Search PubMed⌕ Search

Biomedical subjects

T Shay

Publications and source records attributed to T Shay.

9 recordsLinked to original sources

Docking to single-domain and multiple-domain proteins: old and new challenges.

The diverse selection of targets in the CAPRI experiments provides grounds for determining the limits of our rigid-body docking program MolFit, and for extending it. We find that the sensitivity of MolFit is high, enabling it to produce reasonably accurate docking solutions when the structures undergo moderate local conformation changes upon complex formation or when the docked molecules are modeled. Yet the ranks of these solutions are sometimes too low to meet the requirements of CAPRI assessment. This indicates that the selectivity of MolFit, which was optimized for docking of unbound X-ray structures, and which relies on the availability of external data from biochemical and bioinformatic sources, needs readjustment in order to meet the challenges presented by NMR or modeled structures. A different challenge is presented by large global conformation changes such as movements of domains. We show that such changes can be accommodated within the rigid-body approximation by employing rigid multibody multistage docking procedures. We also address the difficulty of ranking results from 2-body and multibody docking scans in cases in which there are no external data favoring one option over the other.

Algorithms↗

Temporal association between serum prolactin concentration and exposure to styrene.

BACKGROUND: Previous studies have suggested that occupational exposure to styrene is associated with increased serum levels of the anterior pituitary hormone prolactin (PRL). AIMS: To test the hypotheses that: (1) the effect of styrene exposure on PRL secretion is an acute effect, not a subchronic or chronic effect; (2) blood styrene, as a measure of absorbed dose, is a stronger predictor of serum PRL level than personal breathing zone air styrene concentration. METHODS: Subjects were recruited from 17 workplaces in the reinforced plastics industry. Personal breathing zone air styrene, whole blood styrene, and serum PRL were measured during one to three sessions, approximately one year apart. Linear multiple regression was used to model the relations between acute (air styrene or blood styrene obtained at same time as PRL), subchronic (average air or blood styrene over two or three sessions), and chronic (years of work in industry or facility times average air styrene over all sessions) indices of styrene exposure and serum PRL. RESULTS: Acute blood styrene concentration was the strongest predictor of serum PRL concentration, with the model predicting a 2.06-fold increase in PRL (95% CI 1.11 to 3.84) for every 10-fold increase in blood styrene. Serum PRL tended to increase with increasing styrene exposure in both men and women; however, women tended to have higher PRL levels. For women, the change in blood styrene between sessions 1 and 2 was a significant predictor of the change in serum PRL between sessions. CONCLUSIONS: Results confirm that styrene exposure enhances serum PRL concentrations and support an acute effect of styrene on PRL secretion.

Adolescent↗

The callipyge mutation enhances the expression of coregulated imprinted genes in cis without affecting their imprinting status.

The callipyge (CLPG) phenotype (from kappa(alpha)lambda(iota), "beautiful," and pi(iota)gamma(epsilon), "buttocks") described in sheep is an inherited muscular hypertrophy that is subject to an unusual parent-of-origin effect referred to as polar overdominance: only heterozygous individuals having inherited the CLPG mutation from their sire exhibit the muscular hypertrophy. The callipyge (clpg) locus was mapped to a chromosome segment of approximately 400 kb (refs. 2-4), which was shown to contain four genes (DLK1, GTL2, PEG11 and MEG8) that are preferentially expressed in skeletal muscle and subject to parental imprinting in this tissue. Here we describe the effect of the CLPG mutation on the expression of these four genes, and demonstrate that callipyge individuals have a unique expression profile that may account for the observed polar overdominance.

Animals↗

Human-ovine comparative sequencing of a 250-kb imprinted domain encompassing the callipyge (clpg) locus and identification of six imprinted transcripts: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8.

Two ovine BAC clones and a connecting long-range PCR product, jointly spanning approximately 250 kb and representing most of the MULGE5-OY3 marker interval known to contain the clpg locus, were completely sequenced. The resulting genomic sequence was aligned with its human ortholog and extensively annotated. Six transcripts, four of which were novel, were predicted to originate from within the analyzed region and their existence confirmed experimentally: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8. RT-PCR experiments performed on a range of tissues sampled from an 8-wk-old animal demonstrated the preferential expression of all six transcripts in skeletal muscle, which suggests that they are under control of common regulatory elements. The six transcripts were also shown to be subject to parental imprinting: DLK1, DAT, and PEG11 were shown to be paternally expressed and GTL2, antiPEG11, and MEG8 to be maternally expressed.

Animals↗

Construction and characterization of an ovine BAC contig spanning the callipyge locus.

We describe the construction of an ovine BAC contig spanning a 4.6 centimorgan (cM) chromosome segment known to contain the callipyge (CLPG) locus. The contig comprises 21 ovine BAC clones jointly covering approximately 900 kilobases (Kb). Two gaps in the BAC contig, spanning 10 and 7.5 Kb, respectively, were bridged by long range PCR. The corresponding chromosome region was shown to be characterized by an unusually low Kb to cM ratio (164 Kb/cM) and a high density of Not1 sites (1:126 Kb) possibly reflecting a high gene density in the corresponding chromosome region. Equivalent amplification of 64 sequence tagged sites spanning the corresponding region from homozygous +/+ and CLPG/CLPG individuals disproves the hypothesis of a major deletion causing the CLPG mutation.

Animals↗

Martial arts.

The martial arts have a reputation for being a high-risk activity, but are generally practiced in a safe environment. This article presents the results of a survey which is used to calculate risk of injury per 1000 hours of practice. The injury rate compares favorably with other mainstream activities; in fact, the martial arts are generally considered safer than most. The most common injuries occur to the wrist, hand, finger, foot, knee, head, and thigh. Special issues of importance for prevention and treatment of these injuries are discussed.

Athletic Injuries↗