65 research outputs found

    HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

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    BAckground:HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs). RESULTS: MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPAR\u3b3 activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. CONCLUSIONS: The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients

    Social Psychology, Consumer Culture and Neoliberal Political Economy

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    © 2017 John Wiley & Sons Ltd. Consumer culture and neoliberal political economy are often viewed by social psychologists as topics reserved for anthropologists, economists, political scientists and sociologists. This paper takes an alternative view arguing that social psychology needs to better understand these two intertwined institutions as they can both challenge and provide a number of important insights into social psychological theories of self-identity and their related concepts. These include personality traits, self-esteem, social comparisons, self-enhancement, impression management, self-regulation and social identity. To illustrate, we examine how elements of consumer culture and neoliberal political economy intersect with social psychological concepts of self-identity through three main topics: 'the commodification of self-identity', 'social categories, culture and power relations' and the 'governing of self-regulating consumers'. In conclusion, we recommend a decommodified approach to research with the aim of producing social psychological knowledge that avoids becoming enmeshed with consumer culture and neoliberalism

    Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

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    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses

    Studies on the cold hardiness of the peach-potato aphid Myzus persicae (Sulzer)

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    A system incorporating a prototype automatic thermoelectric cooling method with computer-based recording of aphid supercooling points was developed and formed the basis of cold hardiness assessment. Under laboratory culture all developmental stages of Myzus persicae had a mean inherent supercooling potential below -20°C, with first instar nymphs the most cold hardy. When maintained at 5°C, younger instars demonstrated acclimation ability unlike adult aphids, and in an insecticide resistant strain, adults lost cold hardiness. When in contact with surface moisture, the majority of aphids did not experience inoculative nucleation. Sexual morphs of M. persicae possessed supercooling ability comparable with laboratory maintained parthenogenetic morphs; eggs supercooled to below -30°C. Seasonal studies of supercooling ability demonstrated that all aphid stages were most cold hardy in summer. Younger instars showed natural acclimatisation and were cold hardy throughout the year. Overall adults lost cold hardiness as winter progressed, exhibiting bimodal supercooling point distributions in two winters, with distinct high (HG) and low (LG) groups and mean supercooling points of approximately -20°C and -10 oe respectively. Clonal differences and adult age did not account for this pattern. Following experimental starvation at 5°C, first instars of M. persicae maintained extensive supercooling potential but adults exhibited losses of cold hardiness comparable with those in natural overwintering populations, suggesting that feeding may be necessary to maintain adult cold hardiness levels during winter. Subsequent starvation experiments did not reproduce the dramatic losses of cold hardiness implying that the feeding influence was more complex than the availability of food per se. In a series of host transfer experiments the mean supercooling point of Aphis fabae adults could be shifted by over 10°C, increasing when they fed on beans and reduced when transferred back to spindle; the LG (spindle/poor supercoolers) to HG (bean/good supercoolers) shift was more difficult to achieve and suggested a nucleating agent in spindle sap. Trimethylsilyl derivatised carbohydrate extracts of M. persicae and A. fabae were analysed by capillary gas-liquid chromatography. Glucose, glycerol, fructose, mannitol, sucrose, and trehalose were detected in samples of both species, together with trace amounts of unidentified carbohydrates in M. persicae samples. Dulcitol was present in spindle-fed A. fabae only. There was no obvious correlation between carbohydrate content and supercooling ability but high total percentage body carbohydrate levels were revealed and may have a solute effect, enhancing inherent supercooling potential and dependent on carbohydrate-rich sap intake. Laboratory cultured A. fabae were capable of extensive supercooling, as were individuals collected from summer herbaceous hosts; first instars were the most cold hardy. When associated with the primary host, spindle, all aphids showed poor supercooling potential, less than -15°C; overwintering eggs were capable of supercooling to below -30°C and acclimatised in winter. Eggs and oviparae were not subject to inoculative nucleation. Preliminary experiments to relate supercooling ability to mortality at sub-zero temperatures proved inconclusive and were terminated when temperature shock and/or desiccation were thought to have induced premature mortality. The results demonstrate that the cold hardiness characteristics of M. persicae are atypical of those observed in other freezing-susceptible arthropods. It is proposed that continued feeding during mild winters maintains cold hardiness levels in adult M. persicae and this influence may provide a possible explanation for the successful anholocyclic overwintering of this aphid during such winters. Avenues of research to further investigate this proposal are suggested
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