Dealcoholized red wine reverse vascular remodeling in an experimental model of metabolic syndrome: role of NAD(P)H oxidase and eNOS activity

The present study examines the effect of chronic administration of dealcoholized red wine Malbec (DRW) on vascular remodeling and NAD(P)H oxidase and endothelial nitric oxide synthase activity (eNOS) in an experimental model of metabolic syndrome induced by fructose administration. Thirty-day old male Wistar rats were fed a normal rat diet (control) or the same diet plus 10% fructose in drinking water (FFR). During the last 4 weeks of a 10-week period of the corresponding diet, a subgroup of control and FFR (n=8 each) received DRW in their drinking water. Systolic blood pressure (SBP), a homeostasis model assessment of insulin resistance (HOMA-IR), aortic NAD(P)H oxidase and eNOS activity in the heart and vascular tissue were evaluated. Vascular remodeling was evaluated in the left carotid artery (CA) and interlobar, arcuate and interlobular renal arteries (RA) through lumen to media (L/M) ratio determination. At the end of the study FFR increased the SBP (p < 0.001), HOMA-IR (p < 0.001), and aortic NAD(P)H oxidase activity (p < 0,05) but reduced cardiac and vascular eNOS activity (p < 0.01), L/M ratio in CA (p < 0.001) and RA (p < 0.01) compared with the C group. DRW reduced SBP (p < 0.05), aortic NAD(P)H oxidase (p < 0.05), and recovered eNOS activity (p < 0.001) and L/M in CA (p < 0.001) and RA (p < 0.001) compared with FFR. This study provides new data about the beneficial effect of DRW on oxidative stress and vascular remodeling in the experimental model of metabolic syndrome. Data suggest the participation of mechanisms involving oxidative stress in FFR alterations and the usefulness of natural antioxidant substances present in red wine in the reversion of these changes.     

Method for retrospective collection of work-related psychosocial risk factors for musculoskeletal disorders: Reliability and aggregation.

Information on psychosocial work conditions during a 24-year period for 484 participants was collected retrospectively. Analyses were made of the interrater reliability, stability, specificity, and aggregation of data. The main finding was that it is possible to collect reliable information about psychosocial work conditions retrospectively for a long period of years when using a time ruler in a structured interview when earlier conditions are compared with the present. Interrater agreement was satisfactory for the larger part of the studied retrospective psychosocial risk factors and excellent for some of them. For most of the studied risk factors, the risk of overreporting exposure was low. The aggregation of data resulted in 2 indexes: poor social relations at work and low influence over work conditions. In conclusion, an individual time ruler works satisfactorily as a method of collecting retrospective information about psychosocial risk factors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Grain-Boundary-Rich Triphasic Artificial Hybrid Interphase Toward Practical Magnesium Metal Anodes

Magnesium metal anodes have attracted widespread attention for their high volumetric capacity and natural abundance, but are precluded from practical applications by poor rate capability and limited lifespan due to sluggish ion-transfer kinetics and uneven deposition behavior. Herein, for the first time a grain-boundary-rich triphasic artificial hybrid interphase, consisting of Sb metal, Mg₃Sb₂ alloy, and MgCl₂, is designed on Mg anode surface by a facile solution treatment method, enabling high-rate and long-cycle Mg plating/stripping behavior. The triphasic artificial hybrid interphase affords high magnesiophilicity and ionic conductivity to reduce the energy barriers for Mg²⁺ desolvation and deposition. Meanwhile, the abundant grain boundaries redistribute Mg²⁺ flux at the electrode-electrolyte interface and guide uniform Mg deposition. Accordingly, the as-designed Mg metal anode achieves ultralong cycling life of 350 h at a high current density of 5 mA cm⁻² and a large areal capacity of 5 mAh cm⁻², outperforming previously reported Mg metal anodes with artificial interphases. Full cells with Mo₆ cathode also show extraordinary stability over a long lifespan of 8000 cycles at a high rate of 5 C. The rational artificial interphase design and the understanding of composition-structure-function relationships shed deep insights into the development of fast-charging and long-cycling Mg metal batteries.     

Valuations for spike train prediction

The ultimate product of an electrophysiology experiment is often a decision on which biological hypothesis or model best explains the observed data. We outline a paradigm designed for comparison of different models, which we refer to as spike train prediction. A key ingredient of this paradigm is a prediction quality valuation that estimates how close a predicted conditional intensity function is to an actual observed spike train. Although a valuation based on log likelihood (L) is most natural, it has various complications in this context. We propose that a quadratic valuation (Q) can be used as an alternative to L. Q shares some important theoretical properties with L, including consistency, and the two valuations perform similarly on simulated and experimental data. Moreover, Q is more robust than L, and optimization with Q can dramatically improve computational efficiency. We illustrate the utility of Q for comparing models of peer prediction, where it can be computed directly from cross-correlograms. Although Q does not have a straightforward probabilistic interpretation, Q is essentially given by Euclidean distance.     

Robust discrimination between long‐range dependence and a change in mean

In this article we introduce a robust to outliers Wilcoxon change‐point testing procedure, for distinguishing between short‐range dependent time series with a change in mean at unknown time and stationary long‐range dependent time series. We establish the asymptotic distribution of the test statistic under the null hypothesis for L₁ near epoch dependent processes and show its consistency under the alternative. The Wilcoxon‐type testing procedure similarly as the CUSUM‐type testing procedure (of Berkes I., Horváth L., Kokoszka P. and Shao Q. 2006. Ann.Statist. 34:1140–1165), requires estimation of the location of a possible change‐point, and then using pre‐ and post‐break subsamples to discriminate between short and long‐range dependence. A simulation study examines the empirical size and power of the Wilcoxon‐type testing procedure in standard cases and with disturbances by outliers. It shows that in standard cases the Wilcoxon‐type testing procedure behaves equally well as the CUSUM‐type testing procedure but outperforms it in presence of outliers. We also apply both testing procedure to hydrologic data.     

Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.     

Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction

Nitric oxide (NO) is essential in the control of fetoplacental vascular tone, maintaining a high flow−low resistance circulation that favors oxygen and nutrient delivery to the fetus. Reduced fetoplacental blood flow is associated with pregnancy complications and is one of the major causes of fetal growth restriction (FGR). The reduction of dietary nitrate to nitrite and subsequently NO may provide an alternative source of NO in vivo. We have previously shown that nitrite induces vasorelaxation in placental blood vessels from normal pregnancies, and that this effect is enhanced under conditions of hypoxia. Herein, we aimed to determine whether nitrite could also act as a vasodilator in FGR. Using wire myography, vasorelaxant effects of nitrite were assessed on pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) from normal and FGR pregnancies under normoxic and hypoxic conditions. Responses to the NO donor, sodium nitroprusside (SNP), were assessed in parallel. Nitrate and nitrite concentrations were measured in fetal plasma. Hypoxia significantly enhanced vasorelaxation to nitrite in FGR CPAs (p < 0.001), and in both normal (p < 0.001) and FGR (p < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (p < 0.0001) and FGR (p < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (p < 0.01). Fetal plasma concentrations of nitrate and nitrite were not different between normal and FGR pregnancies. Together, these data show that nitrite-mediated vasorelaxation is preserved in FGR, suggesting that interventions targeting this pathway have the potential to improve fetoplacental blood flow in FGR pregnancies.     

Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium

Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain (COL1A2) mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-luteal phases at 24 or 48 h of treatment. The COL1A2 mRNA was evaluated by qPCR and COL1 protein relative abundance by Western blot. In equine endometrial explants, ELA increased COL 1 expression, while NOSC inhibited it at both estrous cycle phases and treatment times. These findings contribute to the future development of new endometrosis treatment approaches. Noscapine could be a drug capable of preventing collagen synthesis in mare’s endometrium and facilitate the therapeutic approach.     

68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System

The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of ⁶⁸Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [⁶⁸Ga]Ga-HBED-hexadiyne-tropane, showed an IC₅₀ value of 66 nM, together with a log D_7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.     

Deletion of six open reading frames from the left arm of chromosome IV of Saccharomyces cerevisiae

The construction of six deletion mutants of Saccharomyces cerevisiae and their basic phenotypic characterization are described. Open reading frames YDL148c, YDL109c, YDL021w, YDL019c, YDL018c and YDL015c from the left arm of chromosome IV were deleted using a polymerase chain reaction (PCR)‐based disruption technique, introducing the kanMX4 resistance marker into the respective genes. Gene replacement cassettes (pYORCs) for use in other strain backgrounds were cloned by PCR using DNA templates from haploid or diploid deletion mutants, and inserted into episomal plasmids. Cognate clones of all six ORFs were obtained by gap repair. Deletions were carried out in diploid cells and, after sporulation, yielded four viable spores for clones disrupted in YDL109c, YDL021w, YDL019c and YDL018c. Spores harbouring disruptions in ORFs YDL148c and YDL015c germinated but underwent only a few divisions before ceasing growth, suggesting that the respective genes are essential for vegetative growth on YPD complete media. The other deletion mutants grew like wild‐type at different temperatures and on different carbon sources. A brief computational analysis of the six ORFs studied in this work is presented. Copyright © 1999 John Wiley & Sons, Ltd.