Effects of diets high in animal or plant protein on oxidative stress in individuals with type 2 diabetes: a randomized clinical trial

High-protein diet is a promising strategy for diabetes treatment supporting body weight control, improving glycaemic status, cardiovascular risk factors and reducing liver fat. Here, we investigated effects of diets high in animal (AP) or plant (PP) protein on oxidative stress and antioxidant status in individuals with type 2 diabetes (T2DM). 37 obese individuals (age 64.3 ± 1.0 years) with T2DM were randomized to an isocaloric diet (30 energy(E)% protein, 30E% fat and 40E% carbohydrates) rich in AP or PP for 6 weeks. Markers of oxidative and nitrosative stress and antioxidant status in plasma and nitrate/nitrite levels in urine were assessed. Gene expression in subcutaneous adipose tissue (SAT) was analyzed by RNA-Seq and real-time PCR.Both AP and PP diets similarly reduced plasma levels of malondialdehyde (P(AP) = 0.003, P(PP) = 1.6x10(-4)) and protein carbonyls (P(AP) = 1.2x10(-4), P(PP) = 3.0x10(-5)) over 6 weeks. Nitrotyrosine (NT) increased upon both AP and PP diets (PAP = 0.005,PPP = 0.004). SAT expression of genes involved in nitric oxide (NO) and oxidative stress metabolism and urine NO metabolite (nitrate/nitrite) levels were not changed upon both diets. Plasma levels of carotenoids increased upon PP diet, whereas retinol, alpha- and gamma-tocopherol slightly decreased upon both diets. AP and PP diets similarly improve oxidative stress but increase nitrosative stress markers in individuals with T2DM. Mechanisms of the NT regulation upon high-protein diets need further investigation

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy

The CogBIAS longitudinal study protocol: cognitive and genetic factors influencing psychological functioning in adolescence.

BACKGROUND: Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample. METHODS: CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships. DISCUSSION: CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.This work was supported by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement no: [324176]

Temporal Variability of Fluvial Sand Composition: An Annual Time Series From Four Rivers in SW Germany

AbstractThe sampling of fluvial sediment is subject to many sources of uncertainty, for example, time and location, and the number of samples collected. It is nevertheless commonly assumed that a sample taken at one time and location provides a somewhat averaged compositional signal. Any spatial or temporal variability of this signal is often neglected. This study investigates how the composition of bed load sand changes over an observation period of 1 year in four river basins with differing bedrock geology in southwestern Germany. Up to 12 bulk sediment samples were taken at the same locations using the same approach and analyzed for their granulometry and geochemistry. The results indicate that (a) different grain sizes yield different compositions due to source rock composition and hydraulic sorting effects, (b) bulk sediment composition changes temporally due to changing grain‐size distribution, and (c) compared to the bulk sample, the composition of narrow grain sizes is temporally more stable but nevertheless has an average variability of 15%. Because heavy mineral‐bound elements such as Zr have the highest variability, we relate a major component of compositional variability to temporally varying heavy mineral concentrations in response to hydrodynamic processes. Mixing modeling demonstrates that the fluvial sand faithfully reflects its catchment geology and that the sediment sources do not change substantially during the observation period, even during a flooding event. We conclude (a) that the causes for compositional variability may be disentangled using chemical and granulometric time series data and (b) that narrow grain sizes yield representative source rock contributions.Plain Language Summary: Sediment transported by rivers is generated by the erosion of the rocks present within the river catchment area. The composition of this sediment is controlled by various processes in the catchment, for example, climate, rock type, weathering, and flow strength. Geoscientists can use modern river sediment to understand how these processes impact sediment composition, and then apply this information to the geologic time. Sampling the river sediment is often the first step in such studies, but few studies consider the sources of uncertainty during sampling, for example, time and location of sampling, and number of collected samples. For this study, we returned to the same river location during the course of 1 year to take bulk sediment samples and analyzed how variable the size of sediment grains and the sediment chemistry are. We discovered that different grain sizes yield different chemical compositions, and this is caused by differences in rock type and hydraulic processes. Because the proportion of different grain sizes in the bulk sediment changes over the year due to water flow conditions, the chemistry of the bulk sediment sample changes over the year. We provide some quantitative estimates for this variability that should be considered in similar studies.Key Points: Bed load sand from 4 rivers was sampled monthly over the course of 1 year to analyze the temporal compositional variability. Composition is grain‐size‐dependent, and narrow grain‐size fractions show less variability than bulk sediment samples. Composition changes during the year, and this is related to changing grain‐size distributions rather than changing sediment sources.https://doi.pangaea.de/10.1594/PANGAEA.95900

Temporal Variability of Fluvial Sand Composition: An Annual Time Series From Four Rivers in SW Germany

The sampling of fluvial sediment is subject to many sources of uncertainty, for example, time and location, and the number of samples collected. It is nevertheless commonly assumed that a sample taken at one time and location provides a somewhat averaged compositional signal. Any spatial or temporal variability of this signal is often neglected. This study investigates how the composition of bed load sand changes over an observation period of 1 year in four river basins with differing bedrock geology in southwestern Germany. Up to 12 bulk sediment samples were taken at the same locations using the same approach and analyzed for their granulometry and geochemistry. The results indicate that (a) different grain sizes yield different compositions due to source rock composition and hydraulic sorting effects, (b) bulk sediment composition changes temporally due to changing grain‐size distribution, and (c) compared to the bulk sample, the composition of narrow grain sizes is temporally more stable but nevertheless has an average variability of 15%. Because heavy mineral‐bound elements such as Zr have the highest variability, we relate a major component of compositional variability to temporally varying heavy mineral concentrations in response to hydrodynamic processes. Mixing modeling demonstrates that the fluvial sand faithfully reflects its catchment geology and that the sediment sources do not change substantially during the observation period, even during a flooding event. We conclude (a) that the causes for compositional variability may be disentangled using chemical and granulometric time series data and (b) that narrow grain sizes yield representative source rock contributions

Role of endocytosis in cellular uptake of sex steroids

Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs