10,482 research outputs found
A Note on the Log-Alpha-Skew-Normal Model with Geochemical Applications.
In this paper we introduce an extension of the log-normal distribution, based on the alpha-skew-normal distribution introduced by Elal-Olivero [10]. Basic properties, moments, moment estimators, maximum likelihood estimators and a simulation study are discussed. We apply the approach developed in this paper to data sets related to neodymium and nickel concentrations in soil samples. Model fit indicates good performance of the proposed model when compared with less flexible models
Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A
Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endolysosomal iron storage, cytosolic iron levels are modulated by NAADP, and increased cytosolic iron is detected when overexpressing active, but not inactive TPCNs, indicating that these channels can modulate endolysosomal iron release. Cell death triggered by altered intralysosomal iron handling is abrogated in the presence of an NAADP antagonist or when inhibiting RAB7A activity. Taken together, our results suggest that increased endolysosomal iron causes cell death associated with increased cytosolic oxidative stress as well as autophagic impairments, and these effects are subject to modulation by endolysosomal ion channel activity in a RAB7A-dependent manner. These data highlight alternative therapeutic strategies for neurodegenerative disorders associated with increased intracellular iron load
How to Improve the Functional Capacity of Frail and Pre-Frail Elderly People? Health, Nutritional Status and Exercise Intervention. The EXERNET-Elder 3.0 Project
Aging is associated with the impairment of health and functional capacity, and physical exercise seems to be an effective tool in frailty prevention and treatment. The purpose of this study was to present the methodology used in the EXERNET-Elder 3.0 project that aims to evaluate the immediate and residual effects and of a multicomponent exercise training program called Elder-fit on frailty, fitness, body composition and quality of life, and also to analyse a possible dietary intake interaction according to health and metabolic status. A total of 110 frail and pre-frail elders participated in this study and were divided into a control group (CG = 52) and an intervention group (IG = 58). The IG performed a supervised multicomponent exercise training program of 6 months and 3 days per week, which included strength, endurance, balance, coordination and flexibility exercises, while the CG continued with their usual daily activities. Both groups received four speeches about healthy habits along the project. Four evaluations were performed: at baseline, after 3 months of training, at the end of the training program (6 months) and 4 months after the program had ended to examine the effects of detraining. Evaluating the efficacy, safety and feasibility of this program will help to develop efficacious physical interventions against frailty. Further, protocols should be described accurately to allow exercise programs to be successfully replicated
Systemic sclerosis and pregnancy outcomes. A retrospective study from a single center
Background: Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC).
Methods: A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed.
Results: The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70-56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29-9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19-31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1-29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery.
Conclusions: We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended
Cyclin-Dependent Kinase Inhibitor p21 Controls Adult Neural Stem Cell Expansion by Regulating Sox2 Gene Expression
In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis
ACTN3 R577X Polymorphism does not Influence Explosive Leg Muscle Power in Elite Volleyball Players
We examined the association of R577X polymorphism (rs1815739) in the α-actinin-3 (ACTN3) gene with “explosive” leg muscle power performance in a group of male and female elite volleyball players (n=66, 31 men, 35 women) and in a group of non-athletic male and female young adults (n=334, 243 men, 91 women). We assessed power performance by means of the vertical squat and counter-movement jump tests. We also determined whether the genotypic frequencies of the ACTN3 R577X genotypes differed between groups. We did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in both groups, regardless of gender (all P>0.05). Genotype frequencies were similar between volleyball and control groups (P=0.095). Moreover, we did not find an association between the ACTN3 R577X polymorphism and the likelihood of being an elite volleyball player using the dominant (RR vs RX+XX) and the recessive model (RR+RX vs XX). In summary, these findings suggest that the ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players
Systemic sclerosis and pregnancy outcomes: a retrospective study from a single center.
Background: Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC). Methods: A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed. Results: The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70-56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29-9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19-31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1-29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery. Conclusions: We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended
Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes
Caveolins are 21-24 kDa integral membrane proteins that serve as
scaffolds to recruit numerous signaling molecules. Specific subclasses of
caveolae carry out specific functions in cell metabolism. In particular,
triglycerides are synthesized at the site of fatty acid entry in one of these
caveolae classes. OBJECTIVE AND METHODS: We studied the expression of caveolin-1
(CAV-1) gene in association with metabolic variables in 90 visceral and 55
subcutaneous adipose tissue samples from subjects with a wide range of fat mass,
in the stromovascular fraction (SVC) and isolated adipocytes, and during
differentiation of human adipocytes. RESULTS: CAV-1 gene expression was
significantly decreased in visceral adipose tissue (v-CAV-1) of obese subjects.
v-CAV-1 was positively associated with several lipogenic genes such as acetyl-coA
carboxylase (ACACA, r = 0.34, p = 0.004) and spot-14 (r = 0.33, p = 0.004). In
non-obese subjects v-CAV-1 also correlated with fatty acid synthase (FAS, r =
0.60, p < 0.0001). Subcutaneous (sc) adipose tissue (sc-CAV-1) gene expression
was not associated with these lipogenic factors when obese and non-obese subjects
were studied together. In obese subjects, however, sc-CAV-1 was associated with
fatty acid synthase (FAS, r = 0.36, p = 0.02), sterol regulatory element binding
protein-1c (SREBP-1c (r = 0.58, p < 0.0001), ACACA (r = 0.33, p = 0.03), spot-14
(r = 0.36, p = 0.02), PPAR-gamma co-activator-1 (PGC-1, r = 0.88, n = 19). In
these obese subjects, sc-CAV-1 was also associated with fasting triglycerides (r
= -0.50, p < 0.0001).CAV-1 expression in mature adipocytes was significantly
higher than in stromal vascular cells. CAV-1 gene expression in adipocytes from
subcutaneous adipose tissue (but not in adipocytes from visceral adipose tissue)
was significatively associated with fasting triglycerides. CAV-1 gene expression
did not change significantly during differentiation of human preadipocytes from
lean or obese subjects despite significant increase of FAS gene expression.
CONCLUSION: Decreased CAV-1 gene expression was simultaneously linked to
increased triglycerides and decreased lipogenic gene expression among obese
subjects, paralleling the observations of hypertriglyceridemia in CAV-1 knockout
mice. However, the regulation of CAV-1 gene expression seems independent of the
adipogenic program
Nuclear medium modification of the F2 structure function
We study the nuclear effects in the electromagnetic structure function
F2(x,Q^2) in nuclei in the deep inelastic lepton nucleus scattering process by
taking into account Fermi motion, binding, pion and rho meson cloud
contributions. Calculations have been done in a local density approximation
using relativistic nuclear spectral functions which include nucleon
correlations for nuclear matter. The ratios over deuteron structure function
are obtained and compared with the recent JLAB results for light nuclei with
special attention to the slope of the x distributions. This magnitude shows a
non trivial A dependence and it is insensitive to possible normalization
uncertainties. The results have also been compared with some of the older
experiments using intermediate mass nuclei.Comment: 19 pages, 8 figures. This version matches accepted version to be
published in Nuclear Physics
C2D Spitzer-IRS spectra of disks around T Tauri stars: I. Silicate emission and grain growth
Infrared ~5--35 um spectra for 40 solar-mass T Tauri stars and 7
intermediate-mass Herbig Ae stars with circumstellar disks were obtained using
the Spitzer Space Telescope as part of the c2d IRS survey. This work
complements prior spectroscopic studies of silicate infrared emission from
disks, which were focused on intermediate-mass stars, with observations of
solar-mass stars limited primarily to the 10 um region. The observed 10 and 20
um silicate feature strengths/shapes are consistent with source-to-source
variations in grain size. A large fraction of the features are weak and flat,
consistent with um-sized grains indicating fast grain growth (from 0.1--1.0 um
in radius). In addition, approximately half of the T Tauri star spectra show
crystalline silicate features near 28 and 33 um indicating significant
processing when compared to interstellar grains. A few sources show large
10-to-20 um ratios and require even larger grains emitting at 20 um than at 10
um. This size difference may arise from the difference in the depth into the
disk probed by the two silicate emission bands in disks where dust settling has
occurred. The 10 um feature strength vs. shape trend is not correlated with age
or Halpha equivalent width, suggesting that some amount of turbulent mixing and
regeneration of small grains is occurring. The strength vs. shape trend is
related to spectral type, however, with M stars showing significantly flatter
10 um features (larger grain sizes) than A/B stars. The connection between
spectral type and grain size is interpreted in terms of the variation in the
silicate emission radius as a function of stellar luminosity, but could also be
indicative of other spectral-type dependent factors (e.g, X-rays, UV radiation,
stellar/disk winds, etc.).Comment: 17 pages, 13 figures, accepted for publication by ApJ, formatted with
emulateapj using revtex4 v4.
- …