Abstract
Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An ...unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise,
n
= 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX
n
= 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control;
n
= 35, MOD-EX;
n
= 31, and VIG-EX;
n
= 31). We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6 ml; Δ MOD-EX: −15.5 ± 62.1 ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or
18
F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1 ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1;
p
= 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.
Objective To examine the teratogenic potential of statins.Design Cohort study.Setting United States.Participants A cohort of 886 996 completed pregnancies linked to liveborn infants of women enrolled ...in Medicaid from 2000 to 2007.Methods We examined the risk of major congenital malformations and organ specific malformations in offspring associated with maternal use of a statin in the first trimester. Propensity score based methods were used to control for potential confounders, including maternal demographic characteristics, obstetric and medical conditions, and use of other drugs.Results 1152 (0.13%) women used a statin during the first trimester. In unadjusted analyses, the prevalence of malformations in the offspring of these women was 6.34% compared with 3.55% in those of women who did not use a statin in the first trimester (relative risk 1.79, 95% confidence interval 1.43 to 2.23). Controlling for confounders, particularly pre-existing diabetes, accounted for this increase in risk (1.07, 0.85 to 1.37). There were also no statistically significant increases in any of the organ specific malformations assessed after accounting for confounders. Results were similar across a range of sensitivity analyses.Conclusions Our analysis did not find a significant teratogenic effect from maternal use of statins in the first trimester. However, these findings need to be replicated in other large studies, and the long term effects of in utero exposure to statins needs to be assessed, before use of statins in pregnancy can be considered safe.
Autophagy malfunctioning occurs in multiple human disorders, making attractive the idea of chemically modulating it with therapeutic purposes. However, for many types of autophagy, a clear ...understanding of tissue-specific differences in their activity and regulation is missing because of lack of methods to monitor these processes in vivo. Chaperone-mediated autophagy (CMA) is a selective type of autophagy that until now has only been studied in vitro and not in the tissue context at single cell resolution. Here, we develop a transgenic reporter mouse that allows dynamic measurement of CMA activity in vivo using image-based procedures. We identify previously unknown spatial and temporal differences in CMA activity in multiple organs and in response to stress. We illustrate the versatility of this model for monitoring CMA in live animals, organotypic cultures and cell cultures from these mice, and provide practical examples of multiorgan response to drugs that modulate CMA.
Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD), affecting ~40 to 60% of individuals with AD (AD with psychosis (AD+P)). In ...comparison with AD subjects without psychosis, AD+P subjects have more rapid cognitive decline and poor outcomes. Prior studies have estimated the heritability of psychosis in AD at 61%, but the underlying genetic sources of this risk are not known. We evaluated a Discovery Cohort of 2876 AD subjects with (N=1761) or without psychosis (N=1115). All subjects were genotyped using a custom genotyping array designed to evaluate single-nucleotide polymorphisms (SNPs) with evidence of genetic association with AD+P and include SNPs affecting or putatively affecting risk for schizophrenia and AD. Results were replicated in an independent cohort of 2194 AD subjects with (N=734) or without psychosis (N=1460). We found that AD+P is associated with polygenic risk for a set of novel loci and inversely associated with polygenic risk for schizophrenia. Among the biologic pathways identified by the associations of schizophrenia SNPs with AD+P are endosomal trafficking, autophagy and calcium channel signaling. To the best of our knowledge, these findings provide the first clear demonstration that AD+P is associated with common genetic variation. In addition, they provide an unbiased link between polygenic risk for schizophrenia and a lower risk of psychosis in AD. This provides an opportunity to leverage progress made in identifying the biologic effects of schizophrenia alleles to identify novel mechanisms protecting against more rapid cognitive decline and psychosis risk in AD.
In a randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in increased fluid overload without improvement in clinical outcomes.
The present work investigates the quality and the chemical effects of dehydration, using a novel dehydration system based on an electromagnetic induction and low pressures technique, comparing it ...with the thermo-solar drying system. High oleic sunflower seeds, which are an important oil seed crop, were used due to the fact that they have a special place in the food industry. The seed samples were exposed to electromagnetic induction and low pressures by 0.5 and 1 h, then several chemical characterizations were carried out, in the electrophoresis study, it was found that most proteins in the hull were degraded or denatured, some of them were lost during the time in the thermosolar dryer while in kernel keeps 94.9% of the concentration in control proteins. Otherwise, the electromagnetic induction dryer did not lose the most of proteins in the kernel keeping 99.1% in 0.5 h and 98.4% in 1 h, just degrading its concentration. Germination viability results did not show changes after 0.5 h in the electromagnetic fields, but they decreased in 1 h from 66 to 40% until the thermosolar method fell to 24% in 4 h, both analysis results change proportionally with the treatment time and moisture content and the amount of the oxygen.
Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in patients with acute heart failure (HF) and neoplastic diseases. We investigated the association between ...NLR and mortality or cardiac transplantation in a retrospective cohort of 527 patients presented to the Cleveland Clinic for evaluation of advanced HF therapy options from 2007 to 2010. Patients were divided according to low, intermediate, and high tertiles of NLR and were followed longitudinally for time to all-cause mortality or heart transplantation (primary outcome). The median NLR was 3.9 (interquartile range 2.5 to 6.5). In univariate analysis, intermediate and highest tertiles of NLR had a higher risk than the lowest tertile for the primary outcome and all-causes mortality. Compared with the lowest tertile, there was no difference in the risk of heart transplantation for intermediate and high tertiles. In multivariate analysis, compared with the lowest tertile, the intermediate and high NLR tertiles remained significantly associated with the primary outcome (hazard ratio HR = 1.61, 95% confidence interval CI 1.10 to 2.37 and HR = 1.55, 95% CI 1.02 to 2.36, respectively) and all-cause mortality (HR = 1.83, 95% CI 1.07 to 3.14 and HR = 2.16, 95% CI 1.21 to 3.83, respectively). In conclusion, elevated NLR is associated with increased mortality or heart transplantation risk in patients with advanced HF.
To evaluate the hydrogeochemical processes related to the presence, mobility, and transport of uranium and thorium in the southeastern Sierra de Guanajuato of the Bajio Guanajuatense, Mexico, the ...concentration of these elements in volcanic rocks and in groundwater were determined. Acidic volcanic rocks contained uranium concentrations of 1.04–6.88 ppm and thorium concentrations of 3.13–15.58 ppm. A basalt rock sample contained 2.58 and 4.07 ppm of uranium and thorium, respectively, and an andesite rock sample contained 4.07 and 8.7 ppm of uranium and thorium, respectively. Scanning electron microscopy with energy-dispersive X-ray spectroscopy showed that U and Th are disseminated throughout the matrix of felsic rocks; in addition, phosphate minerals (probably monazite) containing both elements are present. The concentration of uranium in water samples ranged from 2.23 to 10.3 ppb and of thorium ranged from 0.33 to 0.39 ppb. Geochemical modeling indicated that uranium was mobilized through the transport of the uranyl ions (UO
2
2+
) and their complexes, especially carbonates, although other elements such as Fe, Mg, HCO
3
, and Ca could also be involved in the mobility and transportation of uranium. The obtained results suggest that the mobilization of thorium is very low, almost negligible in some cases, so this element did not present a quantifiable hydrogeochemical pattern. In spite of the low concentrations of U and Th, the existence of high radon concentrations in several samples indicates that additional radioactive species could be naturally present in the hydrogeological environment.
Different kinds of materials are broadly employed to manufacture bioimplants. Metals are commonly used for the fabrication of lower body components such as knee prostheses and hip replacements ...because of their good mechanical properties. Among the available metallic biomaterials, cobalt alloys are commonly used. However, the hostile environment of the human body promotes the corrosion of the metallic bioimplant, and the wear due to the sliding contact could also increase the corrosion. There is, therefore, a constant attempt to study the surface of metallic biomaterials to enhance their functionality. In the present work, two kinds of surface modification techniques were employed on ASTM F-1537 cobalt alloy samples: laser surface texturing and boriding. Tribocorrosion tests were carried out using a linear reciprocating tribometer coupled with a standard three-electrode electrochemical cell. Tafel polarization plots were used to calculate the material loss due to corrosion. Also, non-contact profilometry was employed to estimate the tribocorrosion volume loss. In addition, the worn tracks were analyzed by scanning electron microscopy and energy-dispersive X-ray spectroscopy. The textured + borided samples increased 1.5 times the tribocorrosion resistance compared to the untreated samples. The differences in the tribocorrosion performance among the modified surfaces were discussed in this paper.
•The texturing and boriding increased the tribocorrosion resistance of the surface.•The material loss due to corrosion was lower than the material loss due to tribocorrosion.•The texturing decreased the real contact area and the boriding retarded wear.
Frankia strains are nitrogen-fixing soil actinobacteria that can form root symbioses with actinorhizal plants. Phylogenetically, symbiotic frankiae can be divided into three clusters, and this ...division also corresponds to host specificity groups. The strains of cluster II which form symbioses with actinorhizal Rosales and Cucurbitales, thus displaying a broad host range, show suprisingly low genetic diversity and to date can not be cultured. The genome of the first representative of this cluster, Candidatus Frankia datiscae Dg1 (Dg1), a microsymbiont of Datisca glomerata, was recently sequenced. A phylogenetic analysis of 50 different housekeeping genes of Dg1 and three published Frankia genomes showed that cluster II is basal among the symbiotic Frankia clusters. Detailed analysis showed that nodules of D. glomerata, independent of the origin of the inoculum, contain several closely related cluster II Frankia operational taxonomic units. Actinorhizal plants and legumes both belong to the nitrogen-fixing plant clade, and bacterial signaling in both groups involves the common symbiotic pathway also used by arbuscular mycorrhizal fungi. However, so far, no molecules resembling rhizobial Nod factors could be isolated from Frankia cultures. Alone among Frankia genomes available to date, the genome of Dg1 contains the canonical nod genes nodA, nodB and nodC known from rhizobia, and these genes are arranged in two operons which are expressed in D. glomerata nodules. Furthermore, Frankia Dg1 nodC was able to partially complement a Rhizobium leguminosarum A34 nodC::Tn5 mutant. Phylogenetic analysis showed that Dg1 Nod proteins are positioned at the root of both α- and β-rhizobial NodABC proteins. NodA-like acyl transferases were found across the phylum Actinobacteria, but among Proteobacteria only in nodulators. Taken together, our evidence indicates an Actinobacterial origin of rhizobial Nod factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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