195 research outputs found

    A multimodal approach for tracing lateralization along the olfactory pathway in the honeybee through electrophysiological recordings, morpho-functional imaging, and behavioural studies

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    Recent studies have revealed asymmetries between the left and right sides of the brain in invertebrate species. Here we present a review of a series of recent studies from our labs, aimed at tracing asymmetries at different stages along the honeybee's (Apis mellifera) olfactory pathway. These include estimates of the number of sensilla present on the two antennae, obtained by scanning electron microscopy, as well as electroantennography recordings of the left and right antennal responses to odorants. We describe investigative studies of the antennal lobes, where multi-photon microscopy is used to search for possible morphological asymmetries between the two brain sides. Moreover, we report on recently published results obtained by two-photon calcium imaging for functional mapping of the antennal lobe aimed at comparing patterns of activity evoked by different odours. Finally, possible links to the results of behavioural tests, measuring asymmetries in single-sided olfactory memory recall, are discussed.Comment: 28 pages, 8 figure

    PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers

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    <p>Abstract</p> <p>Background</p> <p>To better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM<sub>2.5</sub>) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM<sub>2.5 </sub>and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.</p> <p>Methods</p> <p>Twenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM<sub>2.5 </sub>samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM<sub>2.5 </sub>metal exposures both with and without adjustment for total PM<sub>2.5</sub>. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM<sub>2.5 </sub>and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM<sub>2.5 </sub>as surrogates for the differential effects of metal exposures in models for night rMSSD.</p> <p>Results</p> <p>The median PM<sub>2.5 </sub>exposure was 650 ΞΌg/m<sup>3</sup>; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 ΞΌg/m<sup>3 </sup>to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 ΞΌg/m<sup>3 </sup>increase in manganese. However, even after adjusting for individual metals, increases in total PM<sub>2.5 </sub>exposures were associated with declines in night rMSSD.</p> <p>Conclusion</p> <p>These results support the cardiotoxicity of PM<sub>2.5 </sub>metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.</p

    A Review of Metallothionein Isoforms and their Role in Pathophysiology

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    The Metallothionein (MT) is a protein which has several interesting biological effects and has been demonstrated increase focus on the role of MT in various biological systems in the past three decades. The studies on the role of MT were limited with few areas like apoptosis and antioxidants in selected organs even fifty years after its discovery. Now acknowledge the exploration of various isoforms of MT such as MT-I, MT-II, MT-III and MT-IV and other isoforms in various biological systems

    An initial psychometric evaluation and exploratory cross-sectional study of the Body Checking Questionnaire among Brazilian women

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    Body checking is considered an expression of an excessive preoccupation with appearance. The first aim of this study was to evaluate the psychometric properties of a Brazilian Portuguese version of the Body Checking Questionnaire (BCQ). Additionally, we wanted to examine the questionnaire’s associations with body avoidance behaviour, body mass index, dietary habits, and the intensity, frequency, and length of physical exercise. Finally, we also examined the differences between the total BCQ score and the individual BCQ factor scores. Differences between active and sedentary persons and between non-dieters and those on weight-loss diets were also analyzed. For the psychometric study, 546 female public university students from four different courses were surveyed. Two minor samples of university students and eating disorders women were also recruited. In the second part of the study, 403 women were recruited from weight-loss programs, gyms, and a university. All participants were verbally invited to participate in the research and voluntarily took part. Confirmatory factor analysis showed a good fit to the original model of the Brazilian BCQ that retained all 23 items. Satisfactory evidence of construct validity and internal consistency were also generated through analysis of factor loadings, t-values, Cronbach’s alpha, and construct reliability tests. The results also showed associations among body checking and body avoidance, body satisfaction, social anxiety, body mass index, and the frequency and intensity of physical exercise. Significant differences were found between non-dieters and weight-loss dieters for all BCQ factors and the total BCQ score. For physically active and sedentary persons, a significant difference was only observed for idiosyncratic checking behaviour. In conclusion, the BCQ appears to be a valid and reliable scale for Brazilian research, and the associations and differences found in this study suggest that women at gyms and especially in weight-loss programs should be targeted for future body checking studies

    Clarifying mammalian RISC assembly in vitro

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    <p>Abstract</p> <p>Background</p> <p>Argonaute, the core component of the RNA induced silencing complex (RISC), binds to mature miRNAs and regulates gene expression at transcriptional or post-transcriptional level. We recently reported that Argonaute 2 (Ago2) also assembles into complexes with miRNA precursors (pre-miRNAs). These Ago2:pre-miRNA complexes are catalytically active <it>in vitro </it>and constitute non-canonical RISCs.</p> <p>Results</p> <p>The use of pre-miRNAs as guides by Ago2 bypasses Dicer activity and complicates <it>in vitro </it>RISC reconstitution. In this work, we characterized Ago2:pre-miRNA complexes and identified RNAs that are targeted by miRNAs but not their corresponding pre-miRNAs. Using these target RNAs we were able to recapitulate <it>in vitro </it>pre-miRNA processing and canonical RISC loading, and define the minimal factors required for these processes.</p> <p>Conclusions</p> <p>Our results indicate that Ago2 and Dicer are sufficient for processing and loading of miRNAs into RISC. Furthermore, our studies suggest that Ago2 binds primarily to the 5'- and alternatively, to the 3'-end of select pre-miRNAs.</p

    HIV-1 Efficient Entry in Inner Foreskin Is Mediated by Elevated CCL5/RANTES that Recruits T Cells and Fuels Conjugate Formation with Langerhans Cells

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    Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs) and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold) and decreased CCL20/MIP-3-alpha (0.62-fold) secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site

    SHIV-162P3 Infection of Rhesus Macaques Given Maraviroc Gel Vaginally Does Not Involve Resistant Viruses

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    Maraviroc (MVC) gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0) but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls. The infecting SHIV-162P3 stock had an overall mean genetic distance of 0.294Β±0.027%; limited entropy changes were noted across the envelope (gp160). No envelope mutations were observed consistently in viruses isolated from infected macaques at days 14–21, the time of first detectable viremia, nor selected at later time points, days 42–70. No statistically significant differences in MVC susceptibilities were observed between the SHIV inoculum (50% inhibitory concentration [IC50] 1.87 nM) and virus isolated from the three MVC-treated macaques (MVC IC50 1.18 nM, 1.69 nM, and 1.53 nM, respectively). Highlighter plot analyses suggested that infection was established in each MVC-treated animal by one founder virus genotype. The expected Poisson distribution of pairwise Hamming Distance frequency counts was observed and a phylogenetic analysis did not identify infections with distinct lineages from the challenge stock. These data suggest that breakthrough infections most likely result from incomplete viral inhibition and not the selection of MVC-resistant variants

    Deciphering von Hippel-Lindau (VHL/Vhl)-Associated Pancreatic Manifestations by Inactivating Vhl in Specific Pancreatic Cell Populations

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    The von Hippel-Lindau (VHL) syndrome is a pleomorphic familial disease characterized by the development of highly vascularized tumors, such as hemangioblastomas of the central nervous system, pheochromocytomas, renal cell carcinomas, cysts and neuroendocrine tumors of the pancreas. Up to 75% of VHL patients are affected by VHL-associated pancreatic lesions; however, very few reports in the published literature have described the cellular origins and biological roles of VHL in the pancreas. Since homozygous loss of Vhl in mice resulted in embryonic lethality, this study aimed to characterize the functional significance of VHL in the pancreas by conditionally inactivating Vhl utilizing the Cre/LoxP system. Specifically, Vhl was inactivated in different pancreatic cell populations distinguished by their roles during embryonic organ development and their endocrine lineage commitment. With Cre recombinase expression directed by a glucagon promoter in Ξ±-cells or an insulin promoter in Ξ²-cells, we showed that deletion of Vhl is dispensable for normal functions of the endocrine pancreas. In addition, deficiency of VHL protein (pVHL) in terminally differentiated Ξ±-cells or Ξ²-cells is insufficient to induce pancreatic neuroendocrine tumorigenesis. Most significantly, we presented the first mouse model of VHL-associated pancreatic disease in mice lacking pVHL utilizing Pdx1-Cre transgenic mice to inactivate Vhl in pancreatic progenitor cells. The highly vascularized microcystic adenomas and hyperplastic islets that developed in Pdx1-Cre;Vhl f/f homozygous mice exhibited clinical features similar to VHL patients. Establishment of three different, cell-specific Vhl knockouts in the pancreas have allowed us to provide evidence suggesting that VHL is functionally important for postnatal ductal and exocrine pancreas, and that VHL-associated pancreatic lesions are likely to originate from progenitor cells, not mature endocrine cells. The novel model systems reported here will provide the basis for further functional and genetic studies to define molecular mechanisms involved in VHL-associated pancreatic diseases
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