bluuebunny/crossref_metadata_2025_split huggingface dataset:
Striking In Vivo Phenotype of a Disease-Associated Human
SCN5A
Mutation Producing Minimal Changes in Vitro
Authors: Watanabe Hiroshi , Yang Tao , Stroud Dina Myers , Lowe John S. , Harris Louise , Atack Thomas C. , Wang Dao W. , Hipkens Susan B. , Leake Brenda , Hall Lynn , Kupershmidt Sabina , Chopra Nagesh , Magnuson Mark A. , Tanabe Naohito , Knollmann Björn C. , George Alfred L. , Roden Dan M. 
Published: August 2011

Background—

The D1275N
SCN5A
mutation has been associated with a range of unusual phenotypes, including conduction disease and dilated cardiomyopathy, as well as atrial and ventricular tachyarrhythmias. However, when D1275N is studied in heterologous expression systems, most studies show near-normal sodium channel function. Thus, the relationship of the variant to the clinical phenotypes remains uncertain.

Methods and Results—

We identified D1275N in a patient with atrial flutter, atrial standstill, conduction disease, and sinus node dysfunction. There was no major difference in biophysical properties between wild-type and D1275N channels expressed in Chinese hamster ovary cells or tsA201 cells in the absence or presence of β1 subunits. To determine D1275N function in vivo, the
Scn5a
locus was modified to knock out the mouse gene, and the full-length wild-type (H) or D1275N (DN) human
SCN5A
cDNAs were then inserted at the modified locus by recombinase mediated cassette exchange. Mice carrying the DN allele displayed slow conduction, heart block, atrial fibrillation, ventricular tachycardia, and a dilated cardiomyopathy phenotype, with no significant fibrosis or myocyte disarray on histological examination. The DN allele conferred gene-dose–dependent increases in
SCN5A
mRNA abundance but reduced sodium channel protein abundance and peak sodium current amplitudes (H/H, 41.0±2.9 pA/pF at −30 mV; DN/H, 19.2±3.1 pA/pF,
P
<0.001 vs H/H; DN/DN, 9.3±1.1 pA/pF,
P
<0.001 versus H/H).

Conclusions—
Although D1275N produces near-normal currents in multiple heterologous expression experiments, our data establish this variant as a pathological mutation that generates conduction slowing, arrhythmias, and a dilated cardiomyopathy phenotype by reducing cardiac sodium current.
Phylogeny and reclassification of Laelius (Hymenoptera: Bethylidae) and description of four new species
Authors: Azevedo Celso , Barbosa Diego 
Published: August 2011

AbstractAs currently recognised, Laelius Ashmead contains 47 known species worldwide and is found on all continents except Australia (until this study). In this paper, we examined the taxonomic limits of this genus and tested whether species of the genera Laelius and Prolaelius Kieffer constitute a monophyletic group. We also tested whether the junior synonyms Allepyris Kieffer and Paralaelius Kieffer are supported by cladistic analyses. Our initial analysis indicated that these genera form a single clade. Cladistic analyses were based on 108 female structural characters. The data set was analyzed under equal-weights parsimony and implied weighting. In both analyses, Laelius was retrieved as a polyphyletic group because Prolaelius Kieffer was always nested within Laelius and Allepyris berlandi Benoit always remained in the outgroup and was retrieved as the sister group of Disepyris sp. Based on our analyses, we propose nine nomenclatural acts and recognise 52 valid species of Laelius. The following four new species are described: Laelius haplos sp.n. and L. quadrangulus sp.n. from Australia and L. ogmos sp.n. and L. titanokkos sp.n. from ailand. The following new generic synonym is proposed: Prolaelius Kieffer syn.n. of Laelius Ashmead. The following three new combinations are proposed: Disepyris berlandi (Benoit) comb.n. from Laelius, Laelius firmipennis (Cameron) comb.n. and Laelius glossinae (Turner & Waterston) comb.n. from Prolaelius. Additionally, a lectotype is designated for Laelius fulvipes Kieffer.
Mesoscale Surface Analysis System for the Australian Domain: Design Issues, Development Status, and System Validation
Authors: Glowacki Tomasz J. , Xiao Yi , Steinle Peter 
Published: August 2011

Abstract
An operational surface analysis system for the continent of Australia is presented. The system is specifically designed to mitigate problems that arise when analyzing surface data with a highly inhomogeneous distribution. Hourly analyses of atmospheric pressure at mean sea level, potential temperature, 2-m dewpoint temperature, and 10-m wind components are generated on a ~4-km grid. The system employs a statistical interpolation technique using observations of pressure, temperature, dewpoint, and wind data. The problem of data gaps in space and time is addressed by introducing pseudo-observations. For stations missing a report at analysis time, estimates are reconstructed by interpolating off-time reports. Underobserved areas in the network are identified from precalculated, gridded observation densities for each analysis time, which also yield weights to combine preliminary analysis and first-guess data into pseudo-observations. A regression-based pressure reduction technique, consistent with local reductions at observing sites and devised specifically for this system, is used for accurate and fast conversion of pressure and, indirectly, temperature variables within the system. Analysis accuracy is verified by withholding observations for specific periods. Analyzed fields are shown to be significantly more accurate than the current operational numerical model fields used as a first guess for the high-resolution surface analysis. The system design and analysis accuracies are also assessed within this context and compared with similar overseas developments.
Lack of Association between Eotaxin‐1 Gene Polymorphisms and Nasal Polyposis
Authors: Ekinci Suna , Erbek Selim S. , Yurtcu Erkan , Sahin Feride I. 
Published: August 2011

ObjectiveTo examine whether there is an association of eotaxin‐1 gene polymorphisms with nasal polyposis (NP).Study DesignCross‐sectional study.SettingTertiary referral center.Subjects and MethodsThe study group included 85 patients with NP and 93 controls without sinonasal disease. Genotypes of eotaxin‐1 (−384 A>G and +67 G>A) were identified by restriction fragment length polymorphism analyses after polymerase chain reaction.ResultsThe −384 A>G and +67 G>A single nucleotide polymorphisms were higher in patients with NP than in controls (P =. 044 and P =. 019, respectively). However, their relation was statistically poor (association coefficient = 0.18). Consistent with this result, comparisons of allele frequencies for both single nucleotide polymorphisms were not significantly different (−384 A>G, P =. 164; +67 G>A, P =. 144).ConclusionIn this study, eotaxin‐1 −384 A>G or 67 G>A genotypes were not associated with susceptibility to NP.
The role of the endocannabinoid system in the neuroendocrine regulation of energy balance
Authors: Bermudez-Silva Francisco Javier , Cardinal Pierre , Cota Daniela 
Published: August 2011

Animal and human studies carried out so far have established a role for the endocannabinoid system (ECS) in the regulation of energy balance. Here we critically discuss the role of the endocannabinoid signalling in brain structures, such as the hypothalamus and reward-related areas, and its interaction with neurotransmitter and neuropeptide systems involved in the regulation of food intake and body weight. The ECS has been found to interact with peripheral signals, like leptin, insulin, ghrelin and satiety hormones and the resulting effects on both central and peripheral mechanisms affecting energy balance and adiposity will be described. Furthermore, ECS dysregulation has been associated with the development of dyslipidemia, glucose intolerance and obesity; phenomena that are often accompanied by a plethora of neuroendocrine alterations which might play a causal role in determining ECS dysregulation. Despite the withdrawal of the first generation of cannabinoid type 1 receptor (CB1) antagonists from the pharmaceutical market due to the occurrence of psychiatric adverse events, new evidence suggests that peripherally restricted CB1 antagonists might be efficacious for the treatment of obesity and its associated metabolic disorders. Thus, a perspective on new promising strategies to selectively target the ECS in the context of energy balance regulation is given.
Preventive Effect of Eccentric Training on Acute Hamstring Injuries in Men’s Soccer
Authors: Petersen Jesper , Thorborg Kristian , Nielsen Michael Bachmann , Budtz-Jørgensen Esben , Hölmich Per 
Published: August 2011

Background: The incidence of acute hamstring injuries is high in several sports, including the different forms of football. Purpose: The authors investigated the preventive effect of eccentric strengthening of the hamstring muscles using the Nordic hamstring exercise compared with no additional hamstring exercise on the rate of acute hamstring injuries in male soccer players. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Fifty Danish male professional and amateur soccer teams (942 players) were allocated to an intervention group (461 players) or a control group (481 players). Players in the intervention group conducted a 10-week progressive eccentric training program followed by a weekly seasonal program, whereas players in the control group followed their usual training program. The main outcome measures were numbers of overall, new, and recurrent acute hamstring injuries during 1 full soccer season. Results: Fifty-two acute hamstring injuries in the control group compared with 15 injuries in the intervention group were registered. Comparing intervention versus the control group, overall acute hamstring injury rates per 100 player seasons were 3.8 versus 13.1 (adjusted rate ratio [RR], 0.293; 95% confidence interval [CI], 0.150-0.572; P < .001). New injury rates per 100 player seasons were 3.1 versus 8.1 (RR, 0.410; 95% CI, 0.180-0.933; P = .034), whereas recurrent injury rates per 100 player seasons were 7.1 versus 45.8 (RR, 0.137; 95% CI, 0.037-0.509; P = .003). Number needed to treat [NNT] to prevent 1 acute hamstring injury (new or recurrent) is 13 (95% CI, 9-23) players. The NNT to prevent 1 new injury is 25 (95% CI, 15-72) players, and NNT to prevent 1 recurrent injury is 3 (95% CI, 2-6) players. Conclusion: In male professional and amateur soccer players, additional eccentric hamstring exercise decreased the rate of overall, new, and recurrent acute hamstring injuries.
Impact of aliskiren treatment on urinary aldosterone levels in patients with type 2 diabetes and nephropathy: an AVOID substudy
Authors: Persson Frederik , Lewis Julia B , Lewis Edmund J , Rossing Peter , Hollenberg Norman K , Hans-Henrik Parving 
Published: August 2011

Introduction: Aldosterone blockade reduces albuminuria in diabetic patients with chronic kidney disease (CKD), and improves prognosis in chronic heart failure. This study assessed the effects of direct renin inhibition with aliskiren in combination with losartan and optimal antihypertensive therapy on urinary aldosterone, plasma renin activity (PRA) and plasma renin concentration (PRC). Materials and methods: In the AVOID study, 599 patients with type 2 diabetes, hypertension and nephropathy received 6 months aliskiren (150 mg force titrated to 300 mg once daily after 3 months) or placebo added to losartan 100 mg and optimal antihypertensive therapy. Urinary aldosterone excretion, PRA and PRC were measured at baseline and after 24 weeks in a prespecified subset of 133 patients. Results: Aliskiren added to losartan provided reductions from baseline in urinary aldosterone compared with adding placebo (−24% vs. −4%, p = 0.017) at week 24. There was no significant difference between the aliskiren and placebo groups in the proportion of patients with aldosterone breakthrough (aliskiren 35%, placebo 46%, p = 0.199). Aliskiren treatment reduced PRA by 90% at 24 weeks and increased PRC by 328%. Conclusions: Adding aliskiren to recommended renoprotective treatment with losartan and optimal antihypertensive therapy provided significant reductions in urinary aldosterone excretion which may attenuate decline in kidney function.
BKM-react, an integrated biochemical reaction database
Authors: Lang Maren , Stelzer Michael , Schomburg Dietmar 
Published: August 2011

Abstract

Background
The systematic, complete and correct reconstruction of genome-scale metabolic networks or metabolic pathways is one of the most challenging tasks in systems biology research. An essential requirement is the access to the complete biochemical knowledge - especially on the biochemical reactions. This knowledge is extracted from the scientific literature and collected in biological databases. Since the available databases differ in the number of biochemical reactions and the annotation of the reactions, an integrated knowledge resource would be of great value.

Results
We developed a comprehensive non-redundant reaction database containing known enzyme-catalyzed and spontaneous reactions. Currently, it comprises 18,172 unique biochemical reactions. As source databases the biochemical databases BRENDA, KEGG, and MetaCyc were used. Reactions of these databases were matched and integrated by aligning substrates and products. For the latter a two-step comparison using their structures (via InChIs) and names was performed. Each biochemical reaction given as a reaction equation occurring in at least one of the databases was included.

Conclusions
An integrated non-redundant reaction database has been developed and is made available to users. The database can significantly facilitate and accelerate the construction of accurate biochemical models.
Genome-wide prediction of splice-modifying SNPs in human genes using a new analysis pipeline called AASsites
Authors: Faber Kirsten , Glatting Karl-Heinz , Mueller Phillip J , Risch Angela , Hotz-Wagenblatt Agnes 
Published: August 2011

Abstract

Background
Some single nucleotide polymorphisms (SNPs) are known to modify the risk of developing certain diseases or the reaction to drugs. Due to next generation sequencing methods the number of known human SNPs has grown. Not all SNPs lead to a modified protein, which may be the origin of a disease. Therefore, the recognition of functional SNPs is needed. Because most SNP annotation tools look for SNPs which lead to an amino acid exchange or a premature stop, we designed a new tool called AASsites which searches for SNPs which modify splicing.

Results
AASsites uses several gene prediction programs and open reading frame prediction to compare the wild type (wt) and the variant gene sequence. The results of the comparison are combined by a handmade rule system to classify a change in splicing as “likely, probable, unlikely”. Having received good results from tests with SNPs known for changing the splicing pattern we checked 80,000 SNPs from the human genome which are located near splice sites for their ability to change the splicing pattern of the gene and hereby result in a different protein. We identified 301 “likely” and 985 “probable” classified SNPs with such characteristics. Within this set 33 SNPs are described in the ssSNP Target database to cause modified splicing.

Conclusions
With AASsites single SNPs can be checked for those causing splice modifications. Screening 80,000 known human SNPs we detected about 1,200 SNPs which probably modify splicing. AASsites is available at http://genius.embnet.dkfz-heidelberg.de/menu/biounit/open-husar using any web browser.
A robust approach to optimizing multi-source information for enhancing genomics retrieval performance
Authors: Hu Qinmin , Huang Jimmy Xiangji , Miao Jun 
Published: August 2011

AbstractBackgroundThe users desire to be provided short, specific answers to questions and put them in context by linking original sources from the biomedical literature. Through the use of information retrieval technologies, information systems retrieve information to index data based on all kinds of pre-defined searching techniques/functions such that various ranking strategies are designed depending on different sources. In this paper, we propose a robust approach to optimizing multi-source information for improving genomics retrieval performance.ResultsIn the proposed approach, we first consider a common scenario for a metasearch system that has access to multiple baselines with retrieving and ranking documents/passages by their own models. Then, given selected baselines from multiple sources, we investigate three modified fusion methods in the proposed approach, reciprocal, CombMNZ and CombSUM, to re-rank the candidates as the outputs for evaluation. Our empirical study on both 2007 and 2006 genomics data sets demonstrates the viability of the proposed approach for obtaining better performance. Furthermore, the experimental results show that the reciprocal method provides notable improvements on the individual baseline, especially on the passage2-level MAP and the aspect-level MAP.ConclusionsFrom the extensive experiments on two TREC genomics data sets, we draw the following conclusions. For the three fusion methods proposed in the robust approach, the reciprocal method outperforms the CombMNZ and CombSUM methods obviously, and CombSUM works well on the passage2-level when compared with CombMNZ. Based on the multiple sources of DFR, BM25 and language model, we can observe that the alliance of giants achieves the best result. Meanwhile, under the same combination, the better the baseline performance is, the more contribution the baseline provides. These conclusions are very useful to direct the fusion work in the field of biomedical information retrieval.
Strong differences in the clonal variation of two Daphnia species from mountain lakes affected by overwintering strategy
Authors: Hamrová Eva , Mergeay Joachim , Petrusek Adam 
Published: August 2011

AbstractBackgroundThe population structure of cyclical parthenogens such as water fleas is strongly influenced by the frequency of alternations between sexual and asexual (parthenogenetic) reproduction, which may differ among populations and species. We studied genetic variation within six populations of two closely related species of water fleas of the genusDaphnia(Crustacea, Cladocera).D. galeataandD. longispinaboth occur in lakes in the Tatra Mountains (Central Europe), but their populations show distinct life history strategies in that region. In three studied lakes inhabited byD. galeata, daphnids overwinter under the ice as adult females. In contrast, in lakes inhabited byD. longispina, populations apparently disappear from the water column and overwinter as dormant eggs in lake sediments. We investigated to what extent these different strategies lead to differences in the clonal composition of late summer populations.ResultsAnalysis of genetic variation at nine microsatellite loci revealed that clonal richness (expressed as the proportion of different multilocus genotypes, MLGs, in the whole analysed sample) consistently differed between the two studied species. In the threeD. longispinapopulations, very high clonal richness was found (MLG/N ranging from 0.97 to 1.00), whereas inD. galeatait was much lower (0.05 to 0.50). The dominant MLGs in allD. galeatapopulations were heterozygous at five or more loci, suggesting that such individuals all represented the same clonal lineages rather than insufficiently resolved groups of different clones.ConclusionsThe low clonal diversities and significant deviations from Hardy-Weinberg equilibrium inD. galeatapopulations were likely a consequence of strong clonal erosion over extended periods of time (several years or even decades) and the limited influence of sexual reproduction. Our data reveal that populations of closely relatedDaphniaspecies living in relatively similar habitats (permanent, oligotrophic mountain lakes) within the same region may show strikingly different genetic structures, which most likely depend on their reproductive strategy during unfavourable periods. We assume that similar impacts of life history on population structures are also relevant for other cyclical parthenogen groups. In extreme cases, prolonged clonal erosion may result in the dominance of a single clone within a population, which might limit its microevolutionary potential if selection pressures suddenly change.
Molecular evolution of a chordate specific family of G protein-coupled receptors
Authors: Kurtenbach Stefan , Mayer Christoph , Pelz Thomas , Hatt Hanns , Leese Florian , Neuhaus Eva M 
Published: August 2011

Abstract

Background
Chordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental complexity in vertebrates, since mutations modifying the function of a duplicated protein can lead to novel functions, improving the evolutionary success.

Results
We analyzed here the evolution of the GPRC5 family of G protein-coupled receptors by comprehensive similarity searches and found that the receptors are only present in chordates and that the size of the receptor family expanded, likely due to genome duplication events in the early history of vertebrate evolution. We propose that a single GPRC5 receptor coding gene originated in a stem chordate ancestor and gave rise by duplication events to a gene family comprising three receptor types (GPRC5A-C) in vertebrates, and a fourth homologue present only in mammals (GPRC5D). Additional duplications of GPRC5B and GPRC5C sequences occurred in teleost fishes. The finding that the expression patterns of the receptors are evolutionarily conserved indicates an important biological function of these receptors. Moreover, we found that expression of GPRC5B is regulated by vitamin A in vivo, confirming previous findings that linked receptor expression to retinoic acid levels in tumor cell lines and strengthening the link between the receptor expression and the development of a complex nervous system in chordates, known to be dependent on retinoic acid signaling.

Conclusions
GPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non-chordates to become chordates.