Entropy-driven genome organization

DNA and RNA polymerases active on bacterial and human genomes in the crowded environment of a cell are modeled as beads spaced along a string. Aggregation of the large polymerizing complexes increases the entropy of the system through an increase in entropy of the many small crowding molecules; this occurs despite the entropic costs of looping the intervening DNA. Results of a quantitative cost/benefit analysis are consistent with observations that active polymerases cluster into replication and transcription “factories” in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs

Phenotypic and functional analysis of bovine peripheral blood dendritic before parturition by a novel purification methods

Dendritic cells (DCs) are specialized antigen presenting cells specializing in antigen uptake and processing, and play an important role in the innate and adaptive immune response. A subset of bovine peripheral blood DCs was identified as CD172a+/CD11c+/MHC (major histocompatibility complex) class II+ cells. Although DCs are identified at 0.1%?0.7% of peripheral blood mononuclear cells (PBMC), the phenotype and function of DCs remain poorly understood with regard to maintaining tolerance during the pregnancy. All cattle used in this study were 1 month before parturition. We have established a novel method for the purification of DCs from PBMC using magnetic?activated cell sorting, and purified the CD172a+/CD11c+ DCs, with high expression of MHC class II and CD40, at 84.8% purity. There were individual differences in the expressions of CD205 and co?stimulatory molecules CD80 and CD86 on DCs. There were positive correlations between expression of cytokine and co?stimulatory molecules in DCs, and the DCs maintained their immune tolerance, evidenced by their low expressions of the co?stimulatory molecules and cytokine production. These results suggest that before parturition a half of DCs may be immature and tend to maintain tolerance based on the low cytokine production, and the other DCs with high co?stimulatory molecules may already have the ability of modulating the T?cell linagepublishersversionPeer reviewe

Detection and remediation of organophosphorus compounds by oximate containing organogels

A series of supramolecular diamide organogels containing a reactive compound for the remediation of organophosphorus (OP) species, in particular OP chemical warfare agents (CWAs), has been prepared in DMSO. The organogels have been found to absorb, encapsulate and decontaminate various OP CWA simulants in situ. At high simulant concentrations the gels also undergo a gel–sol transition releasing high local concentrations of remediation agent

Effect of Food Residues on Norovirus Survival on Stainless Steel Surfaces

Background: In households and food processing plants, minute food residues left behind from improper cleaning may influence the survivability of human norovirus on surfaces. In this study, the survivability of norovirus on desiccated food residue-attached stainless steel coupons was investigated. Methodology/Principal Findings: Using murine norovirus-1 (MNV-1) as a surrogate of human norovirus, the survivability of norovirus was investigated on lettuce, cabbage, or ground pork-attached stainless steel coupons. A 6.2 log MPN/ml of MNV-1 infectivity was completely lost at day 30 in residue-free coupons, whereas only a 1.4 log MPN/ml reduction was observed in coupons with residues. Moreover, the disinfective effect of sodium hypochlorite was reduced when residues were present on the coupons. Conclusions/Significance: This study revealed that the food residues increased the survivability and the resistance to chemicals of norovirus, indicating the need of thorough cleaning in food processing plants and household settings

THE NEUTRAL INTERSTELLAR GAS TOWARD SNR W44: CANDIDATES FOR TARGET PROTONS IN HADRONIC γ-RAY PRODUCTION IN A MIDDLE-AGED SUPERNOVA REMNANT

We present an analysis of the interstellar medium (ISM) toward the γ-ray supernova remnant (SNR) W44. We used NANTEN2 12CO(J = 2-1) and 12CO(J = 1-0) data and Arecibo H I data in order to identify the molecular and atomic gas in the SNR. We confirmed that the molecular gas is located in the SNR shell with a primary peak toward the eastern edge of the shell. We newly identified high-excitation molecular gas along the eastern shell of the SNR in addition to the high-excitation broad gas previously observed inside the shell; the line intensity ratio between the 12CO(J = 2-1) and 12CO(J = 1-0) transitions in these regions is greater than ~1.0, suggesting a kinetic temperature of 30 K or higher, which is most likely due to heating by shock interaction. By comparing the ISM with γ-rays, we find that target protons of hadronic origin are dominated by molecular protons of average density around 200 cm–3, where the possible contribution of atomic protons is 10% or less. This average density is consistent with the recent discovery of the low-energy γ-rays suppressed in 50 MeV-10 GeV as observed with AGILE and Fermi. The γ-ray spectrum differs from place to place in the SNR, suggesting that the cosmic-ray (CR) proton spectrum significantly changes within the middle-aged SNR perhaps due to the energy-dependent escape of CR protons from the acceleration site. We finally derive a total CR proton energy of ~1049 erg, consistent with the SN origin of the majority of the CRs in the Galaxy

Interleukin-6 secretion is limited by self-signaling in endosomes

Contains fulltext : 202589.pdf (publisher's version ) (Open Access

Conditional Stat1 Ablation Reveals the Importance of Interferon Signaling for Immunity to Listeria monocytogenes Infection

Signal transducer and activator of transcription 1 (Stat1) is a key player in responses to interferons (IFN). Mutations of Stat1 cause severe immune deficiencies in humans and mice. Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellular bacterial pathogen Listeria monocytogenes (Lm). Cell type-restricted ablation of the Stat1 gene in naïve animals revealed unique roles in three cell types: macrophage Stat1 signaling protected against lethal Lm infection, whereas Stat1 ablation in dendritic cells (DC) did not affect survival. T lymphocyte Stat1 reduced survival. Type I IFN (IFN-I) signaling in T lymphocytes reportedly weakens innate resistance to Lm. Surprisingly, the effect of Stat1 signaling was much more pronounced, indicating a contribution of Stat1 to pathways other than the IFN-I pathway. In stark contrast, Stat1 activity in both DC and T cells contributed positively to secondary immune responses against Lm in immunized animals, while macrophage Stat1 was dispensable. Our findings provide the first genetic evidence that Stat1 signaling in different cell types produces antagonistic effects on innate protection against Lm that are obscured in mice with complete Stat1 deficiency. They further demonstrate a drastic change in the cell type-dependent Stat1 requirement for memory responses to Lm infection

Transcription-driven genome organization::A model for chromosome structure and the regulation of gene expression tested through simulations

Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and topologically-associating domains (TADs), to contact domains stabilized by cohesin and CTCF. However, molecular mechanisms underlying this folding, and the way folding affects transcriptional activity, remain obscure. Here we review physical principles driving proteins bound to long polymers into clusters surrounded by loops, and present a parsimonious yet comprehensive model for the way the organization determines function. We argue that clusters of active RNA polymerases and their transcription factors are major architectural features; then, contact domains, TADs and compartments just reflect one or more loops and clusters. We suggest tethering a gene close to a cluster containing appropriate factors—a transcription factory—increases the firing frequency, and offer solutions to many current puzzles concerning the actions of enhancers, super-enhancers, boundaries and eQTLs (expression quantitative trait loci). As a result, the activity of any gene is directly influenced by the activity of other transcription units around it in 3D space, and this is supported by Brownian-dynamics simulations of transcription factors binding to cognate sites on long polymers