bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kaviar: an accessible system for testing SNV novelty
Authors: Glusman Gustavo , Caballero Juan , Mauldin Denise E. , Hood Leroy , Roach Jared C. 
Published: September 2011

Abstract
Summary: With the rapidly expanding availability of data from personal genomes, exomes and transcriptomes, medical researchers will frequently need to test whether observed genomic variants are novel or known. This task requires downloading and handling large and diverse datasets from a variety of sources, and processing them with bioinformatics tools and pipelines. Alternatively, researchers can upload data to online tools, which may conflict with privacy requirements. We present here Kaviar, a tool that greatly simplifies the assessment of novel variants. Kaviar includes: (i) an integrated and growing database of genomic variation from diverse sources, including over 55 million variants from personal genomes, family genomes, transcriptomes, SNV databases and population surveys; and (ii) software for querying the database efficiently.
Availability: Kaviar is programmed in Perl and offered free of charge as Open Source Software. Kaviar may be used online as a programmatic web service or downloaded for local use from http://db.systemsbiology.net/kaviar. The database is also provided.
Contact: gustavo@systemsbiology.org
Supplementary Information: Supplementary data are available at Bioinformatics online.
HHfrag: HMM-based fragment detection using HHpred
Authors: Kalev Ivan , Habeck Michael 
Published: September 2011

Abstract
Motivation: Over the last decade, both static and dynamic fragment libraries for protein structure prediction have been introduced. The former are built from clusters in either sequence or structure space and aim to extract a universal structural alphabet. The latter are tailored for a particular query protein sequence and aim to provide local structural templates that need to be assembled in order to build the full-length structure.
Results: Here, we introduce HHfrag, a dynamic HMM-based fragment search method built on the profile–profile comparison tool HHpred. We show that HHfrag provides advantages over existing fragment assignment methods in that it: (i) improves the precision of the fragments at the expense of a minor loss in sequence coverage; (ii) detects fragments of variable length (6–21 amino acid residues); (iii) allows for gapped fragments and (iv) does not assign fragments to regions where there is no clear sequence conservation. We illustrate the usefulness of fragments detected by HHfrag on targets from most recent CASP.
Availability: A web server for running HHfrag is available at http://toolkit.tuebingen.mpg.de/hhfrag. The source code is available at http://www.eb.tuebingen.mpg.de/departments/1-protein-evolution/michael-habeck/HHfrag.tar.gz
Contact: michael.habeck@tuebingen.mpg.de
Supplementary Information: Supplementary data are available at Bioinformatics online.
TFRank: network-based prioritization of regulatory associations underlying transcriptional responses
Authors: Gonçalves Joana P. , Francisco Alexandre P. , Mira Nuno P. , Teixeira Miguel C. , Sá-Correia Isabel , Oliveira Arlindo L. , Madeira Sara C. 
Published: September 2011

Abstract
Motivation: Uncovering mechanisms underlying gene expression control is crucial to understand complex cellular responses. Studies in gene regulation often aim to identify regulatory players involved in a biological process of interest, either transcription factors coregulating a set of target genes or genes eventually controlled by a set of regulators. These are frequently prioritized with respect to a context-specific relevance score. Current approaches rely on relevance measures accounting exclusively for direct transcription factor–target interactions, namely overrepresentation of binding sites or target ratios. Gene regulation has, however, intricate behavior with overlapping, indirect effect that should not be neglected. In addition, the rapid accumulation of regulatory data already enables the prediction of large-scale networks suitable for higher level exploration by methods based on graph theory. A paradigm shift is thus emerging, where isolated and constrained analyses will likely be replaced by whole-network, systemic-aware strategies.
Results: We present TFRank, a graph-based framework to prioritize regulatory players involved in transcriptional responses within the regulatory network of an organism, whereby every regulatory path containing genes of interest is explored and incorporated into the analysis. TFRank selected important regulators of yeast adaptation to stress induced by quinine and acetic acid, which were missed by a direct effect approach. Notably, they reportedly confer resistance toward the chemicals. In a preliminary study in human, TFRank unveiled regulators involved in breast tumor growth and metastasis when applied to genes whose expression signatures correlated with short interval to metastasis.
Availability: Prototype at http://kdbio.inesc-id.pt/software/tfrank/.
Contact: jpg@kdbio.inesc-id.pt; sara.madeira@ist.utl.pt;
Supplementary Information: Supplementary data are available at Bioinformatics online.
An investigation of human vs. technology-induced variation in catchability for a selection of European fishing fleets
Authors: Mahévas Stéphanie , Vermard Youen , Hutton Trevor , Iriondo Ane , Jadaud Angélique , Maravelias Christos D. , Punzón Antonio , Sacchi Jacques , Tidd Alex , Tsitsika Efthymia , Marchal Paul , Goascoz Nicolas , Mortreux Serge , Roos David 
Published: September 2011

Abstract
Mahévas, S., Vermard, Y., Hutton, T., Iriondo, A., Jadaud, A., Maravelias, C. D., Punzón, A., Sacchi, J., Tidd, A., Tsitsika, E., Marchal, P., Goascoz, N., Mortreux, S., and Roos, D. 2011. An investigation of human vs. technology-induced variation in catchability for a selection of European fishing fleets. – ICES Journal of Marine Science, 68: 2252–2263. The impact of the fishing effort exerted by a vessel on a population depends on catchability, which depends on population accessibility and fishing power. The work investigated whether the variation in fishing power could be the result of the technical characteristics of a vessel and/or its gear or whether it is a reflection of inter-vessel differences not accounted for by the technical attributes. These inter-vessel differences could be indicative of a skipper/crew experience effect. To improve understanding of the relationships, landings per unit effort (lpue) from logbooks and technical information on vessels and gears (collected during interviews) were used to identify variables that explained variations in fishing power. The analysis was undertaken by applying a combination of generalized additive models and generalized linear models to data from several European fleets. The study highlights the fact that taking into account information that is not routinely collected, e.g. length of headline, weight of otter boards, or type of groundrope, will significantly improve the modelled relationships between lpue and the variables that measure relative fishing power. The magnitude of the skipper/crew experience effect was weaker than the technical effect of the vessel and/or its gear.
The Sink-Specific Plastidic Phosphate Transporter PHT4;2 Influences Starch Accumulation and Leaf Size in Arabidopsis
Authors: Irigoyen Sonia , Karlsson Patrik M. , Kuruvilla Jacob , Spetea Cornelia , Versaw Wayne K. 
Published: September 2011

AbstractNonphotosynthetic plastids are important sites for the biosynthesis of starch, fatty acids, and amino acids. The uptake and subsequent use of cytosolic ATP to fuel these and other anabolic processes would lead to the accumulation of inorganic phosphate (Pi) if not balanced by a Pi export activity. However, the identity of the transporter(s) responsible for Pi export is unclear. The plastid-localized Pi transporter PHT4;2 of Arabidopsis (Arabidopsis thaliana) is expressed in multiple sink organs but is nearly restricted to roots during vegetative growth. We identified and used pht4;2 null mutants to confirm that PHT4;2 contributes to Pi transport in isolated root plastids. Starch accumulation was limited in pht4;2 roots, which is consistent with the inhibition of starch synthesis by excess Pi as a result of a defect in Pi export. Reduced starch accumulation in leaves and altered expression patterns for starch synthesis genes and other plastid transporter genes suggest metabolic adaptation to the defect in roots. Moreover, pht4;2 rosettes, but not roots, were significantly larger than those of the wild type, with 40% greater leaf area and twice the biomass when plants were grown with a short (8-h) photoperiod. Increased cell proliferation accounted for the larger leaf size and biomass, as no changes were detected in mature cell size, specific leaf area, or relative photosynthetic electron transport activity. These data suggest novel signaling between roots and leaves that contributes to the regulation of leaf size.
Assessment of serum vascular endothelial growth factor and nail fold capillaroscopy changes in systemic lupus erythematosus with and without cutaneous manifestations
Authors: MONEIB Hoda A. , SALEM Samar A. M. , ALY Dalia G. , KHEDR Heba T. M. , WAFAEY Hanaa A. , HASSAN Hanan E. 
Published: September 2011

AbstractAngiogenesis and microvascular endothelial injury play a role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and nail fold capillaroscopy (NFC) have been investigated in few studies in SLE with no reports targeting SLE with cutaneous manifestations. To evaluate NFC changes and VEGF serum level in relation to disease activity in SLE patients with versus without cutaneous manifestations. Thirty SLE patients (15 with cutaneous manifestations [group I], 15 without [group II]) and 15 healthy controls were evaluated for VEGF serum levels, NFC changes and were related to disease activity. VEGF serum levels were significantly higher in patients than controls (median and interquartile range [IQR]: 2110.77, 471.09–4714.30 vs 60.00, 14–366, respectively, P < 0.0001). VEGF cut‐off value to predict SLE patients was more than 293 and to detect moderate and severe SLE activity was more than 422 pg/mL and more than 3800 pg/mL, respectively. Serum VEGF levels increased with increased disease activity (P < 0.05). It was significantly higher in group I than group II (median and IQR: 2624.74, 1801.39–4141.70 vs 862.50, 180–2426.95, respectively, P < 0.05). Mean serum VEGF was significantly higher with NFC score 3 than 1 (P = 0.008). NFC score and SLE activity were significantly associated in patients (P < 0.05). Serum VEGF is significantly elevated in SLE patients with cutaneous manifestations and its cut‐off values to detect different activity grades of SLE are identified. Abnormalities in NFC reflect the extent of microvascular involvement in SLE.
Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects
Authors: McGready Rose , Phyo Aung Pyae , Rijken Marcus J. , Tarning Joel , Lindegardh Niklas , Hanpithakpon Warunee , Than Hla Hla , Hlaing Nathar , Zin Naw Thida , Singhasivanon Pratap , White Nicholas J. , Nosten François 
Published: September 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Lowered plasma concentrations of artesunate have been reported in uncomplicated malaria in pregnancy which could risk the life of the mother and fetus.• The reason for lowered plasma concentrations in pregnancy is unexplained.• Oral artesunate is hydrolyzed rapidly in the stomach to the biologically active metabolite dihyroartemisinin.WHAT THIS STUDY ADDS• Following i.v. artesunate administration for malaria in pregnancy the disposition of artesunate and dihydroartemisinin were similar to controls (the same women studied post partum without malaria).• Higher concentrations of artesunate and dihydroartemisinin were observed after oral administration i.e the disease reduced the pre‐systemic metabolism of artesunate.• This study did not confirm previous reports and is reassuring regarding current dosing for artesunate in pregnancy.AIM To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance.METHODS In a sequentially assigned crossover treatment study, pregnant women with uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4 mg kg−1) on the first day and oral ARS (4 mg kg−1) on the second, or, oral on the first and i.v. on the second, in both groups followed by oral ARS (4 mg kg−1 day−1) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid chromatography‐mass‐spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (3 months post partum).RESULTS I.v. ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n= 20) and in controls (n= 14). Oral administration resulted in higher total drug exposure in pregnancy [AUC (95% CI) in (ng ml−1 h)/(mg kg−1)] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS, P= 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P= 0.007. The corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs. 9.9 (6.0, 36.81) for ARS (P= 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7) for DHA, P= 0.033. Total DHA exposure was lower at day 6 in pregnant women with malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P= 0.084).CONCLUSIONS This study demonstrates the effects of malaria on oral ARS drug disposition are greater than those of pregnancy. This probably results from a disease related reduction in first pass metabolism. The data are reassuring regarding current dosing recommendations.
Nitric oxide and related enzymes in asthma: relation to severity, enzyme function and inflammation
Authors: Yamamoto M. , Tochino Y. , Chibana K. , Trudeau J. B. , Holguin F. , Wenzel S. E. 
Published: September 2011

SummaryBackgroundExhaled nitric oxide (FeNO) associates with asthma and eosinophilic inflammation. However, relationships between nitric oxide synthases, arginase, FeNO, asthma severity and inflammation remain poorly understood.ObjectivesTo determine the relationships of iNOS expression/activation and arginase 2 expression with asthma severity, FeNO, nitrotyrosine (NT) and eosinophilic inflammation.MethodsBronchial brushings and sputum were obtained from 25 normal controls, eight mild/no inhaled corticosteroids (ICS), 16 mild‐moderate/with ICS and 35 severe asthmatics. The FeNO was measured the same day by ATS/ERS standards. The iNOS, arginase2 mRNA/protein and NT protein were measured in lysates from bronchial brushings by quantitative real‐time PCR and Western blot. Induced sputum differentials were obtained.ResultsSevere asthma was associated with the highest levels of iNOS protein and mRNA, although the index of iNOS mRNA to arginase2 mRNA most strongly differentiated severe from milder asthma. When evaluating NO‐related enzyme functionality, iNOS mRNA/protein expression both strongly predicted FeNO (r = 0.61, P < 0.0001 for both). Only iNOS protein predicted NT levels (r = 0.48, P = 0.003) with the strongest relationship in severe asthma (r = 0.61, P = 0.009). The iNOS protein, FeNO and NT, all correlated with sputum eosinophils, but the relationships were again strongest in severe asthma. Controlling for arginase 2 mRNA/protein did not impact any functional outcome.Conclusions and Clinical RelevanceThese data suggest that while iNOS expression from epithelial brushings is highest in severe asthma, factors controlling arginase2 mRNA expression significantly improve differentiation of severity. In contrast, functionality of the NO pathway as measured by FeNO, NT and eosinophilic inflammation, is strongly associated with iNOS expression alone, particularly in severe asthma.
The role of mitochondria in energy production for human sperm motility
Authors: Piomboni P. , Focarelli R. , Stendardi A. , Ferramosca A. , Zara V. 
Published: September 2011

SummaryMitochondria of spermatozoa are different from the corresponding organelles of somatic cells, in both their morphology and biochemistry. The biochemical differences are essentially related to the existence of specific enzyme isoforms, which are characterized by peculiar kinetic and regulatory properties. As mitochondrial energy metabolism is a key factor supporting several sperm functions, these organelles host critical metabolic pathways during germ cell development and fertilization. Furthermore, spermatozoa can use different substrates, and therefore activate different metabolic pathways, depending on the available substrates and the physico‐chemical conditions in which they operate. This versatility is critical to ensure fertilization success. However, the most valuable aspect of mitochondria function in all types of cells is the production of chemical energy in the form of ATP which can be used, in the case of spermatozoa, for sustaining sperm motility. The latter, on the other hand, represents one of the major determinants of male fertility. Accordingly, the presence of structural and functional alterations in mitochondria from asthenozoospermic subjects confirms the important role played by these organelles in energy maintenance of sperm motility. The present study gives an overview of the current knowledge on the energy‐producing metabolic pathways operating inside human sperm mitochondria and critically analyse the differences with respect to somatic mitochondria. Such a comparison has also been carried out between the functional characteristics of human sperm mitochondria and those of other mammalian species. A deeper understanding of mitochondrial energy metabolism could open up new avenues of investigation in bioenergetics of human sperm mitochondria, both in physiological and pathological conditions.
Early loss to follow‐up of recently diagnosed HIV‐infected adults from routine pre‐ART care in a rural district hospital in Kenya: a cohort study
Authors: Hassan Amin S. , Fielding Katherine L. , Thuo Nahashon M. , Nabwera Helen M. , Sanders Eduard J. , Berkley James A. 
Published: September 2011

AbstractObjective  To determine the rate and predictors of early loss to follow‐up (LTFU) for recently diagnosed HIV‐infected, antiretroviral therapy (ART)‐ineligible adults in rural Kenya.Methods  Prospective cohort study. Clients registering for HIV care between July 2008 and August 2009 were followed up for 6 months. Baseline data were used to assess predictors of pre‐ART LTFU (not returning for care within 2 months of a scheduled appointment), LTFU before the second visit and LTFU after the second visit. Logistic regression was used to determine factors associated with LTFU before the second visit, while Cox regression was used to assess predictors of time to LTFU and LTFU after the second visit.Results  Of 530 eligible clients, 178 (33.6%) were LTFU from pre‐ART care (11.1/100 person‐months). Of these, 96 (53.9%) were LTFU before the second visit. Distance (>5 km vs. <1 km: adjusted hazard ratio 2.6 [1.9–3.7], P < 0.01) and marital status (married vs. single: 0.5 [0.3–0.6], P < 0.01) independently predicted pre‐ART LTFU. Distance and marital status were independently associated with LTFU before the second visit, while distance, education status and seasonality showed weak evidence of predicting LTFU after the second visit. HIV disease severity did not predict pre‐ART LTFU.Conclusions  A third of recently diagnosed HIV‐infected, ART‐ineligible clients were LTFU within 6 months of registration. Predictors of LTFU among ART‐ineligible clients are different from those among clients on ART. These findings warrant consideration of an enhanced pre‐ART care package aimed at improving retention and timely ART initiation.
Deficiency of CRTAP in non‐lethal recessive osteogenesis imperfecta reduces collagen deposition into matrix
Authors: Valli M , Barnes AM , Gallanti A , Cabral WA , Viglio S , Weis MA , Makareeva E , Eyre D , Leikin S , Antoniazzi F , Marini JC , Mottes M 
Published: September 2011

Valli M, Barnes AM, Gallanti A, Cabral WA, Viglio S, Weis MA, Makareeva E, Eyre D, Leikin S, Antoniazzi F, Marini JC, Mottes M. Deficiency of CRTAP in non‐lethal recessive osteogenesis imperfecta reduces collagen deposition into matrix.Deficiency of any component of the ER‐resident collagen prolyl 3‐hydroxylation complex causes recessive osteogenesis imperfecta (OI). The complex modifies the α1(I)Pro986 residue and contains cartilage‐associated protein (CRTAP), prolyl 3‐hydroxylase 1 (P3H1) and cyclophilin B (CyPB). Fibroblasts normally secrete about 10% of CRTAP. Most CRTAP mutations cause a null allele and lethal type VII OI. We identified a 7‐year‐old Egyptian boy with non‐lethal type VII OI and investigated the effects of his null CRTAP mutation on collagen biochemistry, the prolyl 3‐hydroxylation complex, and collagen in extracellular matrix. The proband is homozygous for an insertion/deletion in CRTAP (c.118_133del16insTACCC). His dermal fibroblasts synthesize fully overmodified type I collagen, and 3‐hydroxylate only 5% of α1(I)Pro986. CRTAP transcripts are 10% of control. CRTAP protein is absent from proband cells, with residual P3H1 and normal CyPB levels. Dermal collagen fibril diameters are significantly increased. By immunofluorescence of long‐term cultures, we identified a severe deficiency (10–15% of control) of collagen deposited in extracellular matrix, with disorganization of the minimal fibrillar network. Quantitative pulse‐chase experiments corroborate deficiency of matrix deposition, rather than increased matrix turnover. We conclude that defects of extracellular matrix, as well as intracellular defects in collagen modification, contribute to the pathology of type VII OI.
Differential mRNA Expression and Promoter Methylation Status of SYCP3 Gene in Testes of Yaks and Cattle‐Yaks
Authors: Wang S , Pan Z , Zhang Q , Xie Z , Liu H , Li Q 
Published: September 2011

ContentsSynaptonemal complex protein 3 (SYCP3) is a DNA‐binding protein located on the lateral elements of the synaptonemal complex. This protein plays an important role in homologous chromosome pairing and is necessary for male meiosis of spermatogenesis. To further understand the SYCP3 gene function and its relationship to cattle‐yak male sterility, we investigated the characteristics of the bovine SYCP3 (bSYCP3) gene as well as its transcription level and epigenetic modification status. The bSYCP3 gene encodes a 225‐amino acid protein with the Cor1 motif and two coiled‐coil‐forming regions, homologous with other mammals (59–77% identity overall). Real‐time PCR analysis indicated that the expression level of bSYCP3 mRNA in yak testes was significantly higher than that in cattle‐yak (p < 0.05). The methylation level of the bSYCP3 promoter (mainly 7th, 13th and 17th CpG sites) in cattle‐yaks (40%) was significantly higher than that in yaks (0%) (p < 0.05). This suggests that bSYCP3 plays an important role in meiosis of bovine spermatogenesis; further, interspecific hybridization between yak and cattle might influence bSYCP3 gene expression in cattle‐yak testes, which might be influenced by bSYCP3 gene promoter methylation.