SNAP-25 deficit and hippocampal connectivity in schizophrenia

Regional abnormalities of brain connectivity may be an important substrate for the expression of schizophrenia, a severe form of mental illness. Brain imaging and postmortem morphometric studies indicate hippocampal structure is abnormal in schizophrenia. To study molecular components of hippocampal connectivity the presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in schizophrenia compared to controls, particularly in the terminal fields of entorhinal cortex projections. Although there were no overall changes in synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus synaptophysin immunoreactivity was increased in schizophrenia. These results indicate that disconnection of a subset of hippocampal circuitry from the entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may contribute to the mechanism of illness in schizophrenia.      

Inhibition of calcineurin phosphatase activity in adult bone marrow transplant patients treated with cyclosporine A

In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (< 100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (> 100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD.     

Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum

Background

Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.

Methods

To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.

Results

We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.

Conclusion

Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.     

“...And Then There was the Down Low”: Introduction to Black and Latino Male Bisexualities

Although a recent proliferation of mass media has drawn attention to "the new Down Low phenomenon" (presumably "secretive" homosexuality among married Black men), relatively little research has explored bisexual behavior and identity among ethnic minority men in the United States or elsewhere. Although the study of bisexuality in Black and Latino men is significant in its own right, disproportionate rates of HIV/AIDS among these men make the current dearth of scientific information even more urgent and concerning. In this special section, we have compiled a diverse array of empirical and theoretical perspectives on Black and Latino male bisexualities. A wide range of information on the individual, social, and sexual lives of these men, and potential relations to risk behavior, are presented. This article introduces this new body of work and offers suggestions for future research directions for culturally appropriate interventions for Black and Latino bisexual men.     

Intergroup contact, attitudes toward homosexuality, and the role of acceptance of gender non-conformity in young adolescents

This study explored how contact with gay and lesbian persons affects adolescents' attitudes toward them, and whether this association is mediated or moderated by one's acceptance of gender non-conformity. We analyzed survey responses from 456 Dutch adolescents aged 12-15 who reported having no same-sex attractions. Data were collected in 2008 at 8 schools in Amsterdam, the Netherlands. Preliminary analyses showed that contact with lesbian/gay persons outside of school was positively associated with attitudes toward lesbians and gay men. Multilevel analyses showed that acceptance of gender non-conformity mediated rather than moderated the relationship between intergroup contact and sexual prejudice in males. The effect of intergroup contact on females' attitudes toward lesbian women was no longer significant in multilevel analyses. The findings suggest that attention to both intergroup contact and acceptance of gender non-conformity would enhance our understanding of attitudes toward homosexuality in adolescents.     

PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1α

Tumor cell resistance to ionizing radiation and chemotherapy is a major obstacle in cancer therapy. One factor contributing to this is integrin-mediated adhesion to ECM. The adapter protein particularly interesting new cysteine-histidine-rich 1 (PINCH1) is recruited to integrin adhesion sites and promotes cell survival, but the mechanisms underlying this effect are not well understood. Here we have shown that PINCH1 is expressed at elevated levels in human tumors of diverse origins relative to normal tissue. Furthermore, PINCH1 promoted cell survival upon treatment with ionizing radiation in vitro and in vivo by perpetuating Akt1 phosphorylation and activity. Mechanistically, PINCH1 was found to directly bind to protein phosphatase 1α (PP1α) — an Akt1-regulating protein — and inhibit PP1α activity, resulting in increased Akt1 phosphorylation and enhanced radioresistance. Thus, our data suggest that targeting signaling molecules such as PINCH1 that function downstream of focal adhesions (the complexes that mediate tumor cell adhesion to ECM) may overcome radio- and chemoresistance, providing new therapeutic approaches for cancer.     

Studies on the origin of redox enzymes in seminal plasma and their relationship with results of in-vitro fertilization

Glutathione (GSH), GSH peroxidase (GPX), GSH reductase (GRD), superoxide dismutase (SOD) and catalase-like enzyme activity were quantified in seminal plasma from normozoospermic patients, men with known distal ductal occlusion, proven fathers and male partners of couples receiving in-vitro fertilization (IVF) treatment for both male and female causes. Glutathione was non-detectable (< 2.5 microM) in seminal plasma. None of the enzyme activities per unit volume were lower in semen from vasectomized men, suggesting that they did not originate substantially from the testis or epididymis. The strongest relationships between enzyme activities and accessory gland markers were between zinc and GRD (r = 0.678), SOD (r = 0.602) and GPX (r = 0.548), suggesting a largely prostatic origin of these enzymes. Only weak relationships between accessory gland markers and catalase-like activity suggested a multi-glandular source of this enzyme. There was no relationship between the activity of any of the enzymes in the IVF patients with their fertilization rates in vitro or the establishment of pregnancy after IVF. Nor was there any correlation of enzyme activity with the morphology and percentage of motile spermatozoa in semen or with the percentage motility of spermatozoa immediately after swim-up or after overnight incubation. These findings suggest that the protective enzymes in the seminal plasma are contributed largely by the prostate and little by the epididymis, and that in most cases of IVF, they have no major influence on the outcome.      

Gender Differences in Affective Responses to Sexual Rejection

The aim of this study was to answer the following questions: (1) Are affective responses to sexual rejection different for men and women? (2) Do positive emotions to sexual rejection occur and how do they balance with negative emotions? (3) How can gender differences in affective responses to sexual rejection be explained? A sample of 67 men and 65 women (age 18–30 years) completed a questionnaire in which they rated their affective responses to a hypothetical situation of sexual rejection. Analyses of variance revealed gender differences: men anticipated a less negative and more positive affective response to sexual rejection than women did. Men also reported they would experience a more positive than negative affective response after supposedly being sexually rejected. Hierarchical multiple regression analyses showed that differences between men and women were mediated by the respondents' expectations in the stimulus situation, their interest in casual sex, and their masculinity.