Human depression: a new approach in quantitative psychiatry

The biomolecular approach to major depression disorder is explained by the different steps that involve cell membrane viscosity, Gsα protein and tubulin. For the first time it is hypothesised that a biomolecular pathway exists, moving from cell membrane viscosity through Gsα protein and Tubulin, which can condition the conscious state and is measurable by electroencephalogram study of the brain's γ wave synchrony

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

Independent Component Analysis of Resting State Activity in Pediatric Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty-three pediatric OCD patients and 23 healthy volunteers (age range 9-17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children\u27s Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified three components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity=78.3% and specificity=73.9%). Independent component expression scores were significantly higher in patients compared with healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention. Hum Brain Mapp 35:5306-5315, 2014. (c) 2014 Wiley Periodicals, Inc

Recognition of dance-like actions: memory for static posture or dynamic movement?

Dance-like actions are complex visual stimuli involving multiple changes in body posture across time and space. Visual perception research has demonstrated a difference between the processing of dynamic body movement and the processing of static body posture. Yet, it is unclear whether this processing dissociation continues during the retention of body movement and body form in visual working memory (VWM). When observing a dance-like action, it is likely that static snapshot images of body posture will be retained alongside dynamic images of the complete motion. Therefore, we hypothesized that, as in perception, posture and movement would differ in VWM. Additionally, if body posture and body movement are separable in VWM, as form- and motion-based items, respectively, then differential interference from intervening form and motion tasks should occur during recognition. In two experiments, we examined these hypotheses. In Experiment 1, the recognition of postures and movements was tested in conditions in which the formats of the study and test stimuli matched (movement-study to movement-test, posture-study to posture-test) or mismatched (movement-study to posture-test, posture-study to movement-test). In Experiment 2, the recognition of postures and movements was compared after intervening form and motion tasks. These results indicated that (1) the recognition of body movement based only on posture is possible, but it is significantly poorer than recognition based on the entire movement stimulus, and (2) form-based interference does not impair memory for movements, although motion-based interference does. We concluded that, whereas static posture information is encoded during the observation of dance-like actions, body movement and body posture differ in VWM

A reflection on HIV/AIDS research after 25 years

Dr. Robert C. Gallo provides a personal reflection on the 25 year history of AIDS

In Vivo CD8+ T-Cell Suppression of SIV Viremia Is Not Mediated by CTL Clearance of Productively Infected Cells

The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV

Magnetic Properties of Single Transition-Metal Atom Absorbed Graphdiyne and Graphyne Sheet

The electronic and magnetic properties of single 3d transition-metal(TM) atom (V, Cr, Mn, Fe, Co, and Ni) adsorbed graphdiyne (GDY) and graphyne (GY) are systematically studied using first-principles calculations within the density functional framework. We find that the adsorption of TM atom not only efficiently modulates the electronic structures of GDY/GY system, but also introduces excellent magnetic properties, such as half-metal and spin-select half-semiconductor. Such modulation originates from the charge transfer between TM adatom and the GDY/GY sheet as well as the electron redistribution of the TM intra-atomic s, p, and d orbitals. Our results indicate that the TM adsorbed GDY/GY are excellent candidates for spintronics.Comment: 8 pages, 7 figure

Chemokine Coreceptor Signaling in HIV-1 Infection and Pathogenesis

Binding of the HIV-1 envelope to its chemokine coreceptors mediates two major biological events: membrane fusion and signaling transduction. The fusion process has been well studied, yet the role of chemokine coreceptor signaling in viral infection has remained elusive through the past decade. With the recent demonstration of the signaling requirement for HIV latent infection of resting CD4 T cells, the issue of coreceptor signaling needs to be thoroughly revisited. It is likely that virus-mediated signaling events may facilitate infection in various immunologic settings in vivo where cellular conditions need to be primed; in other words, HIV may exploit the chemokine signaling network shared among immune cells to gain access to downstream cellular components, which can then serve as effective tools to break cellular barriers. This virus-hijacked aberrant signaling process may in turn facilitate pathogenesis. In this review, we summarize past and present studies on HIV coreceptor signaling. We also discuss possible roles of coreceptor signaling in facilitating viral infection and pathogenesis

Cell-to-Cell Interactions and Signals Involved in the Reconstitution of Peripheral CD8+ TCM and TEM Cell Pools

We here describe novel aspects of CD8+ and CD4+ T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8+ T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8+ T cells and their differentiation of effector functions is limited, but both dramatically increase upon the co-transfer of CD4+ T cells. This helper effect is complex and determined by multiple factors. It was directly correlated to the number of helper cells, required the continuous presence of the CD4+ T cells, dependent on host antigen-presenting cells (APCs) expressing CD40 and on the formation of CD4/CD8/APC cell clusters. By comparing the recovery of (CD44+CD62Lhigh) TCM and (CD44+CD62Llow) TEM CD8+ T cells, we found that the accumulation of TCM and TEM subsets is differentially regulated. TCM-cell accumulation depended mainly on type I interferons, interleukin (IL)-6, and IL-15, but was independent of CD4+ T-cell help. In contrast, TEM-cell expansion was mainly determined by CD4+ T-cell help and dependent on the expression of IL-2Rβ by CD8 cells, on IL-2 produced by CD4+ T-cells, on IL-15 and to a minor extent on IL-6