276 research outputs found

    Genetic imprint of vaccination on simian/human immunodeficiency virus type 1 transmitted viral genomes in rhesus macaques.

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    Understanding the genetic, antigenic and structural changes that occur during HIV-1 infection in response to pre-existing immunity will facilitate current efforts to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the population level but little with regard to specific changes occurring in the envelope glycoprotein within a host in response to immune pressure elicited by antibodies. The aim of this study was to track and map specific early genetic changes occurring in the viral envelope gene following vaccination using a highly controlled viral challenge setting in the SHIV macaque model. We generated 449 full-length env sequences from vaccinees, and 63 from the virus inoculum. Analysis revealed a different pattern in the distribution and frequency of mutations in the regions of the envelope gene targeted by the vaccine as well as different patterns of diversification between animals in the naïve control group and vaccinees. Given the high stringency of the model it is remarkable that we were able to identify genetic changes associated with the vaccination. This work provides insight into the characterization of breakthrough viral populations in less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV challenge model in macaques to unravel the mechanisms driving HIV-1 envelope genetic diversity in the presence of vaccine induced-responses.Evolutionary analysis was supported by a Wellcome Intermediate Clinical Fellowship while the animal work by National Institutes of Health (NIH) grant 1P01AI06628. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Shrinking and Splitting of drainage basins in orogenic landscapes from the migration of the main drainage divide

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    International audienceClimate, and in particular **the spatial pattern of precipitation, is thought to affect* *the topographic and tectonic evolution of mountain belts through erosion. Numerical model simulations of landscape erosion controlled **by horizontal tectonic motion or orographic precipitation result in the asymmetric topography that characterizes most natural mountain belts, and in a continuous migration of the main drainage divide. The effects of such a migration have, however, been challenging to observe in natural settings. Here I document the effects of a lateral precipitation gradient on a landscape undergoing constant uplift in a laboratory modelling experiment. In the experiment, the drainage divide migrates towards the drier, leeward side of the mountain range, causing the drainage basins on the leeward side to shrink and split into* *smaller basins. This mechanism results in a progressively increasing number of drainage basins on the leeward side of the mountain range as the divide migrates, such that the expected relationship between the spacing of drainage basins and the location of the main drainage divide is maintained. I propose that this mechanism could clarify the drainage divide migration and topographic asymmetry found in active orogenic mountain ranges, as exemplified by the Aconquija Range of Argentin

    Observation of the Fractional Quantum Hall Effect in Graphene

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    When electrons are confined in two dimensions and subjected to strong magnetic fields, the Coulomb interactions between them become dominant and can lead to novel states of matter such as fractional quantum Hall liquids. In these liquids electrons linked to magnetic flux quanta form complex composite quasipartices, which are manifested in the quantization of the Hall conductivity as rational fractions of the conductance quantum. The recent experimental discovery of an anomalous integer quantum Hall effect in graphene has opened up a new avenue in the study of correlated 2D electronic systems, in which the interacting electron wavefunctions are those of massless chiral fermions. However, due to the prevailing disorder, graphene has thus far exhibited only weak signatures of correlated electron phenomena, despite concerted experimental efforts and intense theoretical interest. Here, we report the observation of the fractional quantum Hall effect in ultraclean suspended graphene, supporting the existence of strongly correlated electron states in the presence of a magnetic field. In addition, at low carrier density graphene becomes an insulator with an energy gap tunable by magnetic field. These newly discovered quantum states offer the opportunity to study a new state of matter of strongly correlated Dirac fermions in the presence of large magnetic fields

    Healthy Eating Index scores associated with symptoms of depression in Cuban-Americans with and without type 2 diabetes: a cross sectional study

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    <p>Abstract</p> <p>Background</p> <p>Low diet quality and depression symptoms are independently associated with poor glycemic control in subjects with type 2 diabetes (T2D); however, the relationship between them is unclear. The aim of this study was to determine the association between diet quality and symptoms of depression among Cuban-Americans with and without T2D living in South Florida.</p> <p>Methods</p> <p>Subjects (n = 356) were recruited from randomly selected mailing list. Diet quality was determined using the Healthy Eating Index-2005 (HEI-05) score. Symptoms of depression were assessed using the Beck Depression Inventory (BDI). Both linear and logistic regression analyses were run to determine whether or not these two variables were related. Symptoms of depression was the dependent variable and independent variables included HEI-05, gender, age, marital status, BMI, education level, A1C, employment status, depression medication, duration of diabetes, and diabetes status. Analysis of covariance was used to test for interactions among variables.</p> <p>Results</p> <p>An interaction between diabetes status, gender and HEI-05 was found (<it>P </it>= 0.011). Among males with a HEI-05 score ≤ 55.6, those with T2D had a higher mean BDI score than those without T2D (11.6 vs. 6.6 respectively, <it>P </it>= 0.028). Among males and females with a HEI-05 score ≤ 55.6, females without T2D had a higher mean BDI score compared to males without T2D (11.0 vs. 6.6 respectively, <it>P </it>= 0.012)</p> <p>Conclusions</p> <p>Differences in symptoms of depression according to diabetes status and gender are found in Cuban-Americans with low diet quality.</p

    Overeating, caloric restriction and breast cancer risk by pathologic subtype: the EPIGEICAM study

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    This study analyzes the association of excessive energy intake and caloric restriction with breast cancer (BC) risk taking into account the individual energy needs of Spanish women. We conducted a multicenter matched case-control study where 973 pairs completed lifestyle and food frequency questionnaires. Expected caloric intake was predicted from a linear regression model in controls, including calories consumed as dependent variable, basal metabolic rate as an offset and physical activity as explanatory. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. The association with BC risk, overall and by pathologic subtype, was evaluated using conditional and multinomial logistic regression models. While premenopausal women that consumed few calories (>20% below predicted) had lower BC risk (OR = 0.36; 95% CI = 0.21–0.63), postmenopausal women with an excessive intake (≥40% above predicted) showed an increased risk (OR = 2.81; 95% CI = 1.65–4.79). For every 20% increase in relative (observed/predicted) caloric intake the risk of hormone receptor positive (p-trend < 0.001) and HER2+ (p-trend = 0.015) tumours increased 13%, being this figure 7% for triple negative tumours. While high energy intake increases BC risk, caloric restriction could be protective. Moderate caloric restriction, in combination with regular physical activity, could be a good strategy for BC prevention

    Epidemiology of cardiovascular risk factors in Greece: aims, design and baseline characteristics of the ATTICA study

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    BACKGROUND: In an attempt to evaluate the levels of several cardiovascular risk factors in Greece we conducted a population-based health and nutrition survey, the "ATTICA study". In this work we present the design and the methodology of the study, as well as the status of various baseline characteristics of the participants. METHODS: From May 2001 to December 2002 we randomly enrolled 1514 adult men and 1528 adult women, stratified by age – gender (census 2000), from the greater area of Athens. More than 300 demographic, lifestyle, behavioral, dietary, clinical and biochemical variables have been recorded. RESULTS: Regarding the frequency of the classical cardiovascular risk factors we observed that 51% of men and 39% of women reported smokers (p < 0.05), 37% of men and 25% of women were defined as hypertensives (p < 0.05), 46% of men and 40% of women had total serum cholesterol levels above 200 mg/dl (p < 0.05) and 8% of men and 6% of women had history of diabetes mellitus. Moreover, 20% of men and 15% of women were obese (p < 0.05), while men were more physically active as compared to women (42% vs. 39%, p < 0.05). 19% of men and 38% of women had mild to severe depressive symptoms (p < 0.01). Finally, 72 men (5%) and 45 (3%) women reported history of coronary heart disease at entry evaluation. CONCLUSIONS: The prevalence of the common cardiovascular risk factors in our population seems high. As a consequence a considerable proportion of Greek adults are at "high-risk" for future cardiovascular events

    Current opportunities to catalyze research in nutrition and cancer prevention – an interdisciplinary perspective

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    Cancer Research UK and Ludwig Cancer Research convened an inaugural international Cancer Prevention and Nutrition Conference in London on December 3–4, 2018. Much of the discussion focused on the need for systematic, interdisciplinary approaches to better understand the relationships of nutrition, exercise, obesity and metabolic dysfunction with cancer development. Scientists at the meeting underscored the importance of studying the temporal natural history of exposures that may cumulatively impact cancer risk later in life. A robust dialogue identified obesity as a major risk for cancer, and the food environment, especially high energy and low nutrient processed foods, as strong and prevalent risk factors for obesity. Further engagement highlighted challenges in the post-diagnostic setting, where similar opportunities to understand the complex interplay of nutrition, physical activity, and weight will inform better health outcomes. Going forward, holistic research approaches, encompassing insights from multiple disciplines and perspectives, will catalyze progress urgently needed to prevent cancer and improve public health

    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 μg/m<sup>3</sup>; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/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 μg/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

    Maternal characteristics associated with the dietary intake of nitrates, nitrites, and nitrosamines in women of child-bearing age: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Multiple <it>N</it>-nitroso compounds have been observed in animal studies to be both mutagenic and teratogenic. Human exposure to <it>N</it>-nitroso compounds and their precursors, nitrates and nitrites, can occur through exogenous sources, such as diet, drinking water, occupation, or environmental exposures, and through endogenous exposures resulting from the formation of <it>N</it>-nitroso compounds in the body. Very little information is available on intake of nitrates, nitrites, and nitrosamines and factors related to increased consumption of these compounds.</p> <p>Methods</p> <p>Using survey and dietary intake information from control women (with deliveries of live births without major congenital malformations during 1997-2004) who participated in the National Birth Defects Prevention Study (NBDPS), we examined the relation between various maternal characteristics and intake of nitrates, nitrites, and nitrosamines from dietary sources. Estimated intake of these compounds was obtained from the Willet Food Frequency Questionnaire as adapted for the NBDPS. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the consumption of these compounds by self-reported race/ethnicity and other maternal characteristics.</p> <p>Results</p> <p>Median intake per day for nitrates, nitrites, total nitrites (nitrites + 5% nitrates), and nitrosamines was estimated at 40.48 mg, 1.53 mg, 3.69 mg, and 0.472 μg respectively. With the lowest quartile of intake as the referent category and controlling for daily caloric intake, factors predicting intake of these compounds included maternal race/ethnicity, education, body mass index, household income, area of residence, folate intake, and percent of daily calories from dietary fat. Non-Hispanic White participants were less likely to consume nitrates, nitrites, and total nitrites per day, but more likely to consume dietary nitrosamines than other participants that participated in the NBDPS. Primary food sources of these compounds also varied by maternal race/ethnicity.</p> <p>Conclusions</p> <p>Results of this study indicate that intake of nitrates, nitrites, and nitrosamines vary considerably by race/ethnicity, education, body mass index, and other characteristics. Further research is needed regarding how consumption of foods high in nitrosamines and <it>N</it>-nitroso precursors might relate to risk of adverse pregnancy outcomes and chronic diseases.</p
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