Fibrillar beta-amyloid peptide Aβ1–40 activates microglial proliferation via stimulating TNF-α release and H2O2 derived from NADPH oxidase: a cell culture study

Background  

Alzheimer's disease is characterized by the accumulation of neuritic plaques, containing activated microglia and β-amyloid peptides (Aβ). Fibrillar Aβ can activate microglia, resulting in production of toxic and inflammatory mediators like hydrogen peroxide, nitric oxide, and cytokines. We have recently found that microglial proliferation is regulated by hydrogen peroxide derived from NADPH oxidase. Thus, in this study, we investigated whether Aβ can stimulate microglial proliferation and cytokine production via activation of NADPH oxidase to produce hydrogen peroxide.     

Investigation of the hostile attribution bias toward ambiguous facial cues in antisocial violent offenders

Aggressive individuals exhibit a strong tendency to attribute hostile intent to the behavior of others, which may lead to provocation and aggravation of socially inappropriate reactions. Limited research has investigated the hostile attribution bias in the perception of facial affect. This study examined a hostile response bias to emotionally ambiguous faces in a population of 55 incarcerated antisocial violent offenders as compared to matched control subjects. Results suggest that aggression is associated with a strong preference to interpret ambiguous stimuli containing proportions of an angry expression as hostile, while there was no evidence for a generally biased interpretation of distress cues under conditions of uncertainty. Thus, the tendency to misinterpret nonverbal cues in social interactions may at least partly underlie aggressive–impulsive behavior in susceptible individuals.     

Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes

BACKGROUND & AIMS: Studies on the early steps in the life cycle of hepatitis B virus have been hampered by the lack of readily available target cells. In this study, we mapped a defined virus attachment site to primary hepatocytes that is essential for infection. METHODS: We used purified virus particles from human carrier plasma as an inoculum and primary cultures of tupaia hepatocytes as susceptible target cells and studied the inhibitory effect of amino-terminally acylated preS1-derived lipopeptides on infection interference. RESULTS: Infectivity of virus could be blocked efficiently in this system by amino-terminally acylated peptides containing amino acids 2-18 from the preS1 domain. The addition of amino acids 28-48 enhanced the inhibitory capacity, whereas amino acids 49-78 did not contribute to inhibition. Myristoylated preS1 peptides 2-48 bound strongly to tupaia hepatocytes but not to nonhepatic cells or rodent hepatocytes and thereby inhibited infection even at concentrations of 1 nmol/L completely. Particles consisting only of the small hepatitis B surface protein-the active component of current hepatitis B vaccines-did not bind at all to tupaia hepatocytes, but the addition of the preS1 domain to the particles allowed binding. CONCLUSIONS: The preS1 sequence 2-48 mediates attachment of the virus to its target cells, whereas the small surface protein seems to be involved in other steps. These findings indicate that the current subunit hepatitis B vaccines may be improved by the addition of distinct preS1 epitopes. Moreover, preS1 lipopeptides are promising candidates for specific antiviral therapy against hepatitis B infections.     

Nitric oxide and calcium together inactivate mitochondrial complex I and induce cytochrome c release

Cellular nitric oxide (NO) and calcium levels have been reported to increase during various pathologies, including particularly ischaemia. In this study, we investigated whether elevated NO and calcium levels can synergistically damage isolated rat heart mitochondria. We found that NO and calcium together inhibited the oxygen consumption of mitochondria respiring on pyruvate + malate, but not mitochondria respiring on succinate. In the same conditions, complex I activity was synergistically inhibited by NO and calcium, and this inhibition was completely prevented by superoxide dismutase or urate, suggesting that the inhibition was mediated by peroxynitrite. Indeed, we found NO and calcium-stimulated mitochondrial production of peroxynitrite. The inhibition of complex I activity by NO and calcium was reversed by reduced thiols or light (as was complex I inhibition by S-nitrosothiols or peroxynitrite) suggesting that the inhibition may involve S-nitrosation or Fe-nitrosylation of complex I. However, NO and calcium also caused loss of mitochondrial cytochrome c, and the induced inhibition of respiration was partially reversed by addition of exogenous cytochrome c. Thus, NO and calcium appear to synergistically inhibit mitochondrial respiration, partly by inactivation of complex I and partly by inducing cytochrome c release.     

Generation of recombinant virus-like particles of human and non-human polyomaviruses in yeast Saccharomyces cerevisiae

OBJECTIVES: Non-viral methods of gene transfer have been preferred in gene therapy approaches for several reasons, particularly for their safety, simplicity and convenience in introducing heterologous DNA into cells. Polyomavirus virus-like particles (VLPs) represent a promising carrier for encapsidation of foreign nucleic acids for gene therapy. For the development of such gene delivery systems as well as for providing reagents for improving virus diagnostics, an efficient yeast expression system for the generation of different polyomavirus VLPs was established. METHODS: A galactose-inducible Saccharomyces cerevisiae yeast expression system was used. Formation of empty VLPs was confirmed by cesium chloride ultracentrifugation, agarose gel electrophoresis and electron microscopy. Cross-reactivity of the major capsid proteins (VP1) of different polyomaviruses was analyzed by Western blot using rabbit and mice sera raised against the VP1 proteins. RESULTS: VP1 of polyomaviruses from humans (JC polyomavirus and serotypes AS and SB of BK polyomavirus), rhesus monkeys (simian virus 40), hamsters (hamster polyomavirus), mice (murine polyomavirus) and birds (budgerigar fledgling disease virus) were expressed at high levels in yeast. Empty VLPs formed by all yeast-expressed VP1 proteins were dissociated into pentamers and reassociated into VLPs by defined ion and pH conditions. Different patterns of cross-reactivity of the VP1 proteins with heterologous mice and rabbit sera were observed. CONCLUSION: The developed heterologous yeast expression system is suitable for high-level production of polyomavirus VLPs. Yeast-derived VLPs are generally free of toxins, host cell DNA and proteins. These VLPs might be useful for the generation of new diagnostical tools, gene delivery systems and antiviral vaccines.     

Suicidal ideation in patients undergoing brain tumor surgery: prevalence and risk factors

Purpose

Suicidal ideation (SI) is an important complication in cancer patients that should be promptly recognized and adequately managed. We investigated the prevalence rate and correlates of pre-operative SI in brain tumor (BT) patients admitted for elective BT surgery.

Methods

Two hundred and eleven consecutive patients (70 % women; mean age 55.9 ± 15.4 years) scheduled for BT surgery were evaluated for SI (“suicidal thought” item from the Beck Depression Inventory-II), depressive/anxiety symptom severity (Hospital Anxiety and Depression scale (HADS)), health-related quality of life (SF-36 scale), functional status (Barthel Index), and psychiatric histories and treatments. The majority of patients were diagnosed with meningioma (39 %) and high-grade glioma (17 %).

Results

SI was self-reported by 12 (6 %) patients. Patients expressing SI were most commonly diagnosed with meningioma (50 %). Patients with SI were more likely to have a past history of psychiatric disorders, scored higher on the HADS anxiety subscale, and reported worse health-related quality of life across physical and mental health domains. In multivariate regression analyses, worse perceived mental health was associated with increased risk for SI independently from clinical, sociodemographic, and other patient-oriented variables considered in the study.

Conclusions

SI was self-reported by 6 % of BT patients before surgical intervention and was associated with a past history of psychiatric disorders and worse perceived health status. Poor mental health was an independent correlate of SI. The perception of health status by a patient should be considered as an important determinant of poor mental health in BT patients.

     

Social distance in Lithuanian psychology and social work students and professionals

Purpose

This cross-sectional study aimed to compare desire for social distance from people with mental illness in the disciplines of social work and psychology, and among students and professionals having different professional experience.

Methods

948 respondents (715 students and 233 professionals) from Lithuanian educational and mental health-care institutions participated in an anonymous survey. Social distance was measured using Lithuanian Social Distance Scale which was created for this study. Participants also answered questions about familiarity with mental illness. Bias of social desirability was measured using the balanced inventory of desirable responding.

Results

Series of ANCOVA analysis revealed that psychology and social work master’s and PhD students reported less social distance from people with mental illness when compared with bachelor’s students. Familiarity with mental illness was significantly related to less social distance in the student sample, but not in professionals’ sample. The strongest desire for social distance in the professionals’ sample was observed in social workers having less than 5 years of professional practice and most experienced psychologists with more than 10 years of professional practice.

Conclusions

Social distance from people with mental illness decreases through the study years; however, results of professional psychologists and social workers illustrate different trajectories in social distance through the professional career. The results of this study support the need for anti-stigma programmes and initiatives orientated towards mental health professionals.

     

Gender-specific knowledge on sex

Purpose  

A study of what sources of knowledge on sex education, reproductive physiology and abortion was sought by adolescents at school.     

S-nitrosothiol-induced rapid cytochrome c release, caspase activation and mitochondrial permeability transition in perfused heart

Nitric oxide (NO) is a physiological signalling molecule, however, at high concentrations NO is cytotoxic, and has been implicated in a wide range of inflammatory, ischaemic and degenerative diseases, including heart failure. We investigated whether NO or S-nitrosothiols can induce apoptosis in perfused heart, and whether it is mediated via the mitochondrial pathway of caspase activation. We found that perfusion of rat hearts with a physiological S-nitrosothiol, S-nitrosoglutathione, at 0.4-1mM concentrations for just 10 min caused the release of cytochrome c from mitochondria into the cytosol, inhibition of mitochondrial respiration and caspase activation. Inhibited mitochondrial respiration was restored when exogenous cytochrome c was added to mitochondria, indicating that respiratory inhibition was caused by lack of cytochrome c in mitochondria. Release of cytochrome c, respiratory inhibition and caspase activation were prevented when hearts were pre-perfused with cyclosporin A, suggesting that mitochondrial permeability transition pore was involved. In contrast, perfusion of the hearts with diethylenetriamine/NO adduct releasing similar levels of NO to the S-nitrosoglutathione had no measurable effect on the heart. These data suggest that S-nitrosothiols are potent inducers of apoptosis in the heart and that S-nitrosothiol-induced apoptosis is mediated by mitochondrial permeability transition but not via NO.