Revealing hidden interval graph structure in STS-content data.

MOTIVATION: STS-content data for genomic mapping contain numerous errors and anomalies resulting in cross-links among distant regions of the genome. Identification of contigs within the data is an important and difficult problem. RESULTS: This paper introduces a graph algorithm which creates a simplified view of STS-content data. The shape of the resulting structure graph provides a quality check - coherent data produce a straight line, while anomalous data produce branches and loops. In the latter case, it is sometimes possible to disentangle the various paths into subsets of the data covering contiguous regions of the genome, i.e. contigs. These straight subgraphs can then be analyzed in standard ways to construct a physical map. A theoretical basis for the method is presented along with examples of its application to current STS data from human genome centers. AVAILABILITY: Freely available on request.     

Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging

BACKGROUND: Concern has been raised about the potential for adverse cognitive effects associated with the use of calcium-channel blockers (CCBs) in older people. This study was undertaken to examine prospectively the association between the use of these and other antihypertensive drugs and cognitive function. METHODS: The authors examined data from the Canadian Study of Health and Aging (CSHA), a population-based, prospective 5-year investigation of the epidemiology of dementia and other health problems in Canadians 65 years of age and older. The risk of cognitive decline, as indicated by a decline in performance on the Modified Mini-Mental State (3MS) examination over the 5-year period, was assessed in relation to the use of antihypertensive and diuretic drugs by 205 subjects with a history of hypertension and no evidence of dementia at baseline. RESULTS: The proportion of subjects whose cognitive performance declined over the study period was significantly higher in the group using CCBs than in the group using other antihypertensive agents (75% v. 59%). The adjusted odds ratio (OR) for a significant decline in cognitive performance (defined as a decrease in 3MS score of 10 points or more) was 2.28 (95% confidence interval [CI] 1.12-4.66) for subjects using CCBs. The adjusted ORs (and 95% CIs) for cognitive decline in subjects using selected antihypertensive agents or diuretics relative to those exposed to beta-blockers were as follows: angiotensin-converting-enzyme inhibitor, OR 1.36 (95% CI 0.41-4.55); diuretic or other antihypertensive drug, OR 1.45 (95% CI 0.51-4.14); dihydropyridine CCB (nifedipine), OR 1.94 (95% CI 0.52-7.27) and non-dihydropyridine CCB (diltiazem or verapamil), OR 3.72 (95% CI 1.22-11.36). INTERPRETATION: Older people taking CCBs were significantly more likely than those using other agents to experience cognitive decline. These findings are consistent with the results of previous cross-sectional research and emphasize the need for further trials to examine the associations between CCB use, blood pressure and cognitive impairment in elderly patients.     

α‐ketoglutarate delays age‐related fertility decline in mammals

The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.