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At least 397 records · Page 22Linked to original sources
PubMed2002

Evidence for dynamic alteration in histone gene clusters of Caenorhabditis elegans: a topoisomerase II connection?

Chromatin integrity is maintained throughout the cell cycle through repair mechanisms and intrinsically by the ordered packaging of DNA in association with histone proteins; however, aberrant rearrangements within and between chromosomes do occur. The role of the nuclear matrix protein topoisomerase II (TopoII) in generating chromosome breakpoints has been a focus of recent investigations. TopoII preferentially binds in vitro to scaffold-associated regions (SARs) and is involved in many DNA processing activities that require chromosome untangling. SARs, biochemically defined DNA elements rich in A + T, have been proposed to serve as structural boundaries for chromatin loops and to delineate functional domains. In our investigation of gene compartmentalization in a eukaryotic genome, SAR-associated nucleotide motifs from Drosophila were mapped in the regions of three histone gene clusters in an in silico analysis of the genome of Caenorhabditis elegans. Sites with similarity to the 15 bp consensus for TopoII cleavage were found predominantly in A + T enriched intergenic regions. Reiteration of sites matching the TopoII core consensus led to the identification of a novel core histone gene on chromosome IV and provided evidence for duplication and inversion in each of the three histone gene clusters. Breakpoint analysis of DNA flanking reiterated regions revealed potential sites for TopoII cleavage and a base composition phenomenon suggestive of a trigger for inversion events.

Amino Acid Sequence↗
PubMed2001

Physiologic functions of activating natural killer (NK) complex-encoded receptors on NK cells.

Natural killer (NK) cells express a superfamily of surface proteins that share common structural features: dimeric type II integral membrane proteins with extracellular domains resembling C-type lectins. These receptors are encoded by a single genetic region called the NK complex (NKC). The NKC encompasses several families of genes including NKR-PI, Ly-49, CD94/NKG2, and NKG2D. Different NKC-encoded receptors have been shown to activate or to inhibit NK-cell function, and different receptors within the same family can have opposing functions. Within an individual NK cell, inhibitory receptors typically predominate over stimulatory receptors, calling into question the teleologic requirement or physiologic significance of lectin-like activating receptors in NK cells. Despite the widespread expression of inhibitory receptors, however, subtle features of activating receptor biology enable them to stimulate effector functions in vivo and in vitro. Activating receptors and inhibitory receptors differ in their subset expression, in their structural constraints for binding to common ligands, in their ligand repertoires, and in that divergent families of activating receptors utilize different signaling pathways. These subset, binding, repertoire, and signaling diversities may allow activating receptors to manifest their effects in spite of inhibitory receptor functions during pathologic conditions in vivo. In this review, we will present a detailed analysis of the data supporting this hypothesis with particular relevance toward physiologic NK-cell functions.

Amino Acid Sequence↗
PubMed2007

Human obesity and insulin resistance: lessons from experiments of nature.

Examination of individuals with 'extreme phenotypes' has revealed some rare monogenic disorders that were previously unknown. This identification can shed light on physiological pathways that are also important in normal physiology and how their impairment leads to more common, milder, multigenic forms of the disease. Ultimately, this is a potential route to treatment of both disease types. This approach is discussed in relation to Type 2 diabetes, arising from both insufficient insulin production and insulin resistance.

Diabetes Mellitus, Type 2↗
PubMed1996

Quantitative analysis of the metabolism of soluble cytoplasmic peptidoglycan precursors of glycopeptide-resistant enterococci.

Transposon Tn1546 from Enterococcus faecium BM4147 mediates high-level resistance to the glycopeptide antibiotics vancomycin and teicoplanin. Tn 1546 encodes a dehydrogenase (VanH) and a ligase (VanA) that synthesize D-alanyl-D-lactate (D-Ala-D-Lac), a D,D-dipeptidase (VanX) that hydrolyses D-Ala-D-Ala and a two-component regulatory system (VanR-VanS) that controls transcription of the vanHAX operon. Strains of Enterococcus faecalis harbouring various copy numbers of the vanRSHAX cluster were tested to determine if there was a correlation between the levels of resistance to glycopeptides, the levels of expression of the corresponding resistance genes and the relative proportions of the different cytoplasmic peptidoglycan precursors. Increased transcription of the vanHAX operon was associated with increased incorporation of D-Ala-D-Lac into peptidoglycan precursors to the detriment of D-Ala-D-Ala, and with a gradual increase in the vancomycin-resistance levels. More complete elimination of D-Ala-D-Ala-containing precursors was required for teicoplanin resistance. The VanY and VanZ proteins also encoded by Tn1546 were not effectors of the regulation of the vanHAX operon but contributed to vancomycin and teicoplanin resistance, respectively. Differences at the regulatory level accounted for phenotypic diversity in acquired glycopeptide resistance by production of D-lac-ending precursors.

Anti-Bacterial Agents↗
PubMed1996

Polymorphism of the human Ca(2+)-sensing receptor gene in Japanese individuals: no relation to non-insulin dependent diabetes mellitus.

A missense mutation in the Ca(2+)-sensing receptor (CaSR) gene was previously identified in a Japanese family with familial hypocalciuric hypercalcemia. Five members of this family with the mutation in the CaSR gene also showed abnormal glucose tolerance, whereas family members homozygous for the wildtype CaSR gene were normal in this respect. The potential relation between mutations in the CaSR gene and the incidence of diabetes mellitus was therefore investigated in 27 non-insulin dependent diabetic and 40 normal Japanese subjects. Each exon of the CaSR gene was amplified by the polymerase chain reaction and subjected to single-strand conformation polymorphism (SSCP) analysis. The region of the gene containing the sixth exon showed three distinct patterns on SSCP analysis in both diabetic patients and normal subjects. Direct sequencing of DNA revealed a T/C polymorphism in the fifth intron. The TT genotype was apparent in 59.3% of diabetic patients and in 45.0% of normal subjects. The CC genotype was present in 25.9% of diabetics and in 22.5% of normal subjects. The diabetic patients were divided into three groups on the basis of genotype for the polymorphism (TT, TC, or CC). However, there was no significant difference among the three groups with regard to the method of therapy, the incidence or severity of diabetic complications, duration or family history of disease, HbA1c level, or laboratory data. The polymorphism in the fifth intron of the CaSR gene does not therefore appear to be associated with non-insulin dependent diabetes mellitus.

Adult↗
PubMed2002

A poxvirus-like type IB topoisomerase family in bacteria.

We report that diverse species of bacteria encode a type IB DNA topoisomerase that resembles vaccinia virus topoisomerase. Deinococcus radiodurans topoisomerase IB (DraTopIB), an exemplary member of this family, relaxes supercoiled DNA in the absence of a divalent cation or ATP. DraTopIB has a compact size (346 aa) and is a monomer in solution. Mutational analysis shows that the active site of DraTopIB is composed of the same constellation of catalytic side chains as the vaccinia enzyme. Sequence comparisons and limited proteolysis suggest that their folds are conserved. These findings imply an intimate evolutionary relationship between the poxvirus and bacterial type IB enzymes, and they engender a scheme for the evolution of topoisomerase IB and tyrosine recombinases from a common ancestral strand transferase in the bacterial domain. Remarkably, bacteria that possess topoisomerase IB appear to lack DNA topoisomerase III.

Amino Acid Motifs↗
PubMed1989

A single DNA response element can confer inducibility by both alpha- and gamma-interferons.

Genomic and cDNA clones corresponding to 9-27, a member of the human 1-8 gene family highly inducible by alpha- and gamma-interferons (IFNs), have been isolated and characterized. A 1.7-kilobase genomic clone contains a complete functional gene with two exons, encoding a 125-amino acid polypeptide of unknown function. The 5' flanking region of the gene contains a 13-base-pair IFN-stimulable response element (ISRE), homologous to the ISREs of the 6-16, ISG 15, and ISG 54 genes, which are predominantly inducible by IFN-alpha, beta. Analysis of constructs containing native and mutated ISREs suggests that this motif is essential for the response of 9-27 to IFN-gamma as well as IFN-alpha. Furthermore, the 9-27 (GGAAATAGAAACT) and 6-16 (GGGAAAATGAAACT) ISREs can each confer a response to both types of IFN when placed on the 5' side of a marker gene. Since the 6-16 gene does not normally respond to IFN-gamma, the context of the ISRE must determine the specificity of the response.

Amino Acid Sequence↗
PubMed1995

Mixing of connexins in gap junction membrane channels.

Gap junctions are plaque-like clusters of intercellular channels that mediate intercellular communication. Each of two adjoining cells contains a connexon unit which makes up half of the whole channel. Gap junction channels are formed from a multigene family of proteins called connexins, and different connexins may be coexpressed by a single cell type and found within the same plaque. Rodent gap junctions contain two proteins, connexins 32 and 26. Use of a scanning transmission electron microscope for mass analysis of rodent gap junction plaques and split gap junctions prvided evidence consistent with a model in which the channels may be made from (i) solely connexin 26, (ii) solely connexin 32, or (iii) mixtures of connexin 26 and connexin 32 in which the two connexons are made entirely of connexin 26 and connexin 32. The different types of channels segregate into distinct domains, implying tha connexon channels self-associate to give a non-random distribution within tissues. Since each connexin confers distinct physiological properties on its membrane channels, these results imply that the physiological properties of channels can be tailored by mixing the constituent proteins within these macromolecular structures.

Animals↗
PubMed1991

Differential response of the human 6-16 and 9-27 genes to alpha and gamma interferons.

9-27 mRNA is expressed to a high level in response to both alpha and gamma interferons. In contrast, 6-16 mRNA is expressed well in response to alpha but very poorly in response to gamma interferon in human cells. The factors governing these different levels of expression were investigated. For both genes the major effect of both interferons is on transcription. A transcriptional bias in the 6-16 promoter/enhancer accounts in large part for the differential response of 6-16 to the two interferons. No single DNA element appears responsible; the smaller the 5' region analysed the lower the absolute activity and the smaller the differential response to alpha and gamma interferons observed. Both the 6-16 and 9-27 mRNAs are very stable and no effect of the interferons on stability was detected. Nor was any direct evidence obtained for preferential processing of the 9-27 mRNA. Nevertheless, differentials between the transcription and accumulation of mature mRNAs, particularly for 6-16 mRNA in response to gamma interferon, suggest that post-transcriptional control(s) must additionally operate. The 9-27 5' promoter/enhancer is much less active than that from 6-16 when placed 5' of a marker gene, despite the similar response of the two genes to alpha interferon.

Blotting, Northern↗
PubMed2006

Clonal distribution and differential occurrence of the enterotoxin gene cluster, egc, in carriage- versus bacteremia-associated isolates of Staphylococcus aureus.

The Staphylococcus aureus enterotoxin gene cluster, egc, was detected in isolates from healthy individuals and in those from patients with bacteremia. The egc genes cooccur and are slightly enriched in strains from healthy carriers (present in 63.7% of carriage-associated isolates versus 52.9% of invasive isolates; P = 0.03). Multilocus sequence typing revealed that successful staphylococcal clones usually harbor the egc locus.

Bacteremia↗
PubMed1991

Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons.

The gene encoding a 67-kDa cytoplasmic guanylate-binding protein (GBP) is transcriptionally induced in cells exposed to interferon of either type I (alpha interferon [IFN-alpha] or type II (IFN-gamma). The promoter of the GBP gene was cloned and found to contain an IFN-alpha-stimulated response element, which mediated the response of the GBP gene to IFN-alpha. On the basis of transfection experiments with recombinant plasmids, two different elements were delineated. Both were required to obtain the maximal response of the GBP gene to IFN-gamma: the IFN-alpha-stimulated response element and an overlapping element termed the IFN-gamma activation site. Different proteins that act on each element were investigated, and their possible involvement in IFN-gamma-induced transcriptional regulation is discussed.

Base Sequence↗
PubMed2005

Molecular analysis of Shigella boydii O1 O-antigen gene cluster and its PCR typing.

Shigella is an important human pathogen and is closely related to Escherichia coli. O-antigen is the most variable part of the lipopolysaccharide on the cell surface of Gram-negative bacteria and plays an important role in pathogenicity. The O-antigen gene cluster of S. boydii O1 was sequenced. The putative genes encoding enzymes for rhamnose synthesis, transferases, O-unit flippase, and O-unit polymerase were identified on the basis of homology. The O-antigen gene clusters of S. boydii O1 and E. coli O149, which share the same O-antigen form, were found to have the same genes and organization by adjacent gene PCR assay. Two genes specific for S. boydii O1 and E. coli O149 were identified by PCR screening against E. coli- and Shigella-type strains of the 186 known O-antigen forms and 39 E. coli clinical isolates. A PCR sensitivity of 103 to 104 CFU/mL overnight culture of S. boydii O1 and E. coli O149 was obtained. S. boydii O1 and E. coli O149 were differentiated by PCR using lacZ- and cadA-based primers.

Bacterial Typing Techniques↗
PubMed1994

Homozygous factor X deficiency associated with familial hypercholesterolemia, mitral valve prolapse, and hypertrophic cardiomyopathy.

The family investigated showed the presence of multiple genetic disorders among their members. The presumable defective genes were related to coagulation factor X, familial hypercholesterolemia, mitral valve prolapse, and hypertrophic cardiomyopathy. The parents were offspring of two siblings, and their children comprised a nonidentical twin. While the proband demonstrated factor X deficiency, obstructive hypertrophic cardiomyopathy, and primary hypercholesterolemia, her parents and her elder sister were considered heterozygous for factor X. In addition, her mother had elevated plasma cholesterol levels, and her father primary hypercholesterolemia as well as mitral valve prolapse. The twin sister, heterozygous for factor X deficiency, displayed mitral valve prolapse. The clustering of defective genes in this family was considered to represent 'coincidental' occurrences rather than being linked to each other.

Adolescent↗
PubMed2005

NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS.

Intracellular trafficking of endothelial nitric oxide synthase (eNOS) between different compartments is incompletely understood. Recently, we described a novel eNOS-interacting protein, NOSTRIN, which upon overexpression drives eNOS away from the plasma membrane towards intracellular compartments. Sequence similarity of NOSTRIN and pacsins/syndapins suggested a role for NOSTRIN in endocytosis. Accordingly, we show here that NOSTRIN interacts with the large GTPase dynamin and the actin nucleation promoting factor N-WASP by means of its SH3 domain, which also represents the docking site for eNOS. Via a coiled-coil region in the C-terminal portion of the protein, NOSTRIN oligomerizes, mainly forming trimers, which would allow simultaneous interaction with multiple binding partners of the SH3 domain. Consistent with this notion, expression of dynamin-2-GFP in CHO cells stably expressing eNOS (CHO-eNOS) results in recruitment of eNOS to dynamin-positive structures, only when NOSTRIN is present as well. Similarly, when N-WASP-GFP and NOSTRIN are co-expressed in CHO-eNOS cells, both proteins strongly co-localize with eNOS and are recruited to structures running along actin filaments. If, however, the actin cytoskeleton is depolymerized by cytochalasin D, NOSTRIN and eNOS are associated with extended structures in the cell periphery, possibly being unable to leave the plasma membrane. Together, these results indicate that NOSTRIN may facilitate endocytosis of eNOS by coordinating the function of dynamin and N-WASP.

Actins↗
PubMed1994

AE3 anion exchanger isoforms in the vertebrate retina: developmental regulation and differential expression in neurons and glia.

Plasma membrane anion exchangers constitute a multigene family that contributes to the regulation of intracellular pH and chloride concentration in many cell types. We have characterized two polypeptide isoforms of the AE3 gene that are expressed in the rat retina. Using antipeptide antibodies specific for defined NH2-terminal and COOH-terminal epitopes, we have identified a 165 kDa polypeptide whose expression is restricted to the primary glial cell type of the retina, the Müller cell, and a 125 kDa polypeptide that is expressed in horizontal neurons. Expression of the Müller cell isoform exhibits a polarized distribution and is highest in basal endfoot processes. These AE3 isoforms exhibit a distinct developmental expression pattern in postnatal rat retina. The neuronal isoform is undetectable in neonatal retina until postnatal day 10-15, correlating strongly with the onset of retinal function.

Aging↗
PubMed1993

Cloning and functional expression of a Dictyostelium discoideum protein tyrosine phosphatase.

Using polymerase chain reaction methods, we cloned a 1.7-kilobase cDNA, denoted DdPTPa, that has high homology with other known eukaryotic protein tyrosine phosphatases. DdPTPa possess a 241-amino acid protein tyrosine phosphatase domain located in the C terminus, which exhibits a 39-43% amino acid sequence identity with published protein tyrosine phosphatases. Absence of a characteristic signal sequence and transmembrane domain suggests that DdPTPa is a nonreceptor type cytoplasmic protein tyrosine phosphatase. Southern blot analysis of genomic DNA indicates the presence of a multigene protein tyrosine phosphatase family in Dictyostelium. Northern blot analysis reveals four species of mRNA that hybridize to the DdPTPa probe, at least three of which are developmentally regulated. The entire coding sequence of DdPTPa was subcloned into the pET15-b vector and expressed in Escherichia coli. Affinity-purified DdPTPa protein efficiently dephosphorylates both p-nitrophenyl phosphate and tyrosine-phosphorylated reduced, carboxyamidomethylated, and maleylated lysozyme. A Dictyostelium transformant overexpressing DdPTPa does not develop normally. The overexpresser fails to aggregate, in contrast to the control transformant containing vector alone, and after 24 h gives rise to only a few abnormal slugs and small fruiting bodies.

Amino Acid Sequence↗