bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced transient receptor potential channel‐mediated Ca2+ influx in the cells with phospholipase C‐δ1 overexpression: its possible role in coronary artery spasm
Authors: Murakami Kazuo , Osanai Tomohiro , Tanaka Makoto , Nishizaki Kimitaka , Kinjo Takahiko , Tanno Tomohiro , Ishida Yuji , Suzuki Akiko , Endo Tomohide , Tomita Hirofumi , Okumura Ken 
Published: January 2017

AbstractWe reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)‐δ1 activity. We investigated the effect of enhanced PLC‐δ1 on Ca2+ influx and its underlying mechanisms. We used human embryonic kidney (HEK)‐293 and coronary arteries smooth muscle cells (CASMC). Intracellular free Ca2+ concentration ([Ca2+]i; nm) was measured by fura‐2, and Ca2+ influx was evaluated by the increase in [Ca2+]i after addition of extracellular Ca2+. Acetylcholine (ACh) was used to induce Ca2+ influx. ACh‐induced peak Ca2+ influx was 19 ± 3 in control HEK‐293 cells and 71 ± 8 in the cells with PLC‐δ1 overexpression (P < 0.05 between two groups). Nifedipine partially suppressed this Ca2+ influx, whereas either 2‐APB or knockdown of classical transient receptor potential channel 6 (TRPC6) blocked this Ca2+ influx. In the human CASMC, ACh‐induced peak Ca2+ influx was 29 ± 6 in the control and was increased to 45 ± 16 by PLC‐δ1 overexpression (P < 0.05). Like HEK‐293 cells, pretreatment with nifedipine partially suppressed Ca2+ influx, whereas either 2‐APB or knockdown of TRPC6 blocked it. ACh‐induced Ca2+ influx was enhanced by PLC‐δ1 overexpression, and was blocked partially by nifedipine and completely by 2‐APB. TRPC‐mediated Ca2+ influx may be related to the enhanced Ca2+ influx in PLC‐δ1 overexpression.
Structure of the Arabidopsis thaliana NADPH‐cytochrome P450 reductase 2 (ATR2) provides insight into its function
Authors: Niu Guoqi , Zhao Shun , Wang Lei , Dong Wei , Liu Lin , He Yikun 
Published: January 2017

Members of the cytochrome P450 family catalyze a variety of mono‐oxygenase reactions, and for the eukaryotic membrane‐bound members, NADPH is typically used as the reducing agent. The flavoprotein NADPH‐cytochrome P450 reductase (CPR) enables electron transfer from NADPH to cytochrome P450 via its flavin cofactors. ATR2 is one of the two authentic CPR genes in the genome of the model plant Arabidopsis thaliana, and its product has been physiologically and kinetically characterized. Here, we report the 2.3 Å structure of Arabidopsis thaliana NADPH‐cytochrome P450 reductase 2 (ATR2) and find that the position of the two flavin cofactors differs from that of other known CPR structures. Mutation of residues related to possible interflavin electron transfer retains the reductase activity of ATR2, which suggests a direct electron transfer pathway between the flavins. In contrast, mutation of a single residue (R708) mediating interdomain interaction abolishes this activity. Because this residue is only conserved in plant CPRs, we speculate a plant‐specific working mechanism as observed in ATR2.DatabaseAtomic coordinates and structure factors of ATR2 are available in the Protein Data Bank under the accession code 5GXU.
Efficient synthesis of α‐galactosyl oligosaccharides using a mutant Bacteroides thetaiotaomicron retaining α‐galactosidase (BtGH97b)
Authors: Okuyama Masayuki , Matsunaga Kana , Watanabe Ken‐ichi , Yamashita Keitaro , Tagami Takayoshi , Kikuchi Asako , Ma Min , Klahan Patcharapa , Mori Haruhide , Yao Min , Kimura Atsuo 
Published: January 2017

The preparation of a glycosynthase, a catalytic nucleophile mutant of a glycosidase, is a well‐established strategy for the effective synthesis of glycosidic linkages. However, glycosynthases derived from α‐glycosidases can give poor yields of desired products because they require generally unstable β‐glycosyl fluoride donors. Here, we investigate a transglycosylation catalyzed by a catalytic nucleophile mutant derived from a glycoside hydrolase family (GH) 97 α‐galactosidase, using more stable β‐galactosyl azide and α‐galactosyl fluoride donors. The mutant enzyme catalyzes the glycosynthase reaction using β‐galactosyl azide and α‐galactosyl transfer from α‐galactosyl fluoride with assistance of external anions. Formate was more effective at restoring transfer activity than azide. Kinetic analysis suggests that poor transglycosylation in the presence of the azide is because of low activity of the ternary complex between enzyme, β‐galactosyl azide and acceptor. A three‐dimensional structure of the mutant enzyme in complex with the transglycosylation product, β‐lactosyl α‐d‐galactoside, was solved to elucidate the ligand‐binding aspects of the α‐galactosidase. Subtle differences at the β→α loops 1, 2 and 3 of the catalytic TIM barrel of the α‐galactosidase from those of a homologous GH97 α‐glucoside hydrolase seem to be involved in substrate recognitions. In particular, the Trp residues in β→α loop 1 have separate roles. Trp312 of the α‐galactosidase appears to exclude the equatorial hydroxy group at C4 of glucosides, whereas the corresponding Trp residue in the α‐glucoside hydrolase makes a hydrogen bond with this hydroxy group. The mechanism of α‐galactoside recognition is conserved among GH27, 31, 36 and 97 α‐galactosidases.DatabaseThe atomic coordinates (code: 5E1Q) have been deposited in the Protein Data Bank.
Assessing the influence of gilthead sea bream escapees in landings of Mediterranean fisheries through a scale‐based methodology
Authors: Izquierdo‐Gómez D. , Arechavala‐Lopez P. , Bayle‐Sempere J. T. , Sánchez‐Jerez P. 
Published: January 2017

AbstractGilthead sea bream (Sparus aurata L.) aquaculture has rapidly spread around the Mediterranean Sea. Fish escapes from sea cages are one of the major problems for the industry and also represent a threat to the marine environment. Fishery catches are also influenced by escape events, being mirrored in increased landings of cultured species. However, within the Mediterranean, studies shedding light on the incidence of escaped individuals in fisheries landings are scarce. Firstly, the present study describes a simple scale‐examination methodology to distinguish escaped from wild S. aurata landed by coastal fisheries. Secondarily, the incidence of escapees is assessed within landings of the species in the western Mediterranean. The scale readings revealed a monthly incidence of escapees between 11.2 and 20.8%, representing 6.8% of the total income derived from these landings. Moreover, morphological differences between wild fish captured near and far from fish farms point towards escape events as a source of potential genetic admixture between cultured and wild genotypes. Socio‐economic and ecological implications of escapees are discussed, and a set of management guidelines proposed, to prevent and/or mitigate the negative influences of escaped fish on the ecosystem and traditional users of the coast such as fisheries.
Aquatic food‐web structure along a salinized dryland river
Authors: East Jessica L. , Wilcut Christopher , Pease Allison A. 
Published: January 2017

Summary

Very little is known about the ecosystem impacts of river salinization despite expectations for global increases in salinization with growing water demand and climate change. In some rivers in the southwestern United States, salinization has occurred as a result of natural saline inputs exacerbated by flow alteration and other anthropogenic impacts. Salinization in the Pecos River has been linked to declines in fish diversity, but impacts on the structure of aquatic food webs have not been investigated.

We assessed variation in local food webs along the longitudinal gradient of the main stem Pecos River by estimating carbon sources, trophic positions and assemblage‐wide trophic structure for aquatic consumers at 12 sites using stable isotope analysis (δ13C and δ15N). Temporal variation across seasons was also examined for common fish species at a subset of sites.

Consumer richness, food‐chain length and assemblage‐wide niche breadth were inversely related to specific conductivity. Mixing models revealed differences in sources of dietary carbon supporting fish production along the longitudinal fluvial gradient, with a shift towards reliance on algal production in the salinized reaches of the river. Trophic niche breadth was greatest for assemblages in less degraded sites with higher fish species richness. Local food webs in salinized sites were dominated by euryhaline species and had shorter food chains and narrower assemblage‐wide niche breadths. Across seasons, δ13C and δ15N signatures remained fairly constant for five common fish species.

Our results suggest that salinization in portions of the Pecos River constrains the diversity of consumers and trophic resources in local food webs. Characterising changes in food‐web structure in relation to salinization and other environmental changes is important for habitat assessment, stream restoration and other conservation strategies.
Temporal variation in phytoplankton beta diversity patterns and metacommunity structures across subtropical reservoirs
Authors: Wojciechowski Juliana , Heino Jani , Bini Luis M. , Padial André A. 
Published: January 2017

Summary

Analysing the beta diversity components and spatial patterns of species distribution may provide key insights into how local communities respond to human‐induced environmental changes. Indeed, analysing temporal variation in spatial patterns of species distribution may reveal trends of biotic homogenisation and its likely causes.

We used an eight‐year phytoplankton data set generated from to 17 reservoirs in Brazil to analyse the temporal variability in beta diversity and its turnover and nestedness components. This data set was also used to determine metacommunity structures across these subtropical reservoirs. We tested whether there was any long‐term temporal trend in beta diversity that might be indicative of biotic homogenisation or differentiation. We also tested how temporal variation was related to climatic conditions, environmental heterogeneity, productivity and cyanobacterial dominance. Lastly, we verified whether the phytoplankton metacommunity showed non‐random structure.

We did not find supporting evidence for biotic homogenisation among the reservoirs. Rather, we did find that nestedness decreased during the study. Environmental heterogeneity was the main variable positively related to phytoplankton beta diversity, while high ammonium concentration and cyanobacterial abundance were negatively correlated with spatial variation among the reservoirs. Despite the noticeable temporal variation in metacommunity structures, the phytoplankton species responded similar to latent environmental gradients. Clementsian patterns found mainly in fall and winter were consistent with differences in species composition between sites, reinforcing the role of environmental filtering in driving changes in these metacommunities.

Our results suggest that eutrophication control is essential to prevent biotic homogenisation, at least in our study system. We also highlight that metacommunity patterns detected in snapshot surveys should not be extrapolated temporally.
Incidence, clinicopathological features and fusion transcript landscape of translocation renal cell carcinomas
Authors: Classe Marion , Malouf Gabriel G , Su Xiaoping , Yao Hui , Thompson Erika J , Doss Denaha J , Grégoire Valérie , Lenobin Julien , Fantoni Jean‐Christophe , Sudour‐Bonnange Hélène , Khayat David , Aubert Sébastien , Tannir Nizar M , Leroy Xavier 
Published: January 2017

AimsTranslocation renal cell carcinoma (tRCC) is a rare subtype of kidney tumour characterized by translocations involving the transcription factor TFE3 or TFEB. tRCC was introduced into the World Health Organization classification in 2004, but much is still unknown about the natural history, clinicopathological features and outcomes of the disease. The aim of this study was to describe the landscape of fusion transcript in a large single‐institution series of fluorescence in‐situ hybridization (FISH)‐confirmed tRCCs and then to compare it to morphological and clinical data.Methods and resultsPaired‐end RNA sequencing was performed within a prospective database of the Department of Pathology, Centre Hospitalier Régional Universitaire (Lille, France). The diagnosis of tRCC was confirmed by FISH. Among a total of 1130 identified renal cell carcinomas, 21 cases (1.9%) showed rearrangement of the TFE3 (n = 20) or (TFEB) (n = 1) gene. Median patient age was 31 years (range = 15–47), and the female‐to‐male ratio was 6:1. Five different TFE3 fusion transcripts were identified; the most frequent TFE3 partners were PRCC (n = 4) and SFPQ (n = 4). The other partners involved were ASPCR1 (n = 1) and MED15 (n = 1) genes as well as a novel TFE3 partner, GRIPAP1.ConclusionsWe identified a new fusion partner, GRIPAP1. The prognostic role of transcript type could not be determined because our number of cases was too small. Four patients (19%) died of the disease, all of which presented with a lymph node involvement at diagnosis. We confirm that tRCC can be an aggressive tumour, especially those of advanced clinical stage.
Lung cancer and socio‐economic status: inextricably linked to place of residence
Authors: Denton Eve J. , Hart David , Russell Prue A. , Wright Gavin , Conron Matthew 
Published: January 2017

BackgroundThe association between socio‐economic status (SES) and lung cancer is internationally established, but in Australia this relationship remains ill defined.AimsTo examine the association between SES, place of residence and lung cancer outcomes in a large Australian cohort.MethodsA total of 2369 consecutive lung cancer patients managed by St Vincent's Hospital lung multidisciplinary meeting between 2001 and 2014 were included. Postcode data stratified participants by Socio‐economic indexes for areas, a validated measure of SES, and by geographical location, an important socio‐economic factor in Australia.ResultsThere was no difference between socio‐economic groups in age (68 years), sex (63% males) or presentation (75% symptomatic). Low socio‐economic patients had increased smoking rates and a trend towards less adenocarcinoma. More low SES patients were from rural locations, had a greater frequency of earlier stage disease and curative treatment with higher overall survival even after multivariate analysis. When stratified for SES, overall 5‐year survival was significantly better in the low SES group (33 vs 24%, n = 2275, P = 0.02), although stage‐stratified survival was similar in all socio‐economic groups.ConclusionsLow SES patients were more frequently from rural locations and unexpectedly had earlier stage disease and higher overall survival. The excellent outcomes in rural and lower SES patients are reassuring, but suggest that there is a population of these patients with advanced lung cancer who are not referred for multidisciplinary care. Further studies are required to define this group better and determine the barriers to referral to improve overall lung cancer outcomes.
Urinary fluoride excretion after application of fluoride varnish and use of fluoride toothpaste in young children
Authors: Lockner Frida , Twetman Svante , Stecksén‐Blicks Christina 
Published: January 2017

BackgroundThe efficacy and safety of combined use of topical fluoride products are essential issues that must be monitored.AimTo assess urinary excretion of fluoride after application of two different dental varnishes containing 2.26% fluoride in 3‐ to 4‐year‐old children and to compare the levels with and without parallel use of fluoride toothpaste.DesignFifteen healthy children were enrolled to a randomized crossover trial that was performed in two parts: Part I with twice‐daily tooth brushing with fluoride toothpaste and Part II with twice‐daily brushing with a non‐fluoride toothpaste. After a 1‐week run‐in period, 0.1 mL of the two fluoride varnishes (Duraphat and Profluorid Varnish) was topically applied in a randomized order. Baseline and experimental urine was collected during 6‐h periods. The fluoride content was determined with an ion‐sensitive electrode.ResultsThere was a statistically significant increase in the 6‐h fluoride excretion after application of both experimental varnishes, with and without parallel use of fluoride toothpaste (P < 0.01). When fluoridated toothpaste was used, the mean fluoride excretion was 0.20 mg/6 h after application of Duraphat and 0.29 mg/6 h after application of Profluorid Varnish (P = 0.18).ConclusionsTopical applications of 0.1 mL of fluoride varnish significantly increased the 6‐h fluoride excretion. As some individuals displayed excretion levels exceeding the optimal fluoride exposure, a restricted use of fluoride toothpaste in connection with the varnish applications would decrease fluoride exposure.
Self‐administered health literacy instruments for people with diabetes: systematic review of measurement properties
Authors: Lee Eun‐Hyun , Kim Chun‐Ja , Lee Jiyeon , Moon Seung Hei 
Published: January 2017

AbstractAimsThe aims of this study were to identify all available self‐administered instruments measuring health literacy in people with diabetes and to determine the current instrument that is the most appropriate for applying to this population in both practice and research.DesignA systematic review of measurement properties.Data sourcesMEDLINE, EMBASE and CINAHL electronic databases from their inception up to 28 March 2016.Review methodThe methodological quality of each included study was assessed using the COnsensus‐based Standards for the selection of health Measurement INstruments checklist. The reported results for measurement properties in the studies were assessed according to Terwee's quality criteria.ResultsThirteen self‐administered instruments measuring health literacy in people with diabetes were identified, of which six (44%) were diabetes‐specific instruments. The instruments that covered the broadest contents of health literacy were the Health Literacy Scale and Health Literacy Questionnaire. The (test–retest) reliability, measurement error and responsiveness were not evaluated for any instrument, while internal consistency and hypothesis testing validity were the most frequently assessed measurement properties.ConclusionsWith the current evidence, the Health Literacy Scale may be the most appropriate instrument for patients with diabetes in practice and research. However, the structural validity of this scale needs to be further established, particularly in other language versions. It is also recommended to use the Diabetes Numeracy Test‐15 along with the Health Literacy Scale to complement the lack of numeracy measures in the Health Literacy Scale.
Rare human leukocyte antigen genotype in two siblings with type 1 diabetes in a Japanese family clustered with type 1 diabetes
Authors: Ina Yujiro , Kawabata Yumiko , Sakamoto Ryuichi , Sekiguchi Naotaka , Ikegami Hiroshi 
Published: January 2017

AbstractMultiplex families with type 1 diabetes are important for identification of rare variants that cannot be identified in case–control association studies. The very low incidence of type 1 diabetes in the Japanese population, however, makes identification of such families difficult. We identified a Japanese family in which three members developed type 1 diabetes, and studied the genotype of the human leukocyte antigen. All three members with type 1 diabetes had the DRB1*08:02‐DQB1*03:02 haplotype, which is specific to the Asian population and strongly susceptible for type 1 diabetes. In particular, a proband and his sister had the same genotype, DRB1*08:02‐DQB1*03:02/DRB1*08:02‐DQB1*03:02, which is extremely rare even in the Japanese population. Both parents also had DRB1*08:02‐DQB1*03:02, but in combination with different human leukocyte antigen haplotypes. Weakly susceptible DRB1*13:02‐DQB1*06:04 was present in the affected mother, and resistant DRB1*15:01‐DQB1*06:02 in the unaffected father. These data suggest DRB1*08:02‐DQB1*03:02 to be a contributing factor for familial clustering of type 1 diabetes in this family.
Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy
Authors: Sun Li‐Jing , Sun Yan‐Ni , Shan Jian‐Ping , Jiang Geng‐Ru 
Published: January 2017

AbstractAims/IntroductionWe aimed to evaluate the potential benefits and adverse effects of adding a mineralocorticoid receptor antagonist (MRA) to angiotensin‐converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), as standard treatment in patients with diabetic nephropathy.Materials and MethodsWe scanned the Embase, PubMed and Cochrane Central Register of Controlled Trials databases for human clinical trials published in English until June 2016, evaluating renal outcomes in patients with diabetic nephropathy.ResultsA total of 18 randomized controlled trials involving 1,786 patients were included. Compared with ACEI/ARB alone, co‐administration of MRA and ACEI/ARB significantly reduced urinary albumin excretion and the urinary albumin–creatinine ratio (mean difference −69.38, 95% confidence intervals −103.53 to −35.22, P < 0.0001; mean difference −215.74, 95% confidence intervals −409.22 to −22.26, P = 0.03, respectively). A decrease of blood pressure was also found in the co‐administration of MRA and ACEI/ARB groups. However, we did not observe any improvement in the glomerular filtration rate. There was a significant increase in the risk of hyperkalemia on the addition of MRA to ACEI/ARB treatment (relative risk 3.74, 95% confidence intervals 2.30–6.09, P < 0.00001).ConclusionsThese findings suggest that co‐administration of MRA and ACEI/ARB has beneficial effects on renal outcomes with increasing the incidence of hyperkalemia.
iDermatoPath – a novel software tool for mitosis detection in H&E‐stained tissue sections of malignant melanoma
Authors: Andres C. , Andres‐Belloni B. , Hein R. , Biedermann T. , Schäpe A. , Brieu N. , Schönmeyer R. , Yigitsoy M. , Ring J. , Schmidt G. , Harder N. 
Published: January 2017

AbstractBackgroundMalignant Melanoma (MM) is characterized by a growing incidence and a high malignant potential. Besides well‐defined prognostic factors such as tumour thickness and ulceration, the Mitotic Rate (MR) was included in the AJCC recommendations for diagnosis and treatment of MM. In daily routine, the identification of a single mitosis can be difficult on haematoxylin and eosin slides alone. Several studies showed a big inter‐ and intra‐individual variability in detecting the MR in MM even by very experienced investigators, thus raising the question for a computer‐assisted method.ObjectiveThe objective was to develop a software system for mitosis detection in MM on H&E slides based on machine learning for diagnostic support.MethodsWe developed a computer‐aided staging support system based on image analysis and machine learning on the basis of 59 MM specimens. Our approach automatically detects tumour regions, identifies mitotic nuclei and classifies them with respect to their diagnostic relevance. A convenient user interface enables the investigator to browse through the proposed mitoses for fast and efficient diagnosing.ResultsA quantitative evaluation on manually labelled ground truth data revealed that the tumour region detection yields a medium spatial overlap index (dice coefficient) of 0.72. For the mitosis detection, we obtained high accuracies of above 83%.ConclusionOn the technical side, the developed iDermatoPath software tool provides a novel approach for mitosis detection in MM, which can be further improved using more training data such as dermatopathologist annotations. On the practical side, a first evaluation of the clinical utility was positive, albeit this approach provides most benefit for difficult cases in a research setting. Assuming all slides to be digitally processed and reported in the near future, this method could become a helpful additional tool for the pathologist.