The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders, and schizophrenia specifically. We enriched for this anatomical structure, in the ...anterior cingulate cortex, of 20 schizophrenia samples and 20 controls from the Stanley Medical Research Institute, and used unbiased shotgun proteomics incorporating label-free quantitation to identify differentially expressed proteins. Quantitative investigation of the PSD revealed more than 700 protein identifications and 143 differentially expressed proteins. Prominent among these were altered expression of proteins involved in clathrin-mediated endocytosis (CME) (Dynamin-1, adaptor protein 2) and N-methyl-D-aspartate (NMDA)-interacting proteins such as CYFIP2, SYNPO, SHANK3, ESYT and MAPK3 (all P<0.0015). Pathway analysis of the differentially expressed proteins implicated the cellular processes of endocytosis, long-term potentiation and calcium signaling. Both single-gene and gene-set enrichment analyses in genome-wide association data from the largest schizophrenia sample to date of 13,689 cases and 18,226 controls show significant association of HIST1H1E and MAPK3, and enrichment of our PSD proteome. Taken together, our data provide robust evidence implicating PSD-associated proteins and genes in schizophrenia, and suggest that within the PSD, NMDA-interacting and endocytosis-related proteins contribute to disease pathophysiology.
In this review we summarize the epidemiological, cross-sectional, and interventional studies examining the association between physical activity and brain volume, function, and risk for Alzheimer's ...disease. The epidemiological literature provides compelling evidence that greater amounts of physical activity are associated with a reduced risk of dementia in late life. In addition, randomized interventions using neuroimaging tools have reported that participation in physical activity increases the size of prefrontal and hippocampal brain areas, which may lead to a reduction in memory impairments. Consistent with these findings, longitudinal studies using neuroimaging tools also find that the volume of prefrontal and hippocampal brain areas are larger in individuals who engaged in more physical activity earlier in life. We conclude from this review that there is convincing evidence that physical activity has a consistent and robust association with brain regions implicated in age-related cognitive decline and Alzheimer's disease. In addition to summarizing this literature we provide recommendations for future research on physical activity and brain health.
Changes in the distribution of the demersal fish species have been identified in north-European Atlantic waters. The consequence of these changes has been a northward shift of the distribution limits ...and changes in richness. In this study a notable increase in demersal fish species richness per sampling station was detected in the southern Bay of Biscay. This rise was due to an increase in frequency of occurrence and abundance of the majority of fish species in the area (53% from the total species). A fisheries relate explanation was discarded because the mismatch between the changes in the fishing effort and the augment in frequency of occurrence and abundance. On the contrary, these changes are in agreement with expected response under the increasing temperature of the sea observed over the last three decades, associated to global warming. These changes were positively correlated with an increase in temperature of intermediate waters in the study area. In addition, some of these species showed a notable western displacements of the Centre of Gravity in the study area, which would be expected if temperate water species would be favoured by an increase in water temperature. Our results are consistent with studies in the North Sea, where many of these species showing widened distribution limits towards north. The analysis of the results shows that the studied ecosystem, the Bay of Biscay is under a meridionalization process. On the other hand, only one tropicalization event (Lepidotrigla dieuzeidei), was recorded, maybe due to the conservative restrictions applied in species selection.
•There is an increase in spatial–temporal fish richness in the studied ecosystem.•It has been tested an increase of FO and abundance of the 53% of the fish species.•Global warming seems to be responsible of the observed changes in fish community.•Meridionalization is the process that better explain the observed changes.
Summary Research findings on the hypothalamic–pituitary–adrenal (HPA) axis and pediatric depression reflect a variety of methodological approaches that tap different facets of HPA-axis functions. ...Partly owing to the methodological heterogeneity of studies, descriptive reviews of this area have produced inconsistent conclusions. Therefore, we conducted formal meta-analyses of pertinent studies in order to advance our understanding of HPA-axis dysregulation in pediatric depression. We examined: (a) 17 published studies of HPA-axis response to the dexamethasone suppression test (DST) in depressed youth (DST; N = 926) and (b) 17 studies of basal HPA-axis functioning ( N = 1332). We also examined descriptively studies that used corticotropin-releasing hormone (CRH) infusion, and those that used psychological probes of the HPA-axis. The global standardized mean effect size difference in HPA-axis response to the DST between depressed and non-depressed youth was 0.57, z = 4.18, p < 0.01. The global standardized mean difference effect size in basal HPA-axis functioning was 0.20, z = 4.53, p < 0.01. Age, sex, timing of sampling, dexamethasone dosage, or type of control group was not a significant source of variability for the DST or basal studies. In addition, when compared to non-depressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors. In conclusion, the HPA-axis system tends to be dysregulated in depressed youth, as evidenced by atypical responses to the DST, higher baseline cortisol values, and an overactive response to psychological stressors. This pattern of dysregulation suggests anomalies within the axis's negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.
Arabinoxylans (AX) microcapsules loaded with insulin were prepared by enzymatic gelation of AX, using a triaxial electrospray method. The microcapsules presented a spherical shape, with an average ...size of 250 µm. The behavior of AX microcapsules was evaluated using a simulator of the human intestinal microbial ecosystem. AX microcapsules were mainly (70%) degraded in the ascending colon. The fermentation was completed in the descending colon, increasing the production of acetic, propionic, and butyric acids. In the three regions of the colon, the fermentation of AX microcapsules significantly increased populations of Bifidobacterium and Lactobacillus and decreased the population of Enterobacteriaceae. In addition, the results found in this in vitro model showed that the AX microcapsules could resist the simulated conditions of the upper gastrointestinal system and be a carrier for insulin delivery to the colon. The pharmacological activity of insulin-loaded AX microcapsules was evaluated after oral delivery in diabetic rats. AX microcapsules lowered the serum glucose levels in diabetic rats by 75%, with insulin doses of 25 and 50 IU/kg. The hypoglycemic effect and the insulin levels remained for more than 48 h. Oral relative bioavailability was 13 and 8.7% for the 25 and 50 IU/kg doses, respectively. These results indicate that AX microcapsules are a promising microbiota-activated system for oral insulin delivery in the colon.
The confirmation of the discrepancy with the Standard Model predictions in the anomalous magnetic moment by the Muon g-2 experiment at Fermilab points to a low scale of new physics. Flavour ...symmetries broken at low energies can account for this discrepancy but these models are much more restricted, as they would also generate off-diagonal entries in the dipole moment matrix. Therefore, if we assume that the observed discrepancy in the muon
g
-
2
is explained by the contributions of a low-energy flavor symmetry, lepton flavour violating processes can constrain the structure of the lepton mass matrices and therefore the flavour symmetries themselves predicting these structures. We apply these ideas to several discrete flavour symmetries popular in the leptonic sector, such as
Δ
(
27
)
,
A
4
, and
A
5
⋉
CP
.
Host-parasite coevolution is believed to influence a range of evolutionary and ecological processes, including population dynamics, evolution of diversity, sexual reproduction and parasite virulence. ...The impact of coevolution on these processes will depend on its rate, which is likely to be affected by the energy flowing through an ecosystem, or productivity. We addressed how productivity affected rates of coevolution during a coevolutionary arms race between experimental populations of bacteria and their parasitic viruses (phages). As hypothesized, the rate of coevolution between bacterial resistance and phage infectivity increased with increased productivity. This relationship can in part be explained by reduced competitiveness of resistant bacteria in low compared with high productivity environments, leading to weaker selection for resistance in the former. The data further suggest that variation in productivity can generate variation in selection for resistance across landscapes, a result that is crucial to the geographic mosaic theory of coevolution.
Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these ...inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline.
We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9.
We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk.
We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline.
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•Higher baseline blood C-reactive protein levels were correlated with thinner posterior cingulate cortex, at study year 9.•Higher metabolic risk was strongly associated with higher blood CRP levels.•Higher blood CRP levels mediated an effect between higher metabolic risk and thinner cortex.•A polygenic score of AD risk variants in immune-related genes was associated with thinner cortex but not with CRP levels.
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