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These results indicate that post-weaning HFD intake progressively leads to bidirectional modulation of hippocampal and amygdala synaptic plasticity, as we previously demonstrated for related memory processes, yet with a different temporal dynamic.
To assess the effects of dapagliflozin, metformin and exercise treatment on changes in plasma glucagon concentrations in individuals with overweight and HbA1c-defined prediabetes.

One-hundred and twenty individuals with overweight (body mass index ≥ 25 kg/m
) and prediabetes (HbA1c of 39-47 mmol/mol) were randomized to a 13-week intervention with dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (30 minutes of interval training 5 days per week) or control (habitual living). A 75-g oral glucose tolerance test (OGTT) (0, 30, 60 and 120 minutes) was administered at baseline, at 13 weeks (end of intervention) and at 26 weeks (end of follow-up). Linear mixed effects models with participant-specific random intercepts were used to investigate associations of the interventions with fasting plasma glucagon concentration, insulin/glucagon ratio and glucagon suppression during the OGTT.

At baseline, the median (Q1; Q3) age was 62 (54; 68) years, median fasting plasma glucagon concentration was 11 (7; 15) pmol/L, mean (SD) HbA1c was 40.9 (2.3) mmol/mol and 56% were women. Compared with the control group, fasting glucagon did not change in any of the groups from baseline to the end of the intervention (dapagliflozin group -5% [95% CI -29; 26]; exercise group -8% [95% CI -31; 24]; metformin group -2% [95% CI -27; 30]). Likewise, there were no differences in insulin/glucagon ratio and glucagon suppression during the OGTT between the groups.

In individuals with prediabetes, 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations.
In individuals with prediabetes, 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations.Birefringence is a fundamental optical property for linear and nonlinear optical (NLO) materials. Thus far, it has proved to be very difficult to engineer large birefringence in optical crystals functioning in the UV region. Herein, we report the first 2D rare-earth iodate-nitrate crystal Sc(IO3 )2 (NO3 ) (SINO), which is shown to exhibit giant optical anisotropy. Air-stable SINO possesses a short UV absorption edge (298 nm), a strong NLO response (4.0 times that of benchmark KH2 PO4 ) for the nitrate family, and the largest birefringence (Δn=0.348 at 546 nm) of inorganic oxide optical crystals. The unusually large birefringence and NLO response can be attributed to an optimized 2D layered structure, combined with highly polarizable and anisotropic building units [IO3 ]- and [NO3 ]- . These findings will facilitate the development of UV linear and NLO materials with giant optical anisotropy and promote their potential application in optoelectronic devices.Learning of complex auditory sequences such as music can be thought of as optimizing an internal model of regularities through unpredicted events (or "prediction errors"). We used dynamic causal modeling (DCM) and parametric empirical Bayes on functional magnetic resonance imaging (fMRI) data to identify modulation of effective brain connectivity that takes place during perceptual learning of complex tone patterns. Our approach differs from previous studies in two aspects. First, we used a complex oddball paradigm based on tone patterns as opposed to simple deviant tones. Second, the use of fMRI allowed us to identify cortical regions with high spatial accuracy. These regions served as empirical regions-of-interest for the analysis of effective connectivity. Deviant patterns induced an increased blood oxygenation level-dependent response, compared to standards, in early auditory (Heschl's gyrus [HG]) and association auditory areas (planum temporale [PT]) bilaterally. Within this network, we found a left-lateralized increase in feedforward connectivity from HG to PT during deviant responses and an increase in excitation within left HG. In contrast to previous findings, we did not find frontal activity, nor did we find modulations of backward connections in response to oddball sounds. Our results suggest that complex auditory prediction errors are encoded by changes in feedforward and intrinsic connections, confined to superior temporal gyrus.Nanoscale materials display unique physical and chemical properties that enable their assimilation into a variety of industrial and consumer products. Amongst the widely used nanomaterials, silver nanoparticles (AgNPs) have gained tremendous recognition for various applications, owing to their extraordinary plasmonic and bactericidal properties. Despite of the extensive usage of AgNPs in various sectors, its impact on human health remains ambiguous. Zilurgisertib fumarate ic50 Several studies have established that higher doses of AgNPs are detrimental to organismal health. In order to attain the best from these versatile nanoparticles, a recent advent of green nanotechnology, that is, employment of metal nanoparticles synthesized using plant extracts, has emerged. Here, using Drosophila as a model system, we tested if adding curcumin, a biologically active polyphenolic compound present in turmeric, having multitudes of therapeutic properties, could mitigate AgNP-mediated biotoxicity. We found that co-administration of AgNPs with curcumin in the fly food could alleviate several harmful effects evoked by AgNPs ingestion in Drosophila model. Addition of curcumin superseded reduction in feeding, pupation, eclosion, pigmentation, and fertility caused by AgNPs ingestion. Interestingly, impairment in ovary development observed in flies reared on AgNPs-supplemented food was also partially restored by co-administration of AgNPs with curcumin. Furthermore, substantial alleviation of reactive oxygen species level and cell death was observed in larval tissues upon co-supplementation of AgNPs with curcumin. We therefore propose that curcumin, when administered with AgNPs, can abrogate the toxic manifestations of AgNPs ingestion and hence can be incorporated in various consumer products encompassing it.
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