Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets

Abstract The gastrointestinal microbiota plays a critical role on host health and metabolism. This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production. A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants. The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish. The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients. Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP. By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential. By inferring the adaptive fitness to the fish gut and the amenability to industrial processing, we identified the best two candidates to become industrially valuable probiotics. This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices

Genome-wide association study of Alzheimer's disease

In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P<0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at ∼2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P<0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69–180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P=3.05E–07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

The bounds of education in the human brain connectome

Inter-individual heterogeneity is evident in aging; education level is known to contribute for this heterogeneity. Using a cross-sectional study design and network inference applied to resting-state fMRI data, we show that aging was associated with decreased functional connectivity in a large cortical network. On the other hand, education level, as measured by years of formal education, produced an opposite effect on the long-term. These results demonstrate the increased brain efficiency in individuals with higher education level that may mitigate the impact of age on brain functional connectivity.This work was funded by the European Commission (FP7): “SwitchBox” (Contract HEALTH-F2-2010-259772) and co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). José M. Soares, Paulo Marques, and Nadine C. Santos are supported by fellowships of the project “SwitchBox”; Ricardo Magalhães is supported by a fellowship from the project FCT ANR/NEU-OSD/0258/2012 funded by FCT/MEC (www.fct.pt) and by ON.2 – ONOVONORTE – North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/2013, through FEDER

Developmental learning impairments in a rodent model of nodular heterotopia

Developmental malformations of neocortex—including microgyria, ectopias, and periventricular nodular heterotopia (PNH)—have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21–42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60–100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America

Background & Aims: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. / Methods: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. / Results: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03–1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84–3.58) for Native American race vs European American race. / Conclusions: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment