Trained immunity or tolerance : opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors

Article Accepted Date: 29 January 2014. ACKNOWLEDGMENTS D.C.I. received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-2010-260338 (“Fungi in the setting of inflammation, allergy and autoimmune diseases: translating basic science into clinical practices” [ALLFUN]) (awarded to M.G.N.). M.G.N. and J.Q. were supported by a Vici grant of the Netherlands Organization of Scientific Research (awarded to M.G.N.). This work was supported, in part, by National Institutes of Health grant GM53522 to D.L.W. N.A.R.G. was supported by the Wellcome Trust.Peer reviewedPublisher PD

A Simple Microbiome in the European Common Cuttlefish, Sepia officinalis.

The European common cuttlefish, Sepia officinalis, is used extensively in biological and biomedical research, yet its microbiome remains poorly characterized. We analyzed the microbiota of the digestive tract, gills, and skin in mariculture-raised S. officinalis using a combination of 16S rRNA amplicon sequencing, quantitative PCR (qPCR), and fluorescence spectral imaging. Sequencing revealed a highly simplified microbiota consisting largely of two single bacterial amplicon sequence variants (ASVs) of Vibrionaceae and Piscirickettsiaceae The esophagus was dominated by a single ASV of the genus Vibrio Imaging revealed bacteria in the family Vibrionaceae distributed in a discrete layer that lines the esophagus. This Vibrio was also the primary ASV found in the microbiota of the stomach, cecum, and intestine, but occurred at lower abundance, as determined by qPCR, and was found only scattered in the lumen rather than in a discrete layer via imaging analysis. Treatment of animals with the commonly used antibiotic enrofloxacin led to a nearly 80% reduction of the dominant Vibrio ASV in the esophagus but did not significantly alter the relative abundance of bacteria overall between treated versus control animals. Data from the gills were dominated by a single ASV in the family Piscirickettsiaceae, which imaging visualized as small clusters of cells. We conclude that bacteria belonging to the Gammaproteobacteria are the major symbionts of the cuttlefish Sepia officinalis cultured from eggs in captivity and that the esophagus and gills are major colonization sites.IMPORTANCE Microbes can play critical roles in the physiology of their animal hosts, as evidenced in cephalopods by the role of Vibrio (Aliivibrio) fischeri in the light organ of the bobtail squid and the role of Alpha- and Gammaproteobacteria in the reproductive system and egg defense in a variety of cephalopods. We sampled the cuttlefish microbiome throughout the digestive tract, gills, and skin and found dense colonization of an unexpected site, the esophagus, by a microbe of the genus Vibrio, as well as colonization of gills by Piscirickettsiaceae This finding expands the range of organisms and body sites known to be associated with Vibrio and is of potential significance for understanding host-symbiont associations, as well as for understanding and maintaining the health of cephalopods in mariculture

Interprofessional Team Collaboration for Routine and Emergent Mental Health Concerns Among Collegiate Student-Athletes: A Case Series from the Association for Athletic Training Education Research Network

Collegiate student-athletes experience an increasing number of mental health concerns. To help address these concerns and provide high-quality health care for student-athletes, institutions of higher education are being encouraged to create interprofessional health care teams that are specifically dedicated to managing mental health. We interviewed 3 interprofessional health care teams who collaborate to manage routine and emergency mental health conditions in collegiate student-athletes. Teams represented all 3 National Collegiate Athletics Association (NCAA) divisions and included athletic trainers, clinical psychologists, psychiatrists, dietitians and nutritionists, social workers, nurses, and physician assistants (associates). The interprofessional teams indicated that the existing NCAA recommendations helped to solidify members and roles of the mental health care team; however, they all believed their teams would benefit from more counselors and psychiatrists. Teams had different mechanisms for referral and accessing mental health resources on their campuses, which may make on-the-job training for new members of the team an organizational necessity

Crab-fishing by chimpanzees in the Nimba Mountains, Guinea

The significance of aquatic food resources for hominins is poorly understood, despite evidence of consumption as early as 1.95 million years ago (Ma). Here we present the first evidence of a non-human ape habitually catching and consuming aquatic crabs. Chimpanzees (Pan troglodytes verus) in the rainforest of the Nimba Mountains (Guinea) consumed freshwater crabs year-round, irrespective of rainfall or ripe fruit availability. Parties of females and offspring fished for crabs more than predicted and for longer durations than adult males. Across months, crab-fishing was negatively correlated with ant-dipping, suggesting a similar nutritional role. These findings contribute to our understanding of aquatic faunivory among hominins. First, aquatic faunivory can occur in closed forests in addition to open wetlands. Second, aquatic fauna could have been a staple part of some hominin diets, rather than merely a fallback food. Third, the habitual consumption of aquatic fauna could have been especially important for females and their immature offspring. In addition to providing small amounts of essential fatty acids, crabs might also be eaten for their micronutrients such as sodium and calcium, especially by females and young individuals who may have limited access to meat

Estimating behavior in a black box : how coastal oceanographic dynamics influence yearling Chinook salmon marine growth and migration behaviors

Ocean currents or temperature may substantially influence migration behavior in many marine species. However, high-resolution data on animal movement in the marine environment are scarce; therefore, analysts and managers must typically rely on unvalidated assumptions regarding movement, behavior, and habitat use. We used a spatially explicit, individual-based model of early marine migration with two stocks of yearling Chinook salmon to quantify the influence of external forces on estimates of swim speed, consumption, and growth. Model results suggest that salmon behaviorally compensate for changes in the strength and direction of ocean currents. These compensations can result in salmon swimming several times farther than their net movement (straight-line distance) would indicate. However, the magnitude of discrepancy between compensated and straight-line distances varied between oceanographic models. Nevertheless, estimates of relative swim speed among fish groups were less sensitive to the choice of model than estimates of absolute individual swim speed. By comparing groups of fish, this tool can be applied to management questions, such as how experiences and behavior may differ between groups of hatchery fish released early vs. later in the season. By taking into account the experiences and behavior of individual fish, as well as the influence of physical ocean processes, our approach helps illuminate the “black box” of juvenile salmon behavior in the early marine phase of the life cycle

Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus, a New Twist on ATP Formation.

UnlabelledSyntrophus aciditrophicus is a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation by S. aciditrophicus However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome of S. aciditrophicus leaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show that S. aciditrophicus uses AMP-forming, acetyl-CoA synthetase (Acs1) for ATP synthesis from acetyl-CoA. acs1 mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, of S. aciditrophicus grown in pure culture and coculture. Cell extracts of S. aciditrophicus had low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified from S. aciditrophicus and recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) in S. aciditrophicus cells support the operation of Acs1 in the acetate-forming direction. Thus, S. aciditrophicus has a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase.ImportanceBacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA. Syntrophus aciditrophicus apparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as its genome does not have homologs to the genes for phosphate acetyltransferase and acetate kinase. Here, we show that S. aciditrophicus uses an alternative approach, an AMP-forming, acetyl-CoA synthetase, to make ATP from acetyl-CoA. AMP-forming, acetyl-CoA synthetases were previously thought to function only in the activation of acetate to acetyl-CoA

Exposure to dietary mercury alters cognition and behavior of zebra finches

Environmental stressors can negatively affect avian cognitive abilities, potentially reducing fitness, for example by altering response to predators, display to mates, or memory of locations of food. We expand on current knowledge by investigating the effects of dietary mercury, a ubiquitous environmental pollutant and known neurotoxin, on avian cognition. Zebra finches Taeniopygia guttata were dosed for their entire lives with sub-lethal levels of mercury, at the environmentally relevant dose of 1.2 parts per million. In our first study, we compared the dosed birds with controls of the same age using tests of three cognitive abilities: spatial memory, inhibitory control, and color association. In the spatial memory assay, birds were tested on their ability to learn and remember the location of hidden food in their cage. The inhibitory control assay measured their ability to ignore visible but inaccessible food in favor of a learned behavior that provided the same reward. Finally, the color association task tested each bird\u27s ability to associate a specific color with the presence of hidden food. Dietary mercury negatively affected spatial memory ability but not inhibitory control or color association. Our second study focused on three behavioral assays not tied to a specific skill or problem-solving: activity level, neophobia, and social dominance. Zebra finches exposed to dietary mercury throughout their lives were subordinate to, and more active than, control birds. We found no evidence that mercury exposure influenced our metric of neophobia. Together, these results suggest that sub-lethal exposure to environmental mercury selectively harms neurological pathways that control different cognitive abilities, with complex effects on behavior and fitness

Mice Lacking Gpr37 Exhibit Decreased Expression of the Myelin-Associated Glycoprotein Mag and Increased Susceptibility to Demyelination

GPR37 is an orphan G protein-coupled receptor that is predominantly expressed in the brain and found at particularly high levels in oligodendrocytes. GPR37 has been shown to exert effects on oligodendrocyte differentiation and myelination during development, but the molecular basis of these actions is incompletely understood and moreover nothing is known about the potential role(s) of this receptor under demyelinating conditions. To shed light on the fundamental biology of GPR37, we performed proteomic studies comparing protein expression levels in the brains of mice lacking GPR37 and its close relative GPR37-like 1 (GPR37L1). These studies revealed that one of the proteins most sharply decreased in the brains of Gpr37/Gpr37L1 double knockout mice is the myelin-associated glycoprotein MAG. Follow-up Western blot studies confirmed this finding and demonstrated that genetic deletion of Gpr37, but not Gpr37L1, results in strikingly decreased brain expression of MAG. Further in vitro studies demonstrated that GPR37 and MAG form a complex when expressed together in cells. As loss of MAG has previously been shown to result in increased susceptibility to brain insults, we additionally assessed Gpr37-knockout (Gpr37−/−) vs. wild-type mice in the cuprizone model of demyelination. These studies revealed that Gpr37−/− mice exhibit dramatically increased loss of myelin in response to cuprizone, yet do not show any increased loss of oligodendrocyte precursor cells or mature oligodendrocytes. These findings reveal that loss of GPR37 alters oligodendrocyte physiology and increases susceptibility to demyelination, indicating that GPR37 could be a potential drug target for the treatment of demyelinating diseases such as multiple sclerosis

Recalculation of dose for each fraction of treatment on TomoTherapy.

OBJECTIVE: The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20-37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. METHODS: Data are extracted from the TomoTherapy(®) archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose-volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan-Vese algorithm. RESULTS: On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. CONCLUSION: We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. ADVANCES IN KNOWLEDGE: The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies.JES is supported by Cancer Research UK through the Cambridge Cancer Centre. MR, AB and KH are supported by Cancer Research UK through the VoxTox Research Programme. NGB is supported by the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from British Institute of Radiology via http://dx.doi.org/10.1259/bjr.2015077

Evaluating the Peer Education Project in secondary schools

Purpose The purpose of this paper is to determine the efficacy of the Peer Education Project (PEP), a school-based, peer-led intervention designed to support secondary school students to develop the skills and knowledge they need to safeguard their mental health and that of their peers. Design/methodology/approach Six schools from across England and the Channel Islands took part in an evaluation of the PEP across the 2016/2017 academic year. In total, 45 trained peer educators from the sixth form and 455 Year 7 students completed pre- and post-questionnaires assessing their emotional and behavioural difficulties, perceived school climate, and knowledge, skills and confidence related to mental health. Findings Results indicate that participation in the PEP is associated with significant improvement in key skills among both peer educators and student trainees, and in understanding of key terms and readiness to support others among trainees. Most students would recommend participation in the programme to other students. Originality/value While peer education has been found to be effective in some areas of health promotion, research on the effectiveness of peer-led mental health education programmes in schools is limited. This study contributes evidence around the efficacy of a new peer education programme that can be implemented in secondary schools. </jats:sec