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17:21
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Developmental Biology
Publication year: 2012
Source: Cell Stem Cell, Volume 10, Issue 2, 3 February 2012, Pages ix
[No author name available]
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17:21
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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.
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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.
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17:21
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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.
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17:21
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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.
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17:21
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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.
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17:21
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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.
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17:21
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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.
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17:21
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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.
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17:21
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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.
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17:21
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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.
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17:21
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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
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17:21
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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
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17:21
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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
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17:21
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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
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17:21
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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
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17:21
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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
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17:01
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Lancet
Leading influenza researchers have agreed to a voluntary 60-day pause on controversial research involving mutant H5N1 virus strains that are transmissible in mammals. In an announcement on Jan 20, the scientists said the hiatus will allow time for governments, organisations, and the scientific community to discuss potential safety concerns.
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17:01
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Lancet
This week we publish surprising and, on the face of it, disturbing findings. According to Christopher Murray and colleagues at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle, there were 1·24 million deaths (95% uncertainty interval 0·93–1·69 million) from malaria worldwide in 2010—around twice the figure of 655 000 estimated by WHO for the same year. How should the malaria community interpret this finding? Before we answer that question, we need to look beneath the surface of this striking overall mortality figure.
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17:01
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Lancet
An independent advisory group has urged the UK Government to integrate genomic medicine into the National Health Service (NHS). The Human Genomics Strategy Group (HGSG), established in 2010 after a House of Lords inquiry into genomic medicine, set out their recommendations in a report published on Jan 25. First, the group proposed that the government outline a policy for expansion of genomic technology in the NHS; HGSG emphasised that commissioning of cost-effectiveness studies will be a necessary step.
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17:01
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Lancet
In July, 2011, the UK's medical regulator, the General Medical Council (GMC), was told by the Commons Health Select Committee to send a “clear signal” to doctors that they were failing in their duties if they did not report concerns about patients' safety. That signal has now come in Raising and acting on concerns about patient safety—new GMC guidance published on Jan 26, which advises doctors about the best ways to alert employers and health-care regulators about poor quality care.
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17:01
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Lancet
The National Health Service (NHS) in England has been a leading international model of tax-financed, universal health care. Legal analysis shows that the Health and Social Care Bill currently making its way through the UK Parliament would abolish that model and pave the way for the introduction of a US-style health system by eroding entitlement to equality of health-care provision. The Bill severs the duty of the Secretary of State for Health to secure comprehensive health care throughout England and introduces competitive markets and structures consistent with greater inequality of provision, mixed funding, and widespread provision by private health corporations.
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17:01
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Lancet
In The Lancet, the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) report meta-analyses of outcomes in 100 000 women with early breast cancer in more than 100 trials of adjuvant chemotherapy, which include the first EBCTCG meta-analyses of adjuvant taxane treatment. This study comes 35 years after the first report of the benefit of adjuvant chemotherapy, and is the 16th publication in the group's 28-year history of bringing together individual patient data from all randomised trials worldwide.
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17:01
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Lancet
The nature, scale, and interactions of behavioural disorders after neonatal and perinatal insults, including preterm birth and infectious diseases, are not well understood. In The Lancet, Michael Mwaniki and colleagues present a broad systematic review of the type and probability of development of a range of neurodevelopmental sequelae, in which they have included 153 research studies and 22 161 liveborn children. The authors report a very high overall prevalence of at least one deficit in any domain (median risk 39·4%, IQR 20·0–54·8%).
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Lancet
“The rapid advances in cardiology during the first half of the 20th century may be fairly ascribed to the introduction of new techniques.”Paul Wood, 1951
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17:01
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Lancet
Antisocial behaviour in adolescence can be associated with ill health in the form of self-harm, drug abuse, and mental disorders, and may presage criminal activity later in life. This is a worldwide problem with far-reaching social and economic implications, for individuals as well as for society as a whole.
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17:01
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Lancet
Seen on a plate somewhere in Italy. Brains. Quite a delicacy. Not a chance.
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17:01
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Lancet
Scientific papers on chronic fatigue syndrome (CFS) often evoke much debate and emotional reaction, as exemplified by the recent discussions in The Lancet on the PACE trial. Also, the potential role of a retrovirus in CFS kindled a fierce controversy which has recently culminated. In 2009, in Science, Lombardi and colleagues described the occurrence of the xenotropic murine leukaemia virus (MLV)-related virus (XMRV), a gammaretrovirus, in white blood cells in 67% of patients with CFS and in 3·7% of healthy controls.
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17:01
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Lancet
Harm-reduction programmes are remarkably successful in controlling HIV in injecting drug users worldwide, but more effort is needed to prevent even more HIV infections in this group. Recent reviews individual behavioural approaches, and medical treatment and care. Still, little is known about evidence-based educational intervention effects of harm-reduction programmes for injecting drug users.
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17:01
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Lancet
Ethical violations in clinical trials in India have exposed gaping holes in the country's regulatory system, which has struggled to oversee the booming industry. Amy Yee reports from New Delhi.
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17:01
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Lancet
New NICE guidelines on epilepsies have come under fire by several experts who say that they do not reflect clinical experience and focus too much on drug cost effectiveness. David Holmes reports.
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17:01
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Lancet
Portugal's debt crisis is forcing hospital closures and hasty reform of the National Health Service, causing some observers to raise concerns about patient care. Gonçalo Figueiredo Augusto reports.
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17:01
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Lancet
Arriving at Washington DC's Reagan National airport last year, I, like other visitors, was greeted with large signs featuring the Statue of Liberty and the words: “Welcome to America, home to 5% of the world's people and 25% of the world's prisoners.” The posters were produced by the National Association for the Advancement of Colored People (NAACP) to help publicise their “Misplaced Priority: Over Incarcerate, Under Educate” campaign.
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Lancet
[Perspectives] The sound of silence
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Lancet
[Perspectives] Joseph Lau: mastering the meta-analysis
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17:01
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Lancet
The place that for many years served London's Middlesex Hospital as its Outpatient Department is not a beautiful building. Yet it's the oldest element of that great London hospital still standing on Cleveland Street, diagonally across from the vast field the institution used to fill, now sadly strewn with dust and broken bricks. This building has recently been the subject of a very public tussle: the owner intent on its replacement by a huge apartment block; locals and others (myself among them) equally determined to preserve it.
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17:01
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Lancet
[Obituary] Thomas E Bryant
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17:01
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Lancet
Robert Greenberg and colleagues (Aug 6, p 507) are to be commended for doing a mass screening and treatment trial for Helicobacter pylori in the general population of Latin America. There is evidence to suggest that population screening and treatment can reduce the incidence of gastric cancer and lessen the economic burden from dyspepsia. However, we are not sure that Greenberg and colleagues' conclusion that 14-day triple therapy is preferable to 5-day concomitant therapy in this setting is warranted.
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17:01
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Lancet
Robert Greenberg and colleagues found that, in seven Latin American sites, the probability of Helicobacter pylori eradication with triple therapy lasting 14 days (TT-14) was 82·2%, which was 8·6% higher than with concomitant therapy lasting 5 days (CT-5) and 5·6% higher than with sequential therapy (ST). However, these data deserve further analysis.
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17:01
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Lancet
In their multisite study, Robert Greenberg and colleagues attempted to identify a reliably effective treatment for Helicobacter pylori for use in Latin America. Each study site used locally available drugs and the regimens all contained clarithromycin or clarithromycin–metronidazole, despite the unacceptably low success of triple therapies elsewhere and a high expected prevalence of metronidazole resistance. The success of treatments for infectious diseases is mainly related to the absence of antimicrobial resistance and is predictable if one knows the pattern of resistance and the effect of resistance on the regimens tested.
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17:01
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Lancet
Claire Slater and Alexander Ford note that all three treatments compared in our trial achieved eradication probabilities similar to those reported from previous community-based programmes of Helicobacter pylori screening and treatment and that the less-expensive concomitant regimen might be preferable to the more effective, but more costly, triple therapy regimen in a low-resource environment. We agree with both of these points and said as much in our report. The purchase price of the three regimens varied widely between the seven study sites, with a range of US$12–120 for 14-day triple therapy, $7–56 for 10-day sequential therapy, and $6–44 for 5-day concomitant therapy.
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17:01
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Lancet
Sania Nishtar and Ahmed Mehboob (Aug 20, p 648) make a convincing case for retaining a federal institution to take care of national responsibilities in health in Pakistan. Despite the technical appeal of alternative options, the most striking feature of this debate is the low level of response from stakeholders to the threatened abolition of the Ministry of Health, compared with the vigorous backlash against the proposed devolution of the Higher Education Commission.
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Lancet
Sania Nishtar and Ahmed Mehboob's discussion of the abolition of the Health Ministry in Pakistan raises the question of whether the health care problems in Pakistan could be solved by such a move.
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Lancet
Pakistan lags far behind in meeting the Millennium Development Goals. Neonatal mortality is responsible for 57% of all deaths in children younger than 5 years in the country, and Pakistan has the highest neonatal mortality rate in the region. The under-5 mortality rate has decreased by 24% since 1990. However, both rates have remained more or less static in the poorest income quintile. With the devolution of the Ministry of Health last year, Pakistan faces the challenge of developing the much needed provincial infrastructure that would integrate the comprehensive efforts of various stakeholders in promoting better health outcomes.
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17:01
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Lancet
The International Food & Beverage Alliance (IFBA) includes ten global food and non-alcoholic beverage manufacturers (Coca-Cola Company, Ferrero, General Mills, Grupo Bimbo, Kellogg's, Kraft Foods, Mars, Nestlé, PepsiCo, and Unilever). Although we cannot speak for the entire food and non-alcoholic beverage industry, nor any other industry, our member companies support initiatives to address the global non-communicable disease (NCD) problem and commend the UN for bringing global attention to this issue, particularly in developing countries.
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Lancet
In 2006, the Integrated Academic Training programme was initiated in the UK as a result of the Walport report on the crisis of decreasing clinical academic numbers. In Oxford, we decided that the most effective way to manage the programme would be to create a dedicated Oxford University Clinical Academic Graduate School ( OUCAGS). We wish to highlight both some advantages of this approach and challenges within the overall programme.
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17:01
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Lancet
Dengue fever is a mosquito-borne disease caused by dengue viruses—members of the family Flaviviridae. Severe forms of dengue infection can be fatal and are a leading cause of hospital admission in many parts of the world, placing tremendous pressure on medical resources and having a heavy economic and societal effect. There has been a 30-fold increase in the number of dengue cases over the past 50 years. Recent studies estimate 50–100 million infections each year, although, owing to under-reporting, this figure could be even higher.
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Lancet
In his Correspondence (Nov 5, p 1626), Syed Wamique Yusuf reports the fact that, after acceptance and revision of the proofs, one of his case reports was deemed no longer suitable for publication when he did not comply with the obligatory subscription to the journal.
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Lancet
I fully agree with Syed Wamique Yusuf that the governance of journals should be taken seriously. This is one of the functions of the Committee on Publication Ethics ( COPE). Since 2003, COPE has promoted a Code of Conduct among our members (which now number almost 7000 journal editors worldwide). If anybody feels that a member has not followed this code, they can bring a complaint against them which COPE will consider. The code states that journals should “preclude business needs from compromising intellectual standards” and goes on to state that “editors should make decisions on which articles to publish based on quality and suitability for readers rather than for immediate financial or political gain”.
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Lancet
Your Editorial “Torture in Syria's hospitals” (Nov 5, p 1606) relays the allegation of Amnesty International's report that patients in state-run hospitals were being targeted and tortured by authorities to “quell dissent”. The undermining of the independence and work of medical personnel has unfortunately been a theme of recent conflicts.
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Lancet
A 40-year-old woman was sent to our service for a bronchoscopy owing to multiple interstitial pulmonary infiltrates. She complained of a dry cough, dyspnoea, and wheezing of 4 months' duration. She also reported bronchospasm episodes in childhood. The patient had already been seen by three different clinicians and brought with her several test results, including a thorax CT. She had been treated with antibiotics, bronchodilators, and steroids, without improvement.
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Lancet
Abraham WT, Adamson PB, Bourge RC, et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet 2011; 377: 658–66—In this Article (Feb 19), the first sentence of the fifth paragraph in the Statistical analysis section on page 661 should have started: “Prespecified supplementary analyses were heart-failure-related hospitalisations during the entire randomised follow-up (Andersen-Gill model)…” Additionally, during internal auditing of this study in preparation for data presentation to regulatory authorities, a small number of unreported events were uncovered.
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Lancet
Glazener C, Boachie C, Buckley B, et al. Urinary incontinence in men after formal one-to-one pelvic-floor muscle training following radical prostatectomy or transurethral resection of the prostate (MAPS): two parallel randomised controlled trials. Lancet 2011; 378: 328–37—This Article (July 23) should have contained the following conflicts of interest statement: “BB has received travel expenses from Astellas, Medtronic, and Pfizer. All other authors declare no conflicts of interest”. This correction has been made to the online version as of Feb 3, 2012.
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Lancet
Our findings show that the malaria mortality burden is larger than previously estimated, especially in adults. There has been a rapid decrease in malaria mortality in Africa because of the scaling up of control activities supported by international donors. Donor support, however, needs to be increased if malaria elimination and eradication and broader health and development goals are to be met.
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Lancet
10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both.
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Lancet
Intrauterine and neonatal insults have a high risk of causing substantial long-term neurological morbidity. Comparable cohort studies in resource-poor regions should be done to properly assess the burden of these conditions, and long-term outcomes, such as chronic disease, and to inform policy and programme investments.
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Lancet
CE-MARC is the largest, prospective, real world evaluation of CMR and has established CMR's high diagnostic accuracy in coronary heart disease and CMR's superiority over SPECT. It should be adopted more widely than at present for the investigation of coronary heart disease.
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Lancet
Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries.
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Lancet
Hereditary angio-oedema is caused by a heterozygous deficiency of C1 inhibitor. This inhibitor regulates several inflammatory pathways, and patients with hereditary angio-oedema have intermittent cutaneous or mucosal swellings because of a failure to control local production of bradykinin. Swellings typically evolve in several hours and persist for a few days. In addition to orofacial angio-oedema, painless swellings affect peripheries, which causes disfigurement or interference with work and other activities of daily living.
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Lancet
Non-specific low back pain has become a major public health problem worldwide. The lifetime prevalence of low back pain is reported to be as high as 84%, and the prevalence of chronic low back pain is about 23%, with 11–12% of the population being disabled by low back pain. Mechanical factors, such as lifting and carrying, probably do not have a major pathogenic role, but genetic constitution is important. History taking and clinical examination are included in most diagnostic guidelines, but the use of clinical imaging for diagnosis should be restricted.
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Lancet
In October, 2010, a 29-year-old man initially presented to a primary care clinic with fevers, sore throat, and odynophagia, and was treated with oral phenoxymethylpenicillin 250 mg four times daily for tonsillitis. He re-presented 72 h later with persisting symptoms and fever of 38·4°C, and was administered 1 000 000 units of intramuscular procaine benzylpenicillin. 4–5 min later, he collapsed with no cardiac output, and cardiopulmonary resuscitation was commenced. Paramedic staff arrived within 20 min and monitoring showed ventricular fibrillation.
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16:30
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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.
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16:30
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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.
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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.
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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.
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16:20
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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
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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.
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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.
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14:40
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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.
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14:40
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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.
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14:40
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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.
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14:40
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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.
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14:40
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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.
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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.
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Science
Author: Philip E. Hulme
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Science
Authors: Michael T. Burrows, David S. Schoeman, Carlos M. Duarte, Mary I. O'Connor, Lauren B. Buckley, Carrie V. Kappel, Camille Parmesan, Benjamin S. Halpern, Chris Brown, Keith M. Brander, John F. Bruno, John M. Pandolfi, William J. Sydeman, Pippa Moore, Wolfgang Kiessling, Anthony J. Richardson, Elvira S. Poloczanska
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Science
[Correction] Corrections and Clarifications
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Science
Authors: Andrew D. Czaja, Clark M. Johnson, Kosei E. Yamaguchi, Brian L. Beard
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Science
Authors: Romain Guilbaud, Ian B. Butler, Rob M. Ellam
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Science
Author: Robert Dickinson
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Science
Guillemin describes the aftermath of and investigation into the fall 2001 anthrax letters.
Author: David A. Relman
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Science
Analyzing incentives in terms of power rather than as trades, Grant concludes that their use to further desired social and political goals raises some ethical concerns.
Author: Tyler Cowen
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Science
A
listing of books received at
Science during the week ending 27 January 2012.
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Science
Many journal editors appear to strategically target authors and papers to pressure them into citing the editors' journals.
Authors: Allen W. Wilhite, Eric A. Fong
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Science
Women's willingness to compete can be increased through appropriate affirmative action.
Author: Marie Claire Villeval
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Science
Natural variations in a single gene of wild C. elegans populations confer resistance to the bacterial toxin avermectin.
Author: Adrian J. Wolstenholme
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Science
Does chronic drug abuse cause brain abnormalities, or do they develop before the onset of dependence?
Authors: Nora D. Volkow, Ruben D. Baler
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Science
A cave record from Peru closely matches climate patterns seen in cores from Greenland and the North Atlantic Ocean.
Author: Donald T. Rodbell
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Science
The universal thermodynamic functions of a superfluid formed from a fermion gas of strongly interacting lithium atoms have been measured precisely.
Author: Wilhelm Zwerger
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Science
Super high-resolution microscopy resolves neuron dynamics in the cerebral cortex of a living mouse.
Authors: Sebastian Berning, Katrin I. Willig, Heinz Steffens, Payam Dibaj, Stefan W. Hell
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Science
During yeast sporulation, the production of most proteins is tightly regulated by both messenger RNA levels and translational control.
Authors: Gloria A. Brar, Moran Yassour, Nir Friedman, Aviv Regev, Nicholas T. Ingolia, Jonathan S. Weissman
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Science
Radiocarbon measurements of deep-sea corals reveal the presence of old, carbon-rich water in the Southern Ocean.
Authors: Andrea Burke, Laura F. Robinson
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Science
Numerical calculations show that processes responsible for spinning up millisecond pulsars may also lead them to slow down.
Author: Thomas M. Tauris
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Science
Thermodynamic quantities for the superfluid transition of a strongly interacting atomic Fermi gas were measured.
Authors: Mark J. H. Ku, Ariel T. Sommer, Lawrence W. Cheuk, Martin W. Zwierlein
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Science
Iron catalysts offer a potentially cheaper route than platinum for certain commercially useful carbon-silicon compounds.
Authors: Aaron M. Tondreau, Crisita Carmen Hojilla Atienza, Keith J. Weller, Susan A. Nye, Kenrick M. Lewis, Johannes G. P. Delis, Paul J. Chirik
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