Clinically significant depressive symptoms and sexual behaviour among men who have sex with men.

BACKGROUND: The relationship between depression and sexual behaviour among men who have sex with men (MSM) is poorly understood. AIMS: To investigate prevalence and correlates of depressive symptoms (Patient Health Questionnaire-9 score ≥10) and the relationship between depressive symptoms and sexual behaviour among MSM reporting recent sex. METHOD: The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary medicine clinic attendees without diagnosed HIV (2013-2014). RESULTS: Among 1340 MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic disadvantage and lower supportive network. Adjusted for key sociodemographic factors, depressive symptoms were associated with measures of condomless sex partners in the past 3 months (≥2 (prevalence ratio (PR) 1.42, 95% CI 1.17-1.74; P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20-1.71; P<0.001)), sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19-1.79; P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33-2.50; P<0.001). CONCLUSIONS: Management of mental health may play a role in HIV and STI prevention. DECLARATION OF INTEREST: A.N.P. has received payments for presentations made at meetings sponsored by Gilead in spring 2015. N.C.N. has received support for attendance at conferences, speaker fees and payments for attendance at advisory boards from Gilead Sciences, Viiv Healthcare, Janssen Pharmaceuticals and Bristol-Myers Squibb and a research grant from Gilead Sciences. D.A. served on the advisory board for Gilead in January 2016. M.M.G. has had sponsorship to attend conferences by Bristol-Myers Squibb, been on the BioCryst advisory board and run trials for Merck, Gilead, SSAT, BioCryst and Novartis. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license

Development of a 3D workspace Shoulder Assessment Tool Incorporating Electromyography and an Inertial Measurement Unit - A preliminary study

Traditional shoulder Range of Movement (ROM) measurement tools suffer from inaccuracy or from long experimental set-up times. Recently, it has been demonstrated that relatively low-cost wearable inertial measurement unit (IMU) sensors can overcome many of the limitations of traditional motion tracking systems. The aim of this study is to develop and evaluate a single IMU combined with an Electromyography (EMG) sensor to monitor the 3D reachable workspace with simultaneous measurement of deltoid muscle activity across the shoulder ROM. Six volunteer subjects with healthy shoulders and one participant with a ‘frozen’ shoulder were recruited to the study. Arm movement in 3D space was plotted in spherical coordinates while the relative EMG intensity of any arm position is presented graphically. The results showed that there was an average ROM surface area of 27291±538 deg2 among all six healthy individuals and a ROM surface area of 13571±308 deg2 for the subject with frozen shoulder. All three sections of the deltoid show greater EMG activity at higher elevation angles. Using such tools enables individuals, surgeons and physiotherapists to measure the maximum envelope of motion in conjunction with muscle activity in order to provide an objective assessment of shoulder performance in the voluntary 3D workspace

Creatine ingestion augments dietary carbohydrate mediated muscle glycogen supercomposition during the initial 24 hrs of recovery following prolonged exhaustive exercise in humans

Muscle glycogen availability can limit endurance exercise performance. We previously demonstrated 5 days of creatine (Cr) and carbohydrate (CHO) ingestion augmented post-exercise muscle glycogen storage compared to CHO feeding alone in healthy volunteers. Here we aimed to characterise the time-course of this Cr-induced response under more stringent and controlled experimental conditions and identify potential mechanisms underpinning this phenomenon. Fourteen healthy, male volunteers cycled to exhaustion at 70% VO2peak. Muscle biopsies were obtained at rest immediately post-exercise and after 1, 3 and 6 days of recovery, during which Cr or placebo supplements (20g.day-1) were ingested along with a prescribed high CHO diet (37.5 kcal.kg body mass-1.day-1, >80% calories CHO). Oral-glucose tolerance tests (oral-GTT) were performed pre-exercise and after 1, 3 and 6 days of Cr and placebo supplementation. Exercise depleted muscle glycogen content to the same extent in both treatment groups. Creatine supplementation increased muscle total-Cr, free-Cr and phosphocreatine (PCr) content above placebo following 1, 3 and 6 days of supplementation (all P<0.05). Creatine supplementation also increased muscle glycogen content noticeably above placebo after 1 day of supplementation (P<0.05), which was sustained thereafter. This study confirmed dietary Cr augments post-exercise muscle glycogen super-compensation, and demonstrates this occurred during the initial 24 h of post-exercise recovery (when muscle total-Cr had increased by <10%). This marked response ensued without apparent treatment differences in muscle insulin sensitivity (oral-GTT, muscle GLUT4 mRNA), osmotic stress (muscle c-fos and HSP72 mRNA) or muscle cell volume (muscle water content) responses, such that another mechanism must be causative

Hydrophobic CDR3 residues promote the development of self-reactive T cells

Studies of individual T cell antigen receptors (TCRs) have shed some light on structural features that underlie self-reactivity. However, the general rules that can be used to predict whether TCRs are self-reactive have not been fully elucidated. Here we found that the interfacial hydrophobicity of amino acids at positions 6 and 7 of the complementarity-determining region CDR3β robustly promoted the development of self-reactive TCRs. This property was found irrespective of the member of the β-chain variable region (V[subscript β]) family present in the TCR or the length of the CDR3β. An index based on these findings distinguished V[subscript β]2[superscript +], V[subscript β]6[superscript +] and V[subscript β]8.2[superscript +] regulatory T cells from conventional T cells and also distinguished CD4[superscript +] T cells selected by the major histocompatibility complex (MHC) class II molecule I-A[superscript g7] (associated with the development of type 1 diabetes in NOD mice) from those selected by a non–autoimmunity-promoting MHC class II molecule I-Ab. Our results provide a means for distinguishing normal T cell repertoires versus autoimmunity-prone T cell repertoires

alphabeta T cell receptors as predictors of health and disease

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR \u27signatures\u27 raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome

Production of ultrasonic vocalizations by Peromyscus mice in the wild

BACKGROUND: There has been considerable research on rodent ultrasound in the laboratory and these sounds have been well quantified and characterized. Despite the value of research on ultrasound produced by mice in the lab, it is unclear if, and when, these sounds are produced in the wild, and how they function in natural habitats. RESULTS: We have made the first recordings of ultrasonic vocalizations produced by two free-living species of mice in the genus Peromyscus (P. californicus and P. boylii) on long term study grids in California. Over 6 nights, we recorded 65 unique ultrasonic vocalization phrases from Peromyscus. The ultrasonic vocalizations we recorded represent 7 different motifs. Within each motif, there was considerable variation in the acoustic characteristics suggesting individual and contextual variation in the production of ultrasound by these species. CONCLUSION: The discovery of the production of ultrasonic vocalizations by Peromyscus in the wild highlights an underappreciated component in the behavior of these model organisms. The ability to examine the production of ultrasonic vocalizations in the wild offers excellent opportunities to test hypotheses regarding the function of ultrasound produced by rodents in a natural context

Transcriptome profiling of Pinus radiata juvenile wood with contrasting stiffness identifies putative candidate genes involved in microfibril orientation and cell wall mechanics

<p>Abstract</p> <p>Background</p> <p>The mechanical properties of wood are largely determined by the orientation of cellulose microfibrils in secondary cell walls. Several genes and their allelic variants have previously been found to affect microfibril angle (MFA) and wood stiffness; however, the molecular mechanisms controlling microfibril orientation and mechanical strength are largely uncharacterised. In the present study, cDNA microarrays were used to compare gene expression in developing xylem with contrasting stiffness and MFA in juvenile <it>Pinus radiata </it>trees in order to gain further insights into the molecular mechanisms underlying microfibril orientation and cell wall mechanics.</p> <p>Results</p> <p>Juvenile radiata pine trees with higher stiffness (HS) had lower MFA in the earlywood and latewood of each ring compared to low stiffness (LS) trees. Approximately 3.4 to 14.5% out of 3, 320 xylem unigenes on cDNA microarrays were differentially regulated in juvenile wood with contrasting stiffness and MFA. Greater variation in MFA and stiffness was observed in earlywood compared to latewood, suggesting earlywood contributes most to differences in stiffness; however, 3-4 times more genes were differentially regulated in latewood than in earlywood. A total of 108 xylem unigenes were differentially regulated in juvenile wood with HS and LS in at least two seasons, including 43 unigenes with unknown functions. Many genes involved in cytoskeleton development and secondary wall formation (cellulose and lignin biosynthesis) were preferentially transcribed in wood with HS and low MFA. In contrast, several genes involved in cell division and primary wall synthesis were more abundantly transcribed in LS wood with high MFA.</p> <p>Conclusions</p> <p>Microarray expression profiles in <it>Pinus radiata </it>juvenile wood with contrasting stiffness has shed more light on the transcriptional control of microfibril orientation and the mechanical properties of wood. The identified candidate genes provide an invaluable resource for further gene function and association genetics studies aimed at deepening our understanding of cell wall biomechanics with a view to improving the mechanical properties of wood.</p

Efficacy of a Non-Hypercalcemic Vitamin-D2 Derived Anti-Cancer Agent (MT19c) and Inhibition of Fatty Acid Synthesis in an Ovarian Cancer Xenograft Model

BACKGROUND:Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING:Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3) xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR) antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN) activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K) activity independently of PPAR-gamma protein. SIGNIFICANCE:Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis