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At least 235 records · Page 13Linked to original sources
PubMed1992

Behavioral analysis of Vibrio parahaemolyticus variants in high- and low-viscosity microenvironments by use of digital image processing.

Digital image analysis and light microscopy were used to study and quantify the growth and behavior of two variants and selected flagellar mutants of Vibrio parahaemolyticus in glass flow cells under high- and low-viscosity conditions. The observations showed a series of surface-associated behaviors, including attachment, microcolony formation, migration, chemotactic movements, and aggregation, indicating a substantial degree of adaptive flexibility and multicellular behavior during growth of V. parahaemolyticus at interfaces.

Bacterial Adhesion↗
PubMed1990

Alpha 1-antitrypsin Wbethesda: molecular basis of an unusual alpha 1-antitrypsin deficiency variant.

Molecular analysis of alpha 1-antitrypsin (alpha 1AT) Wbethesda revealed that it differs from the normal M1 (Ala213) allele by a single base mutation causing an amino acid substitution Ala336 GCT----Thr ACT. Evaluation of alpha 1AT biosynthesis directed by the Wbethesda allele showed that although Wbethesda alpha 1AT mRNA was translated normally in vitro, transfection of the Wbethesda cDNA into COS-I cells was associated with human alpha 1AT secretion of 50% that of cells transfected with a normal alpha 1AT cDNA. The pattern of alpha 1AT biosynthesis was not intracellular accumulation as observed with the common Z alpha 1AT deficiency allele, but reduced intracellular alpha 1AT, suggesting intracellular degradation of the newly synthesized Wbethesda molecule. Together these observations suggest that in heterozygous combination with a Z or Null alpha 1AT allele, the Wbethesda variant causes "alpha 1AT deficiency", thus classifying it as an alpha 1AT "at risk" allele for emphysema.

Alleles↗
PubMed1978

[Characteristics of the polysaccharide-containing somatic antigens isolated from the K-1 strain of the plague microbe and its antibiotic-resistant variants].

Immunochemical analysis of 2 polysaccharide-containing structures of the lypopolysaccharide of the plague causative agent (main somatic antigen and lipopolysaccharide) isolated from K-1 strain and a number of its antibiotic resistant mutants was carried out. It was shown that development of resistance to streptomycin alone or its combination with monomycin did not cause detectable changes in the monosaccharide composition and serological properties of the cultures tested. More significant changes associated with development of complex resistance, i.e. K-1 (Strr leads to Penr leads to Tetr) were accompanied by a decrease in the content of hexozamine and serological activity of the main somatic antigen determining the O-specificity of the lipopolysaccharide. Defective changes in the monosaccharide composition and serological properties of both the main somatic antigen and the polysaccharide were observed in the yellow variant of the streptomycin resistant mutant K-1.

Anti-Bacterial Agents↗
PubMed1992

Decreased stress inducibility of the HSP68 protein in a rat hepatoma variant clone.

Analysis of the stress response of closely related rat hepatoma clones revealed that the major inducible heat-shock protein 68 (HSP68) was only slightly inducible upon stress in the glucocorticoid-resistant, dedifferentiated clone-2 cells, but strongly activated in the differentiated, glucocorticoid-sensitive Faza 967 cells from which clone 2 was derived. The decreased inducibility of HSP68 in clone-2 cells was not the consequence of altered kinetics of protein synthesis recovery, was not correlated with the deficient inducibility of other major heat-shock proteins and had no effect on the heat sensitivity of the cells. This deficiency was observed after treatment with mild and strong heat and various chemicals. The results of nuclear run-on experiments suggested that the impairment of HSP68 mRNA induction most likely occurs at the transcriptional level and is probably specific for the corresponding gene. In Faza 967 and clone-2 cells, stress activated comparable levels of heat-shock-factor binding to the heat-shock element, and the expression of a reporter gene under the control of murine HSP70.1 promoter was strongly stimulated in both cells. Therefore, our results raise the possibility that the deficient stress inducibility of HSP68 is due to some specific regulation of the endogeneous HSP68 gene, rather than to a deficiency of the heat-shock factor or mutation of the corresponding gene.

Animals↗
PubMed1985

[Rapid immunoenzyme analysis].

A variant of the immunoenzyme assay, reducing the duration of the assay procedure by 3 hours in comparison with the standard technique, is presented. This rapid variant is sufficiently sensitive and reproducible.

Antigens, Bacterial↗
PubMed2026

Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios reveals novel genetic drivers of disease.

BACKGROUND: Orofacial clefts (OFCs) and other palate abnormalities (PAs) are among the most common birth defects worldwide and are characterized by the abnormal formation of the lip and/or palate. Genetic studies have traditionally classified OFC cases as either syndromic, involving OFCs alongside other congenital anomalies, or nonsyndromic, which represent the majority of cases and occur in isolation. Emerging genomic evidence indicates that genes traditionally associated with syndromic forms of OFC can also harbor variants contributing to isolated cases, challenging the notion of a strict dichotomy between these categories and supporting their integration for gene discovery. METHODS: In this study, we applied multiple analytic approaches to characterize the genetic architecture of OFC and PAs by integrating genomic data from 2,497 trios with probands diagnosed with an OFC (n=2,080) or PA (n=417). We compared these findings across OFC subtypes and syndromic status with those from 5,515 control trios to identify enriched biological pathways and mechanisms and to prioritize candidate genes using variant burden testing. RESULTS: We observed a significant enrichment of de novo protein-truncating and damaging missense variants in cases compared to controls (OR = 2.17, p = 1.21×10-32), with particularly strong signals in biologically relevant gene sets involving OFC-associated, constrained, Mendelian disorder, and mouse candidate genes. Variant burden testing identified 39 OFC risk genes at FDR ≤ 0.05, which we then integrated with 593 established OFC genes to interrogate the functional underpinnings of OFC via network analysis. This analysis revealed 309 high-order interactor genes not previously associated with OFC. Notably, this OFC network clustered into ten distinct biological pathways, with nucleosome-associated genes showing significant enrichment among cases in our cohort (OR = 14.8, p = 8.1×10-4). In a final integrative step, we combined evidence across all analyses to nominate 231 candidate genes, 32 of which contained at least two deleterious de novo variants in our cohort. CONCLUSIONS: These findings underscore the value of integrating diverse OFC and PA subtypes, syndromic status, and variant classes to elucidate the genetic architecture of these disorders, highlighting both phenotypic expansion of known disease genes and the emergence of novel gene-phenotype associations.

De Novo Variant Enrichment↗
PubMed1992

Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding.

Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver, epithelial and endothelial cells. Structurally, it has similarities to kringle-containing serine proteases, although it does not possess proteolytic activity. A structure-activity relationship study of human HGF was performed by functional analysis of HGF substitution and deletion variants. Analysis of HGF variants was accomplished by defining their ability to induce DNA synthesis on hepatocytes in primary culture and to compete with wild-type HGF for binding to a soluble form of the HGF receptor. Three groups of variants were made: (i) substitutions at the cleavage site, (ii) substitutions within the protease-like domain and (iii) deletions of the beta-chain and/or kringle domains. Our results show that: (i) single-chain HGF is a zymogen-like promitogen in that cleavage into a two-chain form is required for biological activity, however, the single chain form of HGF still retains substantial receptor binding capacity; (ii) certain mutations in the protease-like domain result in variants that are completely defective for mitogenic activity, yet exhibit apparent receptor binding affinities similar to wild-type HGF (Kd approximately 50-70 pM); and (iii) a variant containing the N-terminal 272 residues of mature HGF showed only a 4-fold increase in Kd when compared with wild-type HGF indicating that a primary receptor binding determinant is located within this sequence.

Animals↗
PubMed1981

Structural analysis of human hemoglobin variants with field desorption mass spectrometry.

Tryptic hydrolyzates of normal and abnormal human globin chains were analyzed with mass spectrometry, using field desorption ionization technique. All the peptides, including core peptides, were detected as protonated molecular ions in field desorption mass spectra. Since the technique makes it possible to determine the mass number of each peptide, it is very useful for structural analysis of human hemoglobin variants, even those with electrophoretically and chromatographically silent mutations.

Adult↗
PubMed1979

Dedifferentiated variants of a rat hepatoma: analysis by cell hybridization.

Two independent dedifferentiated variants, H5 and FaoflC2, derived from the Reuber H35 hepatoma, produce trans-acting diffusible substances(s) that extinguish the expression of liver-specific proteins when hybridized with a well-differentiated cell line of the same origin (Fao and Fu5-5, respectively). H5 x Fao hybrids show total and stable extinction of four liver functions and clonal variability in the expression of three others. FaoflC2 x Fu5-5 hybrids are initially flat (like FaoflC2 cells), and die in glucose-free medium where survival requires expression of hepatic gluconeogenic enzymes, but then evolve to hepatoma-like and finally round morphology; these latter cells express all liver functions analyzed including the gluconeogenic enzymes. Two exceptional clones that remained flat long enough for complete analysis showed extinction of all hepatic functions not expressed by FaoflC2 cells. We conclude that this transitory extinction reflects the action and then loss of extinguishing factor(s) contributed by FaoflC2. When crossed with BW1-J mouse hepatoma cells. FaoflC2 causes stable extinction of mouse aldolase B. We propose that production of extinguishing factor(s) is the rule for dedifferentiated variants.

Animals↗
PubMed2026

Biallelic VPS41 Variants in Autosomal Recessive Spinocerebellar Ataxia 29 Resolved by Long-Read Sequencing and RNA Analysis.

BACKGROUND: Biallelic variants in VPS41, encoding a subunit of the HOPS complex, cause autosomal recessive spinocerebellar ataxia 29 (SCAR29), a rare neurodevelopmental disorder with an incompletely defined phenotypic and molecular spectrum. METHODS: We investigated a 24-year-old man with cerebellar ataxia, hypotonia, and intellectual disability. Exome sequencing identified four candidate VPS41 variants. Because maternal DNA was unavailable, long-read genome sequencing was performed to determine allelic configuration, followed by RNA and protein analyses. RESULTS: In addition to typical SCAR29 features, the patient showed previously unreported findings, including swan-neck deformities and pes cavus. Long-read genome sequencing demonstrated that two VPS41 variants were in trans. RNA analysis revealed distinct splicing consequences: one allele produced an out-of-frame transcript predicted to undergo nonsense-mediated decay, whereas the other generated an in-frame exon-skipped transcript. These complementary defects reduced VPS41 expression at both transcript and protein levels, supporting pathogenicity and variant reclassification. CONCLUSION: Our findings expand the phenotypic spectrum of VPS41-related disease and highlight the value of long-read allelic resolution in clarifying pathogenic mechanisms in rare genetic disorders.

Humans↗
PubMed1984

Molecular cloning and analysis of a new variant of human T-cell leukemia virus (HTLV-ib) from an African patient with adult T-cell leukemia-lymphoma.

We report the identification and characterization of a new variant of HTLV-I in an African patient with adult T-cell leukemia/lymphoma (ATL). Proviral sequences were detected by Southern blot analysis in three T-cell lines established from this patient's peripheral blood lymphocytes (PBL) and lymph-node cells. We molecularly cloned and analyzed proviruses from two of these cells lines, one established by direct culture of PBL and one established by co-cultivation of PBL with cord-blood T cells. These two HTLV clones contained full-length proviruses which were identical to each other in 44 out of 44 restriction enzyme sites. They were closely related to, but distinct from, the prototype HTLV-I, having divergence in their envelope and 5' pX regions and therefore represented a new variant of HTLV-I. We designated it as HTLV-Ib. Despite the genomic differences, however, HTLV-Ib retained its tropism for OKT4+ lymphocytes as well as its ability to initiate and maintain transformation of these cells. The finding of a variant of HTLV-I in this African ATL patient, along with the results of recent seroepidemiological studies, extends to the African continent the prevalence of HTLV-I associated malignancy previously identified in the Caribbean and Japan.

Adult↗
PubMed1989

Complex segregation analysis of dental morphological variants.

A set of 20 morphological variants of the dental crowns and four characteristics of the jaws are tested for probable mode of inheritance using the complex segregation analysis method of Morton et al. (Am. J. Hum. Genet. 23:602-611, 1971). Models tested include three two-allele single-locus models (dominant, codominant, and recessive) and a model employing the polychotomized normal distribution of liability (an additive polygenic model), with transmissibility estimated via maximum likelihood. Most of the traits studied are observed using ordinal scales with several grades, and many are tested using more than one dichotomy of their scale. These multiple analyses allow for an examination of such factors as trait incidence on the results of the statistical analysis. The results of the analysis yield propositions of major genes for 13 of the 24 traits examined. Two traits give good evidence of being polygenic in origin. The remaining nine characters present methodological problems that do not allow for a definite conclusion on their mode of inheritance at this time. The ability to test varying levels of transmissibility in the polygenic model allows for an estimation of the percentage of trait variance determined by familial factors. Estimates of transmissibility for all characters examined range from 0 to 1, with a mean of 0.36. These findings may suggest a large environmental role in the development of dental crown morphology. However, the possibility exists that difficulties in the ability to classify the expression of certain traits consistently result in overestimates of the environmental influences on the development of those characters.

Anthropology, Physical↗
PubMed1983

Biochemical and molecular analysis of naturally occurring Adh variants in Drosophila melanogaster.

The results of a detailed analysis of the biochemical and molecular basis of alcohol dehydrogenase (ADH) activity variation existing among six naturally occurring and one ethyl methanesulfonate-induced Adh variant strain of Drosophila melanogaster are presented. Significant specific activity differences exist among the strains but the majority of ADH activity variation can be accounted for by differences in levels of ADH protein. These protein level differences can, in turn, be accounted for by ADH synthesis rate variation, which positively correlates with in vivo levels of cytoplasmic Adh mRNA. The functional variability is correlated with known structural variation in and around the area of the Adh gene.

Alcohol Dehydrogenase↗
PubMed1989

Isolation and characterization of a mouse L cell variant deficient in glucocorticoid receptors.

The growth of mouse L cell fibroblasts is inhibited by glucocorticoids, and we have selected spontaneous glucocorticoid-resistant L cells in culture. One cloned variant exhibits a stable phenotype in the absence of selective conditions. This variant contains no specific glucocorticoid-binding capacity, no immunoreactive glucocorticoid receptor protein, and no detectable glucocorticoid receptor messenger RNA. A glucocorticoid-dependent reporter gene requires exogenous glucocorticoid receptor cDNA and steroid in order to be expressed in this variant. Genomic DNA analysis of the variant cell line indicates that there has been no gross alteration in receptor gene structure. These results suggest that the variant may be deficient in transcription of the glucocorticoid receptor gene.

Animals↗
PubMed1984

Polar encapsidation of adenovirus DNA: evolutionary variants reveal dispensable sequences near the left ends of Ad3 genomes.

Repeated passage of adenovirus type 3 in HeLa cells has led to a novel stock of variant genomes, characterized by deletions and substitutions of DNA sequences within the left-end 750 base pairs. This heterogeneous stock retains few if any parental genomes--the majority of variants appear viable. Analysis of viable variants with deleted sequences reveals the 182 nucleotides proximal to the left-end inverted terminal repeat (136-318 bp) are not required for Ad3 infectivity in cultured human cell lines nor for maintenance of viral DNA encapsidation polarity.

Adenoviruses, Human↗
PubMed2026

Analysis of CYLD gene variants in 41 patients with multiple familial trichoepithelioma.

OBJECTIVE: To investigate the variants of the CYLD gene in Chinese patients with multiple familial trichoepithelioma (MFT), aiming to provide a scientific basis for genetic counseling and prenatal diagnosis, thereby creating favorable conditions for intervention treatment and improving the prognosis of patients. PATIENTS AND METHODS: Whole-exome sequencing (WES) was performed in patients from eleven families to identify candidate variants, which were subsequently confirmed by Sanger sequencing. The minigene technique was used to perform functional analyses of the variants c.2342-8C>G and c.1685-9T>G. Whole-genome sequencing (WGS) was applied in patients with negative WES results. RESULTS: All 41 patients presented with multiple papules or nodules on the nose. We identified six novel pathogenic variants and three recurrent pathogenic variants. Conversely, no gene variants were detected in four patients. The c.1685-9T>G variant caused aberrant mRNA splicing, resulting in the insertion of an 8-base intronic sequence into the mRNA and subsequent premature termination, while the variant c.2342-8C>G led to premature mRNA splicing seven bases upstream of the canonical splice site. CONCLUSIONS: This study identified six novel and three recurrent pathogenic variants in the CYLD gene among 41 patients with MFT. Comprising the largest sample size report in this field to date, this work considerably expands the mutational spectrum of the CYLD gene (currently comprising 144 variants) and carries important implications for genetic counseling.

Humans↗
PubMed1993

Assessment of autonomic nervous activity by heart rate spectral analysis in patients with variant angina.

The purpose of this study was to assess the role of the autonomic nervous system in the pathogenesis of coronary artery spasm in patients with variant angina. We evaluated cardiac sympathetic and parasympathetic activity from the power (logarithmic scale) of the low-frequency (approximately 0.04 to 0.12 Hz) and the high-frequency (approximately 0.22 to 0.32 Hz) spectral components of heart rate variability with Holter monitoring in seven patients with nocturnal variant angina and in 11 healthy men who served as control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. Low-frequency and high-frequency logarithmic values were calculated for each 5-minute period from 30 minutes before to immediately before each angina attack. The logarithmic low-frequency value during the 5-to-0-minute period was greater than the low-frequency values during most of the other periods (p < 0.05 - p < 0.01). The logarithmic high-frequency values during the 10-to-5-minute and 5-to-0-minute periods were greater than those during the 30-to-25-minute period (p < 0.05 and p < 0.01, respectively). These data indicate that parasympathetic activity increased during the 10 minutes before attacks of nocturnal variant angina, whereas sympathetic activity with vagal modulation increased during the 5 minutes before such attacks. The same pattern of changes in heart rate variability was found in the absence of ST-segment elevation in patients and in control subjects. So this phenomenon was not just associated with coronary spasm and variant angina. It is suggested that circadian variation in disease activity is also associated with spontaneous attacks.

Adult↗
PubMed1991

Cleavage by protease from Staphylococcus aureus V8: an improvement in the sequence analysis of human hemoglobin variants.

Protease from Staphylococcus aureus V8 cleaves either at glutamic residues or at both aspartic and glutamic residues, depending on the experimental conditions. In structural analyses of human hemoglobin variants, the specificity of this enzyme is of considerable interest to localize substitutions occurring in medium or large size peptides as it cleaves in smaller fragments which may be unambiguously characterized. It may also recognize the replacement of an acidic residue by the corresponding amide, or vice versa, avoiding protein sequence analysis. The various aspects of the use of protease V8 are illustrated by the study of four alpha chain hemoglobin variants concerning peptides alpha T-9 and alpha T-12b.

Amino Acid Sequence↗