bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic lethal targeting of DNA double‐strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors
Authors: Sultana Rebeka , McNeill Daniel R. , Abbotts Rachel , Mohammed Mohammed Z. , Zdzienicka Malgorzata Z. , Qutob Haitham , Seedhouse Claire , Laughton Charles A. , Fischer Peter M. , Patel Poulam M. , Wilson David M. , Madhusudan Srinivasan 
Published: February 2012

AbstractAn apurinic/apyrimidinic (AP) site is an obligatory cytotoxic intermediate in DNA Base Excision Repair (BER) that is processed by human AP endonuclease 1 (APE1). APE1 is essential for BER and an emerging drug target in cancer. We have isolated novel small molecule inhibitors of APE1. In this study, we have investigated the ability of APE1 inhibitors to induce synthetic lethality (SL) in a panel of DNA double‐strand break (DSB) repair deficient and proficient cells; i) Chinese hamster (CH) cells: BRCA2 deficient (V‐C8), ATM deficient (V‐E5), wild type (V79) and BRCA2 revertant [V‐C8(Rev1)]. ii) Human cancer cells: BRCA1 deficient (MDA‐MB‐436), BRCA1 proficient (MCF‐7), BRCA2 deficient (CAPAN‐1 and HeLa SilenciX cells), BRCA2 proficient (PANC1 and control SilenciX cells). We also tested SL in CH ovary cells expressing a dominant‐negative form of APE1 (E8 cells) using ATM inhibitors and DNA‐PKcs inhibitors (DSB inhibitors). APE1 inhibitors are synthetically lethal in BRCA and ATM deficient cells. APE1 inhibition resulted in accumulation of DNA DSBs and G2/M cell cycle arrest. SL was also demonstrated in CH cells expressing a dominant‐negative form of APE1 treated with ATM or DNA‐PKcs inhibitors. We conclude that APE1 is a promising SL target in cancer.
Annexin A1 mediates the anti‐inflammatory effects during the granulocytic differentiation process in all‐trans retinoic acid‐treated acute promyelocytic leukemic cells
Authors: Tsai Wen‐Hui , Chien Hong‐Yu , Shih Chung‐Hung , Lai Shu‐Lien , Li I‐Ting , Hsu Shau‐Chieh , Kou Yu Ru , Hsu Hui‐Chi 
Published: February 2012

AbstractAnnexin A1 (AnxA1) originating from mature neutrophils and their microparticles (MPs) plays an important anti‐inflammatory role during the resolution phase of inflammation. However, the role of AnxA1 during the process of granulocytic differentiation is still unknown. All‐trans retinoic acid (ATRA) can induce acute promyelocytic leukemic (APL) cells to differentiate along the granulocytic lineage and has been used successfully in treating APL patients. In this study, we investigated whether or not AnxA1 contributed to the anti‐inflammatory properties of ATRA‐treated APL (NB4; ATRA‐NB) cells using the transmigratory and adhesive assays. We found that ATRA was able to enhance the surface expression of AnxA1 and its receptor (FPR2/ALX) and the release of AnxA1‐containing MPs from ATRA‐NB4 cells, while the expression of annexin V was not elevated on the latter cells. Further studies demonstrated that exogenous AnxA1 could inhibit ATRA‐NB4 cells in their transmigratory activity and adhesion to endothelial cells. In addition, the transmigratory activity of ATRA‐NB4 cells can be significantly enhanced by pretreatment with a FPR2/ALX neutralizing antibody, suggesting that endogenous AnxA1 may contribute to the anti‐migratory effects. Finally, ATRA‐NB4‐derived MPs could also inhibit recipient cells in their transmigratory and adhesive activities and these anti‐inflammatory effects could be inhibited by pretreatment of MPs with a specific anti‐AnxA1 antibody. Flowcytometry studies further demonstrated that FITC‐labeled AnxA1 could be transported from MPs to the membrane of recipient ATRA‐NB4 cells. We conclude that biologically active AnxA1 may play a role in the anti‐inflammatory properties of ATRA‐treated APL cells during the process of granulocytic differentiation. J. Cell. Physiol. 227: 3661–3669, 2012. © 2012 Wiley Periodicals, Inc.
Cooperation of Epac1/Rap1/Akt and PKA in prostaglandin E2‐induced proliferation of human umbilical cord blood derived mesenchymal stem cells: Involvement of c‐Myc and VEGF expression
Authors: Jang Min Woo , Yun Seung Pil , Park Jae Hong , Ryu Jung Min , Lee Jang Hern , Han Ho Jae 
Published: February 2012

AbstractProstaglandin E2 (PGE2) is well known to regulate cell functions through cAMP; however, the role of exchange protein directly activated by cAMP (Epac1) and protein kinase A (PKA) in modulating such functions is unknown in human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs). Therefore, we investigated the relationship between Epac1 and PKA during PGE2‐induced hUCB‐MSC proliferation and its related signaling pathways. PGE2 increased cell proliferation, and E‐type prostaglandin (EP) 2 receptor mRNA expression level and activated cAMP generation, which were blocked by EP2 receptor selective antagonist AH 6809. PGE2 increased Epac1 expression, Ras‐related protein 1 (Rap1) activation level, and Akt phosphorylation, which were inhibited by AH 6809, adenylyl cyclase inhibitor SQ 22536, and Epac1/Rap1‐specific siRNA. Also, PGE2 increased PKA activity, which was inhibited by AH 6809, SQ 22536, and PKA inhibitor PKI. HUCB‐MSCs were incubated with the Epac agonist 8‐pCPT‐cAMP or the PKA agonist 6‐phe‐cAMP to examine whether Epac1/Rap1/Akt activation was independent of PKA activation. 8‐pCPT‐cAMP increased Akt phosphorylation but not PKA activity. 6‐Phe‐cAMP increased PKA activity, but not Akt phosphorylation. Additionally, an Akt inhibitor or PKA inhibitor (PKI) did not block the PGE2‐induced increase in PKA activity or Akt phosphorylation, respectively. Moreover, PGE2 increased glycogen synthase kinase (GSK)‐3β phosphorylation and nuclear translocation of active‐β‐catenin, which were inhibited by Akt inhibitor or/and PKI. PGE2 increased c‐Myc and vascular endothelial growth factor (VEGF) expression levels, which were blocked by β‐catenin siRNA. In conclusion, PGE2 stimulated hUCB‐MSC proliferation through β‐catenin‐mediated c‐Myc and VEGF expression via Epac/Rap1/Akt and PKA cooperation. J. Cell. Physiol. 227: 3756–3767, 2012. © 2012 Wiley Periodicals, Inc.
Primary care physicians' use of publicly reported quality data in hospital referral decisions
Authors: Morsi Elizabeth , Lindenauer Peter K. , Rothberg Michael B. 
Published: February 2012

AbstractBACKGROUND:Despite government investment in public reporting of hospital quality data, patients still rely on recommendations from their primary care physicians (PCPs). Little is known about how physicians make hospital referrals.OBJECTIVE:To characterize factors that influence PCPs' hospital referral choices.DESIGN:Web‐based physician survey.PARTICIPANTS:PCPs affiliated with 3 Massachusetts hospitals.MAIN MEASURES:Physician demographics, familiarity with public reporting, and opinions about which factors would influence hospital referral decisions for an elderly patient with pneumonia.RESULTS:Of 194 PCPs who received invitations, 92 (47%) responded. Although 93% maintained admitting privileges, only 20% admitted patients. The following were considered “very” important in referral decisions: “familiarity with the hospital” (70%), “patient preference” (62%), and “admitting arrangements with a hospitalist group” (62%). “Publicly available quality measures” were “not at all” important to 42%. Only 61% were aware of hospital quality reporting; 16% were familiar with Hospital Compare, a Centers for Medicare and Medicaid Services (CMS) Web site. No physicians reported ever using quality information to make a referral decision or discussing it with patients. No physician factors were associated with awareness of publicly reported data. PCPs identified the following factors as being “very” important in determining the quality of pneumonia care: antibiotics within 6 hours of arrival (66%), appropriate initial antibiotic (63%), and blood cultures performed prior to the administration of antibiotics (51%).CONCLUSIONS:Although PCPs most valued the information available through Hospital Compare, only 16% were aware of it, and none used publicly reported quality data in referral decisions. Medicare and high‐performing hospitals should consider marketing Hospital Compare to PCPs. Journal of Hospital Medicine 2012;. © 2012 Society of Hospital Medicine
Succession of bird communities in young temperate rainforests following thinning
Authors: Matsuoka Steven M. , Johnson James A. , Dellasala Dominick A. 
Published: March 2012

AbstractWe repeated bird and vegetation surveys in 1991–1992 and 2005–2006 among young managed stands and old‐growth forests in southeast Alaska to evaluate whether pre‐commercial thinning of managed stands influenced the bird community. We compared decadal changes in bird densities and forest vegetation among 3 stand types: managed stands originating from clearcuts 35 years ago that were left untreated (unthinned), managed stands thinned at uniform spacing (thinned), and old growth with no prior timber harvest. We did not detect differences in decadal trends in avian densities between thinned and unthinned stands for 15 of 16 common bird species using a repeated‐measures design. Thinning did not result in greater recruitment of overstory‐nesting species as predicted. This was likely because of 1) similar increases in tree heights (${\bar {x}}$ = 9–10 m) and canopy cover (${\bar {x}}$ = 29–43%) between unthinned and thinned stands across decades and 2) the relatively young successional stage of these stands, which had only begun to recruit medium and large size conifers (dbh ≥ 36 cm). Decadal trends in densities of most (88%) understory‐nesting bird species did not differ between thinned and unthinned stands. Shrub cover decreased by 22% and 31% across decades in thinned and unthinned stands, respectively. Bird community composition in managed stands reflected the general decadal changes in forest vegetation with a shift in dominance from understory species in the early 1990s (80–85% of total bird density) to an equal abundance of understory (45–54%) and overstory species in the mid‐2000s. The latter was more similar to old‐growth stands, which were dominated by overstory species (67–71%). Overstory‐nesting birds in old growth increased in density by 49% across decades. Densities of cavity‐nesting species remained unchanged in managed stands and less than densities in old growth across decades, possibly because of a lack of large trees and snags for nest sites. Overall, thinning of clearcut stands, the primary silvicultural system in the region, had few measurable benefits to birds nearly 20 years after treatment. Monitoring over the 70–100‐year harvest rotation may be necessary to fully test whether thinning accelerates succession of bird communities in clearcut stands. However, partial harvests that retain large trees and snags should also be explored as alternatives to better maintain late‐succession avifauna throughout the harvest rotation in southeast Alaska. © 2012 The Wildlife Society.
Genetic structure of red deer population in northeastern Poland in relation to the history of human interventions
Authors: Niedziałkowska Magdalena , Jędrzejewska Bogumiła , Wójcik Jan M. , Goodman Simon J. 
Published: March 2012

AbstractWe studied the genetic structure of a red deer (Cervus elaphus) population in 8 woodlands of northeastern Poland and 1 in western Belarus and compared it with the documented history of the population in the region. Red deer nearly went extinct in the region in the 18th and 19th centuries. In the mid‐19th century, reintroductions began and continued until the mid‐1960s. Animals were translocated from various sites in Poland and other European countries. We genotyped 303 individuals using 14 microsatellite loci and sequenced 253 individuals for a fragment of the control region (mitochondrial DNA [mtDNA]). The microsatellite analyses demonstrate that 3 genetically separate subpopulations exist, but 4 according to mtDNA. All haplotypes found in northeastern Poland are closely related to haplotypes from northern and northwestern Europe. The only individuals that could have originated from autochthonous red deer populations, rather than introductions, were found in Napiwoda Forest. The present regional genetic structure of the species is consistent with the known history of red deer translocations. Current patterns of genetic diversity in these populations are determined by the interaction of past human management and contemporary natural migrations. © 2012 The Wildlife Society.
Site occupancy dynamics of northern spotted owls in managed interior Douglas fir forests, California, USA, 1995–2009
Authors: Farber Stuart L. , Kroll Andrew J. 
Published: March 2012

AbstractNorthern spotted owls (Strix occidentalis caurina) have received intense research and management interest since their listing as a threatened species by the United States Fish and Wildlife Service in 1990. For example, public and private forest managers in the Pacific Northwest, USA, conduct surveys to determine presence or absence of spotted owls prior to timber harvest operations. However, although recently developed statistical methods have been applied to presence–absence data collected during research surveys, the effectiveness of operational surveys for detecting spotted owls and evaluating site occupancy dynamics is not known. We used spotted owl survey data collected from 1995 to 2009 on a study area in interior northern California, USA, to evaluate competing occupancy models from Program PRESENCE using Akaike's Information Criterion (AIC). During 1,282 individual surveys, we recorded 480 spotted owl detections (37.4%) and 13 barred owl (1.0%) detections. Average per visit detection probability (85% CL) for single and paired spotted owls was 0.93 (0.90–0.96) for informed daytime, stand‐based searches and 0.47 (0.43–0.51) for nighttime, station‐based surveys (estimated from the best model); the average per visit detection probability from the null model was 0.67 (0.64–0.70). Average pair‐only detection probabilities were 0.86 (0.81–0.90) for informed daytime, stand‐based searches and 0.23 (0.18–0.29) for nighttime, station‐based surveys; the average per visit detection probability from the null model was 0.63 (0.58–0.68). Site occupancy for any owl declined from 0.81 (0.59–0.93) in 1995 to 0.50 (0.39–0.60) in 2009; pair occupancy declined from 0.75 (0.56–0.87) to 0.46 (0.31–0.61). Our results suggest that a combination of 1 informed stand and 2 station‐based operational surveys can support determinations of spotted owl site status (either a single or a pair) at desired levels of confidence. However, our information was collected in an area where barred owls were rarely detected. Surveys conducted in areas that support well‐established barred owl populations are likely to be less effective for determining presence or absence of spotted owls and may require more surveys and/or different survey methods to determine site status with confidence. © 2012 The Wildlife Society.
Cyclodextrin encapsulation of the functional group diminishes an antioxidant's free radical scavenging rates
Authors: Ishikawa Misa , Sueishi Yoshimi , Endo Nobuyuki , Oowada Shigeru , Shimmei Masashi , Fujii Hirotada , Kotake Yashige 
Published: March 2012

AbstractScavenging rates of cyclodextrin‐solubilized lipophilic antioxidants, namely catechin, epicatechin, epigallocatechin gallate, and resveratrol, against alkoxyl (RO•) radical were measured with the use of electron paramagnetic resonance (EPR) spin‐trapping method. Results indicated that the scavenging rates of catechin and resveratrol were notably dependent on the solubilizer used, i.e., native β‐cyclodextrin (β‐CD) or heptakis(2,6‐di‐O‐methyl)‐β‐cyclodextrin (DM‐β‐CD). But, epicatechin and epigallocatechin gallate showed almost no dependence on the cyclodextrin used. Catechin's scavenging rate in β‐CD was 66% lower than in DM‐β‐CD; in contrast, resveratrol in β‐CD showed 45% higher rate than in DM‐β‐CD. Based on the reported solution‐NMR structure of the inclusion complex of these antioxidants, it was concluded that the scavenging rate is decreased when the cyclodextrin cavity preferentially encapsulates the antioxidant‐function bearing group, i.e., O‐ and p‐quinolinol group in catechin and resveratrol, respectively. The depth of inclusion of the functional group determines the extent of the scavenging rate difference, suggesting that the cavity wall of the cyclodextrin acts like a barrier that hinders the approach of attacking free radicals. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 598–603, 2012
Kinetic and thermodynamic analysis of degradation of doripenem in the solid state
Authors: Cielecka‐Piontek Judyta , JelińSka Anna , Dołhań Agnieszka , Zalewski Przemysław 
Published: March 2012

AbstractThe kinetic and thermodynamic parameters of degradation of doripenem were studied using a high‐performance liquid chromatography method. In dry air, the degradation of doripenem was a first‐order reaction depending on the substrate concentration. At increased relative air humidity, doripenem was degraded according to the autocatalysis kinetic model. The dependence ln k = f1/T) was described by the equations ln k = 5.10 ± 13.06 − (7576 ± 4939)(1/T) in dry air and ln k = 46.70 ± 22.44 − (19,959 ± 8031)(1/T) at 76.4% relative humidity (RH). The thermodynamic parameters Ea, ΔH≠a, and ΔS≠a of the degradation of doripenem were calculated. The dependence ln k = f (RH%) was described by the equation ln k = (0.155 ± 0.077) × 10−1 (RH%) − (3.45 ± 21.8) × 10−10. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 722–728, 2012
Mass spectrometry detection in comprehensive liquid chromatography: Basic concepts, instrumental aspects, applications and trends
Authors: Donato Paola , Cacciola Francesco , Tranchida Peter Quinto , Dugo Paola , Mondello Luigi 
Published: March 2012

AbstractThe review, as can be deduced from the title, focuses on both theoretical and practical aspects of the use of mass spectrometry as a third, added dimension to a comprehensive LC (LC × LC) system, generating the most powerful analytical tool today for non‐volatile analytes. The first part deals with the technical requirements for linkage of an LC × LC system to an MS one, including the choice of the mobile phase (buffer and salts), flow rate (splitting), type of ionization (interface); advantages and disadvantages of off‐line and on‐line methods are discussed, as well. A discussion of the various aspects of instrumentation is provided, both from a chromatographic and mass spectrometry standpoint, with particular emphasis directed to the choice of column sets, spatial resolution, mass resolving power, mass accuracy, and tandem‐MS capabilities. The extent to which mass spectrometry may be of aid in unraveling column‐outlet multicompound bands is highlighted, along with its effectiveness as a chromatographic detector of excellent sensitivity, universality yet with potential in terms of selectivity and amenability to quantitative analysis over a wide dynamic range. The following section of the review contains significant applications of comprehensive two‐dimensional LC coupled to MS in different areas of research, with details on interfaces, column stationary phases, modulation and MS parameters. It is not the intention of the authors to provide a comprehensive description of the techniques, but merely to discuss only those aspects which are essential for successful applications of the LC–MS combination. The reader will be acquainted with the enormous potential of this hyphenated technique, and the factors and instrumental developments that have concurred to make it emerge to a central role in specialized fields, such as proteomics. © 2012 Wiley Periodicals, Inc. Mass Spec Rev 31:523–559, 2012
Association of Baseline urodynamic measures of urethral function with clinical, demographic, and other urodynamic variables in women prior to undergoing midurethral sling surgery
Authors: Chai Toby C. , Huang Liyuan , Kenton Kim , Richter Holly E. , Baker Jan , Kraus Stephen , Litman Heather ,   for the Urinary Incontinence Treatment Network (UITN)
Published: February 2012

AbstractAimsTo explore how baseline demographic, clinical, and urodynamic (UDS) variables correlate with measures of urethral function in women planning midurethral sling surgery.MethodsWomen with predominant stress urinary incontinence (SUI) as part of the trial of mid‐urethral slings (TOMUS) were characterized preoperatively including: demographics, body mass index (BMI), responses to the Medical and Epidemiologic Social Aspects of Aging (MESA) and Urogenital Distress Inventory (UDI) questionnaires, pad weight (PW), incontinence duration, prior SUI surgery, prolapse, strength of pelvic contraction, Q‐tip test, uroflow, cystometrogram, and detrusor pressures at maximum flow (Pdet at Qmax). Multivariate regression analysis and modeling confirmed variables with significant correlations with maximal urethral closure pressure (MUCP), functional urethral length (FUL), and Valsalva leak point pressure (VLPP).ResultsFive‐hundred thirty‐nine women were included in the analysis. In multivariable analyses, PW (P = 0.045) and age (P < 0.0001) were negatively correlated with MUCP (as PW and age increased, MUCP decreased); BMI (P = 0.02) and Pdet at Qmax (P < 0.0001) were positively correlated with MUCP (as BMI and Pdet at Qmax increased, MUCP increased). Age (P = 0.002) was negatively correlated with FUL; Qtip delta (P = 0.006), pelvic organ prolapse quantification examination (POPQ) stage (P = 0.002) and strength of pelvic contraction (P = 0.03) were positively correlated with FUL. Duration of incontinence (P = 0.01) was negatively correlated with VLPP; Qtip delta (P = 0.02), BMI (P = 0.0005) and Pdet at Qmax (P = 0.0005) were positively correlated with VLPP.ConclusionsAge, BMI, Qtip delta, and Pdet at Qmax were variables that correlated with two or more measures of urethral function. These correlations may help direct future research in female urethral function. Neurourol. Urodynam. 31:496–501, 2012. © 2012 Wiley Periodicals, Inc.
Water‐soluble meta‐poly(phenylene ethynylene) oligomers with stable helical secondary structure
Authors: Nguyen Ha H. , McAliley James H. , Bruce David A. 
Published: February 2012

AbstractTwo novel water‐soluble meta‐poly(phenylene ethynylene) (mPPE) copolymers were synthesized and characterized, each contained ester and amine functional groups attached to exohelix positions on the phenylene rings and one contained methoxy endohelix functional groups. Secondary structure formation was investigated for these materials in aqueous solutions using ultraviolet and fluorescence spectroscopy. Additionally, the folding behaviors are reported for the mPPEs and their protected amine precursors in other protic and aprotic solvents. Results indicate that both mPPEs are able to form stable helical structures in water, while only the nonmethoxylated polymer exhibited a helical structure in acetonitrile and several alcohols. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012