Monocyclic aromatic amines as potential human carcinogens: old is new again

Alkylanilines are a group of chemicals whose ubiquitous presence in the environment is a result of the multitude of sources from which they originate. Exposure assessments indicate that most individuals experience lifelong exposure to these compounds. Many alkylanilines have biological activity similar to that of the carcinogenic multi-ring aromatic amines. This review provides an overview of human exposure and biological effects. It also describes recent investigations into the biochemical mechanisms of action that lead to the assessment that they are most probably more complex than those of the more extensively investigated multi-ring aromatic amines. Not only is nitrenium ion chemistry implicated in DNA damage by alkylanilines but also reactions involving quinone imines and perhaps reactive oxygen species. Recent results described here indicate that alkylanilines can be potent genotoxins for cultured mammalian cells when activated by exogenous or endogenous phase I and phase II xenobiotic-metabolizing enzymes. The nature of specific DNA damage products responsible for mutagenicity remains to be identified but evidence to date supports mechanisms of activation through obligatory N-hydroxylation as well as subsequent conjugation by sulfation and/or acetylation. A fuller understanding of the mechanisms of alkylaniline genotoxicity is expected to provide important insights into the environmental and genetic origins of one or more human cancers and may reveal a substantial role for this group of compounds as potential human chemical carcinogens.National Institute of Environmental Health Sciences (PO1-ES006052)National Institute of Environmental Health Sciences (P30-ES002109

Potential for Prebiotics as Feed Additives to Limit Foodborne Campylobacter Establishment in the Poultry Gastrointestinal Tract

Campylobacter as an inhabitant of the poultry gastrointestinal tract has proven to be difficult to reduce with most feed additives. In-feed antibiotics have been taken out of poultry diets due to the negative reactions of consumers along with concerns regarding the generation of antibiotic resistant bacteria. Consequently, interest in alternative feed supplements to antibiotics has grown. One of these alternatives, prebiotics, has been examined as a potential animal and poultry feed additive. Prebiotics are non-digestible ingredients by host enzymes that enhance growth of indigenous gastrointestinal bacteria that elicit metabolic characteristics considered beneficial to the host and depending on the type of metabolite, antagonistic to establishment of pathogens. There are several carbohydrate polymers that qualify as prebiotics and have been fed to poultry. These include mannan-oligosaccharides and fructooligosaccharides as the most common ones marketed commercially that have been used as feed supplements in poultry. More recently, several other non-digestible oligosaccharides have also been identified as possessing prebiotic properties when implemented as feed supplements. While there is evidence that prebiotics may be effective in poultry and limit establishment of foodborne pathogens such as Salmonella in the gastrointestinal tract, less is known about their impact on Campylobacter. This review will focus on the potential of prebiotics to limit establishment of Campylobacter in the poultry gastrointestinal tract and future research directions

The Potential Link between Thermal Resistance and Virulence in Salmonella: A Review

In some animals, the typical body temperature can be higher than humans, for example, 42°C in poultry and 40°C in rabbits which can be a potential thermal stress challenge for pathogens. Even in animals with lower body temperatures, when infection occurs, the immune system may increase body temperature to reduce the chance of survival for pathogens. However, some pathogens can still easily overcome higher body temperatures and/or rise in body temperatures through expression of stress response mechanisms. Salmonella is the causative agent of one of the most prevalent foodborne illnesses, salmonellosis, and can readily survive over a wide range of temperatures due to the efficient expression of the heat (thermal) stress response. Therefore, thermal resistance mechanisms can provide cross protection against other stresses including the non-specific host defenses found within the human body thus increasing pathogenic potential. Understanding the molecular mechanisms associated with thermal responses in Salmonella is crucial in designing and developing more effective or new treatments for reducing and eliminating infection caused by Salmonella that have survived heat stress. In this review, Salmonella thermal resistance is assessed followed by an overview of the thermal stress responses with a focus on gene regulation by sigma factors, heat shock proteins, along with the corresponding thermosensors and their association with virulence expression including a focus on a potential link between heat resistance and potential for infection

In silico analyses of diversity and dissemination of antimicrobial resistance genes and mobile genetics elements, for plasmids of enteric pathogens

IntroductionThe antimicrobial resistance (AMR) mobilome plays a key role in the dissemination of resistance genes encoded by mobile genetics elements (MGEs) including plasmids, transposons (Tns), and insertion sequences (ISs). These MGEs contribute to the dissemination of multidrug resistance (MDR) in enteric bacterial pathogens which have been considered as a global public health risk.MethodsTo further understand the diversity and distribution of AMR genes and MGEs across different plasmid types, we utilized multiple sequence-based computational approaches to evaluate AMR-associated plasmid genetics. A collection of 1,309 complete plasmid sequences from Gammaproteobacterial species, including 100 plasmids from each of the following 14 incompatibility (Inc) types: A/C, BO, FIA, FIB, FIC, FIIA, HI1, HI2, I1, K, M, N, P except W, where only 9 sequences were available, was extracted from the National Center for Biotechnology Information (NCBI) GenBank database using BLAST tools. The extracted FASTA files were analyzed using the AMRFinderPlus web-based tools to detect antimicrobial, disinfectant, biocide, and heavy metal resistance genes and ISFinder to identify IS/Tn MGEs within the plasmid sequences.Results and DiscussionIn silico prediction based on plasmid replicon types showed that the resistance genes were diverse among plasmids, yet multiple genes were widely distributed across the plasmids from enteric bacterial species. These findings provide insights into the diversity of resistance genes and that MGEs mediate potential transmission of these genes across multiple plasmid replicon types. This notion was supported by the observation that many IS/Tn MGEs and resistance genes known to be associated with them were common across multiple different plasmid types. Our results provide critical insights about how the diverse population of resistance genes that are carried by the different plasmid types can allow for the dissemination of AMR across enteric bacteria. The results also highlight the value of computational-based approaches and in silico analyses for the assessment of AMR and MGEs, which are important elements of molecular epidemiology and public health outcomes

The GALFA-HI Survey: Data Release 1

We present the Galactic Arecibo L-Band Feed Array HI (GALFA-HI) survey, and its first full data release (DR1). GALFA-HI is a high resolution (~ 4'), large area (13000 deg^2), high spectral resolution (0.18 km/s), wide band (-700 < v_LSR < +700 km/s) survey of the Galactic interstellar medium in the 21-cm line hyperfine transition of neutral hydrogen conducted at Arecibo Observatory. Typical noise levels are 80 mK RMS in an integrated 1 km/s channel. GALFA-HI is a dramatic step forward in high-resolution, large-area Galactic HI surveys, and we compare GALFA-HI to past, present, and future Galactic HI surveys. We describe in detail new techniques we have developed to reduce these data in the presence of fixed pattern noise, gain variation, and inconsistent beam shapes, and we show how we have largely mitigated these effects. We present our first full data release, covering 7520 square degrees of sky and representing 3046 hours of integration time, and discuss the details of these data.Comment: Accepted to the ApJ

Compact HI clouds from the GALFA-HI survey

The Galactic Arecibo L-band Feed Array HI (GALFA-HI) survey is mapping the entire Arecibo sky at 21-cm, over a velocity range of -700 to +700 km/s (LSR), at a velocity resolution of 0.18 km/s and a spatial resolution of 3.5 arcmin. The unprecedented resolution and sensitivity of the GALFA-HI survey have resulted in the detection of numerous isolated, very compact HI clouds at low Galactic velocities, which are distinctly separated from the HI disk emission. In the limited area of ~4600 deg$^2$ surveyed so far, we have detected 96 of such compact clouds. The detected clouds are cold with a median T$_{k,max}$ (the kinetic temperature in the case in which there is no non-thermal broadening) of 300 K. Moreover, these clouds are quite compact and faint, with median values of 5 arcmin in angular size, 0.75 K in peak brightness temperature, and $5 \times 10^{18}$ cm$^{-2}$ in HI column density. Most of the clouds deviate from Galactic rotation at the 20-30 km/s level, and a significant fraction show evidence for a multiphase medium and velocity gradients. No counterparts for these clouds were found in other wavebands. From the modeling of spatial and velocity distributions of the whole compact cloud population, we find that the bulk of the compact clouds are related to the Galactic disk, and their distances are likely to be in the range of 0.1 to a few kpc. We discuss various possible scenarios for the formation and maintenance of this cloud population and its significance for Galactic ISM studies.Comment: Accepted for publication in the Astrophysical Journa

The genome of the freshwater monogonont rotifer Brachionus calyciflorus

Monogononta is the most speciose class of rotifers, with more than 2,000 species. The monogonont genus Brachionus is widely distributed at a global scale, and a few of its species are commonly used as ecological and evolutionary models to address questions related to aquatic ecology, cryptic speciation, evolutionary ecology, the evolution of sex and ecotoxicology. With the importance of Brachionus species in many areas of research, it is remarkable that the genome has not been characterized. This study aims to address this lacuna by presenting, for the first time, the whole‐genome assembly of the freshwater species Brachionus calyciflorus. The total length of the assembled genome was 129.6 Mb, with 1,041 scaffolds. The N50 value was 786.6 kb, and the GC content was 24%. A total of 16,114 genes were annotated with repeat sequences, accounting for 21% of the assembled genome. This assembled genome may form a basis for future studies addressing key questions on the evolution of monogonont rotifers. It will also provide the necessary molecular resources to mechanistically investigate ecophysiological and ecotoxicological responses. </p

NCoR Repression of LXRs Restricts Macrophage Biosynthesis of Insulin-Sensitizing Omega 3 Fatty Acids

SummaryMacrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and ω3 fatty acids. Remarkably, the increased ω3 fatty acid levels primarily inhibit NF-κB-dependent inflammatory responses by uncoupling NF-κB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies