5-HT1A receptor blockade reverses GABAA receptor α3 subunit-mediated anxiolytic effects on stress-induced hyperthermia

Stress-related disorders are associated with dysfunction of both serotonergic and GABAergic pathways, and clinically effective anxiolytics act via both neurotransmitter systems. As there is evidence that the GABA(A) and the serotonin receptor system interact, a serotonergic component in the anxiolytic actions of benzodiazepines could be present. The main aim of the present study was to investigate whether the anxiolytic effects of (non-)selective alpha subunit GABA(A) receptor agonists could be reversed with 5-HT1A receptor blockade using the stress-induced hyperthermia (SIH) paradigm. The 5-HT1A receptor antagonist WAY-100635 (0.1-1 mg/kg) reversed the SIH-reducing effects of the non-alpha-subunit selective GABA(A) receptor agonist diazepam (1-4 mg/kg) and the GABA(A) receptor alpha(3)-subunit selective agonist TP003 (1 mg/kg), whereas WAY-100635 alone was without effect on the SIH response or basal body temperature. At the same time, co-administration of WAY-100635 with diazepam or TP003 reduced basal body temperature. WAY-100635 did not affect the SIH response when combined with the preferential alpha(1)-subunit GABA(A) receptor agonist zolpidem (10 mg/kg), although zolpidem markedly reduced basal body temperature. The present study suggests an interaction between GABA(A) receptor alpha-subunits and 5-HT1A receptor activation in the SIH response. Specifically, our data indicate that benzodiazepines affect serotonergic signaling via GABA(A) receptor alpha(3)-subunits. Further understanding of the interactions between the GABA(A) and serotonin system in reaction to stress may be valuable in the search for novel anxiolytic drugs

Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner

HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -α and -δ, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs

Infection of Semen-Producing Organs by SIV during the Acute and Chronic Stages of the Disease

International audienceBACKGROUND: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected. CONCLUSIONS/SIGNIFICANCE: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen

Reproductive performance and diving behaviour share a common sea-ice concentration optimum in Adélie penguins (Pygoscelis adeliae)

This study was financially supported by the following institutions: the WWF-UK through R. Downie, the Japanese Mombukagakusho and the Japanese Society for the Promotion of Science, the Zone Atelier Antarctique et Subantarctique –LTER France of the CNRS.The Southern Ocean is currently experiencing major environmental changes, including in sea‐ice cover. Such changes strongly influence ecosystem structure and functioning and affect the survival and reproduction of predators such as seabirds. These effects are likely mediated by reduced availability of food resources. As such, seabirds are reliable eco‐indicators of environmental conditions in the Antarctic region. Here, based on 9 years of sea‐ice data, we found that the breeding success of Adélie penguins (Pygoscelis adeliae) reaches a peak at intermediate sea‐ice cover (ca. 20%). We further examined the effects of sea‐ice conditions on the foraging activity of penguins, measured at multiple scales from individual dives to foraging trips. Analysis of temporal organisation of dives, including fractal and bout analyses, revealed an increasingly consistent behaviour during years with extensive sea‐ice cover. The relationship between several dive parameters and sea‐ice cover in the foraging area appears to be quadratic. In years of low and high sea‐ice cover, individuals adjusted their diving effort by generally diving deeper, more frequently and by resting at the surface between dives for shorter periods of time than in years with intermediate sea‐ice cover. Our study therefore suggests that sea‐ice cover is likely to affect the reproductive performance of Adélie penguins through its effects on foraging behaviour, as breeding success and most diving parameters share a common optimum. Some years, however, deviated from this general trend, suggesting that other factors (e.g. precipitation during the breeding season) might sometimes become preponderant over the sea‐ice effects on breeding and foraging performance. Our study highlights the value of monitoring fitness parameters and individual behaviour concomitantly over the long‐term to better characterize optimal environmental conditions and potential resilience of wildlife. Such an approach is crucial if we want to anticipate the effects of environmental change on Antarctic penguin populations.PostprintPeer reviewe

Mesure de très basses tensions interfaciales et d'angles de contact sous hautes pressions et températures élevées

Au cours de ces dernières années, les basses tensions interfaciales ont été mesurées surtout par la méthode de la goutte tournante . Des considérations théoriques montrent que les méthodes de la goutte posée ou de la goutte pendante sont aussi utilisables pour ce type de mesure à la condition de pouvoir former de très petites gouttes. Ces méthodes présentent de plus l'avantage d'être plus facilement adaptables aux fortes pressions et aux températures élevées. Un appareillage pour ce type de mesure et des exemples de résultats sont présentés

Gentlemen first? 'Broken stick' modelling reveals sex-related homing decision date in migrating seabirds

Technical progress in animal-borne tracking and movement data analysis has facilitated the understanding of the interplay between successive periods in the life cycle of migratory animals. We investigated how sex differences on the constraints of homing may influence migration to breeding areas in crested penguins (genus Eudyptes). We used a novel approach to infer homing decision date, a precise point in time that translates statistically as a change point in the current distance of the animal to its colony (‘broken stick’ modelling approach, R codes provided here). We applied this approach to geolocation tracking data on migration in three Eudyptes species, from three localities in the southern Indian Ocean (five populations). Sex had a subtle and consistent influence on the temporal activity of the 66 animals during their migratory journey. Males began migration to the breeding localities earlier than females, by an average of 9.1 (range: 4.5–13.5) days. This difference was statistically significant in 4 of 5 populations, and occurred among all species, sites and years surveyed. Our study shows an original application of a recent modelling approach to detect change point in movement data. Our results suggest that sex-specific constraints related to breeding in migrating animals may also modify activity schedules well before breeding commences