175 research outputs found
Excitable human dynamics driven by extrinsic events in massive communities
Using empirical data from a social media site (Twitter) and on trading
volumes of financial securities, we analyze the correlated human activity in
massive social organizations. The activity, typically excited by real-world
events and measured by the occurrence rate of international brand names and
trading volumes, is characterized by intermittent fluctuations with bursts of
high activity separated by quiescent periods. These fluctuations are broadly
distributed with an inverse cubic tail and have long-range temporal
correlations with a power spectrum. We describe the activity by a
stochastic point process and derive the distribution of activity levels from
the corresponding stochastic differential equation. The distribution and the
corresponding power spectrum are fully consistent with the empirical
observations.Comment: 9 pages, 3 figure
Anomalous Transport in Conical Granular Piles
Experiments on 2+1-dimensional piles of elongated particles are performed.
Comparison with previous experiments in 1+1 dimensions shows that the addition
of one extra dimension to the dynamics changes completely the avalanche
properties, appearing a characteristic avalanche size. Nevertheless, the time
single grains need to cross the whole pile varies smoothly between several
orders of magnitude, from a few seconds to more than 100 hours. This behavior
is described by a power-law distribution, signaling the existence of scale
invariance in the transport process.Comment: Accepted in PR
Crystal structure of the P2 C-repressor: a binder of non-palindromic direct DNA repeats
As opposed to the vast majority of prokaryotic repressors, the immunity repressor of temperate Escherichia coli phage P2 (C) recognizes non-palindromic direct repeats of DNA rather than inverted repeats. We have determined the crystal structure of P2 C at 1.8âĂ
. This constitutes the first structure solved from the family of C proteins from P2-like bacteriophages. The structure reveals that the P2 C protein forms a symmetric dimer oriented to bind the major groove of two consecutive turns of the DNA. Surprisingly, P2 C has great similarities to binders of palindromic sequences. Nevertheless, the two identical DNA-binding helixes of the symmetric P2 C dimer have to bind different DNA sequences. Helix 3 is identified as the DNA-recognition motif in P2 C by alanine scanning and the importance for the individual residues in DNA recognition is defined. A truncation mutant shows that the disordered C-terminus is dispensable for repressor function. The short distance between the DNA-binding helices together with a possible interaction between two P2 C dimers are proposed to be responsible for extensive bending of the DNA. The structure provides insight into the mechanisms behind the mutants of P2 C causing dimer disruption, temperature sensitivity and insensitivity to the P4 antirepressor
PAX4 Enhances Beta-Cell Differentiation of Human Embryonic Stem Cells
Background
Human embryonic stem cells (HESC) readily differentiate into an apparently haphazard array of cell types, corresponding to all three germ layers, when their culture conditions are altered, for example by growth in suspension as aggregates known as embryoid bodies (EBs). However, this diversity of differentiation means that the efficiency of producing any one particular cell type is inevitably low. Although pancreatic differentiation has been reported from HESC, practicable applications for the use of ÎČ-cells derived from HESC to treat diabetes will only be possible once techniques are developed to promote efficient differentiation along the pancreatic lineages.
Methods and Findings
Here, we have tested whether the transcription factor, Pax4 can be used to drive the differentiation of HESC to a ÎČ-cell fate in vitro. We constitutively over-expressed Pax4 in HESCs by stable transfection, and used Q-PCR analysis, immunocytochemistry, ELISA, Ca2+ microfluorimetry and cell imaging to assess the role of Pax4 in the differentiation and intracellular Ca2+ homeostasis of ÎČ-cells developing in embryoid bodies produced from such HESC. Cells expressing key ÎČ-cell markers were isolated by fluorescence-activated cell sorting after staining for high zinc content using the vital dye, Newport Green.
Conclusion
Constitutive expression of Pax4 in HESC substantially enhances their propensity to form putative ÎČ-cells. Our findings provide a novel foundation to study the mechanism of pancreatic ÎČ-cells differentiation during early human development and to help evaluate strategies for the generation of purified ÎČ-cells for future clinical applications
Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
Loss of insulin-producing pancreatic islet ÎČ-cells is a hallmark of type 1 diabetes. Several experimental paradigms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these pathways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling pathways should not be seen as âonâ or âoffâ but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play important roles. Thus, a pathway, once considered as âoffâ or âlowâ may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A formidable source of noncanonical signal transduction concepts is neural stem cells because these cells appear to have acquired unusual signaling interpretations to allow them to maintain their unique dual properties (self-renewal and multipotency). We discuss how such findings from the neural field can provide a blueprint for the identification of new molecular mechanisms regulating pancreatic biology, with a focus on Notch, Hes/Hey, and hedgehog pathways
Common Variation in ISL1 Confers Genetic Susceptibility for Human Congenital Heart Disease
Congenital heart disease (CHD) is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1) is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variantâcommon disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations
Forest Fires in Europe, Middle East and North Africa 2017
This report contains the annual summary of the fire season of 2017 with official figures provided by 31 contributing countries for the number of fires, burnt areas and fire prevention efforts, and the analysis of fire danger and areas mapped in the European Forest Fire Information System (EFFIS).JRC.E.1-Disaster Risk Managemen
Environmental factors in early childhood are associated with multiple sclerosis: a case-control study
<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with increasing incidence mainly in high-income countries. One explanation of this phenomenon may be a higher prevalence of allergic and autoimmune diseases in industrialized countries as a consequence of otherwise beneficial advances in sanitation (hygiene hypothesis). We investigated environmental factors in early childhood associated with MS.</p> <p>Methods</p> <p>A case-control study was performed of 245 MS patients and 296 population-based controls in Berlin. The study participants completed a standardized questionnaire on environmental factors in childhood and youth, including aspects of personal and community hygiene. Multivariable logistic regression analysis was performed to investigate factors in childhood and youth associated with the occurrence of MS.</p> <p>Results</p> <p>Mean age was 46 years (range, 20-80) in the MS group and 42 years (range 18-80) in the control group, of which 73.9% in the MS and 61.5% in the control group were female. The multivariable analysis showed that having at least two older siblings (OR 0.54; p = 0.05, for individuals with two older siblings compared to individuals without older siblings), attending a day-care center (OR 0.5; p = 0.004) and growing up in an urban center with more than 100, 000 inhabitants (OR 0.43; p = 0.009) were factors independently associated with a lower chance for MS.</p> <p>Conclusions</p> <p>The hygiene hypothesis may play a role in the occurrence of MS and could explain disease distribution and increasing incidence.</p
Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges
Marine sponges are well known for their associations with highly diverse, yet very specific and often highly similar microbiota. The aim of this study was to identify potential bacterial sub-populations in relation to sponge phylogeny and sampling sites and to define the core bacterial community. 16S ribosomal RNA gene amplicon pyrosequencing was applied to 32 sponge species from eight locations around the world's oceans, thereby generating 2567 operational taxonomic units (OTUs at the 97% sequence similarity level) in total and up to 364 different OTUs per sponge species. The taxonomic richness detected in this study comprised 25 bacterial phyla with Proteobacteria, Chloroflexi and Poribacteria being most diverse in sponges. Among these phyla were nine candidate phyla, six of them found for the first time in sponges. Similarity comparison of bacterial communities revealed no correlation with host phylogeny but a tropical sub-population in that tropical sponges have more similar bacterial communities to each other than to subtropical sponges. A minimal core bacterial community consisting of very few OTUs (97%, 95% and 90%) was found. These microbes have a global distribution and are probably acquired via environmental transmission. In contrast, a large species-specific bacterial community was detected, which is represented by OTUs present in only a single sponge species. The species-specific bacterial community is probably mainly vertically transmitted. It is proposed that different sponges contain different bacterial species, however, these bacteria are still closely related to each other explaining the observed similarity of bacterial communities in sponges in this and previous studies. This global analysis represents the most comprehensive study of bacterial symbionts in sponges to date and provides novel insights into the complex structure of these unique associations
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