Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

Africa in the click stream: audience metrics and foreign correspondents in africa

Digital technologies have transformed the relationship between news outlets, journalists and their audiences. Notably, editors can now monitor their websites and discern the exact news preferences of their readers. Research suggests that some editors are using this data to help them produce more popular, ‘click friendly’ content. To date, research on this phenomenon has focused on journalists working within newsrooms. This article adds to the literature by exploring the relationship of foreign correspondents in Africa with their audiences, and asks whether readership metrics are influencing the journalists’ selection and development of news stories. Drawing on 67 interviews with foreign correspondents in East and West Africa, the article identifies three different approaches to audience metrics: correspondents who are 1) data-driven; 2) data informed; and 3) data denialists. The article discusses the implications of these approaches for the media image of Africa that is distributed around the globe

About females and males: continuity and discontinuity in flies

Through the decades of relentless and dedicated studies in Drosophila melanogaster, the pathway that governs sexual development has been elucidated in great detail and has become a paradigm in understanding fundamental cell-fate decisions. However, recent phylogenetic studies show that the molecular strategy used in Drosophila deviates in some important aspects from those found in other dipteran flies and suggest that the Drosophila pathway is likely to be a derivative of a simpler and more common principle. In this essay, I will discuss the evolutionary plasticity of the sex-determining pathway based on studies in the common housefly, Musca domestica. Diversification appears to primarily arise from subtle differences in the regulation of the key switch gene transformer at the top of the pathway. On the basis of these findings I propose a new idea on how the Drosophila pathway may have evolved from a more archetypal system such as in M. domestica. In essence, the arrival of an X counting mechanism mediated by Sex-lethal to compensate for X linked gene dose differences set the stage for an intimate coupling of the two pathways. Its precedent recruitment to the dosage compensation pathway allowed for an intervention in the regulation of transformer where it gradually and eventually' completely substituted for a need of transformer autoregulation

Teaching computer-assisted qualitative data analysis to a large cohort of undergraduate students

Qualitative research is increasingly being conducted with the support of computer-assisted qualitative data analysis software (CAQDAS), yet limited research has been conducted on integrating the teaching of CAQDAS packages within qualitative methods university courses. Existing research typically focuses on teaching NVivo to small groups of postgraduate (primarily doctoral) students and mostly take the form of reflections of the trainers. In 2011, we implemented the teaching and use of a CAQDAS package, NVivo, within a large third-year undergraduate psychology research methods unit. Sixty-seven students participated in an online survey evaluating the use of NVivo in the unit. In this paper, we present quantitative and qualitative findings related to students' perceptions of the resources provided, their confidence in using NVivo, their satisfaction with the teaching and their intentions to use CAQDAS in the future. Student evaluations were generally positive, but highlighted the need for both increased class time and greater access to the CAQDAS program outside of class time to enhance opportunities for learning

Hybrid multicriteria fuzzy classification of network traffic patterns, anomalies, and protocols

© 2017, Springer-Verlag London Ltd., part of Springer Nature. Traffic classification in computer networks has very significant roles in network operation, management, and security. Examples include controlling the flow of information, allocating resources effectively, provisioning quality of service, detecting intrusions, and blocking malicious and unauthorized access. This problem has attracted a growing attention over years and a number of techniques have been proposed ranging from traditional port-based and payload inspection of TCP/IP packets to supervised, unsupervised, and semi-supervised machine learning paradigms. With the increasing complexity of network environments and support for emerging mobility services and applications, more robust and accurate techniques need to be investigated. In this paper, we propose a new supervised hybrid machine-learning approach for ubiquitous traffic classification based on multicriteria fuzzy decision trees with attribute selection. Moreover, our approach can handle well the imbalanced datasets and zero-day applications (i.e., those without previously known traffic patterns). Evaluating the proposed methodology on several benchmark real-world traffic datasets of different nature demonstrated its capability to effectively discriminate a variety of traffic patterns, anomalies, and protocols for unencrypted and encrypted traffic flows. Comparing with other methods, the performance of the proposed methodology showed remarkably better classification accuracy

Improving Coping Skills for Self-management of Treatment Side Effects Can Reduce Antiretroviral Medication Nonadherence among People Living with HIV

BackgroundHuman immunodeficiency virus (HIV) treatment side effects have a deleterious impact on treatment adherence, which is necessary to optimize treatment outcomes including morbidity and mortality.PurposeTo examine the effect of the Balance Project intervention, a five-session, individually delivered HIV treatment side effects coping skills intervention on antiretroviral medication adherence.MethodsHIV+ men and women (N = 249) on antiretroviral therapy (ART) with self-reported high levels of ART side effect distress were randomized to intervention or treatment as usual. The primary outcome was self-reported ART adherence as measured by a combined 3-day and 30-day adherence assessment.ResultsIntent-to-treat analyses revealed a significant difference in rates of nonadherence between intervention and control participants across the follow-up time points such that those in the intervention condition were less likely to report nonadherence. Secondary analyses revealed that intervention participants were more likely to seek information about side effects and social support in efforts to cope with side effects.ConclusionsInterventions focusing on skills related to ART side-effects management show promise for improving ART adherence among persons experiencing high levels of perceived ART side effects

Complementation of diverse HIV-1 Env defects through cooperative subunit interactions: a general property of the functional trimer

<p>Abstract</p> <p>Background</p> <p>The HIV-1 Env glycoprotein mediates virus entry by catalyzing direct fusion between the virion membrane and the target cell plasma membrane. Env is composed of two subunits: gp120, which binds to CD4 and the coreceptor, and gp41, which is triggered upon coreceptor binding to promote the membrane fusion reaction. Env on the surface of infected cells is a trimer consisting of three gp120/gp41 homo-dimeric protomers. An emerging question concerns cooperative interactions between the protomers in the trimer, and possible implications for Env function.</p> <p>Results</p> <p>We extended studies on cooperative subunit interactions within the HIV-1 Env trimer, using analysis of functional complementation between coexpressed inactive variants harboring different functional deficiencies. In assays of Env-mediated cell fusion, complementation was observed between variants with a wide range of defects in both the gp120 and gp41 subunits. The former included gp120 subunits mutated in the CD4 binding site or incapable of coreceptor interaction due either to mismatched specificity or V3 loop mutation. Defective gp41 variants included point mutations at different residues within the fusion peptide or heptad repeat regions, as well as constructs with modifications or deletions of the membrane proximal tryptophan-rich region or the transmembrane domain. Complementation required the defective variants to be coexpressed in the same cell. The observed complementation activities were highly dependent on the assay system. The most robust activities were obtained with a vaccinia virus-based expression and reporter gene activation assay for cell fusion. In an alternative system involving Env expression from integrated provirus, complementation was detected in cell fusion assays, but not in virus particle entry assays.</p> <p>Conclusion</p> <p>Our results indicate that Env function does not require every subunit in the trimer to be competent for all essential activities. Through cross-talk between subunits, the functional determinants on one defective protomer can cooperatively interact to trigger the functional determinants on an adjacent protomer(s) harboring a different defect, leading to fusion. Cooperative subunit interaction is a general feature of the Env trimer, based on complementation activities observed for a highly diverse range of functional defects.</p

CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics

Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C) HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins—high physical stability, specificity and low production costs—with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development