DNA sense-and-respond protein modules for mammalian cells

We generated synthetic protein components that can detect specific DNA sequences and subsequently trigger a desired intracellular response. These modular sensors exploit the programmability of zinc-finger DNA recognition to drive the intein-mediated splicing of an artificial trans-activator that signals to a genetic circuit containing a given reporter or response gene. We used the sensors to mediate sequence recognition−induced apoptosis as well as to detect and report a viral infection. This work establishes a synthetic biology framework for endowing mammalian cells with sentinel capabilities, which provides a programmable means to cull infected cells. It may also be used to identify positively transduced or transfected cells, isolate recipients of intentional genomic edits and increase the repertoire of inducible parts in synthetic biology.United States. Defense Advanced Research Projects Agency (DARPA-BAA-11-23)Defense Threat Reduction Agency (DTRA) (HDTRA1-14-1-0006)United States. Air Force Office of Scientific Research (FA9550-14-1-0060

An NLO QCD analysis of inclusive cross-section and jet-production data from the ZEUS experiment

The ZEUS inclusive differential cross-section data from HERA, for charged and neutral current processes taken with e+ and e- beams, together with differential cross-section data on inclusive jet production in e+ p scattering and dijet production in \gamma p scattering, have been used in a new NLO QCD analysis to extract the parton distribution functions of the proton. The input of jet data constrains the gluon and allows an accurate extraction of \alpha_s(M_Z) at NLO; \alpha_s(M_Z) = 0.1183 \pm 0.0028(exp.) \pm 0.0008(model) An additional uncertainty from the choice of scales is estimated as \pm 0.005. This is the first extraction of \alpha_s(M_Z) from HERA data alone.Comment: 37 pages, 14 figures, to be submitted to EPJC. PDFs available at http://durpdg.dur.ac.uk/hepdata in LHAPDFv

Forward jet production in deep inelastic ep scattering and low-x parton dynamics at HERA

Differential inclusive jet cross sections in neutral current deep inelastic ep scattering have been measured with the ZEUS detector. Three phase-space regions have been selected in order to study parton dynamics where the effects of BFKL evolution might be present. The measurements have been compared to the predictions of leading-logarithm parton shower Monte Carlo models and fixed-order perturbative QCD calculations. In the forward region, QCD calculations at order alpha_s^1 underestimate the data up to an order of magnitude at low x. An improved description of the data in this region is obtained by including QCD corrections at order alpha_s^2, which account for the lowest-order t-channel gluon-exchange diagrams, highlighting the importance of such terms in parton dynamics at low x.Comment: 25 pages, 4 figure

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age.

The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset - with data collected between 2020 and 2022 - to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Study of deep inelastic inclusive and diffractive scattering with the ZEUS forward plug calorimeter

Deep inelastic scattering and its diffractive component, ep -> e'gamma*p ->e'XN, have been studied at HERA with the ZEUS detector using an integrated luminosity of 4.2 pb-1. The measurement covers a wide range in the gamma*p c.m. energy W (37 - 245 GeV), photon virtuality Q2 (2.2 - 80 GeV2) and mass Mx. The diffractive cross section for Mx > 2 GeV rises strongly with W; the rise is steeper with increasing Q2. The latter observation excludes the description of diffractive deep inelastic scattering in terms of the exchange of a single Pomeron. The ratio of diffractive to total cross section is constant as a function of W, in contradiction to the expectation of Regge phenomenology combined with a naive extension of the optical theorem to gamma*p scattering. Above Mx of 8 GeV, the ratio is flat with Q2, indicating a leading-twist behaviour of the diffractive cross section. The data are also presented in terms of the diffractive structure function, F2D(3)(beta,xpom,Q2), of the proton. For fixed beta, the Q2 dependence of xpom F2D(3) changes with xpom in violation of Regge factorisation. For fixed xpom, xpom F2D(3) rises as beta -> 0, the rise accelerating with increasing Q2. These positive scaling violations suggest substantial contributions of perturbative effects in the diffractive DIS cross section.Comment: 87 pages, 25 figure

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Insatisfação corporal em gestantes: uma revisão integrativa da literatura

Resumo A imagem corporal de gestantes deve ser alvo de atenção por parte dos profissionais, tendo em vista a promoção da saúde materna infantil. O objetivo da presente revisão integrativa foi analisar a literatura sobre imagem e insatisfação corporal em gestantes. Foram buscados artigos nas bases de dados Scopus, PubMed, BVS e PsycINFO utilizando o cruzamento de “pregnancy” com as palavras-chave: “body image” e “body dissatisfaction”. Após a adoção dos critérios de inclusão e exclusão foram analisados 40 estudos. Estes apontam dados inconclusivos quanto à insatisfação corporal durante a gestação. Presença de sintomas depressivos, baixa autoestima, atitude alimentar inadequada e ganho de peso fora dos limites recomendados têm sido associados a uma imagem corporal negativa. Contradições nos achados podem estar relacionados às diferenças nos instrumentos utilizados para mensurar a imagem corporal. Pelo possível impacto de uma imagem corporal negativa durante a gestação na saúde materna e infantil, são recomendadas novas investigações, em especial o desenvolvimento de um instrumento avaliativo de imagem corporal específico para gestantes