Search results for "function"
showing 10 items of 14432 documents
C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation
2021
BACKGROUND. Deciphering the function of the many genes previously classified as uncharacterized open reading frame (ORF) would complete our understanding of a cell’s function and its pathophysiology. METHODS. Whole-exome sequencing, yeast 2-hybrid and transcriptome analyses, and molecular characterization were performed in this study to uncover the function of the C2orf69 gene. RESULTS. We identified loss-of-function mutations in the uncharacterized C2orf69 gene in 8 individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction, and recurrent autoinflammation. C2orf69 contains an N-terminal signal peptide that is required and sufficient for mitochondrial…
Re-definition and supporting evidence toward Fanconi Anemia as a mitochondrial disease: Prospects for new design in clinical management
2021
Fanconi anemia (FA) has been investigated since early studies based on two definitions, namely defective DNA repair and proinflammatory condition. The former definition has built up the grounds for FA diagnosis as excess sensitivity of patients' cells to xenobiotics as diepoxybutane and mitomycin C, resulting in typical chromosomal abnormalities. Another line of studies has related FA phenotype to a prooxidant state, as detected by both in vitro and ex vivo studies. The discovery that the FA group G (FANCG) protein is found in mitochondria (Mukhopadhyay et al., 2006) has been followed by an extensive line of studies providing evidence for multiple links between other FA gene products and mi…
In Vivo 3D Analysis of Thoracic Kinematics: Changes in Size and Shape During Breathing and Their Implications for Respiratory Function in Recent Huma…
2016
The human ribcage expands and contracts during respiration as a result of the interaction between the morphology of the ribs, the costo-vertebral articulations and respiratory muscles. Variations in these factors are said to produce differences in the kinematics of the upper thorax and the lower thorax, but the extent and nature of any such differences and their functional implications have not yet been quantified. Applying geometric morphometrics we measured 402 three-dimensional (3D) landmarks and semilandmarks of 3D models built from computed tomographic scans of thoraces of 20 healthy adult subjects in maximal forced inspiration (FI) and expiration (FE). We addressed the hypothesis that…
DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning
2020
Genome-wide association studies (GWAS) identify genetic variants associated with traits or diseases. GWAS never directly link variants to regulatory mechanisms. Instead, the functional annotation of variants is typically inferred by post hoc analyses. A specific class of deep learning-based methods allows for the prediction of regulatory effects per variant on several cell type-specific chromatin features. We here describe “DeepWAS”, a new approach that integrates these regulatory effect predictions of single variants into a multivariate GWAS setting. Thereby, single variants associated with a trait or disease are directly coupled to their impact on a chromatin feature in a cell type. Up to…
Simple Muscle Architecture Analysis (SMA): An ImageJ macro tool to automate measurements in B-mode ultrasound scans
2020
In vivo measurements of muscle architecture (i.e. the spatial arrangement of muscle fascicles) are routinely included in research and clinical settings to monitor muscle structure, function and plasticity. However, in most cases such measurements are performed manually, and more reliable and time-efficient automated methods are either lacking completely, or are inaccessible to those without expertise in image analysis. In this work, we propose an ImageJ script to automate the entire analysis process of muscle architecture in ultrasound images: Simple Muscle Architecture Analysis (SMA). Images are filtered in the spatial and frequency domains with built-in commands and external plugins to hi…
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
2016
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…
Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases
2016
The function of human nervous system is critically dependent on proper interneuronal communication. Exosomes and other extracellular vesicles are emerging as a novel form of information exchange within the nervous system. Intraluminal vesicles within multivesicular bodies (MVBs) can be transported in neural cells anterogradely or retrogradely in order to be released into the extracellular space as exosomes. RNA loading into exosomes can be either via an interaction between RNA and the raft-like region of the MVB limiting membrane, or via an interaction between an RNA-binding protein-RNA complex with this raft-like region. Outflow of exosomes from neural cells and inflow of exosomes into neu…
Involvement of Thyroid Hormones in Brain Development and Cancer
2021
Simple Summary Development and function of the mammalian brain clearly require precise regulation of gene expression at both the transcriptional and post-transcriptional level. Thyroid hormones have been recognized to play a fundamental role in these processes, by acting at multiple levels and in different brain cell types, through direct effects on transcription, mediated by nuclear receptors, and also by triggering transduction pathways at the plasma membrane. At the same time, due to their effects on proliferation, differentiation, and cell metabolism, thyroid hormones may have a critical role in different kinds of cancer, including brain cancer. Abstract The development and maturation o…
A Systematic Nomenclature for the Drosophila Ventral Nerve Cord.
2020
Drosophila melanogaster is an established model for neuroscience research with relevance in biology and medicine. Until recently, research on the Drosophila brain was hindered by the lack of a complete and uniform nomenclature. Recognizing this, Ito et al. (2014) produced an authoritative nomenclature for the adult insect brain, using Drosophila as the reference. Here, we extend this nomenclature to the adult thoracic and abdominal neuromeres, the ventral nerve cord (VNC), to provide an anatomical description of this major component of the Drosophila nervous system. The VNC is the locus for the reception and integration of sensory information and involved in generating most of the locomotor…
Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their p…
2020
IntroductionThe Tousled-like kinases 1 and 2 (TLK1 and TLK2) are involved in many fundamental processes, including DNA replication, cell cycle checkpoint recovery and chromatin remodelling. Mutations in TLK2 were recently associated with ‘Mental Retardation Autosomal Dominant 57’ (MRD57, MIM# 618050), a neurodevelopmental disorder characterised by a highly variable phenotype, including mild-to-moderate intellectual disability, behavioural abnormalities, facial dysmorphisms, microcephaly, epilepsy and skeletal anomalies.MethodsWe re-evaluate whole exome sequencing and array-CGH data from a large cohort of patients affected by neurodevelopmental disorders. Using spatial proteomics (BioID) and…