Search results for " Mutation"
showing 10 items of 1212 documents
Structural requirements for V2 vasopressin receptor proteolytic cleavage.
1999
The ligand-induced proteolytic cleavage of the V2 vasopressin receptor transiently expressed in COS cells was investigated. After incubation of the cell membranes with a photoreactive ligand possessing full agonistic properties for V2 receptors, approximately 90% of the porcine and bovine V2 vasopressin receptors were cleaved in the upper part of transmembrane helix 2 at a heptapeptide sequence conserved in both vasopressin and oxytocin receptors. The oxytocin receptor was completely resistant to proteolysis after binding the same photoreactive ligand, which is only a partial agonist for this receptor. Chimeric V2/oxytocin receptors obtained by transfer of extracellular domains of the oxyto…
Theoretical Study of Catalytic Efficiency of a Diels–Alderase Catalytic Antibody: An Indirect Effect Produced During the Maturation Process
2007
The Diels–Alder reaction is one of the most important and versatile transformations available to organic chemists for the construction of complex natural products, therapeutics agents, and synthetic materials. Given the lack of efficient enzymes capable of catalyzing this kind of reaction, it is of interest to ask whether a biological catalyst could be designed from an antibody-combining site. In the present work, a theoretical study of the different behavior of a germline catalytic antibody (CA) and its matured form, 39 A-11, that catalyze a Diels–Alder reaction has been carried out. A free-energy perturbation technique based on a hybrid quantum-mechanics/molecular-mechanics scheme, togeth…
Detailed clinical, genetic and neuroimaging characterization of OFD VI syndrome.
2012
Oral-facial-digital syndrome type VI (OFD VI) is characterized by the association of malformations of the face, oral cavity and extremities, distinguished from the 12 other OFD syndromes by cerebellar and metacarpal abnormalities. Cerebellar malformations in OFD VI have been described as a molar tooth sign (MTS), thus, including OFD VI among the "Joubert syndrome related disorders" (JSRD). OFD VI diagnostic criteria have recently been suggested: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of hands or feet; 3) hypothalamic hamartoma. In order to further delineate this rare entity, we present the neuro…
The 5' Untranslated Region of the
2018
Many of the virulence traits that make Candida albicans an important human fungal pathogen are regulated on a transcriptional level. Here, we report an important regulatory contribution of translation, which is exerted by the extensive 5′ untranslated regulatory sequence (5′ UTR) of the transcript for the protein Efg1, which determines growth, metabolism, and filamentation in the fungus. The presence of the 5′ UTR is required for efficient translation of Efg1, to promote filamentation. Because transcripts for many relevant regulators contain extensive 5′ UTR sequences, it appears that the virulence of C. albicans depends on the combination of transcriptional and translational regulatory mec…
The nuclear autoantigen La/SS-associated antigen B: One gene, three functional mRNAs
1997
Transcription of the gene encoding for the nuclear autoantigen La resulted in three mRNA forms. A promoter switching combined with an alternative splicing pathway replaced exon 1 with either exon 1´ or exon 1´´. The exon 1´´ donor splice site was located 4 nts downstream of the exon 1´ donor splice site. All three La mRNA forms were expressed in all the tissues analysed including peripheral blood lymphocytes, liver, fetal spleen, cultured primary endothelial cells, and mouse LTA cell lines permanently transfected with the human La gene. Both the exons 1´ and 1´´ had unusual structures. They contained GC-rich regions and an oligo(U)-tail of 23 uridine residues. Moreover, they encoded for thr…
Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient.
2001
Sialidosis is a lysosomal storage disease caused by the deficiency of K K-N-acetylneuraminidase (NEU1; sialidase), the key enzyme for the intralysosomal catabolism of sialylated glycoconjugates. We have identified a homozygous transversion in the last intron (IVSE +1 Gs C) in neu1 of a sialidosis patient. Sequencing of the truncated cDNA revealed an alternatively spliced neu1 transcript which lacks the complete sequence of exon 5. Skipping of exon 5 leads to a frameshift and results in a premature termination codon. This is the first description of an intronic point mutation causing a complete deficiency of the lysosomal neuraminidase activity. fl 2001 Federation of Euro- pean Biochemical S…
Recapitulating thyroid cancer histotypes through engineering embryonic stem cells
2023
AbstractThyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248…
A Multivariate Analysis on Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors and Resistance Induced by Mutation
2003
This paper describes the use of multivariate statistical procedure PCA as a tool to explore the inhibitory activity of classes of NNRTIs against HIV-1 viruses (wild type and more frequent mutants, Y181C, V106A, K103N, L100I) and against RT enzyme. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the fifty five derivatives considered in this study. The best results were obtained in the case of L100I and K103N mutants for which the higher number of assignments was found when the principal components derived from the descriptors were used. On this basis this statistical approach is proposed as a reliab…
Delayed lysis confers resistance to the nucleoside analogue 5-fluorouracil and alleviates mutation accumulation in the single-stranded DNA bacterioph…
2014
ABSTRACT Rates of spontaneous mutation determine viral fitness and adaptability. In RNA viruses, treatment with mutagenic nucleoside analogues selects for polymerase variants with increased fidelity, showing that viral mutation rates can be adjusted in response to imposed selective pressures. However, this type of resistance is not possible in viruses that do not encode their own polymerases, such as single-stranded DNA viruses. We previously showed that serial passaging of bacteriophage ϕX174 in the presence of the nucleoside analogue 5-fluorouracil (5-FU) favored substitutions in the lysis protein E (P. Domingo-Calap, M. Pereira-Gomez, and R. Sanjuán, J. Virol. 86: 9640–9646, 2012, doi:10…
Temperature dependence of spontaneous mutation rates.
2021
Mutation is the source of genetic variation and the fundament of evolution. Temperature has long been suggested to have a direct impact on realized spontaneous mutation rates. If mutation rates vary in response to environmental conditions, such as the variation of the ambient temperature through space and time, they should no longer be described as species-specific constants. By combining mutation accumulation with whole-genome sequencing in a multicellular organism, we provide empirical support to reject the null hypothesis of a constant, temperature-independent mutation rate. Instead, mutation rates depended on temperature in a U-shaped manner with increasing rates toward both temperature…