Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the connexin 31 (GJB3) gene have been found in subjects with dominant and recessive deafness and in patients with erythrokeratodermia variabilis. We report here a dominant mutation in the GJB3 gene (D66del) in a family affected with peripheral neuropathy and sensorineural hearing impairment. A wide range of disease severity for peripheral neuropathy, from asymptomatic cases to subjects with chronic skin ulcers in their feet and osteomyelitis leading to amputations, was detected in D66del patients. Mild, often asymmetrical, hearing impairment was found in all but one patient with mutation D66del of this family and the same mutation was present in an independent family ascertained because of hearing impairment. We have found mouse connexin 31 (Gjb3) gene expression in the cochlea and in the auditory and sciatic nerves, showing a pattern similar to that of Gjb1 (connexin 32), of which the human ortholog (GJB1) is involved in X-linked peripheral neuropathy. This expression pattern, together with auditory-evoked brainstem anomalous response in D66del patients, indicates that hearing impairment due to GJB3 mutations involves alterations in both the cochlea and the auditory nerve. Peripheral neuropathy is the third phenotypic alteration linked to GJB3 mutations, which enlarges the list of genes that cause this group of heterogeneous disorders.
Hum Mol Genet 2001 Apr 15
PMID:Connexin 31 (GJB3) is expressed in the peripheral and auditory nerves and causes neuropathy and hearing impairment. 1130 68

Asymmetrical patterns of amino acid substitution in proteins of organisms living at moderate and high temperatures (mesophiles and thermophiles, respectively) are generally taken to indicate selection favoring different amino acids at different temperatures due to their biochemical properties. If that were the case, comparisons of different pairs of mesophilic and thermophilic taxa would exhibit similar patterns of substitutional asymmetry. A previous comparison of mesophilic versus thermophilic Methanococcus with mesophilic versus thermophilic Bacillus revealed several pairs of amino acids for which one amino acid was favored in thermophilic Bacillus and the other was favored in thermophilic Methanococcus. Most of this could be explained by the higher G+C content of the DNA of thermophilic Bacillus, a phenomenon not seen in the Methanococcus comparison. Here, I compared the mesophilic bacterium Deinococcus radiodurans and its thermophilic relative Thermus thermophilus, which are similar in G+C content. Of the 190 pairs of amino acids, 83 exhibited significant substitutional asymmetry, consistent with the pervasive effects of selection. Most of these significantly asymmetrical pairs of amino acids were asymmetrical in the direction predicted from the Methanococcus data, consistent with thermal adaptation resulting from universal biochemical properties of the amino acids. However, 12 pairs of amino acids exhibited asymmetry significantly different from and in the opposite direction of that found in the Methanococcus comparison, and 21 pairs of amino acids exhibited asymmetry that was significantly different from that found in the Bacillus comparison and could not be explained by the greater G+C content in thermophilic Bacillus. This suggests that selection due to universal biochemical properties of the amino acids and differences in G+C content are not the only causes of substitutional asymmetry between mesophiles and thermophiles. Instead, selection on taxon-specific properties of amino acids, such as their metabolic cost, may play a role in causing asymmetrical patterns of substitution.
Mol Biol Evol 2001 May
PMID:Patterns of temperature adaptation in proteins from the bacteria Deinococcus radiodurans and Thermus thermophilus. 1131 58

Estrogen-induced signaling mediated by estrogen receptors (ERs) is also affected by aberrant ERs that act as constitutively active or dominant negative modulators. Variant ERs can contribute to carcinogenesis and to the loss of estrogen responsiveness, rendering antiestrogen therapy ineffective. Determining target gene response during co-synthesis of different ER species is difficult, because dimers formed in the presence of more than one ER species are a heterogenous population of homo- or heterodimers. We engineered a homofusion ERalpha as a prototype single-chain receptor by genetically conjugating two ER monomers into a covalently fused single-chain protein to obtain a homogeneous population. This permits analysis of symmetrical or asymmetrical mutations that simulate variant homo- and heterodimers. Although a monomer, the homofusion receptor exhibited similar biochemical and functional properties to the dimeric ERalpha. We used activation function-2 (AF2) defective mutants as a model in either one or both receptor domains for a dominant-negative phenotype by suppressing the reporter activity induced by the WT receptor. When co-expressed with ERalpha, the fusion variant deficient in both AF2 functions suppressed the reporter activity effectively induced by ERalpha. These results show the utility of fusion receptors as models for generation of receptor-based agonists and antagonists.
Mol Cell Endocrinol 2001 Sep
PMID:Fusion estrogen receptor proteins: toward the development of receptor-based agonists and antagonists. 1151 59

In phylogenetically based systematics, Mammalia is the nomenclatural term which designates the clade stemming from the most recent common ancestry of monotremes and theria [, Sys. Biol. 43 (1994) 497]. Considering that locomotor performance is a prevalent function to provide the necessary conditions to survive and transmit genes, it may be questioned if the diverse types of locomotion exhibited by extant mammals could have played a role in their evolution, or have only followed it. We may look after the structural and behavioural features which are involved in mammal locomotion compared to other tetrapods and test if they fit with the proposed phylogeny. Several factors may be checked: scaling effect in relation to gravitational constraints; geometrical distribution of masses in the body, and relative mechanical role of the limbs in the production of the external forces necessary to forward motion. Classically, it was thought that the fastest gaits used by terrestrial mammals were based upon a unique kind of limb motion co-ordination, called asymmetrical gaits, which in turn may be thought to be related to a peculiar neuronal wiring. Kinematic analysis brings an insight to this topic. Is the search for an ancestral mammalian locomotor pattern judicious? Notice the small size of many of the first mammals and their probable locomotor plasticity. (relation between grain size of the elements within the substrate and the organism scale). At a small size, the gravitational constraint is less important, and the distinction between terrestrial and arboreal has probably no sense when the limbs are the principal motor elements. There remains the importance of the geometrical distribution of body elements, the proportions of the limbs and of the head-neck complex, the tail merely as an appendix, a set of factors which may have generated the frame of constraints within which diverse locomotor modes have evolved.
Comp Biochem Physiol A Mol Integr Physiol 2001 Dec
PMID:Comparative aspects of gait, scaling and mechanics in mammals. 1173 71

Caudal epididymal spermatozoa of golden hamsters were incubated in capacitation medium. Their movement patterns changed as they became hyperactivated and underwent the acrosome reaction. To understand the basic mechanism by which changes in movement pattern are brought about, digital image analysis was carried out on the flagellar movements recorded with a video system. The degree of flagellar bending increased with incubation time, especially in the proximal midpiece. The hyperactivated spermatozoa had remarkably asymmetrical flagellar waves of large amplitude because either the bends in the same direction as the hook of the head (referred as the "pro-hook bend") or the bends in the opposite direction to the hook of the head (referred as the "anti-hook bend") extremely increased their curvature; whereas, the acrosome-reacted spermatozoa had relatively symmetrical flagellar waves of large amplitude because both the pro- and anti-hook bends remarkably increased their curvature. Beat frequency significantly decreased while wavelength of flagellar waves increased after hyperactivation and further after the acrosome reaction. These results suggest that both extreme pro- and anti-hook bends are essential in the acrosome-reacted spermatozoa even though beat frequency decreased markedly.
Mol Reprod Dev 2002 Mar
PMID:Quantitative analysis of flagellar movement in hyperactivated and acrosome-reacted golden hamster spermatozoa. 1183 83

We investigate the distribution of sizes of fragments obtained from the amplified fragment length polymorphism (AFLP) marker technique. We find that empirical distributions obtained in two plant species, Phaseolus lunatus and Lolium perenne, are consistent with the expected distributions obtained from analytical theory and from numerical simulations. Our results indicate that the size distribution is strongly asymmetrical, with a much higher proportion of small than large fragments, that it is not influenced by the number of selective nucleotides nor by genome size but that it may vary with genome-wide GC-content, with a higher proportion of small fragments in cases of lower GC-content when considering the standard AFLP protocol with the enzyme MseI. Results from population samples of the two plant species show that there is a negative relationship between AFLP fragment size and fragment population frequency. Monte Carlo simulations reveal that size homoplasy, arising from pulling together nonhomologous fragments of the same size, generates patterns similar to those observed in P. lunatus and L. perenne because of the asymmetry of the size distribution. We discuss the implications of these results in the context of estimating genetic diversity with AFLP markers.
Mol Ecol 2002 Jan
PMID:Data from amplified fragment length polymorphism (AFLP) markers show indication of size homoplasy and of a relationship between degree of homoplasy and fragment size. 1190 11

In A549 cell culture, significant variability was found in sensitivity to actinomycin D. Using limiting dilution, actinomycin D-susceptible (G4S) and -resistant (D3R) subclones were isolated. G4S cells were also susceptible to protein synthesis inhibitors, a redox cycling quinone, and an electrophile with concomitant activation of caspases 3 and 9. D3R cells were resistant to these agents without caspase activation. Antioxidant profiles revealed that D3R cells had significantly higher glutathione and glutathione reductase activity but markedly lower catalase, glutathione peroxidase, and aldehyde reductase activities than G4S cells. Thus A549 cells contain at least two distinct subpopulations with respect to predisposition to cell death and antioxidant profile. Because sensitivities to agents and the antioxidant profile were inconsistent, mechanisms independent of antioxidants, including the apparent inability to activate caspases in D3R cells, may play an important role. Regardless, the results suggest that antioxidant profiles of asymmetrical cell populations cannot predict sensitivity to oxidants and warn that the use of single subclones is advisable for mechanistic studies using A549 or other unstable cell lines.
Am J Physiol Lung Cell Mol Physiol 2002 Oct
PMID:A549 subclones demonstrate heterogeneity in toxicological sensitivity and antioxidant profile. 1222 49

Most duplicate genes are eliminated from a genome shortly after duplication, but those that remain are an important source of biochemical diversity. Here, I present evidence from genome-scale protein-protein interaction data, microarray expression data, and large-scale gene knockout data that this diversification is often asymmetrical: one duplicate usually shows significantly more molecular or genetic interactions than the other. I propose a model that can explain this divergence pattern if asymmetrically diverging duplicate gene pairs show increased robustness to deleterious mutations.
Mol Biol Evol 2002 Oct
PMID:Asymmetric functional divergence of duplicate genes in yeast. 1227 Sep 2

A number of eukaryotic proteins are already known to orchestrate key steps of mRNA metabolism and translation via interactions with the 5' m7GpppN cap. We have characterized a new type of histidine triad (HIT) motif protein (Nhm1) that co-purifies with the cap-binding complex eIF4F of Schizosaccharomyces pombe. Nhm1 is an RNA-binding protein that binds to m7GTP-Sepharose, albeit with lower specificity and affinity for methylated GTP than is typical for the cap-binding protein known as eukaryotic initiation factor 4E. Sequence searches have revealed that proteins with strong sequence similarity over all regions of the new protein exist in a wide range of eukaryotes, yet none has been characterized up to now. However, other proteins that share specific motifs with Nhm1 include the human Fhit tumour suppressor protein and the diadenosine 5', 5"'-P1, P4-tetraphosphate asymmetrical hydrolase of S. pombe. Our experimental work also reveals that Nhm1 inhibits translation in a cell-free extract prepared from S. pombe, and that it is therefore a putative translational modulator. On the other hand, purified Nhm1 manifests mRNA decapping activity, yet is physically distinct from the Saccharomyces cerevisiae decapping enzyme Dcp1. Moreover, fluorescence and immunofluorescence microscopy show that Nhm1 is predominantly, although not exclusively, nuclear. We conclude that Nhm1 has evolved as a special branch of the HIT motif superfamily that has the potential to influence both the metabolism and the translation of mRNA, and that its presence in S. pombe suggests the utilization of a novel decapping pathway.
Mol Microbiol 2002 Oct
PMID:A nuclear protein in Schizosaccharomyces pombe with homology to the human tumour suppressor Fhit has decapping activity. 1236 30

Neuroblast undergoes asymmetrical cell division to produce the neuroblast itself and ganglion mother cell along the apical-basal axis. Inscuteable (Insc) and Partner of Inscuteable (Pins) are translocated to the apical cell cortex during asymmetrical cell division of Drosophila neuroblast. Insc is implicated in the apical-basal orientation of mitotic spindle and the basal localization of Prospero (Pros) and Numb. Here, we identified and characterized human Inscuteable (INSC) gene using bioinformatics. Human INSC gene, consisting of at least 13 exons, was located within human genome draft sequence AC090744.5 (around nucleotide position 150581-16936 in reverse orientation). Human INSC gene, closely linked to CALCB gene with an interval of about 30 kb, was assigned to human chromosome 11p15.2-p15.1. Amino-acid sequence of human INSC polypeptide (579 aa) was determined based on exon sequences of human INSC gene. C. elegans hypothetical protein F43E2.3 (NP_495539), homologous to human INSC, was designated C. elegans Insc. Central INSC homologous (ISH) domain and C-terminal PDZ-binding motif were evolutionary conserved among INSC proteins. The former part of ISH domain is implicated in Pros localization, while function of the latter part of ISH domain and C-terminal PDZ-binding motif remain to be elucidated. Human INSC mRNA was expressed in eye, kidney, fetal cochlea, parathyroid tumor, chondrosarcoma, epidermoid carcinoma, and skin tumor. Because LGN/Pins, PARD3/Par-3Bazooka, PARD6A/Par-6 and PRKCZ/aPKC genes implicated in asymmetrical cell division are evolutionarily and functionally conserved, human INSC protein might be implicated in asymmetrical cell division of human neural stem cells and other stem cells.
Int J Mol Med 2003 Jan
PMID:Identification and characterization of human Inscuteable gene in silico. 1246 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>