Search results for "Ability"
showing 10 items of 18559 documents
A Twin Protection Effect? Explaining Twin Survival Advantages with a Two-Process Mortality Model
2016
Twin studies that focus on the correlation in age-at-death between twin pairs have yielded important insights into the heritability and role of genetic factors in determining lifespan, but less attention is paid to the biological and social role of zygosity itself in determining survival across the entire life course. Using data from the Danish Twin Registry and the Human Mortality Database, we show that monozygotic twins have greater cumulative survival proportions at nearly every age compared to dizygotic twins and the Danish general population. We examine this survival advantage by fitting these data with a two-process mortality model that partitions survivorship patterns into extrinsic …
Cofilin and Neurodegeneration: New Functions for an Old but Gold Protein
2021
Cofilin is an actin-binding protein that plays a major role in the regulation of actin dynamics, an essential cellular process. This protein has emerged as a crucial molecule for functions of the nervous system including motility and guidance of the neuronal growth cone, dendritic spine organization, axonal branching, and synaptic signalling. Recently, other important functions in cell biology such as apoptosis or the control of mitochondrial function have been attributed to cofilin. Moreover, novel mechanisms of cofilin function regulation have also been described. The activity of cofilin is controlled by complex regulatory mechanisms, with phosphorylation being the most important, since t…
Enhanced Prefrontal Neuronal Activity and Social Dominance Behavior in Postnatal Forebrain Excitatory Neuron-Specific Cyfip2 Knock-Out Mice
2020
The cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (CYFIP2) gene is associated with epilepsy, intellectual disability (ID), and developmental delay, suggesting its critical role in proper neuronal development and function. CYFIP2 is involved in regulating cellular actin dynamics and also interacts with RNA-binding proteins. However, the adult brain function of CYFIP2 remains unclear because investigations thus far are limited to Cyfip2 heterozygous (Cyfip2+/- ) mice owing to the perinatal lethality of Cyfip2-null mice. Therefore, we generated Cyfip2 conditional knock-out (cKO) mice with reduced CYFIP2 expression in postnatal forebrain excitatory neurons (CaMKIIα-Cre…
Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins
2016
Longitudinal twin studies on long term conservation of individual metabolic phenotypes can help to explore the genetic and environmental basis in maintaining metabolic homeostasis and metabolic health. We performed a longitudinal twin study on 12 metabolic phenotypes from Danish twins followed up for 12 years and Chinese twins traced for 7 years. The study covered a relatively large sample of 502 pairs of Danish adult twins with a mean age at intake of 38 years and a total of 181 Chinese adult twin pairs with a mean baseline age of 39.5 years. Bivariate twin models were fitted to the longitudinal measurements taken at two time points (at baseline and follow-up) to estimate the genetic and e…
Validity, efficacy and reliability of 3 nutritional screening tools regarding the nutritional assessment in different social and health areas.
2017
Abstract Introduction and objective Nutritional screening allows for the detection of nutritional risk. Validated tools should be implemented, and their usefulness should be contrasted with a gold standard. The aim of this study is to discover the validity, efficacy and reliability of 3 nutritional screening tools in relation to complete nutritional assessment. Material and methodology A sub-analysis of a cross-sectional and descriptive study on the prevalence of disease-related malnutrition. The sample was selected from outpatients, hospitalized and institutionalized patients. MUST, MNAsf and MST screening were employed. A nutritional assessment of all the patients was undertaken. The SENP…
Bioaccessibility study of plant sterol-enriched fermented milks.
2015
The bioaccessibility (BA) of total and individual plant sterols (PS) of four commercial PS-enriched fermented milk beverages (designated as A to D) was evaluated using in vitro gastrointestinal digestion including the formation of mixed micelles. The fat content of the samples ranged from 1.1 to 2.2% (w/w), and PS enrichment was between 1.5 and 2.9% (w/w). β-Sitosterol, contained in all samples, was higher in samples A and B (around 80% of total PS). The campesterol content was C (22%) > A (7%) > B (5%). Sitostanol was the most abundant in sample D (85%). Stigmasterol was only present in sample C (33%). The greatest BA percentage for total PS corresponded to samples A and B (16–17%), follow…
Design, synthesis and preliminary evaluation of dopamine-amino acid conjugates as potential D1 dopaminergic modulators.
2016
Abstract The dopamine-amino acid conjugate DA-Phen was firstly designed to obtain a useful prodrug for the therapy of Parkinson's disease, but experimental evidence shows that it effectively interacts with D1 dopamine receptors (D1DRs), leading to an enhancement in cognitive flexibility and to the development of adaptive strategies in aversive mazes, together with a decrease in despair-like behavior. In this paper, homology modelling, molecular dynamics, and site mapping of D1 receptor were carried out with the aim of further performing docking studies on other dopamine conjugates compared with D1 agonists, in the attempt to identify new compounds with potential dopaminergic activity. Two n…
Targeted delivery of Cyclosporine A by polymeric nanocarriers improves the therapy of inflammatory bowel disease in a relevant mouse model
2017
The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects. As had already been demonstrated in previous studies, nano- to micrometer-sized drug particles will accumulate at inflamed mucosal areas, providing a platform for such purposes. …
Usefulness of Caco-2/HT29-MTX and Caco-2/HT29-MTX/Raji B Coculture Models To Predict Intestinal and Colonic Permeability Compared to Caco-2 Monocultu…
2017
The Caco-2 cellular monolayer is a widely accepted in vitro model to predict human permeability but suffering from several and critical limitations. Therefore, some alternative cell cultures to mimic the human intestinal epithelium, as closely as possible, have been developed to achieve more physiological conditions, as the Caco-2/HT29-MTX coculture and the triple Caco-2/HT29-MTX/Raji B models. In this work the permeability of 12 model drugs of different Biopharmaceutical Classification System (BCS) characteristics, in the coculture and triple coculture models was assessed. Additionally, the utility of both models to classify compounds according to the BCS criteria was scrutinized. The obta…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin
2015
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing ribavirin are reviewed. Ribavirin is highly soluble, but its permeability characteristics are not well defined. Therefore according to the Biopharmaceutical Classification System, and taking a “worst case” approach, ribavirin should be assigned to class III. As ribavirin is transported across the brush border membrane of the human jejunum by hCNT2, it shows saturable uptake in the intestine. However, no common excipients have been shown to compete for ribavirin absorption, nor have problems with BE of immediate release rib…