bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public opinion of organ donation: a survey in Iran
Authors: Broumand Mohammadali , Parsapoor Alireza , Asghari Fariba 
Published: September 2012

AbstractIntroductionThe objective of this study was to assess the views of Tehran citizens in regard to donating their organs in case of brain death.MethodsIn this cross‐sectional study, conducted between February 2009 and November 2010, two interviewers contacted 1379 people through random digit dialing for phone interviews. Phone calls were made between 6 and 9 pmon a workday, and those reaching companies or organizations were excluded. The interviewee was selected randomly from among the household members, and those 18 yr and older were included in the study.ResultsOf the 1379 people eligible for entering the study, 706 consented to have the interview (response rate = 51%). Among the respondents, 84.6% were willing to donate. Of these, 94.6% were willing to complete a donor card as well, but only 10.7% of them already had one.ConclusionThere should be simple processes for the public to declare their decision about organ donation in case of brain death. People should be encouraged to communicate their wishes with others so that family members can decide about their organ donation more easily.
Effects of the dual PPAR‐α/γ agonist aleglitazar on glycaemic control and organ protection in the Zucker diabetic fatty rat
Authors: Bénardeau A. , Verry P. , Atzpodien E.‐A. , Funk J. M. , Meyer M. , Mizrahi J. , Winter M. , Wright M. B. , Uhles S. , Sebokova E. 
Published: September 2012

AimsTo evaluate the effects of aleglitazar, a dual peroxisome proliferator‐activated receptor‐α/γ agonist, on the development of diabetes‐related organ dysfunction, in relation to glycaemic and lipid changes, in Zucker diabetic fatty (ZDF) rats.MethodsSix‐week‐old, male ZDF rats received aleglitazar 0.3 mg/kg/day or vehicle as food admix for 13 weeks (n = 10 per group). Age‐matched male Zucker lean rats served as non‐diabetic controls. Plasma and renal markers were measured at several time points. Histopathology and quantitative immunohistochemistry were performed at 13 weeks.ResultsGlycated haemoglobin (5.4 vs. 9.2%) and blood glucose (8.3 ± 0.3 vs. 26.1 ± 1.0 mmol/l) were significantly reduced at 12 weeks with aleglitazar versus vehicle‐treated ZDF rats (both p < 0.01), while aleglitazar preserved near‐normal plasma insulin levels. Aleglitazar prevented the development of hypertriglyceridaemia (1.4 ± 0.1 vs. 8.5 ± 0.9 mmol/l) and reduced plasma non‐esterified fatty acids (0.09 ± 0.02 vs. 0.26 ± 0.04 mmol/l) relative to vehicle‐treated animals (both p < 0.01). Urinary glucose and protein concentrations were significantly reduced at 13 weeks with aleglitazar versus vehicle‐treated rats (both p < 0.01). Consistent with its effect on glycaemic control, aleglitazar protected β‐cell morphology, as evidenced by preservation of islet integrity, and reduction of β‐cell apoptosis and islet fibrosis. Aleglitazar prevented renal glomerular hypertrophy, podocyte degeneration, glomerulosclerosis, tubulo‐interstitial lesions and development of cataracts.ConclusionsAleglitazar strongly improved glycaemic and lipid parameters while protecting key tissues, including the pancreas, kidneys and eyes, against diabetes‐associated structural and functional changes in the ZDF rat.
KH902 suppresses high glucose‐induced migration and sprouting of human retinal endothelial cells by blocking VEGF and PIGF
Authors: Chen X. , Li J. , Li M. , Zeng M. , Li T. , Xiao W. , Li J. , Wu Q. , Ke X. , Luo D. , Tang S. , Luo Y. 
Published: September 2012

AbstractAimsVascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are upregulated in many ocular neovascular diseases such as diabetic retinopathy (DR). KH902 is a recombinant fusion protein with its binding ligand taken from the domains of VEGF receptor‐1 (VEGFR‐1) and VEGF receptor‐2 (VEGFR‐2) and can bind all VEGF‐A isoforms and PlGF. The aim of this study was to investigate the underlying mechanisms of anti‐angiogenic effects of KH902.MethodsThe toxic effect of KH902 on cultured human retinal endothelial cells (HRECs) was measured by Annexin V/PI staining and MTT assay. The concentrations of secreted VEGF and PlGF were measured by ELISA. The migration of HRECs was assessed by scratch wound and transwell assay. The sprouting of HRECs was determined by tube formation assay. The protein levels of Src, p‐Src, PI3K, Akt1, p‐Akt1, Erk1/2 and p‐Erk1/2 were measured by Western blot.ResultsKH902 at the concentrations from 100 ng/ml to 100 µg/ml had no cytotoxicity to cultured HRECs. KH902 bound not only VEGF165, but also PlGF that were secreted by HRECs under high glucose condition. A 500 ng/ml of KH902 significantly suppressed high glucose‐induced migration and sprouting of HRECs through downregulating the expression of PI3K and inhibiting the activation of Src, Akt1 and Erk1/2.ConclusionOur study indicates that KH902 suppresses high glucose‐induced migration and sprouting of HRECs through not only binding VEGF, but also PlGF to inhibit the activation of Src‐Akt1‐Erk1/2 pathway. KH902 is a drug that potentially inhibits angiogenic pathways involving in DR or other ocular neovascular diseases.
Efficacy and tolerability of taspoglutide versus pioglitazone in subjects with type 2 diabetes uncontrolled with sulphonylurea or sulphonylurea‐metformin therapy: a randomized, double‐blind study (T‐emerge 6)
Authors: Pratley R. E. , Urosevic D. , Boldrin M. , Balena R. ,   for the T‐emerge 6 Study Group
Published: September 2012

AbstractAimsThis study compared the efficacy and tolerability of taspoglutide versus pioglitazone in subjects with type 2 diabetes inadequately controlled with sulphonylurea ± metformin.MethodsIn this double‐blind, double‐dummy, parallel‐group trial, 760 subjects (49% male, age 56.4 years, diabetes duration 8.8 years, body mass index 32.7 kg/m2 and haemoglobin A1c [HbA1c] 8.3%) were randomized (1 : 1 : 1) to subcutaneous injections of taspoglutide 10 or 20 mg once weekly or oral pioglitazone 45 mg daily. The primary endpoint was change in HbA1c after 24 weeks.ResultsMean (±s.e.) HbA1c reductions with taspoglutide 10 (−1.18 ± 0.08%) and 20 mg (−1.36 ± 0.08%) were non‐inferior to pioglitazone (−1.30 ± 0.08%) (p = 0.21 and 0.37, respectively); mean treatment differences were 0.12 (95% confidence interval: −0.03, –0.26) and −0.06 (−0.20, 0.08) for taspoglutide 10 and 20 mg versus pioglitazone. Mean (±s.e.) changes in body weight (kg) were −0.8 ± 0.3, −1.0 ± 0.3 and 3.6 ± 0.3 for taspoglutide 10 and 20 mg and pioglitazone, respectively; 8, 11 and 1% of patients achieved ≥5% weight loss. A higher incidence of adverse events (AEs) occurred with taspoglutide, predominantly gastrointestinal disturbances and injection‐site reactions, resulting in higher rates of discontinuation versus pioglitazone. No treatment differences in serious AEs were observed.ConclusionsTaspoglutide offered good glycaemic control similar to pioglitazone, while achieving beneficial weight loss rather than weight gain, but was associated with more AEs. Due to the higher than expected discontinuation rates, mainly because of gastrointestinal intolerability, the taspoglutide clinical programme was stopped.
Shared influence of pathogen and host genetics on a trade‐off between latent period and spore production capacity in the wheat pathogen, Puccinia triticina
Authors: Pariaud Bénédicte , van den Berg Femke , van den Bosch Frank , Powers Stephen J. , Kaltz Oliver , Lannou Christian 
Published: September 2012

AbstractCrop pathogens are notorious for their rapid adaptation to their host. We still know little about the evolution of their life cycles and whether there might be trade‐offs between fitness components, limiting the evolutionary potential of these pathogens. In this study, we explored a trade‐off between spore production capacity and latent period in Puccinia triticina, a fungal pathogen causing leaf rust on wheat. Using a simple multivariate (manova) technique, we showed that the covariance between the two traits is under shared control of host and pathogen, with contributions from host genotype (57%), pathogen genotype (18.4%) and genotype × genotype interactions (12.5%). We also found variation in sign and strength of genetic correlations for the pathogen, when measured on different host varieties. Our results suggest that these important pathogen life‐history traits do not freely respond to directional selection and that precise evolutionary trajectories are contingent on the genetic identity of the interacting host and pathogen.
Epidermal morphogenesis during progressive in vitro 3D reconstruction at the air–liquid interface
Authors: Frankart Aurélie , Malaisse Jérémy , De Vuyst Evelyne , Minner Frédéric , de Rouvroit Catherine Lambert , Poumay Yves 
Published: September 2012

AbstractKeratinocyte monolayers, cultured in immersed conditions, constitute a frequently used in vitro model system to study keratinocytes behaviour in response to environmental assaults. However, monolayers lack the keratinocyte terminal differentiation and the organization of the epidermal tissue, which are observed in vivo. Advancements of in vitro techniques were used to reconstruct three‐dimensional equivalents that mimic human epidermis in terms of layering, differentiation and barrier function. Here, we update a published method and illustrate the progressive morphogenesis responsible for in vitro reconstruction. The analysis of cell proliferation, expression of differentiation markers and barrier efficacy demonstrate the excellent similarity of the reconstructed tissue with normal human epidermis. Availability of epidermal tissue during its reconstruction phase in culture appears crucial for studies intending to challenge the barrier function.
Androgen actions on the human hair follicle: perspectives
Authors: Inui Shigeki , Itami Satoshi 
Published: September 2012

AbstractAndrogens stimulate beard growth but suppress hair growth in androgenetic alopecia (AGA). This condition is known as ‘androgen paradox’. Human pilosebaceous units possess enough enzymes to form the active androgens testosterone and dihydrotestosterone. In hair follicles, 5α‐reductase type 1 and 2, androgen receptors (AR) and AR coactivators can regulate androgen sensitivity of dermal papillae (DP). To regulate hair growth, androgens stimulate production of IGF‐1 as positive mediators from beard DP cells and of TGF‐β1, TGF‐β2, dickkopf1 and IL‐6 as negative mediators from balding DP cells. In addition, androgens enhance inducible nitric oxide synthase from occipital DP cells and stem cell factor for positive regulation of hair growth in beard and negative regulation of balding DP cells. Moreover, AGA involves crosstalk between androgen and Wnt/β‐catenin signalling. Finally, recent data on susceptibility genes have provided us with the impetus to investigate the molecular pathogenesis of AGA.
A rising tide of blue‐absorbing biliprotein photoreceptors – characterization of seven such bilin‐binding GAF domains in Nostoc sp. PCC7120
Authors: Ma Qiong , Hua Huan‐Huan , Chen Yu , Liu Bin‐Bin , Krämer Anna Laura , Scheer Hugo , Zhao Kai‐Hong , Zhou Ming 
Published: September 2012

Cyanobacteriochromes are photochromic sensory photoreceptors in cyanobacteria that are related to phytochromes but cover a much broader spectral range. Using a homology search, a group of putative blue‐absorbing photoreceptors was identified in Nostoc sp. PCC 7120 that, in addition to the canonical chromophore‐binding cysteine of cyanobacteriochromes, have a conserved extra cysteine in a DXCF motif. To assess their photochemical activities, putative chromophore‐binding GAF domains were expressed in Escherichia coli together with the genes for phycocyanobilin biosynthesis. All except one covalently bound a chromophore and showed photoreversible photochromic responses, with absorption at approximately 420 nm for the 15Z states formed in the dark, and a variety of red‐shifted absorption peaks in the 490–600 nm range for the 15E states formed after light activation. Under denaturing conditions, the covalently bound chromophores were identified as phycocyanobilin, phycoviolobilin or mixtures of both. The canonical cysteines and those of the DXCF motifs were mutated, singly or together. The canonical cysteine is responsible for stable covalent attachment of the bilin to the apo‐protein at C31. The second linkage from the cysteine in the DXCF motif, probably to C10 of the chromophore, yields blue‐absorbing rubin‐type 15Z chromophores, but is lost in most cases upon photoconversion to the 15E isomers of the chromophores, and also when denatured with acidic urea.
A plant's perspective of extremes: terrestrial plant responses to changing climatic variability
Authors: Reyer Christopher P.O. , Leuzinger Sebastian , Rammig Anja , Wolf Annett , Bartholomeus Ruud P. , Bonfante Antonello , de Lorenzi Francesca , Dury Marie , Gloning Philipp , Abou Jaoudé Renée , Klein Tamir , Kuster Thomas M. , Martins Monica , Niedrist Georg , Riccardi Maria , Wohlfahrt Georg , de Angelis Paolo , de Dato Giovanbattista , François Louis , Menzel Annette , Pereira Marízia 
Published: September 2012

AbstractWe review observational, experimental, and model results on how plants respond to extreme climatic conditions induced by changing climatic variability. Distinguishing between impacts of changing mean climatic conditions and changing climatic variability on terrestrial ecosystems is generally underrated in current studies. The goals of our review are thus (1) to identify plant processes that are vulnerable to changes in the variability of climatic variables rather than to changes in their mean, and (2) to depict/evaluate available study designs to quantify responses of plants to changing climatic variability. We find that phenology is largely affected by changing mean climate but also that impacts of climatic variability are much less studied, although potentially damaging. We note that plant water relations seem to be very vulnerable to extremes driven by changes in temperature and precipitation and that heatwaves and flooding have stronger impacts on physiological processes than changing mean climate. Moreover, interacting phenological and physiological processes are likely to further complicate plant responses to changing climatic variability. Phenological and physiological processes and their interactions culminate in even more sophisticated responses to changing mean climate and climatic variability at the species and community level. Generally, observational studies are well suited to study plant responses to changing mean climate, but less suitable to gain a mechanistic understanding of plant responses to climatic variability. Experiments seem best suited to simulate extreme events. In models, temporal resolution and model structure are crucial to capture plant responses to changing climatic variability. We highlight that a combination of experimental, observational, and/or modeling studies have the potential to overcome important caveats of the respective individual approaches.
Widespread decreases in topsoil inorganic carbon stocks across China's grasslands during 1980s–2000s
Authors: Yang Yuanhe , Fang Jingyun , Ji Chengjun , Ma Wenhong , Mohammat Anwar , Wang Shifeng , Wang Shaopeng , Datta Arindam , Robinson David , Smith Pete 
Published: September 2012

AbstractSoil carbon (C) stocks consist of inorganic and organic components, ~1.7 times larger than the total of the C stored in vegetation and the atmosphere together. Significant soil C losses could thus offset any C sink in vegetation, creating a positive feedback to climate change. However, compared with the susceptible sensitivity of organic matter decay to climate warming, soil inorganic carbon (SIC) stocks are often assumed to be relatively stable. Here, we evaluated SIC changes across China's grasslands over the last two decades using data from a recent regional soil survey during 2001–2005 and historical national soil inventory during the 1980s. Our results showed that SIC stocks in the top 10 cm decreased significantly between the two sampling periods, with a mean rate of 26.8 (95% confidence interval: 15.8–41.7) g C m−2 yr−1. The larger decreases in SIC stocks were observed in those regions with stronger soil acidification and richer soil carbonates. The lost SIC could be released to the atmosphere as carbon dioxide, redistributed to the deeper soil layer, and transferred to the nearby regions. The fraction of soil carbonates entering into the atmosphere may diminish the strength of terrestrial C sequestration and amplify the positive C‐climate feedback.
F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort
Authors: Schwarz J. , Astermark J. , Menius E. D. , Carrington M. , Donfield S. M. , Gomperts E. D. , Nelson G. W. , Oldenburg J. , Pavlova A. , Shapiro A. D. , Winkler C. A. , Berntorp E. ,   from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort
Published: September 2012

SummaryAncestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual.
HLA‐A, ‐B, ‐DR allele group frequencies in 7007 kidney transplant list patients in 27 UK centres
Authors: Burt C. , Cryer C. , Fuggle S. , Little A.‐M. , Dyer P. 
Published: September 2012

SummaryThis observational study aims to determine the HLA specificity frequencies of patients on the UK renal transplant list, which can be used as a resource for those laboratories that support the UK renal transplant programme. Whilst the HLA specificity frequencies may differ from that of the general population, it is the individuals on the transplant list who are in need of a new kidney, which has to be provided from the general population. Any differences in protein allele frequencies between this patient population and the general population are likely to be minimal because of the very large number of patients included. The HLA‐A, ‐B and ‐DR allele group frequencies from 7007 patients on the UK kidney transplant list (August, 2009) were analysed. HLA types had been submitted to NHSBT to register patients on the UK deceased donor kidney waiting list. The data were submitted from 27 different registering centres throughout the UK. Within this data set, 25 different HLA‐A, 50 HLA‐B and 18 HLA‐DR allele groups were present. The most common allele groups at each locus were ‐A2 (phenotype frequency 42.6%), ‐B44 (phenotype frequency 23.3%) and –DR4 (phenotype frequency 29.8%). The least common allele groups at each locus were ‐A19, ‐ A43, ‐B16, ‐B21, ‐B22, ‐B83 and ‐DR5. Reports of HLA frequency (protein allotype) data from populations as large as this are not readily available adding value to this observational study.
A phylogenetic analysis of relationships among genera of Conopidae (Diptera) based on molecular and morphological data
Authors: Gibson Joel F. , Skevington Jeffrey H. , Kelso Scott 
Published: September 2012

AbstractMembers of the family Conopidae (Diptera) have been the focus of little targeted phylogenetic research. The most comprehensive test of phylogenetic support for the present subfamily classification of Conopidae is presented here using 66 specimens, including 59 species of Conopidae and seven outgroup taxa. Relationships among subfamily clades are also explored. A total of 6824 bp of DNA sequence data from five gene regions (12S ribosomal DNA, cytochrome c oxidase subunit I, cytochrome b, 28S ribosomal DNA and alanyl‐tRNA synthetase) are combined with 111 morphological characters in a combined analysis using both parsimony and Bayesian methods. Parsimony analysis recovers three shortest trees. Bayesian analysis recovers a nearly identical tree. Five monophyletic subfamilies of Conopidae are recovered. The rarely acknowledged Zodioninae is restored, including the genera Zodion and Parazodion. The genus Sicus is removed from Myopinae. Morphological synapomorphies are discussed for each subfamily and inter‐subfamily clade, including a comprehensive review of the character interpretaions of previous authors. Included are detailed comparative illustrations of male and female genitalia of representatives of all five subfamilies with new morphological interpretation.
Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
Authors: Hanley Michael J. , Masse Gina , Harmatz Jerold S. , Cancalon Paul F. , Dolnikowski Gregory G. , Court Michael H. , Greenblatt David J. 
Published: September 2012

AimThe present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9).MethodsA 50:50 mixture of lowbush and highbush BBJ was evaluated in vitro as an inhibitor of CYP3A activity (hydroxylation of triazolam and dealkylation of buspirone) and of CYP2C9 activity (flurbiprofen hydroxylation) using human liver microsomes. In clinical studies, clearance of oral buspirone and oral flurbiprofen was studied in healthy volunteers with and without co‐treatment with BBJ.ResultsBBJ inhibited CYP3A and CYP2C9 activity in vitro, with 50% inhibitory concentrations (IC50) of less than 2%, but without evidence of mechanism‐based (irreversible) inhibition. Grapefruit juice (GFJ) also inhibited CYP3A activity, but inhibitory potency was increased by pre‐incubation, consistent with mechanism‐based inhibition. In clinical studies, GFJ significantly increased area under the plasma concentration−time curve (AUC) for the CYP3A substrate buspirone. The geometric mean ratio (GMR = AUC with GFJ divided by AUC with water) was 2.12. In contrast, the effect of BBJ (GMR = 1.39) was not significant. In the study of flurbiprofen (CYP2C9 substrate), the positive control inhibitor fluconazole significantly increased flurbiprofen AUC (GMR = 1.71), but BBJ had no significant effect (GMR = 1.03).ConclusionThe increased buspirone AUC associated with BBJ is quantitatively small and could have occurred by chance. BBJ has no effect on flurbiprofen AUC. The studies provide no evidence for concern about clinically important pharmacokinetic drug interactions of BBJ with substrate drugs metabolized by CYP3A or CYP2C9.