bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases
Authors: Symonds Joseph D. , Joss Shelagh , Metcalfe Kay A. , Somarathi Suresh , Cruden Jamie , Devlin Anita M. , Donaldson Alan , DiDonato Nataliya , Fitzpatrick David , Kaiser Frank J. , Lampe Anne K. , Lees Melissa M. , McLellan Ailsa , Montgomery Tara , Mundada Vivek , Nairn Lesley , Sarkar Ajoy , Schallner Jens , Pozojevic Jelena , Parenti Ilaria , Tan Jeen , Turnpenny Peter , Whitehouse William P. ,   The DDD Study, Zuberi Sameer M. 
Published: February 2017

SummaryObjectiveThe phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X‐linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in‐frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug‐resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation.MethodFemale cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained.ResultsTen cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases.SignificanceTruncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males.
Genomic patterns of diversity and divergence of two introduced salmonid species in Patagonia, South America
Authors: Narum Shawn R. , Gallardo Pablo , Correa Cristian , Matala Amanda , Hasselman Daniel , Sutherland Ben J. G. , Bernatchez Louis 
Published: February 2017

AbstractInvasive species have become widespread in aquatic environments throughout the world, yet there are few studies that have examined genomic variation of multiple introduced species in newly colonized environments. In this study, we contrast genomic variation in two salmonid species (anadromous Chinook Salmon, Oncorhynchus tshawytscha, 11,579 SNPs and resident Brook Charr Salvelinus fontinalis, 13,522 SNPs) with differing invasion success after introduction to new environments in South America relative to populations from their native range in North America. Estimates of genetic diversity were not significantly different between introduced and source populations for either species, indicative of propagule pressure that has been shown to maintain diversity in founding populations relative to their native range. Introduced populations also demonstrated higher connectivity and gene flow than those in their native range. Evidence for candidate loci under divergent selection was observed, but was limited to specific introduced populations and was not widely evident. Patterns of genomic variation were consistent with general dispersal potential of each species and therefore also the notion that life history variation may contribute to both invasion success and subsequent genetic structure of these two salmonids in Patagonia.
Landscape‐scale life‐history gradients in New Zealand freshwater fish
Authors: Jones Peter E. , Augspurger Jason , Closs Gerard P. 
Published: February 2017

Summary

Landscape‐scale clines in environmental parameters can lead to life‐history gradients. Study of interspecific life‐history differences can provide evidence of evolutionary adaptations in response to environmental cues, whereas examination of intraspecific life‐history variation can identify the ecological mechanisms driving trait evolution.

We examined egg size and fecundity variation in three species of closely related freshwater fish (Galaxiidae) which occur across a habitat gradient in South Island, New Zealand. Inter‐population trait variation was assessed in the species with the widest distribution to investigate the ecological mechanisms driving egg size evolution.

Substantial interspecific egg size and fecundity differences were observed. Galaxias paucispondylus, which generally occurs in high altitude headwater streams, showed an average egg size an order of magnitude larger, and fecundity an order of magnitude lower than G. brevipinnis, a species which rears in pelagic environments. Galaxias vulgaris, which rears fluvial environments but is generally distributed in lower catchment reaches than G. paucispondylus, showed intermediate fecundity and egg size traits. This interspecific trait variation is likely to be driven by differences in the larval rearing habitat, i.e. rearing in cold high altitude locations requires large well‐developed larvae (and therefore large eggs) but these come at the cost of maternal fecundity, whereas in rearing in warmer lower catchment watercourses, and pelagic habitats, does not require such large well‐developed larvae. Hence, fitness is maximised by progressively increasing fecundity by reducing egg size across this habitat cline.

Life history‐habitat trends were repeated when intraspecific patterns in the widely distributed G. vulgaris were assessed, with population egg size increasing, and fecundity decreasing, in relation to a suite of interrelated environmental variables up an approximate altitudinal cline.

The results highlight how inter‐ and intraspecific variation in egg size–fecundity trade‐offs in closely related species can interact to drive the evolution of landscape‐scale life‐history gradients. Egg size differences are likely to be driven by differences in the quality of the larval rearing habitat, i.e. rearing in a challenging habitat requires a larger egg whereas in relatively benign larval rearing habitat, fecundity can be maximised by reducing egg size. The interspecific variation observed provides evidence of trait adaptation in response to an environmental cue, while the intraspecific inter‐population differences indicate the potential ecological mechanisms driving trait evolution.
Transport biofuels in global energy–economy modelling – a review of comprehensive energy systems assessment approaches
Authors: Ahlgren Erik O. , Börjesson Hagberg Martin , Grahn Maria 
Published: February 2017

AbstractThe high oil dependence and the growth of energy use in the transport sector have increased the interest in alternative nonfossil fuels as a measure to mitigate climate change and improve energy security. More ambitious energy and environmental targets and larger use of nonfossil energy in the transport sector increase energy–transport interactions and system effects over sector boundaries. While the stationary energy sector (e.g., electricity and heat generation) and the transport sector earlier to large degree could be considered as separate systems with limited interaction, integrated analysis approaches and assessments of energy–transport interactions now grow in importance. In recent years, the scientific literature has presented an increasing number of global energy–economy future studies based on systems modelling treating the transport sector as an integral part of the overall energy system and/or economy. Many of these studies provide important insights regarding transport biofuels. To clarify similarities and differences in approaches and results, the present work reviews studies on transport biofuels in global energy–economy modelling and investigates what future role comprehensive global energy–economy modelling studies portray for transport biofuels in terms of their potential and competitiveness. The results vary widely between the studies, but the resulting transport biofuel market shares are mainly below 40% during the entire time periods analysed. Some of the reviewed studies show higher transport biofuel market shares in the medium (15–30 years) than in the long term (above 30 years), and, in the long‐term models, at the end of the modelling horizon, transport biofuels are often substituted by electric and hydrogen cars.
Mining the global diversity for bioenergy traits of barley straw: genomewide association study under varying plant water status
Authors: Naz Ali A. , Reinert Stephan , Bostanci Cihan , Seperi Bahare , Leon Jens , Böttger Christian , Südekum Karl‐Heinz , Frei Michael 
Published: February 2017

AbstractCereal straws constitute a considerable source of biomass that can be used for bioenergy applications. Its composition is crucial for the energy value in biological or thermochemical conversion processes. Therefore, this study aimed at (i) exploring the global diversity in the composition of barley (Hordeum vulgare L.) straw; (ii) testing the effect of drought on straw composition; (iii) correlating compositional traits with energy value; and (iv) identifying loci associated with straw composition through genomewide association study (GWAS). A population of 179 barley accessions was grown in control and drought conditions, and straw was analyzed for thioglycolic acid lignin (TGAL), total phenolics (TP), carbon, crude protein (CP), C/N ratio, and ash. Substantial variability was observed in all traits. Moreover, drought treatment affected all traits leading to significant decreases in carbon, CP, ash, TGAL and TP concentrations, and a significant increase in C/N ratio. In vitro incubations in rumen fluid were used to estimate the energy value in biological energy conversion, while calorimetry was used to estimate the energy yield in thermochemical energy conversion. Thioglycolic acid lignin was singled out as the most influential trait determining energy value, as it was negatively correlated with the digestibility of organic matter and metabolizable energy in in vitro incubations, but positively correlated with gross energy measured by calorimetry. The GWAS yielded four loci significantly associated with TGAL irrespective of plant water status, which explained between 22.5% and 38.7% of the phenotypic variation. In addition, three loci significantly affected the response of TGAL to plant water status, and explained between 11.2% and 16.6% of the phenotypic variation. These loci contained plausible candidate genes that could be associated with lignin biosynthesis based on their annotations. In conclusion, this study illustrated great potential for the molecular breeding of barley varieties with enhanced straw quality for bioenergy applications.
GNAS mutations are present in colorectal traditional serrated adenomas, serrated tubulovillous adenomas and serrated adenocarcinomas with adverse prognostic features
Authors: Liu Cheng , McKeone Diane M , Walker Neal I , Bettington Mark L , Leggett Barbara A , Whitehall Vicki L J 
Published: February 2017

AimsActivating mutations in GNAS are important in the development of a range of neoplasms, including a small proportion of conventional adenomas and colorectal carcinomas (CRCs). However, their contribution to serrated pathway neoplasia is unclear, as mutations have only been examined in small series of sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), and not in serrated tubulovillous adenomas (sTVAs). The aim of this study was to investigate the frequency and significance of GNAS mutations in colorectal adenomas and CRCs.Methods and resultsUsing a large, well‐characterized series, we identified GNAS mutations in 9.2% (18 of 196) of TSAs, 7.1% (four of 56) of sTVAs and 2.0% (nine of 459) of CRCs. Mutations were absent in SSAs (none of 43), tubular adenomas (none of 50) and conventional tubulovillous adenomas (none of 50). A BRAF or KRAS mutation was seen in 77.4% of GNAS mutant lesions, suggesting a synergistic effect with the mitogen‐activated protein kinase pathway. In CRCs, GNAS mutations were associated with mucinous differentiation and serrated morphological features.ConclusionsGNAS mutations contribute significantly to the development of a subset of serrated adenomas and CRCs.
Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population‐based study
Authors: Hynes Seán O , Coleman Helen G , Kelly Paul J , Irwin Steven , O'Neill Roisin F , Gray Ronan T , McGready Claire , Dunne Philip D , McQuaid Stephen , James Jacqueline A , Salto‐Tellez Manuel , Loughrey Maurice B 
Published: February 2017

AimsBoth morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of the tumour microenvironment has not been adopted into routine practice. The study aim was to identify those tumour microenvironmental features that are most likely to provide prognostic information and be feasible to use in routine pathology reporting practice.Methods and resultsOn the basis of existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative haematoxylin and eosin (H&E)‐stained whole tumour sections from a population‐based cohort of 445 stage II/III colon cancer cases. Moderate/severe peritumoral diffuse lymphoid inflammation and Crohn's disease‐like reaction were associated with significantly reduced risks of CRC‐specific death [adjusted hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.31–0.76, and HR 0.60, 95% CI 0.42–0.84, respectively]. The presence of >50% tumour stromal percentage, as assessed by global evaluation of tumour area, was associated with a significantly increased risk of CRC‐specific death (HR 1.60 95% CI 1.06–2.41). A composite ‘fibroinflammatory score’ (0–3), combining dichotomized scores of these three features, showed a highly significant association with survival outcomes. Those with a score of ≥2 had an almost 2.5‐fold increased risk of CRC‐specific death (HR 2.44, 95% CI 1.56–3.81) as compared with those scoring zero. These associations were stronger in microsatellite instability (MSI)‐high tumours, potentially identifying a subset of MSI‐high colon cancers that lack characteristic morphological features and have an associated worse prognosis.ConclusionsIn summary, reporting on H&E staining of selected microscopic features of the tumour microenvironment, independently or in combination, offers valuable prognostic information in stage II/III colon cancer, and may allow morphological correlation with developing molecular classifications of prognostic and predictive relevance.
Behaviours of students who have repeated urinary tract infections
Authors: Yıldırım Julide Gulizar 
Published: February 2017

ABSTRACTTo determine the behaviours of students and the variables that have an effect on repeated urinary tract infections (UTIs). A cross‐sectional study was implemented on elementary and high school students in Izmir, Turkey. The sample consisted of 318 volunteers from the 6–17 years of age students. Written consent was obtained from parents and institutions. The data were collected through sociodemographic characteristics and a behavioural assessment semi‐structured design questionnaire. The data for closed‐ended questions were evaluated for frequencies, variance, Chi‐square and logistic regression. Content analysis was used for examining the open‐ended questions. Students' mean age was 10·28 ± 2·27 (6–15 years of age), 68·2% were females and 70·4% were in elementary school. Of the students, 26·1% avoided using school toilets, 70·4% held urine too long and 30·2% cleaned the perineum from back‐to‐front. In the prediction of the factors that affect students' behaviours with ages, it was determined that ‘washed the genital area after defecation/urination’, ‘method of cleaning the perineum’, ‘urination status at school’, ‘enuresis’, ‘frequency of changing underwear’ and ‘washing hands before going to the toilet’ increased linearly with age (p < 0·05). Most of the students may have negative perceptions about toilet habits. Students' behaviours are important for improving social well‐being. Health professionals and teachers serve a key role in the psychosocial development of students. They can develop individualized health care plans and help parents and students to understand strategies that can prevent UTIs.
Successful reintroduction of the Critically Endangered Antiguan racer Alsophis antiguae to offshore islands in Antigua, West Indies
Authors: Daltry J. C. , Lindsay K. , Lawrence S. N. , Morton M. N. , Otto A. , Thibou A. 
Published: February 2017

The Critically Endangered Antiguan racer Alsophis antiguae is endemic to Antigua and Barbuda (441 km2 area) but declined following the arrival of invasive mammals. By 1995, only an estimated 51 Antiguan racers survived on an offshore islet (Great Bird Island: 8·4 ha), many of which had injuries consistent with rat bites. To prevent extinction, a consortium of national and international organizations eradicated the Black rats Rattus rattus from Great Bird Island in 1995 and the snake population promptly doubled in size. The agencies then embarked on a programme to eradicate invasive rats and, where present, Small Asian mongooses Herpestes javanicus from a further 14 islands around Antigua. The first reintroduction was carried out in November 1999, with ten wild racers translocated from Great Bird Island to Rabbit Island. Further reintroductions followed to Green Island (from October 2002) and York Island (from January 2008), bringing the total area of occupancy for racers to 63 ha. The translocated racers appeared to thrive in their new habitats and reproduced almost immediately. The reintroduction programme was underpinned by field research, fundraising and an innovative education campaign to address prevailing negative attitudes towards snakes. While the Antiguan racer metapopulation has increased to > 1100 individuals in the wild, lasting success depends on Great Bird, Rabbit, Green and York Islands being fully protected from invasive mammals and harmful developments. To spread the risk, additional reintroduction sites must be identified.
Metabolic syndrome and masked hypertension among African Americans: The Jackson Heart Study
Authors: Colantonio Lisandro D. , Anstey D. Edmund , Carson April P. , Ogedegbe Gbenga , Abdalla Marwah , Sims Mario , Shimbo Daichi , Muntner Paul 
Published: February 2017

The metabolic syndrome is associated with higher ambulatory blood pressure. The authors studied the association of metabolic syndrome and masked hypertension (MHT) among African Americans with clinic‐measured systolic/diastolic blood pressure (SBP/DBP) <140/90 mm Hg in the Jackson Heart Study. MHT was defined as daytime, nighttime, or 24‐hour hypertension on ambulatory blood pressure monitoring. Among 359 participants not taking antihypertensive medication, the metabolic syndrome was associated with MHT (prevalence ratio, 1.38; 95% confidence interval, 1.10–1.74]). When metabolic syndrome components (clinic SBP/DBP 130–139/85–89 mm Hg, abdominal obesity, impaired glucose, low high‐density lipoprotein cholesterol, high triglycerides) were analyzed separately, only clinic SBP/DBP 130–139/85–89 mm Hg was associated with MHT (prevalence ratio, 1.90; 95% confidence interval, 1.56–2.32]). The metabolic syndrome was not associated with MHT among participants not taking antihypertensive medication with SBP/DBP 130–139/85–89 and <130/85 mm Hg, separately, or among participants taking antihypertensive medication (n=393). Ambulatory blood pressure monitoring screening for MHT among African Americans should be considered based on clinic BP, not metabolic syndrome.
Anthropogenic Disturbance by Domestic Extraction of Construction Minerals in Japan
Authors: Yoshida Keisuke , Okuoka Keijiro , Tanikawa Hiroki 
Published: February 2017

SummaryAccompanying the huge amount of material accumulation in the socioeconomic sphere is anthropogenic disturbance, namely, artificial landform transformation attributed to mining, soil excavation, construction, and physical development. Anthropogenic disturbance impacts the natural environment and is strongly related to hidden material flow (HMF). However, only few studies have considered anthropogenic disturbance as the starting point of material transfer in the ecosphere. The objectives of the present study are: (1) to spatially quantify the impact of humans on the natural environment by estimating the anthropogenic disturbance attributed to mining and (2) to contribute to the knowledge of HMF by examining the phenomenon using the relatively unexplored methodology of assessing the relationship between anthropogenic disturbance and material transfer by means of a geographical information system and digital elevation model. Statistical data obtained by the Ministry of Economy, Trade and Industry of Japan were used to account for domestic extraction. By comparing the respective results of bottom‐up and top‐down accountings, we estimated the potential HMF. The database developed in this study not only reflects the amount of anthropogenic disturbance and potential HMF, but also reveals their destructive effect on the environment and the spatial distribution of anthropogenic disturbance.
Calcipotriol inhibits α‐synuclein aggregation in SH‐SY5Y neuroblastoma cells by a Calbindin‐D28k‐dependent mechanism
Authors: Rcom‐H'cheo‐Gauthier Alexandre N. , Meedeniya Adrian C. B. , Pountney Dean L. 
Published: February 2017

AbstractMany neurodegenerative diseases are characterized by the formation of microscopically visible intracellular protein aggregates. α‐Synuclein is the key aggregating protein in Parkinson's disease which is characterized by neuronal cytoplasmic Lewy body inclusions. Previous studies have shown relative sparing of neurons in Parkinson's disease and dementia with Lewy bodies that are positive for the vitamin D‐dependent calcium‐buffering protein, calbindin‐D28k, and that α‐synuclein aggregates are excluded from calbindin‐D28k‐positive neurons. Recent cell culture studies have shown that α‐synuclein aggregation can be induced by raised intracellular‐free Ca(II) and demonstrated that raised intracellular calcium and oxidative stress can act synergistically to promote α‐synuclein aggregation. We hypothesized that calcipotriol, a potent vitamin D analogue used pharmaceutically, may be able to suppress calcium‐dependent α‐synuclein aggregation by inducing calbindin‐D28k expression. Immunofluorescence and western blot analysis showed that calcipotriol potently induced calbindin‐D28k in a dose‐dependent manner in SH‐SY5Y human neuroblastoma cells. Calcipotriol significantly decreased the frequency of α‐synuclein aggregate positive cells subjected to treatments that cause raised intracellular‐free Ca(II) (potassium depolarization, KCl/H2O2 combined treatment, and rotenone) in a dose‐dependent manner and increased viability. Suppression of calbindin‐D28k expression in calcipotriol‐treated cells using calbindin‐D28k‐specific siRNA showed significantly higher α‐synuclein aggregation levels, indicating that calcipotriol‐mediated blocking of calcium‐dependent α‐synuclein aggregation was dependent on the induction of calbindin‐D28k expression. These data indicate that targeting raised intraneuronal‐free Ca(II) in the brain by promoting the expression of calbindin‐D28k at the transcriptional level using calcipotriol could prevent α‐synuclein aggregate formation and ameliorate Parkinson's disease pathogenesis.
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