHknockout strain or mutant expressing MS FimH variant fromS. Enteritidis. The invasive potential of the latter was greatly reduced in chicks since no viable bacteria expressing MS variant of the adhesin could be recovered from intestinal lymphoid tissues or liver over a 6 day course of infection. Together, these results demonstrate that theS. Gallinarum type 1 fimbriae with the endogenous MR variant of the FimH protein increase systemic dissemination ofS. Gallinarum and colonization of internal organs in chicks indicating the importance of these adhesive structures in the virulence ofS. Gallinarum.
  
• 16:30

  Rapid MALDI-TOF mass spectrometry identification ofLeptospiraorganisms

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 2 February 2012
  
  Zoheira Djelouadji, Véronique Roux, Didier Raoult, Angeli Kodjo, Michel Drancourt
  
  Leptospirosis is a worldwide deadly zoonotic disease. Accurate identification of the causativeLeptospiraspp. spirochetes ascertains the pathogenic status of the isolates, identifies potential source of infection and recognises outbreaks. Species identification is currently based on technically demanding, time and resources consuming serological and molecular methods. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) recently emerged as a first-line method for the accurate identification of bacteria, yet no data issued forLeptospiraspp. We investigated the potential of MALDI-TOF-MS for the rapid identification ofLeptospiraisolates.Starting from a 10organisms/mL suspension, MALDI-TOF-MS yielded an unique protein profile for each one of 19Leptospiraspecies reference isolates with a 100% reproducibility over 12 repeats, allowing to create aLeptopsiradatabase. MALDI-TOF-MS further accurately identified 20/21 additional reference isolates representative of various serogroups at the species level asLeptospira interrogans(n = 12),Leptospira kirschneri(n = 5),Leptospira borgopetersenii(n = 3),Leptospira noguchii(n = 1) with identification score value of 2-2.5. Furthermore, six clinical isolates previously identified byrpoB sequencing, were correctly identified by MALDI-TOF-MS asL. interrogans(n = 5) andL. borgpetersenii(n = 1) with identification score value of 2-2.6. Identification was achieved in 40 minutes starting from theLeptospirasuspension.MALDI-TOF-MS could complement serological and sequencing-based methods for the first line, rapid identification ofLeptospiraisolates in the clinical microbiology laboratory.
  
• 16:30

  Occurrence and distribution ofStaphylococcus aureuslineages among zoo animals

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 2 February 2012
  
  Carmen Espinosa-Gongora, Dorota Chrobak, Arshnee Moodley, Mads Frost Bertelsen, Luca Guardabassi
  
  The current knowledge of the occurrence and diversity ofStaphylococcus aureusin animals is largely biased in favour MRSA and domestic animals. In order to generate novel information on the ecology and population structure of this bacterial species in the animal kingdom, we investigated the occurrence and genotypic diversity ofS. aureusin a range of animal species kept at the Copenhagen Zoo. We sampled 146 animals belonging to 25 mammalian species and 21 reptiles belonging to six species. A total of 59S. aureusisolates were found in 10 of the 25 mammalian species tested. All isolates were MSSA belonging to fourteenspatypes, including three novelspatypes. MLST revealed the occurrence of seven STs. The study of the ecology of commensalS. aureusin captive wild animals revealed that ST133 has a broader host range than previously thought.
  
• 16:30

  Staphylococcus aureus (MSSA) and MRSA (CC398) isolated from post-mortem samples from pigs

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 2 February 2012
  
  P.J. Van der Wolf, A. Rothkamp, K. Junker, A.J. de Neeling
  
  There are many reports on the occurrence of Livestock Associated Methicilline resistantStaphylococcus aureus(LA-MRSA, CC398) in healthy pigs. There are however, very few reports of LA-MRSA being associated with pathological lesions in pigs. With this study we try to find the answers to the questions: 1) how often isStaphylococcus aureusfound in post-mortem material from pigs, 2) how many of these isolates are methicillin resistant, 3) are these equally distributed over the years?Here we report the isolation of MRSA and of methicillin sensitiveStaphylococcus (S.) aureus(MSSA) from samples derived from post-mortem examinations at the Animal Health Service in The Netherlands in the period from 2003 through October 2008. The MSSA and MRSA described here were isolated from 159 pathological lesions and from 7 submissions of aborted foetuses derived from a total of 116 animals, representing 103 submissions coming from 92 different herds. This is approximately 0.5% of all pigs submitted for post mortem examination in those years. The proportion of pigs from whichS. aureus(both MSSA and MRSA) was isolated from, did not increase over the years. MSSA (N = 97) and LA-MRSA CC398 (N = 18) were present mainly in (peri)arthritis in over 30% of all cases, but were also isolated from internal organs such as lung, brain, spleen, kidneys, heart, indicating septicaemia. Remarkably, one non-CC398 MRSA (ST1) was isolated in a joint and a kidney of one pig. This isolate was resistant to 5 out of 6 antimicrobials tested. There was no significant difference in the type of lesions in which LA-MRSA was found compared to MSSA. The number of antimicrobials these isolates were resistant to, increased rapidly after 2004. LA-MRSA was isolated for the first time in 2005 and then again in 2007 and 2008, suggesting that this is an emerging pathogen. However, due to changes in the panel of antimicrobials used to testS. aureusfor antimicrobial susceptibility in 2005 and 2007, the possibility exists that we may have missed some MRSA isolates. LA-MRSA isolates are resistant to at least three but sometimes five out of six antimicrobials tested. All isolates were susceptible to the combination of Trimethoprim/Sulfamethaxol.
  
• 16:20

  Conditional ablation of osteoblasts in medaka

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 2 February 2012
  
  Bernd Willems, Anita Büttner, Ann Huysseune, Joerg Renn, P. Eckhard Witten, ...
  
  Different from tetrapods, teleost vertebral centra form without prior establishment of a cartilaginous scaffold, in two steps: First, mineralization of the notochord sheath establishes the vertebral centra. Second, sclerotome derived mesenchymal cells migrate around the notochord sheath. These cells differentiate into osteoblasts and deposit bone onto the mineralized notochord sheath in a process of intramembranous bone formation. In contrast, most skeletal elements of the cranial skeleton arise by chondral bone formation, with remarkably similar mechanisms in fish and tetrapods. To further investigate the role of osteoblasts during formation of the cranial and axial skeleton, we generated a transgenicosx:CFP-NTRmedaka line which enables conditional ablation ofosterixexpressing osteoblasts. By expressing a bacterial Nitroreductase (NTR) fused to Cyan Fluorescent Protein (CFP), under control of theosterixpromoter these cells become sensitive towards Metronidazole (Mtz). Mtz treatment of stableosx:CFP-NTRtransgenic medaka for several consecutive days led to significant loss of osteoblasts by apoptosis. Live staining of mineralized bone matrix revealed reduced ossification in head skeletal elements such as cleithrum and operculum, as well as in the vertebral arches. Interestingly in Mtz treated larvae, intervertebral spaces were missing and the notochord sheath was often continuously mineralized resulting in the fusion of centra. We therefore propose a dual role forosx-positive osteoblasts in fish. Besides a role in bone deposition, we suggest an additional border function during mineralization of the chordal centra. After termination of Mtz treatment, osteoblasts gradually reappeared, indicating regenerative properties in this cell lineage. Taken together, theosx:CFP-NTRmedaka line represents a valuable tool to study osteoblast function and regeneration at different stages of development in whole vertebrate specimensin vivo.
  
  Highlights► First successful application of nitroreductase mediated cell ablation in medaka ► First osteoblast deficient fish model with conditional cell ablation ► Ablatingosxpositive osteoblasts results in demineralization of cranial skeleton► Osxpositive osteoblasts are required for border definition in growing vertebrae ► Osteoblasts recur and bone regenerates after termination of conditional ablation
  
  
• 16:20

  Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 2 February 2012
  
  Min Zou, Shengguo Li, William H. Klein, Mengqing Xiang
  
  The sensory neurons of the dorsal root ganglia (DRG) must project accurately to their central targets to convey proprioceptive, nociceptive and mechanoreceptive information to the spinal cord. How these different sensory modalities and central connectivities are specified and coordinated still remains unclear. Given the expression of the POU homeodomain transcription factors Brn3a/Pou4f1 and Brn3b/Pou4f2 in DRG and spinal cord sensory neurons, we determined the subtype specification of DRG and spinal cord sensory neurons as well as DRG central projections inBrn3aandBrn3bsingle and double mutant mice. Inactivation of either or both genes causes no gross abnormalities in early spinal cord neurogenesis; however, inBrn3asingle andBrn3a;Brn3bdouble mutant mice, sensory afferent axons from the DRG fail to form normal trajectories in the spinal cord. The TrkAafferents remain outside the dorsal horn and fail to extend into the spinal cord, while the projections of TrkCproprioceptive afferents into the ventral horn are also impaired. Moreover,Brn3amutant DRGs are defective in sensory neuron specification, as marked by the excessive generation of TrkBand TrkCneurons as well as TrkA/TrkBand TrkA/TrkCdouble positive cells at early embryonic stages. At later stages in the mutant, TrkB, TrkCand parvalbuminneurons diminish while there is a significant increase of CGRPand c-retneurons. In addition,Brn3amutant DRGs display a dramatic down-regulation ofRunx1expression, suggesting that the regulation of DRG sensory neuron specification by Brn3a is mediated in part by Runx1. Our results together demonstrate a critical role for Brn3a in generating DRG sensory neuron diversity and regulating sensory afferent projections to the central targets.
  
  Highlights► Brn3a inactivation causes improper segregation of Trk receptor expression in the DRG. ► Major sensory neuron subtypes are altered in the Brn3a mutant DRG. ► Brn3a regulates sensory neuron specification in part through Runx1. ► DRG central projections in the spinal cord are defective in Brn3a mutants.
  
  
• 16:20

  Conditions that influence the response to Fgf during otic placode induction

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 1 February 2012
  
  Mahesh S. Padanad, Neha Bhat, BiWei Guo, Bruce B. Riley
  
  Despite the vital importance of Fgf for otic induction, previous attempts to study otic induction through Fgf misexpression have yielded widely varying and contradictory results. There are also discrepancies regarding the ability of Fgf to induce otic tissue in ectopic locations, raising questions about the sufficiency of Fgf and the degree to which other local factors enhance or restrict otic potential. Using heat shock-inducible transgenes to misexpress Fgf3 or Fgf8 in zebrafish, we found that the stage, distribution and level of misexpression strongly influence the response to Fgf. Fgf misexpression during gastrulation can inhibit or promote otic development, depending on context, whereas misexpression after gastrulation leads to expansion of otic markers throughout preplacodal ectoderm surrounding the head. Elevated Fgf also expands expression of the putative competence factor Foxi1, which is required for Fgf to expand other otic markers. Misexpression of downstream factors Pax2a or Pax8 also expands otic markers but cannot bypass the requirement for Fgf or Foxi1. Co-misexpression of Pax2/8 with Fgf8 potentiates formation of ectopic otic vesicles expressing a full range of otic markers. These findings document the variables critically affecting the response to Fgf and clarify the roles offoxi1andpax2/8in the otic response.
  
  Highlights► Fgf misexpression can inhibit or promote otic development, depending on context. ► Optimal Fgf expands expression of early otic markers into anterior cranial ectoderm. ► Misexpression of Pax2a/8 expands some otic markers but cannot bypass Fgf or Foxi1. ► Comisexpression of Pax2a/8 with Fgf8 potentiates formation of ectopic otic vesicles.
  
  
• 14:40

  Genetic variation inCYP2A6predicts neural reactivity to smoking cues as measured using fMRI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 3 February 2012
  
  Deborah W. Tang, Brian Hello, Margaret Mroziewicz, Lesley K. Fellows, Rachel F. Tyndale, ...
  
  Smoking cues trigger craving for cigarettes and relapse. Nicotine metabolism, mediated by the enzyme CYP2A6, also influences smoking behaviour. In this study, we investigated how nicotine metabolism and genetic variation inCYP2A6influences the neural response to smoking cues in humans using functional magnetic resonance imaging (fMRI). We hypothesized that individuals with faster rates of nicotine metabolism would have stronger conditioned responses to smoking cues because of closer coupling in everyday life between exposure to cigarettes and surges in blood nicotine concentration. In contrast, individuals with reduced rates of metabolism, who have relatively constant nicotine blood levels throughout the day, should be less likely to develop conditioned responses to cues. We screened 169 smokers for their rate of nicotine metabolism andCYP2A6genotype, and selected 31 smokers with the fastest and slowest rates for fMRI, matched for daily cigarette intake. We measured their neural response to visual smoking and non-smoking cues using fMRI. As predicted, fast metabolizers, by phenotype or genotype, had significantly greater responses to visual cigarette cues than slow metabolizers in the amygdala, hippocampus, striatum, insula, and cingulate cortex.These results support the theory that drug cues are conditioned stimuli, and explain why fast metabolizers who smoke have lower cessation rates. They also provide insight into how genetics can shape human vulnerability to addiction, and have implications for tailoring smoking cessation programs based on individual genetics.
  
  Highlights► We investigated howCYP2A6genotype influences brain response to smoking cues with fMRI. ► Greater response in fast nicotine metabolizers implies that drug-related stimuli are conditioned cues. ► Nicotine is the ingredient that makes cigarettes reinforcing. ► Results explain howCYP2A6genotype affects severity of nicotine addiction.
  
  
• 14:40

  Spatiotemporal dynamics of early spatial and category-specific attentional modulations

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 3 February 2012
  
  Andreas A. Ioannides, Vahe Poghosyan
  
  Different attention types select and focus brain resources on relevant sensory information. However, key questions remain unresolved: when and where cortical visual processing is first modulated by different types of attention? How do such modulatory effects spread thereafter? Here, we address these issues for spatial and category-specific types of attention using magnetoencephalography (MEG). First we identified the dynamics of visual attention-independent sensory processing to serve as a baseline framework for the attentional modulations of interest. We found that visual information is processed through the entire hierarchy of visual areas in at least two phases, in the 40–130 ms and 130–230 ms periods respectively. Spatial attention modulations were identified from the beginning of the initial stimulus-evoked response in the primary visual cortex ~ 70 ms post-stimulus. Category-specific attention modulated face processing beginning from the first face-specific response in high-level object-related areas ~ 100 ms post-stimulus, substantially earlier than previously reported for face-directed attention. Thus both attention types modulated responses during the first processing phase, beginning at the earliest brain area capable of coding the attentional target. Thereafter attentional effects propagated through the visual cortex together with the stimulus-evoked activity. Category-specific attention did not affect the first-phase responses in low-level strongly retinotopic visual areas, while the second-phase responses were enhanced when the stimulus was the response target and reduced when it was a distractor. Responses during both phases in high-level object-related areas were enhanced by category-specific attention independent of their target/distractor status. Spatial attention effects were stronger in low-level areas, whereas category-specific attention effects were stronger in high-level object-related areas.
  
• 14:40

  Characteristic cortical thickness patterns in adolescents with autism spectrum disorders: Interactions with age and intellectual ability revealed by canonical correlation analysis

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 2 February 2012
  
  Masaya Misaki, Gregory L. Wallace, Nathan Dankner, Alex Martin, Peter A. Bandettini
  
  To investigate patterns and correlates of cortical thickness in adolescent males with autism spectrum disorders (ASD) versus matched typically developing controls, we applied kernel canonical correlation analysis to whole brain cortical thickness with the explaining variables of diagnosis, age, full-scale IQ, and their interactions. The analysis found that canonical variates (patterns of cortical thickness) correlated with each of these variables. The diagnosis- and age-by-diagnosis-related canonical variates showed thinner cortex for participants with ASD, which is consistent with previous studies using a univariate analysis. In addition, the multivariate statistics found larger affected regions with higher sensitivity than those found using univariate analysis. An IQ-related effect was also found with the multivariate analysis. The effects of IQ and age-by-IQ interaction on cortical thickness differed between the diagnostics groups. For typically developing adolescents, IQ was positively correlated with cortical thickness in orbitofrontal, postcentral and superior temporal regions, and greater thinning with age was seen in dorsal frontal areas in the superior IQ (> 120) group. These associations between IQ and cortical thickness were not seen in the ASD group. Differing relationships between IQ and cortical thickness implies independent associations between measures of intelligence and brain structure in ASD versus typically developing controls. We discuss these findings vis-à-vis prior results obtained utilizing univariate methods.
  
• 14:40

  Informing brain connectivity with optogenetic functional magnetic resonance imaging

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 2 February 2012
  
  Jin Hyung Lee, Karl Deisseroth
  
  Optogenetic functional magnetic resonance imaging (ofMRI) combines cell-type specific, temporally precise optogenetic control of neural circuits with high-field fMRI. Optogenetics, is a revolutionary neuro-modulation technology in which light-activated trans-membrane conductance regulators are introduced into specifically targeted cell types and circuit elements to allow millisecond-scale targeted activity modulationin vivo.By combining optogenetics with fMRI, a technique that allows brain-wide, non-invasive monitoring of the brain function, causal communication arising from specific circuit elements can be traced across the whole brain with unprecedented precision. The first published proof of concept study showed highly specificin vivocircuit identification, in which the functional role of cell types defined by genetic identity, cell body location, and axonal projection target can be directly observed and globally mapped in the living mammal. Such capability to trace cell type and temporal encoding specific causal communication will elucidate how circuit elements communicate through the structural connectivity that is in place.
  
  Highlights► ofMRI combines optogenetics with functional Magnetic Resonance Imaging (fMRI). ► Highly specificin vivocircuit identification is possible using ofMRI. ► ofMRI provides new potential to study causal circuit connectivity.
  
  
• 14:40

  Resting state functional connectivity in addiction: Lessons learned and a road ahead

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 1 February 2012
  
  Matthew T. Sutherland, Meredith McHugh, Vani Pariyadath, Elliot A. Stein
  
  Despite intensive scientific investigation and public health imperatives, drug addiction treatment outcomes have not significantly improved in more than 50 years. Non-invasive brain imaging has, over the past several decades, contributed important new insights into the neuroplastic adaptations that result from chronic drug intake, but additional experimental approaches and neurobiological hypotheses are needed to better capture the totality of the motivational, affective, cognitive, genetic and pharmacological complexities of the disease. Recent advances in assessing network dynamics through resting-state functional connectivity (rsFC) may allow for such systems-level assessments. In this review, we first summarize the nascent addiction-related rsFC literature and suggest that in using this tool, circuit connectivity may inform specific neurobiological substrates underlying psychological dysfunctions associated with reward, affective and cognitive processing often observed in drug addicts. Using nicotine addiction as an exemplar, we subsequently provide a heuristic framework to guide future research by linking recent findings from intrinsic network connectivity studies with those interrogating nicotine's neuropharmacological actions. Emerging evidence supports a critical role for the insula in nicotine addiction. Likewise, the anterior insula, potentially together with the anterior cingulate cortex, appears to pivotally influence the dynamics between large-scale brain networks subserving internal (default-mode network) and external (executive control network) information processing. We suggest that a better understanding of how the insula modulates the interaction between these networks is critical for elucidating both the cognitive impairments often associated with withdrawal and the performance-enhancing effects of nicotine administration. Such an understanding may be usefully applied in the design and development of novel smoking cessation treatments.
  
  Highlights► We review the addiction-related resting state functional connectivity (rsFC) literature. ► We propose a framework to guide future research of rsFC in nicotine addiction. ► Nicotine and withdrawal alterrsFC of executive control, default mode and salience networks. ► Insula/dACC salience network plays a critical role in craving and network switching. ► Shifts in rsFC network dynamics underlie cognitive effects of nicotine and withdrawal.
  
  
• 14:40

  Dissociable Roles of Human Inferior Frontal Gyrus during Action Execution and Observation

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 1 February 2012
  
  Clare Press, Nikolaus Weiskopf, James M. Kilner
  
  There has been recent controversy about whether activation in the human inferior frontal gyrus (IFG) and Brodmann Area (BA) 6 when observing actions indicates operation of mirror neurons. Recent functional magnetic resonance imaging (fMRI) data have demonstrated repetition suppression (RS) effects in posterior IFG which are consistent with the presence of mirror neurons in humans. Here we investigated whether there were similar RS effects elsewhere in the IFG and BA6, or whether, instead, activation in other locations may signal operation of alternative mechanisms. Replicating previous findings, we found RS effects in posterior IFG consistent with the operation of mirror neurons. However, these effects were not found in other locations in IFG and BA6. Additionally, activation patterns in anterior regions of IFG suggested dissociable operations when observing and executing actions. Therefore, caution should be exercised when claiming that activations in many locations during action observation indicate the operation of mirror neurons. Activation may instead reflect alternative mechanisms, such as encoding of the semantic features of actions.
  
• January 31, 2012
• 19:57

  Bluetongue virus serotype 6 in Europe in 2008- Emergence and disappearance of an unexpected non-virulent BTV

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 31 January 2012
  
  Piet A. van Rijn, Yvon Geurts, Arco N. van der Spek, Daniel Veldman, René G.P. van Gennip
  
  Bluetongue viruses (BTVs) could invade N-W Europe similar to BTV serotype 8 (BTV8/net06), since the source and route of introduction of this virus has not been solved. Therefore, theDutch survey for Bluetongue by PCRtesting was extended by further analysis of PCRpositives to identify the involved BTV.In late August 2008, BTV wasreported with 12nucleotide differences in the S10amplicon (S10 genotyping). This virus was identified as serotype 6, here named BTV6/net08. Promptly, serotypespecific real-time PCRtests were developed for serotypes 1, 6, and 8 (S2genotyping). Agreement was found between results by S10- and S2genotyping. Further, BTV1 was identified by both S10- and S2genotyping in one imported animal.After initial discovery of BTV6 in the Netherlands, animals from 18 holdings tested PCRpositivefor BTV6/net08 in 2008. Remarkably only one or twoPCRpositive animals per holding were found. Serum neutralization tests did not result in the discovery of more BTV6infected animals. Retrospective studies indicated no evidence for infections by BTV6/net08 prior to the first discovery. Experimental infectionswith BTV6/net08did not cause clinical disease in sheep, calves and cattle, except for a very short fever in some animals. This clearly showed that the vaccine-related BTV6/net08 is not virulent. BTV6/net08 was not found by passive and active surveys in the years after its discovery. Apparently, BTV6/net08 was not efficiently transmittedby endemic species ofCulicoidesin N-W Europe, and disappeared without the need of any control measure.
  
• 19:57

  Occurrence of MRSA in air and housing environment of pig barns

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 31 January 2012
  
  Anika Friese, Jochen Schulz, Laura Hoehle, Alexandra Fetsch, Bernd-Alois Tenhagen, ...
  
  A high prevalence of MRSA among farm animals, especially pigs, has been observed for some time. However, knowledge on transmission routes of MRSA in livestock production is still scarce. Therefore, the aim of this study was to determine the occurrence of MRSA in pig house air as well as in samples from pigs and their housing environment in 27 MRSA positive pig barns of different sizes and production types.In 85.2% of all barns MRSA was detected in the animal house air. Impingement turned out to be a more sensitive sampling technique than filtration. Other environmental samples such as boot swabs or faeces showed prevalences of MRSA from 55.6% to 85.2% at sample level. The level of MRSA was 88.3% for pooled and 82.1% for single nasal swabs, in skin swabs the one was 87.7%, the others was 78.7%.Spatyping of isolates from air and nasal swabs showed predominantlyspatypes t011 and t034. MRSA prevalences in pigs as well as in various environmental samples were significantly higher in fattening farms than in breeding farms. This study provides good reference that there could be an airborne transmission of MRSA within pig herds indicating a potential contamination of the environment of barns.
  
• January 30, 2012
• 14:51

  A geographical history of social cognitive neuroscience

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Matthew D. Lieberman
  
  The history of social cognitive neuroscience (SCN) began with isolated islands of research in Europe and the United States in the 1990s. In the decade between 1995 and 2004 most of the major areas of current SCN research were identified in a series of high profile first studies. This paper reviews the timeline as well as the geography of important moments in the short history of this field. Of note is the different focus seen in European contributions (theory of mind, mirror neurons, and empathy) and the more self-focused U.S. contributions (self-knowledge, emotion regulation, implicit attitudes).
  
  Highlights► Reviews the history of social cognitive neuroscience ► Examines U.S. versus European contributions ► European research focused more on understanding others ► U.S. research focused more on the self
  
  
• 14:51

  Finding the BOLD effect in brain images

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Seiji Ogawa
  
  A brief description of events led to finding BOLD effect in brain images is presented. This is a recollection of what were in this author's mind in pre-1992 period.
  
  Highlights► What were in the author's mind before BOLD effect in MRI was realized. ► Which approaches were taken. ► Observations which led to BOLD finding. ► What were author's MR experiences which bore some relevance for BOLD signal. ► How fMRI with BOLD is provided by Nature to learn brain function.
  
  
• January 28, 2012
• 19:14

  Outer membrane protein P2 of theHaemophilus parasuisSC096 strain contributes to adherence to porcine alveolar macrophages cells

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 28 January 2012
  
  Bin Zhang, Changgang Xu, Ming Liao
  
• 19:14

  Transmissible gastroenteritis virus infection induces apoptosis through FasL- and mitochondria-mediated pathways

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 27 January 2012
  
  Li Ding, Xingang Xu, Yong Huang, Zhaocai Li, Kuan Zhan, ...
  
  Transmissible gastroenteritis virus (TGEV) has been reported to induce apoptosis in swine testis (ST) cells. However, the mechanisms underlying TGEV-induced apoptosis are still unclear. In this study we observed that TGEV infection induced apoptosis in porcine kidney (PK-15) cells in a time- and dose-dependent manner. TGEV infection up-regulated FasL, activated FasL-mediated apoptotic pathway, leading to activation of caspase-8 and cleavage of Bid. In addition, TGEV infection down-regulated Bcl-2, up-regulated Bax expression, promoted translocation of Bax to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c and the activation of caspase-9. Both extrinsic and intrinsic pathways activated downstream effector caspase-3, followed by the cleavage of PARP, resulting in cell apoptosis. Moreover, TGEV infection did not induce significant DNA fragmentation in ammonium chloride (NH4Cl) pretreated PK-15 cells or cells infected with UV-inactivated TGEV. In turn, block of caspases activation also did not affect TGEV replication. Taken together, this study demonstrates that TGEV-induced apoptosis is dependent on viral replication in PK-15 cells and occurs through activation of FasL- and mitochondria-mediated apoptotic pathways.
  
• 19:06

  Embryonic stem cell strategies to explore neural crest development in human embryos

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 28 January 2012
  
  Cécile Milet, Anne H. Monsoro-Burq
  
  Controling embryonic stem cell fatein vitrohas been a major challenge in the past decade. Several protocols have been developed to obtain neural crest derivatives in culture, using more or less defined conditions. Here, we present various strategies used to date to obtain neural crest specification and the markers that can be used to identify human neural crest cells.
  
  Highlights► Human neural crest (NC) cells are still poorly studied ► Several NC markers used in model species have been validated in human ► ES/IPS cells are a promising tool to understand human neural crest development ► Various protocols have been developed to derive neural crest from stem cells
  
  
• 19:06

  Indian hedgehog signaling is required for proper formation, maintenance and migration ofXenopusneural crest

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 28 January 2012
  
  Tristán H. Agüero, Juan P. Fernández, Guillermo A. Vega López, Celeste Tríbulo, Manuel J. Aybar
  
  Neural crest induction is the result of the combined action at the neural plate border of FGF, BMP, and Wnt signals from the neural plate, mesoderm and nonneural ectoderm. In this work we show that the expression ofIndian hedgehog(Ihh, formerly namedBanded hedgehog) and members of the Hedgehog pathway occurs at the prospective neural fold, in the premigratory and migratory neural crest. We performed a functional analysis that revealed the requirement ofIhhsignaling in neural crest development. During the early steps of neural crest induction loss of function experiments with antisense morpholino or locally grafted cyclopamine-loaded beads suppressed the expression of early neural crest markers concomitant with the increase in neural and epidermal markers. We showed that changes inIhhactivity produced no alterations in either cell proliferation or apoptosis, suggesting that this signal involves cell fate decisions. A temporal analysis showed that Hedgehog is continuously required not only in the early and late specification but also during the migration of the neural crest. We also established that the mesodermal source ofIhhis important to maintain specification and also to support the migratory process. By a combination of embryological and molecular approaches our results demonstrated thatIhhsignaling drives in the migration of neural crest cells by autocrine or paracrine mechanisms. Finally, the abrogation ofIhhsignaling strongly affected only the formation of cartilages derived from the neural crest, while no effects were observed on melanocytes. Taken together, our results provide insights into the role of theIhhcell signaling pathway during the early steps of neural crest development.
  
  Highlights► We analyzedIhh(Indian hedgehog,formerlyBanded hedgehog) signaling requirement inXenopusneural crest development. ► Antisense morpholino or locally grafted cyclopamine-loaded beads suppressed the expression of neural crest markers. ► A temporal analysis showed that Hedgehog is continuously required from early specification to the migration stages.► Ihhdrives in the migration by autocrine or paracrine mechanisms.► Ihhknock-down affected only the formation of cartilages derived from the neural crest.
  
  
• 19:06

  Corrigendum to “mitfais required at multiple stages of melanocyte differentiation but not to establish the melanocyte stem cell” [Dev. Biol. 350 (2011) 405–413]

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 28 January 2012
  
  Stephen L. Johnson, AnhThu N. Nguyen, James A. Lister
  
• 19:06

  Maternally localized germ plasm mRNAs and germ cell/stem cell formation in the cnidarianClytia

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 27 January 2012
  
  Lucas Leclère, Muriel Jager, Carine Barreau, Patrick Chang, Hervé Le Guyader, ...
  
  The separation of the germ line from the soma is a classic concept in animal biology, and depending on species is thought to involve fate determination either by maternally localized germ plasm (“preformation” or “maternal inheritance”) or by inductive signalling (classically termed “epigenesis” or “zygotic induction”). The latter mechanism is generally considered to operate in non-bilaterian organisms such as cnidarians and sponges, in which germ cell fate is determined at adult stages from multipotent stem cells. We have found in the hydrozoan cnidarianClytia hemisphaericathat the multipotent “interstitial” cells (i-cells) in larvae and adult medusae, from which germ cells derive, express a set of conserved germ cell markers:Vasa,Nanos1,PiwiandPL10.In situhybridization analyses unexpectedly revealed maternal mRNAs for all these genes highly concentrated in a germ plasm–like region at the egg animal pole and inherited by the i-cell lineage, strongly suggesting i-cell fate determination by inheritance of animal-localized factors. On the other hand, experimental tests showed that i-cells can form by epigenetic mechanisms inClytia, since larvae derived from both animal and vegetal blastomeres separated during cleavage stages developed equivalent i-cell populations. ThusClytiaembryos appear to have maternal germ plasm inherited by i-cells but also the potential to form these cells by zygotic induction. Reassessment of available data indicates that maternally localized germ plasm molecular components were plausibly present in the common cnidarian/bilaterian ancestor, but that their role may not have been strictly deterministic.
  
  Highlights► Nanos, Piwi, Vasa and PL10 are localized in Clytia eggs in a germ plasm-like region. ► The germ plasm-like region is inherited by the interstitial stem cell lineage. ► Preformation and inductive signals are involved in stem cell specification in Clytia. ► Maternal germ plasm was plausibly present in the Cnidaria - Bilateria ancestor.
  
  
• 19:06

  The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 26 January 2012
  
  Bettina C. Kirchmaier, Kar Lai Poon, Thorsten Schwerte, Jan Huisken, Christoph Winkler, ...
  
  The Popeye domain containing (Popdc) genes encode a family of transmembrane proteins with an evolutionary conserved Popeye domain. These genes are abundantly expressed in striated muscle tissue, however their function is not well understood. In this study we have investigated the role of thepopdc2gene in zebrafish.Popdc2transcripts were detected in the embryonic myocardium and transiently in the craniofacial and tail musculature. Morpholino oligonucleotide-mediated knockdown ofpopdc2resulted in aberrant development of skeletal muscle and heart. Muscle segments in the trunk were irregularly shaped and craniofacial muscles were severely reduced or even missing. In the heart, pericardial edema was prevalent in the morphants and heart chambers were elongated and looping was abnormal. These pathologies in muscle and heart were alleviated after reducing the morpholino concentration. However the heart still was abnormal displaying cardiac arrhythmia at later stages of development. Optical recordings of cardiac contractility revealed irregular ventricular contractions with a 2:1, or 3:1 atrial/ventricular conduction ratio, which caused a significant reduction in heart frequency. Recordings of calcium transients with high spatiotemporal resolution using a transgenic calcium indicator line (Tg(cmlc2:gCaMP)) and SPIM microscopy confirmed the presence of a severe arrhythmia phenotype. Our results identifypopdc2as a gene important for striated muscle differentiation and cardiac morphogenesis. In addition it is required for the development of the cardiac conduction system.
  
• 17:37

  The Past, Present and Future of Social Neuroscien A European Perspective

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Tania Singer
  
  This review provides an overview of the field of social neuroscience from a European perspective and focuses mainly on outlining research topics which originated in European laboratories. After a brief historical synopsis of the emergence of this young field, the most relevant findings related to the investigation of the neural networks underlying our capacity to understand the minds of others are summarized. More specifically, three routes of social cognition are distinguished: (1) our capacity to mentalize, or to infer intentions and beliefs of others, (2) our capacity to mimic and understand other's motor actions, and (3) our capacity to empathize, or to share and understand the feelings of others. More recent studies focusing on social emotions such as love, compassion, revenge or our sense of fairness will be discussed linking the field of social neuroscience to the even younger field of neuroeconomics, the study of human social interactions using game theoretical paradigms. Finally, the use of a multi-method and multi-disciplinary research approach combining genetic, pharmacological, computational and developmental aspects is advocated and future directions for the study of interactive minds are discussed.
  
  Highlights► Review of the field of social neuroscience from a European perspective ► Summary of mirror neuron, Theory of Mind and empathy research ► Review of studies focusing on social emotions and social interaction ► Suggestions for the development of real interactive mind paradigms
  
  
• 17:37

  Reactivation of visual cortex during memory retrieval: Content specificity and emotional modulation

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Christoph Hofstetter, Amal Achaibou, Patrik Vuilleumier
  
  Studies on memory retrieval suggest a reactivation of cortical regions engaged during encoding, such that visual or auditory areas reactivate for visual or auditory memories. The content specificity and any emotion dependency of such reactivations are still unclear. Because distinct visual areas are specialized in processing distinct stimulus categories, we tested for face and word specific reactivations during a memory task using functional magnetic resonance imaging (fMRI). Furthermore, because visual processing and memory are both modulated by emotion, we compared reactivation for stimuli encoded in a neutral or emotionally significant context. In the learning phase, participants studied pairs of stimuli that consisted of either a scene and a face, or a scene and a word. Scenes were either neutral or negative, but did not contain faces or words. In the test phase scenes were presented alone (one in turn), and participants indicated whether it was previously paired with a face, a word, or was new. Results from the test phase showed activation in a functionally defined face-responsive region in the right fusiform gyrus, as well as in a word-responsive region in the left inferior temporal gyrus, for scenes previously paired with faces and words, respectively. Reactivation tended to be larger in both the face- and word-responsive regions when the associated scene was negative as compared to neutral. However, relative to neutral context, the recall of faces and words paired with a negative context produced smaller activations in brain regions associated with social and semantic processing, respectively, as well as poorer memory performance overall. Taken together, these results support the idea of cortical memory reactivations, even at a content-specific level, and further suggest that emotional context may produce opposite effects on reactivations in early sensory areas and more elaborate processing in higher-level cortical areas.
  
  Highlights► Content-specific reactivation of visual cortex when recalling faces and words. ► Stronger reactivation with increasing performance for faces. ► Stronger reactivation with emotional compared to neutral cues.
  
  
• 17:37

  The spatial distribution of age-related white matter changes as a function of vascular risk factors - results from the LADIS study

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  E. Rostrup, A.A. Gouw, H. Vrenken, E.C.W. van Straaten, S. Ropele, ...
  
  White matter hyperintensities (WMH) are a frequent finding on brain MRI of elderly subjects, and have been associated with various risk factors, as well as with development of cognitive and functional impairment. While an overall association between WMH load and risk factors is well described, possible spatially restricted vulnerability remains to be established.The aim of this study was to investigate the spatial distribution of WMH in normally functioning elderly subjects. We introduce a voxel-based approach in which lesion probability is mapped as a function of clinical risk factors using logistic regression, and validate the method using simulated datasets. The method was then applied in a total of 605 participants of the LADIS study (age 74 ± 5 years, all with WMH), and the location of manually delineated WMH was investigated after spatial normalisation. Particularly strong and widespread associations were found for age, gender and hypertension. Different distribution patterns were found for men and women. Further, increased probability was found in association with self-reported alcohol and tobacco consumption, as well as in those with a history of migraine. It is concluded that the location of WMH is dependent on the risk factors involved pointing towards a regionally different pathogenesis and/or vulnerability of the white matter.
  
  Highlights► White matter changes are a frequent finding on brain MRI of elderly subjects. ► Overall severity is known to be associated with vascular risk factors. ► The spatial distribution of risk factor impact not well described. ► We apply voxel-based logistic regression to a large group of non-demented elderly. ► Particularly strong associations were found for age, gender and hypertension
  
  
• 17:37

  MRI atrophy of the caudate nucleus and slower walking speed in the elderly

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Julien Dumurgier, Fabrice Crivello, Bernard Mazoyer, Ismaïl Ahmed, Béatrice Tavernier, ...
  
  Cerebral white matter lesions are associated with poorer motor performances in the elderly, but the role of gray matter atrophy remains largely unknown. We investigated the cross-sectional relation between brain regional gray matter volumes and walking speed over 6 meters in the 3 C-Dijon study, a large population-based study of community-dwelling persons aged 65 years and over (N = 1623). Regional gray matter volumes were obtained using an automated anatomical labeling parcellation method. Multivariable analyses were performed using a semi-Bayes approach. After adjustment for potential confounders, persons who walked slower had a smaller volume of basal ganglia (regression coefficient [β] = 0.054, standard error [SE] = 0.028, p = 0.05). In more detailed analyses, the volume of the caudate nucleus had a preponderant role on this association (β = 0.049, SE = 0.019, p = 0.009), and walking speed decreased progressively with the volume of the caudate nucleus (p for linear trend < 0.001). These results underline the role of gray matter subcortical structures, in particular of the caudate nucleus, in the age-related decline of motor performances among community-dwelling elderly subjects.
  
  Highlights► Population-based study among 1623 community-dwelling persons aged 65 years and over. ► Analysis of the relationship between MRI gray matter volumes and walking speed. ► Linear association between volume of caudate nucleus and walking speed. ► Suggestive for the role of gray matter structures in the decline of motor function.
  
  
• 17:37

  Preparation of fixed mouse brains for MRI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Lindsay S. Cahill, Christine L. Laliberté, Jacob Ellegood, Shoshana Spring, Jacqueline A. Gleave, ...
  
  In fixed mouse brain magnetic resonance images, a high prevalence of fixation artifacts have been observed. Of more than 1700 images of fixed brains acquired at our laboratory, fixation artifacts were present in approximately 30%. In this study, two of these artifacts are described and their causes are identified. A hyperintense rim around the brain is observed when using perfusates reconstituted from powder and delivered at a high flow rate. It is proposed that these perfusion conditions cause blockage of the capillary beds and an increase in pressure that ruptures the vessels, resulting in a blister of liquid below the dura mater. Secondly, grey-white matter contrast inversion is observed when too short a fixation time or too low a concentration of fixative is used, resulting in inadequate fixation. The deleterious consequences of these artifacts for quantitative data analysis are discussed, and precautions for their prevention are provided.
  
  Highlights► A high prevalence of fixation artifacts are observed in fixed mouse brain MR images ► Two artifacts from perfusion fixation are described and their causes identified ► Hyperintense rim around brain occurs when using powder perfusates and high flow rate ► Inverse contrast and cerebellar deformation occurs upon inadequate fixation ► These artifacts are unacceptable for quantitative data analysis and must be avoided
  
  
• 17:37

  Detection of epileptic activity in fMRI without recording the EEG

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  R. Lopes, J.M. Lina, F. Fahoum, J. Gotman
  
  EEG-fMRI localizes epileptic foci by detecting cerebral hemodynamic changes that are correlated to epileptic events visible in EEG. However, scalp EEG is insensitive to activity restricted to deep structures and recording the EEG in the scanner is complex and results in major artefacts that are difficult to remove.This study presents a new framework for identifying the BOLD manifestations of epileptic discharges without having to record the EEG. The first stage is based on the detection of epileptic events for each voxel by sparse representation in the wavelet domain. The second stage is to gather voxels according to proximity in time and space of detected activities.This technique was evaluated on data generated by superposing artificial responses at different locations and responses amplitude in the brain for 6 control subject runs. The method was able to detect effectively and consistently for responses amplitude of at least 1% above baseline. 46 runs from 15 patients with focal epilepsy were investigated. The results demonstrate that the method detected at least one concordant event in 37/41 runs. The maps of activation obtained from our method were more similar to those obtained by EEG-fMRI than to those obtained by the other method used in this context, 2D-Temporal Cluster Analysis. For 5 runs without event read on scalp EEG, 3 runs showed an activation concordant with the patient's diagnostic.It may therefore be possible, at least when spikes are infrequent, to detect their BOLD manifestations without having to record the EEG.
  
  Highlights► We, for the first time, report somatic mosaicism in two male patients with X-CGD. ► Cells with normal DNA sequence also had normal gp91expression and ROB activity. ► Cells with normal DNA sequence were also present in buccal swab specimens and PBMC. ► FISH and HLA DNA typing studies indicate these cells are of the patient origin. ► De novo mutations or reversion of mutations during embryogenesis may have occurred.
  
  
• 17:37

  The Coupling Controversy

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Peter T. Fox
  
  Functional magnetic resonance imaging (fMRI) relies on the well-known phenomenon of coupling between neuronal activity and brain blood flow. For nearly a century, the presumption was that hemodynamics were coupled to neuronal activity via energy demand and oxidative metabolism. EarlyO positron-emission tomographic (PET) studies challenged this theory, demonstrating a physiological “uncoupling” between brain blood flow and oxygen metabolism. These PET observations played a pivotal role in guiding the development of fMRI, by demonstrating which physiological parameters were most closely coupled to neuronal activity and by presaging the BOLD-contrast effect. Subsequent PET studies were crucial for constraining theories concerning the physiological mechanisms underlying hemodynamic/neuronal coupling and, thereby, guiding the development of models for quantification of oxygen metabolic rate %∆ from fMRI. A first-person account of the PET “coupling” studies and their influence on the development of fMRI is provided.
  
• 17:37

  Circular representation of human cortical networks for subject and population-level connectomic visualization

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 28 January 2012
  
  Andrei Irimia, Micah C. Chambers, Carinna M. Torgerson, John D. Van Horn
  
  Cortical network architecture has predominantly been investigated visually using graph theory representations. In the context of human connectomics, such representations are not however always satisfactory because canonical methods for vertex-edge relationship representation do not always offer optimal insight regarding functional and structural neural connectivity. This article introduces an innovative framework for the depiction of human connectomics by employing a circular visualization method which is highly suitable to the exploration of central nervous system architecture. This type of representation, which we name a ‘connectogram’, has the capability of classifying neuroconnectivity relationships intuitively and elegantly. A multimodal protocol for MRI/DTI neuroimaging data acquisition is here combined with automatic image segmentation to (1) extract cortical and non-cortical anatomical structures, (2) calculate associated volumetrics and morphometrics, and (3) determine patient-specific connectivity profiles to generate subject-level and population-level connectograms. The scalability of our approach is demonstrated for a population of 50 adults. Two essential advantages of the connectogram are (1) the enormous potential for mapping and analyzing the human connectome, and (2) the unconstrained ability to expand and extend this analysis framework to the investigation of clinical populations and animal models.
  
  Highlights► a framework for visualization and exploration of human connectomics is introduced. ► this ‘connectogram’ representation has significant potential for connectomic analysis . ► connectogram scalability is demonstrated using a population analysis of 50 adults.
  
  
• 17:37

  Embodied empathy for tactile events: Interindividual differences and vicarious somatosensory responses during touch observation

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 27 January 2012
  
  Michael Schaefer, Hans-Jochen Heinze, Michael Rotte
  
  A growing body of evidence suggests an involvement of the somatosensory cortices for social perception. For example, it has been shown that observing touch on other bodies (in the absence of any real touch on the own body) affects somatosensory brain areas. Thus, understanding others sensory experiences seem to rely on vicarious activation of somatosensory cortices. Recent studies also demonstrated that observation of painful and nonpainful touch engages the observer's somatosensory cortex differentially. The somatosensory activation during observation of painful stimulation has been related to trait differences in empathy, thereby drawing the attention to inter-individual differences in vicarious somatosensory activation. The current study aims to test the hypothesis if vicarious somatosensory activation during observation ofnonpainful touch is also linked to inter-individual differences in empathy. We employed a functional magnetic resonance imaging (fMRI) paradigm to present video clips showing simple non-painful touch with a paintbrush to a hand relative to a control condition including the same visual and motion parts. Results revealed vicarious somatosensory activation when seeing the hand being touched. This activation was associated with trait differences in interpersonal reactivity. Thus, we found that the somatosensory response in primary somatosensory cortex (SI) was associated with the empathy subscale perspective taking. This link demonstrates that vicarious somatosensory responses for simple touch are influenced by observer's personality traits, therefore suggesting a role for personality traits in a putative mirror neuron system.
  
• 17:37

  Can target-to-pons ratio be used as a reliable method for the analysis of [C]PIB brain scans?

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 27 January 2012
  
  P. Edison, R. Hinz, A. Ramlackhansingh, J. Thomas, G. Gelosa, ...
  
  Rationale C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [ C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [ C]PIB binding.Methods12 sporadic AD subjects aged 65 ± 4.5 yrs with a mean MMSE 21.4 ± 4 and 10 age-matched control subjects had [ C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomaticpresenilin-1mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the grey matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [ C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (VT) were generated with Logan analysis. Additionally, parametric maps of the 60-90 min target-to-cerebellar ratio (RATIOCER) and the 60-90 min target-to-pons ratio (RATIOPONS) were computed.ResultsAll three approaches were able to differentiate AD from controls (p < 0.0001, nonparametric Wilcoxon rank sum test) in the target regions with RATIOCERand RATIOPONSdifferences higher than VTwith use of an arterial input function. All methods had a good reproducibility (intraclass correlation coefficient > 0.83); RATIOCERperformed best closely followed by RATIOPONS.The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIOCER,but the RATIOPONSapproach revealed higher [ C]PIB binding in cortex and cerebellumConclusionThis study established 60-90 min target-to-pons RATIOs as a reliable method of analysis in [ C]PIB PET studies where cerebellum is not an appropriate reference region.
  
• 17:37

  Gradient Echo Plural Contrast Imaging – signal model and derived contrasts: T2*, T1, Phase, SWI, T1f, FST2*and T2*-SWI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 27 January 2012
  
  Jie Luo, Bharathi D. Jagadeesan, Anne H. Cross, Dmitriy A. Yablonskiy
  
  Gradient Echo Plural Contrast Imaging (GEPCI) is a post processing technique that, based on a widely available multiple gradient echo sequence, allows simultaneous generation of naturally co-registered images with various contrasts: T1 weighted, R2* = 1/T2* maps and frequency (f) maps. Herein, we present results demonstrating the capability of GEPCI technique to generate image sets with additional contrast characteristics obtained by combing the information from these three basic contrast maps. Specifically, we report its ability to generate GEPCI-susceptibility weighted images (GEPCI-SWI) with improved SWI contrast that is free of T1 weighting and RF inhomogeneities; GEPCI-SWI-like images with the contrast similar to original SWI; T1f images that offer superior GM/WM matter contrast obtained by combining the GEPCI T1 and frequency map data; Fluid Suppressed T2* (FST2*) images that utilize GEPCI T1 data to suppress CSF signal in T2* maps and provide contrast similar to FLAIR T2 weighted images; and T2*-SWI images that combine SWI contrast with quantitative T2* map and offer advantages of visualizing venous structure with hyperintense T2* lesions (e.g. MS lesions). To analyze GEPCI images we use an improved algorithm for combining data from multi-channel RF coils and a method for unwrapping phase/frequency maps that takes advantage of the information on phase evolution as a function of gradient echo time in GEPCI echo train.
  
  
  
  
  
  
• 17:37

  Brain ‘talks over’ boring quotes: Top-down activation of voice-selective areas while listening to monotonous direct speech quotations

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 27 January 2012
  
  Bo Yao, Pascal Belin, Christoph Scheepers
  
  In human communication, direct speech (e.g.,Mary said, “I'm hungry”) is perceived as more vivid than indirect speech (e.g.,Mary said that she was hungry). This vividness distinction has previously been found to underlie silent reading of quotations: Using functional magnetic resonance imaging (fMRI), we found that direct speech elicited higher brain activity in the temporal voice areas (TVA) of the auditory cortex than indirect speech, consistent with an “inner voice” experience in reading direct speech. Here we show that listening to monotonously spoken direct versus indirect speech quotations also engenders differential TVA activity. This suggests that individuals engage in top-down simulations or imagery of enriched supra-segmental acoustic representations while listening to monotonous direct speech. The findings shed new light on the acoustic nature of the “inner voice” in understanding direct speech.
  
• 17:37

  Steady-state responses in MEG demonstrate information integration within but not across the auditory and visual senses

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 27 January 2012
  
  Anette S. Giani, Erick B. Ortiz, Paolo Belardinelli, Mario Kleiner, Hubert Preissl, ...
  
  To form a unified percept of our environment, the human brain integrates information within and across the senses. This MEG study investigated interactions within and between sensory modalities using a frequency analysis of steady-state responses that are elicited time-locked to periodically modulated stimuli. Critically, in the frequency domain, interactions between sensory signals are indexed by crossmodulation terms (i.e. the sums and differences of the fundamental frequencies). The 3x2 factorial design, manipulated (1) modality: auditory, visual or audiovisual (2) steady-state modulation: the auditory and visual signals were modulated only in one sensory feature (e.g. visual gratings modulated in luminance at 6 Hz) or in two features (e.g. tones modulated in frequency at 40 Hz & amplitude at 0.2 Hz). This design enabled us to investigate crossmodulation frequencies that are elicited when two stimulus features are modulated concurrently (i) in one sensory modality or (ii) in auditory and visual modalities. In support of within-modality integration, we reliably identified crossmodulation frequencies when two stimulus features in one sensory modality were modulated at different frequencies. In contrast, no crossmodulation frequencies were identified when information needed to be combined from auditory and visual modalities. The absence of audiovisual crossmodulation frequencies suggests that the previously reported audiovisual interactions in primary sensory areas may mediate low level spatiotemporal coincidence detection that is prominent for stimulus transients but less relevant for sustained SSR responses. In conclusion, our results indicate that information in SSRs is integrated over multiple time scales within but not across sensory modalities at the primary cortical level.
  
  Highlights► Information is integrated within the senses across multiple temporal scales ► Crossmodulation frequencies for amplitude and frequency modulated tones ► Crossmodulation frequencies for luminance and size modulated visual gratings ► Absence of AV crossmodulation frequencies indicates no across sensory integration
  
  
• 17:37

  Imaging of lamination patterns of the adult human olfactory bulb and tract: In vitro comparison of standard- and high-resolution 3T MRI, and MR microscopy at 9.4T

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 27 January 2012
  
  Hartmut P. Burmeister, Thomas Bitter, Patrick M. Heiler, Andrey Irintchev, Rosemarie Fröber, ...
  
  PurposeNeurological and smelling disorders (e.g. Alzheimer's disease, sinonasal disease) negatively affect the microstructural integrity of the olfactory bulb's (OB) cortical layers. Recovery processes depend on active restoration of this microstructural integrity enabled by neuroneogenesis in the OB. The aim of this study was to evaluate lamination patterns of the OB and adjacent tract (OT) using high resolution MRI at 3 Tesla (T) as well as MR microscopy at 9.4 T in comparison with histological sections.Material and MethodsTwenty-four human OBs were imaged in vitro using standard (2 mm slice thickness) and high resolution (0.2 mm slice thickness) T1w and T2w MR imaging at 3 T. Based on signal intensity differences, the number of OB layers and the OB lamination patterns were assessed by two observers in consensus. Results were compared using Wilcoxon test. Signal intensity profiles were compared to reference Nissl stained histological sections and imaging results of MR microscopy. OT lamination patterns were assessed and different configurations of cross sectional areas were compared to macroscopic results and OB/OT lamination patterns.ResultsStandard resolution at 3 T identified three layers in 8.3%, two layers in 83.3%, and one layer in 8.3%. High resolution at 3 T (4 layers in 91.7%, 3 layers in 8.3%) significantly performed better (P < 0.001). Signal intensity profile analysis at 3 T and 9.4 T (yielding up to 6 different signal intensities) correlated with histological sections and enabled quantitative evaluation of OB lamination patterns. 3 T MRI of the OT revealed two separate signal intensities in T2w in 73%, a hyperintense core and a hypointense sheath, and the number of OT signal intensities positively correlated (ρ = 0.541, P = 0.006) with the increasing complexity of the OTs' cross sectional area configurations. Additionally, cross sectional area configurations correlated with macroscopic results (ρ = 0.558, P = 0.002) and OB lamination patterns (ρ = 0.446, P = 0.022).Conclusions3 T MRI and MR-microscopy indicate the possibility to identify the lamination pattern of the human OB/OT and to reflect the histological status. If further development will be able to provide technical equipment that complies with the condition of human in vivo high resolution imaging achieving a good enough signal noise ratio, the method of signal intensity profile analysis could prospectively enable scientists to assess the OB's microstructural status in neurological and smelling disorders.
  
• 17:37

  The intravascular susceptibility effect and the underlying physiology of fMRI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 27 January 2012
  
  Arno Villringer
  
  In this article, I will first give a brief account of my work at MGH on characterizing the intravascular susceptibility effect. Then I will describe studies into the underlying physiology of BOLD-fMRI which has become of interest to my group in the following decade. I will touch issues such as signal source of BOLD fMRI, capillary recruitment, the elusive initial dip and others.
  
• 17:37

  Erratum to Construction of a consistent high-definition spatio-temporal atlas of the developing brain using adaptive kernel regression [NeuroImage 59/3(2012) 2255–2265]

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  Ahmed Serag, Paul Aljabar, Gareth Ball, Serena J. Counsell, James P. Boardman, ...
  
• 17:37

  Normative database of judgment of complexity task with functional near infrared spectroscopy – Application for TBI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  Franck Amyot, Trelawny Zimmermann, Jason Riley, Jana M. Kainerstorfer, Victor Chernomordik, ...
  
  The ability to assess frontal lobe function in a rapid, objective, and standardized way, without the need for expertise in cognitive test administration might be particularly helpful in mild traumatic brain injury (TBI), where objective measures are needed. Functional near infrared spectroscopy (fNIRS) is a reliable technique to noninvasively measure local hemodynamic changes in brain areas near the head surface. In this paper, we are combining fNIRS and frameless stereotaxy which allowed us to co-register the functional images with previously acquired anatomical MRI volumes. In our experiment, the subjects were asked to perform a task, evaluating the complexity of daily life activities, previously shown with fMRI to activate areas of the anterior frontal cortex. We reconstructed averaged oxyhemoglobin and deoxyhemoglobin data from 20 healthy subjects in spherical coordinate. The spherical coordinate is a natural representation of surface brain activation projection. Our results show surface activation projected from the medial frontopolar cortex which is consistent with previous fMRI results. With this original technique, we will construct a normative database for a simple cognitive test which can be useful in evaluating cognitive disability such as mild traumatic brain injury.
  
  Highlights► Normative database of activation for the judgment of complexity task ► Functional Near infrared spectroscopy images registered with MRI anatomical image ► Activation in the prefrontal cortex which is consistent with previous fMRI results ► Quick and easy detection of activation of frontal lobe in group study, creation of group data and look their variability
  
  
• 17:37

  Corrigendum to “Functional magnetic resonance inverse imaging of human visuomotor systems using eigenspace linearly constrained minimum amplitude (eLCMA)” Beamformer [NeuroImage 55/1 (March 2011) 87–100]

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  Shr-Tai Liou, Thomas Witzel, Aapo Numenmaa, Wei-Tang Chang, Kevin Wen-Kai Tsai, ...
  
• 17:37

  Interaction ofCOMTvalmet and externalizing behavior: Relation to prefrontal brain activity and behavioral performance

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  Zarrar Shehzad, Colin G. DeYoung, Yoona Kang, Elena L. Grigorenko, Jeremy R. Gray
  
  A promising approach in neuroimaging studies aimed at understanding effects of single genetic variants on behavior is the study of gene-trait interactions. Variation in the catechol-O-methyl-transferase gene (COMT) is associated with the regulation of dopamine levels in prefrontal cortex and with cognitive functioning. Given the involvement of dopaminergic neurotransmission in externalizing behavior, a trait characterized by impulsivity and aggression, especially in men, externalizing (as a trait) may index a set of genetic, environmental, and neural characteristics pertinent to understanding phenotypic effects of genetic variation in theCOMTgene. In the current study, we used a gene-trait approach to investigate effects of the COMT valmet polymorphism and externalizing on brain activity during moments involving low or high demands on cognitive control. In 104 male participants, interference-related activation depended conjointly on externalizing and valmet: Stronger activation in dorsal anterior cingulate and lateral prefrontal cortex was found for val/val individuals with high trait externalizing while stronger activation in cingulate motor areas and sensorimotor precuneus was found for met/met individuals with low externalizing. Our results suggest that the val/val genotype, coupled with high levels of trait externalizing, lowers the efficiency of stimulus conflict resolution, whereas the met/met genotype, coupled with low levels of externalizing, lowers the efficiency of response selection.
  
• 17:37

  Nonlinear denoising and analysis of neuroimages with kernel principal component analysis and pre-image estimation

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  Peter Mondrup Rasmussen, Trine Julie Abrahamsen, Kristoffer Hougaard Madsen, Lars Kai Hansen
  
  We investigate the use of kernel principal component analysis (PCA) and the inverse problem known aspre-imageestimation in neuroimaging: i) We explore kernel PCA and pre-image estimation as a means for image denoising as part of the imagepreprocessing pipeline. Evaluation of the denoising procedure is performed within a data-driven split-half evaluation framework. ii) We introduce manifold navigation for exploration of a nonlinear data manifold, and illustrate how pre-image estimationcan be used to generate brain maps in the continuum between defined experimental brain states/classes. We base these illustrations on two fMRI BOLD data sets - one from a simple finger tapping experiment and the other from an experiment on object recognition in the ventral temporal lobe.
  
• 17:37

  Analysis of automated methods for spatial normalization of lesioned brains

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  P. Ripollés, J. Marco-Pallarés, R. de Diego-Balaguer, J. Miró, M. Falip, ...
  
  Normalization of brain images is a crucial step in MRI data analysis, especially when dealing with abnormal brains. Although cost function masking (CFM) appears to successfully solve this problem and seems to be necessary for patients with chronic stroke lesions, this procedure is very time consuming. The present study sought to find viable, fully automated alternatives to cost function masking, such as Automatic Lesion Identification (ALI) and Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). It also sought to quantitative assess, for the first time, Symmetrical Normalization (SyN) with constrained cost function masking. The second aim of this study was to investigate the normalization process in a group of drug-resistant epileptic patients with large resected regions (temporal lobe and amygdala) and in a group of stroke patients. A dataset of 500 artificially generated lesions was created using ten patients with brain-resected regions (temporal lobectomy), ten stroke patients and twenty five-healthy subjects. The results indicated that although a fully automated method such as DARTEL using New Segment with an extra prior (the mean of the white matter and cerebro-spinal fluid) obtained the most accurate normalization in both patient groups, it produced a shrinkage in lesion volume when compared to Unified Segmentation with CFM. Taken together, these findings suggest that further research is needed in order to improve automatic normalization processes in brains with large lesions and to completely abandon manual, time consuming normalization methods.
  
• 17:37

  Measuring Longitudinal Change in the Hippocampal Formation from In Vivo High-Resolution T2-Weighted MRI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  Sandhitsu R. Das, Brian B. Avants, John Pluta, Hongzhi Wang, Jung Wook Suh, ...
  
  The hippocampal formation (HF) is a brain structure of great interest because of its central role in learning and memory, and its associated vulnerability to several neurological disorders.In vivooblique coronal T2-weighted MRI with high in-plane resolution (∼ 0.5 mm × 0.5 mm) , thick slices (∼ 2.0 mm) , and a field of view tailored to imaging the hippocampal formation (denoted HF-MRI in this paper) has been advanced as a useful imaging modality for detailed hippocampal morphometry. Cross-sectional analysis of volume measurements derived from HF-MRI has shown the modality's promise to yield sensitive imaging-based biomarker for neurological disorders such as Alzheimer's disease. However, the utility of this modality for making measurements of longitudinal change has not yet been demonstrated. In this paper, using an unbiased deformation-based morphometry (DBM) pipeline, we examine the suitability of HF-MRI for estimating longitudinal change by comparing atrophy rates measured in the whole hippocampus from this modality with those measured from more common isotropic (∼ 1 mm) T1-weighted MRI in the same set of individuals, in a cohort of healthy controls and patients with cognitive impairment. While measurements obtained from HF-MRI were largely consistent with those obtained from T1-MRI, HF-MRI yielded slightly larger group effect of greater atrophy rates in patients than in controls. The estimated minimum sample size required for detecting a 25% change in patients’ atrophy rate in the hippocampus compared to the control group with a statistical powerβ = 0.8 wasN = 269. For T1-MRI, the equivalent sample size wasN = 325. Using a dataset of test-retest scans, we show that the measurements were free of additive bias. We also demonstrate that these results were not a confound of certain methodological choices made in the DBM pipeline to address the challenges of making longitudinal measurements from HF-MRI, using a region of interest (ROI) around the HF to globally align serial images, followed by slice-by-slice deformable registration to measure local volume change. Additionally, we present a preliminary study of atrophy rate measurements within hippocampal subfields using HF-MRI. Cross-sectional differences in atrophy rates were detected in several subfields.
  
• 17:37

  Construction of a Neuroanatomical Shape Complex Atlas from 3D MRI Brain Structures

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 26 January 2012
  
  Ting Chen, Anand Rangarajan, Stephan J. Eisenschenk, Baba C. Vemuria
  
  Brain atlas construction has attracted significant attention lately in the neuroimaging community due to its application to the characterization of neuroanatomical shape abnormalities associated with various neurodegenerative diseases or neuropsychiatric disorders. Existingshapeatlas construction techniques usually focus on the analysis of a single anatomical structure in which the important inter-structural information is lost. This paper proposes a novel technique for constructing a neuroanatomicalshape complexatlas based on an information geometry framework. A shape complex is a collection of neighboring shapes—for example, the thalamus, amygdala and the hippocampus circuit—which may exhibit changes in shape across multiple structures during the progression of a disease. In this paper, we represent the boundaries of the entire shape complex using the zero level set of a distance transform functionS(x). We then re-derive the relationship between the stationary state wave functionψ(x) of the Schrödinger equation − ℏ ∇ ψ + ψ = 0 and the eikonal equation ‖ ∇ S‖ = 1 satisfied by any distance function. This leads to a one-to-one map (up to scale) betweenψ(x) andS(x) via an explicit relationship. We further exploit this relationship by mappingψ(x) to a unit hypersphere whose Riemannian structure is fully known, thus effectively turnψ(x) into the square-root of a probability density function. This allows us to make comparisons—using elegant, closed-form analytic expressions—between shape complexes represented as square-root densities. A shape complex atlas is constructed by computing the Karcher meanin the space of square-root densities and then inversely mapping it back to the space of distance transforms in order to realize the atlas shape. We demonstrate the shape complex atlas computation technique via a set of experiments on a population of brain MRI scans including controls and epilepsy patients with either right anterior medial temporal or left anterior medial temporal lobectomies.
  
• 17:37

  Oscillating central motor networks in pathological tremors and voluntary movements. What makes the difference?

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  M. Muthuraman, U. Heute, K. Arning, A.R. Anwar, R. Elble, ...
  
  Parkinsonian tremor (PD), Essential tremor (ET) and voluntarily mimicked tremor represent fundamentally different motor phenomena, yet, magnetoencephalographic and imaging data suggest their origin in the same motor centers of the brain. Using EEG-EMG coherence and coherent source analysis we found a different pattern of corticomuscular delays, time courses and central representations for the basic and double tremor frequencies typical for PD suggesting a wider range defective oscillatory activity. For the basic tremor frequency similar central representations in primary sensorimotor, prefrontal/ premotor and diencephalic (e.g. thalamic) areas were reproduced for all three tremors. But partial directed coherence of the spatially filtered (source) signals revealed a mainly unidirectional flow of information from the diencephalon to cortex in voluntary tremor, e.g. a thalamocortical relay, as opposed to a bidirectional subcortico-cortical flow in PD and ET promoting uncontrollable, e.g. thalamocortical, loop oscillations. Our results help to understand why pathological tremors although originating from the physiological motor network are not under voluntary control and they may contribute to the solution of the puzzle why high frequency thalamic stimulation has a selective effect on pathological tremor leaving voluntary movement performance almost unaltered.
  
• 17:37

  Combining atlas-based parcellation of regional brain data acquired across scanners at 1.5T and 3.0T field strengths

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Adolf Pfefferbaum, Torsten Rohlfing, Margaret J. Rosenbloom, Edith V. Sullivan
  
  Longitudinal brain morphometric studies designed for data acquisition at a single MRI field strength can be seriously limited by system replacements from lower to higher field strength. Merging data across field strengths has not been endorsed for a variety of reasons, yet the ability to combine such data would broaden longitudinal investigations. To determine whether structural T1-weighted MRI data acquired across MR field strengths could be merged, parcellations of archival SPGR data acquired in 114 individuals at 1.5 T and at 3.0 T within 3 weeks of each other were compared. The first set of analyses examined 1) the correspondence between regional tissue volumes derived from data collected at 1.5 T and 3.0 T and 2) whether there were systematic differences for which a correction factor could be determined and applied to improve measurement agreement. Comparability of regional volume determination at 1.5 T and 3.0 T was assessed with intraclass correlation (ICC) computed on volumes derived from the automated and unsupervised SRI24 atlas registration and parcellation method. A second set of analyses measured the reliability of the registration and quantification using the same approach on longitudinal data acquired in 69 healthy adults at a single field strength, 1.5 T, at an interval < 2 years. The mainstay of the analyses was based on the SRI24 method; to examine the potential of merging data across field strengths and across image analysis packages, a secondary set of analyses used FreeSurfer instead of the SRI24 method. For both methods, a regression-based linear correction function significantly improved correspondence. The results indicated high correspondence between most selected cortical, subcortical, and CSF-filled spaces; correspondence was lowest in the globus pallidus, a region rich in iron, which in turn has a considerable field-dependent effect on signal intensity. Thus, the application of a regression-based correction function that improved the correspondence in regional volume estimations argues well for the proposition that selected T1-weighted regional anatomical brain data can be reliably combined across 1.5 T and 3.0 T field strengths with the application of an appropriate correction procedure.
  
  Highlights► SPGR data acquired in 114 adults at 1.5T and 3T were registered, parcellated, and merged. ► Regression-based correction functions improved correspondence in volume estimations across field strengths. ► Selected regional SPGR data can be combined across field strengths and analysis packages with appropriate correction procedures.
  
  
• 17:37

  Evidence of a direct influence between the thalamus and hMT+ independent of V1 in the human brain as measured by fMRI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Anna Gaglianese, Mauro Costagli, Giulio Bernardi, Emiliano Ricciardi, Pietro Pietrini
  
  In the present study we employed Conditional Granger Causality (CGC) and Coherence analysis to investigate whether visual motion-related information reaches the human Middle Temporal complex (hMT +) directly from the Lateral Geniculate Nucleus (LGN) of the thalamus, by-passing the primary visual cortex (V1). Ten healthy human volunteers underwent brain scan examinations by functional magnetic resonance imaging (fMRI) during two optic flow experiments.In addition to the classical LGN-V1-hMT + pathway, our results showed a significant direct influence of the BOLD signal recorded in LGN over that in hMT+, not mediated by V1 activity, which strongly supports the existence of a bilateral pathway that connects LGN directly to hMT + and serves visual motion processing. Furthermore, we evaluated the relative latencies among areas functionally connected in the processing of visual motion. Using LGN as a reference region, hMT + exhibited a statistically significant earlier peak of activation as compared to V1.In conclusion, our findings suggest the co-existence of an alternative route that directly links LGN to hMT+, bypassing V1. This direct pathway may play a significant functional role for the faster detection of motion and may contribute to explain persistence of unconscious motion detection in individuals with severe destruction of primary visual cortex (blindsight).
  
  Highlights► The human middle temporal complex (hMT +) is devoted to motion perception ► We studied whether motion information reaches hMT + directly from the thalamus ► Conditional Granger Causality and Coherence during optic flow were measured by fMRI ► A significant direct influence of LGN on hMT+, independent of V1, was detected ► Shorter latencies suggest an earlier processing of motion in hMT + than in V1
  
  
• 17:37

  Corrigendum to “Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion” [NeuroImage 59 (3) (2012) 2142–2154]

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Jonathan D. Power, Kelly A. Barnes, Abraham Z. Snyder, Bradley L. Schlaggar, Steven E. Petersen
  
• 17:37

  Temporal scaling characteristics of diffusion as a new MRI contrast: Findings in rat hippocampus

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Evren Özarslan, Timothy M. Shepherd, Cheng Guan Koay, Stephen J. Blackband, Peter J. Basser
  
  Features of the diffusion-time dependence of the diffusion-weighted magnetic resonance imaging (MRI) signal provide a new contrast that could be altered by numerous biological processes and pathologies in tissue at microscopic length scales. An anomalous diffusion model, based on the theory of Brownian motion in fractal and disordered media, is used to characterize the temporal scaling (TS) characteristics of diffusion-related quantities, such as moments of the displacement and zero-displacement probabilities, in excised rat hippocampus specimens. To reduce the effect of noise in magnitude-valued MRI data, a novel numerical procedure was employed to yield accurate estimation of these quantities even when the signal falls below the noise floor. The power-law dependencies characterize the TS behavior in all regions of the rat hippocampus, providing unique information about its microscopic architecture. The relationship between the TS characteristics and diffusion anisotropy is investigated by examining the anisotropy of TS, and conversely, the TS of anisotropy. The findings suggest the robustness of the technique as well as the reproducibility of estimates. TS characteristics of the diffusion-weighted signals could be used as a new and useful marker of tissue microstructure.
  
  Highlights► Diffusion-time dependence of the diffusion MR signal leads to a novel contrast in neural tissue. ► Anomalous diffusion was observed via q-space MR experiments on excised rat hippocampi. ► We model the temporal scaling (TS) of the signal using fractal and disordered media concepts. ► We devised a computational framework to remove any bias due to Rician nature of the signal. ► The interplay between TS and diffusion anisotropy was investigated.
  
  
• January 27, 2012
• 15:17

  Serological Assays to Discriminate Rabbit Haemorrhagic Disease Virus from Australian Non-pathogenic Rabbit Calicivirus

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 25 January 2012
  
  June Liu, Peter J. Kerr, John D. Wright, Tanja Strive
  
  Serological cross reactivity between the virulent rabbit haemorrhagic disease virus (RHDV) and the closely related but non-pathogenic rabbit calicivirus (RCV) makes it difficult to study the epidemiology of each virus and the interaction between them when both viruses co-circulate in wild rabbit populations. ELISA methods for the diagnosis of RHDV infection are well characterized, but no specific serological tests for RCV have been developed. Following the characterization of Australian non-pathogenic RCV-A1 strains, we used virus-like-particles (VLPs) and anti-RCV-A1 specific antibodies to establish a set of isotype ELISAs for detection of IgG, IgA and IgM in rabbit sera and secretory mucosal IgA in rectal swabs, and two competition ELISAs. These assays were used to discriminate between anti-RCV-A1 and anti-RHDV antibodies in rabbits. The isotype ELISAs were highly sensitive for detection of anti-RCV-A1 antibodies, but varying levels of cross reactivity from anti-RHDV antibodies occurred in the isotype ELISAs and one competition ELISA. However, the second competition ELISA specifically detected antibodies to RCV-A1 and showed no cross reactivity to anti-RHDV sera. These ELISAs provide important tools to monitor RCV-A1 infection when it occurs alone, and to discriminate between RHDV and RCV-A1 infection when they occur in the same rabbit population. When used in parallel with RHDV serology, they could be used to monitor the dynamics of these two closely related but pathogenically distinct viruses in wild and domestic rabbit populations.
  
• 15:17

  Species and staphylococcal cassette chromosomemec(SCCmec) diversity among methicillin-resistant non-Staphylococcus aureusstaphylococci isolated from pigs

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 25 January 2012
  
  Wannes Vanderhaeghen, Stien Vandendriessche, Florence Crombé, Marc Dispas, Olivier Denis, ...
  
  While methicillin-resistantStaphylococcus aureus(MRSA) ST398 is known to be widespread in pig farms, few studies have investigated the species diversity and SCCmectypes of methicillin-resistant non-S. aureusstaphylococci (MRNAS) residing in the nose of pigs. We examined nasal swab samples of 200 pigs originating from 10 Belgian pig farms previously found positive for MRSA ST398. Suspected staphylococcal isolates were subjected to a 16S rRNA-mecA-nucPCR. Confirmed MRNAS were genotypically identified to the species level and investigated with a SCCmectyping PCR. MRNAS (n = 72) were detected on all 10 farms and were carried by 29.5% of the pigs. Seven MRNAS species were found:S. epidermidis(38.9%),S. sciuri(18.1%),S. pasteuri(18.1%),S. rostri(12.5%),S. warneri(8.3%),S. haemolyticus(2.7%) andS. hominis(1.4%). SCCmeccassettes were of type IVa (29.2%), type IVc (25%), type III (22.2%), type V (5.6%) or could not be assigned to any of the known types (NT types) (18.1%). Five distinct NT types were found. The predominance of methicillin-resistantS. epidermidis(MRSE) in our samples is remarkable, as MRSE is mainly associated with humans. The finding of three different SCCmecelements (IVa, V, NT type 1) in MRNAS that also prevail or predominate in MRSA ST398 shows that MRNAS might be an important SCCmecreservoir for MRSA in pigs. Yet, the occurrence of multiple other SCCmectypes illustrates that further studies are required to understand the presence and spread of SCCmecin methicillin-resistant staphylococci from animals.
  
• 15:17

  Vaccination with inactivated or live-attenuated chimeric PCV1-2 results in decreased viremia in challenge-exposed pigs and may reduce transmission of PCV2

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 25 January 2012
  
  M. Hemann, N.M. Beach, X.J. Meng, P.G. Halbur, T. Opriessnig
  
  The objectives were to determine transmissibility of PCV2 to naïve contact pigs 140 days after infection of resident pigs and the benefit of vaccination with live-attenuated or inactivated chimeric PCV2 vaccines on chronic PCV2 infection. Twelve 6-week old PCV2 naïve pigs were randomly divided into four groups of three pigs: negative controls, positive controls, and pigs vaccinated with either a live-attenuated or inactivated chimeric PCV1-2 vaccine. All animals were bled weekly and tested for anti-PCV2 antibodies and PCV2 and PCV1-2 DNA and all groups except negative controls were challenged at 10 weeks. Two pigs vaccinated with the live PCV2 vaccine were PCV1-2 viremic at a single observation point. Both vaccine regimens induced an anti-PCV2 antibody response which was detected sooner and reached a higher level with the commercial inactivated vaccine. Both vaccines significantly decreased the concentration and duration of PCV2 viremia compared to the positive controls. PCV2 DNA was detected in lymphoid tissues of 1/3 pigs in the live-attenuated vaccine group and 3/3 positive control pigs. Three, 2-week old, PCV2 naïve contact pigs were comingled with each group at 168 days post-vaccination or 140 days post-challenge. After seven days of co-housing, the resident pigs were removed and the contact pigs remained for six weeks. Evidence of chimeric PCV1-2 vaccine or PCV2 challenge virus transmission to naïve contact pigs was lacking in all groups. The results of this study suggest that 140-day closure of a small pig population in a controlled environment may result in stabilization and elimination of PCV2.
  
• 15:17

  Identification of porcine serum proteins modified in response to HP-PRRSV HuN4 infection by two-dimensional differential gel electrophoresis

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 25 January 2012
  
  Yongqian Yang, Tongqing An, Daqing Gong, Dengyun Li, Jinmei Peng, ...
  
  Since 2006, highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has become the major pathogen attributed to the prevalent porcine reproductive and respiratory syndrome (PRRS) in China. The present study aims to identify serum proteins modified in response to infection of HuN4, a HP-PRRSV strain isolated from a farm in 2006. 2-D DIGE analysis allowed for the detection of 19 differentially expressed protein spots, of which 18 were identified by MALDI-TOF/TOF MS. These 18 spots represented for a total of 9 proteins (6 up-regulated and 3 down-regulated), most of which belonged to the acute phase proteins in swine and showed a trend of regression in the late phase of the experiment. One of a series of AGP spots was identified for the first time to be decreased in acute phase of PRRSV infection in swine. But the whole level of the protein in the serum didn’t show significant changes by Western. The rising tendency of Hp was confirmed by Western blot and ELISA. These altered proteins were probably involved in the inflammatory process triggered by HuN4 and in alleviating the oxidative damage occurring in the process. In summary, these results may provide new insights into understanding the mechanisms of HP-PRRSV infection.
  
• 15:17

  Staphylococcus aureusproteins differentially recognized by the ovine immune response in mastitis or nasal carriage

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 24 January 2012
  
  Nubia Seyffert, Caroline Le Maréchal, Julien Jardin, John A. McCulloch, Fabio R. Rosado, ...
  
  Staphylococcus aureusis an opportunistic pathogen in dairy ruminants where it is found in healthy carriage and can be a major cause of mastitis. A better knowledge of the host-pathogen interactions is needed to tackle this serious animal health problem. This study aimed at identifyingS. aureusproteins differentially expressed byS. aureusin nasal colonization versus mastitis. Serological Proteome analysis (SERPA) was used to examine protein samples prepared from culture supernatants ofS. aureusstrains originally isolated from gangrenous mastitis and nasal carriage (O11) or subclinical mastitis (O46) and to compare patterns of immune-reactive proteins. These staphylococcal proteins were revealed by sera obtained from ewes suffering fromS. aureusmastitis and by sera obtained from healthy nulliparous ewes (i.e. no lactation and no mastitis or other symptoms) that were nasally colonized byS. aureus. Altogether 49 staphylococcal immune-reactive proteins were identified in this study. Patterns of proteins revealed by sera from infected- or healthy carrier- animals were comparable and analysis singled out one immune-reactive protein,N-acetylmuramyl-L-alanine amidase, which was recognized by each of the 6 sera from infected animals, when tested individually, and not by the sera of healthy carriers. This is the first study that compares theS. aureusseroproteome in colonization versus mastitis context in ruminants. These results open avenues for studies aiming at a better understanding of the balance between infection and commensal lifestyle in this opportunistic pathogen and at new prevention strategies.
  
• 15:08

  A comprehensive analysis of Delta signaling in pre-gastrular sea urchin embryos

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 27 January 2012
  
  Stefan C. Materna, Eric H. Davidson
  
  In sea urchin embryos Delta signaling specifies non-skeletogenic mesoderm (NSM). Despite the identification of some direct targets, several aspects of Delta Notch (D/N) signaling remain supported only by circumstantial evidence. To obtain a detailed and more complete image of Delta function we followed a systems biology approach and evaluated the effects of D/N perturbation on expression levels of 205 genes up to gastrulation. This gene set includes virtually all transcription factors that are expressed in a localized fashion by mid-gastrulation, and which thus provide spatial regulatory information to the embryo. Also included are signaling factors and some pigment cell differentiation genes. We show that the number of pregastrular D/N signaling targets among these regulatory genes is small and is almost exclusively restricted to non-skeletogenic mesoderm genes. However, Delta signaling also activatesfoxYin the small micromeres. As is the early NSM, the small micromeres are in direct contact with Delta expressing skeletogenic mesoderm. In contrast, no endoderm regulatory genes are activated by Delta signaling even during the second phase ofdeltaexpression, when this gene is transcribed in NSM cells adjacent to the endoderm. During this phase Delta provides an ongoing input which continues to activatefoxYexpression in small micromere progeny. Disruption of the second phase of Delta expression specifically abolishes specification of late mesodermal derivatives such as the coelomic pouches to which the small micromeres contribute.
  
  Highlights► Measured effects of Delta interference on specifically expressed regulatory genes. ► Early (skeletogenic) Delta activates only a small number of mesodermal genes. ► Early Delta activates a single regulatory gene in small micromeres. ► Interference with late (non-skeletogenic mesoderm) Delta affects no endoderm genes. ► Function of late Delta expression is specification of coelomic pouch cells.
  
  
• 15:08

  Single-mindedand the evolution of the ventral midline in arthropods

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 27 January 2012
  
  Viktoria Linne, Bo Joakim Eriksson, Angelika Stollewerk
  
  In insects and crustaceans, ventral midline cells are present that subdivide the CNS into bilateral symmetric halves. In both arthropod groups unpaired midline neurons and glial cells have been identified that contribute to the embryonic patterning mechanisms. In the fruitflyDrosophila melanogaster, for example, the midline cells are involved in neural cell fate specification along the dorso-ventral axis but also in axonal pathfinding and organisation of the axonal scaffold. Both in insects and malacostracan crustaceans, the bHLH-PAS transcription factorsingle-mindedis the master regulator of ventral midline development and homology has been suggested for individual midline precursors in these groups. The conserved arrangement of the axonal scaffold as well as the regular pattern of neural precursors in all euarthropod groups raises the question whether the ventral midline system is conserved in this phylum. In the remaining euarthropod groups, the chelicerates and myriapods, asingle-mindedhomologue has been identified in the spiderAchaearanea tepidariorum(chelicerate), however, the gene is not expressed in the ventral midline but in the median area of the ventral neuroectoderm. Here we show thatAt-simis not required for ventral midline development. Furthermore, we identifysimhomologues in representatives of arthropods that have not yet been analysed: the myriapodStrigamia maritimaand a representative of an outgroup to the euarthropods, the onychophoranEuperipatoides kanangrensis. We compare the expression patterns to theA. tepidariorum simhomologue expression and furthermore analyse the nature of the arthropod midline cells. Our data suggest that in arthropods unpaired midline precursors evolved from the bilateral median domain of the ventral neuroectoderm in the last common ancestor of Mandibulata (insects, crustaceans, myriapods). We hypothesize that simwas expressed in this domain and recruited to ventral midline development. Subsequently,simfunction has evolved in parallel to the evolution of midline cell function in the individual Mandibulata lineages.
  
  Highlights► Unpaired midline precursors are present in myriapods.► Simshows a conserved expression in ventral midline precursors in Mandibulata. ► Unpaired ventral midline precursors are absent in chelicerates and onychophorans.► Simis expressed in median neural cells in chelicerates and onychophorans.► Simis not required for ventral midline development in the spider.
  
  
• 15:08

  Neural crest induction at the neural plate border in vertebrates

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 24 January 2012
  
  Cécile Milet, Anne H. Monsoro-Burq
  
  The neural crest is a transient and multipotent cell population arising at the edge of the neural plate in vertebrates. Recent findings highlight that neural crest patterning is initiated during gastrulation, i.e. earlier than classically described, in a progenitor domain named the neural border. This chapter reviews the dynamic and complex molecular interactions underlying neural border formation and neural crest emergence.
  
  Highlights► Neural crest patterning is initiated during gastrulation in the neural border. ► Dynamic molecular interactions underlie neural border formation.
  
  
• January 25, 2012
• 19:47

  MRI hippocampal and entorhinal cortex mapping in predicting conversion to Alzheimer's disease

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  D.P. Devanand, Ravi Bansal, Jun Liu, Xuejun Hao, Gnanavalli Pradhaban, ...
  
  ObjectiveUsing MRI surface morphometry mapping, to evaluate local deformations of the hippocampus, parahippocampal gyrus, and entorhinal cortex in predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD).MethodsBaseline brain MRI with surface morphological analysis was performed in 130 outpatients with MCI, broadly defined, and 61 healthy controls followed for an average of 4 years in a single site study.ResultsPatients with MCI differed from controls in several regions of the hippocampus and entorhinal cortex, and to a lesser extent in the parahippocampal gyrus. In the MCI sample, Cox regression models were conducted for time to conversion comparing converters to AD (n = 31) and non-converters (n = 99), controlling for age, sex and education. Converters showed greater atrophy in the head of the hippocampus, predominantly in the CA1 region and subiculum, and in the entorhinal cortex, especially in the anterior-inferior pole bilaterally. When distances of specific points representing localized inward deformation were entered together with the corresponding hippocampal or entorhinal cortex volume in the same Cox regression model, the distances remained highly significant whereas the volumes of the corresponding structures were either marginally significant or not significant. Inclusion of cognitive or memory measures or apolipoprotein E ε4 genotype as covariates, or restricting the sample to patients with amnestic MCI (24 converters and 81 non-converters) did not materially change the findings. In the 3-year follow-up sample of patients with MCI, logistic regression analyses using the same measures and covariates yielded similar results.InterpretationThese findings indicate selective early involvement of the CA1 and subiculum regions of the hippocampus and provide new information on early anterior pole involvement in the entorhinal cortex in incipient AD. Fine-grained surface morphometry of medial temporal lobe structures may be superior to volumetric assessment in predicting conversion to AD in patients clinically diagnosed with MCI.
  
  Highlights► MRI surface mapping was used to evaluate conversion to Alzheimer's disease in MCI. ► MCI differed from controls in MRI sub-regions of hippocampus and entorhinal cortex. ► Converters to AD had greater atrophy in hippocampus CA1 region, subiculum. ► Converters to AD had greater anterior-inferior pole atrophy in entorhinal cortex. ► Localized inward deformation in the hippocampus and entorhinal cortex, respectively, retained significance but the corresponding volume lost significance when both measures were entered in the same survival model.
  
  
• 19:47

  Stretched, jumped, and fell: An fMRI investigation of reflexive verbs and other intransitives

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Einat Shetreet, Naama Friedmann
  
  This study used fMRI to inform a debate between two theories concerning the representation of reflexive verbs. Reflexives are verbs that denote an action that the subject applies on herself (e.g.,The woman stretched). These verbs are derived by a lexical operation that creates a reflexive from its transitive counterpart. Theories differ with respect to which thematic role is reduced by the lexical operation: the agent or the theme, and, consequently, whether the construction of sentences with reflexives in subject-verb order include movement of the object to the subject position. To test this, we compared reflexive verbs with unaccusative verbs (e.g.,The woman fell), and with unergative verbs (e.g.,The woman jumped). Unaccusatives are derived by reduction of the role of the agent, and thus SV sentences with unaccusatives include movement to subject position. Unergatives do not undergo lexical operations and do not involve movement in SV sentences. The reflexives behaved like unergatives, and differently from unaccusatives: the activation pattern of unaccusatives compared with reflexives showed similar cortical pattern to that of unaccusatives compared with unergatives, with activations in the left inferior frontal gyrus and the left middle temporal gyrus (MTG). Comparing reflexives and unergatives revealed activation in the right MTG. These results indicate that reflexives differ from unaccusatives in their derivation. That is, reflexives do not involve the reduction of the agent of the parallel transitive, and hence no syntactic movement is involved in sentences in which the subject precedes the reflexive verb.
  
  
  
  Highlights► Intransitive verbs include unergatives(jump) unaccusatives(fall) and reflexives(stretch) ► We explore whether reflexives are derived similarly to unaccusatives ► Brain activations for reflexives and unaccusatives indicate different derivations ► Unaccusatives activate lIFG, related to movement from object to subject position ► Reflexives activate rMTG, related to the identification of the theme with the agent
  
  
• 19:47

  Social status modulates neural activity in the mentalizing network

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Keely A. Muscatell, Sylvia A. Morelli, Emily B. Falk, Baldwin M. Way, Jennifer H. Pfeifer, ...
  
  The current research explored the neural mechanisms linking social status to perceptions of the social world. Two fMRI studies provide converging evidence that individuals lower in social status are more likely to engage neural circuitry often involved in ‘mentalizing’ or thinking about others’ thoughts and feelings. Study 1 found that college students’ perception of their social status in the university community was related to neural activity in the mentalizing network (e.g., DMPFC, MPFC, precuneus/PCC) while encoding social information, with lower social status predicting greater neural activity in this network. Study 2 demonstrated that socioeconomic status, an objective indicator of global standing, predicted adolescents’ neural activity during the processing of threatening faces, with individuals lower in social status displaying greater activity in the DMPFC, previously associated with mentalizing, and the amygdala, previously associated with emotion/salience processing. These studies demonstrate that social status is fundamentally and neurocognitively linked to how people process and navigate their social worlds.
  
• 19:47

  Linear Systems Analysis of the fMRI Signal

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Geoffrey M. Boynton, Stephen A. Engel, David J. Heeger
  
  In 1995 when we began our investigations of the human visual system using fMRI, little was known about the temporal properties of the fMRI signal. Before we felt comfortable making quantitative estimates of neuronal responses with this new technique, we decided to first conduct a basic study of how the time-course of the fMRI response varied with stimulus timing and strength. The results ended up showing strong evidence that to a first approximation the hemodynamic transformation was linear in time. This was both important and remarkable: important because nearly all fMRI data analysis techniques assume or require linearity, and remarkable because the physiological basis of the hemodynamic transformation is so complex that we still have a far from complete understanding of it. In this paper, we provide highlights of the results of our original paper supporting the linear transform hypothesis. A reanalysis of the original data provides some interesting new insights into the published results. We also provide a detailed appendix describing of the properties and predictions of a linear system in time in the context of the transformation between neuronal responses and the BOLD signal.
  
• 19:47

  BrainVoyager - Past, Present, Future

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Rainer Goebel
  
  BrainVoyager started as a simple fMRI analysis tool in the mid 1990s; the software was primarily created to fulfill the needs of its author and his colleagues to analyze anatomical and functional MRI data in a way that would be most appropriate for their research questions in visual and auditory perception. More specifically, the software was designed with three major goals in mind. First, it should allow analyses that would exploit optimally the high-resolution information available in fMRI data. Second, it should integrate volume-based analysis and cortex-based analysis including the possibility to visualize topographic activation data on flattened cortex representations. Third, it should combine hypothesis testing with data-driven analysis including interactive visualization tools that would make it as easy as possible to look at and explore data. A fourth guiding principle was to develop a software package that fulfilled the author's preference for elegant user interfaces, beautiful visualizations and high-performance computing. These major guiding principles from the beginning of BrainVoyager development are still noticeable in the most recent incarnations of the software that has grown from a small fMRI analysis tool on the Windows platform to a comprehensive cross-platform multi-modal software package integrating (real-time) fMRI, DWI/DTI, (i)EEG, MEG, TMS and fNIRS analysis.
  
• 19:47

  DTI Segmentation via the Combined Analysis of Connectivity Maps and Tensor Distances

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 25 January 2012
  
  Sebastiano Barbieri, Miriam H.A. Bauer, Jan Klein, Jan Moltz, Christopher Nimsky, ...
  
  We describe a novel approach to extract the neural tracts of interest from a diffusion tensor image (DTI). Compared to standard streamline tractography, existing probabilistic methods are able to capture fiber paths that deviate from the main tensor diffusion directions. At the same time, tensor clustering methods are able to more precisely delimit the border of the bundle. To the best of our knowledge, we propose the first algorithm which combines the advantages supplied by probabilistic and tensor clustering approaches. The algorithm includes a post-processing step to limit partial-volume related segmentation errors. We extensively test the accuracy of our algorithm on different configurations of a DTI software phantom for which we systematically vary the image noise, the number of gradients, the geometry of the fiber paths and the angle between adjacent and crossing fiber bundles. The reproducibility of the algorithm is supported by the segmentation of the corticospinal tract of nine patients. Additional segmentations of the corticospinal tract, the arcuate fasciculus, and the optic radiations are in accordance with anatomical knowledge. The required user interaction is comparable to that of streamline tractography, which allows for an uncomplicated integration of the algorithm into the clinical routine.
  
• 19:47

  BOLD fMRI Investigation of the Rat Auditory Pathway and Tonotopic Organization

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  Matthew M. Cheung, Condon Lau, Iris Y. Zhou, Kevin C. Chan, Joe S. Cheng, ...
  
  Rodents share general anatomical, physiological and behavioral features in the central auditory system with humans. In this study, monaural broadband noise and pure tone sounds are presented to normal rats and the resulting hemodynamic responses are measured with blood oxygenation level-dependent (BOLD) fMRI using a standard spin-echo echo planar imaging sequence (without sparse temporal sampling). The cochlear nucleus (CN), superior olivary complex, lateral lemniscus, inferior colliculus (IC), medial geniculate body and primary auditory cortex, all major auditory structures, are activated by broadband stimulation. The CN and IC BOLD signal changes increase monotonically with sound pressure level. Pure tone stimulation with three distinct frequencies (7, 20 and 40 kHz) reveals the tonotopic organization of the IC. The activated regions shift from dorsolateral to ventromedial IC with increasing frequency. These results agree with electrophysiology and immunohistochemistry findings, indicating the feasibility of auditory fMRI in rats. This is the first fMRI study of the rodent ascending auditory pathway.
  
  Highlights► fMRI without sparse temporal sampling is used to study the rat auditory system ► Monaural acoustic stimulation activates multiple cortical and subcortical structures ► IC and CN BOLD signal changes increase monotonically with SPL ► In vivo tonotopic mapping using BOLD is demonstrated in inferior colliculus
  
  
• 19:47

  Predicting the development of mild cognitive impairment: A new use of pattern recognition

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  Yue Cui, Perminder S. Sachdev, Darren M. Lipnicki, Jesse S. Jin, Suhuai Luo, ...
  
  While the conversion from mild cognitive impairment to Alzheimer's disease has received much recent attention, the transition from normal cognition to mild cognitive impairment is largely unexplored. The present pattern recognition study addressed this by using neuropsychological test scores and neuroimaging morphological measures to predict the later development of mild cognitive impairment in cognitively normal community-dwelling individuals aged 70 − 90 years. A feature selection algorithm chose a subset of neuropsychological and FreeSurfer-derived morphometric features that optimally differentiated between individuals who developed mild cognitive impairment and individuals who remained cognitively normal. Support vector machines were used to train classifiers and test prediction performance, which was evaluated via 10-fold cross-validation to reduce variability. Prediction performance was greater when using a combination of neuropsychological scores and morphological measures than when using either of these alone. Results for the combined method were: accuracy 78.51%, sensitivity 73.33%, specificity 79.75%, and an area under the receiver operating characteristic curve of 0.841. Of all the features investigated, memory performance and measures of the prefrontal cortex and parietal lobe were the most discriminative. Our prediction method offers the potential to detect elderly individuals with apparently normal cognition at risk of imminent cognitive decline. Identification at this stage will facilitate the early start of interventions designed to prevent or slow the development of Alzheimer's disease and other dementias.
  
• 19:47

  A general Bayesian treatment for MEG source reconstruction incorporating lead field uncertainty

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  J.D. López, W.D. Penny, J.J. Espinosa, G.R. Barnes
  
  There is uncertainty introduced when a cortical surface based model derived from an anatomical MRI is used to reconstruct neural activity with MEG data. This is a specific case of a problem with uncertainty in parameters on which EEG lead fields depend non-linearly. Here we present a general mathematical treatment of any such problem with a particular focus on co-registration. We use a Metropolis search followed by Bayesian Model Averaging over multiple sparse prior source inversions with different headlocation/orientation parameters. Based on MEG alone we can locate the cortex to within 4 mm at empirically realistic signal to noise ratios. We also show that this process gives improved posterior distributions on the estimated current distributions, and can be extended to make inference on the locations of local maxima by providing confidence intervals for each source.
  
  Highlights► We show how to account for lead field uncertainty in the MEG inverse problem ► Co-registration errors propagate through to the final current density estimate ► It is possible to recover the location of the head based on MEG data alone
  
  
• 19:47

  Exploring Resting-State Functional Connectivity with Total Interdependence

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  Xiaotong Wen, Jue Mo, Mingzhou Ding
  
  Resting-state fMRI has become a powerful tool for studying network mechanisms of normal brain functioning and its impairments by neurological and psychiatric disorders. Analytically, independent component analysis and seed-based cross correlation are the main methods for assessing the connectivity of resting-state fMRI time series. A feature common to both methods is that they exploit the covariation structures of contemporaneously (zero-lag) measured data but ignore temporal relations that extend beyond the zero-lag. To examine whether data covariations across different lags can contribute to our understanding of functional brain networks, a measure that can uncover the overall temporal relationship between two resting-state BOLD signals is needed. In this paper we propose such a measure referred as total interdependence (TI). Comparing TI with zero-lag cross correlation (CC) we report three results. First, when combined with a random permutation procedure, TI can reveal the amount of temporal relationship between two resting-state BOLD time series that is not captured by CC. Second, comparing resting-state data with task-state data recorded in the same scanning session, we demonstrate that the resting-state functional networks constructed with TI match more precisely the networks activated by the task. Third, TI is shown to be more statistically sensitive than CC and provides better feature vectors for network clustering analysis.
  
  Highlights► New measure called total interdependence (TI) is introduced to analyze resting-state connectivity. ► TI captures overall temporal relationship between BOLD signals. ► The amount of temporal relationship not captured by CC was revealed. ► TI networks match more precisely the functional networks established by task activation. ► TI is more statistically sensitive than CC in disassociating functional networks.
  
  
• 19:47

  Cortical processing of degraded speech sounds: Effects of distortion type and continuity

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  Ismo Miettinen, Paavo Alku, Santeri Yrttiaho, Patrick J.C. May, Hannu Tiitinen
  
  Human speech perception is highly resilient to acoustic distortions. In addition to distortions from external sound sources, degradation of the acoustic structure of the sound itself can substantially reduce the intelligibility of speech. The degradation of the internal structure of speech happens, for example, when the digital representation of the signal is impoverished by reducing its amplitude resolution. Further, the perception of speech is also influenced by whether the distortion is transient, coinciding with speech, or is heard continuously in the background. However, the complex effects of the acoustic structure and continuity of the distortion on the cortical processing of degraded speech are unclear. In the present magnetoencephalography study, we investigated how the cortical processing of degraded speech sounds as measured through the auditory N1m response is affected by variation of both the distortion type (internal, external) and the continuity of distortion (transient, continuous). We found that when the distortion was continuous, the N1m was significantly delayed, regardless of the type of distortion. The N1m amplitude, in turn, was affected only when speech sounds were degraded with transient internal distortion, which resulted in larger response amplitudes. The results suggest that external and internal distortions of speech result in divergent patterns of activity in the auditory cortex, and that the effects are modulated by the temporal continuity of the distortion.
  
• January 24, 2012
• 18:10

  The Enteric Nervous System

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 24 January 2012
  
  Valentina Sasselli, Vassilis Pachnis, Alan J. Burns
  
  The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, consists of numerous types of neurons, and glial cells, that are distributed in two intramuscular plexuses that extend along the entire length of the gut and control co-ordinated smooth muscle contractile activity and other gut functions. All enteric neurons and glia are derived from neural crest cells (NCC). Vagal (hindbrain) level NCC provide the majority of enteric precursors along the entire length of the gut, while a lesser contribution, that is restricted to the hindgut, arises from the sacral region of the neuraxis. After leaving the dorsal neural tube NCC undergo extensive migration, proliferation, survival and differentiation in order to form a functional ENS. This article reviews the molecular mechanisms underlying these key developmental processes and highlights the major groups of molecules that affect enteric NCC proliferation and survival (Ret/Gdnf and EdnrB/Et-3 pathways, Sox10 and Phox2b transcription factors), cell migration (Ret and EdnrB signalling, semaphorin 3A, cell adhesion molecules, Rho GTPases), and the development of enteric neuronal subtypes and morphologies (Mash1, Gdnf/neurturin, BMPs, Hand2, retinoic acid). Finally, looking to the future, we discuss the need to translate the wealth of data gleaned from animal studies to the clinical area and thus better understand, and develop treatments for, congenital human diseases affecting the ENS.
  
  Highlights► The enteric nervous system is entirely derived from neural crest cells. ► The molecular mechanisms underlying enteric neural crest cell development are reviewed. ► Key processes include cell migration, proliferation, survival, differentiation, and axon guidance.
  
  
• 18:10

  A Protein Kinase A and Wnt-dependent network regulating an intermediate stage in epithelial tubulogenesis during kidney development

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 24 January 2012
  
  Thomas F. Gallegos, Valentina Kouznetsova, Krystyna Kudlicka, Derina E. Sweeney, Kevin T. Bush, ...
  
  Genetic interactions regulating intermediate stages of tubulogenesis in the developing kidney have been difficult to define. A systems biology strategy using microarray was combined with in vitro/ex vivo and genetic approaches to identify pathways regulating specific stages of tubulogenesis. Analysis of the progression of the metanephric mesenchyme (MM) through four stages of tubule induction and differentiation (i.e., epithelialization, tubular organization and elongation and early differentiation) revealed signaling pathways potentially involved at each stage and suggested key roles for a number of signaling molecules. A screen of the signaling pathways on in vitro/ex vivo nephron formation implicated a unique regulatory role for Protein Kinase A (PKA), through PKA-2, in a specific post-epithelialization morphogenetic step (conversion of the renal vesicle to the S-shaped body). Microarray analysis not only confirmed this stage-specificity, but also highlighted upregulation of Wnt genes. Addition of PKA agonists to LIF-induced nephrons (previously shown to be a Wnt/beta-catenin dependent pathway) disrupted normal tubulogenesis in a manner similar to PKA-agonist treated MM/spinal-cord assays, suggesting PKA regulates a Wnt-dependent tubulogenesis step. PKA induction of canonical Wnt signaling during tubulogenesis was confirmed genetically using MM from Batgal-reporter mice. Addition of a Wnt synthesis inhibitor to activated PKA cultures rescued tubulogenesis. By re-analysis of existing microarray data from the FGF8, Lim1 and Wnt4 knockouts, which arrest in early tubulogenesis, a network of genes regulating the transition of nascent epithelial cells to tubular epithelium was derived, helping to reconcile in vivo and in vitro/ex vivo data.
  
  Highlights► PKA activity prohibits tubulogenesis during nephrogenesis. ► Inhibition from PKA is due to signaling from Wnts. ► A network of tubulogenesis genes was built with profiles of similar null mutants.
  
  
• 16:39

  Distinct neural networks underlie encoding of categorical versus coordinate spatial relations during active navigation

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  Oliver Baumann, Edgar Chan, Jason B. Mattingley
  
  It has been proposed that spatial relations are encoded eithercategorically, such that the relative positions of objects are defined in prepositional terms; or in terms of visualcoordinates, such that the precise distances between objects are represented. In humans, it has been assumed that a left hemisphere neural network subserves categorical representations, and that coordinate representations are right lateralised. However, evidence in support of this distinction has been garnered exclusively from tasks that involved static, two-dimensional (2D) arrays. We used functional magnetic resonance imaging (fMRI) to identify neural circuits underlying categorical and coordinate representations during active spatial navigation. Activity in the categorical condition was significantly greater in the parietal cortex, whereas the coordinate condition revealed greater activity in medial temporal cortex and dorsal striatum. In addition, activity in the categorical condition was greater in parietal cortex within the left hemisphere than within the right. Our findings are consistent with analogous studies in rodents, and support the suggestion of distinct neural circuits underlying categorical and coordinate representations during active spatial navigation. The findings also support the claim of a left hemispheric preponderance for the processing of categorical spatial relations.
  
• 16:39

  Abnormal cortical processing of pattern motion in amblyopia: Evidence from fMRI

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  B. Thompson, M.Y. Villeneuve, C. Casanova, R.F. Hess
  
  Converging evidence from human psychophysics and animal neurophysiology indicates that amblyopia is associated with abnormal function of area MT, a motion sensitive region of the extrastriate visual cortex. In this context, the recent finding that amblyopic eyes mediate normal perception of dynamic plaid stimuli was surprising, as neural processing and perception of plaids has been closely linked to MT function. One intriguing potential explanation for this discrepancy is that the amblyopic eye recruits alternative visual brain areas to support plaid perception. This is the hypothesis that we tested. We used functional magnetic resonance imaging (fMRI) to measure the response of the amblyopic visual cortex and thalamus to incoherent and coherent motion of plaid stimuli that were perceived normally by the amblyopic eye. We found a different pattern of responses within the visual cortex when plaids were viewed by amblyopic as opposed to non-amblyopic eyes. The non-amblyopic eyes of amblyopes and control eyes differentially activated the hMT + complex when viewing incoherent vs. coherent plaid motion, consistent with the notion that this region is centrally involved in plaid perception. However, for amblyopic eye viewing, hMT + activation did not vary reliably with motion type. In a sub-set of our participants with amblyopia we were able to localize MT and MST within the larger hMT + complex and found a lack of plaid motion selectivity in both sub-regions. The response of the pulvinar and ventral V3 to plaid stimuli also differed under amblyopic vs. non-amblyopic eye viewing conditions, however the response of these areas did vary according to motion type. These results indicate that while the perception of the plaid stimuli was constant for both amblyopic and non-amblyopic viewing, the network of neural areas that supported this perception was different.
  
• 16:39

  Resting State fMRI: A Personal History

   » ‎ Developmental Biology
  Publication year: 2012
  Source: NeuroImage, Available online 24 January 2012
  
  Bharat B. Biswal
  
  The goal of this review is to describe, from a personal perspective, the development and emergence of the resting state fMRI. In particular, various concepts derived from the resting state data are discussed in detail, including connectivity, amplitude of the fluctuations, analysis techniques, and use in clinical populations. We also briefly summarize our efforts in creating an open data sharing platform as well as both a journal and a conference dedicated to brain connectivity. All three projects are aimed at significantly increasing the impact of resting state fMRI developments and enabling large, collaborative science projects.
  
  Highlights► The development and emergence of the resting state fMRI is presented. ► Various concepts derived from resting state fMRI is discussed. ► We summarize our efforts in creating an open data sharing platform. ► Formation of a journal and a conference dedicated to brain connectivity is discussed.
  
  
• January 21, 2012
• 19:44

  Cdx Function is Required for Maintenance of Intestinal Identity in the Adult

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 21 January 2012
  
  Alexa Hryniuk, Stephanie Grainger, Joanne G.A. Savory, David Lohnes
  
  The homeodomain transcription factors Cdx1 and Cdx2 are expressed in the intestinal epithelium from early development, with expression persisting throughout the life of the animal. While our understanding of the function of Cdx members in intestinal development has advanced significantly, their roles in the adult intestine is relatively poorly understood. In the present study, we found that ablation ofCdx2in the adult small intestine severely impacted villus morphology, proliferation and intestinal gene expression patterns, resulting in the demise of the animal. Long-term loss ofCdx2in a chimeric model resulted in loss of all differentiated intestinal cell types and partial conversion of the mucosa to a gastric-like epithelium. Concomitant loss of Cdx1 did not exacerbate any of these phenotypes. Loss ofCdx2in the colon was associated with a shift to a caecum-like epithelial morphology which was more pronounced with subsequent loss ofCdx1. These findings suggest that Cdx2 is essential for differentiation of the small intestinal epithelium, and that both Cdx1 and Cdx2 contribute to homeostasis of the colon.
  
  Highlights► Cdx2 is critical for differentiation ofallcell types of the adult small intestine ► In the absence of Cdx2, Cdx1 cannot support homeostasis of the small intestine ► The finding of a role for Cdx1 with Cdx2 in patterning of the colon epithelium
  
  
• 19:44

  Roles of N-glycosylation and lipidation in Wg secretion and signaling

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 21 January 2012
  
  Xiaofang Tang, Yihui Wu, Tatyana Y. Belenkaya, Qinzhu Huang, Lorraine Ray, ...
  
  Wnt members act as morphogens essential for embryonic patterning and adult homeostasis. Currently, it is still unclear how Wnt secretion and its gradient formation are regulated. In this study, we examined the roles of N-glycosylation and lipidation/acylation in regulating the activities of Wingless (Wg), the mainDrosophilaWnt member. We show that Wg mutant devoid of all the N-glycosylations exhibits no major defects in either secretion or signaling, indicating that N-glycosylation is dispensable for Wg activities. We demonstrate that lipid modifications at Serine 239 (S239) rather than that at Cysteine 93 (C93) plays a more important role in regulating Wg signaling in multiple developmental contexts. Wg S239 mutant exhibits a reduced ability to bind its receptor,DrosophilaFrizzled 2 (dFz2), suggesting that S239 is involved in the formation of a Wg/receptor complex. Importantly, while single Wg C93 or Wg S239 mutants can be secreted, removal of both acyl groups at C93 and S239 renders Wg incapable of reaching the plasma membrane for secretion. These data argue that lipid modifications at C93 and S239 play major roles in Wg secretion. Further experiments demonstrate that two acyl attachment sites in the Wg protein are required for the interaction of Wg with Wntless (Wls, also known as Evi or Srt), the key cargo protein involved in Wg secretion. Together, our data demonstrate thein vivoroles of N-glycosylation and lipid modification in Wg secretion and signaling.
  
  Highlights► The roles of lipidation and N-glycosylatioin on Wg signaling and secretion are examined. ► N-glycosylation of Wg at Asparagine 103 (N103) and Asparagine 414 (N414) is dispensable for its signaling and secretion. ► Lipidation at Serine 239, but not at Cysteine 93, is absolutely required for Wg signaling possibly via contributing to Wg-Frizzled 2 interaction. ► Wg secretion is impaired when both acylation sites are mutated. Two acylation sites are required for Wg to interact with the carrier protein Wntless.
  
  
• 19:44

  An essential and highly conserved role for Zic3 in left-right patterning, gastrulation and convergent extension morphogenesis

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 21 January 2012
  
  Ashley E. Cast, Chunlei Gao, Jeffrey D. Amack, Stephanie M. Ware
  
  Mutations in ZIC3 result in X-linked heterotaxy in humans, a syndrome consisting of left-right (L-R) patterning defects, midline abnormalities, and cardiac malformations. Similarly, loss of function of Zic3 in mouse results in abnormal L-R patterning and cardiac development. However,Zic3null mice also exhibit defects in gastrulation, neural tube closure, and axial patterning, suggesting the hypothesis that Zic3 is necessary for proper convergent extension (C-E) morphogenesis. To further investigate the role of Zic3 in early embryonic development, we utilized two model systems,Xenopus laevisand zebrafish, and performed loss of function analysis using antisense morpholino-mediated gene knockdown. BothXenopusand zebrafish demonstrated significant impairment of C-E in Zic3 morphants. L-R patterning was also disrupted, indicating that the role of Zic3 in L-R axis development is conserved across species. Correlation of L-R patterning and C-E defects inXenopussuggests early C-E defects may underlie L-R patterning defects at later stages, since Zic3 morphants with moderate to severe C-E defects exhibited an increase in laterality defects. Taken together, these results demonstrate a functional conservation of Zic3 in L-R patterning and uncover a previously unrecognized role for Zic3 in C-E morphogenesis during early vertebrate development.
  
  Highlights► Zebrafish and Xenopus can be used to study human X-linked heterotaxy ► We identify a novel role for Zic3 in convergent-extension morphogenesis ► Early convergent-extension defects may underlie laterality defects at later stages
  
  
• January 20, 2012
• 16:38

  Editorial Board

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Volume 362, Issue 2, 15 February 2012, Pages IFC
  
  [No author name available]
  
• 16:38

  Corrigendum to “Pax2/8 proteins coordinate sequential induction of otic and epibranchial placodes through differential regulation offoxi1,sox3andfgf24” [Dev. Biol. 351 (2011) 90–98]

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Developmental Biology, Available online 20 January 2012
  
  Mahesh S. Padanad, Bruce B. Riley
  
• January 18, 2012
• 20:29

  ANTIMICROBIALS IN BEEKEEPING

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 18 January 2012
  
  Wim Reybroeck, Els Daeseleire, Hubert F. De Brabander, Lieve Herman
  
  The bee diseases American and European foulbrood and nosemosis can be treated with anti-infectious agents. However, in the EU and the USA the use of these agents in beekeeping is strictly regulated due to the lack of tolerance (e.g. Maximum Residue Limit) for residues of antibiotics and chemotherapeutics in honey.This article reviews the literature dealing with antimicrobials of interest in apiculture, stability of these antimicrobials in honey, and disposition of the antimicrobials in honeybee hives.
  
• 20:29

  Identification and molecular characterization of a novel flavivirus isolated from Pekin ducklings in China

   » ‎ Developmental Biology
  Publication year: 2012
  Source: Veterinary Microbiology, Available online 18 January 2012
  
  Yun Tao, Weicheng Ye, Zheng Ni, Dabing Zhang, Cun Zhang
  
  A flavivirus-associated disease of egg-laying ducks was observed in eastern China in 2010, and a novel mosquito-borne flavivirus, Tembusu virus (TMUV), was isolated (Cao et al., 2011). Following up on the earlier study, a virus similar to TMUV was isolated recently from ducklings and characterized. We report that 1) the recently isolated virus, TMUV ZJ-6, replicated in vertebrate cells (DF-1, BHK-21) as well as in mosquito cells (C6/36) and caused cytopathic effect (CPE) in the cell lines tested; 2) extracellular viral particles examined by electron microscopy were approximately 45 nm in diameter and enveloped; 3) the full-length genome of the virus was determined, showing that the TMUV ZJ-6 is more closely related to the Ntaya group of viruses than other members of theFlaviviridaebased on the data of phylogenetic analyses. Most importantly, the disease of ducklings was reproducible after administration of plaque-purified virus by intracerebral (i.c), subcutaneous (s.c) or intranasal (i.n) inoculation. This is the first report that TMUV infects not only egg-laying ducks but also 3-21 days-old ducklings. The findings extend our understanding of how the virus spreads and causes disease.