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Z H Shah

Publications and source records attributed to Z H Shah.

13 recordsLinked to original sources
PubMed2005

Hair barbering in mice: implications for neurobehavioural research.

Barbering (fur/whisker trimming, the Dalila effect) is a behaviour-associated hair and whisker loss frequently seen in laboratory rodents, including mice. Here we analyse barbering behaviour in 129S1, NMRI, C57BL/6 and BALB/c mouse strains and some of their F1 hybrids. Our study shows that barbering in mice, depending on their genotype, is a complex behaviour with several distinct contexts or domains. We observed social (dominant) barbering in NMRI and C57BL/6 mice, sexual over-grooming in 129S1 and C57BL/6 mice, maternal barbering in lactating 129S1 and C57BL/6 mice, and stress-evoked barbering in F1 (NMRIx129S1) hybrids. In contrast, aggressive BALB/c mice and their F1 progeny do not use barbering in their behaviour. We suggest that barbering may be an important complex multi-domain behaviour sensitive to various manipulations, and represent a useful index in neurobehavioural research.

Alopecia↗
PubMed2003

The trends of vasectomy reversal in the forces.

A reversal of a vasectomy is required in about 3% of men who undergo vasectomy. We set out to examine the relationships between the age at which vasectomy was performed and the interval before subsequent reversal within the context of the armed forces. Thirty seven patients were identified from hospital records, as having undergone a reversal of vasectomy in the preceding two years, and thirty one sets of notes were available for inspection. Ages at vasectomy and at reversal were recorded and, where stated in the notes, if there had been a change in partner prior to the reversal request. Twelve (39%) men were under the age of thirty years at the time of their vasectomy, with a mean time to reversal of 4.4 years. Nineteen (61%) were over the age of thirty years at time of the vasectomy and their mean time to reversal was 7.2 years. Where recorded, the reason for requesting a reversal was a change in partner in 90% of men. Men who had their vasectomies before reaching the age of thirty were more likely to undergo reversal in a significantly shorter period of time when compared to those over thirty years. The disseminated criteria for vasectomy should be adhered to and appropriate preoperative counselling by surgeons may be useful.

Adult↗
PubMed2001

Novel coding-region polymorphisms in mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) genes in DFNA4 autosomal dominant deafness families.

Two genes for components of the mitochondrial translational apparatus, mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) lie adjacent to one another on human chromosome 19, within the critical interval for the autosomal dominant deafness locus DFNA4. Both genes are plausible candidates for DFNA4, based on the fact that deafness mutations in mtDNA have been mapped both to tRNA-ser(UCN) and to the accuracy domain of the small subunit rRNA. We have sequenced the coding regions, proximal promoters, 5' and 3' UTR and splice junctional regions of both genes in two families with DFNA4-linked deafness and in controls. Novel polymorphisms 84425C>T, 83907A>G, 79485T>G, 79406C>T, 71755A>C and 68686C>G (numbered as in GenBank AC011455) were found in one or both families, but none is a plausible disease-causing mutation. Although regulatory mutations affecting either gene could still be involved in the phenotype, structural gene mutations affecting SARSM or RPMS12 can be excluded from consideration as the cause of DFNA4-linked deafness, at least in the families identified thus far.

Chromosomes, Human, Pair 19↗
PubMed2001

Technical knockout, a Drosophila model of mitochondrial deafness.

Mutations in mtDNA-encoded components of the mitochondrial translational apparatus are associated with diverse pathological states in humans, notably sensorineural deafness. To develop animal models of such disorders, we have manipulated the nuclear gene for mitochondrial ribosomal protein S12 in Drosophila (technical knockout, tko). The prototypic mutant tko(25t) exhibits developmental delay, bang sensitivity, impaired male courtship, and defective response to sound. On the basis of a transgenic reversion test, these phenotypes are attributable to a single substitution (L85H) at a conserved residue of the tko protein. The mutant is hypersensitive to doxycyclin, an antibiotic that selectively inhibits mitochondrial protein synthesis, and mutant larvae have greatly diminished activities of mitochondrial redox enzymes and decreased levels of mitochondrial small-subunit rRNA. A second mutation in the tko gene, Q116K, which is predicted to impair the accuracy of mitochondrial translation, results in the completely different phenotype of recessive female sterility, based on three independent transgenic insertions. We infer that the tko(25t) mutant provides a model of mitochondrial hearing impairment resulting from a quantitative deficiency of mitochondrial translational capacity.

Animals↗
PubMed2000

The mitochondrial inner membrane AAA metalloprotease family in metazoans.

Three metalloproteases belonging to the AAA superfamily (Yme1p, Afg3p and Rca1p) are involved in protein turnover and respiratory chain complex assembly in the yeast inner mitochondrial membrane. Analysis of the completed genome sequences of Caenorhabditis elegans and Drosophila melanogaster indicates that this gene family typically comprises 3-4 members in metazoans. Phylogenetic analysis reveals three main branches represented, respectively, by Saccharomyces cerevisiae YME1, human SPG7 (paraplegin) and S. cerevisiae AFG3 and RCA1. mt-AAA metalloproteases are weak candidates for several previously studied Drosophila mutants. A full elucidation of the cellular and physiological roles of mt-AAA metalloproteases in metazoans will require the creation of targeted mutations.

Animals↗
PubMed2000

The human homologue of the yeast mitochondrial AAA metalloprotease Yme1p complements a yeast yme1 disruptant.

In yeast, three AAA superfamily metalloproteases (Yme1p, Afg3p and Rca1p) are localized to the mitochondrial inner membrane where they perform roles in the assembly and turnover of the respiratory chain complexes. We have investigated the function of the proposed human orthologue of yeast Yme1p, encoded by the YME1L gene on chromosome 10p. Transfection of both HEK-293EBNA and yeast cells with a green fluorescent protein-tagged YME1L cDNA confirmed mitochondrial targeting. When expressed in a yme1 disruptant yeast strain, YME1L restored growth on glycerol at 37 degrees C. We propose that YME1L plays a phylogenetically conserved role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies.

ATP-Dependent Proteases↗
PubMed1999

Expression of the gene for mitoribosomal protein S12 is controlled in human cells at the levels of transcription, RNA splicing, and translation.

The human gene RPMS12 encodes a protein similar to bacterial ribosomal protein S12 and is proposed to represent the human mitochondrial orthologue. RPMS12 reporter gene expression in cultured human cells supports the idea that the gene product is mitochondrial and is localized to the inner membrane. Human cells contain at least four structurally distinct RPMS12 mRNAs that differ in their 5'-untranslated region (5'-UTR) as a result of alternate splicing and of 5' end heterogeneity. All of them encode the same polypeptide. The full 5'-UTR contains two types of sequence element implicated elsewhere in translational regulation as follows: a short upstream open reading frame and an oligopyrimidine tract similar to that found at the 5' end of mRNAs encoding other growth-regulated proteins, including those of cytosolic ribosomes. The fully spliced (short) mRNA is the predominant form in all cell types studied and is translationally down-regulated in cultured cells in response to serum starvation, even though it lacks both of the putative translational regulatory elements. By contrast, other splice variants containing one or both of these elements are not translationally regulated by growth status but are translated poorly in both growing and non-growing cells. Reporter analysis identified a 26-nucleotide tract of the 5'-UTR of the short mRNA that is essential for translational down-regulation in growth-inhibited cells. Such experiments also confirmed that the 5'-UTR of the longer mRNA variants contains negative regulatory elements for translation. Tissue representation of RPMS12 mRNA is highly variable, following a typical mitochondrial pattern, but the relative levels of the different splice variants are similar in different tissues. These findings indicate a complex, multilevel regulation of RPMS12 gene expression in response to signals mediating growth, tissue specialization, and probably metabolic needs.

Animals↗
PubMed1998

Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1) specifying putative components of the mitochondrial gene expression apparatus.

We have mapped the chromosomal locations of three human nuclear genes for putative components of the apparatus of mitochondrial gene expression, using a combination of in situ hybridization and interspecies hybrid mapping. The genes RPMS12 (mitoribosomal protein S12, a conserved protein component of the mitoribosomal accuracy center), TUFM (mitochondrial elongation factor EF-Tu), and AFG3L1 (similar to the yeast genes Afg3 and Rca1 involved in the turnover of mistranslated or misfolded mtDNA-encoded polypeptides) were initially characterized by a combination of database sequence analysis, PCR, cloning, and DNA sequencing. RPMS12 maps to chromosome 19q13.1, close to the previously mapped gene for autosomal dominant hearing loss DFNA4. The TUFM gene is located on chromosome 16p11.2, with a putative pseudogene or variant (TUFML) located very close to the centromere of chromosome 17. AFG3L1 is located on chromosome 16q24, very close to the telomere. By virtue of their inferred functions in mitochondria, these genes should be regarded as candidates of disorders sharing features with mitochondrial disease syndromes, such as sensorineural deafness, diabetes, and retinopathy.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1997

Metazoan nuclear genes for mitoribosomal protein S12.

We have characterized nuclear genes for mitoribosomal protein S12 (mt-rps12) a major component of the ribosomal accuracy centre, in human, mouse and Drosophila melanogaster. In human and Drosophila, and probably also in mouse, there is a single intron within the coding region, located in the mitochondrial targeting pre-sequence. In humans, the mRNA structure is highly suggestive of translational regulation. In all three species, there is an amino-acid substitution with respect to eubacterial homologues in a residue implicated in aminoglycoside resistance. The only viable mutant allele of the Drosophila gene, associated with a bang-sensitive phenotype (paralysis upon mechanical vibration, arising from a mechanoreceptor cell defect) also has a novel substitution in a conserved region implicated in translational fidelity. Given the involvement of the mitoribosomal accuracy centre in human sensorineural deafness by virtue of rRNA mutations, our results indicate that this fly mutant may be a useful animal model of this disorder, and earmark the gene for mt-rps12 as a candidate in human hearing impairment.

3T3 Cells↗
PubMed1995

A family of cyclin D homologs from plants differentially controlled by growth regulators and containing the conserved retinoblastoma protein interaction motif.

A new family of three related cyclins has been identified in Arabidopsis by complementation of a yeast strain deficient in G1 cyclins. Individual members show tissue-specific expression and are conserved in other plant species. They form a distinctive group of plant cyclins, which we named delta-type cyclins to indicate their similarities with mammalian D-type cyclins. The sequence relationships between delta and D cyclins include the N-terminal sequence LXCXE. This motif was originally identified in certain viral oncoproteins and is strongly implicated in binding to the retinoblastoma protein pRb. By analogy to mammalian cyclin D, these plant homologs may mediate growth and phytohormonal signals into the plant cell cycle. In support of this hypothesis, we show that, on restimulation of suspension-cultured cells, cyclin delta 3 is rapidly induced by the plant growth regulator cytokinin and cyclin delta 2 is induced by carbon source.

Amino Acid Sequence↗