Search results for "CLEO"
showing 10 items of 4423 documents
Next-generation sequencing: big data meets high performance computing
2017
The progress of next-generation sequencing has a major impact on medical and genomic research. This high-throughput technology can now produce billions of short DNA or RNA fragments in excess of a few terabytes of data in a single run. This leads to massive datasets used by a wide range of applications including personalized cancer treatment and precision medicine. In addition to the hugely increased throughput, the cost of using high-throughput technologies has been dramatically decreasing. A low sequencing cost of around US$1000 per genome has now rendered large population-scale projects feasible. However, to make effective use of the produced data, the design of big data algorithms and t…
Deep learning network for exploiting positional information in nucleosome related sequences
2017
A nucleosome is a DNA-histone complex, wrapping about 150 pairs of double-stranded DNA. The role of nucleosomes is to pack the DNA into the nucleus of the Eukaryote cells to form the Chromatin. Nucleosome positioning genome wide play an important role in the regulation of cell type-specific gene activities. Several biological studies have shown sequence specificity of nucleosome presence, clearly underlined by the organization of precise nucleotides substrings. Taking into consideration such advances, the identification of nucleosomes on a genomic scale has been successfully performed by DNA sequence features representation and classical supervised classification methods such as Support Vec…
Rescuing monopronucleated-derived human blastocysts: a model to study chromosomal topography and fingerprinting.
2021
Objective To quantify the percentage of monopronuclear-derived blastocysts (MNBs) that are potentially useful for reproductive purposes using classic and state-of-the-art chromosome analysis approaches, and to study chromosomal distribution in the inner cell mass (ICM) and trophectoderm (TE) for intertissue/intratissue concordance comparison. Design Prospective experimental study. Setting Single-center in vitro fertilization clinic and reproductive genetics laboratory. Patient(s) A total of 1,128 monopronuclear zygotes were obtained between June 2016 and December 2018. Intervention(s) MNBs were whole-fixed or biopsied to obtain a portion of ICM and 2 TE portions (TE1 and TE2) and were subse…
Identification of an optimized 2′-O-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8
2017
Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic when compared with eukaryotic RNA allow innate immune cells to discriminate between “host” and “foreign” RNA. Ribose 2′-O-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2′-O-methylation has to occur to mediate its inhibitory activity remains largely undefined. On the basis of a naturally occurring 2′-O-methylated RNA sequence, we performed a systematic permutation of the …
Dual role of the RNA helicase DDX5 in post-transcriptional regulation of Myelin Basic Protein in oligodendrocytes
2017
In the central nervous system, oligodendroglial expression of Myelin Basic Protein (MBP) is crucial for the assembly and structure of the myelin sheath. MBP synthesis is tightly regulated in space and time, particularly on the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (alias p68) in a complex with Mbp mRNA in oligodendroglial cells. Expression of DDX5 is highest in progenitor cells and immature oligodendrocytes, where it localizes to heterogeneous populations of cytoplasmic ribonucleoprotein (RNP) complexes associated with Mbp mRNA in the cell body and processes. Manipulation of DDX5 protein amounts inversely affects levels of MBP protein. We present evid…
Loss of ISWI Function in Drosophila Nuclear Bodies Drives Cytoplasmic Redistribution of Drosophila TDP-43
2018
Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases. Indeed, sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration share as hallmarks ubiquitin-positive inclusions. Recently, the wide spectrum of neurodegenerative diseases characterized by RBPs functions’ alteration and loss was coll…
GW-Bodies and P-Bodies Constitute Two Separate Pools of Sequestered Non-Translating RNAs
2015
Non-translating RNAs that have undergone active translational repression are culled from the cytoplasm into P-bodies for decapping-dependent decay or for sequestration. Organisms that use microRNA-mediated RNA silencing have an additional pathway to remove RNAs from active translation. Consequently, proteins that govern microRNA-mediated silencing, such as GW182/Gw and AGO1, are often associated with the P-bodies of higher eukaryotic organisms. Due to the presence of Gw, these structures have been referred to as GW-bodies. However, several reports have indicated that GW-bodies have different dynamics to P-bodies. Here, we use live imaging to examine GW-body and P-body dynamics in the early …
Genetic association study of childhood aggression across raters, instruments, and age
2021
AbstractChildhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three sign…
Differential staining of peripheral nuclear chromatin with Acridine orange implies an A-form epichromatin conformation of the DNA
2018
ABSTRACT The chromatin observed by conventional electron microscopy under the nuclear envelope constitutes a single layer of dense 30–35 nm granules, while ∼30 nm fibrils laterally attached to them, form large patches of lamin-associated domains (LADs). This particular surface “epichromatin” can be discerned by specific (H2A+H2B+DNA) conformational antibody at the inner nuclear envelope and around mitotic chromosomes. In order to differentiate the DNA conformation of the peripheral chromatin we applied an Acridine orange (AO) DNA structural test involving RNAse treatment and the addition of AO after acid pre-treatment. MCF-7 cells treated in this way revealed yellow/red patches of LADs atta…
A Comparison of Techniques to Evaluate the Effectiveness of Genome Editing
2018
Genome editing using engineered nucleases (meganucleases, zinc finger nucleases, transcription activator-like effector nucleases) has created many recent breakthroughs. Prescreening for efficiency and specificity is a critical step prior to using any newly designed genome editing tool for experimental purposes. The current standard screening methods of evaluation are based on DNA sequencing or use mismatch-sensitive endonucleases. They can be time-consuming and costly or lack reproducibility. Here, we review and critically compare standard techniques with those more recently developed in terms of reliability, time, cost, and ease of use.