University of North Carolina at Chapel Hill

About: University of North Carolina at Chapel Hill is a education organization based out in Chapel Hill, North Carolina, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 81393 authors who have published 185327 publications receiving 9948508 citations. The organization is also known as: University of North Carolina & North Carolina.

Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair

Abstract: The genomes of all eukaryotes contain tracts of DNA in which a single base or a small number of bases is repeated. Expansions of such tracts have been associated with several human disorders including the fragile X syndrome. In addition, simple repeats are unstable in certain forms of colorectal cancer, suggesting a defect in DNA replication or repair. We show here that mutations in any three yeast genes involved in DNA mismatch repair (PMS1, MLH1 and MSH2) lead to 100- to 700-fold increases in tract instability, whereas mutations that eliminate the proof-reading function of DNA polymerases have little effect. The meiotic stability of the tracts is similar to the mitotic stability. These results suggest that tract instability is associated with DNA polymerases slipping during replication, and that some types of colorectal cancer may reflect mutations in genes involved in DNA mismatch repair.

Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a.

Abstract: Stem-cell ageing is thought to contribute to altered tissue maintenance and repair. Older humans experience increased bone marrow failure and poorer haematologic tolerance of cytotoxic injury. Haematopoietic stem cells (HSCs) in older mice have decreased per-cell repopulating activity, self-renewal and homing abilities, myeloid skewing of differentiation, and increased apoptosis with stress. Here we report that the cyclin-dependent kinase inhibitor p16INK4a, the level of which was previously noted to increase in other cell types with age, accumulates and modulates specific age-associated HSC functions. Notably, in the absence of p16INK4a, HSC repopulating defects and apoptosis were mitigated, improving the stress tolerance of cells and the survival of animals in successive transplants, a stem-cell-autonomous tissue regeneration model. Inhibition of p16INK4a may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue.

Search for Majorana Neutrinos Near the Inverted Mass Hierarchy Region with KamLAND-Zen.

Abstract: We present an improved search for neutrinoless double-beta (0νββ) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>1.07×10^{26} yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.