The rockefeller university

The optimal foraging strategy in a given environment depends on the number of competing individuals and their behavioural strategies. Little is known about the genes and neural circuits that integrate social information into foraging decisions. Here we show that ascaroside pheromones, small glycolipids that signal population density, suppress exploratory foraging in Caenorhabditis elegans, and that heritable variation in this behaviour generates alternative foraging strategies. We find that natural C. elegans isolates differ in their sensitivity to the potent ascaroside icas#9 (IC-asc-C5). A quantitative trait locus (QTL) regulating icas#9 sensitivity includes srx-43, a G-protein-coupled icas#9 receptor that acts in the ASI class of sensory neurons to suppress exploration. Two ancient haplotypes associated with this QTL confer competitive growth advantages that depend on ascaroside secretion, its detection by srx-43 and the distribution of food. These results suggest that balancing selection at the srx-43 locus generates alternative density-dependent behaviours, fulfilling a prediction of foraging game theory.

Acinar cells make up the majority of all cells in the pancreas, yet the source of new acinar cells during homeostasis remains unknown. Using multicolor lineage-tracing and organoid-formation assays, we identified the presence of a progenitor-like acinar cell subpopulation. These cells have long-term self-renewal capacity, albeit in a unipotent fashion. We further demonstrate that binuclear acinar cells are terminally differentiated acinar cells. Transcriptome analysis of single acinar cells revealed the existence of a minor population of cells expressing progenitor markers. Interestingly, a gain of the identified markers accompanied by a transient gain of proliferation was observed following chemically induced pancreatitis. Altogether, our study identifies a functionally and molecularly distinct acinar subpopulation and thus transforms our understanding of the acinar cell compartment as a pool of equipotent secretory cells.

Background: Staphylococcus aureus is the most common cause of Skin and Soft Tissue Infections (SSTIs) in the community in the United States of America. Community Health Centers (CHC) serve as primary care providers for thousands of immigrants in New York. Methods: As part of a research collaborative, 6 New York City-area CHCs recruited patients with SSTIs. Characterization was performed in all S. aureus isolates from wounds and nasal swabs collected from patients. Statistical analysis examined the differences in wound and nasal cultures among immigrant compared to native-born patients. Results: Wound and nasal specimens were recovered from 129 patients and tested for antibiotic susceptibility. 40 patients were immigrants from 15 different countries. Although not statistically significant, immigrants had lower rates of MRSA infections (n = 15) than did native-born participants, and immigrants showed significantly higher rates of MSSA wound cultures (n = 11) (OR = 3.5, 95% CI: 1.3, 9.7). Conclusions: In our study, immigrants were more likely to present with SSTIs caused by MSSA than US-born patients. Immigants also reported lower frequencies of antibiotic prescription or consumption in the months prior to SSTI infection. This suggests that antibiotic resistance may vary regionally and that immigrants presenting with SST's may benefit from a broader range of antibiotics. (C) 2016 Elsevier Ltd. All rights reserved.

Aged skin heals wounds poorly, increasing susceptibility to infections. Restoring homeostasis after wounding requires the coordinated actions of epidermal and immune cells. Here we find that both intrinsic defects and communication with immune cells are impaired in aged keratinocytes, diminishing their efficiency in restoring the skin barrier after wounding. At the wound-edge, aged keratinocytes display reduced proliferation and migration. They also exhibit a dampened ability to transcriptionally activate epithelial-immune crosstalk regulators, including a failure to properly activate/maintain dendritic epithelial T cells (DETCs), which promote re-epithelialization following injury. Probing mechanism, we find that aged keratinocytes near the wound edge don't efficiently upregulate Skints or activate STAT3. Notably, when epidermal Stat3, Skints, or DETCs are silenced in young skin, re-epithelialization following wounding is perturbed. These findings underscore epithelial-immune crosstalk perturbations in general, and Skints in particular, as critical mediators in the age-related decline in wound-repair.

Mild versus severe psoriasis is often distinguished by clinical measures such as the extent of skin involvement or Psoriasis Area and Severity Index score, both of which use arbitrary boundaries. It is widely assumed that severe psoriasis involves higher levels of skin inflammation, but comparative molecular profiles of mild versus severe disease have not been performed. In this study, we used immunohistochemistry, reverse transcription PCR, and gene arrays to determine the phenotype of North American patients with mild psoriasis (n = 34, mean PASI score = 5.5) versus severe psoriasis (n = 23, mean PASI score = 23.2). Overall, skin inflammation, defined as the sum of T-cell infiltration/activation and IL-17-mediated epidermal responses, was not higher in severe psoriasis lesions. Surprisingly, mild psoriasis was characterized by higher numbers of T cells in skin lesions, higher IL-17A expression, and stronger expression of the core psoriasis transcriptome. In contrast, severe psoriasis was characterized by stronger expression of some epidermal response genes (TGFA, CALM1, SMPD3, and IL1RL2). However, a key molecular distinction was higher expression of negative immune regulatory genes (CTLA4, CD69 and PD-L1) in mild lesions compared with severe psoriasis lesions. These data have important implications for treating psoriasis across the spectrum of disease, as well as for potential mechanisms that allow psoriasis to progress to more extensive cutaneous disease.

Background: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Methods: Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n = 163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n = 143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n = 153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). Results: Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR= 0.032; p(corrected) = 0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR = 5.24; p(corrected) = 0.041) (HC vs. NOD). Conclusions: This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Properly condensed chromosomes are necessary for accurate segregation of the sisters after DNA replication. The Escherichia coli condesin is MukB, a structural maintenance of chromosomes (SMC)-like protein, which forms a complex with MukE and the kleisin MukF. MukB is known to be able to mediate knotting of a DNA ring, an intramolecular reaction. In our investigations of how MukB condenses DNA we discovered that it can also mediate catenation of two DNA rings, an intermolecular reaction. This activity of MukB requires DNA binding by the head domains of the protein but does not require either ATP or its partner proteins MukE or MukF. The ability of MukB to mediate DNA catenation underscores its potential for bringing distal regions of a chromosome together.