1,108 research outputs found

    Three‐dimensional turbulence‐resolving simulations of the plunge phenomenon in a tilted channel

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    Hyperpycnal flows are produced when the density of a fluid flowing in a relatively quiescent basin is greater than the density of the fluid in the basin. The density differences can be due to the difference in temperatures, salinity, turbidity, concentration, or a combination of them. When the inflow momentum diminishes, the inflowing fluid eventually plunges under the basin fluid and flows along the bottom floor as an underflow density current. In the present work, 3‐D turbulence‐resolving simulations are performed for an hyperpycnal flow evolving at the bottom floor of a tilted channel. Using advanced numerical techniques designed for supercomputers, the incompressible Navier‐Stokes and transport equations are solved to reproduce numerically the experiments of Lamb et al. (2010, https://doi.org/10.1130/B30125.1) obtained inside a flume with a long tilted ramp. This study focuses on presenting and validating a new numerical framework for the correct reproduction and analysis of the plunge phenomenon and its associated flow features. A very good agreement is found between the experimental data of Lamb et al. (2010), the analytical models of Parker and Toniolo (2007, https://doi.org/10.1061/(ASCE)0733-9429(2007)133:6(690)), and the present turbulence‐resolving simulations. The mixing process between the ambient fluid and the underflow density current is also analyzed thanks to visualizations of vortical structures at the interface

    Expression of the disease on female carriers of X-linked lysosomal disorders: a brief review

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    Most lysosomal diseases (LD) are inherited as autosomal recessive traits, but two important conditions have X-linked inheritance: Fabry disease and Mucopolysaccharidosis II (MPS II). These two diseases show a very different pattern regarding expression on heterozygotes, which does not seem to be explained by the X-inactivation mechanism only. While MPS II heterozygotes are asymptomatic in most instances, in Fabry disease most of female carriers show some disease manifestation, which is sometimes severe. It is known that there is a major difference among X-linked diseases depending on the cell autonomy of the gene product involved and, therefore, on the occurrence of cross-correction. Since lysosomal enzymes are usually secreted and uptaken by neighbor cells, the different findings between MPS II and Fabry disease heterozygotes can also be due to different efficiency of crosscorrection (higher in MPS II and lower in Fabry disease). In this paper, we review these two X-linked LD in order to discuss the mechanisms that could explain the different rates of penetrance and expressivity observed in the heterozygotes; this could be helpful to better understand the expression of X-linked traits

    Mortality among over 6 million internal and international migrants in Brazil: a study using the 100 Million Brazilian Cohort

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    Background: To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. / Methods: We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals' migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants; and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. / Findings: The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR = 0.99, 95% CI = 0.98–0.99), marginally higher mortality for ischaemic heart diseases (aHR = 1.04, 95% CI = 1.03–1.05) and higher for stroke (aHR = 1.11, 95% CI = 1.09–1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR = 0.82, 95% CI = 0.80–0.84), with up to 50% lower mortality from interpersonal violence among men (aHR = 0.50, 95% CI = 0.40–0.64), but higher mortality from avoidable causes related to maternal health (aHR = 2.17, 95% CI = 1.17–4.05). / Interpretation: Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants

    Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

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    Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

    Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

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    ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3ÎČ,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth

    Decreased Fatty Acid Transporter FABP1 and Increased Isoprostanes and Neuroprostanes in the Human Term Placenta: Implications for Inflammation and Birth Weight in Maternal Pre-Gestational Obesity.

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    The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexaenoic (DHA) and arachidonic acid (AA), respectively, neuroprostanes and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function

    MIRRAGGE – Minimum Information Required for Reproducible AGGregation Experiments

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    Reports on phase separation and amyloid formation for multiple proteins and aggregation-prone peptides are recurrently used to explore the molecular mechanisms associated with several human diseases. The information conveyed by these reports can be used directly in translational investigation, e.g., for the design of better drug screening strategies, or be compiled in databases for benchmarking novel aggregation-predicting algorithms. Given that minute protocol variations determine different outcomes of protein aggregation assays, there is a strong urge for standardized descriptions of the different types of aggregates and the detailed methods used in their production. In an attempt to address this need, we assembled the Minimum Information Required for Reproducible Aggregation Experiments (MIRRAGGE) guidelines, considering first-principles and the established literature on protein self-assembly and aggregation. This consensus information aims to cover the major and subtle determinants of experimental reproducibility while avoiding excessive technical details that are of limited practical interest for non-specialized users. The MIRRAGGE table (template available in Supplementary Information) is useful as a guide for the design of new studies and as a checklist during submission of experimental reports for publication. Full disclosure of relevant information also enables other researchers to reproduce results correctly and facilitates systematic data deposition into curated databases.This work was supported by (i) the European Regional Development Fund (ERDF) through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a CiĂȘncia e a Tecnologia (FCT/MCTES) in the framework of grants POCI-01-0145-FEDER-031173, POCI-01-0145-FEDER-007274, POCI-01-0145-FEDER-031323 (“Institute for Research and Innovation in Health Sciences”), UID/Multi/04046/2013 (BioISI) and PTDC/NEUNMC/2138/2014 (to CMG). SV was funded by the Spanish Ministry of Economy and Competitiveness (BIO2016-78310-R) and by ICREA (ICREA-Academia 2015). ZG and ZB were funded by Slovak research agentures VEGA 02/0145/17, 02/0030/18 and APVV-18-0284. RS was funded by VEGA 02/0163/19. DEO was funded by the Lundbeck Foundation (grant no. R276-2018-671) and the Independent Research Foundation Denmark | Natural Sciences (grant no. 8021-00208B). AP research was supported by UK Dementia Research Institute (RE1 3556) and by ARUK (ARUK-PG2019B-020)
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