Herpes simplex virus-1 triggered hemophagocytic lymphohistiocytosis in a patient with granulomatosis with polyangiitis

Hemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive hyperinflammatory syndrome in which an inciting event triggers massive, uninhibited activation of T lymphocytes and macrophages. Although viral infections are the most common trigger of HLH, cases of HSV-1 induced HLH are rare in adults. We present the case and postmortem findings of a 27-year-old woman diagnosed with HLH in the setting of immunosuppression for the treatment of granulomatosis with polyangiitis (GPA). Autopsy revealed evidence of herpes simplex virus-1 (HSV-1) infection and no findings suggestive of GPA recurrence

A novel NGS library preparation method to characterize native termini of fragmented DNA.

Biological and chemical DNA fragmentation generates DNA molecules with a variety of termini, including blunt ends and single-stranded overhangs. We have developed a Next Generation Sequencing (NGS) assay, XACTLY, to interrogate the termini of fragmented DNA, information traditionally lost in standard NGS library preparation methods. Here we describe the XACTLY method, showcase its sensitivity and specificity, and demonstrate its utility in in vitro experiments. The XACTLY assay is able to report relative abundances of all lengths and types (5' and 3') of single-stranded overhangs, if present, on each DNA fragment with an overall accuracy between 80-90%. In addition, XACTLY retains the sequence of each native DNA molecule after fragmentation and can capture the genomic landscape of cleavage events at single nucleotide resolution. The XACTLY assay can be applied as a novel research and discovery tool for fragmentation analyses and in cell-free DNA

Graded supplementation of chestnut tannins to dairy cows fed protein-rich spring pasture: effects on indicators of protein utilization

An on-farm experiment was conducted in order to evaluate effects of graded supplementation with chestnut tannin extract to cows in situations of excessive dietary protein supply on a low-input organic dairy farm. Respectively 10 Swiss Fleckvieh cows received twice per day 1 kg of experimental pellets containing either 0, 50 or 100 g/kg of chestnut extract (targeted at approximately 0, 5 and 10 g extract/kg of total dietary dry matter). Experimental feeding lasted for 21 days. Measurements and collection of milk, faeces and urine spot samples were performed in weeks 0 (baseline), 1 and 3. All cows were kept in one herd on pasture; fresh grass and grass hay were provided in the barn during night. Milk yield was recorded and cows wore sensor halters for recording chewing activity. In urine, total nitrogen and purine derivatives were measured; faeces were analyzed for protein, fibre and particle fractions; in milk, solid concentrations were determined. The data was analyzed with a general linear model. Cows did not show differences in general eating and rumination behaviour, but needed time to accept the tannin-containing pellets. Milk yield and composition were not affected by treatment, except for lactose content. No relevant differences between treatments were found for urinary and faecal parameters. In conclusion, although technically easy to supplement, pellets containing chestnut tannin extract were not readily accepted by the cows and effects on protein digestion and metabolism were not found. Successful on-farm application of chestnut extract in order to improve nitrogen efficiency therefore seems questionable

IMMUNE RESPONSES IN VITRO : XI. Suppression of Primary IgM and IgG Plaque-Forming Cell Responses In Vitro by Alloantisera Against Leukocyte Alloantigens

The effects of alloantisera against leukocyte alloantigens on plaque-forming cell (PFC) responses to sheep erythrocytes and the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) by mouse spleen cells in vitro have been investigated. Polyspecific antibodies against both H-2 and non-H-2 alloantigens on responding spleen cells suppressed both IgM and IgG PFC responses; antisera against alloantigens coded for by the K and I regions, but not the D region, of the H-2 complex also effectively suppressed PFC responses. The suppression was not due to cytotoxicity to the spleen cells or anti-immunoglobulin activity in the sera and was directly related to the amount of antiserum added to the cultures. The suppression was specific for spleen cells against which the alloantiserum was directed. The alloantisera suppressed responses most effectively when present during the first 24 h of incubation, and although not rendering lymphoid cells incapable of developing PFC responses after removal of noncell-bound antibody, did act by interfering with successful initiation of the PFC response. The alloantisera suppressed both IgM and IgG PFC responses when directed against alloantigens only on macrophages, but selectively suppressed IgG responses when directed against alloantigens only on lymphoid cells. The alloantisera did not interfere with the ability of macrophages to bind GAT or to support the viability of the lymphoid cells, but did interfere with the ability of macrophage-associated antigen to effectively stimulate antibody responses by the lymphoid cells. Possible mechanisms for the effects of alloantisera on macrophages and the selective suppression of IgG responses when the antisera are directed against alloantigens on lymphoid cells are discussed with reference to our current understanding of genetic restrictions governing cell interactions in the development of antibody responses in mice

Regulatory T Cells Are Dispensable for Tolerance to RBC Antigens

Autoimmune hemolytic anemia (AIHA) occurs when pathogenic autoantibodies against red blood cell (RBC) antigens are generated. Whilst the basic disease pathology of AIHA is well studied, the underlying mechanism(s) behind the failure in tolerance to RBC autoantigens are poorly understood. Thus, to investigate the tolerance mechanisms required for the establishment and maintenance of tolerance to RBC antigens, we developed a novel murine model. With this model, we evaluated the role of regulatory T cells (Tregs) in tolerance to RBC-specific antigens. Herein, we show that neither sustained depletion of Tregs nor immunization with RBC-specific proteins in conjunction with Treg depletion led to RBC-specific autoantibody generation. Thus, these studies demonstrate that Tregs are not required to prevent autoantibodies to RBCs and suggest that other tolerance mechanisms are likely involved

People should be allowed to do what they like’: Autistic adults’ views and experiences of stimming

This is the final version. Available from the publisher via the DOI in this record.Data from participants who consented will be deposited in the UK Data Service, in 2019.‘Stereotyped or repetitive motor movements’ are characterised as core features in the diagnosis of autism, yet many autistic adults (and the neurodiversity movement) have reclaimed them as ‘stimming’. Supported by a growing body of scientific research, autistic adults argue that these behaviours may serve as useful coping mechanisms, yet little research has examined stimming from the perspective of autistic adults. Through interviews and focus groups, we asked 32 autistic adults to share their perceptions and experiences of stimming, including the reasons they stim, any value doing so may hold for them and their perceptions of others’ reactions to stimming. Using thematic analysis, we identified two themes: stimming as (1) a self-regulatory mechanism and (2) lacking in social acceptance, but can become accepted through understanding. Autistic adults highlighted the importance of stimming as an adaptive mechanism that helps them to soothe or communicate intense emotions or thoughts and thus objected to treatment that aims to eliminate the behaviour.Wellcome TrustLeverhulme Trus

Tectonic evolution of the early Mesozoic blueschist-bearing Qiangtang metamorphic belt, central Tibet

This is the published version. Copyright 2003 American Geophysical Union. All Rights Reserved.A >500-km-long east-west trending metamorphic belt in the Qiangtang terrane of central Tibet consists of tectonic melange that occurs in the footwalls of Late Triassic–Early Jurassic domal low-angle normal faults. The melange is comprised of a strongly deformed matrix of metasedimentary and mafic schists that encloses lesser-deformed blocks of metabasites, Carboniferous–Triassic metasedimentary rocks, and early Paleozoic gneiss. Both the blocks and melange matrix exhibit greenschist, epidote-blueschist, and locally, epidote-amphibolite facies mineral assemblages. Thermobarometry reveals that the metamorphic belt experienced pressures of >10 kbar. Maximum equilibration temperatures for mafic schists in the melange matrix decrease from east to west, from ∼660°C near Shuang Hu (33°N, 89°E), ∼500°C near Rongma (33°N, 87°E), to ∼425°C near Gangma Co (34°N, 84°E). Equilibration at consistently high pressures over a large range of temperatures is compatible with metamorphism of Qiangtang melange within a low-angle subduction zone beneath a continental margin. Coupled structural, thermobarometric, and 40Ar/39Ar studies suggest that Qiangtang melange was exhumed in an intracontinental setting from depths of >35 km to upper crustal levels in <12 Myr by Late Triassic–Early Jurassic crustal-scale normal faulting. Detrital zircons from metasandstones within the melange matrix yield U-Pb ion-microprobe ages that range from early Paleozoic to Early Archean, and could have been sourced from terranes to the north of the Jinsha suture. Our results support a model in which Qiangtang melange was underthrust ∼200 km beneath the Qiangtang terrane during early Mesozoic flat-slab southward subduction of Paleo-Tethyan oceanic lithosphere along the Jinsha suture. This model predicts that significant portions of the central Tibetan continental mantle lithosphere were removed during early Mesozoic low-angle oceanic subduction and that the present-day central Tibetan deeper crust includes large volumes of underthrust early Mesozoic melange

Development of the AASPIRE web accessibility guidelines for autistic web users

Websites figure predominantly in everyday life. However, many websites remain inaccessible to autistic people, and existing efforts to improve accessibility are in early stages, do not directly include autistic users in their development, or have not been empirically evaluated. The Academic Autism Spectrum Partnership in Research and Education (AASPIRE) used a community-based participatory research approach to create a website to improve health care access for autistic adults. We used the creation of that website as a “living laboratory” to develop the AASPIRE Web Accessibility Guidelines for Autistic Web Users. Our guidelines are grounded in accessibility theory, had autistic end-user involvement at all stages, and were empirically evaluated through a usability study and evaluation surveys. We incorporated what we learned into the design of the website, and compiled the accessibility information into a set of guidelines. The guidelines offer recommendations for increasing the physical, intellectual, and social acceptability of websites for use by autistic adults. In the evaluation of the website by 170 autistic end users, nearly all indicated it was easy to use (97%), easy to understand (95%), important (97%), and useful (96%). Ninety-two percent would recommend it to a friend, and 95% would recommend it to a health care provider. There were no significant associations between usability or understandability and education level, receipt of help using the site, browser type (e.g., IE or Safari), or device type (e.g., PC or tablet). We recommend using the guidelines to improve website accessibility for autistic Internet users

Rendimento de grãos de soja: efeito do espaçamento e da densidade.

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