SEARCH · Search PubMed

Results for “ATR”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources

PubMed2004

Spectroscopic imaging of arteries and atherosclerotic plaques.

Fourier transform infrared (FTIR) spectroscopic imaging using a focal plane array detector has been used to study atherosclerotic arteries with a spatial resolution of 3-4 microm, i.e., at a level that is comparable with cellular dimensions. Such high spatial resolution is made possible using a micro-attenuated total reflection (ATR) germanium objective with a high refractive index and therefore high numerical aperture. This micro-ATR approach has enabled small structures within the vessel wall to be imaged for the first time by FTIR. Structures observed include the elastic lamellae of the tunica media and a heterogeneous distribution of small clusters of cholesterol esters within an atherosclerotic lesion, which may correspond to foam cells. A macro-ATR imaging method was also applied, which involves the use of a diamond macro-ATR accessory. This study of atherosclerosis is presented as an illustrative example of the wider potential of these ATR imaging approaches for cardiovascular medicine and biomedical applications.

Animals↗

PubMed2007

Activation of the S phase DNA damage checkpoint by mitomycin C.

We have studied the rate of DNA synthesis, cell cycle distribution, formation of gamma-H2AX, and Rad51 nuclear foci and association of Rad51 with the nuclear matrix after treatment of HeLa cells with the interstrand crosslinking agent mitomycin C (MMC) in the presence of the kinase inhibitors caffeine and wortmannin. The results showed that MMC treatment arrested the cells in S-phase and induced the appearance of gamma-H2AX and Rad51 nuclear foci, accompanied with a sequestering of Rad51 to the nuclear matrix. These effects were abrogated by caffeine, which inhibits the Ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) kinases. However, wortmannin at a concentration that inhibits ATM, but not ATR did not affect cell cycle progression, damage-induced phosphorylation of H2AX and Rad51 foci formation, and association with the nuclear matrix, suggesting that the S-phase arrest induced by MMC is ATR-dependent. These findings were confirmed by experiments with ATR-deficient and AT cells. They indicate that the DNA damage ATR-dependent S-phase checkpoint pathway may regulate the spatiotemporal organization of the process of repair of interstrand crosslinks.

Androstadienes↗

PubMed1994

Efficacy comparison of scopolamine and diazepam against soman-induced debilitation in guinea pigs.

The efficacy of diazepam (DZ) and scopolamine (SCP), in combination with atropine (ATR)+oxime therapy, against soman-induced seizure/convulsive activity and associated brain damage has been demonstrated, but the efficacy of each against the incapacitating effects of soman has not been addressed. Thus, the therapeutic efficacies of SCP (5 doses; 0-0.86 mg/kg) and DZ (5 doses; 0-5 mg/kg), when each was used in conjunction with ATR (3 doses; 0.5-8 mg/kg) + 2-PAM (25 mg/kg) therapy, were compared in groups of pyridostigmine pretreated guinea pigs exposed to 1.6, 2.0, 2.5, or 3.2 LD50s of soman. Response surface methodology was employed to describe the relationship between soman-induced incapacitation and the ATR/DZ or ATR/SCP dosages. Incapacitation was measured by toxicity scores assigned by three graders to test animals at 60 min postsoman. Results show that as the dosage of SCP increased, the mean toxicity scores decreased. Also, within the indicated dose ranges used, the efficacy of SCP was not dependent on the presence of ATR. In contrast, ATR alone was found to be more effective than when combined with DZ at any dose, and indicates that DZ might be temporarily contributing to soman-induced incapacitation. These findings suggest that in guinea pigs, SCP could replace ATR or DZ, or both, as therapy against soman-induced incapacitation.

Animals↗

PubMed1997

A 370-kb cosmid contig of the serpin gene cluster on human chromosome 14q32.1: molecular linkage of the genes encoding alpha 1-antichymotrypsin, protein C inhibitor, kallistatin, alpha 1-antitrypsin, and corticosteroid-binding globulin.

The human genes encoding alpha 1-antitrypsin (alpha 1AT, gene symbol PI), corticosteroid-binding globulin (CBG), alpha 1-antichymotrypsin (AACT), and protein C inhibitor (PCI) are related by descent, and they all map to human chromosome 14q32.1. This serine protease inhibitor (serpin) gene cluster also contains an antitrypsin-related sequence (ATR, gene symbol PIL), but the precise molecular organization of this region has not been defined. In this report we describe the generation and characterization of an approximately 370-kb cosmid contig that includes all five serpin genes. Moreover, a newly described serpin, kallistatin (KAL, gene symbol PI4), was also mapped within the region. Gene order within this interval is cen-CBG-ATR-alpha 1 AT-KAL-PCI-AACT-tel. The genes occupy approximately 320 kb of genomic DNA, and they are organized into two discrete subclusters of three genes each that are separated by approximately 170 kb. The distal subcluster includes KAL, PCI, and AACT; it occupies approximately 63 kb of DNA, and all three genes are transcribed in a proximal-to-distal orientation. Within the subcluster, there is approximately 12 kb of intergenic DNA between KAL and PCI and approximately 19 kb between PCI and AACT. The proximal subcluster includes alpha 1AT, ATR, and CBG; it occupies approximately 90 kb of genomic DNA, with approximately 12 kb of DNA between alpha 1AT and ATR and approximately 40 kb between ATR and CBG. These genes are all transcribed in a distal-to-proximal orientation. This represents the first detailed physical map of the serpin gene cluster on 14q32.1.

Carrier Proteins↗

PubMed1992

Cumulation and reversal with prolonged infusions of atracurium and vecuronium.

A randomized, double-blind study was undertaken to compare the tendencies for cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC) when administered by continuous infusion for long surgical procedures under balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were free of neuromuscular disease. Patients in the ATR group (n = 25) received a loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at 5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg-1.min-1. During surgery, the infusions of both ATR and VEC were titrated in increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90-95%. Neuromuscular block was measured by recording the integrated evoked electromyographic response (EMG) of the first dorsal interosseous muscle in response to supramaximal TOF stimuli on the ulnar nerve. The durations of infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between 4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC, from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study period. The number of adjustments required to maintain 90-95% T1 suppression decreased between the second and fourth hours of administration, but were similar at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Extrarenal and direct renal actions of atractyloside contribute to its acute nephrotoxicity in pentobarbital-anesthetized dogs.

Acute extrarenal and renal changes were noted following the intravenous administration of atractyloside (ATR) (12.97 and 32.40 mumol/kg) to spontaneously-respiring, pentobarbital-anesthetized dogs. Severe hypoglycemia, respiratory depression and hypoxemia developed within 2 h. These extrarenal changes were accompanied by adverse changes in renal function, ultrastructural damage to S1, S2 and S3 cells of the proximal tubule and to thick ascending limb cells and an impaired ability of the kidneys to respond to a known diuretic--ethacrynic acid (EA). Mechanical ventilation of ATR-treated pentobarbital-anesthetized dogs circumvented the development of hypoxemia and all but eliminated the toxicity to S3 and thick ascending limb cells, thereby establishing that ATR's extrarenal actions contributed to its nephrotoxicity. On the other hand, direct renal actions of ATR were evident following its administration into the renal artery; certain important extrarenal effects were minimized, while adverse changes in renal function and ultrastructure of S1 and S2 cells were noted primarily in the ipsilateral kidney. The high degree of variability associated with ATR's systemic toxicity was confirmed and a similar degree of variability in its renal toxicity was established. Our results emphasize the importance of evaluating the extrarenal effects produced by any toxicant when determining its nephrotoxic potential.

Anesthesia↗

PubMed2004

BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation.

In mammalian spermatogenesis, the X and Y chromosomes are transcriptionally silenced during the pachytene stage of meiotic prophase (meiotic sex chromosome inactivation, MSCI), forming a condensed chromatin domain termed the sex or XY body. The nucleosomal core histone H2AX is phosphorylated within the XY chromatin domain just prior to MSCI, and it has been hypothesized that this triggers the chromatin condensation and transcriptional repression. Here, we show that the kinase ATR localizes to XY chromatin at the onset of MSCI and that this localization is disrupted in mice with a mutant form of the tumor suppressor protein BRCA1. In the mutant pachytene cells, ATR is usually present at nonsex chromosomal sites, where it colocalizes with aberrant sites of H2AX phosphorylation; in these cells, there is MSCI failure. In rare pachytene cells, ATR does locate to XY chromatin, H2AX is then phosphorylated, a sex body forms, and MSCI ensues. These observations highlight an important role for BRCA1 in recruiting the kinase ATR to XY chromatin at the onset of MSCI and provide compelling evidence that it is ATR that phosphorylates H2AX and triggers MSCI.

Animals↗

PubMed2026

Multi-omics analysis reveals coordinated epigenetic dysregulation in atrazine-induced dopaminergic neurotoxicity.

Atrazine (ATR), a widely used triazine herbicide, has been linked to neurotoxicity, yet the epigenetic mechanisms underlying its dopaminergic effects remain unclear. This study investigated whether coordinated miRNA dysregulation and DNA methylation alterations contribute to ATR-induced Parkinson's disease (PD)-like neurotoxicity. Male Sprague-Dawley rats were administered ATR (50 mg/kg/day) for 90 days, resulting in motor and cognitive deficits with dopaminergic dysfunction, including increased α-synuclein and reduced tyrosine hydroxylase expression. Small RNA sequencing identified 72 differentially expressed miRNAs in the substantia nigra, enriched in PI3K-Akt, MAPK, and Ras signaling pathways. In a cohort of six PD patients and six matched controls, genome-wide DNA methylation profiling revealed 4694 differentially methylated positions, predominantly hypomethylated, with overlapping enrichment in neuronal signaling pathways. Weighted gene co-expression network analysis identified a PD-associated module strongly correlated with disease status (r = -0.95, P < 0.001). Multi-omics integration identified CASP3 as a central hub gene. External validation supported CASP3 relevance in PD (AUC = 0.833), and molecular docking suggested potential ATR-CASP3 interaction. Further analysis predicted upregulated miR-3552 as a potential upstream regulator of CASP3. These findings indicate that ATR-induced neurotoxicity may be mediated through the miR-3552/CASP3 signaling axis, ultimately regulating apoptosis and contributing to neurodegeneration.

Animals↗

PubMed2006

Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress.

The ATR-mediated checkpoint is not only critical for responding to genotoxic stress but also essential for cell proliferation. The RFC-related checkpoint protein Rad17, a phosphorylation substrate of ATR, is critical for ATR-mediated checkpoint signaling and cell survival. Here, we show that phosphorylation of Rad17 by ATR is important for genomic stability and restraint of S phase but is not essential for cell survival. The phosphomutant Rad17AA exhibits distinct defects in hydroxyurea- (HU) and ultraviolet- (UV) induced Chk1 activation, indicating that separate Rad17 functions are required differently in response to different types of replication interference. Although cells expressing Rad17AA can initiate Chk1 phosphorylation after HU treatment, they fail to sustain Chk1 phosphorylation after withdrawal of HU and are profoundly sensitive to HU. Importantly, we found that phosphorylated Rad17 interacts with Claspin and regulates its phosphorylation. These findings reveal a phosphorylation-dependent function of Rad17 in an ATR-Rad17-Claspin-Chk1-signaling cascade that responds to specific replication stress.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Comparison of hypoxia-induced replication arrest with hydroxyurea and aphidicolin-induced arrest.

Severe levels of hypoxia (oxygen concentrations of less that 0.02%) have been shown to induce a rapid S-phase arrest. The mechanism behind hypoxia-induced S-phase arrest is unclear, we show here that it was not mediated by a shortage of nucleosides and was not dependent on p53, p21 or Hif 1alpha status. The drugs aphidicolin and hydroxyurea both induce rapid replication arrest and have been used throughout the literature to study the ATR-mediated response to stalled replication. We have shown previously that hypoxia induces ATR-dependent phosphorylation of p53, Chk1 and histone H2AX. Using comet-assays to detect DNA-damage we found that both aphidicolin and hydroxyurea induced significant levels of DNA-damage while hypoxia did not. Here we show that like aphidicolin and hydroxyurea, hypoxia induces phosphorylation of Nbs1 at serine 343 and Rad17 serine 645. Hypoxia-dependent phosphorylation of Nbs1 and Rad17 was ATM-independent and therefore likely to be a result of the ATR kinase activity. In contrast, p53 was phosphorylated differentially in response to the three treatments considered here. p53 was phosphorylated at serine 15 in response to all three treatments but was only phosphorylated at serine 20 in response to the drug treatments. We propose that treatment with either aphidicolin or hydroxyurea leads to not only replication arrest but also DNA-damage and therefore both ATM and ATR-mediated signaling. In contrast replication arrest induced by severe hypoxia is sensed exclusively through ATR, with ATM only having a role to play after re-oxygenation.

Animals↗

PubMed2002

Remodeling of Ca(2+)-handling by atrial tachycardia: evidence for a role in loss of rate-adaptation.

BACKGROUND: Loss of rate-dependent action potential (AP) duration (APD) adaptation is a characteristic feature of atrial tachycardia-induced remodeling (ATR). ATR causes sarcolemmal ion-channel remodeling (ICR) and changes in Ca(2+)-handling. The present studies were designed to quantify Ca(2+)-handling changes and then to apply a mathematical AP model to assess the contributions of Ca(2+)-handling abnormalities and ICR to loss of APD rate-adaptation. METHODS: Indo-1 fluorescence was used to measure intracellular Ca(2)-transients and whole-cell patch-clamp to record APs in atrial myocytes from control dogs and dogs subjected to atrial pacing at 400/min for 6 weeks. A previously developed ionic model of the canine atrial AP was modified to reproduce measured Ca(2+)-transients of control and ATR myocytes. RESULTS: In control, APD to 95% repolarization (APD(95)) decreased by 91 ms experimentally and by 88 ms in the model over the 1-6 Hz range. In ATR myocytes, APD(95) failed to decrease over the 1-6 Hz range. Ca(2+)-handling abnormalities in ATR myocytes included slowed upstroke, decreased amplitude and strong single-beat post-rest potentiation. Unaltered Ca(2+)-handling properties included caffeine-releasable Ca(2+)-stores and Ca(2+)-transient relaxation before and after exposure to the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor cyclopiazonic acid (CPA). Including ICR alone in the model accounted for loss of APD(50) rate-adaptation; however, KR alone reduced APD(95) rate-adaptation by only 19% to 71 ms. When both ICR and Ca(2+)-handling changes were incorporated, APD(95) rate-adaptation decreased to 6 ms, accounting for experimental observations. CONCLUSION: ICR alone does not fully account for loss of APD rate-adaptation with atrial remodeling: Ca(2+)-handling changes appear to contribute to this clinically significant phenomenon.

Action Potentials↗

PubMedDate not supplied

Hemoglobin Glycosylation Index is not related with blood glucose.

OBJECTIVE: Accurate assessment of blood glucose control is essential to prevent chronic complications in diabetes. Hemoglobin Glycosylation Index (HGI) quantifies the degree to which individuals demonstrate a HbA(1C) higher or lower than average for the population. This study has aimed to assess the relationship between HGI and blood glucose. METHODS: 25 type 1 diabetes subjects (12 men and 13 women), 22.0+/-5.2 (17-34) years old, were instructed to self-monitor glucose with the One Touch Profile capillary glucose meter. HbA(1C) was determined and self-monitored blood glucose levels were studied every 3 months. Diabetic patients were monitored for 3-9 months and 62 measurements of HbA(1C) were included. HbA(1C) was measured by HPLC. Mean blood glucose (MBG) was calculated from self-monitored blood glucose records. A linear regression was calculated between HbA(1C) and MBG during the 60 days before sampling to determine HbA(1C). For each diabetic patient's MBG, a predicted HbA(1C) was calculated from the population regression equation. HGI was then calculated as HGI=observed HbA(1C)-predicted HbA(1C). Blood glucose was analyzed within target range (WTR), below target range (BTR) and above target range (ATR) according to The European Diabetes Policy Group Consensus for type 1 diabetes. RESULTS: A good linear regression between HbA(1C) and MBG was observed (r=.71, r(2)=.497, P=.000). No correlation was found between HGI and the percentage of WTR, BTR or ATR values. Moreover, the percentage of self-monitored blood glucose ATR and BTR was the same for high glycosylators (HGI<0 and ATR: 56.2+/-20.9%; HGI<0 and BTR: 34.5+/-17.5%) as for low glycosylators (HGI>0 and ATR: 52.8+/-25.5%; HGI>0 and BTR: 25.1+/-15.0%). CONCLUSIONS: HGI is determined for both physiological factors and blood glucose. A prospective study is necessary to assess whether HGI, together with HbA(1C), can predict the incidence and severity of chronic complications in diabetic patients.

Adolescent↗

PubMed2005

Thickness measurement of nanoscale polymer layer on polymer substrates by attenuated total reflection infrared spectroscopy.

For the first time, attenuated total reflection (ATR)-Fourier transform infrared (FT-IR) spectroscopy was utilized to measure the thickness (d0) of a nanoscale polymer layer on polymer substrate with significant credibility. First, a mathematical formula, A/A0 = 1 - 2d0/ d(p), was derived based on a self-defining subsection function (where d(p) was defined as depth of penetration of ATR and A and A0 were defined as the absorption band area of the characteristic functional group only contained in bulk substrate with a thin polymer layer attachment and the same group in blank substrate, respectively). On the mathematical model, through changing incidence angles, a series of values of A (A0) and corresponding d(p) were obtained, and when plotting A/A0 versus 2/d(p), d0 was obtained as the slope. With polystyrene (coating)/olypropylene (substrate) as a model system, we obtained the relevant values (d0). Comparing the results with the values of practical coating thickness (calculation and TEM observation), we found that this method was able to characterize well the thickness of a thin polymer layer on a polymer substrate in the range from 10 to 110 nm. Errors in the measurement were given and analyzed. Furthermore, this method was well applied in the thickness measurement of a polyacrylamide graft layer on a polypropylene film surface. The effect of pressure in the ATR technique on the coating thickness measurement was also discussed. In comparison with other methods such as XPS, SEM, TEM, and AFM, this approach based on a universal ATR technique was very convenient and fast. This method is expected to widen the application of the ATR-FT-IR technique and stimulate the further development of many fields such as surface self-assembly and surface functionlization.

Journal Article↗

PubMed1985

Comparison of the active sites of atropinesterase and some serine proteases by spin-labeling.

The side chain of the serine residue in the active center of atropinesterase (AtrE), alpha-chymotrypsin (Chymo), and subtilisin A (Sub) was labeled with two paramagnetic reporter groups of different size (label I or II, respectively) by sulfonylation with N-[3-(fluorosulfonyl)phenyl]-1-oxy-2,2,5,5-tetramethyl-pyrroline-3 -carboxamide or N-[6-(fluorosulfonyl)-2-naphthyl]-1-oxy-2,2,5,5-tetramethylpyrroline+ ++-3 -carboxamide. ESR spectra of labeled enzymes in 10 mM phosphate buffer, pH 7.4, were measured at temperatures between 133 and 298 K by using a home-built spectrometer operating in the absorption mode at 10-kHz field modulation. The spectra, in particular those at 276-298 K, were analyzed by computer simulation of the overall line shape according to the methods developed by Freed and co-workers, based on eigenfunction expansion. In the case of AtrE for both labels, the best agreement between experimental and simulated solution spectra was obtained with only one mobility component showing anisotropic, axially symmetric reorientation according to the Egelstaff jump-diffusion model. The axis of preferential reorientation was found to lie in the XZ plane at a polar angle of about 30 degrees with the X axis. The corresponding rotational correlation time (tau parallel) did not show appreciable viscosity/temperature (eta/T) dependence but had a constant value of 4.4 and 2.2 ns for labels I and II, respectively. The rotational correlation time associated with rotation around the axes perpendicular to that of preferential reorientation (tau perpendicular) showed the usual eta/T dependence and had a value of 22.0 ns at 276 K for both labels. The above results strongly suggest that in AtrE both nonpolar reporter groups reside in a pocket near the active serine. Contrary to the situation in AtrE, the overall mobility of the -N-O. fragments in Chymo and Sub was found to result from contributions of at least two distinct motional states, strongly and weakly immobilized. In going from label I to label II, the relative contribution of the latter state increases at the expense of that of the former. This is ascribed to an equilibrium between a relatively free state of the aromatic cores and a firmly bound position in the specificity pocket of these proteases. The apparently more rigid embedding of the spin-labels in the enzyme structure of AtrE suggests that the size of the nonpolar binding pocket in the active center region of this esterase allows a deeper penetration of the aromatic portions of the labels than is possible for the specificity pocket of Chymo or Sub.

Binding Sites↗

PubMed2003

Altered chromatographic behaviour of mitochondrial ADP/ATP translocase induced by stabilization of the protein by binding of 6'-O-fluorescein-atractyloside.

Atractyloside (ATR) is a high-affinity specific inhibitor of the mitochondrial ADP/ATP translocase (AAT). The binding of a fluorescent derivative, 6'- O -fluorescein-ATR (FATR), to mitochondria has been characterized. The binding constants obtained are in agreement with previously published values for ATR, demonstrating that FATR is a suitable probe of the AAT. AAT inhibited by FATR (FATR-AAT) was solubilized in dodecyl maltoside and purified by two separate ion-exchange chromatography steps at different pHs, which allowed FATR-AAT to be purified to homogeneity. The presence of the bound fluorescent probe enabled the inhibited AAT to be distinguished from the unliganded protein during chromatography, as they were markedly different in their chromatographic behaviour. The purified FATR-AAT was dimeric and in a single major conformation containing 1 mole FATR per mole of AAT dimer. In contrast, uninhibited AAT was monomeric and conformationally unstable. Use of the fluorescent ATR derivative in the development of the protocol enabled the stable dimeric AAT to be monitored directly and purified more effectively. The purification protocol was repeated using non-derivatized ATR, and highly pure AAT was obtained that was devoid of other members of the mitochondrial carrier family.

Adenosine Diphosphate↗

PubMed2004

Reduction of febrile but not allergic reactions to RBCs and platelets after conversion to universal prestorage leukoreduction.

BACKGROUND: Between January 1995 and November 1998, at Yale-New Haven Hospital, 25 percent of RBCs transfused were processed through prestorage or bedside leukoreduction filters, chosen on a per patient basis (selective leukoreduction [SLR]). Between January 1995 and July 1999, 30 percent of platelet concentrates (PCs) were infused through bedside leukoreduction filters. In an attempt to decrease febrile nonhemolytic transfusion reactions (FNHTR), a change was made from SLR to universal prestorage leukoreduction (UPL) for RBCs between November 1998 and December 1999 and for random donor PCs between July 1999 and January 2000. FNHTR and allergic transfusion reactions (ATR) reported from January 1995 through December 2002 were reviewed. STUDY DESIGN AND METHODS: For retrospective observational analysis, blood bank data were available on the number of RBCs and PCs transfused, percent products leukoreduced, and rate of FNHTR and ATR from 1995 through December 2002. After dividing this time period into three phases (SLR, transition, and UPL), these data were evaluated using odds ratio (ORs) and Student's t tests. RESULTS: A total of 145,369 RBCs and 137,982 PCs (29,487 PC pools) transfused between January 1995 and December 2002 were evaluated. For RBCs, the relative FNHTR rate decreased 47.1 percent, from 0.34 percent (SLR) to 0.18 percent (UPL) (p < 0.0001). ATR rates for RBCs showed 0.09 percent for both SLR and UPL groups (p > 0.05, NS). For PCs, the FNHTR relative rate decreased 93.1 percent, from 2.18 percent for SLR to 0.15 percent for UPL (p < 0.0001). Rates for ATR were 0.49 percent (SLR) and 0.35 percent (UPL) (p > 0.05, NS). CONCLUSIONS: A significant decrease in the frequency of posttransfusion FNHTR, but not ATR, for RBCs and PCs followed introduction of 100-percent UPL. The data support the hypothesis that the practice of UPL of RBCs and PCs decreases the frequency of FNHTR and thus improves patient care over the practice of selective leukoreduction.

Blood Preservation↗

PubMed2006

ATRIP associates with replication protein A-coated ssDNA through multiple interactions.

The ATR (ATM- and rad3-related)-mediated checkpoint pathway has a crucial role in regulating the cellular responses to DNA damage and DNA-replication stress. ATRIP (ATR-interacting protein), the regulatory partner of ATR, binds directly to replication protein A (RPA)-coated ssDNA and enables the ATR-ATRIP complex to recognize this DNA damage-induced structure. Here, we show that ATRIP associates with RPA-ssDNA through multiple interactions. Two major RPA-ssDNA-interacting domains of ATRIP were mapped to the regions flanking the conserved coiled-coil domain. In contrast to a recent article, we found that ATRIP mutants lacking the N terminus retained the ability to bind to RPA-ssDNA, suggesting that the multiple interactions between ATRIP and RPA-ssDNA may function redundantly in the recruitment of ATR-ATRIP. Unexpectedly, one internal region of ATRIP exhibited affinity to ssDNA, suggesting that ATRIP may interact with ssDNA in the ATRIP-RPA-ssDNA complex. Also, the N terminus of ATRIP associated with RPA-ssDNA in two distinct ways, indicating a dynamic and regulated association between ATRIP and RPA-ssDNA.

Adaptor Proteins, Signal Transducing↗

PubMed1993

Identification of a Drosophila activin receptor.

Activins are cytokines of the transforming growth factor beta superfamily that control various events during vertebrate embryo development and cell differentiation in the adult, and act through transmembrane receptors that contain a cytoplasmic protein-serine/threonine kinase domain. We describe the identification, deduced primary structure, and expression pattern of Atr-II, a receptor serine/threonine kinase found in Drosophila. With the exception of the spacing of 10 cysteine residues, the extracellular domain of Atr-II is very dissimilar from those of vertebrate activin receptors, yet it binds activin with high affinity and specificity. The kinase domain sequence of Atr-II is 60% identical to those of activin receptors from vertebrates, suggesting similarities in their signaling mechanisms. Maternal Atr-II transcript and its product are abundant in the oocyte. During development, the highest levels of Atr-II transcript and protein are observed in the mesoderm and gut. The possible role of an activin signaling system in Drosophila development is discussed.

Activin Receptors↗