Features of Chronic Bronchitis in Different Age Groups

Background: Lung diseases are assuming greater relevance and importance today. Chronic bronchitis is a self-nosology, which may precede the development of COPD, the importance of which can hardly be overestimated. The main problem in this disease is caused by late diagnosis and treatment due to the delay by patients in seeking medical help. The aim of the work was to study the distribution and exposure to tobacco smoke, especially chronic bronchitis, depending on various factors, including age. Methods: We examined 1779 persons, including 855 men and 924 women. The mean age of the population was 35.83±8.3 years. We conducted surveys and spirometry. The outcome was assessed after a bronchodilation test was performed with salbutamol 400 mcg. We performed all statistical analysis using software package Statistica 10. Results: We identified chronic bronchitis in 9.2% of the cases in the group of younger individuals and in 14.9% of the cases in the group of older individuals, during the active detection of chronic bronchitis using questionnaires. The prevalence of cigarette smoking was slightly higher among the younger (39.5%) than the older persons (33.6%); the frequency of smoking in a group of chronic bronchitis was reliably higher. Also, in this group, the performance spirometry reliably decreased. Conclusions: Outpatient survey is an effective method of identifying chronic bronchitis. Smoking is a major risk factor in the group of young respondents and the prevalence of smoking is inversely related to the education level of the respondents, regardless of age. As the decline in the Forced Expiratory Volume (FEV1 and FEV1/FVC) is the main criterion diagnosis of COPD, it revealed significant declines in the FEV1 of the younger smoking individuals, which may help to predict the development of COPD in the older age group

NMR Structure and Dynamics of the C-Terminal Domain from Human Rev1 and Its Complex with Rev1 Interacting Region of DNA Polymerase η

Rev1 is a translesion synthesis (TLS) DNA polymerase essential for DNA damage tolerance in eukaryotes. In the process of TLS stalled high-fidelity replicative DNA polymerases are temporarily replaced by specialized TLS enzymes that can bypass sites of DNA damage (lesions), thus allowing replication to continue or postreplicational gaps to be filled. Despite its limited catalytic activity, human Rev1 plays a key role in TLS by serving as a scaffold that provides an access of Y-family TLS polymerases polη, ι, and κ to their cognate DNA lesions and facilitates their subsequent exchange to polζ that extends the distorted DNA primer–template. Rev1 interaction with the other major human TLS polymerases, polη, ι, κ, and the regulatory subunit Rev7 of polζ, is mediated by Rev1 C-terminal domain (Rev1-CT). We used NMR spectroscopy to determine the spatial structure of the Rev1-CT domain (residues 1157–1251) and its complex with Rev1 interacting region (RIR) from polη (residues 524–539). The domain forms a four-helix bundle with a well-structured N-terminal β-hairpin docking against helices 1 and 2, creating a binding pocket for the two conserved Phe residues of the RIR motif that upon binding folds into an α-helix. NMR spin-relaxation and NMR relaxation dispersion measurements suggest that free Rev1-CT and Rev1-CT/polη-RIR complex exhibit μs-ms conformational dynamics encompassing the RIR binding site, which might facilitate selection of the molecular configuration optimal for binding. These results offer new insights into the control of TLS in human cells by providing a structural basis for understanding the recognition of the Rev1-CT by Y-family DNA polymerases.National Institute of Environmental Health Sciences (ES015818)Massachusetts Institute of Technology. Center for Environmental Health Sciences (Grant P30 ES002109