Xeroderma pigmentosum complementation group C protein (XPC) serves as a general sensor of damaged DNA

The Xeroderma pigmentosum complementation group C protein (XPC) serves as the primary initiating factor in the global genome nucleotide excision repair pathway (GG-NER). Recent reports suggest XPC also stimulates repair of oxidative lesions by base excision repair. However, whether XPC distinguishes among various types of DNA lesions remains unclear. Although the DNA binding properties of XPC have been studied by several groups, there is a lack of consensus over whether XPC discriminates between DNA damaged by lesions associated with NER activity versus those that are not. In this study we report a high-throughput fluorescence anisotropy assay used to measure the DNA binding affinity of XPC for a panel of DNA substrates containing a range of chemical lesions in a common sequence. Our results demonstrate that while XPC displays a preference for binding damaged DNA, the identity of the lesion has little effect on the binding affinity of XPC. Moreover, XPC was equally capable of binding to DNA substrates containing lesions not repaired by GG-NER. Our results suggest XPC may act as a general sensor of damaged DNA that is capable of recognizing DNA containing lesions not repaired by NER.     

The Association between Cultural Orientation and Drinking Behaviors among University Students in Wuhan,China

Objectives

This study examines the association between cultural orientation and drinking behaviors among university students. Cultural orientation is the measure of how the cultural values of individuals living in their own society are influenced by cultural values introduced from the outside.

Methods

In 2011, a cross-sectional survey collected data from 1279 university students from six universities in central China. Participants used a likert scale to rank a series of statements reflecting cultural values from the previously validated Chinese Cultural Orientation Scale and answered questions about their drinking behaviors and socio-demographic characteristics.

Results

Statistically significant differences in cultural orientation were observed for gender, hometown and type of university attendance. Traditional-oriented students were more likely to be occasional drinkers or nondrinkers, while marginal-oriented students, bicultural-oriented students and western-oriented students were more likely to be regular drinkers. Bicultural orientation (OR = 1.80, P<0.05) and marginal orientation (OR = 1.64, P<0.05) increased the likelihood of the student being regular drinking, compared to students with traditional orientations. Males (OR = 4.40, P<0.05) had a higher likelihood of regular drinking than females, graduate students (OR = 2.59, P<0.05) had a higher likelihood of regular drinking than undergraduates, students from urban areas (OR = 1.79, P<0.05) had a higher likelihood of regular drinking than those from towns/rural areas, and students attending key universities (OR = 0.48, P<0.05) had a lower likelihood of regular drinking than those attending general universities.

Conclusions

Cultural orientation influences drinking behaviors. Traditional cultural orientation was associated with less drinking while western cultural orientation, marginal cultural orientation and bicultural orientation were associated with more drinking. The role of gender, hometown and university attendance is partially moderated through the influence of cultural orientation. The relationship between a traditional cultural orientation and alcohol drinking suggests that traditional Chinese cultural values should be examined for their role in possibly reducing alcohol-related risks through education and policy initiatives.     

Recent and rapid diversification of the small carpenter bees in eastern North America

Bees fulfil a critical ecological role as pollinators, significantly contributing to the reproductive success of myriad angiosperm species. Although increasingly appreciated for their agricultural contributions, relatively little is yet known about the natural history of the vast majority of the more than 20 000 wild bee species worldwide. The small carpenter bee genus Ceratina occurs globally, and is represented in North America by its most recently diverged subgenera, Ceratinula and Zadontomerus. Recent genetic analysis of eastern Ceratina (Zadontomerus) supports the existence of five closely related, yet genetically distinct species living in sympatry. This phylogeographical study employs molecular barcoding of the most comprehensive specimen collection yet assembled to confirm the identities of these recently diverged eastern North American Ceratina (Zadontomerus) species. Delineation of extant population structure, evolutionary history and known range of this emerging model native pollinator are greatly improved by this study. We consider ecological and behavioural factors potentially contributing to the maintenance of genetic identity among these sympatric species.     

A model of canine leukocyte telomere dynamics

Recent studies have found associations of leukocyte telomere length (TL) with diseases of aging and with longevity. However, it is unknown whether birth leukocyte TL or its age-dependent attrition--the two factors that determine leukocyte TL dynamics--explains these associations because acquiring this information entails monitoring individuals over their entire life course. We tested in dogs a model of leukocyte TL dynamics, based on the following premises: (i) TL is synchronized among somatic tissues; (ii) TL in skeletal muscle, which is largely postmitotic, is a measure of TL in early development; and (iii) the difference between TL in leukocytes and muscle (ΔLMTL) is the extent of leukocyte TL shortening since early development. Using this model, we observed in 83 dogs (ages, 4-42 months) no significant change with age in TLs of skeletal muscle and a shorter TL in leukocytes than in skeletal muscle (P<0.0001). Age explained 43% of the variation in ΔLMTL (P<0.00001), but only 6% of the variation in leukocyte TL (P=0.035) among dogs. Accordingly, muscle TL and ΔLMTL provide the two essential factors of leukocyte TL dynamics in the individual dog. When applied to humans, the partition of the contribution of leukocyte TL during early development vs. telomere shortening afterward might provide information about whether the individual's longevity is calibrated to either one or both factors that define leukocyte TL dynamics.     

DNA damage recognition of mutated forms of UvrB proteins in nucleotide excision repair

The DNA repair protein UvrB plays an indispensable role in the stepwise and sequential damage recognition of nucleotide excision repair in Escherichia coli. Our previous studies suggested that UvrB is responsible for the chemical damage recognition only upon a strand opening mediated by UvrA. Difficulties were encountered in studying the direct interaction of UvrB with adducts due to the presence of UvrA. We report herein that a single point mutation of Y95W in which a tyrosine is replaced by a tryptophan results in an UvrB mutant that is capable of efficiently binding to structure-specific DNA adducts even in the absence of UvrA. This mutant is fully functional in the UvrABC incisions. The dissociation constant for the mutant-DNA adduct interaction was less than 100 nM at physiological temperatures as determined by fluorescence spectroscopy. In contrast, similar substitutions at other residues in the beta-hairpin with tryptophan or phenylalanine do not confer UvrB such binding ability. Homology modeling of the structure of E. coli UvrB shows that the aromatic ring of residue Y95 and only Y95 directly points into the DNA binding cleft. We have also examined UvrB recognition of both "normal" bulky BPDE-DNA and protein-cross-linked DNA (DPC) adducts and the roles of aromatic residues of the beta-hairpin in the recognition of these lesions. A mutation of Y92W resulted in an obvious decrease in the efficiency of UvrABC incisions of normal adducts, while the incision of the DPC adduct is dramatically increased. Our results suggest that Y92 may function differently with these two types of adducts, while the Y95 residue plays an unique role in stabilizing the interaction of UvrB with DNA damage, most likely by a hydrophobic stacking.     

Studies on antigenic competition. V. Evidence for the involvement of a thymic-derived cortisone-sensitive cell in the mediation of antigenic competition

Animals depleted of lymphoid subpopulations by neonatal thymectomy, by adult thymectomy, irradiation, and bone marrow reconstitution, or by hydrocortisone treatment did not exhibit antigenic competition. In contrast, injection of anti-lymphocyte serum, while depressing the magnitude of the immune response, did not effect antigenic competition. It is concluded that a thymic-dependent cortisone-sensitive cell population is involved in the initiation of antigenic competition.