An Evolutionary Perspective on Human Cross-sensitivity to Tree Nut and Seed Allergens

Tree nut allergies are some of the most common and serious allergies in the United States. Patients who are sensitive to nuts or to seeds commonly called nuts are advised to avoid consuming a variety of different species, even though these may be distantly related in terms of their evolutionary history. This is because studies in the literature report that patients often display sensitivity to multiple nut species (cross-sensitivity) if they have an existing nut allergy. These reports suggest that cross-sensitivity in patients with nut allergies may be caused by an IgE antibody reacting with epitopes present in the seed proteins of different species (cross-reactivity), for example, if IgE isolated from the serum of a patient were able to bind to both almond and peanut allergens. We hypothesize that allergenic proteins in seeds may have similar amino acid sequences that cause the observed cross-sensitivity. Here, we test the hypothesis that similarity in the protein sequences of allergenic nuts drives cross-sensitivity and cross-reactivity by reconstructing the gene trees of three allergenic seed-storage proteins (vicilin, legumin, and 2S albumin) from species sampled across vascular plants. We generate estimates of their phylogenetic relationships and compare these to the allergen cross-sensitivity and cross-reactivity data that is reported in the literature. In general, evolutionary relationships of the three proteins are congruent with the current understanding of plant species relationships. However, we find little evidence that distantly related nut species reported to be cross-reactive share similar vicilin, legumin, or 2S albumin amino acid sequences. Our data thus suggest that features of the proteins other than their amino acid sequences may be driving the cross-reactivity observed during in vitro tests and skin tests. Our results support current treatment guidelines to limit nut and seed consumption if allergies are present in a patient. More studies are necessary to better understand the characteristics of allergenic proteins and patterns of cross-sensitivity in patients who suffer from nut allergies

Phylogeny of Dyschoriste (Acanthaceae)

The pantropical and poorly known genus Dyschoriste (Acanthaceae) is sister to Strobilanthopsis within subtribe Petalidiinae. The present study included 38 accessions of 28 species as sources of DNA data for one nuclear (nrITS) and four chloroplast (intergenic spacers: psbA-trnH, trnS-trnG, ndhF-rpl32, rpl32- trnL(uag)) regions to provide an estimate of the phylogeny of the genus. We found that Dyschoriste is strongly supported as monophyletic inclusive of Apassalus, Chaetacanthus, and Sautiera. Within Dyschoriste, three geographically cohesive lineages were recovered with moderate to strong support: a mainland African clade, a Caribbean and southeastern United States clade, and a South and Central America clade. A third New World clade composed of accessions from the south central through southwestern US to Mexico is weakly supported and corresponds to the D. linearis species complex recognized by previous researchers (six of the ten taxa putatively part of this complex were sampled). A second Old World clade unites taxa from across the Old World tropics (mainland Africa, Madagascar and southeast Asia). Some aspects of relationships among these main clades were unresolved or not strongly supported, and two Old World taxa, south Asian D. dalzellii and the wide-ranging D. nagchana, were not placed with confidence in any of these clades. The simplest explanation for the current distribution of the genus is that there was a single dispersal event of Dyschoriste from the Old to the New World, with a subsequent radiation in the New World

Characterization of Murine Thymic Stromal-Cell Lines Immortalized by Temperature-Sensitive Simian Virus 40 Large T or Adenovirus 5 E1a

The heterogeneity of thymic stromal cells is probably related to their role in providing different microenvironments where T cells can develop. We have immortalized thymic stromal elements using recombinant retroviral constructs containing a temperature-sensitive simian virus 40 (SV40tsA58) large-T antigen gene or the adenovirus 5 E1a region linked to the gene coding for resistance to G418. Cell lines containing the thermolabile large T antigen encoded by SV40 proliferate at the permissive temperature of 33°C and arrest growth when transferred to the nonpermissive temperature of 39°C. At the nonpermissive temperature, ts-derived cell lines are shown to alter their phenotype but remain metabolically active, as indicated by the inducible expression of class I and class II MHC antigens. Here we describe the generation of a total of 84 thymic stromal-cell lines, many of which show distinct morphologic, phenotypic, and functional properties consistent with fibroblastoid, epithelial, or monocytoid origins. Several E1a and SV40tsA58-derived cell lines generated exhibit the epithelial characteristic of desmosome formation and, in addition, two of these lines (15.5 and 15.18) form multicellular complexes (rosettes) when incubated with unfractionated thymocytes from syngeneic mice. A single line (14.5) displays very strong nonspecific esterase activity, suggesting it may represent a macrophagelike cell type. We describe the generation of stromal cell lines with different properties, which is consistent with the heterogeneity found in the thymic microenvironment. In addition to documenting this diversity, these cell lines may be useful tools for studying T-cell development in vitro and give access to model systems in which stromal-thymocyte interactions can be examined

Centromeric Repositioning of Coreceptor Loci Predicts Their Stable Silencing and the CD4/CD8 Lineage Choice

The differentiation of CD4+ CD8+ double positive (DP) thymocytes requires the irreversible choice between two alternative lineages, distinguished by the mutually exclusive expression of either CD4 or CD8. Differentiating DP cells transiently down-regulate both CD4 and CD8, and this has complicated the debate whether the mechanism of CD4/CD8 lineage choice is instructive, stochastic/selective, or more complex in nature. Using fluorescence in situ hybridization, we show that the stable silencing of coreceptor loci, and ultimately lineage choice, is predicted by the spatial repositioning of coreceptor alleles to centromeric heterochromatin domains. These data provide evidence that lineage-specific developmental programs are established early during the transition from the DP to the single positive stage

Investigating the veracity of a sample of divergent published trial data in spinal pain

Evidence-based medicine is replete with studies assessing quality and bias, but few evaluating research integrity or trustworthiness. A recent Cochrane review of psychological interventions for chronic pain identified trials with a shared lead author with highly divergent results. We sought to systematically identify all similar trials from this author to explore their risk of bias, governance procedures, and trustworthiness. We searched OVID MEDLINE, EMBASE, CENTRAL, and PEDro from 2010 to December 22, 2021 for trials. We contacted the authors requesting details of trial registration, ethical approval, protocol, and access to the trial data for verification. We used the Cochrane risk-of-bias tool and the Cochrane Pregnancy and Childbirth group's Trustworthiness Screening Tool to guide systematic exploration of trustworthiness. Ten trials were included: 9 compared cognitive behavioural therapy and physical exercise to usual care, exercise alone, or physiotherapy and 1 compared 2 brief cognitive behavioural therapy programmes. Eight trials reported results divergent from the evidence base. Assessment of risk of bias and participant characteristics identified no substantial concerns. Responses from the lead author did not satisfactorily explain this divergence. Trustworthiness screening identified concerns about research governance, data plausibility at baseline, the results, and apparent data duplication. We discuss the findings within the context of methods for establishing the trustworthiness of research findings generally. Important concerns regarding the trustworthiness of these trials reduce our confidence in them. They should probably not be used to inform the results and conclusions of systematic reviews, in clinical training, policy documents, or any relevant instruction regarding adult chronic pain management

The VIRUS-P Exploration of Nearby Galaxies (VENGA): Survey Design, Data Processing, and Spectral Analysis Methods

We present the survey design, data reduction, and spectral fitting pipeline for the VIRUS-P Exploration of Nearby Galaxies (VENGA). VENGA is an integral field spectroscopic survey, which maps the disks of 30 nearby spiral galaxies. Targets span a wide range in Hubble type, star formation activity, morphology, and inclination. The VENGA data-cubes have 5.6'' FWHM spatial resolution, ~5A FWHM spectral resolution, sample the 3600A-6800A range, and cover large areas typically sampling galaxies out to ~0.7 R_25. These data-cubes can be used to produce 2D maps of the star formation rate, dust extinction, electron density, stellar population parameters, the kinematics and chemical abundances of both stars and ionized gas, and other physical quantities derived from the fitting of the stellar spectrum and the measurement of nebular emission lines. To exemplify our methods and the quality of the data, we present the VENGA data-cube on the face-on Sc galaxy NGC 628 (a.k.a. M 74). The VENGA observations of NGC 628 are described, as well as the construction of the data-cube, our spectral fitting method, and the fitting of the stellar and ionized gas velocity fields. We also propose a new method to measure the inclination of nearly face-on systems based on the matching of the stellar and gas rotation curves using asymmetric drift corrections. VENGA will measure relevant physical parameters across different environments within these galaxies, allowing a series of studies on star formation, structure assembly, stellar populations, chemical evolution, galactic feedback, nuclear activity, and the properties of the interstellar medium in massive disk galaxies.Comment: Accepted for publication in AJ, 25 pages, 18 figures, 6 table

MISSION Diversion & Recovery for Traumatized Veterans (MISSION DIRECT VET): Early Findings and Lessons Learned

MISSION DIRECT VET is a SAMHSA- funded, court based diversion program targeting veterans in Massachusetts with trauma-related mental health and substance use problems. MISSION-DIRECT VET seeks to: Reduce criminal justice involvement Treat mental health, substance abuse and other trauma related symptoms Use a systematic wrap-around model Provide care coordination, peer support and trauma informed services Develop interagency partnerships to serve veterans with co-occurring disorder