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Biomedical subjects

A Whiting

Publications and source records attributed to A Whiting.

10 recordsLinked to original sources
PubMed2006

Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T cells express high levels of the Th1-chemokine receptor CC chemokine receptor 5 (CCR5), which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA-affected sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly undertransmitted to children with early-onset JRA (P<0.01). C-1835T was genotyped in 424 additional simplex and multiplex families. CCR5-1835T allele was undertransmitted in the cohort of all probands with JRA (P<0.02), as well as in those with early-onset (P<0.01) or pauciarticular JRA (P<0.05). Another variant, a 32-bp deletion in the open reading frame of CCR5 (CCR5-Delta32) was also tested in approximately 700 simplex and multiplex families. CCR5-Delta32 was also significantly undertransmitted to probands with early-onset JRA (P<0.05). Both variants are in regions under natural selection, and result in functional consequences. Our results suggest these CCR5 variants are protective against early-onset JRA.

Arthritis, Juvenile↗
PubMed2002

The validity of the inter- and/or intrahemispheric deficit hypothesis as an explanation of the co-occurrence of motor and language impairments.

From an initial cohort of 15 children, between the ages of 5 and 10 years, who had expressive oral language problems, 4 were shown in an earlier study to be both motor and language impaired. Two explanatory hypotheses were proposed to account for this communality: (a) cerebellar deficit; (b) inter- and/or intrahemispheric deficit. In order to explore the validity of the latter explanation, the same group of children, together with a matched control group, were required to carry out two sensory matching tests designed to tap inter- and intrahemispheric information processing abilities: hand-hand and foot-hand. The results, discussed in the light of Liederman's shielding model, provided more support for the hypothesis of an interhemispheric information processing problem from left to right rather than an intrahemispheric problem.

Cerebral Cortex↗
PubMed2001

Direct evidence for a ruthenium(IV) oxo complex-mediated oxidation of a hydroxamic acid in the presence of phosphine oxide donors.

Ruthenium(II) complexes can be used to oxidise N-Boc hydroxylamine the the presence of tert-butylhydroperoxide to the corresponding nitroso dienophile, which is trapped using cyclohexa-1,3-diene as the hetero-Diels-Alder adduct; direct evidence has been obtained for the intervention of a triphenylphosphine oxide-stabilised ruthenium(IV) oxocomplex as the catalytically active species.

Journal Article↗
PubMed1997

Speed discrimination of stereoscopic (cyclopean) motion.

This study investigated the degree to which speed of stereoscopic translational motion (i.e. moving binocular disparity information) can be discriminated in a display that minimizes position information. Observers viewed dynamic random-element stereograms depicting arrays of randomly positioned stereoscopic dots that moved bidirectionally. Two tasks were performed: a speed discrimination task and a displacement discrimination task. Across a range of conditions, speed could be discriminated under conditions in which displacement could not. Thus, speed of stereoscopic motion can be discriminated when position information is minimal. This result indicates that stereoscopic motion is sensed in a way that cannot be explained by feature tracking or by inferring the motion from memory of position and time.

Depth Perception↗
PubMed1990

A regular pattern of two types of 100-residue motif in the sequence of titin.

Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle. Its molecules are string-like and in vivo span from the M to Z-lines. I-band regions of titin are thought to make elastic connections between the thick filament and the Z-line, thereby forming a third type of sarcomere filament. These would centre the A-band in the sarcomere and provide structural continuity in relaxed myofibrils. The A-band region of titin seems to be bound to the thick filament, where it has been proposed to act as a 'molecular ruler' regulating filament length and assembly. Here, we show that partial titin complementary DNAs encode a regular pattern of two types of 100-residue motif, each of which probably folds into a separate domain type. Such motifs are present in several evolutionarily divergent muscle proteins, all of which are likely to interact with myosin. One or both of the domain types is therefore likely to bind to myosin.

Amino Acid Sequence↗
PubMed1989

Does titin regulate the length of muscle thick filaments?

The protein titin has been localized by electron microscopy of myofibrils labelled with monoclonal antibodies. The data are consistent with individual titin molecules extending from near the M-line to beyond the ends of thick filaments, a distance of approximately 1 micron. In the A-band, titin appears to be bound to thick filaments, probably to the outside of the filament shaft. Molecules of titin in this configuration provided an obvious mechanism by which the length of thick filaments could be regulated accurately.

Animals↗
PubMed1984

Purification and properties of native titin.

A procedure has been developed for the extraction and purification of the massive myofibrillar protein titin without exposing it to denaturing conditions. The form of the molecule that has been isolated is soluble at high ionic strength and alkaline pH, but precipitates in low salt or at pH values below 7. Sedimentation velocity experiments indicate that titin is a highly asymmetric molecule with a sedimentation coefficient of 13.4 S. This asymmetry is confirmed by electron microscopy of rotary-shadowed specimens, which shows string-like structures of diameter 40 A and lengths up to 8000 A. Significant differences were observed depending on whether the electron microscope specimens were prepared by spraying or by layering of the titin onto a mica substrate; we tentatively attribute these differences to elasticity in the titin, revealed by the high shearing forces that accompany spraying. In accord with this, the circular dichroism spectrum of titin indicates that its secondary structure is largely random coil, a conformation characteristic of elastic proteins such as elastin. Negative staining of titin again shows long string-like structures, but these can now be seen to have an appearance similar to a string of beads, where the spacing between successive beads is about 40 A. Very similar beaded strings have been observed also associated with negatively stained separated native thick filaments; these are found running alongside the cross-bridge regions and in coils near the filament ends. Since the periodicity of the strings is similar to that of end-filaments, recently identified structures at the tips of thick filaments, it is likely that end-filaments are formed from titin. Titin comprises approximately 9% of the myofibrillar mass, which means that it is the third most abundant protein in muscle. The possible role of titin in forming elastic filaments within myofibrils is discussed.

Animals↗