Biomedical subjects

Philip Tucker

Publications and source records attributed to Philip Tucker.

7 recordsLinked to original sources

PubMed2006

The impact of rest breaks on temporal trends in injury risk.

This study examined the impact of rest breaks on temporal trends in industrial accident risks in an attempt to replicate earlier findings of a linear increase in risk as a function of elapsed time on task. In two separate studies, the trend in work-related injuries were studied in relation to the timing of rest breaks. In study one, comparisons were made between on- and off-track workers on weekly rotating three-shift systems operating in a large engineering company. Records of on-duty injuries that occurred over 12 months were examined (N = 4645 incidents). Study two involved interviewing patients who had suffered work-related hand injuries in a variety of occupational settings (N = 407 patients). Hierarchical log linear analysis was used in both studies. In study one, risk increased from the first to the second half-hour of continuous work following a break, but then remained relatively constant in subsequent half-hour periods, although there was a fall in the third half-hour for on-track workers. In some of the data, there was also a decrease in risk in the period leading up to the end of a work period. There was a sharp decline in reported injuries toward the very end of a shift, but otherwise the observed trends did not differ between successive periods of continuous work or between morning, afternoon, and night shifts. In study two, risk increased from the first to the second half-hour of continuous work and then remained relatively constant in the third half-hour. The contrast between the current and previous findings may be due to the relatively unique work environment of the previous study. It is suggested that the current trends reflect the effects of working in a relatively unconstrained task environment, and that causes other than fatigue may underlie the trends observed in both the previous and current studies.

Accident Prevention↗

PubMed2005

Moderators of the relationship between long work hours and health.

The authors examined how associations between work hours and self-reported health are moderated by the reasons given for working overtime, by schedule autonomy, and by the degree of social support experienced, in a survey of 372 train drivers. Respondents who lacked both schedule autonomy and social support demonstrated positive associations between the number of hours worked per week and frequency of physical health symptoms. Conversely, negative associations were observed among respondents reporting low schedule autonomy together with high social support. There were no such interactions in the analyses of fatigue and psychological health outcomes. The findings are discussed in terms of the fit between an individual's actual and desired work hours. The problems of identifying appropriate limits for work hours are highlighted.

Adult↗

PubMed2005

Role for PSF in mediating transcriptional activator-dependent stimulation of pre-mRNA processing in vivo.

In a recent study, we provided evidence that strong promoter-bound transcriptional activators result in higher levels of splicing and 3'-end cleavage of nascent pre-mRNA than do weak promoter-bound activators and that this effect of strong activators requires the carboxyl-terminal domain (CTD) of RNA polymerase II (pol II). In the present study, we have investigated the mechanism of activator- and CTD-mediated stimulation of pre-mRNA processing. Affinity chromatography experiments reveal that two factors previously implicated in the coupling of transcription and pre-mRNA processing, PSF and p54(nrb)/NonO, preferentially bind a strong rather than a weak activation domain. Elevated expression in human 293 cells of PSF bypasses the requirement for a strong activator to promote efficient splicing and 3'-end cleavage. Truncation of the pol II CTD, which consists of 52 repeats of the consensus heptapeptide sequence YSPTSPS, to 15 heptapeptide repeats prevents PSF-dependent stimulation of splicing and 3'-end cleavage. Moreover, PSF and p54(nrb)/NonO bind in vitro to the wild-type CTD but not to the truncated 15-repeat CTD, and domains in PSF that are required for binding to activators and to the CTD are also important for the stimulation of pre-mRNA processing. Interestingly, activator- and CTD-dependent stimulation of splicing mediated by PSF appears to primarily affect the removal of first introns. Collectively, these results suggest that the recruitment of PSF to activated promoters and the pol II CTD provides a mechanism by which transcription and pre-mRNA processing are coordinated within the cell.

Cell Line↗

PubMed2004

SMAR1 and Cux/CDP modulate chromatin and act as negative regulators of the TCRbeta enhancer (Ebeta).

Chromatin modulation at various cis-acting elements is critical for V(D)J recombination during T and B cell development. MARbeta, a matrix-associated region (MAR) located upstream of the T cell receptor beta (TCRbeta) enhancer (Ebeta), serves a crucial role in silencing Ebeta-mediated TCR activation. By DNaseI hypersensitivity assays, we show here that overexpression of the MAR binding proteins SMAR1 and Cux/CDP modulate the chromatin structure at MARbeta. We further demonstrate that the silencer function of MARbeta is mediated independently by SMAR1 and Cux/CDP as judged by their ability to repress Ebeta-dependent reporter gene expression. Moreover, the repressor activity of SMAR1 is strongly enhanced in the presence of Cux/CDP. These two proteins physically interact with each other and colocalize within the perinuclear region through a SMAR1 domain required for repression. The repression domain of SMAR1 is separate from the MARbeta binding domain and contains a nuclear localization signal and an arginine-serine (RS)-rich domain, characteristic of pre-mRNA splicing regulators. Our data suggest that at the double positive stage of T cell development, cis-acting MARbeta elements recruit the strong negative regulators Cux and SMAR1 to control Ebeta-mediated recombination and transcription.

Amino Acid Sequence↗

PubMed2004

Purification and identification of protein-tyrosine kinase-binding proteins using synthetic phosphopeptides as affinity reagents.

Protein-tyrosine kinases are known regulators of cell division that have been implicated in the onset of a variety of malignancies. They act through cellular signaling proteins that bind to specific autophosphorylation sites. To find out whether these autophosphorylation sites can be used to identify downstream signaling proteins, synthetic peptides based on an autophosphorylation site in the colony-stimulating factor-1 (CSF-1) receptor were linked to agarose beads and incubated with lysates from macrophages. Bound proteins were analyzed by MS, leading to the identification of both known and novel CSF-1 receptor-interacting proteins. The approach presented here can be applied to phosphorylation sites in a wide variety of proteins. It will lead to the identification of novel protein-protein interactions and provide new insights into the mechanics of signal transduction. Novel protein-protein interactions may provide useful targets for the development of drugs that interfere with the activation of signaling cascades used by protein-tyrosine kinases to turn on cell division.

Affinity Labels↗

PubMed2003

Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors.

The Foxp subfamily of forkhead/HNF3 transcription factors has recently been recognized because of its involvement in autoimmune disease, speech and language disorders, and lung development. Domains unique to this subfamily include a divergent DNA-binding winged helix, a leucine zipper, a zinc finger, and a polyglutamine tract. Little is known about the properties of these proteins that are fundamental to their function as transcription factors nor how the Foxp sequence motifs regulate their transcriptional regulatory properties. We report here a structure/function analysis of the Foxp1 protein. We have analyzed the alternative splice isoforms 1A and 1C and also report the cloning and characterization of a novel isoform Foxp1D that lacks the polyglutamine domain. We have isolated the preferred DNA-binding sites for Foxp1 transcription factors. Foxp1A, C, and D isoforms and the related Foxp2 protein repress gene transcription via binding to this consensus site or to a naturally occurring site within the SV40 and the interleukin-2 promoters. In some cases the strength of Foxp1 repression is mediated by the polyglutamine domain. Unlike previously characterized forkhead factors, Foxp1 proteins can form homodimers or heterodimers with subfamily members. The dimerization domain was localized to an evolutionarily conserved C2H2 zinc finger and leucine zipper motif. Finally, we demonstrate that Foxp1, although broadly expressed, is further regulated by tissue-specific alternative splicing of these functionally important sequence domains. These results suggest that Foxp1 proteins have diverse functional roles in different cell and tissue types.

Alternative Splicing↗

PubMed2003

Shift work, safety and productivity.

The arguments in favour of introducing shift work clearly depend on productivity and safety being maintained at an acceptable level. However, the evidence reviewed in this paper clearly indicates that both productivity and safety may be compromised at night. More specifically, safety declines over successive night shifts, with increasing hours on duty and between successive rest breaks. The only known way to minimize these problems is to improve shift systems with respect to these factors. However, these factors need to be considered in combination with one another since, for example, a long night shift that includes frequent rest breaks might well prove safer than a shorter night shift with less frequent breaks.

Accidents, Occupational↗