Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable ...of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms of PD, remains unclear. Here, we used transgenic mice overexpressing human wild-type (WT) or A30P aSyn to compare the transcriptional profiles of the two animal models. We found that A30P aSyn promotes strong transcriptional deregulation and increases DNA binding. Interestingly, COL4A2, a major component of basement membranes, was found to be upregulated in both A30P aSyn transgenic mice and in dopaminergic neurons expressing A30P aSyn, suggesting a crucial role for collagen related genes in aSyn-induced toxicity. Finally, we observed that A30P aSyn alters Golgi morphology and increases the susceptibility to endoplasmic reticulum (ER) stress in dopaminergic cells. In total, our findings provide novel insight into the putative role of aSyn on transcription and on the molecular mechanisms involved, thereby opening novel avenues for future therapeutic interventions in PD and other synucleinopathies.
•A30P aSyn exhibits robust transcriptional deregulation in transgenic mice.•ER-related pathways are found deregulated in A30P aSyn transgenic mice.•A30P aSyn binds to several regions of DNA and affects exon usage.•A30P aSyn upregulates COL4A2, a major component of basement membranes.•A30P aSyn alters Golgi morphology and increases the susceptibility to ER stress.
Defining the metabolic syndrome (MetS) in children remains challenging. Furthermore, a dichotomous MetS diagnosis can limit the power to study associations. We sought to characterize the serum ...metabolite signature of the MetS in early childhood using high-throughput metabolomic technologies that allow comprehensive profiling of metabolic status from a biospecimen.
In the Family Atherosclerosis Monitoring In earLY life (FAMILY) prospective birth cohort study, we selected 228 cases of MetS and 228 matched controls among children age 5 years. In addition, a continuous MetS risk score was calculated for all 456 participants. Comprehensive metabolite profiling was performed on fasting serum samples using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariable regression models were applied to test metabolite associations with MetS adjusting for covariates of screen time, diet quality, physical activity, night sleep, socioeconomic status, age, and sex.
Compared to controls, thirteen serum metabolites were identified in MetS cases when using multivariable regression models, and using the quantitative MetS score, an additional eight metabolites were identified. These included metabolites associated with gluconeogenesis (glucose (odds ratio (OR) 1.55 95% CI 1.25-1.93) and glutamine/glutamate ratio (OR 0.82 95% CI 0.67-1.00)) and the alanine-glucose cycle (alanine (OR 1.41 95% CI 1.16-1.73)), amino acids metabolism (tyrosine (OR 1.33 95% CI 1.10-1.63), threonine (OR 1.24 95% CI 1.02-1.51), monomethylarginine (OR 1.33 95% CI 1.09-1.64) and lysine (OR 1.23 95% CI 1.01-1.50)), tryptophan metabolism (tryptophan (OR 0.78 95% CI 0.64-0.95)), and fatty acids metabolism (carnitine (OR 1.24 95% CI 1.02-1.51)). The quantitative MetS risk score was more powerful than the dichotomous outcome in consistently detecting this metabolite signature.
A distinct metabolite signature of pediatric MetS is detectable in children as young as 5 years old and may improve risk assessment at early stages of development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims/hypothesis
The aim of this study was to compare estimates of body fat content, i.e. body adiposity index (BAI), BMI and waist and hip circumferences, with respect to their ability to predict the ...percentage of body fat (PBF; confirmed by magnetic resonance tomography) and incident type 2 diabetes.
Methods
Associations between anthropometric measurements and PBF were evaluated in the Tübingen Lifestyle Intervention Program (TULIP; 138 men, 222 women), and between these measurements and incident type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (9,729 men, 15,438 women) and the Cooperative Health Research in the Region of Augsburg (KORA) study (5,573 men, 5,628 women), using correlation and multivariate Cox regression analyses.
Results
BMI more strongly correlated with PBF (men:
r
= 0.81, women:
r
= 0.84) than BAI (
r
= 0.68 and 0.81, respectively), while waist circumference among men (
r
= 0.84) and hip circumference among women (
r
= 0.88) showed the strongest correlations. BAI overestimated PBF among men (mean difference −3.0%), and this error was dependent on the value of PBF. BAI was more weakly associated with diabetes risk (RRs for 1 SD, EPIC-Potsdam men: 1.62 95% CI 1.52, 1.72, women: 1.67 95% CI 1.55, 1.80; KORA men: 1.62 95% CI 1.48, 1.78, women: 1.82 95% CI 1.65, 2.02) compared with BMI (RRs, EPIC-Potsdam men: 1.95 95% CI 1.83, 2.09, women 1.88 95% CI 1.76, 2.02, KORA men 1.75 95% CI 1.62, 1.89, women 2.00 95% CI 1.81, 2.22), while waist circumference showed the strongest associations (RRs: 2.17 95% CI 2.01, 2.35, 2.33 95% CI 2.15, 2.53, 1.81 95% CI 1.66, 1.96 and 2.29 95% CI 2.05, 2.57 for EPIC-Potsdam men and women and KORA men and women, respectively).
Conclusions/interpretation
Waist circumference in men and hip circumference in women are better predictors of PBF than BAI and BMI. BAI was not as strong a predictor of diabetes as BMI, while waist circumference was the strongest predictor.
Childhood obesity is a world-wide concern due to its growing prevalence and association with cardiometabolic risk factors in childhood and subsequent adult cardiovascular disease. In young pre-school ...children, there is uncertainty regarding which of the commonly used anthropometric measures of childhood obesity is best associated with cardiometabolic risk factors. This study compared the utility of common measures used in identifying obesity in these young children.
The four commonly used metrics for identifying obesity in children: body fat percentage ≥ 90th percentile, waist circumference ≥ 90th percentile, BMI z score > 2 SD and waist-to-height ratio (WHtR) ≥ 0.5, were measured in a cohort of children born singleton, at full term and followed from birth (n = 761) to 5 years of age (n = 513). The utility of each in identifying cardiometabolic risk factors (fasting lipid profile, fasting blood glucose and blood pressure) was examined.
At age 5 years, children with percent body fat ≥ 90th percentile or waist circumference ≥ 90th percentile, were associated with higher levels of triglycerides, glucose, and systolic and diastolic blood pressures than those < 90th percentile, respectively. Such differences were not obvious at age 3 years or at birth. A BMI z-score > 2 SD was associated with higher levels of triglycerides and systolic and diastolic blood pressure but not glucose at age 5 years. Differences in HDL cholesterol, fasting glucose and systolic blood pressure were observed in children with BMI z score > 2 SD at age 3 years but not with the other indices of obesity. As almost all children had WHtR ≥ 0.5 at birth, ages 1 and 3 years, this measure could not differentiate increased cardiometabolic risk. At age 5 years, the differences were much more obvious, with significant differences in triglycerides and systolic and diastolic blood pressures between those with WHtR ≥ 0.5 and those with < 0.5.
Each of the four commonly used measures of childhood obesity shows moderate associations with cardiometabolic risk factors at 5 years, with no advantage of one measure over the other. These associations were less consistent at 3 years of age or younger. These observations have not been reported previously.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Freshly collected boar spermatozoa are sensitive to a fast reduction in temperature because of lipid phase transition and phase separation processes. Temperature management during semen processing ...may determine the quality of stored samples. The aim of this study was to evaluate the influence of isothermic and hypothermic semen processing protocols on boar sperm quality under laboratory and field conditions. In the laboratory study, ejaculates (n = 12) were first diluted (1:1) with Beltsville Thawing Solution (BTS) at 32 °C, then processed either with isothermic (32 °C) or hypothermic (21 °C) BTS, stored at 17 °C, and assessed on days 1, 3, and 6. Temperature curves showed that 150 minutes after the first dilution, semen doses of both groups reached the same temperature. Two-step hypothermic processing resulted in lower sperm motility on days 1 and 6 (P < 0.05). Concomitantly, hypothermally processed samples contained less membrane intact sperm on days 3 and 6 (P < 0.05). Using AndroStar Plus extender instead of BTS reduced the negative effect of hypothermic processing. In the field study, 15 semen samples from each of 23 European artificial insemination studs were evaluated as part of an external quality control program. Semen quality based on motility, membrane integrity, mitochondrial activity, and a thermoresistance test was higher for stations using one-step isothermic dilutions (n = 7) compared with artificial insemination centers using two-step hypothermic protocols (n = 16). Both studies show that chilling injury associated with hypothermic dilution results in lower quality of stored boar semen compared with isothermic dilution and that the type of semen extender affects the outcomes.
Blood proportions of fatty acids (FAs) and FA-ratios reflecting desaturase activity are associated with the risk of chronic diseases like type 2 diabetes mellitus or cardiovascular diseases. ...Biomarkers of dyslipidemia are considered as potential mediators of this association. We evaluated associations of erythrocyte membrane proportions of individual disease-related polyunsaturated fatty acids (PUFAs), trans-FAs, dairy-derived saturated FAs (SFAs) (15:0, 17:0) and FA-ratios with biomarkers of dyslipidemia (high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, non-HDL-cholesterol, triglycerides).
We conducted a cross-sectional analysis of a subsample (n=1759) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. Associations of individual FAs and FA-ratios with plasma biomarkers of dyslipidemia were evaluated by linear multivariable regression.
Most notably, FA-ratios reflecting activity of Δ6-desaturase (D6D) and stearoyl-coenzyme A-desaturase (SCD) were positively associated with triglyceride and LDL-cholesterol concentrations (adjusted means (95% confidence interval (CI)) of triglycerides (mg/dl) across D6D tertiles: men--102 (94.7-110), 111 (104-120), 144 (134-156) and women--73.5 (70.0-77.2), 82.9 (79.0-86.9), 94.2 (89.7-98.9)); across SCD tertiles: men--99.0 (91.8-107), 115 (107-124), 144 (134-156) and women--72.4 (69.0-76.0), 81.5 (77.8-85.5), 97.2 (92.6-102)), whereas inverse associations with triglycerides were observed for the estimated Δ5-desaturase (D5D) activity (adjusted means (95% CI) of triglycerides (mg/dl) across D5D tertiles: men--128 (119-138), 121 (113-131), 106 (97.9-114) and women--92.0 (87.6-96.6), 82.8 (78.9-86.9), 75.3 (71.6-79.1), P-values for trend at least 0.0006). Furthermore, we observed generally weaker and less consistent associations of dairy-derived SFAs (mainly 17:0) with triglycerides and HDL-cholesterol. Individual PUFAs and trans-FAs were, if at all, only weakly associated with dyslipidemia markers.
Our findings suggest that triglyceride and LDL-cholesterol concentrations may be mediators that link intake and metabolism of FAs to metabolic risk.
•TransportLog 1.0 has been programmed for monitoring transport stress on boar semen.•Maximal vibration emissions of 300 rpm have a negative impact on boar semen quality.•A new monitoring tool for ...boar semen shipping was established using mobile sensing.
The shipping of semen doses to sow farms can impair boar semen quality. Unfortunately, there is currently no practice-oriented information available regarding general shipping conditions of boar semen. For this reason, a special mobile sensing app (TransportLog 1.0), utilizing the built-in sensors of smartphones, has been programmed to capture vibration emissions during shipping of semen doses (QuickTip Flexitubes®, Minitüb). Data were analyzed, transformed and used as standards for simulating vibration emissions from an orbital shaker IKA MTS 4 (Laborgeräte München) in a spermatological reference laboratory. Twenty ejaculates were collected randomly and diluted using a one-step isothermal process in a split-sample procedure in Beltsville Thawing Solution (BTS, Minitüb). The sperm concentration was adjusted to 24 × 106 sperm/mL. The dose filling volume was 85 ± 1 mL. Samples were stored for seven days at 17 °C. The results showed that circular horizontal vibration emissions with frequencies of 300 rpm for a duration of 6 h led to a significant alkalization of the BTS-extended semen. Semen motility, mitochondrial activity, acrosome and plasma membrane integrity as well as thermo-resistance all demonstrated a frequency-dependent negative response to vibration emissions during long-term storage. This study leads to new insights and recommendations for the shipping of boar semen in the artificial insemination industry. Furthermore, a new monitoring tool for boar semen shipping was established using mobile sensing.
Purpose
To investigate efficacy and patency status of stent graft implantation in the treatment of hepatic artery pseudoaneurysm.
Materials and Methods
A retrospective analysis of patients who had ...undergone endovascular treatment of hepatic artery pseudoaneurysms between 2011 and 2020 was performed. Medical records were examined to obtain patients’ surgical histories and to screen for active bleeding. Angiographic data on vascular access, target vessel, material used and technical success, defined as the exclusion of the pseudoaneurysm by means of a stent graft with sufficient control of bleeding, were collected. Vessel patency at follow-up CT was analyzed and classified as short-term (< 6 weeks), mid-term (between 6 weeks and 1 year), and long-term patency (> 1 year). In case of stent occlusion, collateralization and signs of hepatic hypoperfusion were examined.
Results
In total, 30 patients were included and of these, 25 and 5 had undergone stent graft implantation and coiling, respectively. In patients with implanted stent grafts, technical success was achieved in 23/25 patients (92%). Follow-up CT scans were available in 16 patients, showing stent graft patency in 9/16 patients (56%). Short-term, mid-term, and long-term short-term stent patency was found in 81% (13/16), 40% (4/10), and 50% (2/4). In patients with stent graft occlusion, 86% (6/7) exhibited maintenance of arterial liver perfusion via collaterals and 14% (1/7) exhibited liver abscess during follow-up.
Conclusion
Stent graft provides an effective treatment for hepatic artery pseudoaneurysms. Even though patency rates decreased as a function of time, stent occlusion was mainly asymptomatic due to sufficient collateralization.
PDF
