325 research outputs found

    Quantum Fluctuations and the Unruh Effect in Strongly-Coupled Conformal Field Theories

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    Through the AdS/CFT correspondence, we study a uniformly accelerated quark in the vacuum of strongly-coupled conformal field theories in various dimensions, and determine the resulting stochastic fluctuations of the quark trajectory. From the perspective of an inertial observer, these are quantum fluctuations induced by the gluonic radiation emitted by the accelerated quark. From the point of view of the quark itself, they originate from the thermal medium predicted by the Unruh effect. We scrutinize the relation between these two descriptions in the gravity side of the correspondence, and show in particular that upon transforming the conformal field theory from Rindler space to the open Einstein universe, the acceleration horizon disappears from the boundary theory but is preserved in the bulk. This transformation allows us to directly connect our calculation of radiation-induced fluctuations in vacuum with the analysis by de Boer et al. of the Brownian motion of a quark that is on average static within a thermal medium. Combining this same bulk transformation with previous results of Emparan, we are also able to compute the stress-energy tensor of the Unruh thermal medium.Comment: 1+31 pages; v2: reference adde

    Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

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    Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

    A New Integrated Variable Based on Thermometry, Actimetry and Body Position (TAP) to Evaluate Circadian System Status in Humans

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    The disruption of the circadian system in humans has been associated with the development of chronic illnesses and the worsening of pre-existing pathologies. Therefore, the assessment of human circadian system function under free living conditions using non-invasive techniques needs further research. Traditionally, overt rhythms such as activity and body temperature have been analyzed separately; however, a comprehensive index could reduce individual recording artifacts. Thus, a new variable (TAP), based on the integrated analysis of three simultaneous recordings: skin wrist temperature (T), motor activity (A) and body position (P) has been developed. Furthermore, we also tested the reliability of a single numerical index, the Circadian Function Index (CFI), to determine the circadian robustness. An actimeter and a temperature sensor were placed on the arm and wrist of the non-dominant hand, respectively, of 49 healthy young volunteers for a period of one week. T, A and P values were normalized for each subject. A non-parametric analysis was applied to both TAP and the separate variables to calculate their interdaily stability, intradaily variability and relative amplitude, and these values were then used for the CFI calculation. Modeling analyses were performed in order to determine TAP and CFI reliability. Each variable (T, A, P or TAP) was independently correlated with rest-activity logs kept by the volunteers. The highest correlation (r = −0.993, p<0.0001), along with highest specificity (0.870), sensitivity (0.740) and accuracy (0.904), were obtained when rest-activity records were compared to TAP. Furthermore, the CFI proved to be very sensitive to changes in circadian robustness. Our results demonstrate that the integrated TAP variable and the CFI calculation are powerful methods to assess circadian system status, improving sensitivity, specificity and accuracy in differentiating activity from rest over the analysis of wrist temperature, body position or activity alone

    A study of the dry forest communities in the Dominican Republic

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    This paper is a floristic and phytosociological study of the dry forest communities of the Dominican Republic. A total of 69 relevés in dry forest biotopes were carried out. The samples were subsequently subjected to Detrended Correspondence Analysis for the determination and study of possible groupings. The study does not cover tree formations growing on serpentines, nor the so-called semideciduous forests, peculiar to areas with higher rainfall. A total of nine phytocoenoses were identified. The most significant results led to the description of six new phytosociological associations: Simaroubetum berteroani (thorny dry forest on coastal dunes), Phyllostylo rhamnoidis-Prosopidetum juliflorae (southern Dominican disturbed dry forest), Consoleo moniliformis-Camerarietum linearifoliae (dry forest on hard limestones), Lemaireocereo hystricis-Prosopidetum juliflorae (northern Dominican disturbed dry forest), Lycio americani-Prosopidetum juliflorae (disturbed dry forest on saline soils) and Guettardo ellipticae-Guapiretum discoloris (dry forest on flat-topped hillocks in Montecristi). This is an important step forward in the phytosociological and floristic studies of the Caribbean territories.Este trabalho apresenta um estudo florístico e fitossociológico das comunidades de florestas secas da República Dominicana. Um total de 69 amostras foram obtidas pelo método relevé em biótopos florestais secos. As amostras foram posteriormente submetidas à análise de correspondência destendenciada para a determinação e estudo de possíveis agrupamentos. O estudo não abrange formações arbóreas desenvolvidas sobre serpentinitos, nem as chamadas florestas semideciduais, peculiares às áreas de maior pluviosidade. Foram identificados nove fitocenoses. Os resultados mais significativos levaram à descrição de seis novas associações fitossociológicas: Simaroubetum berteroani (floresta espinhosa seca em dunas costeiras), Phyllostylo rhamnoidis-Prosopidetum juliflorae (floresta seca perturbada do sul da República Dominicana), Consoleo moniliformis-Camerarietum linearifoliae (floresta seca sobre calcários compactos), Lemaireocereo hystricis-Prosopidetum juliflorae (floresta seca perturbada do norte da República Dominicana), Lycio americani-Prosopidetum juliflorae (floresta seca perturbada desenvolvida em solos salinos) Guettardo ellipticae-Guapiretum discoloris (floresta seca em colinas de topo achatado em Montecristi). O trabalho realizado representa um importante avanço nos estudos fitossociológicos e florísticos dos territórios do Caribe.This research paper was possible thanks to the sponsorship of the Agencia Española de Cooperación Internacional para el Desarrollo (AECID), under the auspices of the Ministerio de Asuntos Exteriores y de Cooperación de España, which funded the project (cod. A/3499/05)

    Socioeconomic status, urbanicity and risk behaviors in Mexican youth: an analysis of three cross-sectional surveys

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    <p>Abstract</p> <p>Background</p> <p>The relationship between urbanicity and adolescent health is a critical issue for which little empirical evidence has been reported. Although an association has been suggested, a dichotomous rural versus urban comparison may not succeed in identifying differences between adolescent contexts. This study aims to assess the influence of locality size on risk behaviors in a national sample of young Mexicans living in low-income households, while considering the moderating effect of socioeconomic status (SES).</p> <p>Methods</p> <p>This is a secondary analysis of three national surveys of low-income households in Mexico in different settings: rural, semi-urban and urban areas. We analyzed risk behaviors in 15-21-year-olds and their potential relation to urbanicity. The risk behaviors explored were: tobacco and alcohol consumption, sexual initiation and condom use. The adolescents' localities of residence were classified according to the number of inhabitants in each locality. We used a logistical model to identify an association between locality size and risk behaviors, including an interaction term with SES.</p> <p>Results</p> <p>The final sample included 17,974 adolescents from 704 localities in Mexico. Locality size was associated with tobacco and alcohol consumption, showing a similar effect throughout all SES levels: the larger the size of the locality, the lower the risk of consuming tobacco or alcohol compared with rural settings. The effect of locality size on sexual behavior was more complex. The odds of adolescent condom use were higher in larger localities only among adolescents in the lowest SES levels. We found no statically significant association between locality size and sexual initiation.</p> <p>Conclusions</p> <p>The results suggest that in this sample of adolescents from low-income areas in Mexico, risk behaviors are related to locality size (number of inhabitants). Furthermore, for condom use, this relation is moderated by SES. Such heterogeneity suggests the need for more detailed analyses of both the effects of urbanicity on behavior, and the responses--which are also heterogeneous--required to address this situation.</p

    Podocyte-Specific Overexpression of Wild Type or Mutant Trpc6 in Mice Is Sufficient to Cause Glomerular Disease

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    Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2–3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease

    Stage-Specific Effects of Candidate Heterochronic Genes on Variation in Developmental Time along an Altitudinal Cline of Drosophila melanogaster

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    Background: Previously, we have shown there is clinal variation for egg-to-adult developmental time along geographic gradients in Drosophila melanogaster. Further, we also have identified mutations in genes involved in metabolic and neurogenic pathways that affect development time (heterochronic genes). However, we do not know whether these loci affect variation in developmental time in natural populations. Methodology/Principal Findings: Here, we constructed second chromosome substitution lines from natural populations of Drosophila melanogaster from an altitudinal cline, and measured egg-adult development time for each line. We found not only a large amount of genetic variation for developmental time, but also positive associations of the development time with thermal amplitude and altitude. We performed genetic complementation tests using substitution lines with the longest and shortest developmental times and heterochronic mutations. We identified segregating variation for neurogenic and metabolic genes that largely affected the duration of the larval stages but had no impact on the timing of metamorphosis. Conclusions/Significance: Altitudinal clinal variation in developmental time for natural chromosome substitution lines provides a unique opportunity to dissect the response of heterochronic genes to environmental gradients. Ontogenetic stage-specific variation in invected, mastermind, cricklet and CG14591 may affect natural variation in development time an

    Menstrual and Reproductive Factors and Risk of Gastric and Colorectal Cancer in Spain

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    BACKGROUND: Sex hormones play a role in gastric cancer and colorectal cancer etiology, however, epidemiological evidence is inconsistent. This study examines the influence of menstrual and reproductive factors over the risk of both tumors. METHODS: In this case-control study 128 women with gastric cancer and 1293 controls, as well as 562 female and colorectal cancer cases and 1605 controls were recruited in 9 and 11 Spanish provinces, respectively. Population controls were frequency matched to cases by age and province. Demographic and reproductive data were directly surveyed by trained staff. The association with gastric, colon and rectal cancer was assessed using logistic and multinomial mixed regression models. RESULTS: Our results show an inverse association of age at first birth with gastric cancer risk (five-year trend: OR = 0.69; p-value = 0.006). Ever users of hormonal contraception presented a decreased risk of gastric (OR = 0.42; 95%CI = 0.26-0.69), colon (OR = 0.64; 95%CI = 0.48-0.86) and rectal cancer (OR = 0.61; 95%CI = 0.43-0.88). Postmenopausal women who used hormone replacement therapy showed a decreased risk of colon and rectal tumors. A significant interaction of educational level with parity and months of first child lactation was also observed. CONCLUSION: These findings suggest a protective role of exogenous hormones in gastric and colorectal cancer risk. The role of endogenous hormones remains unclear

    What do parents think about parental participation in school-based interventions on energy balance-related behaviours? a qualitative study in 4 countries

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    <p>Abstract</p> <p>Background</p> <p>Overweight and obesity in youth has increased dramatically. Therefore, overweight prevention initiatives should start early in life and target modifiable energy balance-related behaviours. Parental participation is often advocated as important for school-based interventions, however, getting parents involved in school-based interventions appears to be challenging based on earlier intervention experiences. The purpose of this study was to get insight into the determinants of and perspectives on parental participation in school-interventions on energy balance-related behaviours (physical activity, healthy eating, sedentary behaviours) in parents of ten- to twelve-year olds in order to develop an effective parental module for school-based interventions concerning energy balance-related behaviours.</p> <p>Methods</p> <p>Four countries (Belgium, Hungary, Norway and Spain) conducted the focus group research based on a standardised protocol and a semi-structured questioning route. A variation in parental socio-economic status (SES) and parental school involvement was taken into account when recruiting the parents. The audio taped interviews were transcribed, and a qualitative content analysis of the transcripts was conducted in each country.</p> <p>Results</p> <p>Seventeen focus group interviews were conducted with a total of 92 parents (12 men, 80 women). Physical activity was considered to be a joint responsibility of school and parents, nutrition as parent's responsibility but supported by the school, and prevention of sedentary behaviours as parent's sole responsibility. Parents proposed interactive and practical activities together with their child as the best way to involve them such as cooking, food tasting, nutrition workshops, walking or cycling tours, sport initiations together with their child. Activities should be cheap, on a convenient moment, focused on their children and not on themselves, not tutoring, not theoretical, and school-or home-based.</p> <p>Conclusions</p> <p>Parents want to be involved in activities related to energy balance-related behaviours if this implies 'doing things together' with their child at school or at home.</p

    Instability of aquaglyceroporin (Aqp) 2 contributes to drug resistance in trypanosoma brucei

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    Defining mode of action is vital for both developing new drugs and predicting potential resistance mechanisms. Sensitivity of African trypanosomes to pentamidine and melarsoprol is predominantly mediated by aquaglyceroporin 2 (TbAQP2), a channel associated with water/glycerol transport. TbAQP2 is expressed at the flagellar pocket membrane and chimerisation with TbAQP3 renders parasites resistant to both drugs. Two models for how TbAQP2 mediates pentamidine sensitivity have emerged; that TbAQP2 mediates pentamidine translocation across the plasma membrane or via binding to TbAQP2, with subsequent endocytosis and presumably transport across the endosomal/lysosomal membrane, but as trafficking and regulation of TbAQPs is uncharacterised this remains unresolved. We demonstrate that TbAQP2 is organised as a high order complex, is ubiquitylated and is transported to the lysosome. Unexpectedly, mutation of potential ubiquitin conjugation sites, i.e. cytoplasmic-oriented lysine residues, reduced folding and tetramerization efficiency and triggered ER retention. Moreover, TbAQP2/TbAQP3 chimerisation, as observed in pentamidine-resistant parasites, also leads to impaired oligomerisation, mislocalisation and increased turnover. These data suggest that TbAQP2 stability is highly sensitive to mutation and that instability contributes towards the emergence of drug resistance
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