Site structure analysis and optimization

The article contains information about current situation of site development, reasons why sites are so essential for activity of organizations and why researches of their structure improvement are so important. Short analysis of previous researches is provided, with their negative features and ways for further researches being exposed. Several ways to formulate recommendations and requirements for site structure are suggested, as well as methods for its optimization. A method for implementation of research results as software product is proposed. The information about an example of such software which performs analysis of sites of educational institution is provided too

Site structure analysis and optimization

The article contains information about current situation of site development, reasons why sites are so essential for activity of organizations and why researches of their structure improvement are so important. Short analysis of previous researches is provided, with their negative features and ways for further researches being exposed. Several ways to formulate recommendations and requirements for site structure are suggested, as well as methods for its optimization. A method for implementation of research results as software product is proposed. The information about an example of such software which performs analysis of sites of educational institution is provided too

Common Transcriptional Signatures in Brain Tissue from Patients with HIV-Associated Neurocognitive Disorders, Alzheimer’s Disease, and Multiple Sclerosis

HIV-Associated Neurocognitive Disorders (HAND) is a common manifestation of HIV infection that afflicts about 50 % of HIV-positive individuals. As people with access to antiretroviral treatments live longer, HAND can be found in increasing segments of populations at risk for other chronic, neurodegenerative conditions such as Alzheimer’s disease (AD) and Multiple Sclerosis (MS). If brain diseases of diverse etiologies utilize similar biological pathways in the brain, they may coexist in a patient and possibly exacerbate neuropathogenesis and morbidity. To test this proposition, we conducted comparative meta-analysis of selected publicly available microarray datasets from brain tissues of patients with HAND, AD, and MS. In pair-wise and three-way analyses, we found a large number of dysregulated genes and biological processes common to either HAND and AD or HAND and MS, or to all three diseases. The common characteristic of all three diseases was up-regulation of broadly ranging immune responses in the brain. In addition, HAND and AD share down-modulation of processes involved, among others, in synaptic transmission and cell-cell signaling while HAND and MS share defective processes of neurogenesis and calcium/calmodulin-dependent protein kinase activity. Our approach could provide insight into the identification of common disease mechanisms and better intervention strategies for complex neurocognitive disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11481-012-9409-5) contains supplementary material, which is available to authorized users

Expression of the T4 molecule (AIDS virus receptor) by human brain-derived cells

AbstractThree human cell lines of astrocytic origin were evaluated for expression of a human T-lymphocyte surface glycoprotein, T4, which also serves as a cellular receptor for the human immunodeficiency virus (AIDS virus, HIV). T4 antigen was detected on the cell surface of 2 of these cell lines using monoclonal OKT-4 antibody and flow cytometry. Gene transcripts encoding the T4 molecule were detected by a ribonuclease protection assay in surface T4-positive and -negative cells. Our results suggest that astrocytes may serve as targets for HIV infection in the brain

Human Immunodeficiency Virus Type 1 (HIV-1) Infection of Herpesvirus Saimiri-Immortalized Human CD4-Positive T Lymphoblastoid Cells: Evidence of Enhanced HIV-1 Replication and Cytopathic Effects Caused by Endogenous Interferon-γ

AbstractHerpesvirus saimiri (HVS) is a nonhuman primate gamma herpesvirus which can immortalize human T lymphocytes similar to Epstein–Barr virus immortalization of B cells. The HVS-immortalized T cell lines can be cloned and they remain functional, including susceptibility of CD4 expressing T cells to infection with human immunodeficiency virus type 1 (HIV-1). In this report, we have used five such HVS-transformed CD4-positive T cell clones to reevaluate the role of endogenous interferon gamma (IFNγ) in HIV-1 replication in T cells. All five clones had similar phenotypes; and four clones constitutively produced IFNγ and one clone did not. All five clones could be efficiently infected with HIV-1. HIV-1 infection of the IFNγ-positive cells also upregulated IFNγ mRNA production and IFNγ secretion but not production of IL-2 or IL-4. In contrast, infection of IFNγ-negative cells did not induce IFNγ, IL-2, or IL-4. Exposure to anti-IFNγ antibodies after HIV-1 infection significantly reduced virus production and inhibited virus-induced death of IFNγ-positive cells but had no effect on IFNγ-negative cells. We conclude that in CD4-positive T lymphocytes immortalized by HVS endogenous IFNγ does not inhibit HIV-1 but enhances HIV-1 replication and cytolysis. The potential augmenting effects of IFNγ on HIV-1 replication in CD4-positive T cells recommend caution in a therapeutic use of this cytokine in AIDS

HIV induces expression of complement component C3 in astrocytes by NF-κB-dependent activation of interleukin-6 synthesis

Background Abnormal activation of the complement system contributes to some central nervous system diseases but the role of complement in HIV-associated neurocognitive disorder (HAND) is unclear. Methods We used real-time PCR and immunohistochemistry to detect complement expression in postmortem brain tissue from HAND patients and controls. To further investigate the basis for viral induction of gene expression in the brain, we studied the effect of HIV on C3 expression by astrocytes, innate immune effector cells, and targets of HIV. Human fetal astrocytes (HFA) were infected with HIV in culture and cellular pathways and factors involved in signaling to C3 expression were elucidated using pharmacological pathway inhibitors, antisense RNA, promoter mutational analysis, and fluorescence microscopy. Results We found significantly increased expression of complement components including C3 in brain tissues from patients with HAND and C3 was identified by immunocytochemistry in astrocytes and neurons. Exposure of HFA to HIV in culture-induced C3 promoter activity, mRNA expression, and protein production. Use of pharmacological inhibitors indicated that induction of C3 expression by HIV requires NF-κB and protein kinase signaling. The relevance of NF-κB regulation to C3 induction was confirmed through detection of NF-κB translocation into nuclei and inhibition through overexpression of the physiological NF-κB inhibitor, I-κBα. C3 promoter mutation analysis revealed that the NF-κB and SP binding sites are dispensable for the induction by HIV, while the proximal IL-1β/IL-6 responsive element is essential. HIV-treated HFA secreted IL-6, exogenous IL-6 activated the C3 promoter, and anti-IL-6 antibodies blocked HIV activation of the C3 promoter. The activation of IL-6 transcription by HIV was dependent upon an NF-κB element within the IL-6 promoter. Conclusions These results suggest that HIV activates C3 expression in primary astrocytes indirectly, through NF-κB-dependent induction of IL-6, which in turn activates the C3 promoter. HIV induction of C3 and IL-6 in astrocytes may contribute to HIV-mediated inflammation in the brain and cognitive dysfunction

Human immunodeficiency virus type 1 efficiently binds to human fetal astrocytes and induces neuroinflammatory responses independent of infection

<p>Abstract</p> <p>Background</p> <p>HIV-1 infects human astrocytes <it>in vitro </it>and <it>in vivo </it>but the frequency of infected cells is low and its biological significance is unknown. In studies <it>in vitro</it>, recombinant gp120 alone can induce profound effects on astrocyte biology, suggesting that HIV-1 interaction with astrocytes and its functional consequences extend beyond the limited levels of infection in these cells. Here we determined the relative efficiencies of HIV-1 binding and infection in human fetal astrocytes (HFA), mainly at the single cell level, using HIV-1 tagged with green fluorescence protein (GFP)-Vpr fusion proteins, termed HIV-GFP, to detect virus binding and HIV-1 expressing Rev and NefGFP fusion proteins to detect productive infection.</p> <p>Results</p> <p>Essentially all HFA in a population bound HIV-GFP specifically and independently of CCR5 and CXCR4. The dynamics of this binding at 37°C resembled binding of an HIV fusion mutant to CD4-positive cells, indicating that most of HIV-GFP arrested infection of HFA at the stage of virus-cell fusion. Despite extensive binding, only about 1% of HFA were detectably infected by HIV-RevGFP or HIV-NefGFP, but this proportion increased to the majority of HFA when the viruses were pseudotyped with vesicular stomatitis virus envelope glycoprotein G, confirming that HFA impose a restriction upon HIV-1 entry. Exposure of HFA to HIV-1 through its native proteins rapidly induced synthesis of interleukin-6 and interleukin-8 with increased mRNA detected within 3 h and increased protein detected within 18 h of exposure.</p> <p>Conclusion</p> <p>Our results indicate that HIV-1 binding to human astrocytes, although extensive, is not generally followed by virus entry and replication. Astrocytes respond to HIV-1 binding by rapidly increased cytokine production suggesting a role of this virus-brain cell interaction in HIV-1 neuropathogenesis.</p

Intimacy, marital satisfaction, and sexuality in mature couples

The present study investigated the relationship between intimacy and marital satisfaction, as well as between intimacy and sexuality. Participants were 30 couples, with a mean age of 49. Participants had been involved in a romantic relationship for an average of 20 years. Couples were asked to complete a variety of questionnaires on intimacy, marital, and sexual functioning. Results indicated no sex differences in levels of overall intimacy, or in levels of sexual satisfaction, however the men were experiencing more sexual problems than the women. For men, sexual and emotional intimacy predicted marital satisfaction, whereas for women, recreational and emotional intimacy were the significant predictors. High discrepancies between perceived and desired levels of intimacy were not related to lower marital satisfaction. Few dimensions of intimacy were related to sexual satisfaction and functioning. The finding that different types of intimacy are important to marital satisfaction for men and women has implications for the areas of focus in marital therapy. The finding that large discrepancies between perceived and desired intimacy levels did not decrease marital satisfaction suggests that individuals find ways to compensate for a lack of intimacy in their relationship. Other implications of the present findings, as well as how they relate to past research and theory, are discussed