Search results for "Frame"
showing 10 items of 1767 documents
PDXK mutations cause polyneuropathy responsive to pyridoxal 5′‐phosphate supplementation
2019
OBJECTIVE: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating sc…
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…
Mitochondrial introgression suggests extensive ancestral hybridization events among Saccharomyces species.
2017
Horizontal gene transfer (HGT) in eukaryotic plastids and mitochondrial genomes is common, and plays an important role in organism evolution. In yeasts, recent mitochondrial HGT has been suggested between S. cerevisiae and S. paradoxus. However, few strains have been explored given the lack of accurate mitochondrial genome annotations. Mitochondrial genome sequences are important to understand how frequent these introgressions occur, and their role in cytonuclear incompatibilities and fitness. Indeed, most of the Bateson-Dobzhansky-Muller genetic incompatibilities described in yeasts are driven by cytonuclear incompatibilities. We herein explored the mitochondrial inheritance of several wor…
Stable radical anions generated from a porous perylenediimide metal-organic framework for boosting near-infrared photothermal conversion
2019
Radical anions of electron-deficient systems are widely used, but are easily reoxidized upon exposure to air. Therefore, the stabilization of radical anions under ambient conditions is of great significance, but still remains a scientific challenge. Herein, perylenediimide is employed to prepare a crystalline metal-organic framework for stabilizing radical anions without extensive chemical modification. The porous, three-dimensional framework of perylenediimide can trap electron donors such as amine vapors and produce radical anions in-situ through photo-induced electron transfer. The radical anions are protected against quenching by shielding effect in air and remain unobstructed in air fo…
The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution
2020
The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and to neoantigen-inducing translational frameshifts. Here, we develop a tool to quantify frameshift mutations in MSI colorectal and endometrial cancer. Our results show that frameshift mutation frequency is negatively correlated to the predicted immunogenicity of the resulting peptides, suggesting counterselection of cell clones with highly immunogenic frameshift peptid…
Autosomal recessive truncatingMAB21L1mutation associated with a syndromic scrotal agenesis
2016
We report on a boy with a rare malformative association of scrotum agenesis, ophthalmological anomalies, cerebellar malformation, facial dysmorphism and global development delay. The reported patient was carrying a homozygous frameshift in MAB21L1 detected by whole-exome sequencing, considered as the most likely disease-causing variant. Mab21l1 knockout mice present a strikingly similar malformative association of ophthalmological malformations of the anterior chamber and preputial glands hypoplasia. We hypothesize that MAB21L1 haploinsufficiency cause a previously undescribed syndrome with scrotal agenesis, ophthalmological anomalies, facial dysmorphism and gross psychomotor delay as remar…
Dynamic evolution of mitochondrial genomes in Trebouxiophyceae, including the first completely assembled mtDNA from a lichen-symbiont microalga (Treb…
2019
AbstractTrebouxiophyceae (Chlorophyta) is a species-rich class of green algae with a remarkable morphological and ecological diversity. Currently, there are a few completely sequenced mitochondrial genomes (mtDNA) from diverse Trebouxiophyceae but none from lichen symbionts. Here, we report the mitochondrial genome sequence of Trebouxia sp. TR9 as the first complete mtDNA sequence available for a lichen-symbiont microalga. A comparative study of the mitochondrial genome of Trebouxia sp. TR9 with other chlorophytes showed important organizational changes, even between closely related taxa. The most remarkable change is the enlargement of the genome in certain Trebouxiophyceae, which is princ…
On the structural connectivity of large-scale models of brain networks at cellular level
2021
AbstractThe brain’s structural connectivity plays a fundamental role in determining how neuron networks generate, process, and transfer information within and between brain regions. The underlying mechanisms are extremely difficult to study experimentally and, in many cases, large-scale model networks are of great help. However, the implementation of these models relies on experimental findings that are often sparse and limited. Their predicting power ultimately depends on how closely a model’s connectivity represents the real system. Here we argue that the data-driven probabilistic rules, widely used to build neuronal network models, may not be appropriate to represent the dynamics of the …
CHANGING THE NATIONAL HEIGHT SYSTEM AND GEOID MODEL IN LATVIA
2016
According to the decision of IAG Reference Frame Sub-commission for Europe (EUREF) the EVRF2007 solution as the vertical reference has to be deployed in EU countries.The new height system LAS-2000,5 had been enacted as the European Vertical Reference System‘s EVRF2007 realization in Latvia and the new geoid model LV‘14 had been introduced by Latvian authority Latvian Geospatial Information Agency. However, the appreciation of the quality of quasi-geoid model LV‘14 is rather contradictious among the users in Latvia. The independent estimate and comparison of the two Latvian geoid models developed till now has been performed by the Institute of Geodesy and Geoinformatics. Previous geoid model…
Hot1 factor recruits co-activator Sub1 and elongation complex Spt4/5 to osmostress genes.
2016
Hyperosmotic stress response involves the adaptative mechanisms needed for cell survival. Under high osmolarity conditions, many stress response genes are activated by several unrelated transcription factors that are controlled by the Hog1 kinase. Osmostress transcription factor Hot1 regulates the expression of several genes involved in glycerol biosynthesis, and the presence of this transcription factor in their promoters is essential for RNApol II recruitment. The physical association between Hog1 and Hot1 activates this transcription factor and directs the RNA polymerase II localization at these promoters. We, herein, demonstrate that physical and genetic interactions exist between Hot1 …