Search results for "Mutant"

Investigating REPAIRv2 as a Tool to Edit CFTR mRNA with Premature Stop Codons

2020

Cystic fibrosis (CF) is caused by mutations in the gene encoding the transmembrane conductance regulator (CFTR) protein. Some CF patients are compound heterozygous or homozygous for nonsense mutations in the CFTR gene. This implies the presence in the transcript of premature termination codons (PTCs) responsible for a truncated CFTR protein and a more severe form of the disease. Aminoglycoside and PTC124 derivatives have been used for the read-through of PTCs to restore the full-length CFTR protein. However, in a precision medicine framework, the CRISPR/dCas13b-based molecular tool &ldquo

Deregulated Splicing Is a Major Mechanism of RNA-Induced Toxicity in Huntington's Disease.

2019

Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant…

P826 Unexplained higher frequency of mutant thiopurine S-methyltransferase genotypes in inflammatory bowel disease patients of Latvia population

2019

Elpošanas ķēdes loma piruvātu producējošos Zymomonas mobilis celmos

2018

Lai novirzītu Zymomonas mobilis katabolismu no etanola producēšanas uz piruvāta producēšanu, jāatrod veids, kā oksidēt to NADH, kas parasti tiek izmantots etanola sintēzei, bet nav nepieciešams piruvāta producēšanai. Elpošana ir viens veidiem, kā oksidēt NADH. Lai gūtu priekšstatu par elpošanas ķēdes ietekmi uz piruvāta akumulēšanos Z. mobilis, tika salīdzināti vairāki elpošanas ķēdes mutantie celmi. Uz daļēji inaktivētas piruvātdekarboksilāzes (PDC) fona darbā izdevās iegūt celmu ar pārekspresētu membrānsaistīto D-laktātdehidrogenāzi (LDH), bet neizdevās iegūt celmu ar pārekspresētu NADH dehidrogenāzi. Novērojām, ka elpošanas ķēdes NADH dehidrogenāzes un LDH aktivitātes aerobi augošās Z.mo…

De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

2014

Activating mutations in genes encoding phosphatidylinositol 3-kinase (PI3K)-AKT pathway components cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH, OMIM 603387)(1-3). Here we report that individuals with MPPH lacking upstream PI3K-AKT pathway mutations carry de novo mutations in CCND2 (encoding cyclin D2) that are clustered around a residue that can be phosphorylated by glycogen synthase kinase 313 (GSK-3 beta)(4). Mutant CCND2 was resistant to proteasomal degradation in vitro compared to wild-type CCND2. The PI3K-AKT pathway modulates GSK-3 beta activity(4), and cells from individuals with PIK3CA, PIK3R2 or AKT3 mutations showed similar CCND2 accumulation. CCND…

A New Mutation in the Promoter Region of the PAX8 Gene Causes True Congenital Hypothyroidism with Thyroid Hypoplasia in a Girl with Down's Syndrome

2014

Thyroid dysfunction is common in newborn infants with Down's syndrome (DS), but defects causing classic thyroid dysgenesis (TD) with permanent congenital hypothyroidism (CH) have not been described.We studied a girl with DS and CH who had a mutation in the promoter sequence of the PAX8 gene.A female infant was found to have trisomy 21 and CH, with a venous thyrotropin (TSH) of150 mU/L and a free thyroxine (fT4) of 15.1 pmol/L (day 12). Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. Scintigraphy showed normal uptake, but ultrasound identified a small gland with heterogenous echotexture and cystic changes. Sequence analysis of the PAX8 gene revealed a new heterozygo…

Involvement of an Alkane Hydroxylase System of Gordonia sp. Strain SoCg in Degradation of Solid n-Alkanes▿

2010

ABSTRACT Enzymes involved in oxidation of long-chain n -alkanes are still not well known, especially those in Gram-positive bacteria. This work describes the alkane degradation system of the n -alkane degrader actinobacterium Gordonia sp. strain SoCg, which is able to grow on n -alkanes from dodecane (C 12 ) to hexatriacontane (C 36 ) as the sole C source. SoCg harbors in its chromosome a single alk locus carrying six open reading frames (ORFs), which shows 78 to 79% identity with the alkane hydroxylase (AH)-encoding systems of other alkane-degrading actinobacteria. Quantitative reverse transcription-PCR showed that the genes encoding AlkB (alkane 1-monooxygenase), RubA3 (rubredoxin), RubA4…

EXTRA VIRGIN OLIVE OIL IMPROVES LEARNING AND MEMORY IN SAMP8 MICE

2011

Abstract. Polyphenols are potent antioxidants found in extra virgin olive oil (EVOO); antioxidants have been shown to reverse age- and disease-related learning and memory deficits. We examined the effects of EVOO on learning and memory in SAMP8 mice, an age-related learning/memory impairment model associated with increased amyloid- protein and brain oxidative damage. We administered EVOO, coconut oil, or butter to 11 month old SAMP8 mice for 6 weeks. Mice were tested in T-maze foot shock avoidance and one-trial novel object recognition with a 24 h delay. Mice which received EVOO had improved acquisition in the T-maze and spent more time with the novel object in one-trial novel object recogni…

Analysis of pteridines in Pyrrhocoris apterus (L.) (Heteroptera, Pyrrhocoridae) during development and in body-color mutants

1997

By using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), five different pteridines have been quantified in extracts from Pyrrhocoris apterus: neopterin, isoxanthopterin, isoxantholumazine (violapterin), 7-methylxanthopterin, and erythropterin. Biopterin was also detected using HPLC. Pteridines have been analyzed separately in bodies and eyes of the wild type regarding developmental stage and sex. The pteridine content in both bodies and eyes increased from nymphs to 2-day-old adults. After this period, the concentration of pteridines in the eyes of adults remained approximately constant, while in the bodies isoxantholumazine, 7-methylxanthopterin, and isox…

Pigment patterns in mutants affecting the biosynthesis of pteridines and xanthommatin in Drosophila melanogaster.

1986

Eye-color mutants of Drosophila melanogaster have been analyzed for their pigment content and related metabolites. Xanthommatin and dihydroxanthommatin (pigments causing brown eye color) were measured after selective extraction in acidified butanol. Pteridines (pigments causing red eye color) were quantitated after separation of 28 spots by thin-layer chromatography, most of which are pteridines and a few of which are fluorescent metabolites from the xanthommatin pathway. Pigment patterns have been studied in 45 loci. The pteridine pathway ramifies into two double branches giving rise to isoxanthopterin, “drosopterins,” and biopterin as final products. The regulatory relationship among the …