A critique of the World Resources Institute's report "Pesticides and the immune system: the public health risks".

A recent World Resources Institute (WRI) report concluded that pesticides are a likely cause of immune suppression for millions of people throughout the world. The gravity of this conclusion motivated us to review the scientific evidence cited in the report. The predominant human evidence came from cross-sectional studies conducted in the former Soviet Union.These studies were difficult to evaluate due to incomplete reporting and had obvious limitations in terms of subject selection, exposure assessment,lack of quality control, statistical analysis, adequacy of the comparison group, and confounding. The toxicologic evidence was comprised mainly of acute high-dose studies in which the exposure conditions resulted in systemic toxicity. The relevance of these studies to effects at typical human exposure levels is questionable. We did not find consistent, credible evidence to support the conclusion of widespread pesticide-related immune suppression. Nonetheless, the WRI report is an important document because it focuses attention on a potentially important issue for future research and brings a substantial literature of foreign language studies to the attention of Western scientists

A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome

Purpose: To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1). Methods: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism. Results: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition. Conclusion: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.16-17/10/Newlife - The Charity for Disabled Children FS/13/32/30069/BHF_/British Heart Foundation/United Kingdom 72160007/Chile's National Commission for Scientific and Technological Research MR/K011154/1/MRC_/Medical Research Council/United Kingdom WT_/Wellcome Trust/United Kingdompre-prin

Measurement of the photon+b+b-jet production differential cross section in ppˉp\bar{p} collisions at \sqrt{s}=1.96~\TeV

We present measurements of the differential cross section dsigma/dpT_gamma for the inclusive production of a photon in association with a b-quark jet for photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is the photon transverse momentum. The b-quark jets are required to have pT>15 GeV and rapidity |y_jet| < 1.5. The results are based on data corresponding to an integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the Fermilab Tevatron $p\bar{p}$ Collider at sqrt(s)=1.96 TeV. The measured cross sections are compared with next-to-leading order perturbative QCD calculations using different sets of parton distribution functions as well as to predictions based on the kT-factorization QCD approach, and those from the Sherpa and Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.

Experimental mutation-accumulation on the X chromosome of Drosophila melanogaster reveals stronger selection on males than females

<p>Abstract</p> <p>Background</p> <p>Sex differences in the magnitude or direction of mutational effect may be important to a variety of population processes, shaping the mutation load and affecting the cost of sex itself. These differences are expected to be greatest after sexual maturity. Mutation-accumulation (MA) experiments provide the most direct way to examine the consequences of new mutations, but most studies have focused on juvenile viability without regard to sex, and on autosomes rather than sex chromosomes; both adult fitness and X-linkage have been little studied. We therefore investigated the effects of 50 generations of X-chromosome mutation accumulation on the fitness of males and females derived from an outbred population of <it>Drosophila melanogaster</it>.</p> <p>Results</p> <p>Fitness declined rapidly in both sexes as a result of MA, but adult males showed markedly greater fitness loss relative to their controls compared to females expressing identical genotypes, even when females were made homozygous for the X. We estimate that these mutations are partially additive (h ~ 0.3) in females. In addition, the majority of new mutations appear to harm both males and females.</p> <p>Conclusions</p> <p>Our data helps fill a gap in our understanding of the consequences of sexual selection for genetic load, and suggests that stronger selection on males may indeed purge deleterious mutations affecting female fitness.</p

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Do you get us? A multi-experiment, meta-analytic test of the effect of felt understanding in intergroup relations

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record Data and materials for all studies are available on the project OSF page: https://osf.io/3ye72/?view_only=13a1c3aef3044bc78d94b6ca9c8cf05a.Felt understanding is a key determinant of positive inter-personal relations, but its role and potential benefits in intergroup relations have been neglected. In the first multi-study, pre-registered test of its intergroup effects, we manipulated intergroup felt understanding (understood vs. misunderstood by an outgroup) in six studies (N = 1195) and meta-analyzed its effects. The results in most intergroup contexts supported the prediction that feeling understood (vs. misunderstood) would lead to more positive intergroup orientations (r = 0.25) and action intentions (r = 0.12). These effects were distinct from the effects of feeling liked by an outgroup, which was also manipulated in each study. An important caveat was that the felt understanding manipulation's effect reversed when the outgroup was stereotypically low in competence, but high in warmth (older adults). Overall, the findings indicate the value of incorporating felt understanding into models of intergroup relations and how those relations can be improved

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe