Nuclear hormone receptors in human skin.

Nuclear hormone receptors are of critical importance for skin homeostasis where they modulate cellular metabolism, proliferation, differentiation, cell death, and inflammation. The cutaneous role of the glucocorticoid, androgen, and estrogen receptors was explored initially. In recent years, sequence homology comparisons have uncovered the complete superfamily of related receptors, many of which are also implicated in cutaneous homeostasis. A subgroup of these receptors acts in concert with the retinoid X receptor by heterodimerization and has been successfully targeted for dermatologic therapy; i.e., the retinoic acid receptor and the vitamin D receptor. Ongoing research is aimed at delineating the cutaneous effects of additional members of this subgroup including the peroxisome proliferator-activated receptors and the liver X receptors. The various receptors exert differential effects in skin and can be rationally chosen as drug targets for the treatment of cutaneous pathologies.     

Validation and estimation of parameters for a general probabilistic model of the PCR process.

Earlier work rigorously derived a general probabilistic model for the PCR process that includes as a special case the Velikanov-Kapral model where all nucleotide reaction rates are the same. In this model, the probability of binding of deoxy-nucleoside triphosphate (dNTP) molecules with template strands is derived from the microscopic chemical kinetics. A recursive solution for the probability function of binding of dNTPs is developed for a single cycle and is used to calculate expected yield for a multicycle PCR. The model is able to reproduce important features of the PCR amplification process quantitatively.With a set of favorable reaction conditions, the amplification of the target sequence is fast enough to rapidly outnumber all side products. Furthermore, the final yield of the target sequence in a multicycle PCR run always approaches an asymptotic limit that is less than one. The amplification process itself is highly sensitive to initial concentrations and the reaction rates of addition to the template strand of each type of dNTP in the solution. This paper extends the earlier Saha model with a physics based model of the dependence of the reaction rates on temperature, and estimates parameters in this new model by nonlinear regression. The calibrated model is validated using RT-PCR data.     

Multiple measures of laterality in Garnett's bushbaby (Otolemur garnettii)

Behavioral laterality, a common measure of hemispheric specialization of the brain, has been examined in multiple tasks across several species of prosimian primates; however, there is inconsistency among findings between and within species that leaves many questions about laterality unanswered. Most studies have employed few measures of laterality, most commonly handedness. This study examined multiple measures of laterality within subjects in 17 captive‐born Garnett's bushbabies (Otolemur garnettii) to assess the consistency of lateralized behaviors and to examine possible influences such as age, posture, novelty, and arousal to elucidate the relations between direction and strength of laterality. We measured reaching, turning bias, scent marking, tail wrapping, leading foot, side‐of‐mouth preference, and hand use in prey capture. Because autonomic arousal has been invoked as a determinant of strength of lateralization, we included multiple tasks that would allow us to test this hypothesis. All subjects were significantly lateralized on simple reaching tasks (P<0.01) and tail wrapping (P<0.01). Moreover, the number of animals lateralized on turning (P<0.01), leading limb (P<0.05), mouth use (P<0.01), and prey capture (P<0.01) was greater than would be expected by chance alone. There was consistency in the strength and direction of hand biases across different postures. Tasks requiring hand use were more strongly lateralized than tasks not involving hand use (P<0.001). The data do not support the assumption that arousal (as subjectively categorized) or novelty strengthens lateralized responding. The results of this study are discussed in terms of the effects of arousal, posture, and age on lateralized behavior. Am. J. Primatol. 72:206–216, 2010. © 2009 Wiley‐Liss, Inc.     

Structural and functional characterization of a triple mutant form of S100A7 defective for Jab1 binding

S100A7 (psoriasin) is a calcium‐ and zinc‐binding protein implicated in breast cancer. We have shown previously that S100A7 enhances survival mechanisms in breast cells through an interaction with c‐jun activation domain binding protein 1 (Jab1), and an engineered S100A7 triple mutant (Asp⁵⁶Gly, Leu⁷⁸Met, and Gln⁸⁸Lys—S100A7₃) ablates Jab1 binding. We extend these results to include defined breast cancer cell lines and demonstrate a disrupted S100A7₃/Jab1 phenotype is maintained. To establish the basis for the abrogated Jab1 binding, we have recombinantly produced S100A7₃, demonstrated that it retains the ability to form an exceptionally thermostable dimer, and solved the three dimensional crystal structure to 1.6 Å. Despite being positioned at the dimer interface, the Leu⁷⁸Met mutation is easily accommodated and contributes to a methionine‐rich pocket formed by Met¹², Met¹⁵, and Met³⁴. In addition to altering the surface charge, the Gln⁸⁸Lys mutation results in a nearby rotameric shift in Tyr⁸⁵, leading to a substantially reorganized surface cavity and may influence zinc binding. The final mutation of Asp⁵⁶ to Gly results in the largest structural perturbation shortening helix IV by one full turn. It is noteworthy that position 56 lies in one of two divergent clusters between S100A7 and the functionally distinct yet highly homologous S100A15. The structure of S100A7₃ provides a unique perspective from which to characterize the S100A7‐Jab1 interaction and better understand the distinct functions between S100A7, and it is closely related paralog S100A15.     

Are healthcare workers in England and Wales at increased risk of tuberculosis?

OBJECTIVE: To determine whether healthcare workers in England and Wales are at increased risk of tuberculosis and to examine the frequency of drug resistance in this population. DESIGN: Comparison of notification rates by occupation obtained from national tuberculosis notification surveys in 1988 and 1993, with denominators from the 1991 census. SUBJECTS: People with notified tuberculosis in professional and associate professional occupations from the two surveys. MAIN OUTCOME MEASURES: Rates of notified tuberculosis in health professionals (mainly doctors) and health associate professionals (mainly nurses) compared with rates in other professional and associate professional occupations, adjusted for ethnic group, sex, and age. RESULTS: 119 cases of tuberculosis were identified in healthcare workers, including 61 nurses and 42 doctors. The crude notification rate in healthcare workers was 11.8 per 100,000 per year (95% confidence interval 9.8 to 14.1) compared with 3.3 per 100,000 per year (2.9 to 3.6) in other professional and associate professional occupations; rate ratios were higher (range 1.7 to 3.2) in all ethnic groups. The relative risk adjusted for ethnic group, sex, and age was 2.4 (95% confidence interval 2.0 to 3.0), slightly higher for health professionals (2.7 (1.9 to 3.8)) than for associate professionals (2.0 (1.5 to 2.6)). No multiple drug resistant strains of tuberculosis were identified in healthcare workers. CONCLUSIONS: Better detection and notification of cases of tuberculosis in healthcare workers may account for some of the apparent increased risk, but these findings imply that tuberculosis remains a hazard for healthcare workers and highlight the importance of ensuring that occupational health monitoring and protection workers are not neglected.     

Ixodes scapularis Say on white-tailed deer (Odocoileus virginianus) from Long Point, Ontario.

Ixodes scapularis Say was the only species of tick found on white-tailed deer, Odocoileus virginianus, collected at Long Point, Ontario from October 1972 to August 1973. Adults were most abundant from September 1972 to April 1973. Larvae were found throughout the study period except during February. Nymphs were scarce during winter months but fairly common during spring and summer. Most adults were found on the neck and shoulders. Larvae occurred mainly on lower regions of the body and nymphs mainly on the head, shoulders, forelegs and brisket.     

THE SUSCEPTIBILITY OF THE PLANT CELL TO VIRUS DISEASE

A number of spraying experiments showed that the virus cannot enter a plant unless some of the cells are injured. It is not essential that such injury should be brought about in the presence of the virus. The chances of infection fall off rapidly in the first few minutes after injury, but infection occurs occasionally as long as half an hour after the cell is damaged.
Inoculations by micropipette into single cells of the host plant yielded only about one-tenth of the expected number of infections. This suggests differences in the susceptibility of the cells to virus attack.