Epstein Barr Virus-Induced 3 (EBI3) Together with IL-12 Negatively Regulates T Helper 17-Mediated Immunity to Listeria monocytogenes Infection

10.1371/journal.ppat.1003628PLoS Pathogens99

Effects of cover crops on phosphatase activity in a clay arable soil in the UK

The effect of five cover crop species (radish, buckwheat, vetch, phacelia and oat) alongside an un-cropped control, on the activity and persistence of soil acid and alkaline phosphatase activity was investigated. There was no effect on alkaline phosphatase activity at the time of cover crop incorporation (March), but by the point of maturation of the following oat cash crop (June) significant differences were detected, with the greatest activity following an oat cover crop. Acid phosphatase activity showed species-related significant differences at both sampling dates, with the magnitude increasing by June. Again, plots following an oat cover crop showed the greatest activity, followed by phacelia. This has shown that soil phosphatase enzymes are affected by the presence of a cover crop, that this effect is apparently species-dependent – and not dependent on the amount of biomass from the cover crop – and that cover crops could be a potential means to enhance soil phosphorus cycling

A terminal assessment of stages theory : introducing a dynamic states approach to entrepreneurship

Stages of Growth models were the most frequent theoretical approach to understanding entrepreneurial business growth from 1962 to 2006; they built on the growth imperative and developmental models of that time. An analysis of the universe of such models (N=104) published in the management literature shows no consensus on basic constructs of the approach, nor is there any empirical confirmations of stages theory. However, by changing two propositions of the stages models, a new dynamic states approach is derived. The dynamic states approach has far greater explanatory power than its precursor, and is compatible with leading edge research in entrepreneurship

Resident Cellular Components of the Human Lung Current Knowledge and Goals for Research on Cell Phenotyping and Function

The purpose of the workshop was to identify still obscure or novel cellular components of the lung, to determine cell function in lung development and in health that impacts on disease, and to decide promising avenues for future research to extract and phenotype these cells. Since robust technologies are now available to identify, sort, purify, culture, and phenotype cells, progress is now within sight to unravel the origins and functional capabilities of lung cells in developmental stages and in disease. The Workshop's agenda was to first discuss the lung's embryologic development, including progenitor and stem cells, and then assess the functional and structural cells in three main compartments of the lung: (1) airway cells in bronchial and bronchiolar epithelium and bronchial glands (basal, secretory, ciliated, Clara, and neuroendocrine cells); (2) alveolar unit cells (Type 1 cells, Type 2 cells, and fibroblasts in the interstitium); and (3) pulmonary vascular cells (endothelial cells from different vascular structures, smooth muscle cells, and adventitial fibroblasts). The main recommendations were to: (1) characterize with better cell markers, both surface and nonsurface, the various cells within the lung, including progenitor cells and stem cells; (2) obtain more knowledge about gene expression in specific cell types in health and disease, which will provide insights into biological and pathologic processes; (3) develop more methodologies for cell culture, isolation, sorting, co-culture, and immortalization; and (4) promote tissue banks to facilitate the procurement of tissue from normal and from diseased lung for analysis at all levels

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The study protocol including the statistical analysis plan is available at https://www.clarityibd.org/. Individual participant de-identified data that underlie the results reported in this article will be available immediately after publication for a period of 5 years. Due to the sensitive nature of the data, this will be made available to investigators whose proposed use of the data has been approved by an independent review committee. Analyses will be restricted to the aims in the approved proposal. Proposals should be directed to [email protected]. To gain access data requestors will need to sign a data access agreement. Data from the Virus Watch study is currently being archived on the Office of National Statistics Secure Research Service and will be available shortly. Source data are provided with this paper in the Source Data file. Source data are provided with this paper.Code availability: Statistical analyses were undertaken in R 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria. Code has been made available at: https://github.com/exeteribd/clarityibd-public.Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements

A search for resonances decaying into a Higgs boson and a new particle X in the XH → qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson (H) and a new particle (X) is reported, utilizing 36.1 fb−1 of proton–proton collision data at collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle X is assumed to decay to a pair of light quarks, and the fully hadronic final state is analysed. The search considers the regime of high XH resonance masses, where the X and H bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of XH mass versus X mass is scanned for evidence of a signal, over a range of XH resonance mass values between 1 TeV and 4 TeV, and for X particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of XH and X masses, on the production cross-section of the resonance