Showing papers by "University of Göttingen published in 2007"
TL;DR: It is found that fruit, vegetable or seed production from 87 of the leading global food crops is dependent upon animal pollination, while 28 crops do not rely upon animalPollination, however, global production volumes give a contrasting perspective.
Abstract: The extent of our reliance on animal pollination for world crop production for human food has not previously been evaluated and the previous estimates for countries or continents have seldom used primary data. In this review, we expand the previous estimates using novel primary data from 200 countries and found that fruit, vegetable or seed production from 87 of the leading global food crops is dependent upon animal pollination, while 28 crops do not rely upon animal pollination. However, global production volumes give a contrasting perspective, since 60% of global production comes from crops that do not depend on animal pollination, 35% from crops that depend on pollinators, and 5% are unevaluated. Using all crops traded on the world market and setting aside crops that are solely passively self-pollinated, wind-pollinated or parthenocarpic, we then evaluated the level of dependence on animal-mediated pollination for crops that are directly consumed by humans. We found that pollinators are essential for 13 crops, production is highly pollinator dependent for 30, moderately for 27, slightly for 21, unimportant for 7, and is of unknown significance for the remaining 9. We further evaluated whether local and landscape-wide management for natural pollination services could help to sustain crop diversity and production. Case studies for nine crops on four continents revealed that agricultural intensification jeopardizes wild bee communities and their stabilizing effect on pollination services at the landscape scale.
4,830 citations
TL;DR: This review focuses on several key observations that illustrate the multi-faceted activities of microglia in the normal and pathologic brain.
Abstract: Microglial cells constitute the resident macrophage population of the CNS. Recent in vivo studies have shown that microglia carry out active tissue scanning, which challenges the traditional notion of 'resting' microglia in the normal brain. Transformation of microglia to reactive states in response to pathology has been known for decades as microglial activation, but seems to be more diverse and dynamic than ever anticipated—in both transcriptional and nontranscriptional features and functional consequences. This may help to explain why engagement of microglia can be either neuroprotective or neurotoxic, resulting in containment or aggravation of disease progression. Moreover, little is known about the heterogeneity of microglial responses in different pathologic contexts that results from regional adaptations or from the progression of a disease. In this review, we focus on several key observations that illustrate the multi-faceted activities of microglia in the normal and pathologic brain.
3,238 citations
VU University Medical Center1, Charité2, Keele University3, University of Erlangen-Nuremberg4, Katholieke Universiteit Leuven5, University of Eastern Piedmont6, Oslo University Hospital7, University of Porto8, University of Debrecen9, Maastricht University10, University of Göttingen11, Stavanger University Hospital12, Cardiff University13
TL;DR: The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies forHFNEF.
Abstract: Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) 16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF.
2,578 citations
TL;DR: The Raf/MEK/ERK pathway has different effects on growth, prevention of apoptosis, cell cycle arrest and induction of drug resistance in cells of various lineages which may be due to the presence of functional p53 and PTEN and the expression of lineage specific factors.
2,096 citations
TL;DR: A decade has passed since SUMO was discovered to be a reversible post-translational protein modifier and many enzymes that participate in regulated SUMO-conjugation and -deconjugation pathways have been identified and characterized.
Abstract: A decade has passed since SUMO (small ubiquitin-related modifier) was discovered to be a reversible post-translational protein modifier. During this time many enzymes that participate in regulated SUMO-conjugation and -deconjugation pathways have been identified and characterized. In parallel, the search for SUMO substrates has produced a long list of targets, which appear to be involved in most cellular functions. Sumoylation is a highly dynamic process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified protein. At first glance, these effects have nothing in common; however, it seems that they all result from changes in the molecular interactions of the sumoylated proteins.
1,663 citations
University of California, Berkeley1, Bryn Mawr College2, Food and Agriculture Organization3, San Francisco State University4, University of Rochester5, York University6, University of Reading7, University of Virginia8, University of Bayreuth9, University of Montana10, University of California, Davis11, University of Texas at Austin12, University of Göttingen13, University of California, Santa Barbara14
TL;DR: A conceptual model for exploring how one mobile-agent-based ecosystem service (MABES), pollination, is affected by land-use change, and then generalize the model to other MABES is developed.
Abstract: Many ecosystem services are delivered by organisms that depend on habitats that are segregated spatially or temporally from the location where services are provided. Management of mobile organisms contributing to ecosystem services requires consideration not only of the local scale where services are delivered, but also the distribution of resources at the landscape scale, and the foraging ranges and dispersal movements of the mobile agents. We develop a conceptual model for exploring how one such mobile-agent-based ecosystem service (MABES), pollination, is affected by land-use change, and then generalize the model to other MABES. The model includes interactions and feedbacks among policies affecting land use, market forces and the biology of the organisms involved. Animal-mediated pollination contributes to the production of goods of value to humans such as crops; it also bolsters reproduction of wild plants on which other services or service-providing organisms depend. About onethird of crop production depends on animal pollinators, while 60–90% of plant species require an animal pollinator. The sensitivity of mobile organisms to ecological factors that operate across spatial scales makes the services provided by a given community of mobile agents highly contextual. Services vary, depending on the spatial and temporal distribution of resources surrounding the site, and on biotic interactions occurring locally, such as competition among pollinators for resources, and among plants for pollinators. The value of the resulting goods or services may feed back via market-based forces to influence land-use policies, which in turn influence land management practices that alter local habitat conditions and landscape structure. Developing conceptual
1,277 citations
TL;DR: In this article, the SOM fractions obtained with such operational fractionation procedures are described in terms of their pool sizes, chemical properties, and turnover rates, and the main objective is to evaluate these operationally defined fractions with respect to their suitability to describe functional SOM pools that could be used to parameterize SOM turnover models.
Abstract: Soil organic matter (SOM) consists of various functional pools that are stabilized by specific mechanisms and have certain turnover rates. For the development of mechanistic models that predict changes in SOM storage, these pools have to be quantified and characterized. In the past, numerous fractionation schemes have been developed to separate and analyse such SOM fractions. In this review, the SOM fractions obtained with such operational fractionation procedures are described in terms of their pool sizes, chemical properties, and turnover rates. The main objective of this review is to evaluate these operationally defined fractions with respect to their suitability to describe functional SOM pools that could be used to parameterize SOM turnover models. Fractionation procedures include (1) physical separation of SOM into aggregate, particle size, and density fractions and fractions according to their magnetic susceptibility, and (2) various wet chemical procedures that fractionate SOM according to solubility, hydrolysability, and resistance to oxidation or by destruction of the mineral phase. Furthermore, combinations of fractionation methods are evaluated. The active SOM pool with turnover rates
1,172 citations
TL;DR: In the literature, there are numerous reports of net negative fluxes of N2O, (i.e. fluxes from the atmosphere to the soil) such fluxes are frequent and substantial and cannot simply be dismissed as experimental noise as discussed by the authors.
Abstract: Soils are the main sources of the greenhouse gas nitrous oxide (N2O). The N2O emission at the soil surface is the result of production and consumption processes. So far, research has concentrated on net N2O production. However, in the literature, there are numerous reports of net negative fluxes of N2O, (i.e. fluxes from the atmosphere to the soil). Such fluxes are frequent and substantial and cannot simply be dismissed as experimental noise.
Net N2O consumption has been measured under various conditions from the tropics to temperate areas, in natural and agricultural systems. Low mineral N and large moisture contents have sometimes been found to favour N2O consumption. This fits in with denitrification as the responsible process, reducing N2O to N2. However, it has also been reported that nitrifiers consume N2O in nitrifier denitrification. A contribution of various processes could explain the wide range of conditions found to allow N2O consumption, ranging from low to high temperatures, wet to dry soils, and fertilized to unfertilized plots. Generally, conditions interfering with N2O diffusion in the soil seem to enhance N2O consumption. However, the factors regulating N2O consumption are not yet well understood and merit further study.
Frequent literature reports of net N2O consumption suggest that a soil sink could help account for the current imbalance in estimated global budgets of N2O. Therefore, a systematic investigation into N2O consumption is necessary. This should concentrate on the organisms, reactions, and environmental factors involved.
1,160 citations
J. Craig Venter Institute1, Broad Institute2, Virginia Tech3, Johns Hopkins University4, University of Notre Dame5, Harvard University6, Colorado State University7, Northwestern University8, University of California, Riverside9, University of Oxford10, Purdue University11, Pasteur Institute12, University of São Paulo13, University of Geneva14, University of Massachusetts Amherst15, Instituto Butantan16, University of A Coruña17, University of Göttingen18
TL;DR: A draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genomes of the malaria vector Anopheles gambiae was presented in this paper.
Abstract: We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
1,107 citations
TL;DR: Recent evidence is described that the spectrum of MS pathology is much broader, including demyelination in the cortex and deep gray matter nuclei, as well as diffuse injury of the normal‐appearing white matter.
Abstract: Multiple sclerosis (MS) is traditionally seen as an inflammatory demyelinating disease, characterized by the formation of focal demyelinated plaques in the white matter of the central nervous system. In this review we describe recent evidence that the spectrum of MS pathology is much broader. This includes demyelination in the cortex and deep gray matter nuclei, as well as diffuse injury of the normal-appearing white matter. The mechanisms responsible for the formation of focal lesions in different patients and in different stages of the disease as well as those involved in the induction of diffuse brain damage are complex and heterogeneous. This heterogeneity is reflected by different clinical manifestations of the disease, such as relapsing or progressive MS, and also explains at least in part the relation of MS to other inflammatory demyelinating diseases.
1,055 citations
TL;DR: The results suggest that tDCS applied to motor and non-motor areas according to the present tDCS safety guidelines, is associated with relatively minor adverse effects in healthy humans and patients with varying neurological disorders.
TL;DR: Using a panel of bone marrow chimeric and adoptive transfer experiments, it is found that circulating Ly-6ChiCCR2+ monocytes were preferentially recruited to the lesioned brain and differentiated into microglia.
Abstract: Microglia are crucially important myeloid cells in the CNS and constitute the first immunological barrier against pathogens and environmental insults. The factors controlling microglia recruitment from the blood remain elusive and the direct circulating microglia precursor has not yet been identified in vivo. Using a panel of bone marrow chimeric and adoptive transfer experiments, we found that circulating Ly-6C(hi)CCR2(+) monocytes were preferentially recruited to the lesioned brain and differentiated into microglia. Notably, microglia engraftment in CNS pathologies, which are not associated with overt blood-brain barrier disruption, required previous conditioning of brain (for example, by direct tissue irradiation). Our results identify Ly-6C(hi)CCR2(+) monocytes as direct precursors of microglia in the adult brain and establish the importance of local factors in the adult CNS for microglia engraftment.
TL;DR: It is shown that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulatesAutophagy and has a crucial role in embryogenesis, and provides in vivo evidence supporting the existence of a complex interplay between autphagy, cell growth and cell death required for neural development in mammals.
Abstract: Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized. Beclin1 (Becn1; coiled-coil, myosin-like BCL2-interacting protein) is a principal regulator in autophagosome formation, and its deficiency results in early embryonic lethality. Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy, as revealed by its overexpression and by RNA interference experiments in vitro. Notably, Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death. In addition to identifying a new and essential element regulating the autophagy programme, our results provide in vivo evidence supporting the existence of a complex interplay between autophagy, cell growth and cell death required for neural development in mammals.
TL;DR: A quantitative theoretical model is presented connecting the large-scale properties of this active gel to molecular force generation and qualitatively changing the viscoelastic response of the network in an adenosine triphosphate–dependent manner.
Abstract: Cells both actively generate and sensitively react to forces through their mechanical framework, the cytoskeleton, which is a nonequilibrium composite material including polymers and motor proteins. We measured the dynamics and mechanical properties of a simple three-component model system consisting of myosin II, actin filaments, and cross-linkers. In this system, stresses arising from motor activity controlled the cytoskeletal network mechanics, increasing stiffness by a factor of nearly 100 and qualitatively changing the viscoelastic response of the network in an adenosine triphosphate–dependent manner. We present a quantitative theoretical model connecting the large-scale properties of this active gel to molecular force generation.
TL;DR: Altered interaction structure represents an insidious and functionally important hidden effect of habitat modification by humans, indicating that perturbation of the structure and function of ecological communities might be overlooked in studies that do not document and quantify species interactions.
Abstract: Global conversion of natural habitats to agriculture has led to marked changes in species diversity and composition. However, it is less clear how habitat modification affects interactions among species. Networks of feeding interactions (food webs) describe the underlying structure of ecological communities, and might be crucially linked to their stability and function. Here, we analyse 48 quantitative food webs for cavity-nesting bees, wasps and their parasitoids across five tropical habitat types. We found marked changes in food-web structure across the modification gradient, despite little variation in species richness. The evenness of interaction frequencies declined with habitat modification, with most energy flowing along one or a few pathways in intensively managed agricultural habitats. In modified habitats there was a higher ratio of parasitoid to host species and increased parasitism rates, with implications for the important ecosystem services, such as pollination and biological control, that are performed by host bees and wasps. The most abundant parasitoid species was more specialized in modified habitats, with reduced attack rates on alternative hosts. Conventional community descriptors failed to discriminate adequately among habitats, indicating that perturbation of the structure and function of ecological communities might be overlooked in studies that do not document and quantify species interactions. Altered interaction structure therefore represents an insidious and functionally important hidden effect of habitat modification by humans.
TL;DR: It is not proven by prospective clinical studies whether the incidence of secondary caries can be significantly reduced by the fluoride release of restorative materials, but fluoride-releasing materials, predominantly glass-ionomers and compomers, did show cariostatic properties and may affect bacterial metabolism under simulated cariogenic conditions in vitro.
TL;DR: The B. amyloliquefaciens FZB42 genome reveals an unexpected potential to produce secondary metabolites, including the polyketides bacillaene and difficidin, and identifies four giant gene clusters absent in B. subtilis 168.
Abstract: Bacillus amyloliquefaciens FZB42 is a Gram-positive, plant-associated bacterium, which stimulates plant growth and produces secondary metabolites that suppress soil-borne plant pathogens. Its 3,918-kb genome, containing an estimated 3,693 protein-coding sequences, lacks extended phage insertions, which occur ubiquitously in the closely related Bacillus subtilis 168 genome. The B. amyloliquefaciens FZB42 genome reveals an unexpected potential to produce secondary metabolites, including the polyketides bacillaene and difficidin. More than 8.5% of the genome is devoted to synthesizing antibiotics and siderophores by pathways not involving ribosomes. Besides five gene clusters, known from B. subtilis to mediate nonribosomal synthesis of secondary metabolites, we identified four giant gene clusters absent in B. subtilis 168. The pks2 gene cluster encodes the components to synthesize the macrolactin core skeleton.
TL;DR: A large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) offers new insights into the prognostic significance of rare chromosomal abnormalities and specific karyotypic combinations in MDS.
TL;DR: Increased focality of tDCS might improve the interpretation of the functional effects of stimulation because it will restrict its effects to more clearly defined cortical areas, and such paradigms may help to achieve more selective tDCS effects.
Abstract: Transcranial DC stimulation (tDCS) induces stimulation polarity-dependent neuroplastic excitability shifts in the human brain. Because it accomplishes long-lasting effects and its application is si...
TL;DR: It is shown that IRF4 is also critical for the generation of interleukin 17–producing T helper cells (TH-17 cells), which are associated with experimental autoimmune encephalomyelitis.
Abstract: Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper type 2 cells. Here we show that IRF4 is also critical for the generation of interleukin 17-producing T helper cells (T(H)-17 cells), which are associated with experimental autoimmune encephalomyelitis. IRF4-deficient (Irf4(-/-)) mice did not develop experimental autoimmune encephalomyelitis, and T helper cells from such mice failed to differentiate into T(H)-17 cells. Transfer of wild-type T helper cells into Irf4(-/-) mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4(-/-) T helper cells had less expression of RORgammat and more expression of Foxp3, transcription factors important for the differentiation of T(H)-17 and regulatory T cells, respectively. Altered regulation of both transcription factors contributed to the phenotype of Irf4(-/-) T helper cells. Our data position IRF4 at the center of T helper cell development, influencing not only T helper type 2 but also T(H)-17 differentiation.
TL;DR: A genome-wide association study found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q.
Abstract: Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.
TL;DR: The data show that expression of many microRNAs is altered in heart disease and that different types of heart disease are associated with distinct changes in microRNA expression.
Abstract: MicroRNAs are recently discovered regulators of gene expression and are becoming increasingly recognized as important regulators of heart function. Genome-wide profiling of microRNAs in human heart...
TL;DR: Synthetic tools and high-throughput experiments such as carbohydrate arrays are beginning to affect biological research, and are being applied to the development of carbohydrate-based diagnostics, vaccines and therapeutics.
Abstract: Our understanding of the different glycoconjugates present on cells, proteins and entire organisms is lagging far behind advances in genomics and proteomics. Carbohydrate sequencing and the synthesis of defined oligosaccharides are two key technologies that have contributed to progress in glycomics research. Synthetic tools and high-throughput experiments such as carbohydrate arrays are beginning to affect biological research. These techniques are now being applied to the development of carbohydrate-based diagnostics, vaccines and therapeutics.
TL;DR: PP2A phosphatase is identified as an important regulator of PIN apical-basal targeting and auxin distribution and switches in the direction of intercellular auxin fluxes, which mediate differential growth, tissue patterning, and organogenesis in plants.
TL;DR: In this article, the authors proposed a landscape management perspective for conservation biological control in agroecosystems, where most arthropod species experience their habitat at spatial scales beyond the plot level, and there is spillover of natural enemies across the crop-noncrop interface.
Leipzig University1, University of Jena2, University of Münster3, Martin Luther University of Halle-Wittenberg4, University of Greifswald5, Heidelberg University6, Augsburg College7, University of Erlangen-Nuremberg8, University of Giessen9, Charité10, University of Göttingen11, Dresden University of Technology12, RWTH Aachen University13, University of Bonn14, University of Kiel15, Hannover Medical School16
TL;DR: The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76–110 per 100,000 adult inhabitants and future epidemiological studies should use standardized study methodologies with respect to sepsi definitions, hospital size, and daily and monthly variability.
Abstract: To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. Prospective, observational, cross-sectional 1-day point-prevalence study. 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9–13.8%) for sepsis and 11.0% (95% CI, 9.7–12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (≤ 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76–110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.
J. Craig Venter Institute1, University of Pittsburgh2, Imperial College London3, University of Dundee4, New England Biolabs5, University of Edinburgh6, Lyon College7, Australian National University8, University of Toledo9, University of California, Davis10, Smith College11, Washington University in St. Louis12, New York Blood Center13, National Institutes of Health14, University of Göttingen15, University of Alabama at Birmingham16, Johns Hopkins University17
TL;DR: In this article, the authors sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predicted ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence.
Abstract: Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.
TL;DR: It is demonstrated analytically and numerically that by assuming (biologically more realistic) dynamical synapses in a spiking neural network, the neuronal avalanches turn from an exceptional phenomenon into a typical and robust self-organized critical behaviour, if the total resources of neurotransmitter are sufficiently large.
Abstract: Self-organized criticality1 is one of the key concepts to describe the emergence of complexity in natural systems. The concept asserts that a system self-organizes into a critical state where system observables are distributed according to a power law. Prominent examples of self-organized critical dynamics include piling of granular media2, plate tectonics3 and stick–slip motion4. Critical behaviour has been shown to bring about optimal computational capabilities5, optimal transmission6, storage of information7 and sensitivity to sensory stimuli8,9,10. In neuronal systems, the existence of critical avalanches was predicted11 and later observed experimentally6,12,13. However, whereas in the experiments generic critical avalanches were found, in the model of ref. 11 they only show up if the set of parameters is fine-tuned externally to a critical transition state. Here, we demonstrate analytically and numerically that by assuming (biologically more realistic) dynamical synapses14 in a spiking neural network, the neuronal avalanches turn from an exceptional phenomenon into a typical and robust self-organized critical behaviour, if the total resources of neurotransmitter are sufficiently large.
TL;DR: It is shown that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane invaginations in human and mouse cells and model membranes, and it is concluded that the B- subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules.
Abstract: Clathrin seems to be dispensable for some endocytic processes and, in several instances, no cytosolic coat protein complexes could be detected at sites of membrane invagination. Hence, new principles must in these cases be invoked to account for the mechanical force driving membrane shape changes. Here we show that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane invaginations in human and mouse cells and model membranes. In cells, tubule occurrence increases on energy depletion and inhibition of dynamin or actin functions. Our data thus demonstrate that active cellular processes are needed for tubule scission rather than tubule formation. We conclude that the B-subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules. Our findings support a model in which the lateral growth of B-subunit–Gb3 microdomains is limited by the invagination process, which itself is regulated by membrane tension. The physical principles underlying this basic cargo-induced membrane uptake may also be relevant to other internalization processes, creating a rationale for conceptualizing the perplexing diversity of endocytic routes. An imaging study of an early step of bacterial toxin intake into cells — membrane invagination — reveals a cargo-induced mechanism that may also apply to other pathogens and more generally to other endocytosis events. The B subunit of Shiga toxin (from Shigella dysenteriae) is seen to enter cells via narrow tubular membrane invaginations. The toxin induces membrane reorganization prior to formation of tubular invaginations, which occurs independently of protein complexes (like clathrin) that have been ascribed membrane deforming capacities, and also when cellular energy is depleted. So membrane invagination relies on physical principles and can occur spontaneously, without the need for sophisticated cellular machinery. A study of endocytosis of Shigella toxin shows that it enters cells via narrow tubular membrane invaginations, with similar properties on cell and model membranes. The toxin induces membrane reorganisation before the formation of tubular invaginations.
ETH Zurich1, Paul Sabatier University2, University of Minnesota3, University of California, Santa Barbara4, University of Göttingen5, University of Hong Kong6, University of Tokyo7, Russian Academy of Sciences8, University of Stuttgart9, University of Marburg10, RWTH Aachen University11, Graz University of Technology12, Columbia University13
TL;DR: Changes in the new release of the ALPS project include a DMRG program for interacting models, support for translation symmetries in the diagonalization programs, the ability to define custom measurement operators, and support for inhomogeneous systems, such as lattice models with traps.