Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells

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Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay

BackgroundIn a previous work we showed the feasibility of an interferon gamma release assay (IGRA) for detecting latent infection by Histoplasma capsulatum. While in that proof-of-concept study we used crude fungal extracts as antigens, the newest IGRAs developed for other infections are based on molecularly defined antigens, mostly on mixtures of immunogenic peptides.AimsTo identify proteins in H. capsulatum that might serve as molecularly defined antigens for an IGRA test.MethodsWe surveyed the literature looking for known H. capsulatum-immunogenic proteins and assayed two of them as antigens in an IGRA test, in a study that involved 80 volunteers. Furthermore, we used several bioinformatics tools to identify specific H. capsulatum proteins and to analyze possible strategies for the design of H. capsulatum-specific immunogenic peptides.ResultsSeven H. capsulatum-immunogenic proteins were retrieved from the literature. IGRA tests using either the heat shock protein 60 or the M antigen showed high sensitivities but low specificities, most likely due to the high sequence similarity with the corresponding orthologs in other pathogenic microorganisms. We identified around 2000 H. capsulatum-specific proteins, most of which remain unannotated. Class II T-cell epitope predictions for a small number of these proteins showed a great variability among different alleles, prompting for a “brute force” approach for peptide design.ConclusionsThe H. capsulatum genome encodes a large number of distinctive proteins, which represent a valuable source of potential specific antigens for an IGRA test. Among them, the Cfp4 protein stands out as a very attractive candidate.     

Anthropogenic modifications to fire regimes in the wider Serengeti‐Mara ecosystem

Fire is a key driver in savannah systems and widely used as a land management tool. Intensifying human land uses are leading to rapid changes in the fire regimes, with consequences for ecosystem functioning and composition. We undertake a novel analysis describing spatial patterns in the fire regime of the Serengeti‐Mara ecosystem, document multidecadal temporal changes and investigate the factors underlying these patterns. We used MODIS active fire and burned area products from 2001 to 2014 to identify individual fires; summarizing four characteristics for each detected fire: size, ignition date, time since last fire and radiative power. Using satellite imagery, we estimated the rate of change in the density of livestock bomas as a proxy for livestock density. We used these metrics to model drivers of variation in the four fire characteristics, as well as total number of fires and total area burned. Fires in the Serengeti‐Mara show high spatial variability—with number of fires and ignition date mirroring mean annual precipitation. The short‐term effect of rainfall decreases fire size and intensity but cumulative rainfall over several years leads to increased standing grass biomass and fuel loads, and, therefore, in larger and hotter fires. Our study reveals dramatic changes over time, with a reduction in total number of fires and total area burned, to the point where some areas now experience virtually no fire. We suggest that increasing livestock numbers are driving this decline, presumably by inhibiting fire spread. These temporal patterns are part of a global decline in total area burned, especially in savannahs, and we caution that ecosystem functioning may have been compromised. Land managers and policy formulators need to factor in rapid fire regime modifications to achieve management objectives and maintain the ecological function of savannah ecosystems.     

Tryptamine derivatives disarm colistin resistance in polymyxin-resistant gram-negative bacteria

The last three decades have seen a dwindling number of novel antibiotic classes approved for clinical use and a concurrent increase in levels of antibiotic resistance, necessitating alternative methods to combat the rise of multi-drug resistant bacteria. A promising strategy employs antibiotic adjuvants, non-toxic molecules that disarm antibiotic resistance. When co-dosed with antibiotics, these compounds restore antibiotic efficacy in drug-resistant strains. Herein we identify derivatives of tryptamine, a ubiquitous biochemical scaffold containing an indole ring system, capable of disarming colistin resistance in the Gram-negative bacterial pathogens Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli while having no inherent bacterial toxicity. Resistance was overcome in strains carrying endogenous chromosomally-encoded colistin resistance machinery, as well as resistance conferred by the mobile colistin resistance-1 (mcr-1) plasmid-borne gene. These compounds restore a colistin minimum inhibitory concentration (MIC) below the Clinical & Laboratory Sciences Institute (CLSI) breakpoint in all resistant strains.     

Liver size and lipid content differences between BALB/c and BALB/cJ mice on a high-fat diet are due,in part,to Zhx2

Mammalian Genome - BALB/cJ mice exhibit considerable phenotypic differences with other BALB/c substrains. Some of these traits involve the liver, including persistent postnatal expression of genes...     

Does plant allometry predict biased sex allocation in Triadica sebifera (L.) small (Euphorbiaceae)?

Plant Ecology - Early seed production by non-native plants may be important to their successful establishment and spread. Understanding the mechanisms underlying age- or size-biased seed production...     

Oxidative stress in primary culture hepatocytes isolated from partially hepatectomized rats

The aim of this study was to evaluate the influence of partial hepatectomy prior to cell isolation on hepatocytes in vitro. We characterized the possible changes of various stress oxidative parameters within the first 24 h after seeding. Male Wistar rats served as donors. Hepatocytes were isolated by collagenase digestion from either liver of simulated surgery (SH) or from liver 1 h after 70% hepatectomy (PH), and the changes in stress parameters were analyzed after 1, 3, 18, and 24 h in culture. At 24 h, only hepatocytes from PH maintained significantly increased reactive oxygen species production, oxidized glutathione percentage, and Cu/Zn superoxide dismutase and catalase activities. Our results show that hepatocytes suffer significant cell injury as a result of the isolation procedure, but primary cultured cells from SH metabolically recover from this stress after 18 h. After this time, primary culture hepatocytes primed by PH maintain their in vivo-like metabolic activities (increase in both oxidative stress and antioxidant status).