It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the ...renin–angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.
Neurodegenerative diseases affect millions of people worldwide and there are currently no cures. Two types of common neurodegenerative diseases are Alzheimer’s (AD) and Parkinson’s disease (PD). ...Single-cell and single-nuclei RNA sequencing (scRNA-seq and snRNA-seq) have become powerful tools to elucidate the inherent complexity and dynamics of the central nervous system at cellular resolution. This technology has allowed the identification of cell types and states, providing new insights into cellular susceptibilities and molecular mechanisms underlying neurodegenerative conditions. Exciting research using high throughput scRNA-seq and snRNA-seq technologies to study AD and PD is emerging. Herein we review the recent progress in understanding these neurodegenerative diseases using these state-of-the-art technologies. We discuss the fundamental principles and implications of single-cell sequencing of the human brain. Moreover, we review some examples of the computational and analytical tools required to interpret the extensive amount of data generated from these assays. We conclude by highlighting challenges and limitations in the application of these technologies in the study of AD and PD.
In today's Spain a wide range of perspectives about national identity coexist. Some argue that Spain is a diverse country where the Spanish citizen has a triple identity: regional, state, and ...European. Others think that a Spanish national identity does not exist at all. Still others see Spain as a country united by a unified nation. Here, Vega-Duran discusses North African immigration and the idea of Spanishness from a new perspective.
Neural induction, both
in vivo
and
in vitro
, includes cellular and molecular changes that result in phenotypic specialization related to specific transcriptional patterns. These changes are achieved ...through the implementation of complex gene regulatory networks. Furthermore, these regulatory networks are influenced by epigenetic mechanisms that drive cell heterogeneity and cell-type specificity, in a controlled and complex manner. Epigenetic marks, such as DNA methylation and histone residue modifications, are highly dynamic and stage-specific during neurogenesis. Genome-wide assessment of these modifications has allowed the identification of distinct non-coding regulatory regions involved in neural cell differentiation, maturation, and plasticity. Enhancers are short DNA regulatory regions that bind transcription factors (TFs) and interact with gene promoters to increase transcriptional activity. They are of special interest in neuroscience because they are enriched in neurons and underlie the cell-type-specificity and dynamic gene expression profiles. Classification of the full epigenomic landscape of neural subtypes is important to better understand gene regulation in brain health and during diseases. Advances in novel next-generation high-throughput sequencing technologies, genome editing, Genome-wide association studies (GWAS), stem cell differentiation, and brain organoids are allowing researchers to study brain development and neurodegenerative diseases with an unprecedented resolution. Herein, we describe important epigenetic mechanisms related to neurogenesis in mammals. We focus on the potential roles of neural enhancers in neurogenesis, cell-fate commitment, and neuronal plasticity. We review recent findings on epigenetic regulatory mechanisms involved in neurogenesis and discuss how sequence variations within enhancers may be associated with genetic risk for neurological and psychiatric disorders.
The aim of this study has been to assess the composition and antioxidant activities of rice bran extracts submitted to a human simulated digestion, which extraction process was previously optimized. ...In order to adjust the optimum values for the extraction, D-optimal experimental design and response surface methodology have been applied. Phenolic compounds and γ-oryzanol contents have been used as response parameters. In this way, two different extracts have been obtained. The first one, was obtained with 100% water as solvent, and it was mainly composed by phenolic acids. Ferulic acid was the majority compound found with a concentration of 1.00 ± 0.03 mg/g extract, followed by p-coumaric acid (0.19 ± 0.02 mg/g), The second extract, extracted with ethanol as solvent, was a γ-oryzanol enriched fraction with a content of 14.41 ± 0.26 mg/g extract. The optimized rice bran extracts thus obtained were subjected to a process of human in-vitro digestion. In the first extract, with high polyphenol content, the phenolic content was oscillating during the digestion, like antioxidant activity. The oryzanol content found in this fraction (0.079 ± 0.002 mg/g) has not been detected in any phase of digestion. In the second extract, with a high oryzanol content at the beginning, oryzanol content was not detected in any of digestion steps. However, phenolic composition was stable in all phases of simulation (ranging from 0.117 and 0.094 mg/g in the case of ferulic acid). This fact evidence that oryzanol is not a bioavailability fraction, while phenolic compounds support to some extent, the conditions of digestion.
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•The RSM has been used to optimize the extraction process.•Higher performance of oryzanol have been obtained with 100% ethanol.•100% water was the best solvent for phenolic compounds.•Results showed limited bioavailability of phenolic acid fraction of rice bran.•γ-oryzanol is not detected after the digestion process.
Reseña sobre María Castañeda de la Paz, Verdades y mentiras en torno a don Diego de Mendoza Austria Moctezuma. México: Universidad Nacional Autónoma de México, Instituto de Investigaciones ...Antropológicas/El Colegio Mexiquense/Universidad Intercultural del Estado de Hidalgo, 2017.
Abstract To date, a large spectrum of genetic variants has been related to familial and sporadic Parkinson's disease (PD) in diverse populations worldwide. However, very little is known about the ...genetic landscape of PD in Southern Spain, despite its particular genetic landscape coming from multiple historical migrations. We included 134 PD patients in this study, of which 97 individuals were diagnosed with late-onset sporadic PD (LOPD), 28 with early-onset sporadic PD (EOPD), and 9 with familial PD (FPD). Genetic analysis was performed through a next-generation sequencing panel to screen 8 PD-related genes ( LRRK2 , SNCA , PARKIN , PINK1 , DJ-1 , VPS35 , GBA , and GCH1) in EOPD and FPD groups and direct Sanger sequencing of GBA exons 8–11 and LRRK2 exons 31 and 41 in the LOPD group. In the EOPD and FPD groups, we identified 11 known pathogenic mutations among 15 patients (40.5 %). GBA (E326K, N370S, D409H, L444P) mutations were identified in 7 patients (18.9 %); LRRK2 (p.R1441G and p.G2019S) in 3 patients (8.1 %); biallelic PARK2 mutations (p.N52fs, p.V56E, p.C212Y) in 4 cases (10.8%) and PINK1 homozygous p.G309D in 1 patient (2.7 %). An EOPD patient carried a single PARK2 heterozygous mutation (p.R402C), and another had a novel heterozygous mutation in VPS35 (p.R32S), both of unknown significance. Moreover, pathogenic mutations in GBA (E326K, T369M, N370S, D409H, L444P) and LRRK2 (p.R1441G and p.G2019S) were identified in 13 patients (13.4 %) and 4 patients (4.1 %), respectively, in the LOPD group. A large number of known pathogenic mutations related to PD have been identified. In particular, GBA and LRRK2 mutations appear to be considerably frequent in our population, suggesting a strong Jewish influence. Further research is needed to study the contribution of the novel found mutation p.R32S in VPS35 to the pathogenesis of PD.
IMPORTANCE: Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased ...risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. OBJECTIVE: To investigate what genes and genomic processes underlie the risk of sporadic PD. DESIGN AND SETTING: This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression GTEx, and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. MAIN OUTCOMES AND MEASURES: It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. RESULTS: Gene-level analysis of expression revealed 5 genes (WDR6 OMIM 606031, CD38 OMIM 107270, GPNMB OMIM 604368, RAB29 OMIM 603949, and TMEM163 OMIM 618978) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 OMIM 615655, PCGF3 OMIM 617543, NEK1 OMIM 604588, NUPL2 NCBI 11097, GALC OMIM 606890, and CTSB OMIM 116810) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. CONCLUSIONS AND RELEVANCE: Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies.
Brain dopamine, in relation to the limbic system, is involved in cognition and emotion. These functions are asymmetrically processed. Hypertension not only alters such functions but also their ...asymmetric brain pattern as well as their bilateral pattern of neurovisceral integration. The central and peripheral renin-angiotensin systems, particularly the aminopeptidases involved in its enzymatic cascade, play an important role in blood pressure control. In the present study, we report how these aminopeptidases from left and right cortico-limbic locations, plasma and systolic blood pressure interact among them in spontaneously hypertensive rats (SHR) unilaterally depleted of dopamine. The study comprises left and right sham and left and right lesioned (dopamine-depleted) rats as research groups. Results revealed important differences in the bilateral behavior comparing sham left versus sham right, lesioned left versus lesioned right, and sham versus lesioned animals. Results also suggest an important role for the asymmetrical functioning of the amygdala in cardiovascular control and an asymmetrical behavior in the interaction between the medial prefrontal cortex, hippocampus and amygdala with plasma, depending on the left or right depletion of dopamine. Compared with previous results of a similar study in Wistar-Kyoto (WKY) normotensive rats, the asymmetrical behaviors differ significantly between both WKY and SHR strains.
The WorkingAge project aims at improving the psycho-physical condition of workers, with a special focus on ageing subjects. In this context, a Decision Support System, based on a hybrid ...data-driven/model-driven approach, fed with data coming from environmental and wearable sensors, aims to provide personalised advises to the worker. In this paper we briefly present the WorkingAge project and architecture, and then focus on the decision-making pipeline that, starting from raw data, generates the advises.
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