1010 N. Kansas Wcgme
Wichita KS 67214
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 7150
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SMARCAL1 and telomeres: Replicating the troublesome ends. - Nucleus (Austin, Tex.)
DNA replication is constantly challenged by both endogenous and exogenous sources of replication stress. SMARCAL1, an SNF2 family DNA translocase, functions in the DNA damage response to address these obstacles and promote the completion of replication. Most studies examining the function of SMARCAL1 and related enzymes have relied on the addition of exogenous genotoxic agents, but SMARCAL1 is needed even in the absence of these drugs to maintain genome stability during DNA replication. We recently determined that SMARCAL1 functions to limit DNA damage during replication of difficult-to-replicate telomere sequences. SMARCAL1-deficient cells display several markers of telomere instability including extrachromosomal telomere circles and co-localization with DNA damage markers. Furthermore, cells lacking the highly related proteins ZRANB3 and HLTF do not exhibit similar problems suggesting a unique function for SMARCAL1. These studies identified the first source of endogenous replication stress that SMARCAL1 resolves and provide insight into the mechanism of SMARCAL1 function in maintaining genome stability.
SMARCAL1 maintains telomere integrity during DNA replication. - Proceedings of the National Academy of Sciences of the United States of America
The SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) DNA translocase is one of several related enzymes, including ZRANB3 (zinc finger, RAN-binding domain containing 3) and HLTF (helicase-like transcription factor), that are recruited to stalled replication forks to promote repair and restart replication. These enzymes can perform similar biochemical reactions such as fork reversal; however, genetic studies indicate they must have unique cellular activities. Here, we present data showing that SMARCAL1 has an important function at telomeres, which present an endogenous source of replication stress. SMARCAL1-deficient cells accumulate telomere-associated DNA damage and have greatly elevated levels of extrachromosomal telomere DNA (C-circles). Although these telomere phenotypes are often found in tumor cells using the alternative lengthening of telomeres (ALT) pathway for telomere elongation, SMARCAL1 deficiency does not yield other ALT phenotypes such as elevated telomere recombination. The activity of SMARCAL1 at telomeres can be separated from its genome-maintenance activity in bulk chromosomal replication because it does not require interaction with replication protein A. Finally, this telomere-maintenance function is not shared by ZRANB3 or HLTF. Our results provide the first identification, to our knowledge, of an endogenous source of replication stress that requires SMARCAL1 for resolution and define differences between members of this class of replication fork-repair enzymes.
An audit of the use of the Barthel Index in palliative care. - International journal of palliative nursing
The Barthel Index (Mahoney and Barthel, 1965) is an objective tool which assesses an individual's ability to perform activities of daily living; for example, personal care, mobility, transfers, bathing and feeding. The purpose of this study was to investigate whether the Index could be used with patients with life-threatening illnesses who are admitted to the inpatient intermediate care unit, to aid clinical practice, establish patients' current level of function, and highlight any progress or deterioration in abilities. The overall aim was to facilitate discharge planning and ensure that patients were managed in their preferred place of care. This was a clearly defined group of patients in a specific clinical area. The authors recognise that to improve consistency of findings, the study may need to be applied to a larger cohort of patients with a greater research emphasis. The article presents the results of an audit of 50 patients. The findings suggest that those patients with a low Barthel score on admission, or those with a score dropping by ten or more per week, are significant predictors of a short prognosis. It concludes that the Barthel Index would be a useful tool in the community to prevent inappropriate admission for those with a low score where the patient wishes to die at home. It could also be used as a monitoring tool to help discharge planning and fast-tracking to the preferred place of care in inpatient settings, and may also assist in community health care (CHC) planning.
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1010 N. Kansas Wcgme Wichita, KS 67214