bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renin‐Angiotensin‐Aldosterone System Activity in Hyperthyroid Cats with and without Concurrent Hypertension
Authors: Williams T.L. , Elliott J. , Syme H.M. 
Published: March 2013

BackgroundHypertension is present in some hyperthyroid cats at diagnosis or can develop after treatment for hyperthyroidism. Activation of the renin‐angiotensin‐aldosterone system (RAAS) could be involved in the pathogenesis of hypertension.HypothesisHyperthyroid cats that develop hypertension before or after treatment for hyperthyroidism will have greaterRAASactivation than normotensive cats.AnimalsNinety‐nine hyperthyroid cats.MethodsRetrospective case–control study. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in untreated hyperthyroid hypertensive cats (HT‐Pre group), initially normotensive hyperthyroid cats that develop hypertension after treatment (HT‐Post group), and hyperthyroid cats that are normotensive (NTgroup). Data are presented as median [25th, 75th percentile].ResultsBaselinePRAwas not significantly different among the 3 groups (HT‐Pre group 1.50 [0.05, 2.37] ng/mL/h,HT‐Post group 0.66 [0.17, 2.31] ng/mL/h,NTgroup 1.11 [0.57, 2.18] ng/mL/h;P = .44).PRAdecreased significantly after treatment in theNTgroup (1.09 [0.53, 2.47] versus 0.22 [0.05, 0.76] ng/mL/h;P < .001) and theHT‐Post group (0.71 [0.17, 2.33] versus 0.28 [0.07, 0.57] ng/mL/h;P = .006). BaselinePACwas not significantly different among the 3 groups (HT‐Pre group 72.2 [40.0, 145.6] pg/mL,HT‐Post group 69.7 [43.3, 142.6] pg/mL,NTgroup 109.0 [68.2, 184.6] pg/mL;P = .10).PACdecreased significantly after treatment in theNTgroup (114.4 [56.6, 204.1] versus 59.5 [32.4, 98.2] pg/mL;P < .001) but did not change significantly in theHT‐Post group (61.2 [44.9, 124.0] versus 58.4 [42.0, 97.7] pg/mL;P = .59).Conclusions and Clinical ImportanceRAASactivation occurs in hyperthyroid cats, but is not associated with the development of hypertension.PACis not influenced by changes inPRAin hyperthyroid cats that develop hypertension after treatment, perhaps indicatingRAASdysfunction in these cats.
Grazing by goats on islands affects the populations of an endemic Mediterranean lizard
Authors: Pafilis P. , Anastasiou I. , Sagonas K. , Valakos E. D. 
Published: March 2013

AbstractGrazing of goats on Mediterranean islets is a common practice. Its consequences on plant communities are well documented, although not on vertebrates. We aim to shed light on the effect of livestock farming on lizards by investigating five populations of the insular lizard, Podarcis gaigeae, differing in the duration and intensity of grazing. Data on grazing regime, invertebrate abundance, tick prevalence, infestation levels, gull nests and lizard densities were collected during a period of 6 consecutive years. Grazing had a negative impact on insect populations, thus decreasing food availability for lizards. Tick prevalence and infestation levels were higher in places of continuous grazing. Goat activity disturbed gulls, which avoid nesting, so depriving the islets of marine subsidies. As a consequence of all these factors, lizard densities were higher in ungrazed and lower in grazed biotopes. Grazing effects were more severe on islets communities than on the main island populations. Our data imply that management action should be taken to conserve the highly diverse islet populations.
Genetic diversity of Bartonella quintana in macaques suggests zoonotic origin of trench fever
Authors: Li Hao , Bai Jie‐Ying , Wang Li‐Yuan , Zeng Lin , Shi Yan‐Sheng , Qiu Zheng‐Liang , Ye Hua‐Hu , Zhang Xiao‐Fei , Lu Qing‐Bin , Kosoy Michael , Liu Wei , Cao Wu‐Chun 
Published: March 2013

AbstractBartonella quintana is a bacterium that causes a broad spectrum of diseases in humans including trench fever. Humans were previously considered to be the primary, if not the only, reservoir hosts for B. quintana. To identify the animal reservoir and extend our understanding of the ecological and evolutionary history of B. quintana, we examined blood samples from macaques and performed multilocus sequence typing (MLST) analysis. We demonstrated the prevalence of B. quintana infection was common in macaques from main primate centres in mainland China. Overall, 18.0% (59/328) of rhesus macaques and 12.7% (39/308) of cynomolgus macaques were found to be infected with B. quintana by blood culture and/or polymerase chain reaction. The infection was more frequently identified in juvenile and young monkeys compared with adult animals. In contrast with the relatively low level of sequence divergence of B. quintana reported in humans, our investigation revealed much higher genetic diversity in nonhuman primates. We identified 44 new nucleotide variable sites and 14 novel sequence types (STs) among the B. quintana isolates by MLST analysis. Some STs were found only in cynomolgus macaques, while some others were detected only in rhesus macaques, suggesting evidence of host‐cospeciation, which were further confirmed by phylogenetic analysis and Splits decomposition analysis. Our findings suggest that trench fever may primarily be a zoonotic disease with macaques as the natural hosts.
Post‐transcriptional regulation of GORK channels by superoxide anion contributes to increases in outward‐rectifying K+ currents
Authors: Tran Daniel , El‐Maarouf‐Bouteau Hayat , Rossi Marika , Biligui Bernadette , Briand Joël , Kawano Tomonori , Mancuso Stefano , Bouteau François 
Published: March 2013

Summary

Ion fluxes are ubiquitous processes in the plant and animal kingdoms, controlled by fine‐tuned regulations of ion channel activity. Yet the mechanism that cells employ to achieve the modification of ion homeostasis at the molecular level still remains unclear. This is especially true when it comes to the mechanisms that lead to cell death.

In this study, Arabidopsis thaliana cells were exposed to ozone (O3). Ion flux variations were analyzed by electrophysiological measurements and their transcriptional regulation by RT‐PCR. Reactive oxygen species (ROS) generation was quantified by luminescence techniques and caspase‐like activities were investigated by laser confocal microscopy.

We highlighted the delayed activation of K+ outward‐rectifying currents after an O3‐induced oxidative stress leading to programmed cell death (PCD). Caspase‐like activities are detected under O3 exposure and could be decreased by K+ channel blocker. Molecular experiments revealed that the sustained activation of K+ outward current could be the result of an unexpected post‐transcriptional regulation of the guard cell outward‐rectifying K+ (GORK) channels.

This consists of a likely new mode of regulating the processing of the GORK mRNA, in a ROS‐dependent manner, to allow sustained K+ effluxes during PCD. These data provide new mechanistic insights into K+ channel regulation during an oxidative stress response.
Age of myopia onset in a British population‐based twin cohort
Authors: Williams Katie M , Hysi Pirro G , Nag Abhishek , Yonova‐Doing Ekaterina , Venturini Cristina , Hammond Christopher J 
Published: March 2013

AbstractPurposeSchool‐age myopia is becoming more common in Asia and North America; data from the United Kingdom has suggested a significant amount of myopia develops after the age of 17 years. Age of spectacle wear has been used as a proxy of myopia severity in a recent large genome‐wide association study. The purpose of this study was to examine the age of onset of spectacle wear in a large British twin cohort, to examine the reliability and reproducibility of self‐reported age of onset as a proxy measure of myopia severity, and to see if there is evidence in the UK of a rising prevalence of myopia.MethodsNon‐cycloplegic autorefraction was performed on over 6000 subjects from the TwinsUK cohort, a large, well‐characterized volunteer cohort of British, predominantly Caucasian female twins, between 1998 and 2010. Questionnaires asking age of first spectacle wear were conducted in 2003 and 2008. Myopia was defined as worse than or equal to −1.00 Dioptres, and adult onset myopia as occurring on or after the age of 17 years.ResultsAutorefractive data was available on 6097 participants at a mean age of 53 years. The mean S.E. was −0.36 D (S.D. 2.67, range −25.13 to +9.38). 1705 subjects (28%) were myopic with a mean refractive error of −3.54 (S.D. 2.51, range −25.13 to −1.00) and the median age of first glasses wear was 15 years (mean 18.4 years, S.D. 12.24, range 0–74). Of those who provided an age at which they first wore glasses in both questionnaire sources (n = 628), there was median difference in response of 0 years (S.D. 7.18, mean 0.7, maximum 53). A statistically significant cohort effect for increased myopia prevalence across a range of age groups between 1998–1999 and 2008–2010 was identified, with myopia prevalence increasing from 27% to 34% in those aged 50–54 and from 16% to 32% in those aged 55–59.ConclusionsAlmost half the myopes in this UK‐based population wore glasses after the age of 17; further research into adult‐onset myopia is required. Although self‐reported age of glasses is reproducible and reflects severity, it only explains approximately 15% of the variance of spherical equivalent, so is a rough proxy of refractive error, but still may be useful in large‐scale population studies without access to refraction. We have demonstrated a significant cohort effect for increased myopia prevalence in the UK population over a 10‐year period.
Asymptotics of the Discrete Log-Concave Maximum Likelihood Estimator and Related Applications
Authors: Balabdaoui Fadoua , Jankowski Hanna , Rufibach Kaspar , Pavlides Marios 
Published: March 2013

SummaryThe assumption of log-concavity is a flexible and appealing non-parametric shape constraint in distribution modelling. In this work, we study the log-concave maximum likelihood estimator of a probability mass function. We show that the maximum likelihood estimator is strongly consistent and we derive its pointwise asymptotic theory under both the well-specified and misspecified settings. Our asymptotic results are used to calculate confidence intervals for the true log-concave probability mass function. Both the maximum likelihood estimator and the associated confidence intervals may be easily computed by using the R package logcondiscr. We illustrate our theoretical results by using recent data from the H1N1 pandemic in Ontario, Canada.
Outlier Robust Small Area Estimation
Authors: Chambers Ray , Chandra Hukum , Salvati Nicola , Tzavidis Nikos 
Published: March 2013

SummaryRecently proposed outlier robust small area estimators can be substantially biased when outliers are drawn from a distribution that has a different mean from that of the rest of the survey data. This naturally leads one to consider an outlier robust bias correction for these estimators. We develop this idea, proposing two different analytical mean-squared error estimators for the ensuing bias-corrected outlier robust estimators. Simulations based on realistic outlier-contaminated data show that the bias correction proposed often leads to more efficient estimators. Furthermore, the mean-squared error estimation methods proposed appear to perform well with a variety of outlier robust small area estimators.
Canine DLA‐79 gene: an improved typing method, identification of new alleles and its role in graft rejection and graft‐versus‐host disease
Authors: Venkataraman G. M. , Geraghty D. , Fox J. , Graves S. S. , Zellmer E. , Storer B. E. , Torok‐Storb B. J. , Storb R. 
Published: March 2013

AbstractDeveloping a preclinical canine model that predicts outcomes for hematopoietic cell transplantation in humans requires a model that mimics the degree of matching between human donor and recipient major histocompatibility complex (MHC) genes. The polymorphic class I and class II genes in mammals are typically located in a single chromosome as part of the MHC complex. However, a divergent class I gene in dogs, designated dog leukocyte antigen‐79 (DLA‐79), is located on chromosome 18 while other MHC genes are on chromosome 12. This gene is not taken into account while DLA matching for transplantation. Though divergent, this gene shares significant similarity in sequence and exon–intron architecture with other class I genes, and is transcribed. Little is known about the polymorphisms of DLA‐79 and their potential role in transplantation. This study was aimed at exploring the reason for high rate of rejection seen in DLA‐matched dogs given reduced intensity conditioning, in particular, the possibility that DLA‐79 allele mismatches may be the cause. We found that about 82% of 407 dogs typed were homozygous for a single, reference allele. Owing to the high prevalence of a single allele, 87 of the 108 dogs (∼80%) transplanted were matched for DLA‐79 with their donor. In conclusion, we have developed an efficient method to type alleles of a divergent MHC gene in dogs and identified two new alleles. We did not find any statistical correlation between DLA‐79 allele disparity and graft rejection or graft‐versus‐host disease, among our transplant dogs.
Identification of novel tumour‐associated antigens in canine mammary gland tumour
Authors: Furuya M. , Funasaki M. , Tani H. , Sasai K. 
Published: March 2013

AbstractCanine mammary gland tumour (MGT) is the most common neoplasm in female dogs and has similar biological characteristics to humanMGT. Spontaneous canineMGTis a more attractive clinical model in oncological research than that of the murine experimental model. Tumour‐associated antigens (TAAs), which are produced in tumour cells, are applied as tumour markers, tumour vaccine antigens and molecular targets of therapeutic drugs. In this study, we have primarily identified 13 differentTAAsof canineMGTby serological immunoscreening ofcDNAexpression library. The results of serological mini‐arrays of identified antigens showed thatCCDC41antigen specially reacted with 35% of sera fromMGT‐dogs and did not react with control sera. We also found thatHSPH1 mRNAexpression levels increased significantly inMGTtissues. These findings will contribute to the development of diagnostic technologies and translational target therapies for dogs.Clinical relevance: HSPH1, which is strongly expressed in the tumour tissue, will be a possible vaccine antigen of canine MGT.
Feasibility of producing a short, high energy s‐band linear accelerator using a klystron power source
Authors: Baillie Devin , Aubin J. St. , Fallone B. G. , Steciw S. 
Published: March 2013

Purpose:To use a finite‐element method (FEM) model to study the feasibility of producing a short s‐band (2.9985 GHz) waveguide capable of producing x‐rays energies up to 10 MV, for applications in a linac‐MR, as well as conventional radiotherapy.Methods:An existing waveguide FEM model developed by the authors' group is used to simulate replacing the magnetron power source with a klystron. Peak fields within the waveguide are compared with a published experimental threshold for electric breakdown. The RF fields in the first accelerating cavity are scaled, approximating the effect of modifications to the first coupling cavity. Electron trajectories are calculated within the RF fields, and the energy spectrum, beam current, and focal spot of the electron beam are analyzed. One electron spectrum is selected for Monte Carlo simulations and the resulting PDD compared to measurement.Results:When the first cavity fields are scaled by a factor of 0.475, the peak magnitude of the electric fields within the waveguide are calculated to be 223.1 MV/m, 29% lower than the published threshold for breakdown at this operating frequency. Maximum electron energy increased from 6.2 to 10.4 MeV, and beam current increased from 134 to 170 mA. The focal spot FWHM is decreased slightly from 0.07 to 0.05 mm, and the width of the energy spectrum increased slightly from 0.44 to 0.70 MeV. Monte Carlo results show dmax is at 2.15 cm for a 10 × 10 cm2 field, compared with 2.3 cm for a Varian 10 MV linac, while the penumbral widths are 4.8 and 5.6 mm, respectively.Conclusions:The authors' simulation results show that a short, high‐energy, s‐band accelerator is feasible and electric breakdown is not expected to interfere with operation at these field strengths. With minor modifications to the first coupling cavity, all electron beam parameters are improved.
The utility of Advanced Trauma Life Support (ATLS) clinical shock grading in assessment of trauma
Authors: Lawton Luke D , Roncal Sue , Leonard Elizabeth , Stack Amanda , Dinh Michael M , Byrne Christopher M , Petchell Jeffrey 
Published: March 2013

BackgroundAcute haemorrhage is a major contributor to trauma related morbidity and mortality. Quantifying blood loss acutely and accurately is a difficult task and no currently accepted standard exists. We introduce a simple shock grading tool incorporating vital signs, fluid response and estimated blood loss to describe shock grade during the primary survey based on the original Advanced Trauma Life Support (ATLS) classification.MethodsWe performed a prospective cohort study of all trauma patients admitted to our emergency room over a 1-year period to evaluate the utility of this tool for emergency physicians to detect significant haemorrhage in the trauma patient. Shock grades were prospectively assigned to patients by the trauma team as part of the primary survey, and followed up to assess for outcomes. The primary outcome was a composite endpoint of clinical, radiological and operative findings consistent with significant haemorrhage. Data were analysed using linear and logistic regression to assess predictive ability and receiver operator characteristic curve to assess overall diagnostic accuracy.ResultsThe overall sensitivity of the shock grading tool was 83%. The diagnostic accuracy based on area under receiver operator characteristic curve was 0.86. There was also a significant association between increasing shock grade and both injury severity score (β coefficient 7.0, p<0.001, 95% CI 6.2 to 7.8) and the presence of significant haemorrhage (OR 5.1, p<0.001, 95% CI 3.6 to 7.3).ConclusionsWe conclude that a simple ATLS based clinical tool that objectively categorises haemorrhagic shock is a useful part of the primary survey of the trauma patient, although a larger study with higher statistical power is required to evaluate this conclusion further.
Emergency department reported head injuries from skiing and snowboarding among children and adolescents, 1996–2010
Authors: Graves Janessa M , Whitehill Jennifer M , Stream Joshua O , Vavilala Monica S , Rivara Frederick P 
Published: March 2013

ObjectivesTo evaluate the incidence of snow-sports-related head injuries among children and adolescents reported to emergency departments (EDs), and to examine the trend from 1996 to 2010 in ED visits for snow-sports-related traumatic brain injury (TBI) among children and adolescents.MethodsA retrospective, population-based cohort study was conducted using data from the National Electronic Injury Surveillance System for patients (aged ≤17 years) treated in EDs in the USA from 1996 to 2010, for TBIs associated with snow sports (defined as skiing or snowboarding). National estimates of snow sports participation were obtained from the National Ski Area Association and utilised to calculate incidence rates. Analyses were conducted separately for children (aged 4–12 years) and adolescents (aged 13–17 years).ResultsAn estimated number of 78 538 (95% CI 66 350 to 90 727) snow sports-related head injuries among children and adolescents were treated in EDs during the 14-year study period. Among these, 77.2% were TBIs (intracranial injury, concussion or fracture). The annual average incidence rate of TBI was 2.24 per 10 000 resort visits for children compared with 3.13 per 10 000 visits for adolescents. The incidence of TBI increased from 1996 to 2010 among adolescents (p<0.003).ConclusionsGiven the increasing incidence of TBI among adolescents and the increased recognition of the importance of concussions, greater awareness efforts may be needed to ensure safety, especially helmet use, as youth engage in snow sports.
Preclinical Evaluation of a Novel ATM Inhibitor, KU59403, In Vitro and In Vivo in p53 Functional and Dysfunctional Models of Human Cancer
Authors: Batey Michael A. , Zhao Yan , Kyle Suzanne , Richardson Caroline , Slade Andrew , Martin Niall M.B. , Lau Alan , Newell David R. , Curtin Nicola J. 
Published: March 2013

Abstract
Ataxia telangiectasia mutated (ATM) kinase signals DNA double-strand breaks (DSB) to cell-cycle arrest via p53 and DNA repair. ATM-defective cells are sensitive to DSB-inducing agents, making ATM an attractive target for anticancer chemo- and radiosensitization. KU59403 is an ATM inhibitor with the potency, selectivity, and solubility for advanced preclinical evaluation. KU59403 was not cytotoxic to human cancer cell lines (SW620, LoVo, HCT116, and MDA-MB-231) per se but significantly increased the cytotoxicity of topoisomerase I and II poisons: camptothecin, etoposide, and doxorubicin. Chemo- and radiosensitization by ATM inhibition was not p53-dependent. Following administration to mice, KU59403 distributed to tissues and concentrations exceeding those required for in vitro activity were maintained for at least 4 hours in tumor xenografts. KU59403 significantly enhanced the antitumor activity of topoisomerase poisons in mice bearing human colon cancer xenografts (SW620 and HCT116) at doses that were nontoxic alone and well-tolerated in combination. Chemosensitization was both dose- and schedule-dependent. KU59403 represents a major advance in ATM inhibitor development, being the first compound to show good tissue distribution and significant chemosensitization in in vivo models of human cancer, without major toxicity. KU59403 provides the first proof-of-principle preclinical data to support the future clinical development of ATM inhibitors. Mol Cancer Ther; 12(6); 959–67. ©2013 AACR.
The Tyrosine Phosphatase SHP2 Regulates Focal Adhesion Kinase to Promote EGF-Induced Lamellipodia Persistence and Cell Migration
Authors: Hartman Zachary R. , Schaller Michael D. , Agazie Yehenew M. 
Published: March 2013

Abstract
The Src homology phosphotyrosyl phosphatase 2 (SHP2) is a positive effector of receptor tyrosine kinases (RTK) signaling. Furthermore, SHP2 is known to promote cell migration and invasiveness, key steps in cancer metastasis. To date, however, the mechanism by which SHP2 regulates cell movement is not fully understood. In the current report, a new role for SHP2 in regulating cell migration has been suggested. We show that SHP2 mediates lamellipodia persistence and cell polarity to promote directional cell migration in the MDA-MB231 and the MDA-MB468 basal-like and triple-negative breast cancer cell lines. We further show that SHP2 modulates the activity of focal adhesion kinase (FAK) by dephosphorylating pTyr397, the autophosphorylation site that primes FAK function. Because hyperactivation of FAK is known to counter the maturation of nascent focal complexes to focal adhesions, we propose that one of the mechanisms by which SHP2 promotes lamellipodia persistence is by downregulating FAK activity through dephosphorylation of pTyr397. The finding that inhibition of FAK activity partially restores EGF-induced lamellipodia persistence and cell migration in SHP2-silenced cells supports our proposition that SHP2 promotes growth factor–induced cell movement by acting, at least in part, on FAK. However, the effect of SHP2 inhibition in nonstimulated cells seems FAK independent as there was no significant difference between the control and the SHP2-silenced cells in pY397-FAK levels. Also, FAK inhibition did not rescue Golgi orientation defects in SHP2-silenced cells, suggesting that SHP2 acts through other mechanisms to promote cell polarity. Mol Cancer Res; 11(6); 651–64. ©2013 AACR.