bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring hidden dimensions of soil fungal biodiversity: A simple technique to detect soil fungi resistant to antifungal compounds
Authors: Velho-Pereira Sonashia , Kamat Nandkumar 
Published: February 2010

AbstractSoils are known to be ultimate and complex reservoirs of microbial diversity. The complex dimensions of bacterial and fungal diversity in tropical soils and microbial community dynamics are underexplored. Isolation techniques aimed at Actinomycetes generally employ highly selective media, powerful antibiotics and antifungal compounds to suppress undesirable bacteria and fungi. However some soil fungi may show their resistance towards these antifungal compounds. During our work to explore soil actinomycetes diversity, slides coated with Arginine Vitamin agar (AVA) incorporating a cocktail of antibiotics and antifungal compounds such as Nystatin, Cycloheximide, Terbinafin, Griseofulvin, and Fluconazole were exposed to soil environment and were retrieved at intervals of 4, 7, 15 and 28 days for detail microscopic studies of surface colonies. Along with actinomycetes the presence of unidentified aseptate and septate fungi was revealed indicating their resistance to combination and concentration of antifungals. Heat treatment of the soil was found to cause considerable decrease in fungal contamination probably due to elimination of heat labile fungi. Our results have led us to develop a simple procedure to sample the interesting and industrially useful strains of soil fungi resistant to common antifungal compounds. Some fungal strains are reported resistant to certain antifungals with resulting therapeutic failures as use of these antifungals inevitably selects resistant fungi, thereby pressing the urge for continuing and cyclical need of new antifungals (Augustin et al., 2004). This technique could prove useful to detect novel antifungal resistant strains with potential to emerge as novel human pathogens. It has not escaped our notice that the probability of such finding could also help to verify whether these fungi could utilize such antifungal compounds through use of hitherto undiscovered metabolic pathways and novel enzymes leading to identification of genes responsible for antifungal resistance.
Digital Image Analysis of Actinomycetes Colonies as a Potential Aid for Rapid Taxonomic Identification
Authors: Velho-Pereira Sonashia , Kamat Nandkumar 
Published: February 2010

AbstractHigh frequency isolation of actinomycetes poses a challenge for the taxonomists hence simple and rapid identification methods are required. Our work to catalogue biodiversity of actinomycetes of Goa yielded several distinct morphotypes. After their tentative identification, the feasibility to distinguish these using digital image analyses (DIA) was explored. Digital images of wild colony morphotypes were processed using public domain SCION image analysis software. DIA revealed some intricate digital characters. A combination of these with standard morphological and microscopic characters could be potentially useful for preparing a digital identification key of the actinomycetes strains with potential application in rapid taxonomic identification.
Insertion of an NPVY sequence into the cytosolic domain of the erythropoietin receptor selectively affects erythropoietin-mediated signalling and function
Authors: Liron Tamar , Nahari Tal , Souroujon Miriam C. , Neumann Drorit 
Published: February 2010

EPO (erythropoietin), the major hormone regulating erythropoiesis, functions via activation of its cell-surface receptor (EPO-R) present on erythroid progenitor cells. One of the most striking properties of EPO-R is its low expression on the cell surface, as opposed to its high intracellular levels. The low cell-surface expression of EPO-R may thus limit the efficacy of EPO that is routinely used to treat primary and secondary anaemia. In a recent study [Nahari, Barzilay, Hirschberg and Neumann (2008) Biochem. J. 410, 409–416] we have shown that insertion of an NPVY sequence into the intracellular domain of EPO-R increases its cell-surface expression. In the present study we demonstrate that this NPVY EPO-R insert has a selective effect on EPO-mediated downstream signalling in Ba/F3 cells expressing this receptor (NPVY-EPO-R). This is monitored by increased phosphorylation of the NPVY-EPO-R (on Tyr479), Akt, JAK2 (Janus kinase 2) and ERK1/2 (extracellular-signal-regulated kinase 1/2), but not STAT5 (signal transducer and activator of transcription 5), as compared with cells expressing wild-type EPO-R. This enhanced signalling is reflected in augmented proliferation at low EPO levels (0.05 units/ml) and protection against etoposide-induced apoptosis. Increased cell-surface levels of NPVY-EPO-R are most probably not sufficient to mediate these effects as the A234E-EPO-R mutant that is expressed at high cell-surface levels does not confer an augmented response to EPO. Taken together, we demonstrate that insertion of an NPVY sequence into the cytosolic domain of the EPO-R confers not only improved maturation, but also selectively affects EPO-mediated signalling resulting in an improved responsiveness to EPO reflected in cell proliferation and protection against apoptosis.
Regulatory impact factors: unraveling the transcriptional regulation of complex traits from expression data
Authors: Reverter Antonio , Hudson Nicholas J. , Nagaraj Shivashankar H. , Pérez-Enciso Miguel , Dalrymple Brian P. 
Published: February 2010

Abstract
Motivation: Although transcription factors (TF) play a central regulatory role, their detection from expression data is limited due to their low, and often sparse, expression. In order to fill this gap, we propose a regulatory impact factor (RIF) metric to identify critical TF from gene expression data.
Results: To substantiate the generality of RIF, we explore a set of experiments spanning a wide range of scenarios including breast cancer survival, fat, gonads and sex differentiation. We show that the strength of RIF lies in its ability to simultaneously integrate three sources of information into a single measure: (i) the change in correlation existing between the TF and the differentially expressed (DE) genes; (ii) the amount of differential expression of DE genes; and (iii) the abundance of DE genes. As a result, RIF analysis assigns an extreme score to those TF that are consistently most differentially co-expressed with the highly abundant and highly DE genes (RIF1), and to those TF with the most altered ability to predict the abundance of DE genes (RIF2). We show that RIF analysis alone recovers well-known experimentally validated TF for the processes studied. The TF identified confirm the importance of PPAR signaling in adipose development and the importance of transduction of estrogen signals in breast cancer survival and sexual differentiation. We argue that RIF has universal applicability, and advocate its use as a promising hypotheses generating tool for the systematic identification of novel TF not yet documented as critical.
Contact: tony.reverter-gomez@csiro.au
Supplementary information: Supplementary data are available at Bioinformatics online.
Bymovirus reverse genetics: requirements for RNA2‐encoded proteins in systemic infection
Authors: YOU YUAN , SHIRAKO YUKIO 
Published: February 2010

SUMMARY Barley yellow mosaic virus (BaYMV), the type species of the genus Bymovirus in the family Potyviridae in the picornavirus‐like superfamily, causes a yellow mosaic disease of winter barley with significant yield losses in Europe and East Asia. Until now, infectious in vitro transcripts for the bipartite plus‐sense RNA genome of any bymovirus species have not been available, rendering molecular analyses of bymovirus pathogenicity and the host resistance mechanisms difficult. In this study, we constructed the first cDNA clones of BaYMV RNA1 and RNA2, from which infectious RNA can be transcribed in vitro. Using in vitro transcripts, we showed that RNA1, which encodes eight proteins, including a viral proteinase NIa‐Pro, the RNA‐dependent RNA polymerase NIb, genome‐linked viral protein VPg and the capsid protein CP, replicated autonomously in barley mesophyll protoplasts in the absence of RNA2 optimally at 15 °C, a temperature similar to the optimum for causing disease in barley fields. For systemic infection of barley plants, RNA1 alone was not sufficient and RNA2 was also required. Of the two proteins encoded on RNA2 (P1 with cysteine proteinase activity and P2 with unknown functions), P1 was essential and P2 was dispensable for systemic infectivity. The expression of both P1 and P2, but not the precursor polyprotein, together with RNA1 increased systemic infection and caused mosaic leaf symptoms. The infectious cDNA clones of BaYMV will be vital for future studies of bymovirus–host–vector interactions at the molecular level.
Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome ‐ a randomized, double‐blind, placebo‐controlled study
Authors: WITTMANN T. , PARADOWSKI L. , DUCROTTÉ P. , BUENO L. , ANDRO DELESTRAIN M.‐C. 
Published: February 2010

Aliment Pharmacol Ther 31, 615–624SummaryBackground  Alverine citrate and simeticone combination has been used for almost 20 years in irritable bowel syndrome (IBS), but supportive scientific evidence of efficacy was limited.Aim  To evaluate the efficacy of alverine citrate and simeticone combination in patients with IBS‐related abdominal pain/discomfort.Methods  A total of 412 IBS patients meeting ROME III criteria were included in this double‐blind randomized placebo‐controlled study if their abdominal pain/discomfort intensity was at least 60 mm on a 0–100 mm visual analogue scale (VAS) during a 2‐week run‐in treatment‐free period. Patients were randomly assigned through the use of Interactive Voice Response System to receive either alverine citrate 60 mg with simeticone 300 mg three times daily or matching placebo for 4 weeks.Results  The full analysis set included 409 patients (71.4% female: mean age: 46.2 ± 13.9 years). At week 4, alverine citrate and simeticone group had lower VAS scores of abdominal pain/discomfort (median: 40 mm vs. 50 mm, P = 0.047) and higher responder rate (46.8% vs. 34.3%, OR = 1.3; P = 0.01) as compared with placebo group. Patient receiving alverine citrate and simeticone reported greater global symptom improvement compared with those receiving placebo (P = 0.0001). Reported adverse events were similar in both groups.Conclusion  Alverine citrate/simeticone combination was significantly more effective than placebo in relieving abdominal pain/discomfort in patients with IBS.
A pneumatic dilation strategy in achalasia: prospective outcome and effects on oesophageal motor function in the long term
Authors: BRAVI I. , NICITA M. T. , DUCA P. , GRIGOLON A. , CANTÙ P. , CAPARELLO C. , PENAGINI R. 
Published: February 2010

Aliment Pharmacol Ther 31, 658–665SummaryBackground  Long‐term follow‐up studies of achalasia after pneumatic dilation, mostly retrospective, have shown variable results.Aim  To examine the outcome of achalasia after pneumatic dilation using a prospective follow‐up programme.Methods  One or two dilations (first dilation treatment) in 77 patients to achieve stable (>1 year) remission and patients followed up with yearly clinical and manometric assessments. Endoscopy, pH monitoring and barium swallow were also performed.Results  A total of 69 patients achieved stable remission and were followed up for 5.6 years (3–10.7) [median (IQ range)], whereas six patients underwent cardiomyotomy and two experienced a perforation. Twelve of the 69 patients relapsed after 2.6 years (1.7–5.1): nine of 12 underwent one to two further dilations. Six‐year remission rate (by Kaplan–Meyer estimates) was 82% after first dilation treatment and 96% after all dilations. Continuous antisecretory treatment was clinically needed in 16%, oesophagitis present in 7% and reflux pathological in 28% of the patients. Beneficial effects of dilation on oesophageal motility and on diameter of the oesophageal body at barium swallow were maintained during follow‐up.Conclusions  A management strategy including sessions of pneumatic dilation until stable remission and a standardized follow‐up is highly successful in the long term. Gastro‐oesophageal reflux is clinically relevant in a minority of patients.
The clinical presentation and prognostic factors for intrahepatic and extrahepatic cholangiocarcinoma in a tertiary care centre
Authors: SINGAL A. G. , RAKOSKI M. O. , SALGIA R. , PELLETIER S. , WELLING T. H. , FONTANA R. J. , LOK A. S. , MARRERO J. A. 
Published: February 2010

Aliment Pharmacol Ther 31, 625–633SummaryBackground  The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined.Aim  To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients.Methods  Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed.Results  In all, 136 patients had cholangiocarcinoma (79 intra‐ and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months–25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01–1.07), CA 19‐9 levels >100 U/mL (HR 1.90, 95%CI 1.17–3.08) and stage of disease (HR 1.51, 95%CI 1.16–1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26–0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra‐ and extrahepatic cholangiocarcinoma.Conclusions  Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra‐ and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19‐9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.
Low‐dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease
Authors: ANSARI A. , PATEL N. , SANDERSON J. , O’DONOHUE J. , DULEY J. A. , FLORIN T. H. J. 
Published: February 2010

Aliment Pharmacol Ther 31, 640–647SummaryBackground  The thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently.Aim  To study combination of allopurinol with reduced‐dose thiopurine in an attempt to avoid adverse drug reactions in the treatment of IBD.Methods  Patients with drug reactions to full‐dose thiopurines were recruited for combination therapy in two IBD centres in this retrospective study. Dosing was guided by measuring thiopurine methyltransferase (for UK patients) or thioguanine nucleotides and methyl‐6MP (Australian patients). Response was monitored by clinical activity indices.Results  Of 41 patients, 25 had non‐hepatic and 16 had hepatitic reactions. Clinical remission was achieved in 32 patients (78%) with a median follow‐up of 41 weeks (range 0.5–400). Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. The relative risk of having an adverse reaction with methyl‐6MP in the top interquartile range was 2.7 (1.3–28) times that with methyl‐6MP in the lower three quartiles (95% confidence interval).Conclusion  The combined experience from our centres is the largest reported experience of this combination therapy strategy in IBD, and the first to provide evidence for benefit in thiopurine and allopurinol co‐therapy to avoid non‐hepatitic adverse drug reactions.
CCR6 identifies lymphoid tissue inducer cells within cryptopatches
Authors: Lügering A , Ross M , Sieker M , Heidemann J , Williams I R , Domschke W , Kucharzik T 
Published: February 2010

Summary
The chemokine receptor CCR6 is expressed by dendritic cells, B and T cells predominantly within the organized structures of the gut-associated lymphatic tissue. Its ligand CCL20 is synthesized by the follicle-associated epithelium and is crucial for the development of M cells within Peyer's patches. In addition, lineage-negative c-kit positive lymphocytes within cryptopatches (CP) express CCR6. CCR6-deficient mice exhibit an altered intestinal immune system containing increased amounts of intraepithelial lymphocytes and show smaller Peyer's patches, while progression of cryptopatches to mature isolated lymphoid follicles (ILF) is inhibited. In this report, we show that lin- c-kit+ lymphocytes express a variety of different chemokine receptors and that CCR6 identifies those cells located within CP. In contrast, cells found outside CP are positive for CXCR3 and exhibit a different surface marker profile, suggesting that at least two different populations of lin- c-kit+ cells are present. The presence of CCR6 does not influence the expression of Notch molecules on lin- c-kit+ cells, nor does it influence Notch ligand expression on bone marrow-derived dendritic cells. In the human gut, CCR6 identifies clusters of lymphocytes resembling murine CP. CCR6 seems to have an important role for lin- c-kit+ cells inside CP, is expressed in a regulated manner and identifies potential human CP.
Interleukin-10 inhibitsMycobacterium bovisbacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against bladder cancer cells
Authors: Luo Y , Han R , Evanoff D P , Chen X 
Published: February 2010

SummaryThe mechanisms underlying bacillus Calmette–Guérin (BCG) immunotherapy of bladder cancer currently remain elusive. Previously, we demonstrated that macrophages were cytotoxic to bladder cancer cells upon BCG stimulation in vitro. However, macrophages from C57BL/6 mice were less potent than those from C3H/HeN mice for the killing of bladder cancer cells. This study was to determine whether interleukin (IL)-10 produced by macrophages in response to BCG is a causative factor for the reduced cytotoxicity in BCG-stimulated C57BL/6 macrophages. Thioglycollate-elicited peritoneal macrophages were prepared and analysed for the BCG induction of cytotoxicity, cytokines and nitric oxide (NO) in vitro. Compared to BCG-stimulated C3H/HeN macrophages, BCG-stimulated C57BL/6 macrophages exhibited reduced killing of bladder cancer MBT-2 cells and MB49 cells. Studies demonstrated further that BCG-stimulated C57BL/6 macrophages produced a high level of IL-10, which correlated with reduced production of tumour necrosis factor (TNF)-α, IL-6 and NO. Neutralizing endogenous IL-10 during BCG stimulation increased C57BL/6 macrophage cytotoxicity against MB49 cells by 3·2-fold, along with increased production of TNF-α by 6·4-fold and NO by 3·6-fold, respectively. Macrophages from C57BL/6 IL-10−/− mice also exhibited increased killing of MB49 cells and production of TNF-α and NO upon BCG stimulation. In addition, supplementation of exogenous recombinant IL-10 reduced BCG-induced C3H/HeN macrophage cytotoxicity against both MBT-2 cells and MB49 cells in a dose-dependent manner. These results reveal the inhibitory role of IL-10 in BCG-induced macrophage cytotoxicity, suggesting that blockage of IL-10 may potentially enhance the effect of BCG in the treatment of bladder cancer patients.
Association of FcGRIIa with Graves’ disease: a potential role for dysregulated autoantibody clearance in disease onset/progression
Authors: Yesmin Kadija , Hargreaves Chantal , Newby Paul R. , Brand Oliver J. , Heward Joanne M. , Franklyn Jayne A. , Gough Stephen C. L. , Simmonds Matthew J. 
Published: February 2010

SummaryObjective  Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves’ disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region.Design  A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region.Patients  A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort.Measurements  We used the χ2‐test to investigate association between the Tag SNPs and GD.Results  Association between the rs1801274 (P = 0·003, OR = 1·12 [95% CI = 1·03–1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83‐0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes.Conclusions  This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general.
Influence of parental origin of the X chromosome on physical phenotypes and GH responsiveness of patients with Turner syndrome
Authors: Ko Jung Min , Kim Jae‐Min , Kim Gu‐Hwan , Lee Beom Hee , Yoo Han‐Wook 
Published: February 2010

SummaryObjective  Previous studies have reported the effects of parental origin of the X chromosome on specific phenotypic and cognitive profiles in Turner syndrome (TS). Here, we investigate the possible parent‐of‐origin effects on physical phenotypes and responsiveness to GH in Korean patients with TS.Design and patients  Thirty‐three patients with TS with nonmosaic karyotype and their parents participated in this study. The parental origin of the normal X chromosome was determined by comparing parental DNA polymorphisms using nine highly polymorphic microsatellite markers on the X chromosome. For the evaluation of parent‐of‐origin effects, typical phenotypic traits, including congenital malformations, auxological and endocrinological profiles, were compared.Results  The retained X chromosome was of maternal (Xm) origin in 60·6% patients and paternal (Xp) origin in 39·4% patients. No significant parent‐of‐origin effects on stature, body mass index, cardiac, renal, skeletal, lymphatic, hearing or ocular systems were evident. We observed no differences in height gain after GH treatment. In patients with the 45,X karyotype, patient height was positively correlated with maternal height in the Xm group (r = 0·60, P = 0·04). Moreover, patient height was more significantly correlated with maternal than paternal height, irrespective of the parental origin of the retained X chromosome.Conclusion  While we observed no significant impact of parental origin of the X chromosome on several phenotypic traits in patients with TS, a maternal imprinting effect on stature was suggested at least in patients with 45,X. Further studies on a larger number of patients with TS are essential to define the potential imprinting effects of undetermined genes on the X chromosome.