Fission yeast centromeres vary in size but are organized in a similar fashion. Each consists of two distinct domains, namely, the -15-kilobase (kb) central region (cnt + imr), containing chromosome-specific low copy number sequences, and 20-to 100-kb outer surrounding sequences (otr) with highly repetitive motifs common to all centromeres. The central region consists of an inner asymmetric sequence flanked by inverted repeats that exhibit strict identity with each other. Nucleotide changes in the left repeat are always accompanied with the same changes in the right. The chromatin structure of the central region is unusual. A nucleosomal nuclease digestion pattern formed on unstable plasmids but not on stable chromosome. DNase I hypersensitive sites correlate with the location of tRNA genes in the central region. Autonomously replicating sequences are also present in the central region. The behavior of truncated minichromosomes suggested that the central region is essential, but not sufficient, to confer transmission stability. A portion of the outer repetitive region is also required. A larger outer region is necessary to ensure correct meiotic behavior. Fluorescence in situ hybridization identified individual cens. In the interphase, they cluster near the nuclear periphery. The central sequence (cnt + imr) may play a role in positioning individual chromosomes within the nucleus, whereas the outer regions (otr) may interact with each other to form the higher-order complex structure.
Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf mutant stock are resistant, in vitro, to the cytotoxic effects of H2O2, cadmium, UV light, paraquat, and heat. We show here that similar resistance profiles are seen in fibroblast cells derived from a related mutant, the Ames dwarf mouse, and that cells from growth hormone receptor-null mice are resistant to H2O2, paraquat, and UV but not to cadmium. Resistance to UV light, cadmium, and H2O2are similar in cells derived from 1-wk-old Snell dwarf or normal mice, and thus the resistance of cell lines derived from young adult donors reflects developmental processes, presumably hormone dependent, that take place in the first few months of life. The resistance of cells from Snell dwarf mice to these stresses does not reflect merely antioxidant defenses: dwarf-derived cells are also resistant to the DNA-alkylating agent methyl methanesulfonate. Furthermore, inhibitor studies show that fibroblast resistance to UV light is unaffected by the antioxidants ascorbic acid and N-acetyl-l-cysteine. These data suggest that postnatal exposure to altered levels of pituitary hormones leads to development of cellular resistance to oxidative and nonoxidative stressors, which are stable through many rounds of in vitro cell division and could contribute to the remarkable disease resistance of long-lived mutant mice.
Mutations that extend nematode longevity by interference with IGF-I/insulin sensing pathways also lead to resistance to multiple forms of stress. Here, we report that skin-derived fibroblasts from Snell dwarf mice, already known to show increased longevity and delayed aspects of aging, are resistant to multiple forms of cellular stress, including UV light, heat, paraquat, H2O2, and the toxic metal cadmium. The findings suggest that increases in cellular resistance to stress may mediate extended longevity in mammals.
In the afternoon of March 11, 2011, the eastern Japan was severely attacked by the 2011 off the Pacific coast of Tohoku earthquake (the Great East Japan earthquake). Nearly 30,000 people were killed or are still missing by that earthquake and the ensuing monster tsunami as of April 11, 2011. This paper reports some aspects of this devastating earthquake which hit an advanced country in seismic resistant design. It has been reported that long-period ground motions were induced in Tokyo, Nagoya and Osaka. The properties of these long-period ground motions are discussed from the viewpoint of critical excitation and the seismic behavior of two steel buildings of 40 and 60 stories subjected to the long-period ground motion recorded at Shinjuku, Tokyo is determined and discussed. This paper also reports the effectiveness of visco-elastic dampers like high-hardness rubber dampers in the reduction of responses of super high-rise buildings subjected to such long-period ground motions. The response reduction rate is investigated in detail in addition to the maximum response reduction. In December 2010 before this earthquake, simulated long-period ground motions for earthquake resistant design of high-rise buildings were provided in three large cities in Japan (Tokyo, Nagoya and Osaka) and nine areas were classified. Two 40-story steel buildings (slightly flexible and stiff) are subjected to these long-period ground motions in those nine areas for the detailed investigation of response characteristics of super high-rise buildings in various areas.
Mutations in the insulin/IGF-1 neuroendocrine pathway extend lifespan and affect development, metabolism, and other biological processes in Caenorhabditis elegans and in other species. In addition, they may play a role in learning and memory. Investigation of the insulin/IGF-1 pathway may provide clues for the prevention of age-related declines in cognitive functions. Here, we examined the effects of the life-extending (Age) mutations, such as the age-1 (phosphatidylinositol 3-OH kinase) and daf-2 (insulin/IGF-1 receptor) mutations, on associative learning behavior called isothermal tracking. This thermotaxis learning behavior associates paired stimuli, temperature, and food. The age-1 mutation delayed the age-related decline of isothermal tracking, resulting in a 210% extension of the period that ensures it. The effect is dramatic compared with the extension of other physiological health spans. In addition, young adults of various Age mutants (age-1, daf-2, clk-1, and eat-2) showed increased consistency of temperature-food association, which may be caused by a common feature of the mutants, such as the secondary effects of life extension (i.e., enhanced maintenance of neural mechanisms). The age-1 and daf-2 mutants but not the other Age mutants showed an increase in temperature-starvation association through a different mechanism. Increased temperature-food association of the daf-2 mutant was dependent on neuronal Ca 2ϩ -sensor ncs-1, which modulates isothermal tracking in the AIY interneuron. Interestingly, mutations in the daf-7 TGF␤ gene, which functions in parallel to the insulin/IGF-1 pathway, caused deficits in acquisition of temperature-food and temperature-starvation association. This study highlights roles of the Age mutations in modulation of certain behavioral plasticity.
In the last decade it has become evident that many laboratory manipulations, both genetic and environmental, can lead to significant life extension. All or almost all of the observed life-extension phenotypes are associated with increased resistance and/or ability to respond to environmental stress. These observations show dramatically that life span is not maximized. We suggest that latent within many species-perhaps even humans-is the ability for large increases of life expectancy. The striking correlation between the increased stress resistance of all long-lived mutants in C. elegans and other species and the increased resistance of dietary restricted rodents to environmental toxins is consistent with an evolutionary conservation of a life-span maintenance/environmental stress resistance program. We suggest that it may be possible to develop methods for life extension in mammals, including humans, using relatively straightforward manipulations, such as drug treatments. It should be obvious that these findings have tremendous implications for human society at large, and we suggest that the implications of these findings should be explored.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.