bluuebunny/crossref_metadata_2025 huggingface dataset:
A Gibbs sampling strategy applied to the mapping of ambiguous short-sequence tags
Authors: Wang Jianrong , Huda Ahsan , Lunyak Victoria V. , Jordan I. King
Published: September 2010

Motivation: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is widely used in biological research. ChIP-seq experiments yield many ambiguous tags that can be mapped with equal probability to multiple genomic sites. Such ambiguous tags are typically eliminated from consideration resulting in a potential loss of important biological information.

Results: We have developed a Gibbs sampling-based algorithm for the genomic mapping of ambiguous sequence tags. Our algorithm relies on the local genomic tag context to guide the mapping of ambiguous tags. The Gibbs sampling procedure we use simultaneously maps ambiguous tags and updates the probabilities used to infer correct tag map positions. We show that our algorithm is able to correctly map more ambiguous tags than existing mapping methods. Our approach is also able to uncover mapped genomic sites from highly repetitive sequences that can not be detected based on unique tags alone, including transposable elements, segmental duplications and peri-centromeric regions. This mapping approach should prove to be useful for increasing biological knowledge on the too often neglected repetitive genomic regions.

Availability:  http://esbg.gatech.edu/jordan/software/map

Contact:  king.jordan@biology.gatech.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
SimiCon: a web tool for protein–ligand model comparison through calculation of equivalent atomic contacts
Authors: Rueda Manuel , Katritch Vsevolod , Raush Eugene , Abagyan Ruben
Published: September 2010

Summary: SimiCon is a web server designed for an automated identification of equivalent protein–ligand atomic contacts in different conformational models of a complex. The contacts are computed with internal coordinate mechanics (ICM) software with respect to molecular symmetry and the results are shown in the browser as text, tables and interactive 3D graphics. The web server can be executed remotely without a browser to allow users to automate multiple calculations.

Availability: SimiCon is freely available at http://abagyan.ucsd.edu/SimiCon

Contact:  rabagyan@ucsd.edu
RAPID detection of gene–gene interactions in genome-wide association studies
Authors: Brinza Dumitru , Schultz Matthew , Tesler Glenn , Bafna Vineet
Published: September 2010

Motivation: In complex disorders, independently evolving locus pairs might interact to confer disease susceptibility, with only a modest effect at each locus. With genome-wide association studies on large cohorts, testing all pairs for interaction confers a heavy computational burden, and a loss of power due to large Bonferroni-like corrections. Correspondingly, limiting the tests to pairs that show marginal effect at either locus, also has reduced power. Here, we describe an algorithm that discovers interacting locus pairs without explicitly testing all pairs, or requiring a marginal effect at each locus. The central idea is a mathematical transformation that maps ‘statistical correlation between locus pairs’ to ‘distance between two points in a Euclidean space’. This enables the use of geometric properties to identify proximal points (correlated locus pairs), without testing each pair explicitly. For large datasets (∼106 SNPs), this reduces the number of tests from 1012 to 106, significantly reducing the computational burden, without loss of power. The speed of the test allows for correction using permutation-based tests. The algorithm is encoded in a tool called Rapid (RApid Pair IDentification) for identifying paired interactions in case–control GWAS.

Results: We validated Rapid with extensive tests on simulated and real datasets. On simulated models of interaction, Rapid easily identified pairs with small marginal effects. On the benchmark disease, datasets from The Wellcome Trust Case Control Consortium, Rapid ran in about 1 CPU-hour per dataset, and identified many significant interactions. In many cases, the interacting loci were known to be important for the disease, but were not individually associated in the genome-wide scan.

Availability:  http://bix.ucsd.edu/projects/rapid

Contact:  vbafna@cs.ucsd.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
SylArray: a web server for automated detection of miRNA effects from expression data
Authors: Bartonicek Nenad , Enright Anton J.
Published: September 2010

Summary: A useful step for understanding the function of microRNAs (miRNA) or siRNAs is the detection of their effects on genome-wide expression profiles. Typically, approaches look for enrichment of words in the 3′UTR sequences of the most deregulated genes. A number of tools are available for this purpose, but they require either in-depth computational knowledge, filtered 3′UTR sequences for the genome of interest, or a set of genes acquired through an arbitrary expression cutoff. To this end, we have developed SylArray; a web-based resource designed for the analysis of large-scale expression datasets. It simply requires the user to submit a sorted list of genes from an expression experiment. SylArray utilizes curated sets of 3′UTRs to attach sequences to these genes and then applies the Sylamer algorithm for detection of miRNA or siRNA signatures in those sequences. An intuitive system for visualization and interpretation of the small RNA signatures is included.

Availability: SylArray is written in Perl-CGI, Perl and Java and also uses the R statistical package. The source-code, database and web resource are freely available under GNU Public License (GPL). The web server is freely accessible at http://www.ebi.ac.uk/enright/sylarray.

Contact:  aje@ebi.ac.uk
HybridNET: a tool for constructing hybridization networks
Authors: Chen Zhi-Zhong , Wang Lusheng
Published: September 2010

Motivations: When reticulation events occur, the evolutionary history of a set of existing species can be represented by a hybridization network instead of an evolutionary tree. When studying the evolutionary history of a set of existing species, one can obtain a phylogenetic tree of the set of species with high confidence by looking at a segment of sequences or a set of genes. When looking at another segment of sequences, a different phylogenetic tree can be obtained with high confidence too. This indicates that reticulation events may occur. Thus, we have the following problem: given two rooted phylogenetic trees on a set of species that correctly represent the tree-like evolution of different parts of their genomes, what is the hybridization network with the smallest number of reticulation events to explain the evolution of the set of species under consideration?

Results: We develop a program, named HybridNet, for constructing a hybridization network with the minimum number of reticulate vertices from two input trees. We first implement the O(3dn)-time algorithm by Whidden et al. for computing a maximum (acyclic) agreement forest. Our program can output all the maximum (acyclic) agreement forests. We then augment the program so that it can construct an optimal hybridization network for each given maximum acyclic agreement forest. To our knowledge, this is the first time that optimal hybridization networks can be rapidly constructed.

Availability: The program is available for non-commercial use, at http://www.cs.cityu.edu.hk/∼lwang/software/Hn/treeComp.html

Contact:  zzchen@mail.dendai.ac.jp; lwang@cs.cityu.edu.hk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Mitochondrial Malate Dehydrogenase Lowers Leaf Respiration and Alters Photorespiration and Plant Growth in Arabidopsis
Authors: Tomaz Tiago , Bagard Matthieu , Pracharoenwattana Itsara , Lindén Pernilla , Lee Chun Pong , Carroll Adam J. , Ströher Elke , Smith Steven M. , Gardeström Per , Millar A. Harvey
Published: September 2010

Malate dehydrogenase (MDH) catalyzes a reversible NAD+-dependent-dehydrogenase reaction involved in central metabolism and redox homeostasis between organelle compartments. To explore the role of mitochondrial MDH (mMDH) in Arabidopsis (Arabidopsis thaliana), knockout single and double mutants for the highly expressed mMDH1 and lower expressed mMDH2 isoforms were constructed and analyzed. A mmdh1mmdh2 mutant has no detectable mMDH activity but is viable, albeit small and slow growing. Quantitative proteome analysis of mitochondria shows changes in other mitochondrial NAD-linked dehydrogenases, indicating a reorganization of such enzymes in the mitochondrial matrix. The slow-growing mmdh1mmdh2 mutant has elevated leaf respiration rate in the dark and light, without loss of photosynthetic capacity, suggesting that mMDH normally uses NADH to reduce oxaloacetate to malate, which is then exported to the cytosol, rather than to drive mitochondrial respiration. Increased respiratory rate in leaves can account in part for the low net CO2 assimilation and slow growth rate of mmdh1mmdh2. Loss of mMDH also affects photorespiration, as evidenced by a lower postillumination burst, alterations in CO2 assimilation/intercellular CO2 curves at low CO2, and the light-dependent elevated concentration of photorespiratory metabolites. Complementation of mmdh1mmdh2 with an mMDH cDNA recovered mMDH activity, suppressed respiratory rate, ameliorated changes to photorespiration, and increased plant growth. A previously established inverse correlation between mMDH and ascorbate content in tomato (Solanum lycopersicum) has been consolidated in Arabidopsis and may potentially be linked to decreased galactonolactone dehydrogenase content in mitochondria in the mutant. Overall, a central yet complex role for mMDH emerges in the partitioning of carbon and energy in leaves, providing new directions for bioengineering of plant growth rate and a new insight into the molecular mechanisms linking respiration and photosynthesis in plants.
Nontransgenic Genome Modification in Plant Cells
Authors: Marton Ira , Zuker Amir , Shklarman Elena , Zeevi Vardit , Tovkach Andrey , Roffe Suzy , Ovadis Marianna , Tzfira Tzvi , Vainstein Alexander
Published: September 2010

Zinc finger nucleases (ZFNs) are a powerful tool for genome editing in eukaryotic cells. ZFNs have been used for targeted mutagenesis in model and crop species. In animal and human cells, transient ZFN expression is often achieved by direct gene transfer into the target cells. Stable transformation, however, is the preferred method for gene expression in plant species, and ZFN-expressing transgenic plants have been used for recovery of mutants that are likely to be classified as transgenic due to the use of direct gene-transfer methods into the target cells. Here we present an alternative, nontransgenic approach for ZFN delivery and production of mutant plants using a novel Tobacco rattle virus (TRV)-based expression system for indirect transient delivery of ZFNs into a variety of tissues and cells of intact plants. TRV systemically infected its hosts and virus ZFN-mediated targeted mutagenesis could be clearly observed in newly developed infected tissues as measured by activation of a mutated reporter transgene in tobacco (Nicotiana tabacum) and petunia (Petunia hybrida) plants. The ability of TRV to move to developing buds and regenerating tissues enabled recovery of mutated tobacco and petunia plants. Sequence analysis and transmission of the mutations to the next generation confirmed the stability of the ZFN-induced genetic changes. Because TRV is an RNA virus that can infect a wide range of plant species, it provides a viable alternative to the production of ZFN-mediated mutants while avoiding the use of direct plant-transformation methods.
Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in collagen disease patient
Authors: NOMURA Masayo , MAEDA Manabu , SEISHIMA Mariko
Published: September 2010

Phaeohyphomycosis is a rare fungal infection that is more commonly associated with compromised patients. We present herein an 81‐year‐old man with collagen disease and chronic interstitial pneumonia who developed subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei. The main pathogen of phaeohyphomycosis had been considered to be E. jeanselmei complex. This has recently been divided into several species by using a molecular technique. The main pathogen of phaeohyphomycosis is Exophiala xenobiotica, and E. jeanselmei is rather a rare pathogen of this disease. Although p.o. itraconazole and terbinafine administration was not effective for this patient, these antifungal agents were used for preventing systemic dissemination in this immunocompromised host.
Impact of a focussed teaching programme on practical prescribing skills among final year medical students
Authors: Sandilands Euan A. , Reid Karen , Shaw Laura , Bateman D. Nicholas , Webb David J. , Dhaun Neeraj , Kluth David C.
Published: September 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Medication errors, and particularly prescribing errors, are common in UK hospitals.

• Junior doctors make the majority of prescribing errors.

• Deficiencies in prescribing education and training have been closely linked to the high frequency of medication errors.

WHAT THIS STUDY ADDS

• Focussed prescribing teaching can lead to an improvement in prescribing ability.

• Prescribing confidence can be significantly improved through education.

• Education is insufficient alone in eradicating prescribing errors.

AIM To assess the impact of prescribing teaching on final year medical students.

METHODS Students randomly allocated to two hospitals completed a prescribing assessment. Prescribing teaching was delivered to the intervention group while no additional teaching was provided for the control group. All students then completed a second prescribing assessment.

RESULTS Teaching improved the assessment score: mean assessment 2 vs. 1, 70% vs. 62%, P= 0.007; allergy documentation: 98% vs. 74%, P= 0.0001; and confidence. However, 30% of prescriptions continued to include prescribing errors.

CONCLUSION Medical students make significant errors in prescribing. Teaching improves ability and confidence but is insufficient alone in eradicating errors.
Effects of imatinib mesylate on the pharmacokinetics of paracetamol (acetaminophen) in Korean patients with chronic myelogenous leukaemia
Authors: Kim Dong‐Wook , Tan Eugene Y. , Jin Yu , Park Sahee , Hayes Michael , Demirhan Eren , Schran Horst , Wang Yanfeng
Published: September 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Imatinib mesylate, a tyrosine kinase inhibitor, exhibits a weak competitive inhibition on paracetamol (acetaminophen) O‐glucuronidation with an inhibition constant (Ki) value of 59 µm. However, the clinical significance of the inhibition has not been evaluated. The pharmacokinetics of imatinib have been studied in white patients with chronic myelogenous leukaemia (CML), but not in Korean patients with CML.

WHAT THIS STUDY ADDS

• Imatinib (400 mg once daily) had no clinically relevant effect on the plasma exposure and the pharmacokinetics of paracetamol (1000 mg once daily) in patients with CML.

• The pharmacokinetic profile of imatinib in Korean patients with CML was similar to that in whites.

AIMS The major objective of the present study was to investigate the effect of imatinib on the pharmacokinetics of paracetamol in patients with chronic myelogenous leukaemia (CML).

METHODS Patients (n= 12) received a single oral dose of acetaminophen 1000 mg on day 1 (control). On days 2–8, imatinib 400 mg was administered daily. On day 8 (treatment), another 1000 mg dose of paracetamol was administered 1 h after the morning dose of imatinib 400 mg. Blood and urine samples were collected for bioanalytical analyses.

RESULTS The area under the plasma concentration–time curve (AUC) for paracetamol, paracetamol glucuronide and paracetamol sulphate under control conditions was similar to that after treatment with imatinib; the 90% confidence interval of the log AUC ratio was within 0.8 to 1.25. Urinary excretion of paracetamol, paracetamol glucuronide and paracetamol sulphate was also unaffected by imatinib. The pharmacokinetics of paracetamol and imatinib in Korean patients with CML were similar to previous pharmacokinetic results in white patients with CML. Co‐administration of a single dose of paracetamol and multiple doses of imatinib was well tolerated and safety profiles were similar to those of either drug alone.

CONCLUSIONS The pharmacokinetics of paracetamol and its major metabolites in the presence of imatinib were similar to those of the control conditions and the combination was well tolerated. These findings suggest that imatinib can be safely administered with paracetamol without dose adjustment of either drug.
Gender differences in the association of C‐reactive protein with coronary artery calcium in Type‐2 diabetes
Authors: Qasim Atif N. , Budharaju Venkata , Mehta Nehal N. , St Clair Caitlin , Farouk Samira , Braunstein Seth , Schutta Mark , Iqbal Nayyar , Rader Daniel J. , Reilly Muredach P.
Published: September 2010

Objectives  Plasma C‐reactive protein (CRP) is associated with cardiovascular disease (CVD), but effects may vary by gender and degree of CVD risk. Whether CRP has value as a CVD risk marker in type‐2 diabetes (T2DM) is unclear. We examined whether CRP has gender differences in association with coronary artery calcium (CAC) in diabetic and nondiabetic samples without clinical CVD.

Methods  We performed cross‐sectional analyses of gender influence on CRP association with CAC in the Penn Diabetes Heart Study (N = 1299 with T2DM), the Study of Inherited Risk of Coronary Atherosclerosis (N = 860 nondiabetic subjects) and a combined sample.

Results  Female gender was associated with higher plasma CRP in diabetic and nondiabetic samples after adjustment for covariates. There was a strong interaction by gender in the association of CRP with CAC (interaction P < 0·001). In diabetic women, CRP was associated with higher CAC even after further adjustment for age, race, medications, metabolic syndrome, Framingham risk score and body mass index [Tobit ratio 1·60, 95% CI (1·03–2·47)]. Although this relationship was attenuated in nondiabetic women, the combined sample maintained this association in fully adjusted models [1·44, 95% CI (1·13–1·83)]. There was no association of CRP with CAC in either diabetic or nondiabetic men.

Conclusions  CRP may be a useful marker of cardiovascular risk in women, particularly in diabetic women who otherwise have no known CVD. Prospective studies are needed to better assess the gender differences in CRP utility and the use of CRP in T2DM.
Immunohistochemical classification of ductular reactions in human liver
Authors: Turányi Eszter , Dezsö Katalin , Csomor Judit , Schaff Zsuzsa , Paku Sándor , Nagy Péter
Published: September 2010

Turányi E, Dezsö K, Csomor J, Schaff Z, Paku S & Nagy P (2010) Histopathology 57, 607–614 Immunohistochemical classification of ductular reactions in human liver

Aims:  Ductular reactions occur in a wide variety of liver diseases. Their origin and function is still debated. Our understanding of these histological reactions is impaired by their great diversity; therefore rational classification should precede further detailed analysis. The aim was to achieve a reproducible classification of hepatic ductular reactions based on their immunophenotype.

Methods and results:  Sixty‐nine liver specimens with ductular reactions were analysed by immunohistochemistry. The majority of the samples could be classified into three categories based on their immunophenotype. Type P(rimitive) reaction is characterized by CD56 immunoreactivity. Most primary biliary cirrhosis and focal nodular hyperplasia samples fall into this group; these ductules do not show any sign of differentiation. Type D(ifferentiating) ductules are positive for CD56, epithelial membrane antigen (EMA) and CD10. Cirrhotic samples and regenerating livers following fulminant hepatic failure contain such ductular reactions; this immunophenotype indicates hepatocytic differentiation. Biliary obstruction results in EMA‐positive type O(bstructive) reactions; these ductules are similar to the normal interlobular bile ducts.

Conclusion:  Ductular reactions can be classified based on their immunophenotype. Our results may initiate further, similar, studies resulting in a generally accepted rational classification. We believe that such categorization is necessary for elucidating their biological and clinical significance.
Family doctors and psychologists working together: doctors' and patients' perspectives
Authors: Chomienne Marie‐Hélène , Grenier Jean , Gaboury Isabelle , Hogg William , Ritchie Pierre , Farmanova‐Haynes Elina
Published: September 2010

Background  Strategies to improve primary care in the Canadian Primary Care Reform include integrating different professionals to the medical team.

Objective  This demonstration project explores the perceived impact on doctors and patients, of having family doctors and psychologists work together.

Setting  Two family practices of Eastern Ontario, Canada

Methods  Two board certified psychologists (one per practice) were integrated in the practices for 12 months. Psychologists conducted assessments, consultations and short‐term treatments, as well as knowledge‐transfer sessions for doctors. Outcome measures included referral patterns, patient outcomes, patient and provider satisfaction as well as doctors' billing.

Results  Three hundred and seventy‐six participants received psychological care; most were women (68%) and between the ages of 25–64 (67%). Anxiety and depression were the most prevalent diagnoses. Reasons for referral included: psychological treatment (70%); emotional support and counselling (35%); clarification of diagnosis and case conceptualization (25%). Referrals could be for more than one reason. After intervention, 60% of patients had improvement on the outcome questionnaire‐45 (OQ‐45). Quality of life as measured by the EuroQol‐5D also improved (P < 0.001). Over 77% of patients reported increased confidence in handling their problems after treatment. Compared with their family doctor, patients felt the psychologist had more time and was better trained (75%) Doctors felt mental health problems were diagnosed more rapidly, patient care improved as well as their own knowledge of psychological management and treatment. Doctors felt it freed up their time and improved working conditions. Audit of the doctors' billing showed reduction in doctors' mental health billing.

Conclusions  Having an on‐site psychologist was highly satisfactory for patients and providers, resulting in improved patient care and outcomes.
Could azathioprine be considered as a therapeutic alternative in the treatment of alopecia areata? A pilot study
Authors: Farshi Susan , Mansouri Parvin , Safar Farid , Khiabanloo Samad Rezaee
Published: September 2010

Alopecia areata is an autoimmune disease resulting in partial or total nonscarring hair loss and the treatment of severe alopecia areata is difficult. The aim of this study was to evaluate the efficacy and safety of azathioprine as a systemic monotherapy for moderate to severe alopecia areata. A total of 20 patients [14 men (70%) and six women (30%)] with minimum 6 months history of alopecia areata were included. The extent of scalp hair regrowth during and after the completion of the 6 months treatment was evaluated by the Severity of Alopecia Tool (the SALT score). The daily drug intake was calculated as 2 mg/kg of body weight. Mean duration of current episode of scalp hair loss was 26.4 (26.4 ± 17) months. Mean regrowth percentage was 52.3% (52.3 ± 38.4). Mean hair loss percentage before treatment was 72.7% (72.7 ± 28.3) compared with 33.5% (33.5 ± 30.7) after 6 months of azathioprine treatment. This showed a highly significant statistical difference (Paired t‐test, CI 95% = 21.5–54.1). Mean hair loss score (S0–S5) before treatment was 3.9 (3.9 ± 1.6) and after 6 months of azathioprine treatment was 1.8 (1.8 ± 1.3). Assessment showed significant difference from baseline score (sign test, P < 0.0001). No significant statistical difference was observed with respect to gender before and after azathioprine treatment. Treatment with azathioprine as a systemic monotherapy clinically produces relevant improvement in moderate‐to‐severe alopecia areata. Generally azathioprine is a low‐cost and well‐tolerated drug and with controlled studies on larger number of patients, long‐term efficacy and safety of this treatment should be investigated.
Cutaneous myiasis: a review of the common types of myiasis
Authors: Robbins Kerri , Khachemoune Amor
Published: September 2010

Myiasis is derived from the Greek word, myia, meaning fly. The term was first introduced by Hope in 1840 and refers to the infestation of live human and vertebrate animals with dipterous (two‐winged) larvae (maggots) which, at least for a certain period, feed on the host’s dead or living tissue, liquid body‐substance, or ingested food. Myiasis is the fourth most common travel‐associated skin disease and cutaneous myiasis is the most frequently encountered clinical form. Cutaneous myiasis can be divided into three main clinical manifestations: furuncular, creeping (migratory), and wound (traumatic) myiasis. The flies that produce a furuncular myiasis include Dermatobia hominis, Cordylobia anthropophaga, Wohlfahrtia vigil, and the Cuterebra species. Gasterophilus and Hypoderma are two flies that produce a creeping myiasis. Flies that cause wound myiasis include screwworm flies such as Cochliomyia hominivorax and Chrysomya bezziana, and Wohlfahrtia magnifica. This article reviews current literature, provides general descriptions, and discusses life cycles of each species. It also gives treatment techniques and descriptions of each type of illness that results from interaction/infestation.
Natural variation of drought response in Brachypodium distachyon
Authors: Luo Na , Liu Jianxiu , Yu Xiaoqing , Jiang Yiwei
Published: September 2010

Brachypodium distachyon (Brachypodium) is a temperate wild grass species and is a powerful model system for studying grain, energy, forage and turf grasses. Exploring the natural variation in the drought response of Brachypodium provides an important basis for dissecting the genetic network of drought tolerance. Two experiments were conducted in a greenhouse to assess the drought tolerance of 57 natural populations of Brachypodium. Principle component analysis revealed that reductions in chlorophyll fluorescence (Fv/Fm) and leaf water content (LWC) under drought stress explained most of the phenotypic variation, which was used to classify the tolerant and susceptible accessions. Four groups of accessions differing in drought tolerance were identified, with 3 tolerant, 16 moderately tolerant, 32 susceptible and 6 most susceptible accessions. The tolerant group had little leaf wilting and fewer reductions in Fv/Fm and LWC, while the most susceptible groups showed severe leaf wilting and more reductions in Fv/Fm and LWC. Drought stress increased total water soluble sugar (WSS) concentration, but no differences in the increased WSS were found among different groups of accessions. The large phenotypic variation of Brachypodium in response to drought stress can be used to identify genes and alleles important for the complex trait of drought tolerance.
Steady and dynamic photosynthetic responses of seedlings from contrasting successional groups under low‐light growth conditions
Authors: Chen Jun‐Wen , Zhang Qiang , Li Xiao‐Shuang , Cao Kun‐Fang
Published: September 2010

To test the hypothesis that leaf‐level photosynthetic‐related traits might confer late successionals a competitive advantage over early successionals in low‐light growth conditions, steady photosynthetic assimilation‐ and dynamic photosynthetic induction‐related traits were examined in low‐light‐grown seedlings with contrasting successional status. Compared with the early successionals, late successionals as a group significantly exhibited lower leaf gas exchange rates. While late successionals required a longer time to respond to simulated sunflecks, they had lower rates of induction losses after sunflecks. Such photosynthetic induction traits allowed late successionals to more effectively utilize subsequent sunflecks. It was observed that plants with lower gas exchange rates responded more slowly to simulated sunfelcks, but they had lower rates of induction losses after sunflecks. In addition, the rate of response to sunflecks was positively correlated with the rate of induction loss after sunflecks across the successional status of species. A principal components analysis (PCA) demonstrated that early and late successionals were separated along the first axis of the PCA, and that early successionals were grouped on the right and were associated with higher gas exchange rates, fast responses to sunflecks, and rapid rates of induction loss after sunflecks; late successionals held an opposite pattern. Overall, our results suggest that smaller respiratory carbon losses and lower metabolic costs give late successionals a competitive advantage in low‐light growth conditions, that late successionals have an advantage over early successionals in utilizing sunflecks, and thus that the successional status of species are mainly associated with the leaf‐level photosynthetic‐related traits.
Superoxide anion radicals generated by methylviologen in photosystem I damage photosystem II
Authors: Krieger‐Liszkay Anja , Kós Péter B. , Hideg Éva
Published: September 2010

The effect of superoxide anion radicals on the photosynthetic electron transport chain was studied in leaves and isolated thylakoids from tobacco. Superoxide was generated by methylviologen (MV) in the light at the acceptor side of photosystem I (PSI). In isolated thylakoids, the largest damage was observed at the level of the water‐splitting activity in photosystem II (PSII), whereas PSI was hardly affected at the light intensities used. Addition of reactive oxygen scavengers protected PSII against damage. In leaves in the presence of MV, the quantum yield of PSII decreased during illumination whereas the size of the P700 signal remained constant. There was no D1 protein loss in leaves illuminated in the presence of MV and lincomycin, but a modification to a slightly higher molecular mass was observed. These data show that PSII is more sensitive to superoxide or superoxide‐derived reactive oxygen species (ROS) than PSI. In our experiments, this susceptibility was not because of any action of the ROS on the translation of the D1 protein or on the repair cycle of photosystem.
A comprehensive assessment of geographic variation in heat tolerance and hardening capacity in populations of Drosophila melanogaster from eastern Australia
Authors: SGRÒ C. M. , OVERGAARD J. , KRISTENSEN T. N. , MITCHELL K. A. , COCKERELL F. E. , HOFFMANN A. A.
Published: September 2010

We examined latitudinal variation in adult and larval heat tolerance in Drosophila melanogaster from eastern Australia. Adults were assessed using static and ramping assays. Basal and hardened static heat knockdown time showed significant linear clines; heat tolerance increased towards the tropics, particularly for hardened flies, suggesting that tropical populations have a greater hardening response. A similar pattern was evident for ramping heat knockdown time at 0.06 °C min−1 increase. There was no cline for ramping heat knockdown temperature (CTmax) at 0.1 °C min−1 increase. Acute (static) heat knockdown temperature increased towards temperate latitudes, probably reflecting a greater capacity of temperate flies to withstand sudden temperature increases during summer in temperate Australia. Larval viability showed a quadratic association with latitude under heat stress. Thus, patterns of heat resistance depend on assay methods. Genetic correlations in thermotolerance across life stages and evolutionary potential for critical thermal limits should be the focus of future studies.
Ex vivo generation of a functional and regenerative wound epithelium from axolotl (Ambystoma mexicanum) skin
Authors: Ferris Donald R. , Satoh Akira , Mandefro Berhan , Cummings Gillian M. , Gardiner David M. , Rugg Elizabeth L.
Published: September 2010

Urodele amphibians (salamanders) are unique among adult vertebrates in their ability to regenerate structurally complete and fully functional limbs. Regeneration is a stepwise process that requires interactions between keratinocytes, nerves and fibroblasts. The formation of a wound epithelium covering the amputation site is an early and necessary event in the process but the molecular mechanisms that underlie the role of the wound epithelium in regeneration remain unclear. We have developed an ex vivo model that recapitulates many features of in vivo wound healing. The model comprises a circular explant of axolotl (Ambystoma mexicanum) limb skin with a central circular, full thickness wound. Re‐epithelialization of the wound area is rapid (typically <11 h) and is dependent on metalloproteinase activity. The ex vivo wound epithelium is viable, responds to neuronal signals and is able to participate in ectopic blastema formation and limb regeneration. This ex vivo model provides a reproducible and tractable system in which to study the cellular and molecular events that underlie wound healing and regeneration.
Is the problem with the vehicle or the destination? Does high‐dose ESA or high haemoglobin contribute to poor outcomes in CKD?
Authors: BADVE SUNIL V , HAWLEY CARMEL M , JOHNSON DAVID W
Published: September 2010

Randomized controlled trials have consistently demonstrated adverse outcomes from targeting higher haemoglobin levels in chronic kidney disease patients treated with erythropoiesis‐stimulating agents (ESA). In contrast, observational studies have shown better survival in patients achieving high haemoglobin. Consequently, there is ongoing uncertainty as to whether high haemoglobin or high ESA dose contributes to poor outcomes in ESA‐treated chronic kidney disease patients. The objectives of this article are to review the available evidence pertaining to this contentious area, provide recommendations where possible and suggest directions for future research efforts.
Diurnal cortisol patterns of young male patients with schizophrenia
Authors: Hempel Roelie J. , Tulen Joke H. M. , van Beveren Nico J. M. , Röder Christian H. , de Jong Frank H. , Hengeveld Michiel W.
Published: September 2010

Aims:  It has been suggested that schizophrenic patients are more vulnerable to stress than healthy persons, and that stressors can trigger a psychotic episode or worsen symptoms. The biological system often studied in relation to stress is the hypothalamic–pituitary–adrenal (HPA) axis, which controls the release of cortisol. We investigated whether the diurnal basal activity of the HPA axis differed between young male patients with schizophrenia and healthy controls.

Methods:  Twenty‐seven male patients (mean age 22 ± 5 years) and 38 healthy male control subjects (mean age 22 ± 3 years) were included in the present study. Saliva was sampled at five time points during the day: directly after awakening, 30 min thereafter, and at 12.00 hours, 16.00 hours and 22.00 hours.

Results:  The cortisol concentration decreased significantly more during the day in the patient group thanin the control group. Patients also showed a significantly decreased area under the curve with respect to the increase, again indicating that the cortisol concentrations decreased more during the day in patients than in controls. Both the morning increase and the area under the curve with respect to the increase were significantly negatively correlated with negative symptom severity.

Conclusions:  Patients with schizophrenia showed a different daytime sensitivity of the HPA axis. Our findings further suggest that an increase in negative symptom severity is related to a decreased HPA axis sensitivity.
Quality of life and related factors among cancer caregivers in China
Authors: Lu Lu , Pan Bochen , Sun Wei , Cheng Lili , Chi Tieshuang , Wang Lie
Published: September 2010

Aims:  The present study was designed to investigate quality of life (QOL) among caregivers of cancer inpatients, and to explore the related factors with the long‐term goal to improve QOL of cancer caregivers in China.

Methods:  A cross‐sectional study was performed during the period January–March 2008. Subjects comprised 358 caregivers of cancer inpatients. The questionnaires pertaining to QOL, sociodemographic characteristics, caregiving demands, available social resources, caregiving situation, and caregiver's health status were used. Data were collected by nurses through interviews.

Results:  The average QOL score of these subjects was 5.26. General linear model analysis showed that caregiver's QOL was significantly associated with, in standardized estimate sequence, spousal relationship, patient's activities of daily living, and chronic disease (no). Overall spousal relationship to patient had the strongest association with caregiver's QOL.

Conclusions:  Psychological well‐being and social concerns of cancer caregivers were disrupted more seriously than spiritual well‐being and physical well‐being. In addition, spousal relationship, patient's disability, and caregiver's health status could affect the caregiver's QOL.
Severe polyuria after the resection of adrenal pheochromocytoma
Authors: Tobe Musashi , Ito Keiichi , Umeda Shun , Sato Akinori , Adaniya Noriaki , Tanaka Yuji , Hayakawa Masamichi , Asano Tomohiko
Published: September 2010

A 73‐year‐old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and 131I‐MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH‐secreting tumor. Urinary β2‐microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date.
A strategic plan for an Australian Long‐Term Environmental Monitoring Network
Authors: LIKENS GENE E. , LINDENMAYER DAVID B.
Published: September 2010

Because of the urgent need for robust, long‐term information on biodiversity loss and environmental change, we have proposed a Long‐Term (>10 years) Environmental Monitoring (LTEM) Network for Australia. The LTEM Network would comprise 25 Nodes distributed throughout Australia, be focused on terrestrial, inland aquatic and coastal estuarine ecosystems, and be established to monitor long‐term biodiversity loss and ecological change (patterns and trends). The LTEM Network would be question‐problem‐process‐driven and not infrastructure‐driven. Thus, the different Nodes in the LTEM Network would explicitly recognize different biota, different environmental problems, different environmental threats and different kinds of management interventions in different ecosystems. We provide a governance structure for the proposed LTEM Network and envisage that it would be characterized by being: (i) lean, yet powerful, agile and adaptive; (ii) both centralized (through a coordinating role by a Federal Government agency), yet decentralized in terms of where the Nodes are located and how they are operated and managed; and (iii) not overly bureaucratic. We also argue that it would be highly cost‐effective; our estimated cost for the establishment of an LTEM Network is $28 million per year or less than 0.25% of the total annual governmental expenditure of $12 billion on environmental management in 2003/2004. The LTEM Network would be a critical part of Australia's environmental infrastructure and provide the Nation, for the first time, with a formal, coordinated, long‐term Network to gauge status and change of biodiversity and environmental condition. We argue that this would allow the Nation to begin to address seriously many of the major data‐related deficiencies that currently exist in the environment and biodiversity conservation sectors in Australia.
DIRECT CHOLANGIOSCOPY USING A DOUBLE‐BALLOON ENTEROSCOPE: CHOLEDOCHOJEJUNOSTOMY WITH INTRADUCTAL BILIARY CARCINOMA
Authors: Okabe Yoshinobu , Kuwaki Kotaro , Kawano Hiroshi , Kaji Ryohei , Sugiyama Gen , Ishida Yusuke , Yasumoto Makiko , Naito Yoshiki , Toyonaga Atsushi , Tsuruta Osamu , Sata Michio
Published: September 2010

A 75‐year‐old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double‐balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary‐like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.
USEFULNESS OF ENDOSCOPIC TREATMENT FOR DUODENAL ADENOMA
Authors: Endo Masaki , Abiko Yukito , Oana Syuhei , Kudara Norihiko , Chiba Toshimi , Suzuki Kazuyuki , Koizuka Hitohiko , Uesugi Noriyuki , Sugai Tamotsu
Published: September 2010

In recent years, due to the increasing prevalence of upper gastrointestinal endoscopy, there have been an increasing number of reports on duodenal adenoma and early stage cancer. However, endoscopic techniques for the resection of duodenal adenomas are difficult, due to the anatomical features of the duodenum, and the long distance to the lesion. There have only been a few reports on the use of endoscopic techniques for duodenal adenomas compared to those focused on the stomach and large intestine. For duodenal adenomas, we used a conventional endoscope for lesions proximal to the major duodenal papilla, and a short‐type double balloon endoscope for lesions distal to the papilla. The en‐bloc resection rate was 93.8%. There was only one case of microperforation. Endoscopic manipulation is considered difficult in the deep areas of the duodenum, but double balloon endoscopy enabled stable manipulation and successful resection of the tumor in the majority of cases.
ANCHOR CLIP TECHNIQUE HELPS IN EASY PREVENTION OF POST‐POLYPECTOMY HEMORRHAGE OF LARGE COLONIC POLYPS
Authors: Mizukami Takeshi , Hiroyuki Imaeda , Hibi Toshifumi
Published: September 2010

Large colonic polyps have large vessels, which often cause post‐polypectomy hemorrhage. Some of the stalks of large pedunculated polyps are formed by the weight of the polyps and disappear after polypectomy. There are some reports suggesting that pre‐ligation with EndoloopR may minimize the risk of post‐polypectomy hemorrhage. However, the current density increases more at the site of pre‐ligation as compared with that at the site of polypectomy, because polypectomy is carried out with gradual snaring. This implies that burn injury may also occur at the site of pre‐ligation, causing the loss of pre‐ligation and, consequently, post‐polypectomy hemorrhage. Ligation of stalks after polypectomy is very difficult. The EndoloopR rolls back when it is tightened, because of the lack of torsional stiffness. We have developed a simple and improved post‐polypectomy ligation technique using the Anchor clip. Before polypectomy, an EndoclipR is placed partially at the base of the pedunculated polyp. When the stalk is tightened completely with the EndoclipR before polypectomy, burn injury occurs around the EndoclipR. The Anchor clip at the base of the pedunculated polyp holds the stalk after polypectomy and the constricted part formed by the Anchor clip prevents the rolling up of the EndoloopR and helps in easy ligation of the stalk. We have used the Anchor clip for 50 patients. Application of the EndoloopR after polypectomy was impossible in two patients. The remaining 48 patients underwent EndoloopR–assisted polypectomy with the Anchor clip, and in none of the cases did bleeding occur after polypectomy.
PSEUDOMEMBRANOUS COLITIS COMPLICATING ULCERATIVE COLITIS
Authors: Kawaratani Hideto , Tsujimoto Tatsuhiro , Toyohara Masahisa , Kin Kenichi , Taniguchi Tomoyasu , Shirai Yasuyo , Ikenaka Yasuhide , Nakayama Masaki , Fujii Hisao , Fukui Hiroshi
Published: September 2010

Clostridium difficile toxin (CD toxin) causes antibiotic‐associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71‐year‐old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3‐week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing.
TRANSGASTRIC TRANSHEPATIC ENDOSONOGRAPHY‐GUIDED BILIARY DRAINAGE: HISTOLOGICAL ASSESSMENT OF ITS SINUS TRACT IN AN AUTOPSY CASE
Authors: Noda Yutaka , Fujita Naotaka , Kobayashi Go , Ito Kei , Obana Takashi , Horaguchi Jun , Koshita Shinsuke , Kanno Yoshihide , Sawai Takashi
Published: September 2010

Endosonography‐guided biliary drainage (ESBD) is gaining attention as a promising drainage technique for obstructive jaundice. However, histological changes resulting from ESBD have not been well understood. We had an opportunity to histologically investigate the influence of ESBD, established between the left hepatic duct and the stomach, on the relevant organs in an autopsy case with bile duct cancer extending from the pancreatic head to the hepatic hilum with duodenal invasion. Localized fibrous connective tissues were present around and along the sinus tract, including the connection between the surfaces of the left lobe of the liver and the gastric serosa, without hemorrhage, inflammatory changes, or cancer invasion. The inside of the ESBD stent was slightly stenotic at the intramural portion of the stomach due to proliferation of granulation tissue. No bile stasis or abscess was observed in the left lobe. These results are quite suggestive of the high safety and efficacy of ESBD with adequate performance.