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Biomedical subjects

Sarah A Martin

Publications and source records attributed to Sarah A Martin.

6 recordsLinked to original sources
PubMed2006

ATM activation by ionizing radiation requires BRCA1-associated BAAT1.

ATM (ataxia telangiectasia mutated) is required for the early response to DNA-damaging agents such as ionizing radiation (IR) that induce DNA double-strand breaks. Cells deficient in ATM are extremely sensitive to IR. It has been shown that IR induces immediate phosphorylation of ATM at Ser(1981), leading to catalytic activation of the protein. We recently isolated a novel BRCA1-associated protein, BAAT1 (BRCA1-associated protein required for ATM activation-1), by yeast two-hybrid screening and found that BAAT1 also binds to ATM, localizes to double-strand breaks, and is required for Ser(1981) phosphorylation of ATM. Small interfering RNA-mediated stable or transient reduction of BAAT1 resulted in decreased phosphorylation of both ATM at Ser(1981) and CHK2 at Thr(68). Treatment of BAAT1-depleted cells with okadaic acid greatly restored phosphorylation of ATM at Ser(1981), suggesting that BAAT1 is involved in the regulation of ATM phosphatase. Protein phosphatase 2A-mediated dephosphorylation of ATM was partially blocked by purified BAAT1 in vitro. Significantly, acute loss of BAAT1 resulted in increased p53, leading to apoptosis. These results demonstrate that DNA damage-induced ATM activation requires a coordinated assembly of BRCA1, BAAT1, and ATM.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2005

BRCA1 phosphorylation regulates caspase-3 activation in UV-induced apoptosis.

Apoptosis is implemented by death machinery that involves the caspase family of proteins, under the condition of a variety of stresses. Previous studies have shown that mouse embryonic stem cells deficient for caspase-3 are resistant to UV-induced apoptosis and that the active form of caspase-3 translocates to the nucleus. It has also been shown that the breast cancer tumor suppressor, BRCA1, is phosphorylated on Ser1423 and Ser1524 by the ataxia telangiectasia mutated-related kinase (ATR) after UV damage. Here, we show that activation of caspase-3 by UV is abrogated in BRCA1-mutated SNU251 and HCC1937 cells but was restored by reexpressing wild-type (wt) BRCA1, but not phosphorylation-deficient BRCA1Ser1423Ala/Ser1524Ala (BRCA1(S1423/1524A)). In SNU251 cells expressing BRCA1(S1423/1524A), the inhibitory interaction between X-linked inhibitor of apoptosis protein (XIAP) and caspase-9 remains intact after UV, compared with cells expressing wt BRCA1. We determined that XIAP and BRCA1 interact and upon phosphorylation this complex is disrupted. Nuclear translocation of active caspase-3 is detected only when wt BRCA1 is reexpressed. Consistent with this, Rad21, a known substrate of caspase-3, is cleaved only when wt BRCA1 is expressed in vivo. These results propose a model that inhibition of BRCA1 phosphorylation leads to the abrogation of a specific form of apoptosis that is mediated by caspase-3.

Apoptosis↗
PubMed2002

EST-based identification of genes expressed in the liver of adult Atlantic salmon (Salmo salar).

A list of genes expressed in the liver of Atlantic salmon was compiled using the expressed sequence tag (EST) strategy. 733 ESTs, derived from 170 abundant and 563 rare mRNA encoding liver cDNA clones, were determined. Bioinformatic analysis revealed that 390 (53%) of the salmon liver ESTs could be ascribed to the transcriptional products of 93 identified genes including 7 previously described in the Atlantic salmon. The identified Atlantic salmon genes were classified with respect to cellular role which showed that 33 (36%) of the identified genes encoded proteins associated with primary liver functions such as transport, acute phase response, and blood clotting. Furthermore, comparative analysis revealed that 12 of the 16 salmon genes that were shown to encode abundant mRNA transcripts in liver had homologues that have also been shown to be highly expressed in mammalian liver systems. Finally, two cDNA variants corresponding to the two cDNA forms of the apolipoprotein A-I gene previously identified in rainbow trout were also found in Atlantic salmon.

Amino Acid Sequence↗
PubMedDate not supplied

Shake, rattle, and roll.

Explore the source record for details and available documents.

Abnormalities, Multiple↗
PubMedDate not supplied

Can there be a standard for temperature measurement in the pediatric intensive care unit?

Temperature measurement is a commonly used assessment parameter when caring for the critically ill child. Interpreting the temperature measurement mode and what constitutes clinically significant thermal instability are poorly defined. Thus, decisions made regarding patient management based on temperature measurement can be challenging for caregivers. Infants and children have unique physioanatomic considerations that impact maintaining thermoregulation. Numerous routes for taking temperature measurements are described including the oral, axillary, tympanic (aural), rectal, skin, urinary bladder, pulmonary artery, esophageal, nasopharyngeal, supralingual (pacifier), and temporal-artery. Numerous studies on temperature measurement have been conducted on children of various ages using a variety of thermometers and routes in both the inpatient and outpatient setting. Although there are limited studies reported on the critically ill child, research data pertinent to the critically ill child from subjects in the neonatal intensive care unit, pediatric intensive care unit, operating room, and inpatient units are summarized.

Body Temperature↗