bluuebunny/crossref_metadata_2025 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

Disease 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

Polyketides 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

Many 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

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

Aim

The 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.

Methods

We 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.

Results

Total 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.

Conclusion

Weight‐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

Many 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

Treatment 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

Worldwide, 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

Aim

Infertility 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.

Method

Mismatch 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.

Results

We 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).

Conclusion

Age‐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

Background

Pharmacologic 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 methods

We 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).

Results

Of 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.

Conclusions

There 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

Background

The 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 methods

Adult 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).

Results

In 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.

Conclusions

The 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

It 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.
Inter‐ and intra‐domain horizontal gene transfer, gain–loss asymmetry and positive selection mark the evolutionary history of the CBM14 family
Authors: Chang Ti‐Cheng , Stergiopoulos Ioannis
Published: March 2015

Protein–carbohydrate interactions are ubiquitous in nature and at the core of many physiological processes of profound importance to health and disease. Specificity in protein–carbohydrate interactions is conferred by carbohydrate‐binding modules (CBMs) that can accurately discriminate among the multitude of saccharides found in nature, thus targeting proteins to their particular substrates. Family 14 carbohydrate‐binding modules (CBM14s), more specifically, are short modules that bind explicitly to chitin, the second most abundant carbohydrate in nature. Although considerable effort has been placed in elucidating protein–carbohydrate interactions at the molecular level for biological and biotechnological applications, in contrast the evolutionary relationships among these modules are minimally understood. Using the CBM14 family as an example, here we describe one of the first global molecular evolutionary analyses of a CBM family across all domains of life, with an emphasis on its origin, taxonomic distribution and pattern of diversification as a result of gene and module duplication, and positive selection. Our genome‐wide searches recovered an impressive number of CBM14s from diverse lineages across nearly all domains of life. However, their highly disseminated distribution in taxa outside the Opisthokonta group strongly suggests a later evolutionary origin and elevated rates of inter‐ and intra‐domain horizontal gene transfer. Moreover, accelerated rates of asymmetric gains and losses reveal a dynamic mode of birth‐and‐death evolution, whereas positive selection acting on paralogous CBM14‐containing proteins suggest changes in substrate specificity and an increase in the functional promiscuity of this ancient CBM family. The importance of these results is discussed.
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.
Phenological plasticity will not help all species adapt to climate change
Authors: Duputié Anne , Rutschmann Alexis , Ronce Ophélie , Chuine Isabelle
Published: March 2015

Concerns are rising about the capacity of species to adapt quickly enough to climate change. In long‐lived organisms such as trees, genetic adaptation is slow, and how much phenotypic plasticity can help them cope with climate change remains largely unknown. Here, we assess whether, where and when phenological plasticity is and will be adaptive in three major European tree species. We use a process‐based species distribution model, parameterized with extensive ecological data, and manipulate plasticity to suppress phenological variations due to interannual, geographical and trend climate variability, under current and projected climatic conditions. We show that phenological plasticity is not always adaptive and mostly affects fitness at the margins of the species' distribution and climatic niche. Under current climatic conditions, phenological plasticity constrains the northern range limit of oak and beech and the southern range limit of pine. Under future climatic conditions, phenological plasticity becomes strongly adaptive towards the trailing edges of beech and oak, but severely constrains the range and niche of pine. Our results call for caution when interpreting geographical variation in trait means as adaptive, and strongly point towards species distribution models explicitly taking phenotypic plasticity into account when forecasting species distribution under climate change scenarios.
Effects of climate extremes on the terrestrial carbon cycle: concepts, processes and potential future impacts
Authors: Frank Dorothea , Reichstein Markus , Bahn Michael , Thonicke Kirsten , Frank David , Mahecha Miguel D. , Smith Pete , van der Velde Marijn , Vicca Sara , Babst Flurin , Beer Christian , Buchmann Nina , Canadell Josep G. , Ciais Philippe , Cramer Wolfgang , Ibrom Andreas , Miglietta Franco , Poulter Ben , Rammig Anja , Seneviratne Sonia I. , Walz Ariane , Wattenbach Martin , Zavala Miguel A. , Zscheischler Jakob
Published: March 2015

Extreme droughts, heat waves, frosts, precipitation, wind storms and other climate extremes may impact the structure, composition and functioning of terrestrial ecosystems, and thus carbon cycling and its feedbacks to the climate system. Yet, the interconnected avenues through which climate extremes drive ecological and physiological processes and alter the carbon balance are poorly understood. Here, we review the literature on carbon cycle relevant responses of ecosystems to extreme climatic events. Given that impacts of climate extremes are considered disturbances, we assume the respective general disturbance‐induced mechanisms and processes to also operate in an extreme context. The paucity of well‐defined studies currently renders a quantitative meta‐analysis impossible, but permits us to develop a deductive framework for identifying the main mechanisms (and coupling thereof) through which climate extremes may act on the carbon cycle. We find that ecosystem responses can exceed the duration of the climate impacts via lagged effects on the carbon cycle. The expected regional impacts of future climate extremes will depend on changes in the probability and severity of their occurrence, on the compound effects and timing of different climate extremes, and on the vulnerability of each land‐cover type modulated by management. Although processes and sensitivities differ among biomes, based on expert opinion, we expect forests to exhibit the largest net effect of extremes due to their large carbon pools and fluxes, potentially large indirect and lagged impacts, and long recovery time to regain previous stocks. At the global scale, we presume that droughts have the strongest and most widespread effects on terrestrial carbon cycling. Comparing impacts of climate extremes identified via remote sensing vs. ground‐based observational case studies reveals that many regions in the (sub‐)tropics are understudied. Hence, regional investigations are needed to allow a global upscaling of the impacts of climate extremes on global carbon–climate feedbacks.
Public Drug Coverage and Its Impact on Triptan Use Across Canada: A Population‐Based Study
Authors: Amadio Anthony , Lee Kathy , Yao Zhan , Camacho Ximena , Knowles Sandra , Lay Christine , Paterson J. Michael , Hunt Jordan , Gomes Tara ,   Ontario Drug Policy Research Network
Published: March 2015

Background

Public drug coverage for triptan medications varies across jurisdictions in Canada, which may lead to differences in usage patterns and patient risk for medication overuse headache.

Methods

We conducted a population‐based, cross‐sectional analysis of publicly funded triptan use in seven provinces across Canada from January 1, 2012 to December 31, 2012. All patients who had filled at least one prescription for a triptan during the study period were included. We defined quantity limits of 6, 12, and 18 triptan units per month to assess the prevalence of high volumes of triptan use, which may place patients at risk for medication overuse headaches, and compared this prevalence between provinces with different funding restrictions.

Results

We identified 14,085 publicly funded users of triptans in 2012 in the seven provinces studied, 82.5% of whom were aged less than 65 years (N = 11,631). The prevalence of triptan use ranged substantially by province, from 0.04% in Ontario to a maximum of 1.0% in Manitoba (P < .001). Furthermore, the percentage of patients in each province using more than 6, 12, or 18 units per month differed significantly between provinces (P < .001). In particular, the percentage of patients treated with more than 6 units per month ranged from as low as 2.1% in Saskatchewan to 43.8% in Ontario.

Conclusions

Differing public drug reimbursement criteria for triptans may be one contributing factor that has led to our observation of considerable variation in both prevalence of triptan prescribing and potential overuse of these medications. We offer that monthly quantity limits may be considered as a tool to decrease risks for medication overuse headache.
Symptoms and Physiological Responses to Prolonged, Repeated, Low‐Level Tooth Clenching in Humans
Authors: Takeuchi Tamiyo , Arima Taro , Ernberg Malin , Yamaguchi Taihiko , Ohata Noboru , Svensson Peter
Published: March 2015

Background

The traditional view contends bruxism, such as tooth grinding/clenching, is part of the etiology of temporomandibular disorders (TMD) including some subtypes of headaches. The purpose of this study is to investigate if a low‐level but long‐lasting tooth‐clenching task initiates TMD symptoms/signs.

Methods

Eighteen healthy participants (mean age ± SD, 24.0 ± 4.3 years) performed and repeated an experimental 2‐hour tooth‐clenching task at 10% maximal voluntary occlusal bite force at incisors (11.1 ± 4.6 N) for three consecutive days (Days 1‐3). Pain and cardiovascular parameters were estimated during the experiment.

Results

The task evoked pain in the masseter/temporalis muscles and temporomandibular joint after 40.0 ± 18.0 minutes with a peak intensity of 1.6 ± 0.4 on 0‐10 numerical rating scale (NRS) after 105.0 ± 5.0 minutes (Day 1). On Day 2 and Day 3, pain had disappeared but the tasks, again, evoked pain with similar intensities. The onset and peak levels of pain were not different between the experimental days (P = .977). However, the area under the curve of pain NRS in the masseter on Day 2 and Day 3 were smaller than that on Day 1 (P = .006). Cardiovascular parameters changed during the task but not during the days.

Conclusions

Prolonged, low‐level tooth clenching evoked short‐lived pain like TMD. This intervention study proposes that tooth clenching alone is insufficient to initiate longer lasting and self‐perpetuating symptoms of TMD, which may require other risk factors.
Migraine and Epilepsy: Review of the Literature
Authors: Nye Barbara L. , Thadani Vijay M.
Published: March 2015

Migraine and epilepsy are disorders that are common, paroxysmal, and chronic. In many ways they are clearly different diseases, yet there are some pathophysiological overlaps, and overlaps in clinical symptomatology, particularly with regard to visual and other sensory disturbances, pain, and alterations of consciousness.

Epidemiological studies have revealed that the two diseases are comorbid in a number of individuals. Both are now recognized as originating from electrical disturbances in the brain, although their wider manifestations involve the recruitment of multiple pathogenic mechanisms. An initial excess of neuronal activity in migraine leads to cortical spreading depression and aura, with the subsequent recruitment of the trigeminal nucleus leading to central sensitization and pain. In epilepsy, neuronal overactivity leads to the recruitment of larger populations of neurons firing in a rhythmic manner that constitutes an epileptic seizure. Migraine aura and headaches may act as a trigger for epileptic seizures. Epilepsy is not infrequently accompanied by preictal, ictal, and postictal headaches that often have migrainous features.

Genetic links are also apparent between the two disorders, and are particularly evident in the familial hemiplegic migraine syndromes where different mutations can produce either migraine, epilepsy, or both. Also, various medications are found to be effective for both migraine and epilepsy, again pointing to a commonality and overlap between the two disorders.
Evaluating the effectiveness of knowledge brokering in health research: a systematised review with some bibliometric information
Authors: Elueze Isioma N.
Published: March 2015

Objective

The aim of this study was to identify the effectiveness of knowledge brokering as a knowledge translation (KT) strategy used in promoting evidence‐based decision‐making, evidence‐based practice or collaboration between researchers, health practitioners and policymakers.

Methods

A systematised review of literature was performed using MEDLINE (through ProQuest® Dialog), PubMed and Scopus electronic databases. A search strategy was developed to identify primary studies indexed in these databases on knowledge translation that reported the implementation of knowledge brokering. Sixty‐two titles related to knowledge brokering were identified from the search after the removal of duplicates, and 24 articles met the eligibility criteria following the review of the full text documents. The findings were then synthesised using a narrative approach.

Results

It was found that knowledge brokering has been an effective strategy for knowledge translation.

Conclusion

Although this review shows that knowledge brokering has been an effective strategy for KT, it advocates for more empirical studies to compare the effectiveness of specific knowledge brokering approaches with others. It also calls for empirical studies to explicate the role of library and information science professionals in knowledge brokering.
The Anarchist's Myth: Autonomy, Children, and State Legitimacy
Authors: Ferracioli Luara
Published: March 2015

Philosophical anarchists have made their living criticizing theories of state legitimacy and the duty to obey the law. The most prominent theories of state legitimacy have been called into doubt by the anarchists' insistence that citizens' lack of consent to the state renders the whole justificatory enterprise futile. Autonomy requires consent, they argue, and justification must respect autonomy. In this essay, I want to call into question the weight of consent in protecting our capacity for autonomy. I argue that if we care about all of the preconditions for autonomy, then we have good reasons to leave the state of nature. This leaves the philosophical anarchist with a dilemma. If she truly cares about autonomy, then she must welcome the state. But if she wants to deny the legitimacy of the state because of the value of consent, then she needs to downplay the moral significance of autonomy in people's lives. If autonomy matters, the state does too. If it doesn't, then consent doesn't. The philosophical anarchist can't have it both ways.
The Stereotype Threat Hypothesis: An Assessment from the Philosopher's Armchair, for the Philosopher's Classroom
Authors: Schouten Gina
Published: March 2015

According to Stereotype Threat Hypothesis (STH), fear of confirming gendered stereotypes causes women to experience anxiety in circumstances wherein their performance might potentially confirm those stereotypes, such as high‐stakes testing scenarios in science, technology, engineering, and math (STEM) courses. This anxiety causes women to underperform, which in turn causes them to withdraw from math‐intensive disciplines. STH is thought by many to account for the underrepresentation of women in STEM fields, and a growing body of evidence substantiates this hypothesis. In considering the plausibility of STH as an explanation for women's disproportionate attrition from undergraduate philosophy programs, one is struck by dissimilarities between STEM and philosophy that appear to undermine the applicability of STH to the latter. In this paper, I argue that these dissimilarities are either merely apparent or merely apparently relevant to the plausibility of STH as an explanation for gender disparities in philosophy. I argue further that, if research from STEM uncovers promising strategies for confronting stereotype threat, we should think about how to apply those strategies in our introductory philosophy classrooms.
Postmenopausal Motherhood Reloaded: Advanced Age and In Vitro Derived Gametes
Authors: Cutas Daniela , Smajdor Anna
Published: March 2015

In this paper we look at the implications of an emerging technology for the case in favor of, or against, postmenopausal motherhood. Technologies such as in vitro derived gametes (sperm and eggs derived from nonreproductive cells) have the potential to influence the ways in which reproductive medicine is practiced, and are already bringing new dimensions to debates in this area. We explain what in vitro derived gametes are and how their development may impact on the case of postmenopausal motherhood. We briefly review some of the concerns that postmenopausal motherhood has raised—and the implications that the successful development, and use in reproduction, of artificial gametes might have for such concerns. The concerns addressed include arguments from nature, risks and efficacy, reduced energy of the mother, and maternal life expectancy. We also consider whether the use of in vitro derived gametes to facilitate postmenopausal motherhood would contribute to reinforcing a narrow, geneticized account of reproduction and a pro‐reproductive culture that encourages women to produce genetically related offspring at all costs.
Development Ethics, Gender Complementarianism, and Intrahousehold Inequality
Authors: Khader Serene J.
Published: March 2015

Development ethicists see reducing intrahousehold gender inequality as an important policy aim. However, it is unclear that a minimalist cross‐cultural consensus can be formed around this goal. Inequality on its own may not bring women beneath a minimal welfare threshold. Further, adherents of complementarian metaphysical doctrines may view attempts to reduce intrahousehold inequality as attacks on their worldviews. Complicating the justificatory task is the fact that familiar arguments against intrahousehold inequality, including those from agency and self‐esteem, depart from premises that complementarians reject—premises about the value of independence or the moral irrelevance of gender. I propose that development ethicists should offer complementarianism‐compatible arguments against the norms and practices constitutive of intrahousehold inequality. I develop arguments against two intrahousehold inequality‐supportive practices that depart from complementarian premises. Specifically, I argue that patriarchal risk and gender schemas that devalue women's labor prevent men from discharging complementarian duties to promote women's welfare.
CdS and CdSe Quantum Dot‐Embedded Silicate Glasses for LED Color Converter
Authors: Han Karam , Yoon Sukeun , Chung Woon Jin
Published: March 2015

Silicate glasses with CdS and CdSe quantum dots (QDs) were synthesized for application as an inorganic color converter for a 450‐nm blue light‐emitting diode (LED). CdO and ZnS (or ZnSe) were added, and heat treatment conditions were changed to control QD formation within the silicate matrix. Absorption spectra and high‐resolution transmission electron microscopy confirmed the QD formation. Variations in absorption and photoluminescence (PL) spectra were observed with CdSe QD‐embedded glasses when heat treatment conditions varied, whereas glasses with CdS QDs did not show noticeable variation. QD‐embedded glasses were then mounted on top of a 450‐nm LED chip to make a color‐converted LED, and their electroluminescence and PL spectra as well as CIE color coordinates were investigated. The practical potential of QD‐embedded glasses as an inorganic color converter has been observed, and their spectral properties were discussed.
School performance and oral health conditions: analysis of the impact mediated by socio‐economic factors
Authors: Paula Janice Simpson , Lisboa Cristina Martins , de Castro Meneghim Marcelo , Pereira Antônio Carlos , Ambrosano Glaucia Maria Bovi , Mialhe Fábio Luiz
Published: March 2015

Background

Oral problems can cause strong impact on functional, emotional, and social aspects of children and adolescents, as well as changes in school performance.

Aim

To evaluate the associations of subjective perceptions of parents, socio‐economic factors, and oral clinical conditions of children with their school performance.

Design

A case–control design was used with a sample of 1411 schoolchildren aged 8–10 years from city of Piracicaba, São Paulo, Brazil. Clinical conditions were evaluated using the DMFT and dmft indexes. Socio‐economic data were obtained using a questionnaire sent to schoolchildren's parents. School performance was evaluated by the final scores of each schoolchild at the end of the 2011 school year.

Results

According to the final logistic regression model, the schoolchildren who had carious lesions and underwent curative dental treatment at the beginning of the academic year presented 1.51 more chance of having low performance compared with schoolchildren who had no caries lesions. In addition, socio‐economic and demographic variables were associated with a greater chance of poor school performance.

Conclusion

Socio‐economic factors and presence of caries lesions, even if treated, were risk indicators for poor school performance.
Interaction of Indentation‐Induced Cracks on Single‐Crystal Silicon Carbide
Authors: Kunka Cody , Trachet Alison , Subhash Ghatu
Published: March 2015

Due to its transparency, high hardness, and low density, single‐crystal silicon carbide (SC‐SiC) is a candidate material for transparent armor and bullet‐proof windows. This manuscript explores the fracture anisotropy of the basal plane of two common HCP polytypes: 4H‐SiC and 6H‐SiC. Through single indentation, sequential indentation, and theoretical calculations, the primary and secondary cleavage directions are shown to be <11̄20> and <10̄10>, respectively. It is also shown that no appreciable tertiary cleavage direction exists on the basal plane. This investigation is the first to report how single‐crystal silicon carbide responds to multiple indentation. The results have fundamental value in modeling its fracture behavior.
Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation
Authors: Wei Jia‐Yi , Li Wan‐Ming , Zhou Lin‐Lin , Lu Qiu‐Nan , He Wei
Published: March 2015

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca2+/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.
Morphological examination and phylogenetic position of the newly recorded heterotrophic brackish dinoflagellateDiplopsalis caspica(Dinophyceae) in freshwater habitat from China
Authors: Zhang Qi , Song Hui‐Yin , Hu Zheng‐Yu , Liu Guo‐Xiang
Published: March 2015

A heterotrophic dinoflagellate was identified asDiplopsalis caspicaOstenfeld by morphological characteristics, with the plate formula: Po, x, 3′, 1a, 6″, 4c, 4s, 5″′, 1″″. The newly recorded dinoflagellate was encountered during autumn in the phytoplankton community of Jihongtan Reservoir and some small ponds near the reservoir in Shandong Province, China. The species had been reported only in brackish ecosystems; however, our material fit withD. caspicaoccurred in freshwater habitat. The phylogenetic relationship ofD. caspicawas elucidated through small and large subunit ribosomal DNA sequences. In small and large subunit ribosomal DNA phylogenies, all Protoperidiniaceae species, including diplopsalids andProtoperidiniumBergh, could cluster into a monophyletic group. The molecular phylogenies indicated that the genusDiplopsaliswould provide a link to the common ancestor of thePeridiniumEhrenberg and theProtoperidinium.