Search results for "computational"
showing 10 items of 5884 documents
Up-Regulation of leucocytes Genes Implicated in Telomere Dysfunction and Cellular Senescence Correlates with Depression and Anxiety Severity Scores
2012
BACKGROUND: Major depressive disorder (MDD) is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to eval…
Expression of Toll-Like Receptors in the Developing Brain
2012
Toll-like receptors (TLR) are key players of the innate and adaptive immune response in vertebrates. The original protein Toll in Drosophila melanogaster regulates both host defense and morphogenesis during development. Making use of real-time PCR, in situ hybridization, and immunohistochemistry we systematically examined the expression of TLR1-9 and the intracellular adaptor molecules MyD88 and TRIF during development of the mouse brain. Expression of TLR7 and TLR9 in the brain was strongly regulated during different embryonic, postnatal, and adult stages. In contrast, expression of TLR1-6, TLR8, MyD88, and TRIF mRNA displayed no significant changes in the different phases of brain develop…
Progerin expression induces a significant downregulation of transcription from human repetitive sequences in iPSC-derived dopaminergic neurons.
2019
Repetitive DNA sequences represent about half of the human genome. They have a central role in human biology, especially neurobiology, but are notoriously difficult to study. The purpose of this study was to quantify the transcription from repetitive sequences in a progerin-expressing cellular model of neuronal aging. Progerin is a nuclear protein causative of the Hutchinson–Gilford progeria syndrome that is also incrementally expressed during the normal aging process. A dedicated pipeline of analysis allowed to quantify transcripts containing repetitive sequences from RNAseq datasets oblivious of their genomic localization, tolerating a sufficient degree of mutational noise, all with low c…
Reliability of genomic variants across different next-generation sequencing platforms and bioinformatic processing pipelines
2021
Abstract Background Next Generation Sequencing (NGS) is the fundament of various studies, providing insights into questions from biology and medicine. Nevertheless, integrating data from different experimental backgrounds can introduce strong biases. In order to methodically investigate the magnitude of systematic errors in single nucleotide variant calls, we performed a cross-sectional observational study on a genomic cohort of 99 subjects each sequenced via (i) Illumina HiSeq X, (ii) Illumina HiSeq, and (iii) Complete Genomics and processed with the respective bioinformatic pipeline. We also repeated variant calling for the Illumina cohorts with GATK, which allowed us to investigate the e…
Ankle and knee extensor muscle effort during locomotion in young and older athletes : Implications for understanding age-related locomotor decline
2019
AbstractAge-related reduction in muscle force generation capacity is similarly evident across different lower limb muscle groups, yet decline in locomotor performance with age has been shown to depend primarily on reduced ankle extensor muscle function. To better understand why ageing has the largest detrimental effect on ankle joint function during locomotion, we examined maximal ankle and knee extensor force development during a two-leg hopping test in older and young men, and used these forces as a reference to calculate relative operating efforts for the knee and ankle extensors as participants walked, ran and sprinted. We found that, across locomotion modes in both age groups, ankle ex…
Structural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism
2012
N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that contribute to the signal transmission in the central nervous system. NMDA receptors are heterotetramers that usually consist of two GluN1 and GluN2 monomers. The extracellular ligand-binding domain (LBD) of a monomer is comprised of discontinuous segments that form the functional domains D1 and D2. While the binding of a full agonist glycine to LBD of GluN1 is linked to cleft closure and subsequent ion-channel opening, partial agonists are known to activate the receptor only sub-maximally. Although the crystal structures of the LBD of related GluA2 receptor explain the mechanism for the partial a…
Fibroblast Growth Factor Receptor 1– 5-Hydroxytryptamine 1A Heteroreceptor Complexes and Their Enhancement of Hippocampal Plasticity
2011
Background The hippocampus and its 5-hydroxytryptamine transmission plays an important role in depression related to its involvement in limbic circuit plasticity. Methods The analysis was made with bioluminescence resonance energy transfer, co-immunoprecipitation, in situ proximity ligation assay, binding assay, in cell western and the forced swim test. Results Using bioluminescence resonance energy transfer analysis, fibroblast growth factor receptor 1 (FGFR1)-5-hydroxytryptamine 1A (5-HT1A) receptor complexes have been demonstrated and their specificity and agonist modulation characterized. Their presence based on co-immunoprecipitation and proximity ligation assay has also been indicated…
Aminoacid zwitterions in solution : Geometric, energetic, and vibrational analysis using density functional theory-continuum model calculations
1998
Glycine and alanine aminoacids chemistry in solution is explored using a hybrid three parameters density functional (B3PW91) together with a continuum model. Geometries, energies, and vibrational spectra of glycine and alanine zwitterions are studied at the B3PW91/6-31+G∗∗ level and the results compared with those obtained at the HF and MP2/6-31+G∗∗ levels. Solvents effects are incorporated by means of an ellipsoidal cavity model with a multipolar expansion (up to sixth order) of the solute’s electrostatic potential. Our results confirm the validity of the B3PW91 functional for studying aminoacid chemistry in solution. Taking into account the more favorable scaling behavior of density funct…
Free sequences and the tightness of pseudoradial spaces
2019
Let F(X) be the supremum of cardinalities of free sequences in X. We prove that the radial character of every Lindelof Hausdorff almost radial space X and the set-tightness of every Lindelof Hausdorff space are always bounded above by F(X). We then improve a result of Dow, Juhasz, Soukup, Szentmiklossy and Weiss by proving that if X is a Lindelof Hausdorff space, and $$X_\delta $$ denotes the $$G_\delta $$ topology on X then $$t(X_\delta ) \le 2^{t(X)}$$ . Finally, we exploit this to prove that if X is a Lindelof Hausdorff pseudoradial space then $$F(X_\delta ) \le 2^{F(X)}$$ .
Cardinal estimates involving the weak Lindelöf game
2021
AbstractWe show that if X is a first-countable Urysohn space where player II has a winning strategy in the game $$G^{\omega _1}_1({\mathcal {O}}, {\mathcal {O}}_D)$$ G 1 ω 1 ( O , O D ) (the weak Lindelöf game of length $$\omega _1$$ ω 1 ) then X has cardinality at most continuum. This may be considered a partial answer to an old question of Bell, Ginsburg and Woods. It is also the best result of this kind since there are Hausdorff first-countable spaces of arbitrarily large cardinality where player II has a winning strategy even in the weak Lindelöf game of countable length. We also tackle the problem of finding a bound on the cardinality of a first-countable space where player II has a wi…