bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic copy‐number alterations of MYC and FHIT genes are associated with survival in esophageal squamous‐cell carcinoma
Authors: Miyawaki Yutaka , Kawachi Hiroshi , Ooi Akishi , Eishi Yoshinobu , Kawano Tatsuyuki , Inazawa Johji , Imoto Issei 
Published: May 2012

Esophageal squamous‐cell carcinoma (ESCC) is one of the most common cancers and is associated with a poor prognosis. Studies are warranted on the clinical relevance of its genomic copy‐number alterations (CNA) as prognosticators for ESCC. In the present study, we first screened recurrent CNA by array‐based comparative genomic hybridization using an in‐house focused bacterial artificial chromosome‐based array for 108 loci in 45 ESCC specimens. We detected 14 regions showing recurrent (>20%) CNA (4 losses and 10 gains) by array‐based comparative genomic hybridization in the first cohort. Among them, loss of 3p14.2 and gain of 8q24.21 for the FHIT and MYC genes, respectively, and the accumulation of those two CNA (higher FM‐CNA scores) were significantly associated with a worse overall survival (OS) in the first cohort (P = 0.0273, P = 0.0356 and P = 0.0089, respectively). In the independent validation cohort of 92 resected ESCC cases, loss of FHIT, gain of MYC and higher FM‐CNA scores determined by a quantitative genomic PCR‐based copy‐number analysis were associated with a worse OS (P = 0.0011, P = 0.0104 and P = 0.0008, respectively) and disease‐free survival (P = 0.0038, P = 0.0132 and P = 0.0021, respectively). In addition, the Cox model showed the presence of either CNA to be an independent prognosticator for OS and disease‐free survival in the validation cohort (P = 0.0120 and P = 0.0255, respectively). These results suggest that CNA of MYC and FHIT are poor prognostic markers, and risk stratification based on the copy‐number status of those genes is useful to select the optimal treatment strategy in resected ESCC patients. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02329.x, 2012)
Prospective memory and future event simulation in individuals with alcohol dependence
Authors: Griffiths Alison , Hill Robert , Morgan Celia , Rendell Peter G. , Karimi Khashayar , Wanagaratne Shamil , Curran H. Valerie 
Published: May 2012

AbstractAimTo assess objectively prospective memory (PM) performance of individuals with alcohol dependence and determine whether the use of an imagery technique at the point of encoding can enhance their performance.DesignAn independent group design was used to compare individuals with alcohol dependence with social drinkers.SettingOne UK residential substance misuse service.ParticipantsTwenty‐four abstinent ‘individuals with alcohol dependence’ and 24 social drinkers matched on age, gender and years of education.MeasurementsThe virtual week (VW); story recall; a category fluency task; trail‐making test (TMT); a single digit cancellation task (SDCT); spot‐the‐word; State–Trait Anxiety Inventory (STAI); Beck Depression Inventory (BDI‐II); and the Severity of Alcohol Dependence Questionnaire (SAD‐Q)FindingsEvent‐based PM task performance of individuals with alcohol dependence was associated strongly with indices of alcohol usage (P < 0.001), and was impaired significantly compared to that of social drinkers (P < 0.001). Imagining improved social drinkers' time‐based PM but not that of individuals with alcohol dependence.ConclusionsIndividuals with alcohol dependence may experience prospective memory deficits which may be due to difficulties with effective strategy application.
Amino acids in Tobamovirus coat protein controlling pepper L1a gene‐mediated resistance
Authors: MIZUMOTO HIROYUKI , NAKAMURA IKUMI , SHIMOMOTO YOSHIFUMI , SAWADA HIROMASA , TOMITA REIKO , SEKINE KEN‐TARO , KIBA AKINORI , NISHIGUCHI MASAMICHI , KOBAYASHI KAPPEI , HIKICHI YASUFUMI 
Published: May 2012

SUMMARYIn pepper plants (genus Capsicum), the resistance against Tobamovirus spp. is conferred by L gene alleles. The recently identified L variant L1a can recognize coat proteins (CPs) of Tobacco mild green mosaic virus Japanese strain (TMGMV‐J) and Paprika mild mottle virus Japanese strain (PaMMV‐J), but not of Pepper mild mottle virus (PMMoV), as the elicitor to induce resistance at 24 °C. Interestingly, L1a gene‐mediated resistance against TMGMV‐J, but not PaMMV‐J, is retained at 30 °C. This observation led us to speculate that L1a can discriminate between CPs of TMGMV‐J and PaMMV‐J. In this study, we aimed to determine the region(s) in CP by which L1a distinguishes TMGMV‐J from PaMMV‐J. By using chimeric CPs consisting of TMGMV‐J and PaMMV‐J, we found that the chimeric TMGMV‐J CP, whose residues in the β‐sheet domain were replaced by those of PaMMV‐J, lost its ability to induce L1a gene‐mediated resistance at 30 °C. In contrast, the chimeric PaMMV‐J CP with the β‐sheet domain replaced by TMGMV‐J CP was able to induce L1a gene‐mediated resistance at 30 °C. Furthermore, viral particles were not detected in the leaves inoculated with either chimeric virus. These observations indicated that the amino acids within the β‐sheet domain were involved in both the induction of L1a gene‐mediated resistance and virion formation. Further analyses using chimeric CPs of TMGMV‐J and PMMoV indicated that amino acids within the β‐sheet domain alone were not sufficient for the induction of L1a gene‐mediated resistance by TMGMV‐J CP. These results suggest that multiple regions in Tobamovirus CP are implicated in the induction of L1a gene‐mediated resistance.
Apple juice greatly reduces systemic exposure to atenolol
Authors: Jeon Hyewon , Jang In‐Jin , Lee SeungHwan , Ohashi Kyoichi , Kotegawa Tsutomu , Ieiri Ichiro , Cho Joo‐Youn , Yoon Seo Hyun , Shin Sang‐Goo , Yu Kyung‐Sang , Lim Kyoung Soo 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Atenolol is an antihypertensive drug, of which negligible amounts are metabolized.• Fruit juices may decrease the oral absorption of drugs by inhibiting intestinal drug transporters, as demonstrated in vitro and in vivo.WHAT THIS STUDY ADDS• The pharmacokinetic characteristics of atenolol were determined according to the SLCO2B1 genotype after apple juice administration in healthy Korean volunteers.• Apple juice ingestion markedly reduced the systemic exposure to atenolol, but genetic variations in SLCO2B1 were unlikely to contribute substantial variability to the pharmacokinetics of atenolol.AIM Fruit juice reduces the plasma concentrations of several β‐adrenoceptor blockers, likely by inhibiting OATP2B1‐mediated intestinal absorption. The aim of this study was to investigate the effects of apple juice on the pharmacokinetics of atenolol.METHODS Twelve healthy Korean volunteers with genotypes of SLCO2B1 c.1457C> T (*1/*1 (n= 6) and *3/*3 (n= 6)) were enrolled in this study. In a three‐phase, one‐sequence crossover study, the pharmacokinetics (PK) of atenolol was evaluated after administration of 50 mg atenolol. Subjects received atenolol with either 300 ml water, 1200 ml apple juice or 600 ml apple juice.RESULTS Apple juice markedly reduced the systemic exposure to atenolol. The geometric mean ratios (95% confidence intervals) of apple juice : water were 0.18 (0.13, 0.25, 1200 ml) and 0.42 (0.30, 0.59, 600 ml) for the AUC(0,tlast). In this study, the PK parameters of atenolol responded in a dose‐dependent manner to apple juice.CONCLUSIONS Apple juice markedly reduced systemic exposure to atenolol. The genetic variation of SLCO2B1 c.1457C>T had a minimal effect on the pharmacokinetics of atenolol when the drug was administered with water or apple juice.
The risk of adverse outcomes in association with use of testosterone products: a cohort study using the UK‐based general practice research database
Authors: Jick Susan S. , Hagberg Katrina Wilcox 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Testosterone products are indicated for primary or secondary hypogonadism and can be delivered through various routes including oral and intramuscular injection.• While many clinical trials have evaluated the effectiveness of testosterone therapy, there is little information on safety particularly in different formulations.• Hypertension, polycythemia and prostatic abnormalities (prostatism, benign prostatic hypertrophy or prostate cancer) have been identified as potential adverse effects of testosterone replacement therapy, but data are limited.WHAT THIS STUDY ADDS• Risks of prostate cancer and prostatism were similar in users of the oral and injectable testosterone preparations, but risks were higher for hypertension and polycythemia in the injectable compared with the oral testosterone users.• Risk of benign prostatic hypertrophy was slightly higher in the oral users, but the difference was small and could have been due to bias.AIMS To study the relative safety of the intramuscular injection formulation of testosterone with oral testosterone undecanoate in relation to the risks for hypertension, polycythemia, prostate cancer, benign prostatic hypertrophy (BPH) and prostatism.METHODS We conducted a cohort study of men in the UK based General Practice Research Database who were users of the oral undecanoate and injectable forms of testosterone and calculated rates and relative risks of hypertension, polycythemia and prostate conditions (cancer, BPH and prostatism).RESULTS We identified 5841 men who received at least one study testosterone preparation. There were 202 cases of hypertension (crude incidence rates (IRs) for oral and injectable testosterone respectively 12.3/1000 person‐years (PY) and 14.4/1000 PY). There were 146 cases of polycythemia (IRs 1.2/1000 PY and 10.1/1000 PY), 46 cases of prostate cancer (IRs 2.5/1000 PY and 1.8/1000 PY), 106 cases of BPH (IRs 4.1 /1000 PY and 2.1/1000 PY), and 251 cases of prostatism (IRs 8.4/1000 PY and 6.1/1000 PY respectively). Adjusted relative risks for oral compared with injectable testosterone were 0.8 (95% CI 0.6, 1.2) for hypertension, 0.13 (0.05, 0.35) for polycythemia, 1.1 (0.7, 1.7) for prostate cancer, 1.5 (1.1, 2.2) for BPH and 1.1 (0.8, 1.4) for prostatism.CONCLUSIONS Risks of prostate cancer and prostatism were similar in users of the two preparations, but risks were higher for hypertension and polycythemia in the injectable compared with the oral testosterone users. Risk of BPH was slightly higher in the oral users, but the difference was small and could have been due to bias.
Environmental interactions during host race formation: host fruit environment moderates a seasonal shift in phenology in host races of Rhagoletis pomonella
Authors: Ragland Gregory J. , Sim Sheina B. , Goudarzi Serra , Feder Jeffrey L. , Hahn Daniel A. 
Published: May 2012

Summary1. Host race formation is a common form of ecological speciation during which new populations that exploit a novel host (e.g. nutritional resource) experience divergent natural selection, causing adaptive divergence from the ancestral population. Typically, multiple selection pressures drive this divergence, suggesting that interactions among environmental effects may be critical during the speciation process.2. Host‐race‐forming phytophagous insects often experience divergent natural selection imposed by seasonality and nutritional environment, two factors likely to interact through their effects on growth and life‐history timing. We tested for the presence of such an interaction in the apple maggot fly, Rhagoletis pomonella, asking whether nutritional effects interact with seasonality to determine overwintering success.3. We find evidence for such an interaction, wherein feeding on a novel host fruit actually mitigates the negative effects of novel seasonality. Feeding on apple (novel) compared to hawthorn (ancestral) fruit conferred greater fly lipid reserves the overwintering, diapause stage. Earlier, seasonal emergence characteristic of the apple host race imposes an overwintering survival cost. But feeding on apples offsets this cost, which confers greater pupal lipid reserves and consequently larger adult body size post‐winter. Seasonality and host fruit interact to determine fly lipid reserves, and host race differences in lipid content are maximized under the most stressful conditions typically experienced by the apple host race. F1 rearing and genetic association tests revealed no evidence for genetically based divergence in lipid content, suggesting that differences in lipid storage among the fly host races are driven primarily by the host fruit environment.4. Our results suggest that interactions between seasonality and host plant environment shape natural selection and therefore influence adaptive divergence during host race formation.
Long‐term nitrogen additions increase likelihood of climate stress and affect recovery from wildfire in a lowland heath
Authors: Southon Georgina E. , Green Emma R. , Jones Alan G. , Barker Chris G. , Power Sally A. 
Published: May 2012

AbstractIncreases in the emissions and associated atmospheric deposition of nitrogen (N) have the potential to cause significant changes to the structure and function of N‐limited ecosystems. Here, we present the results of a long‐term (13 year) experiment assessing the impacts of N addition (30 kg ha−1 yr−1) on a UK lowland heathland under a wide range of environmental conditions, including the occurrence of prolonged natural drought episodes and a severe summer fire. Our findings indicate that elevated N deposition results in large, persistent effects on Calluna growth, phenology and chemistry, severe suppression of understorey lichen flora and changes in soil biogeochemistry. Growing season rainfall was found to be a strong driver of inter‐annual variation in Calluna growth and, although interactions between N and rainfall for shoot growth were not significant until the later phase of the experiment, N addition exacerbated the extent of drought injury to Calluna shoots following naturally occurring droughts in 2003 and 2009. Following a severe wildfire at the experimental site in 2006, heathland regeneration dynamics were significantly affected by N, with a greater abundance of pioneering moss species and suppression of the lichen flora in plots receiving N additions. Significant interactions between climate and N were also apparent post fire, with the characteristic stimulation in Calluna growth in +N plots suppressed during dry years. Carbon (C) and N budgets demonstrate large increases in both above‐ and below‐ground stocks of these elements in N‐treated plots prior to the fire, despite higher levels of soil microbial activity and organic matter turnover. Although much of the organic material was removed during the fire, pre‐existing treatment differences were still evident following the burn. Post fire accumulation of below‐ground C and N stocks was increased rapidly in N‐treated plots, highlighting the role of N deposition in ecosystem C sequestration.
Drivers and export performance impacts of IT capability in ‘born‐global’ firms: a cross‐national study
Authors: Zhang Man , Sarker Saonee , Sarker Suprateek 
Published: May 2012

AbstractPast research focusing on large firms has argued that information technology (IT) capability enhances firm performance. However, these studies have seldom explored why firms develop IT capability, and have also left a void the understanding of the role of IT capability in Small‐ and medium‐sized enterprises (SMEs). This study attempts to fill that void by examining the effect of relevant environmental and firm‐level factors on IT capability, and the effect of IT capability on the export performance of Chinese and US born‐global firms, a special breed of export‐focused SMEs. Results indicate that environmental factors such as information intensity, and firm‐level factors such as international entrepreneurial orientation, prompt born‐global firms to develop IT capability. Further, our results also strongly emphasise the positive role that IT capability plays on the performance of born‐global firms. Finally, a comparative analysis of the Chinese and US born‐global firms revealed a lack of a cross‐cultural difference in the factors leading these firms to develop IT capability, therefore supporting the ‘convergence’ perspective in cross‐cultural research.
The Neurohypophysis: Fishing for New Insights
Authors: Gutnick Amos , Levkowitz Gil 
Published: May 2012

SummaryThe neurohypophysis is a neurovascular interface through which the brain regulates peripheral organs to maintain homeostasis. The molecular mechanisms underlying its formation are poorly understood, although the emergence of new genetic and imaging tools has begun to yield new insights. In a recent study, researchers discovered that, in embryonic zebrafish, oxytocin secreted from hypophyseal axons serves as a local angiogenic cue that pulls in nearby blood vessels.
Common misconceptions in molecular ecology: echoes of the modern synthesis
Authors: KARL STEPHEN A. , TOONEN R. J. , GRANT W. S. , BOWEN B. W. 
Published: May 2012

AbstractThe field of molecular ecology has burgeoned into a large discipline spurred on by technical innovations that facilitate the rapid acquisition of large amounts of genotypic data, by the continuing development of theory to interpret results, and by the availability of computer programs to analyse data sets. As the discipline grows, however, misconceptions have become enshrined in the literature and are perpetuated by routine citations to other articles in molecular ecology. These misconceptions hamper a better understanding of the processes that influence genetic variation in natural populations and sometimes lead to erroneous conclusions. Here, we consider eight misconceptions commonly appearing in the literature: (i) some molecular markers are inherently better than other markers; (ii) mtDNA produces higher FST values than nDNA; (iii) estimated population coalescences are real; (iv) more data are always better; (v) one needs to do a Bayesian analysis; (vi) selective sweeps influence mtDNA data; (vii) equilibrium conditions are critical for estimating population parameters; and (viii) having better technology makes us smarter than our predecessors. This is clearly not an exhaustive list and many others can be added. It is, however, sufficient to illustrate why we all need to be more critical of our own understanding of molecular ecology and to be suspicious of self‐evident truths.
Phylodynamics of H5N1 avian influenza virus in Indonesia
Authors: LAM TOMMY TSAN‐YUK , HON CHUNG‐CHAU , LEMEY PHILIPPE , PYBUS OLIVER G. , SHI MANG , TUN HEIN MIN , LI JUN , JIANG JINGWEI , HOLMES EDWARD C. , LEUNG FREDERICK CHI‐CHING 
Published: May 2012

AbstractUnderstanding how pathogens invade and become established in novel host populations is central to the ecology and evolution of infectious disease. Influenza viruses provide unique opportunities to study these processes in nature because of their rapid evolution, extensive surveillance, large data sets and propensity to jump species boundaries. H5N1 highly pathogenic avian influenza virus (HPAIV) is a major animal pathogen and public health threat. The virus is of particular importance in Indonesia, causing severe outbreaks among poultry and sporadic human infections since 2003. However, little is known about how H5N1 HPAIV emerged and established in Indonesia. To address these questions, we analysed Indonesian H5N1 HPAIV gene sequences isolated during 2003–2007. We find that the virus originated from a single introduction into East Java between November 2002 and October 2003. This invasion was characterized by an initially rapid burst of viral genetic diversity followed by a steady rate of lineage replacement and the maintenance of genetic diversity. Several antigenic sites in the haemagglutinin gene were subject to positive selection during the early phase, suggesting that host‐immune‐driven selection played a role in host adaptation and expansion. Phylogeographic analyses show that after the initial invasion of H5N1, genetic variants moved both eastwards and westwards across Java, possibly involving long‐distance transportation by humans. The phylodynamics we uncover share similarities with other recently studied viral invasions, thereby shedding light on the ecological and evolutionary processes that determine disease emergence in a new geographical region.
DWARF50 (D50), a rice (Oryza sativa L.) gene encoding inositol polyphosphate 5‐phosphatase, is required for proper development of intercalary meristem
Authors: SATO‐IZAWA KANNA , NAKABA SATOSHI , TAMURA KATSUNORI , YAMAGISHI YUSUKE , NAKANO YOSHIMI , NISHIKUBO NOBUYUKI , KAWAI SHINYA , KAJITA SHINYA , ASHIKARI MOTOYUKI , FUNADA RYO , KATAYAMA YOSHIHIRO , KITANO HIDEMI 
Published: May 2012

ABSTRACTRice internodes are vital for supporting high‐yield panicles, which are controlled by various factors such as cell division, cell elongation and cell wall biosynthesis. Therefore, formation and regulation of the internode cell‐producing intercalary meristem (IM) are important for determining the shape of internodes. To understand the regulation of internode development, we analysed a rice dwarf mutant, dwarf 50 (d50). Previously, we reported that parenchyma cells in the elongated internodes of d50 ectopically deposit cell wall phenolics. In this study, we revealed that D50 encodes putative inositol polyphosphate 5‐phosphatase (5PTase), which may be involved in phosphoinositide signalling required for many essential cellular functions, such as cytoskeleton organization, endocytosis and vesicular trafficking in eukaryotes. Analysis of the rice genome revealed 20 putative 5PTases including D50. The d50 mutation induced abnormally oriented cell division, irregular deposition of cell wall pectins and thick actin bundles in the parenchyma cells of the IM, resulting in abnormally organized cell files of the internode parenchyma and dwarf phenotype. Our results suggest that the putative 5PTase, encoded by D50, is essential for IM formation, including the direction of cell division, deposition of cell wall pectins and control of actin organization.
Cause of death distribution with InterVA and physician coding in a rural area of Burkina Faso
Authors: Ramroth Heribert , Lorenz Eva , Rankin Johanna C. , Fottrell Edward , Yé Maurice , Neuhann Florian , Ssennono Mark , Sié Ali , Byass Peter , Becher Heiko 
Published: May 2012

AbstractObjectives  To compare the cause of death distribution using the Physician Coded Verbal Autopsy approach versus the Interpreting Verbal Autopsy model, based on information from a French verbal autopsy questionnaire, in rural north‐western Burkina Faso.Methods  Data from 5649 verbal autopsy questionnaires reviewed by local physicians at the Nouna Health and Demographic Surveillance Site between 1998 and 2007 were considered for analyses. Information from VA interviews was extracted to create a set of standard indicators needed to run the Interpreting Verbal Autopsy model. Cause‐specific mortality fractions were used to compare Physician Coded Verbal Autopsy and Interpreting Verbal Autopsy results.Results  At the population level, 62.5% of causes of death using the Interpreting Verbal Autopsy model corresponded with those determined by two or three physicians. Although seven of the 10 main causes of death were present in both approaches, the comparison of percentages of single causes of death shows discrepancies, dominated by higher malaria rates found in the Physician Coded Verbal Autopsy approach.Conclusion  Our results confirm that national mortality statistics, which are partly based on verbal autopsies, must be carefully interpreted. Difficulties in determining malaria as cause of death in holoendemic malaria regions might result in higher discrepancies than those in non‐endemic areas. As neither Physician Coded Verbal Autopsy nor Interpreting Verbal Autopsy results represent a gold standard, uncertainty levels with either procedure are high.