bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo biosynthesis of cytokinins in the biotrophic fungus Claviceps purpurea
Authors: Hinsch Janine , Vrabka Josef , Oeser Birgitt , Novák Ondřej , Galuszka Petr , Tudzynski Paul 
Published: March 2015

SummaryDisease symptoms of some phytopathogenic fungi are associated with changes in cytokinin (CK) levels. Here, we show that the CK profile of ergot‐infected rye plants is also altered, although no pronounced changes occur in the expression of the host plant's CK biosynthesis genes. Instead, we demonstrate a clearly different mechanism: we report on the first fungal de novo CK biosynthesis genes, prove their functions and constitute a biosynthetic pathway. The ergot fungus Claviceps purpurea produces substantial quantities of CKs in culture and, like plants, expresses enzymes containing the isopentenyltransferase and lonely guy domains necessary for de novo isopentenyladenine production. Uniquely, two of these domains are combined in one bifunctional enzyme, CpIPT‐LOG, depicting a novel and potent mechanism for CK production. The fungus also forms trans‐zeatin, a reaction catalysed by a CK‐specific cytochrome P450 monooxygenase, which is encoded by cpp450 forming a small cluster with cpipt‐log. Deletion of cpipt‐log and cpp450 did not affect virulence of the fungus, but Δcpp450 mutants exhibit a hyper‐sporulating phenotype, implying that CKs are environmental factors influencing fungal development.
Biosynthesis of the antifungal haterumalide, oocydin A, in Serratia, and its regulation by quorum sensing, RpoS and Hfq
Authors: Matilla Miguel A. , Leeper Finian J. , Salmond George P. C. 
Published: March 2015

SummaryPolyketides represent an important class of bioactive natural products with a broad range of biological activities. We identified recently a large trans‐acyltransferase (AT) polyketide synthase gene cluster responsible for the biosynthesis of the antifungal, anti‐oomycete and antitumor haterumalide, oocydin A (ooc). Using genome sequencing and comparative genomics, we show that the ooc gene cluster is widespread within biocontrol and phytopathogenic strains of the enterobacteria, Serratia and Dickeya. The analysis of in frame deletion mutants confirmed the role of a hydroxymethylglutaryl‐coenzyme A synthase cassette, three flavin‐dependent tailoring enzymes, a free‐standing acyl carrier protein and two hypothetical proteins in oocydin A biosynthesis. The requirement of the three trans‐acting AT domains for the biosynthesis of the macrolide was also demonstrated. Expression of the ooc gene cluster was shown to be positively regulated by an N‐acyl‐L‐homoserine lactone‐based quorum sensing system, but operating in a strain‐dependent manner. At a post‐transcriptional level, the RNA chaperone, Hfq, plays a key role in oocydin A biosynthesis. The Hfq‐dependent regulation is partially mediated by the stationary phase sigma factor, RpoS, which was also shown to positively regulate the synthesis of the macrolide. Our results reveal differential regulation of the divergently transcribed ooc transcriptional units, highlighting the complexity of oocydin A production.
Metagenome sequence of Elaphomyces granulatus from sporocarp tissue reveals Ascomycota ectomycorrhizal fingerprints of genome expansion and a Proteobacteria‐rich microbiome
Authors: Quandt C. Alisha , Kohler Annegret , Hesse Cedar N. , Sharpton Thomas J. , Martin Francis , Spatafora Joseph W. 
Published: March 2015

SummaryMany obligate symbiotic fungi are difficult to maintain in culture, and there is a growing need for alternative approaches to obtaining tissue and subsequent genomic assemblies from such species. In this study, the genome of Elaphomyces granulatus was sequenced from sporocarp tissue. The genome assembly remains on many contigs, but gene space is estimated to be mostly complete. Phylogenetic analyses revealed that the Elaphomyces lineage is most closely related to Talaromyces and Trichocomaceae s.s. The genome of E. granulatus is reduced in carbohydrate‐active enzymes, despite a large expansion in genome size, both of which are consistent with what is seen in Tuber melanosporum, the other sequenced ectomycorrhizal ascomycete. A large number of transposable elements are predicted in the E. granulatus genome, especially Gypsy‐like long terminal repeats, and there has also been an expansion in helicases. The metagenome is a complex community dominated by bacteria in Bradyrhizobiaceae, and there is evidence to suggest that the community may be reduced in functional capacity as estimated by KEGG pathways. Through the sequencing of sporocarp tissue, this study has provided insights into Elaphomyces phylogenetics, genomics, metagenomics and the evolution of the ectomycorrhizal association.
Inferring species interactions in ecological communities: a comparison of methods at different levels of complexity
Authors: Carrara Francesco , Giometto Andrea , Seymour Mathew , Rinaldo Andrea , Altermatt Florian 
Published: March 2015

Summary

Natural communities commonly contain many different species and functional groups, and multiple types of species interactions act simultaneously, such as competition, predation, commensalism or mutualism. However, experimental and theoretical investigations have generally been limited by focusing on one type of interaction at a time or by a lack of a common methodological and conceptual approach to measure species interactions.

We compared four methods to measure and express species interactions. These approaches are, with increasing degree of model complexity, an extinction‐based model, a relative yield model and two generalized Lotka‐Volterra (LV) models. All four approaches have been individually applied in different fields of community ecology, but rarely integrated. We provide an overview of the definitions, assumptions and data needed for the specific methods and apply them to empirical data by experimentally deriving the interaction matrices among 11 protist and rotifer species, belonging to three functional groups. Furthermore, we compare their advantages and limitations to predict multispecies community dynamics and ecosystem functioning.

The relative yield method is, in terms of final biomass production, the best method in predicting the 11‐species community dynamics from the pairwise competition experiments. The LV model, which is considering equilibrium among the species, suffers from experimental constraints given the strict equilibrium assumption, and this may be rarely satisfied in ecological communities.

We show how simulations of a LV stochastic community model, derived from an empirical interaction matrix, can be used to predict multispecies community dynamics across multiple functional groups.

Our work unites available tools to measure species interactions under one framework. This improves our ability to make management‐oriented predictions of species coexistence/extinction and to compare ecosystem processes across study systems.
A worrying trend in weight‐adjusted paediatric antibiotic use in a Norwegian tertiary care hospital
Authors: Raastad Ragnhild , Tvete Ingunn Fride , Abrahamsen Tore G. , Berild Dag , Leegaard Truls M. , Walberg Mette , Müller Fredrik 
Published: March 2015

AbstractAimThe World Health Organization recommends the defined daily dose (DDD) as the standard unit of measurement for antibiotic use, but this is not applicable in children. We aimed to assess paediatric antibiotic use in a Norwegian tertiary care hospital using a novel weight‐adjusted method.MethodsWe obtained antibiotic purchase data from the hospital pharmacy and administrative data for all admissions from 2002 to 2009 to the paediatric wards at Oslo University Hospital, Rikshospitalet. Recommended daily doses per 100 kg days (RDDs/kg days) were calculated based on national guidelines for paediatric antibiotic use, length of stay and estimated weight for sex and age using national growth references.ResultsTotal antibiotic use increased significantly from 51.8 to 65.5 RDDs/100 kg days. We found statistically significant annual increases in the consumption of carbapenems (18.0%), third‐generation cephalosporins (6.0%) and imidazole derivatives (6.6%) and a considerable difference between total antibiotic use measured in RDDs/100 kg days and DDDs/100 bed days for neonates.ConclusionWeight‐adjusted antibiotic use provided a more meaningful description of the quantities of antibiotics consumed than DDDs/100 bed days, particularly for neonates. Total antibiotic use, use of meropenem, third‐generation cephalosporins and imidazole derivatives increased significantly despite low prevalence of antibiotic‐resistant pathogens.
A phase I study of bendamustine, lenalidomide and rituximab in relapsed and refractory lymphomas
Authors: Cheson Bruce D. , Crawford Jeanette 
Published: March 2015

SummaryMany patients with non‐Hodgkin (NHL) or Hodgkin lymphoma (HL) relapse or are refractory to initial therapy and require additional options. Bendamustine (B), lenalidomide (L) and rituximab (R) each have activity in this setting. This study was performed to determine the safety of BLR and its optimal phase II dose. Patients with NHL or HL failing standard therapies received B (90 mg/m2 days 1, 2 every 28 days), and L (escalating from 5 mg 21/28 days) for six cycles, followed by 6 months of L. At the highest dose R 375 mg/m2 on day one of each cycle was added for patients with B‐NHL. Histologies included diffuse large B‐cell lymphoma (DLBCL, 11), marginal zone lymphoma (3), HL (2), and one each of transformed follicular lymphoma, Sézary syndrome, Waldenström macroglobulinaemia and mantle cell lymphoma. Neutropenia was the most common grade 3 and 4 toxicity, but no maximum tolerated dose was identified. Of 20 patients, seven responded (35%), including four complete remissions, with five unmaintained responses from 28+ to 37+ months, including 2 DLBCL. BR with 20 mg l at, 21/28 days achieved durable responses; however, in light of its modest activity, and the availability of newer targeted therapies, the future of BLR is uncertain.
Role of enhanced half‐life factor VIII and IX in the treatment of haemophilia
Authors: Mahdi Ali J. , Obaji Samya G. , Collins Peter W. 
Published: March 2015

SummaryTreatment of congenital haemophilia with factor VIII and IX concentrates often requires frequent infusions. This has obvious implications in establishing effective administration strategies and, in turn, adherence. To overcome these issues, three main technologies – polyethylene‐glycol, Fc‐neonatal IgG1 and albumin fusion products – have emerged into various stages of clinical development. Published data indicates an approximately 1·5‐ and fivefold increase in half‐life of factor VIII and IX, respectively, compared to standard recombinant concentrates. Studies into efficacy and safety are starting to be published. Monitoring and optimal use of these new concentrates remains unknown. Weekly factor IX prophylaxis appears to be a feasible prophylactic regimen in haemophilia B patients. Weekly longer‐acting FVIII is unlikely to provide adequate prophylaxis in most patients with haemophilia A but may reduce the frequency of infusions. Ongoing clinical trials and real life experience will help shape how these products can be used in practice and their cost effectiveness. The drive for convenience however should not overshadow the ultimate goal of prophylaxis, namely, preventing bleeding and arthropathy.
Negative health implications of sickle cell trait in high income countries: from the football field to the laboratory
Authors: Key Nigel S. , Connes Philippe , Derebail Vimal K. 
Published: March 2015

SummaryWorldwide, sickle cell trait is a highly prevalent gene carrier state. While generally a benign condition with a normal life expectancy, it is becoming increasingly clear that the sickle trait is associated with certain adverse outcomes. This article will focus on three of these outcomes, namely exertional rhabdomyolysis and sudden death, chronic renal dysfunction, and venous thromboembolism. In each case, the epidemiological evidence for the association is reviewed, together with the existing data on potential underlying mechanisms. Because newborn screening programmes for sickle cell anaemia also identify those with sickle cell trait, it is imperative that further studies determine what, if any, preventive measures can be taken to reduce the burden of these uncommon but potentially morbid complications in affected individuals.
Fertility after young‐onset colorectal cancer: a study of subjects with Lynch syndrome
Authors: Stupart D. , Win A. K. , Winship I. M. , Jenkins M. 
Published: March 2015

AbstractAimInfertility is a concern for young survivors of colorectal cancer (CRC), but this risk is not well quantified. Carriers of mismatch repair (MMR) mutations are a useful cohort for studying fertility after CRC as they commonly develop CRC when young, and unaffected family members provide demographically similar controls. The aim of this study was to determine the effect of CRC on fertility in a large cohort of MMR mutation carriers.MethodMismatch repair mutation carriers identified from the Australasian Colorectal Cancer Family Registry were included. For each year of life within the fertile age range (15–49), the number of living individuals and the number of children born to them were determined. Individuals were grouped by whether or not they had had a diagnosis of CRC by that age. Age‐specific and total fertility rates were calculated.ResultsWe identified 1068 subjects (611 women and 457 men), of whom 467 were diagnosed with CRC. There were 1192 births during 18 674 person‐years of follow‐up to the women and 814 births during 14 013 person‐years of follow‐up to the men. The total fertility rate was decreased in women after a diagnosis of CRC compared with those who did not have CRC (1.3 vs 2.2; P = 0.0011), but age‐specific fertility was only reduced in the 20–24‐year age group. In men the total fertility rate was similar for both groups (2.0 vs 1.8; P = 0.27).ConclusionAge‐specific fertility was decreased in female CRC survivors with Lynch syndrome aged 20–24, but not in older women or in men.
Pharmacologic androgen deprivation and cardiovascular disease risk factors: a systematic review
Authors: Romo Matthew L. , McCrillis Aileen M. , Brite Jennifer , Reales Dalicia , Dowd Jennifer B. , Schooling C. Mary 
Published: March 2015

AbstractBackgroundPharmacologic androgen deprivation therapy (ADT) is widely used to treat prostate cancer. Observational studies suggest ADT is associated with cardiovascular disease and its risk factors; however, such studies may be subject to bias. Our objective was to evaluate the effect of ADT on cardiovascular disease risk factors using data from randomized controlled trials (RCTs).Materials and methodsWe conducted a systematic review using MEDLINE and MEDLINE In‐Process (1950–June 2013), EMBASE (1974–June 2013) and Web of Science (1900–June 2013) for all RCTs in men with prostate cancer that compared pharmacologic ADT (i.e. use of gonadotropin‐releasing hormone agonist or antagonist) with a group that did not receive ADT and reported data on cardiovascular disease risk factors including blood pressure, cholesterol, triglycerides, fibrinogen, biomarkers of insulin sensitivity, adiposity and C‐reactive protein. We also searched for ongoing or unpublished trials. This study was registered at the PROSPERO International Prospective Register of Systematic Reviews (CRD42013005035).ResultsOf the 3272 unique publications identified in our systematic review, we did not identify a single RCT that reported data on any cardiovascular disease risk factor. We were unable to locate unreported data from corresponding authors or study sponsors.ConclusionsThere is a lack of published, reliable evidence describing the effects of ADT on cardiovascular disease risk factors. RCTs have likely collected data on these risk factors as part of routine study monitoring; however, these data have not been published. To understand the effect of ADT on cardiovascular morbidity, these data must be made available to the scientific community.
Association of the dispersion in red blood cell volume with mortality
Authors: Horne Benjamin D. , Muhlestein Joseph B. , Bennett Sterling T. , Muhlestein Joseph Boone , Ronnow Brianna S. , May Heidi T. , Bair Tami L. , Anderson Jeffrey L. 
Published: March 2015

AbstractBackgroundThe red cell distribution width (RDW) predicts mortality among many populations. RDW is calculated as the standard deviation (SD) of the red blood cell (RBC) volume divided by mean corpuscular volume (MCV). Because higher MCV also predicts mortality, we hypothesized that the RDW numerator (one SD of RBC volume or 1SD‐RDW) predicts mortality more strongly than the RDW.Material and methodsAdult subjects hospitalized during a contemporary clinical era (10/2005‐1/2014, N = 135 963) and a historical era (1/1999‐9/2005, N = 119 530) were studied. The RDW was obtained from the complete blood count (CBC), while 1SD‐RDW was calculated (RDW multiplied by MCV and divided by 100).ResultsIn univariable Cox regression (2005–2014 cohort), 1SD‐RDW (quintile 5 vs. 1: hazard ratio [HR] = 8·38, 95% confidence interval [CI] = 7·94, 8·85; P < 0·001) was a superior predictor of mortality compared to RDW (quintile 5 vs. 1: HR = 4·78, CI = 4·57, 5·00; P < 0·001). This superiority remained after adjustment for age, sex, basic metabolic profile components and other CBC factors excluding MCV (1SD‐RDW: HR = 2·41, CI = 2·28, 2·55; RDW: HR = 2·01, CI = 1·92, 2·11). Further adjustment for MCV strengthened the RDW association (HR = 2·14, CI = 2·04, 2·24; P < 0·001), becoming indistinct from 1SD‐RDW (HR = 2·20, CI = 2·08, 2·33; P < 0·001). Findings were similar for the 1999–2005 cohort.ConclusionsThe 1SD‐RDW predicted mortality more strongly than RDW, suggesting that 1SD‐RDW is superior to RDW as an individual risk predictor. Further, these results indicate that the dispersion of RBC volume and its mean are independent risk markers. Further research is required to understand the clinical value and mechanistic basis of these associations.
Multiproblem Families Referred to Youth Mental Health: What's in a Name?
Authors: Bodden Denise H.M. , Deković Maja 
Published: March 2015

The purpose of this study was threefold, namely (1) to differentiate between multiproblem families and control families on characteristics and processes within the family based on a theoretical framework, (2) to identify multiproblem families by establishing cut‐off scores on various questionnaires, and (3) to categorize multiproblem families into subtypes by cluster analyses. Various questionnaires were administered to multiproblem families (n = 85) and control families (n = 150). Results showed that what we propose to refer to as multiproblem families present a broad range of problems on seven domains: (1) child factors, (2) parental factors, (3) childrearing problems (inadequate or inconsistent parenting), (4) family functioning problems, (5) contextual problems, (6) social network problems, and (7) mental health care problems. Further, reliable cut‐off scores were established for various questionnaires. Finally, three types of families were found: (1) community‐problem families, (2) multiproblem families, and (3) child‐focused mild‐problem families. This paper looks to advance an evidence‐based definition and assessment of “multiproblem families” suggesting the possible value of defining and assessing multiproblem families in relation to these seven dimensions. Moreover, the classification of multiproblem families stresses the importance of providing tailored treatments.
Effect of the oestrogen receptor antagonist fulvestrant on the cirrhotic rat lung
Authors: Oswald‐Mammosser Monique , Rashid Sherzad , Boehm Nelly , Agin Arnaud , Geny Bernard , Schini‐Kerth Valérie , Charloux Anne 
Published: March 2015

AbstractIt has been postulated that cirrhosis‐related lung vasodilatation and the subsequent hepatopulmonary syndrome are partly explained by an increased estradiol level through an enhanced endothelial formation of nitric oxide (NO). In this study, we assessed whether the oestrogen receptor antagonist fulvestrant (F) improves cirrhosis‐related lung abnormalities. Cirrhosis was induced in rats by chronic bile duct ligation (CBDL). Four groups were studied: CBDL, CBDL+F, sham, and sham+F. Histological, immunohistochemical, and Western blot analyses were performed on lung samples. In the lung, the endothelial NO synthase and the nitrotyrosine protein expressions were increased in CBDL as compared to sham rats. Both parameters were significantly reduced by fulvestrant in the CBDL rats. Surprisingly, the level of pVASP (an indirect marker of NO formation and action) was decreased in CBDL rats, and fulvestrant had no effect on this parameter. The level of the vascular endothelial growth factor, the diameter of small lung vessels, and the number of macrophages were increased in CBDL lungs in comparison with sham lungs, and these parameters were unaffected by fulvestrant treatment. In conclusion, fulvestrant may not be relevant to improve lung abnormalities in cirrhosis because NO may not be biologically active and because key events contributing to the lung abnormalities are not affected by fulvestrant.
Protein disulfide isomerase as a novel target for cyclopentenone prostaglandins: implications for hypoxic ischemic injury
Authors: Liu Hao , Chen Jie , Li Wenjin , Rose Marie E. , Shinde Sunita N. , Balasubramani Manimalha , Uechi Guy T. , Mutus Bülent , Graham Steven H. , Hickey Robert W. 
Published: March 2015

Cyclooxygenase‐2 (COX‐2) is an important contributor to ischemic brain injury. Identification of the downstream mediators of COX‐2 toxicity may allow the development of targeted therapies. Of particular interest is the cyclopentenone family of prostaglandin metabolites. Cyclopentenone prostaglandins (CyPGs) are highly reactive molecules that form covalent bonds with cellular thiols. Protein disulfide isomerase (PDI) is an important molecule for the restoration of denatured proteins following ischemia. Because PDI has several thiols, including thiols within the active thioredoxin‐like domain, we hypothesized that PDI is a target of CyPGs and that CyPG binding of PDI is detrimental. CyPG–PDI binding was detected in vitro via immunoprecipitation and MS. CyPG–PDI binding decreased PDI enzymatic activity in recombinant PDI treated with CyPG, and PDI immunoprecipitated from neuronal culture treated with CyPG or anoxia. Toxic effects of binding were demonstrated in experiments showing that: (a) pharmacologic inhibition of PDI increased cell death in anoxic neurons, (b) PDI overexpression protected neurons exposed to anoxia and SH‐SY5Y cells exposed to CyPG, and (c) PDI overexpression in SH‐SY5Y cells attenuated ubiquitination of proteins and decreased activation of pro‐apoptotic caspases. In conclusion, CyPG production and subsequent binding of PDI is a novel and potentially important mechanism of ischemic brain injury. We show that CyPGs bind to PDI, cyclopentenones inhibit PDI activity, and CyPG–PDI binding is associated with increased neuronal susceptibility to anoxia. Additional studies are necessary to determine the relative role of CyPG‐dependent inhibition of PDI activity in ischemia and other neurodegenerative disorders.