The effect of the timing of exposure to Campylobacter jejuni on the gut microbiome and inflammatory responses of broiler chickens

Background Campylobacters are an unwelcome member of the poultry gut microbiota in terms of food safety. The objective of this study was to compare the microbiota, inflammatory responses, and zootechnical parameters of broiler chickens not exposed to Campylobacter jejuni with those exposed either early at 6 days old or at the age commercial broiler chicken flocks are frequently observed to become colonized at 20 days old. Results Birds infected with Campylobacter at 20 days became cecal colonized within 2 days of exposure, whereas birds infected at 6 days of age did not show complete colonization of the sample cohort until 9 days post-infection. All birds sampled thereafter were colonized until the end of the study at 35 days (mean 6.1 log10 CFU per g of cecal contents). The cecal microbiota of birds infected with Campylobacter were significantly different to age-matched non-infected controls at 2 days post-infection but generally the composition of the cecal microbiota were more affected by bird age as the time post infection increased. The effects of Campylobacter colonization on the cecal microbiota were associated with reductions in the relative abundance of OTUs within the taxonomic family Lactobacillaceae and the Clostridium cluster XIVa. Specific members of the Lachnospiraceae and Ruminococcaceae families exhibit transient shifts in microbial community populations dependent upon the age at which the birds become colonized by C. jejuni. Analysis of ileal and cecal chemokine/cytokine gene expression revealed increases in IL-6, IL-17A and Il-17F consistent with a Th17 response but the persistence of the response was dependent on the stage/time of C. jejuni colonization that coincide with significant reductions in the abundance of Clostridium cluster XIVa. Conclusions This study combines microbiome data, cytokine/chemokine gene expression with intestinal villus and crypt measurements to compare chickens colonized early or late in the rearing cycle to provide insights into the process and outcomes of Campylobacter colonization. Early colonization results in a transient growth rate reduction and pro-inflammatory response but persistent modification of the cecal microbiota. Late colonization produces pro-inflammatory responses with changes in the cecal microbiota that will endure in market ready chickens

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

A life course examination of the physical environmental determinants of physical activity behaviour: A “Determinants of Diet and Physical Activity” (DEDIPAC) umbrella systematic literature review.

Background: Participation in regular physical activity is associated with a multitude of health benefits across the life course. However, many people fail to meet PA recommendations. Despite a plethora of studies, the evidence regarding the environmental (physical) determinants of physical activity remains inconclusive. Objective: To identify the physical environmental determinants that influence PA across the life course. Methods: An online systematic literature search was conducted using MEDLINE, ISI Web of Science, Scopus and SPORTDiscus. The search was limited to studies published in English (January 2004 to April 2016). Only systematic literature reviews (SLRs) and meta-analyses (MAs) of observational studies, that investigated the association between physical determinants and physical activity outcomes, were eligible for inclusion. The extracted data were assessed on the importance of determinants, strength of evidence and methodological quality. Results: The literature search identified 28 SLRs and 3 MAs on 67 physical environmental characteristics potentially related to physical activity that were eligible for inclusion. Among preschool children, a positive association was reported between availability of backyard space and outdoor toys/equipment in the home and overall physical activity. The availability of physical activity programs and equipment within schools, and neighbourhood features such as pedestrian and cyclist safety structure were positively associated with physical activity in children and adolescents. Negative street characteristics, for example, lack of sidewalks and streetlights, were negatively associated with physical activity in adults. Inconsistent associations were reported for the majority of reviewed determinants in adults. Conclusion: This umbrella SLR provided a comprehensive overview of the physical environment determinants of physical activity across the life course and has highlighted, particularly amongst youth, a number of key determinants that may be associated with overall physical activity. Given the limited evidence drawn mostly from cross-sectional studies, longitudinal studies are needed to further explore these associations

Sexual dimorphism in cancer.

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment

Quantification of Biomolecular Dynamics Inside Real and Synthetic Nuclear Pore Complexes Using Time-Resolved Atomic Force Microscopy

Over the past decades, atomic force microscopy (AFM) has emerged as an increasingly powerful tool to study the dynamics of biomolecules at nanometer length scales. However, the more stochastic the nature of such biomolecular dynamics, the harder it becomes to distinguish them from AFM measurement noise. Rapid, stochastic dynamics are inherent to biological systems comprising intrinsically disordered proteins. One role of such proteins is in the formation of the transport barrier of the nuclear pore complex (NPC): the selective gateway for macromolecular traffic entering or exiting the nucleus. Here, we use AFM to observe the dynamics of intrinsically disordered proteins from two systems: the transport barrier of native NPCs and the transport barrier of a mimetic NPC made using a DNA origami scaffold. Analyzing data recorded with 50-200 ms temporal resolution, we highlight the importance of drift correction and appropriate baseline measurements in such experiments. In addition, we describe an autocorrelation analysis to quantify time scales of observed dynamics and to assess their veracity-an analysis protocol that lends itself to the quantification of stochastic fluctuations in other biomolecular systems. The results reveal the surprisingly slow rate of stochastic, collective transitions inside mimetic NPCs, highlighting the importance of FG-nup cohesive interactions

The Present and Future Role of Insect-Resistant Genetically Modified Maize in IPM

Commercial, genetically-modified (GM) maize was first planted in the United States (USA, 1996) and Canada (1997) but now is grown in 13 countries on a total of over 35 million hectares (\u3e24% of area worldwide). The first GM maize plants produced a Cry protein derived from the soil bacteriumBacillus thuringiensis (Bt), which made them resistant to European corn borer and other lepidopteran maize pests. New GM maize hybrids not only have resistance to lepidopteran pests but some have resistance to coleopteran pests and tolerance to specific herbicides. Growers are attracted to the Btmaize hybrids for their convenience and because of yield protection, reduced need for chemical insecticides, and improved grain quality. Yet, most growers worldwide still rely on traditional integrated pest management (IPM) methods to control maize pests. They must weigh the appeal of buying insect protection “in the bag” against questions regarding economics, environmental safety, and insect resistance management (IRM). Traditional management of maize insects and the opportunities and challenges presented by GM maize are considered as they relate to current and future insect-resistant products. Four countries, two that currently have commercialize Bt maize (USA and Spain) and two that do not (China and Kenya), are highlighted. As with other insect management tactics (e.g., insecticide use or tillage), GM maize should not be considered inherently compatible or incompatible with IPM. Rather, the effect of GM insect-resistance on maize IPM likely depends on how the technology is developed and used

Hydrogen peroxide signaling via its transformation to a stereospecific alkyl hydroperoxide that escapes reductive inactivation

During systemic inflammation, indoleamine 2,3-dioxygenase 1 (IDO1) becomes expressed in endothelial cells where it uses hydrogen peroxide (H2O2) to oxidize L-tryptophan to the tricyclic hydroperoxide, cis-WOOH, that then relaxes arteries via oxidation of protein kinase G 1α. Here we show that arterial glutathione peroxidases and peroxiredoxins that rapidly eliminate H2O2, have little impact on relaxation of IDO1-expressing arteries, and that purified IDO1 forms cis-WOOH in the presence of peroxiredoxin 2. cis-WOOH oxidizes protein thiols in a selective and stereospecific manner. Compared with its epimer trans-WOOH and H2O2, cis-WOOH reacts slower with the major arterial forms of glutathione peroxidases and peroxiredoxins while it reacts more readily with its target, protein kinase G 1α. Our results indicate a paradigm of redox signaling by H2O2 via its enzymatic conversion to an amino acid-derived hydroperoxide that ‘escapes’ effective reductive inactivation to engage in selective oxidative activation of key target proteins.</p

The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.

Reversal of ischemia is mediated by neo-angiogenesis requiring endothelial cell (EC) and pericyte interactions to form stable microvascular networks. We describe an unrecognized role for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in potentiating neo-angiogenesis and vessel stabilization. We show that the endothelium is a major source of TRAIL in the healthy circulation compromised in peripheral artery disease (PAD). EC deletion of TRAIL in vivo or in vitro inhibited neo-angiogenesis, pericyte recruitment, and vessel stabilization, resulting in reduced lower-limb blood perfusion with ischemia. Activation of the TRAIL receptor (TRAIL-R) restored blood perfusion and stable blood vessel networks in mice. Proof-of-concept studies showed that Conatumumab, an agonistic TRAIL-R2 antibody, promoted vascular sprouts from explanted patient arteries. Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD

Leaf Morphology, Taxonomy and Geometric Morphometrics: A Simplified Protocol for Beginners

Taxonomy relies greatly on morphology to discriminate groups. Computerized geometric morphometric methods for quantitative shape analysis measure, test and visualize differences in form in a highly effective, reproducible, accurate and statistically powerful way. Plant leaves are commonly used in taxonomic analyses and are particularly suitable to landmark based geometric morphometrics. However, botanists do not yet seem to have taken advantage of this set of methods in their studies as much as zoologists have done. Using free software and an example dataset from two geographical populations of sessile oak leaves, we describe in detailed but simple terms how to: a) compute size and shape variables using Procrustes methods; b) test measurement error and the main levels of variation (population and trees) using a hierachical design; c) estimate the accuracy of group discrimination; d) repeat this estimate after controlling for the effect of size differences on shape (i.e., allometry). Measurement error was completely negligible; individual variation in leaf morphology was large and differences between trees were generally bigger than within trees; differences between the two geographic populations were small in both size and shape; despite a weak allometric trend, controlling for the effect of size on shape slighly increased discrimination accuracy. Procrustes based methods for the analysis of landmarks were highly efficient in measuring the hierarchical structure of differences in leaves and in revealing very small-scale variation. In taxonomy and many other fields of botany and biology, the application of geometric morphometrics contributes to increase scientific rigour in the description of important aspects of the phenotypic dimension of biodiversity. Easy to follow but detailed step by step example studies can promote a more extensive use of these numerical methods, as they provide an introduction to the discipline which, for many biologists, is less intimidating than the often inaccessible specialistic literature

Visceral Leishmaniasis Relapse in Southern Sudan (1999–2007): A Retrospective Study of Risk Factors and Trends

Visceral leishmaniasis (kala-azar) caused by Leishmania donovani is spread from person to person by Phlebotomus sandflies. Major epidemics of visceral leishmaniasis have occurred in Southern Sudan during the 20th century. The worst of these killed 100,000 people in the western Upper Nile area of Southern Sudan from 1984–1994, a loss of one-third of the population. Médecins Sans Frontières has treated 40,000 kala-azar patients in Southern Sudan since the late 1980's. In this study we used routinely collected clinical data to investigate why some patients relapse after treatment. We found that patients with severely enlarged spleens (splenomegaly) are more likely to relapse. Patients treated for 17 days with a combination of two drugs (sodium stibogluconate and paromomycin) were more likely to relapse (but less likely to die) than patients treated for 30 days with a single drug (sodium stibogluconate). However, the transition from sodium stibogluconate to the sodium stibogluconate/paromomycin combination as standard treatment between 2001–2003 has not led to a significant increase in visceral leishmaniasis relapse