Sexuality and mental health: Issues and what next?

Abstract

Human sexuality plays a major role in an individual's existence and functioning. In addition, rightly or wrongly sexuality often defines people and also affects social attitudes. These attitudes, if negative, can contribute to stigma and prevent people from help seeking if they are suffering from mental health problems. Recent changes in policy towards same-sex relationships have been positive in many countries including the UK and the USA, whereas in others such as Russia and Uganda attitudes have become more negative and punitive. Sexual activity is seen as having both pleasurable and procreational functions which contribute to society's attitudes to homosexual behaviour. Inevitably, individual responses to their own sexuality and sexual behaviour will be influenced by social attitudes. To ensure that those with various sexual variations can access psychiatric services without discrimination, various levels of interventions are needed. Here we discuss different levels of intervention and organizational change that may make it possible. Social organization and institutional organization of services need to be sensitive, especially as rates of many mental disorders are high in individuals who may be sexually variant. Those providing services need to understand their own negative attitudes as well as prejudices to ensure that services are emotionally accessible.     

基因组重排的机制研究

基因组结构变异是人类基因组中常见的一种变异形式,往往涉及染色体或大片段染色体区域的改变,将原来两个分开的DNA序列重新连接在一起,从而形成染色体片段的缺失、重复复制、插入、倒位或者易位.在核苷酸水平上对大量重排断裂点接头序列特征的分析,为研究基因组重排的机制提供了宝贵的资源.本文综述了导致基因组重排的同源重组和非同源修复机制,并提出复制过程在基因组重排中发挥了重要作用,是细胞压力和结构变异的潜在桥梁,对于理解人类基因组进化和人类疾病的发生发展具有重要意义.     

Increased endogenous antigen presentation in the periphery enhances susceptibility to inflammation‐induced gastric autoimmunity in mice

How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self‐reactive T cells (A23 T cells) specific for the gastric H⁺/K⁺ ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild‐type BALB/c mice. However, increased presentation of endogenously derived HKα epitopes by dendritic cells (DCs) in the gastric lymph node of IE‐H⁺/K⁺β transgenic mice (IEβ) reduces A23 T‐cell tolerance to gastric antigens after inflammatory activation, with subsequent development of gastritis. While HKα‐specific A23 T cells from immunised wild‐type mice were poorly responsive to in vitro antigen specific activation, A23 T cells from immunised IEβ transgenic mice were readily re‐activated, indicating loss of T‐cell anergy. These findings show that DCs of gastric lymph nodes can maintain tolerance of pathogenic T cells following inflammatory stimulation and that the density of endogenous antigen presented to self‐reactive T cells is critical in the balance between tolerance and autoimmunity.     

BTN3A1‐antibodies and phosphoantigens: TCRVγ9Vδ2 “see” the difference

Human blood γδ T lymphocytes express TCRVγ9Vδ2 and respond to nonpeptide phosphoantigens (PAgs) by a mysterious mechanism involving the BTN3A1 (CD277) molecule 1 . BTN3A1 is a butyrophilin‐like protein related to CD80, PD‐L1, and MHC, and is either a presenting or a co‐stimulatory molecule for PAgs. Although the precise roles and molecular interactions with the TCRVγ9Vδ2 are currently not determined, it is commonly thought that all TCRVγ9Vδ2 lymphocytes ‘see’ PAg and BTN3A1 together, presumably in a single molecular recognition event. But whether this recognition event could be reproduced in a simplified model was not addressed in previous studies. In this issue, Starick et al. (Eur. J. Immunol. 2017. 47: 982–992) compared the response of three TCRVγ9Vδ2 pairs of murine and human cell transfectants to PAg and anti‐BTN3A1 antibodies using IL‐2 release as a readout. The authors found that although the two murine transfectants responded similarly to either stimuli, one murine TCRVγ9Vδ2 transfectant reacted to PAgs but not to anti‐BTN3A1 (mAb 20.1). Human transductants behave in a similar fashion, demonstrating that TCRVγ9Vδ2 lymphocytes differentiate PAg and BTN3A1 signals, while species of the transductants unmask this differential sensitivity. Indeed, understanding the puzzling mode of antigen recognition by γδ T lymphocytes will be essential for developing γδ T‐cell‐based immunotherapies, and the authors of this study now demonstrate that TCRVγ9Vδ2 lymphocytes are able to differentiate the PAg and BTN3A1 stimuli.     

Peptidomic analysis of type 1 diabetes associated HLA‐DQ molecules and the impact of HLA‐DM on peptide repertoire editing

HLA‐DM and class II associated invariant chain (Ii) are key cofactors in the MHC class II (MHCII) antigen processing pathway. We used tandem mass spectrometry sequencing to directly interrogate the global impact of DM and Ii on the repertoire of MHCII‐bound peptides in human embryonic kidney 293T cells expressing HLA‐DQ molecules in the absence or presence of these cofactors. We found that Ii and DM have a major impact on the repertoire of peptides presented by DQ1 and DQ6, with the caveat that this technology is not quantitative. The peptide repertoires of type 1 diabetes (T1D) associated DQ8, DQ2, and DQ8/2 are altered to a lesser degree by DM expression, and these molecules share overlapping features in their peptide binding motifs that are distinct from control DQ1 and DQ6 molecules. Peptides were categorized into DM‐resistant, DM‐dependent, or DM‐sensitive groups based on the mass spectrometry data, and representative peptides were tested in competitive binding assays and peptide dissociation rate experiments with soluble DQ6. Our data support the conclusion that high intrinsic stability of DQ‐peptide complexes is necessary but not sufficient to confer resistance to DM editing, and provide candidate parameters that may be useful in predicting the sensitivity of T‐cell epitopes to DM editing.     

Pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immunopathogenesis: Emerging concepts and perspectives

Pattern Recognition Receptors (PRRs) play a central role in the recognition of numerous pathogens, including Mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. Besides Toll Like Receptors, C-type Lectin Receptors and Nod Like Receptors are now being recognized for their involvement in inducing immune response against M. tuberculosis infection. Although, a functional redundancy of the PRRs has also been reported in many studies, emerging evidences support the notion that a cooperative and coordinated response generated by these receptors is critical to sustain the full immune control of M. tuberculosis infection. Many of the PRRs are now found to be involved in various cellular host defenses, such as inflammasome activation, phagosome biogenesis, endosomal trafficking, and antigen processing pathways that are all very critical for an effective immune response against M. tuberculosis. In support, polymorphism in several of these receptors has also been found associated with increased susceptibility to tuberculosis in humans. Nonetheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to subvert and reprogram PPR-mediated immune responses. In light of these findings, this review analyzes the interaction of bacterial and host factors at the intersections of PRR signaling pathways that could provide integrative insights for the development of better vaccines and therapeutics for tuberculosis.     

片形吸虫病诊断抗原的研究进展

片形吸虫病(fascioliasis)是由片形吸虫(Fasciola spp.),包括肝片形吸虫和大片形吸虫感染引起的人畜共患寄生虫病。牛羊等经济动物的感染可引起产奶、产肉量降低,劳作能力下降,造成巨大的经济损失:人体片形吸虫病可导致感染者严重的肝、胆病理损伤。片形吸虫病的临床表现和影像学诊断与其它肝胆疾病类似,极易被误诊。目前粪便虫卵病原学检测是最常用的片形吸虫病诊断方法,但存在漏诊、需要专业的镜检人员操作等问题。免疫学诊断技术因具有较高的特异性、敏感性且操作简单易行,近年来已成为片形吸虫病最常用的辅助诊断手段。该文主要综述了片形吸虫病免疫诊断抗原的研究进展。