Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages.

The known activities of NSC109268 as proteasome or phosphatase inhibitor could explain the phenotype of S-phase delay by assuming a higher initial DNA damage load, inhibition of DNA translesion synthesis or extended checkpoint arrest.

Asian elders make relatively heavy use of health services: this may be due to higher levels of morbidity, but controlled comparisons have not been carried out. A comparison of the prevalence and severity of chronic diseases and use of health services of Asian and indigenous elders was made. A sample of 59 Gujarati Asians of mean age 62.9 years and 59 indigenous subjects of mean age 63.9 years of whom 42% (25 in each group) were female drawn from a general practice was studied. Asian subjects had a higher prevalence of diagnosed diseases, with the exception of chronic obstructive airways disease, but lower risk of falls and urinary incontinence. Asian subjects had higher life satisfaction scores and lower prevalence of depressed mood. Asian women were more likely to have had contact with primary care services. Both Asian men and women had more frequent hospital admissions, but similar levels of out-patient attendance. Body mass index, blood pressure and shoulder joint range of movement were similar for both Asians and the indigenous population. Asian subjects had significantly lower peak expiratory flow rates and hand grip strength. Asian elders have a higher risk of chronic diseases, but the impact of disease (indicated by life satisfaction, mood, and common disabilities) is less than among the indigenous population. Lower peak expiratory flow rates and grip strength among Asian elders are of concern since they may lead to premature arrival at age-related thresholds of physical capacity essential for independence in activities of daily living.

Stationary phase Saccharomyces cerevisiae can serve as a model for postmitotic cells of higher eukaryotes. Phosphorylation and activation of the checkpoint kinase Rad53 was observed after more than 2 days of culture if two major pathways of oxidative DNA damage repair, base excision repair (BER) and nucleotide excision repair (NER), are inactive. The wild type showed a low degree of Rad53 phosphorylation when the incubation period was drastically increased. In the ber ner strain, Rad53 phosphorylation can be abolished by inclusion of antioxidants or exclusion of oxygen. Furthermore, this modification and enhanced mutagenesis in extended stationary phase were absent in rho° strains, lacking detectable mitochondrial DNA. This checkpoint response is therefore thought to be dependent on reactive oxygen species originating from mitochondrial respiration. There was no evidence for progressive overall telomere shortening during stationary-phase incubation. Since Rad50 (of the MRN complex) and Mec1 (the homolog of ATR) were absolutely required for the observed checkpoint response, we assume that resected random double-strand breaks are the critical lesion. Single-strand resection may be accelerated by unrepaired oxidative base damage in the vicinity of a double-strand break.