DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells

Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mφs), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis–derived material was detected in CD14−HLA-DR+DC-SIGN+ cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN–mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity

Tailoring Anderson localization by disorder correlations in 1D speckle potentials

We study Anderson localization of single particles in continuous, correlated, one-dimensional disordered potentials. We show that tailored correlations can completely change the energy-dependence of the localization length. By considering two suitable models of disorder, we explicitly show that disorder correlations can lead to a nonmonotonic behavior of the localization length versus energy. Numerical calculations performed within the transfer-matrix approach and analytical calculations performed within the phase formalism up to order three show excellent agreement and demonstrate the effect. We finally show how the nonmonotonic behavior of the localization length with energy can be observed using expanding ultracold-atom gases

Heroes and villains of world history across cultures

© 2015 Hanke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedEmergent properties of global political culture were examined using data from the World History Survey (WHS) involving 6,902 university students in 37 countries evaluating 40 figures from world history. Multidimensional scaling and factor analysis techniques found only limited forms of universality in evaluations across Western, Catholic/Orthodox, Muslim, and Asian country clusters. The highest consensus across cultures involved scientific innovators, with Einstein having the most positive evaluation overall. Peaceful humanitarians like Mother Theresa and Gandhi followed. There was much less cross-cultural consistency in the evaluation of negative figures, led by Hitler, Osama bin Laden, and Saddam Hussein. After more traditional empirical methods (e.g., factor analysis) failed to identify meaningful cross-cultural patterns, Latent Profile Analysis (LPA) was used to identify four global representational profiles: Secular and Religious Idealists were overwhelmingly prevalent in Christian countries, and Political Realists were common in Muslim and Asian countries. We discuss possible consequences and interpretations of these different representational profiles.This research was supported by grant RG016-P-10 from the Chiang Ching-Kuo Foundation for International Scholarly Exchange (http://www.cckf.org.tw/). Religion Culture Entropy China Democracy Economic histor

Surveillance of the short-term impact of fine particle air pollution on cardiovascular disease hospitalizations in New York State

<p>Abstract</p> <p>Background</p> <p>Studies have shown that the effects of particulate matter on health vary based on factors including the vulnerability of the population, health care practices, exposure factors, and the pollutant mix.</p> <p>Methods</p> <p>We used time-stratified case-crossover to estimate differences in the short-term impacts of PM_2.5on cardiovascular disease hospital admissions in New York State by geographic area, year, age, gender, co-morbid conditions, and area poverty rates.</p> <p>Results</p> <p>PM_2.5had a stronger impact on heart failure than other cardiovascular diagnoses, with 3.1% of heart failure admissions attributable to short-term PM_2.5exposure over background levels of 5 ug/m³. Older adults were significantly more susceptible to heart failure after short-term ambient PM_2.5exposure than younger adults.</p> <p>Conclusion</p> <p>The short-term impact of PM_2.5on cardiovascular disease admissions, and modifications of that impact, are small and difficult to measure with precision. Multi-state collaborations will be necessary to attain more precision to describe spatiotemporal differences in health impacts.</p

Properties of field functionals and characterization of local functionals

Functionals (i.e. functions of functions) are widely used in quantum field theory and solid-state physics. In this paper, functionals are given a rigorous mathematical framework and their main properties are described. The choice of the proper space of test functions (smooth functions) and of the relevant concept of differential (Bastiani differential) are discussed. The relation between the multiple derivatives of a functional and the corresponding distributions is described in detail. It is proved that, in a neighborhood of every test function, the support of a smooth functional is uniformly compactly supported and the order of the corresponding distribution is uniformly bounded. Relying on a recent work by Yoann Dabrowski, several spaces of functionals are furnished with a complete and nuclear topology. In view of physical applications, it is shown that most formal manipulations can be given a rigorous meaning. A new concept of local functionals is proposed and two characterizations of them are given: the first one uses the additivity (or Hammerstein) property, the second one is a variant of Peetre's theorem. Finally, the first step of a cohomological approach to quantum field theory is carried out by proving a global Poincar\'e lemma and defining multi-vector fields and graded functionals within our framework.Comment: 32 pages, no figur

Syndromic surveillance and heat wave morbidity: a pilot study based on emergency departments in France

<p>Abstract</p> <p>Background</p> <p>The health impacts of heat waves are serious and have prompted the development of heat wave response plans. Even when they are efficient, these plans are developed to limit the health effects of heat waves. This study was designed to determine relevant indicators related to health effects of heat waves and to evaluate the ability of a syndromic surveillance system to monitor variations in the activity of emergency departments over time. The study uses data collected during the summer 2006 when a new heat wave occurred in France.</p> <p>Methods</p> <p>Data recorded from 49 emergency departments since July 2004, were transmitted daily via the Internet to the French Institute for Public Health Surveillance. Items collected on patients included diagnosis (ICD10 codes), outcome, and age. Statistical t-tests were used to compare, for several health conditions, the daily averages of patients within different age groups and periods (whether 'on alert' or 'off alert').</p> <p>Results</p> <p>A limited number of adverse health conditions occurred more frequently during hot period: dehydration, hyperthermia, malaise, hyponatremia, renal colic, and renal failure. Over all health conditions, the total number of patients per day remained equal between the 'on alert' and 'off alert' periods (4,557.7/day vs. 4,511.2/day), but the number of elderly patients increased significantly during the 'on alert' period relative to the 'off alert' period (476.7/day vs. 446.2/day p < 0.05).</p> <p>Conclusion</p> <p>Our results show the interest to monitor specific indicators during hot periods and to focus surveillance efforts on the elderly. Syndromic surveillance allowed the collection of data in real time and the subsequent optimization of the response by public health agencies. This method of surveillance should therefore be considered as an essential part of efforts to prevent the health effects of heat waves.</p

Emergence of semi-localized Anderson modes in a disordered photonic crystal as a result of overlap probability

In this paper we study the effect of positional randomness on transmissional properties of a two dimensional photonic crystal as a function of a randomness parameter $\alpha$ ($\alpha=0$ completely ordered, $\alpha=1$ completely disordered). We use finite-difference time-domain~(FDTD) method to solve the Maxwell's equations in such a medium numerically. We consider two situations: first a 90\degr bent photonic crystal wave-guide and second a centrally pulsed photonic crystal micro-cavity. We plot various figures for each case which characterize the effect of randomness quantitatively. More specifically, in the wave-guide situation, we show that the general shape of the normalized total output energy is a Gaussian function of randomness with wavelength-dependent width. For centrally pulsed PC, the output energy curves display extremum behavior both as a function of time as well as randomness. We explain these effects in terms of two distinct but simultaneous effects which emerge with increasing randomness, namely the creation of semi-localized modes and the shrinking (and eventual destruction) of the photonic band-gaps. Semi-localized (i.e. Anderson localized) modes are seen to arise as a synchronization of internal modes within a cluster of randomly positioned dielectric nano-particles. The general trend we observe shows a sharp change of behavior in the intermediate randomness regime (i.e. $\alpha \approx 0.5$) which we attribute to a similar behavior in the underlying overlap probability of nano-particlesComment: New published version with a new title. This article is featured on the cover of the corresponding journal (Nov. issue of EJPB

Glycosaminoglycan Interactions in Murine Gammaherpesvirus-68 Infection

Glycosaminoglycans (GAGs) commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68) infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces

High Resolution Methylome Map of Rat Indicates Role of Intragenic DNA Methylation in Identification of Coding Region

DNA methylation is crucial for gene regulation and maintenance of genomic stability. Rat has been a key model system in understanding mammalian systemic physiology, however detailed rat methylome remains uncharacterized till date. Here, we present the first high resolution methylome of rat liver generated using Methylated DNA immunoprecipitation and high throughput sequencing (MeDIP-Seq) approach. We observed that within the DNA/RNA repeat elements, simple repeats harbor the highest degree of methylation. Promoter hypomethylation and exon hypermethylation were common features in both RefSeq genes and expressed genes (as evaluated by proteomic approach). We also found that although CpG islands were generally hypomethylated, about 6% of them were methylated and a large proportion (37%) of methylated islands fell within the exons. Notably, we obeserved significant differences in methylation of terminal exons (UTRs); methylation being more pronounced in coding/partially coding exons compared to the non-coding exons. Further, events like alternate exon splicing (cassette exon) and intron retentions were marked by DNA methylation and these regions are retained in the final transcript. Thus, we suggest that DNA methylation could play a crucial role in marking coding regions thereby regulating alternative splicing. Apart from generating the first high resolution methylome map of rat liver tissue, the present study provides several critical insights into methylome organization and extends our understanding of interplay between epigenome, gene expression and genome stability

Detection and Removal of Biases in the Analysis of Next-Generation Sequencing Reads

Since the emergence of next-generation sequencing (NGS) technologies, great effort has been put into the development of tools for analysis of the short reads. In parallel, knowledge is increasing regarding biases inherent in these technologies. Here we discuss four different biases we encountered while analyzing various Illumina datasets. These biases are due to both biological and statistical effects that in particular affect comparisons between different genomic regions. Specifically, we encountered biases pertaining to the distributions of nucleotides across sequencing cycles, to mappability, to contamination of pre-mRNA with mRNA, and to non-uniform hydrolysis of RNA. Most of these biases are not specific to one analyzed dataset, but are present across a variety of datasets and within a variety of genomic contexts. Importantly, some of these biases correlated in a highly significant manner with biological features, including transcript length, gene expression levels, conservation levels, and exon-intron architecture, misleadingly increasing the credibility of results due to them. We also demonstrate the relevance of these biases in the context of analyzing an NGS dataset mapping transcriptionally engaged RNA polymerase II (RNAPII) in the context of exon-intron architecture, and show that elimination of these biases is crucial for avoiding erroneous interpretation of the data. Collectively, our results highlight several important pitfalls, challenges and approaches in the analysis of NGS reads