The HIV‐1 gp41 ectodomain is cleaved by matriptase to produce a chemotactic peptide that acts through FPR2

Several aspects of HIV‐1 virulence and pathogenesis are mediated by the envelope protein gp41. Additionally, peptides derived from the gp41 ectodomain have been shown to induce chemotaxis in monocytes and neutrophils. Whereas this chemotactic activity has been reported, it is not known how these peptides could be produced under biological conditions. The heptad repeat 1 (HR1) region of gp41 is exposed to the extracellular environment and could therefore be susceptible to proteolytic processing into smaller peptides. Matriptase is a serine protease expressed at the surface of most epithelia, including the prostate and mucosal surfaces. Here, we present evidence that matriptase efficiently cleaves the HR1 portion of gp41 into a 22‐residue chemotactic peptide MAT‐1, the sequence of which is highly conserved across HIV‐1 clades. We found that MAT‐1 induced migration of primary neutrophils and monocytes, the latter of which act as a cellular reservoir of HIV during early stage infection. We then used formyl peptide receptor 1 (FPR1) and FPR2 inhibitors, along with HEK 293 cells, to demonstrate that MAT‐1 can induce chemotaxis specifically using FPR2, a receptor found on the surface of monocytes, macrophages and neutrophils. These findings are the first to identify a proteolytic cleavage product of gp41 with chemotactic activity and highlight a potential role for matriptase in HIV‐1 transmission and infection at epithelial surfaces and within tissue reservoirs of HIV‐1.     

Anti-IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function

Genetic variation in the IL-7 receptor-α (IL-7R) gene is associated with susceptibility to human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete remission in newly onset diabetic mice after only two to three injections. IL-7 increases, whereas IL-7Rα antibody therapy reduces, the IFN-γ-producing CD4(+) (T(H)1) and IFN-γ-producing CD8(+) T cells. Conversely, IL-7 decreases and IL-7Rα antibody enhances the inhibitory receptor Programmed Death 1 (PD-1) expression in the effector T cells. Programmed Death 1 blockade reversed the immune tolerance mediated by the IL-7Rα antibody therapy. Furthermore, IL-7Rα antibody therapy increases the frequency of regulatory T cells without affecting their suppressor activity. The durable efficacy and the multipronged tolerogenic mechanisms of IL-7Rα antibody therapy suggest a unique disease-modifying approach to T1D.     

Small steps: physical health promotion for people living with mental illness

Physical health promotion for people with mental illness is vital if the life expectancy of this population group is to be improved. While there is promising evidence of physical health promotion initiatives in the literature in this population group, it is unclear whether these have resulted in long-term gains and actually reduced morbidity and mortality. We aimed to identify which physical health promotion strategies and resources were most likely to resonate with people who have long-term mental health problems and live in the community. We facilitated three focus groups in metropolitan Perth with 27 participants who experienced long-term serious mental health problems for this qualitative study. Participants were clear about which health promotion resources and approaches they did or did not consider would engage them. Participants wanted health messages that were positive, clear and not too wordy. They tended to dislike pamphlets and preferred DVDs. They also preferred to participate in health promotion activities in groups. Participants were aware of the need to engage in health protective behaviours but were often overwhelmed by their mental health problems. Health promotion for this population group ought to capitalise on therapeutic alliances with staff and informal peer networks already established in drop-in centres and clubhouses.     

The Epidemiology and Phenomenology of Non-Suicidal Self-Injurious Behavior Among Adolescents: A Critical Review of the Literature

This article critically reviewed the research addressing the epidemiology and phenomenology of non-suicidal self-injury (NSSI) among adolescents. Articles were identified through a search of Medline and Psychinfo. Findings indicate a lifetime prevalence of NSSI ranging from 13.0% to 23.2%. Reasons for engaging in NSSI include to regulate emotion and to elicit attention. Correlates of NSSI include a history of sexual abuse, depression, anxiety, alexithymia, hostility, smoking, dissociation, suicidal ideation, and suicidal behaviors. Suggested areas of future research include identifying the psychiatric diagnoses associated with NSSI among adolescents, determining the temporal link between NSSI and suicide attempts, learning more about the course of NSSI, understanding the biological underpinnings of NSSI, and identifying effective treatments for NSSI in adolescents.     

A review of physical activity interventions on determinants of mental health in children and adolescents

The purpose of this article was to review the effects of physical activity (PA) lifestyle intervention on determinants of mental health among children and adolescents. A search was performed using the databases Academic Search Premier, CINHAL, EBSCOHost, PsycARTICLES and PsycINFO. Inclusion criteria were studies that utilized PA interventions designed to impact a determinant of mental health in a target population of 6–18 years. From this search, 537 results were identified and eight met the inclusion criteria. All studies reported an inverse relationship between PA and depression. Seven found a significant (p < 0.05) reduction in depression when various aerobic and/or resistance training exercises were introduced. Only one study found a negative correlation between very light intensity activity and determinants of psychological health (e.g. depression and anxiety); however, these results were not statistically significant. In conclusion, promoting PA appears to improve determinants of mental health, such as depression, global self-worth and self-efficacy. Recommendations for enhancing future interventions are presented.