Showing papers by "University of Geneva published in 2003"
01 Jan 2003
1,688 citations
TL;DR: It is suggested to use the Brunswikian lens model as a base for research on the vocal communication of emotion, which allows one to model the complete process, including both encoding, transmission, and decoding of vocal emotion communication.
1,674 citations
TL;DR: The demonstration that fibroblastic cells acquire contractile features during the healing of an open wound, thus modulating into myofibroblasts, has open a new perspective in the understanding of mechanisms leading to wound closure and fibrocontractive diseases.
Abstract: The demonstration that fibroblastic cells acquire contractile features during the healing of an open wound, thus modulating into myofibroblasts, has open a new perspective in the understanding of mechanisms leading to wound closure and fibrocontractive diseases. Myofibroblasts synthesize extracellular matrix components such as collagen types I and III and during normal wound healing disappear by apoptosis when epithelialization occurs. The transition from fibroblasts to myofibroblasts is influenced by mechanical stress, TGF-beta and cellular fibronectin (ED-A splice variant). These factors also play important roles in the development of fibrocontractive changes, such as those observed in liver cirrhosis, renal fibrosis, and stroma reaction to epithelial tumours.
1,560 citations
TL;DR: It is demonstrated that APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-Ahypermutation in the nascent retroviral DNA, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.
Abstract: Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes When produced in the presence of APOBEC3G, vif-defective virus is non-infectious APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens
1,518 citations
TL;DR: An international consortium called `Phaseomics' is formed to establish the necessary framework of knowledge and materials that will result in disease-resistant, stress-tolerant, high-quality protein and high-yielding beans, which will be instrumental in improving living conditions in deprived regions of Africa and the Americas.
Abstract: Globally, 800 million people are malnourished. Heavily subsidised farmers in rich countries produce sufficient surplus food to feed the hungry, but not at a price the poor can afford. Even donating the rich world's surplus to the poor would not solve the problem. Most poor people earn their living from agriculture, so a deluge of free food would destroy their livelihoods. Thus, the only answer to world hunger is to safeguard and improve the productivity of farmers in poor countries. Diets of subsistence level farmers in Africa and Latin America often contain sufficient carbohydrates (through cassava, corn/maize, rice, wheat, etc.), but are poor in proteins. Dietary proteins can take the form of scarce animal products (eggs, milk, meat, etc.), but are usually derived from legumes (plants of the bean and pea family). Legumes are vital in agriculture as they form associations with bacteria that `fix-nitrogen' from the air. Effectively this amounts to internal fertilisation and is the main reason that legumes are richer in proteins than all other plants. Thousands of legume species exist but more common beans (Phaseolus vulgaris L.) are eaten than any other. In some countries such as Mexico and Brazil, beans are the primary source of protein in human diets. As half the grain legumes consumed worldwide are common beans, they represent the species of choice for the study of grain legume nutrition. Unfortunately, the yields of common beans are low even by the standards of legumes, and the quality of their seed proteins is sub-optimal. Most probably this results from millennia of selection for stable rather than high yield, and as such, is a problem that can be redressed by modern genetic techniques. We have formed an international consortium called `Phaseomics' to establish the necessary framework of knowledge and materials that will result in disease-resistant, stress-tolerant, high-quality protein and high-yielding beans. Phaseomics will be instrumental in improving living conditions in deprived regions of Africa and the Americas. It will contribute to social equity and sustainable development and enhance inter- and intra-cultural understanding, knowledge and relationships. A major goal of Phaseomics is to generate new common bean varieties that are not only suitable for but also desired by the local farmer and consumer communities. Therefore, the socio-economic dimension of improved bean production and the analysis of factors influencing the acceptance of novel varieties will be an integral part of the proposed research (see Figure 1). Here, we give an overview of the economic and nutritional importance of common beans as a food crop. Priorities and targets of current breeding programmes are outlined, along with ongoing efforts in genomics. Recommendations for an international coordinated effort to join knowledge, facilities and expertise in a variety of scientific undertakings that will contribute to the overall goal of better beans are given. To be rapid and effective, plant breeding programmes (i.e., those that involve crossing two different `parents') rely heavily on molecular `markers'. These genetic landmarks are used to position
1,255 citations
University of Pennsylvania1, New York University2, National Institutes of Health3, National Institute for Health and Welfare4, Cardiff University5, University of Bonn6, Johns Hopkins University School of Medicine7, Harvard University8, University of Medicine and Dentistry of New Jersey9, Rutgers University10, Columbia University11, University of Louisville12, University College London13, Uppsala University14, University of Utah15, University of California, Irvine16, Queen's University Belfast17, Virginia Commonwealth University18, University of California, Los Angeles19, University of Helsinki20, University of Geneva21, University of Queensland22, Icahn School of Medicine at Mount Sinai23, University of Iowa24, Washington University in St. Louis25, University of Toronto26
TL;DR: The GSMA produced significant genomewide evidence for linkage on chromosome 2q and suggests that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
Abstract: Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
1,176 citations
TL;DR: An activation of pulvinar and superior colliculus by fearful expressions occurred specifically with low-frequency faces, suggesting that these subcortical pathways may provide coarse fear-related inputs to the amygdala.
Abstract: High and low spatial frequency information in visual images is processed by distinct neural channels. Using event-related functional magnetic resonance imaging (fMRI) in humans, we show dissociable roles of such visual channels for processing faces and emotional fearful expressions. Neural responses in fusiform cortex, and effects of repeating the same face identity upon fusiform activity, were greater with intact or high-spatial-frequency face stimuli than with low-frequency faces, regardless of emotional expression. In contrast, amygdala responses to fearful expressions were greater for intact or low-frequency faces than for high-frequency faces. An activation of pulvinar and superior colliculus by fearful expressions occurred specifically with low-frequency faces, suggesting that these subcortical pathways may provide coarse fear-related inputs to the amygdala.
1,062 citations
Book•
01 Jan 2003TL;DR: Baldwin et al. as mentioned in this paper presented and analyzed the widest range of new economic geography models to date, and examined previously unaddressed welfare and policy issues including, in separate sections, trade policy (unilateral, reciprocal, and preferential), tax policy (agglomeration with taxes and public goods, tax competition and agglomeration), and regional policy (infrastructure policies and the political economy of regional subsidies).
Abstract: Research on the spatial aspects of economic activity has flourished over the past decade due to the emergence of new theory, new data, and an intense interest on the part of policymakers, especially in Europe but increasingly in North America and elsewhere as well. However, these efforts - collectively known as the "new economic geography" - have devoted little attention to the policy implications of the new theory. "Economic Geography and Public Policy" fills the gap by illustrating many new policy insights economic geography models can offer to the realm of theoretical policy analysis. Focusing primarily on trade policy, tax policy, and regional policy, Richard Baldwin and coauthors show how these models can be used to make sense of real-world situations. The book not only provides much fresh analysis but also synthesizes insights from the existing literature. The authors begin by presenting and analyzing the widest range of new economic geography models to date. From there, they proceed to examine previously unaddressed welfare and policy issues including, in separate sections, trade policy (unilateral, reciprocal, and preferential), tax policy (agglomeration with taxes and public goods, tax competition and agglomeration), and regional policy (infrastructure policies and the political economy of regional subsidies). A well-organized, engaging narrative that progresses smoothly from fundamentals to more complex material, "Economic Geography and Public Policy" is essential reading for graduate students, researchers, and policymakers seeking new approaches to spatial policy issues.
996 citations
Seconda Università degli Studi di Napoli1, University of Graz2, University of Rome Tor Vergata3, University of Vienna4, University of Naples Federico II5, University of Regensburg6, University of Sydney7, University of L'Aquila8, University of Miami9, University of Ljubljana10, University of Tübingen11, University of Geneva12, University of Buenos Aires13, University of Florence14, Medical College of Wisconsin15, University of Connecticut16, Memorial Sloan Kettering Cancer Center17, Cornell University18, University of Lübeck19, University of Barcelona20, University of Siena21, Rutgers University22, Shinshu University23, University of Modena and Reggio Emilia24, Keio University25, Ludwig Maximilian University of Munich26, New York University27
TL;DR: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.
Abstract: Background: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. Objective: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. Methods: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. κ Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. Results: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean κ value: 0.53). Conclusion: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions. (J Am Acad Dermatol 2003;48:679-93.) J Am Acad Dermatol 2003;48:679-93.
971 citations
TL;DR: New stereologic data indicate that neuronal pathology in hippocampal formation and frontal cortex closely reflects the progression of cognitive deficits in brain aging and AD, and demonstrate that amyloid volume has no additional predictive value, in terms of clinicopathologic correlations, beyond its interaction with NFT.
Abstract: Objective: To examine the relationship between stereologic estimates of AD-related pathology and severity of cognitive deficits in brain aging. Background: Previous studies reported substantial contributions of neurofibrillary tangles (NFT), amyloid deposits, and neuronal loss to the development of dementia. However, the prediction of cognitive status based on nonstereologic quantification of these measures has led to conflicting results. Such studies have measured densities, rather than absolute numbers, and most do not take into account the potential interaction between the above pathologic hallmarks in a global multivariate analysis. Methods: Clinicopathologic study in 22 elderly cases. Cognitive status assessed prospectively using the Mini-Mental State Examination (MMSE); stereologic assessment of NFT, unaffected neurons, and total amyloid volume in the CA1 field of the hippocampus, entorhinal cortex, and area 9. Statistical analysis was performed using both univariate and multivariate linear regression models. Results: High total NFT counts but not amyloid volume were strongly associated with a lower number of unaffected neurons in all areas studied. A high proportion of variability in MMSE scores was explained by NFT and neuronal counts in the CA1 field (83% and 85.4%), entorhinal cortex (87.8% and 83.7%), and area 9 (87% and 79%); amyloid volume in the entorhinal cortex, but not in the CA1 field and area 9, accounted for 58.5% of MMSE variability. Multivariate analyses showed that total NFT counts in the entorhinal cortex and area 9 as well as neuron numbers in the CA1 field were the best predictors of MMSE score. Conclusions: These new stereologic data indicate that neuronal pathology in hippocampal formation and frontal cortex closely reflects the progression of cognitive deficits in brain aging and AD. They also demonstrate that amyloid volume has no additional predictive value, in terms of clinicopathologic correlations, beyond its interaction with NFT.
959 citations
TL;DR: Evidence-based guidelines developed by an international panel of experts for the management of postoperative nausea and vomiting are presented.
Abstract: IMPLICATIONS We present evidence-based guidelines developed by an international panel of experts for the management of postoperative nausea and vomiting.
TL;DR: It is argued that the fundamental criteria for the amygdala to be a modular system are not met and the notion of a specific involvement of the human amygdala in the appraisal of relevant events that include, but are not restricted to, fear-related stimuli is suggested.
Abstract: Evidence from pioneering animal research has suggested that the amygdala is involved in the processing of aversive stimuli, particularly fear-related information. Fear is central in the evolution of the mammalian brain: it is automatically and rapidly elicited by potentially dangerous and deadly events. The view that the amygdala shares the main characteristics of modular systems, e.g. domain specificity, automaticity, and cognitive impenetrability, has become popular in neuroscience. Because of its computational properties, it has been proposed to implement a rapid-response 'fear module'. In this article, we review recent patient and neuroimaging data of the human brain and argue that the fundamental criteria for the amygdala to be a modular system are not met. We propose a different computational view and suggest the notion of a specific involvement of the human amygdala in the appraisal of relevant events that include, but are not restricted to, fear-related stimuli. Considering the amygdala as a 'relevance detector' would integrate the 'fear module' hypothesis with the concept of an evolved neural system devoted to the processing of a broader category of biologically relevant stimuli. In primates, socially relevant events appear to have become, through evolution, the dominant elements of the amygdala's domain of specificity.
TL;DR: The epidemiology of invasive candidiasis in non-immunocompromised, critically ill patients with special emphasis on disease trends over time, pathophysiology, diagnostic approach, risk factors, and impact is reviewed.
Abstract: A substantial proportion of patients become colonised with Candida spp during hospital stay, but only few subsequently develop severe infection Clinical signs of severe infection manifest early but lack specificity until late in the course of the disease, thus representing a particular challenge for diagnosis Mostly nosocomial, invasive candidiasis occurs in only 1-8% of patients admitted to hospitals, but in around 10% of patients housed in intensive care units where it can represent up to 15% of all nosocomial infections We review the epidemiology of invasive candidiasis in non-immunocompromised, critically ill patients with special emphasis on disease trends over time, pathophysiology, diagnostic approach, risk factors, and impact Recent epidemiological data suggesting that the emergence of non-albicans candida strains with reduced susceptibility to azoles, previously linked to the use of new antifungals for empiric and prophylactic therapy in immunocompromised patients, may not have occurred in the critically ill Management of invasive candidiasis in these patients will be addressed in the December issue of The Lancet Infectious Diseases
TL;DR: It is shown that the magnetic monopole can appear in the crystal momentum space of solids in the accessible low-energy region in the context of the anomalous Hall effect.
Abstract: Efforts to find the magnetic monopole in real space have been made in cosmic rays and in particle accelerators, but there has not yet been any firm evidence for its existence because of its very heavy mass, ∼10 16 giga–electron volts We show that the magnetic monopole can appear in the crystal momentum space of solids in the accessible low-energy region (∼01 to 1 electron volts) in the context of the anomalous Hall effect We report experimental results together with first-principles calculations on the ferromagnetic crystal SrRuO 3 that provide evidence for the magnetic monopole in the crystal momentum space
TL;DR: Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
Abstract: Background Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio. Methods Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death. Results The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [9...
TL;DR: A method is described that significantly expands the potential of RNA interference by permitting the conditional suppression of genes in mammalian cells by subjected the polymerase III promoter-dependent production of small interfering RNAs to doxycycline-controllable transcriptional repression.
Abstract: RNA interference has emerged as a powerful technique to downregulate the expression of specific genes in cells and in animals, thus opening new perspectives in fields ranging from developmental genetics to molecular therapeutics. Here, we describe a method that significantly expands the potential of RNA interference by permitting the conditional suppression of genes in mammalian cells. Within a lentivirus vector background, we subjected the polymerase III promoter-dependent production of small interfering RNAs to doxycycline-controllable transcriptional repression. The resulting system can achieve the highly efficient and completely drug-inducible knockdown of cellular genes. As lentivirus vectors can stably transduce a wide variety of targets both in vitro and in vivo and can be used to generate transgenic animals, the present system should have broad applications.
TL;DR: The growing amount of evidence supporting the hypothesis that Alzheimer's disease includes a disconnection syndrome, mainly from neuropathological, electrophysiological, and neuroimaging studies is reviewed.
Abstract: This paper reviews the growing amount of evidence supporting the hypothesis that Alzheimer's disease includes a disconnection syndrome. This evidence came mainly from neuropathological, electrophysiological, and neuroimaging studies. Moreover, a few recent neuropsychological studies have also explored the effects of a disconnection between cerebral areas on cognitive functioning. Finally, and more generally, the contribution of this interpretation to the understanding of Alzheimer's disease cognitive deficits is considered.
TL;DR: In a large cohort of patients with microbiologically confirmed severe sepsis, appropriate initial antimicrobial therapy was an important determinant of survival.
TL;DR: This paper elucidates the main reasons and key motivations behind the convergence of fields with seemingly disparate interests, and shows why developmental robotics might prove to be beneficial for all fields involved.
Abstract: Developmental robotics is an emerging field located at the intersection of robotics, cognitive science and developmental sciences. This paper elucidates the main reasons and key motivations behind the convergence of fields with seemingly disparate interests, and shows why developmental robotics might prove to be beneficial for all fields involved. The methodology advocated is synthetic and two-pronged: on the one hand, it employs robots to instantiate models originating from developmental sciences; on the other hand, it aims to develop better robotic systems by exploiting insights gained from studies on ontogenetic development. This paper gives a survey of the relevant research issues and points to some future research directions.
TL;DR: An overview of the achievements in the field of field-effect transistors is provided and the opportunities brought by the field- effect approach are discussed.
Abstract: Semiconducting field-effect transistors are the workhorses of the modern electronics era. Recently, application of the field-effect approach to compounds other than semiconductors has created opportunities to electrostatically modulate types of correlated electron behaviour—including high-temperature superconductivity and colossal magnetoresistance—and potentially tune the phase transitions in such systems. Here we provide an overview of the achievements in this field and discuss the opportunities brought by the field-effect approach.
TL;DR: In this article, the issue of the number of e-foldings before the end of inflation at which observable perturbations were generated was revisited, and a plausible upper limit on the number was derived for the standard cosmology, with the expectation that the actual value will be up to 10 below this.
Abstract: We reconsider the issue of the number of e-foldings before the end of inflation at which observable perturbations were generated. We determine a plausible upper limit on that number for the standard cosmology which is around 60, with the expectation that the actual value will be up to 10 below this. We also note a special property of the $\ensuremath{\lambda}{\ensuremath{\varphi}}^{4}$ model which reduces the uncertainties in that case and favors a higher value, giving a fairly definite prediction of 64 e-foldings for that model. We note an extreme (and highly implausible) situation where the number of e-foldings can be even higher, possibly up to 100, and discuss the shortcomings of quantifying inflation by e-foldings rather than by the change in $\mathrm{aH}.$ Finally, we discuss the impact of nonstandard evolution between the end of inflation and the present, showing that again the expected number of e-foldings can be modified, and in some cases significantly increased.
TL;DR: In this article, the authors present a cross-section of the recent monograph by Newton-Stormer-Verlet-leapfrog method and its various interpretations, followed by a discussion of geometric properties: reversibility, symplecticity, volume preservation, and conservation of first integrals.
Abstract: The subject of geometric numerical integration deals with numerical integrators that preserve geometric properties of the flow of a differential equation, and it explains how structure preservation leads to an improved long-time behaviour. This article illustrates concepts and results of geometric numerical integration on the important example of the Stormer/Verlet method. It thus presents a cross-section of the recent monograph by the authors, enriched by some additional material. After an introduction to the Newton-Stormer-Verlet-leapfrog method and its various interpretations, there follows a discussion of geometric properties: reversibility, symplecticity, volume preservation, and conservation of first integrals. The extension to Hamiltonian systems on manifolds is also described. The theoretical foundation relies on a backward error analysis, which translates the geometric properties of the method into the structure of a modified differential equation, whose flow is nearly identical to the numerical method. Combined with results from perturbation theory, this explains the excellent long-time behaviour of the method: long-time energy conservation, linear error growth and preservation of invariant tori in near-integrable systems, a discrete virial theorem, preservation of adiabatic invariants.
Trinity College, Dublin1, National Institutes of Health2, University of Pennsylvania3, University College London4, Indiana University – Purdue University Indianapolis5, University of Birmingham6, Johns Hopkins University School of Medicine7, Icahn School of Medicine at Mount Sinai8, University of Chicago9, University of Helsinki10, University of Antwerp11, University of California, San Diego12, Garvan Institute of Medical Research13, University of New South Wales14, Laval University15, University of Utah16, University of Edinburgh17, Washington University in St. Louis18, University of California, Los Angeles19, University of Bonn20, Dalhousie University21, University of Ottawa22, McGill University23, Université libre de Bruxelles24, Umeå University25, University of California, Irvine26, Macquarie University27, University of Texas Health Science Center at San Antonio28, University of California, San Francisco29, University of Costa Rica30, Aarhus University Hospital31, Odense University Hospital32, University of Geneva33, Hacettepe University34
TL;DR: The present results for the very narrow model are promising but suggest that more and larger data sets are needed to support linkage, as well as suggest that linkage might be detected in certain populations or subsets of pedigrees.
Abstract: Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.
TL;DR: The studies show that hFis1 is part of the mammalian fission machinery and suggest that regulation of the fission processes might be involved in apoptotic mechanisms.
TL;DR: A simulation study examining the effect of a recent spatial expansion on the pattern of molecular diversity within a deme finds that the shape of the gene genealogies and the overall pattern of diversity within demes depend not only on the age of the expansion but also on the level of gene flow between neighboring demes, as measured by the product Nm.
Abstract: We report here a simulation study examining the effect of a recent spatial expansion on the pattern of molecular diversity within a deme. We first simulate a range expansion in a virtual world consisting in a two-dimensional array of demes exchanging a given proportion of migrants (m) with their neighbors. The recorded demographic and migration histories are then used under a coalescent approach to generate the genetic diversity in a sample of genes. We find that the shape of the gene genealogies and the overall pattern of diversity within demes depend not only on the age of the expansion but also on the level of gene flow between neighboring demes, as measured by the product Nm, where N is the size of a deme. For small Nm values (< approximately 20 migrants sent outwards per generation), a substantial proportion of coalescent events occur early in the genealogy, whereas with larger levels of gene flow, most coalescent events occur around the time of the onset of the spatial expansion. Gene genealogies are star shaped, and mismatch distributions are unimodal after a range expansion for large Nm values. In contrast, gene genealogies present a mixture of both very short and very long branch lengths, and mismatch distributions are multimodal for small Nm values. It follows that statistics used in tests of selective neutrality like Tajima's D statistic or Fu's F(S) statistic will show very significant negative values after a spatial expansion only in demes with high Nm values. In the context of human evolution, this difference could explain very simply the fact that analyses of samples of mitochondrial DNA sequences reveal multimodal mismatch distributions in hunter-gatherers and unimodal distributions in post-Neolithic populations. Indeed, the current simulations show that a recent increase in deme size (resulting in a larger Nm value) is sufficient to prevent recent coalescent events and thus lead to unimodal mismatch distributions, even if deme sizes (and therefore Nm values) were previously much smaller. The fact that molecular diversity within deme is so dependent on recent levels of gene flow suggests that it should be possible to estimate Nm values from samples drawn from a single deme.
TL;DR: In human islets, the saturated palmitic acid and elevated glucose concentration induce beta-cell apoptosis, decreasebeta-cell proliferation, and impair beta- cell function, which can be prevented by monounsaturated fatty acids.
Abstract: Glucotoxicity and lipotoxicity contribute to the impaired β-cell function observed in type 2 diabetes. Here we examine the effect of saturated and monounsaturated fatty acids at different glucose concentrations on human β-cell turnover and secretory function. Exposure of cultured human islets to saturated fatty acid and/or to an elevated glucose concentration for 4 days increased β-cell DNA fragmentation and decreased β-cell proliferation. In contrast, the monounsaturated palmitoleic acid or oleic acid did not affect DNA fragmentation and induced β-cell proliferation. Moreover, each monounsaturated fatty acid prevented the deleterious effects of both palmitic acid and high glucose concentration. The cell-permeable ceramide analogue C 2 -ceramide mimicked both the palmitic acid-induced β-cell apoptosis and decrease in proliferation. Furthermore, the ceramide synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on β-cell turnover. In addition, palmitic acid decreased Bcl-2 expression and induced release of cytochrome c from the mitochondria into the cytosol, which was prevented by fumonisin B1 and by oleic acid. Finally, each monounsaturated fatty acid improved β-cell secretory function that was reduced by palmitic acid and by high glucose. Thus, in human islets, the saturated palmitic acid and elevated glucose concentration induce β-cell apoptosis, decrease β-cell proliferation, and impair β-cell function, which can be prevented by monounsaturated fatty acids. The deleterious effect of palmitic acid is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway, whereas Bcl-2 may contribute to the protective effect of monounsaturated fatty acids.
TL;DR: A chloroplast thylakoid–associated serine-threonine protein kinase, Stt7, that has homologs in land plants is identified that is required for the phosphorylation of the major light-harvesting protein (LHCII) and for state transition.
Abstract: Photosynthetic organisms adapt to changes in light quality by redistributing light excitation energy between two photosystems through state transition. This reorganization of antenna systems leads to an enhanced photosynthetic yield. Using a genetic approach in Chlamydomonas reinhardtii to dissect the signal transduction pathway of state transition, we identified a chloroplast thylakoid-associated serine-threonine protein kinase, Stt7, that has homologs in land plants. Stt7 is required for the phosphorylation of the major light-harvesting protein (LHCII) and for state transition.
TL;DR: In this paper, the authors examined the properties of Wolf-Rayet (WR) stars predicted by models of rotating stars taking account of the new mass loss rates for O-type stars and WR stars.
Abstract: We examine the properties of Wolf-Rayet (WR) stars predicted by models of rotating stars taking account of the new mass loss rates for O-type stars and WR stars (Vink et al. 2000. 2001; Nugis & Lamers 2000) and of the wind anisotropies induced by rotation. We find that the rotation velocities v of WR stars are modest, i.e. about 50 km s - 1 , not very dependent on the initial ν and masses. For the most massive stars, the evolution of ν is very strongly influenced by the values of the mass loss rates; below 12 M O . the evolution of rotation during the MS phase and later phases is dominated by the internal coupling. Massive stars with extreme rotation may skip the LBV phase. Models having a typical v for the O-type stars have WR lifetimes on the average two times longer than for non-rotating models. The increase of the WR lifetimes is mainly due to that of the H-rich eWNL phase. Rotation allows a transition WN/WC phase to be present for initial masses lower than 60 M O .. The durations of the other WR subphases are less affected by rotation. The mass threshold for forming WR stars is lowered from 37 to 22 M O . for typical rotation. The comparisons of the predicted number ratios WR/O, WN/WC and of the number of transition WN/WC stars show very good agreement with models with rotation, while this is not the case for models with the present-day mass loss rates and no rotation. As to the chemical abundances in WR stars, rotation brings only very small changes for WN stars, since they have equilibrium CNO values. However, WC stars with rotation have on average lower C/He and O/He ratios. The luminosity distribution of WC stars is also influenced by rotation.
TL;DR: This work has shown that during vertebrate development, clustered genes from the Hox family of transcription factors are activated in a precise temporal and spatial sequence that follows their chromosomal order (the “Hox clock”).
Abstract: During vertebrate development, clustered genes from the Hox family of transcription factors are activated in a precise temporal and spatial sequence that follows their chromosomal order (the "Hox clock"). Recent advances in the knowledge of the underlying mechanisms reveal that the embryo uses a variety of strategies to implement this colinear process, depending on both the type and the evolutionary history of axial structures. The search for a universal mechanism has likely hampered our understanding of this enigmatic phenomenon, which may be caused by various and unrelated regulatory processes, as long as the final distribution of proteins (the HOX code) is preserved.