bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallelization and optimization of genetic analyses in isolation by distance web service
Authors: Turner Julia L , Kelley Scott T , Otto James S , Valafar Faramarz , Bohonak Andrew J 
Published: June 2009

Abstract

Background
The Isolation by Distance Web Service (IBDWS) is a user-friendly web interface for analyzing patterns of isolation by distance in population genetic data. IBDWS enables researchers to perform a variety of statistical tests such as Mantel tests and reduced major axis regression (RMA), and returns vector based graphs. The more than 60 citations since 2005 confirm the popularity and utility of this website. Despite its usefulness, the data sets with over 65 populations can take hours or days to complete due to the computational intensity of the statistical tests. This is especially troublesome for web-based software analysis, since users tend to expect real-time results on the order of seconds, or at most, minutes. Moreover, as genetic data continue to increase and diversify, so does the demand for more processing power. In order to increase the speed and efficiency of IBDWS, we first determined which aspects of the code were most time consuming and whether they might be amenable to improvements by parallelization or algorithmic optimization.

Results
Runtime tests uncovered two areas of IBDWS that consumed significant amounts of time: randomizations within the Mantel test and the RMA calculations. We found that these sections of code could be restructured and parallelized to improve efficiency. The code was first optimized by combining two similar randomization routines, implementing a Fisher-Yates shuffling algorithm, and then parallelizing those routines. Tests of the parallelization and Fisher-Yates algorithmic improvements were performed on a variety of data sets ranging from 10 to 150 populations. All tested algorithms showed runtime reductions and a very close fit to the predicted speedups based on time-complexity calculations. In the case of 150 populations with 10,000 randomizations, data were analyzed 23 times faster.

Conclusion
Since the implementation of the new algorithms in late 2007, datasets have continued to increase substantially in size and many exceed the largest population sizes we used in our test sets. The fact that the website has continued to work well in "real-world" tests, and receives a considerable number of new citations provides the strongest testimony to the effectiveness of our improvements. However, we soon expect the need to upgrade the number of nodes in our cluster significantly as dataset sizes continue to expand. The parallel implementation can be found at http://ibdws.sdsu.edu/.
Improved resolution in the position of drought-related QTLs in a single mapping population of rice by meta-analysis
Authors: Khowaja Farkhanda S , Norton Gareth J , Courtois Brigitte , Price Adam H 
Published: June 2009

Abstract

Background
Meta-analysis of QTLs combines the results of several QTL detection studies and provides narrow confidence intervals for meta-QTLs, permitting easier positional candidate gene identification. It is usually applied to multiple mapping populations, but can be applied to one. Here, a meta-analysis of drought related QTLs in the Bala × Azucena mapping population compiles data from 13 experiments and 25 independent screens providing 1,650 individual QTLs separated into 5 trait categories; drought avoidance, plant height, plant biomass, leaf morphology and root traits. A heat map of the overlapping 1 LOD confidence intervals provides an overview of the distribution of QTLs. The programme BioMercator is then used to conduct a formal meta-analysis at example QTL clusters to illustrate the value of meta-analysis of QTLs in this population.

Results
The heat map graphically illustrates the genetic complexity of drought related traits in rice. QTLs can be linked to their physical position on the rice genome using Additional file 1 provided. Formal meta-analysis on chromosome 1, where clusters of QTLs for all trait categories appear close, established that the sd1 semi-dwarfing gene coincided with a plant height meta-QTL, that the drought avoidance meta-QTL was not likely to be associated with this gene, and that this meta-QTL was not pleiotropic with close meta-QTLs for leaf morphology and root traits. On chromosome 5, evidence suggests that a drought avoidance meta-QTL was pleiotropic with leaf morphology and plant biomass meta-QTLs, but not with meta-QTLs for root traits and plant height 10 cM lower down. A region of dense root QTL activity graphically visible on chromosome 9 was dissected into three meta-QTLs within a space of 35 cM. The confidence intervals for meta-QTLs obtained ranged from 5.1 to 14.5 cM with an average of 9.4 cM, which is approximately 180 genes in rice.

Conclusion
The meta-analysis is valuable in providing improved ability to dissect the complex genetic structure of traits, and distinguish between pleiotropy and close linkage. It also provides relatively small target regions for the identification of positional candidate genes.
Carbon and arsenic metabolism in Thiomonas strains: differences revealed diverse adaptation processes
Authors: Bryan Christopher G , Marchal Marie , Battaglia-Brunet Fabienne , Kugler Valérie , Lemaitre-Guillier Christelle , Lièvremont Didier , Bertin Philippe N , Arsène-Ploetze Florence 
Published: June 2009

AbstractBackgroundThiomonasstrains are ubiquitous in arsenic-contaminated environments. Differences betweenThiomonasstrains in the way they have adapted and respond to arsenic have never been studied in detail. For this purpose, fiveThiomonasstrains, that are interesting in terms of arsenic metabolism were selected:T. arsenivorans,Thiomonasspp. WJ68 and 3As are able to oxidise As(III), whileThiomonassp. Ynys1 andT. perometabolisare not. Moreover,T. arsenivoransand 3As present interesting physiological traits, in particular that these strains are able to use As(III) as an electron donor.ResultsThe metabolism of carbon and arsenic was compared in the fiveThiomonasstrains belonging to two distinct phylogenetic groups. Greater physiological differences were found between these strains than might have been suggested by 16S rRNA/rpoAgene phylogeny, especially regarding arsenic metabolism. Physiologically,T. perometabolisand Ynys1 were unable to oxidise As(III) and were less arsenic-resistant than the other strains. Genetically, they appeared to lack theaoxarsenic-oxidising genes and carried only a singlearsarsenic resistance operon.Thiomonas arsenivoransbelonged to a distinct phylogenetic group and increased its autotrophic metabolism when arsenic concentration increased. Differential proteomic analysis revealed that inT. arsenivorans, therbc/cbbgenes involved in the assimilation of inorganic carbon were induced in the presence of arsenic, whereas these genes were repressed inThiomonassp. 3As.ConclusionTaken together, these results show that these closely related bacteria differ substantially in their response to arsenic, amongst other factors, and suggest different relationships between carbon assimilation and arsenic metabolism.
Cloning and analysis of a bifunctional methyltransferase/restriction endonuclease TspGWI, the prototype of a Thermus sp. enzyme family
Authors: Zylicz-Stachula Agnieszka , Bujnicki Janusz M , Skowron Piotr M 
Published: June 2009

Abstract

Background
Restriction-modification systems are a diverse class of enzymes. They are classified into four major types: I, II, III and IV. We have previously proposed the existence of a Thermus sp. enzyme family, which belongs to type II restriction endonucleases (REases), however, it features also some characteristics of types I and III. Members include related thermophilic endonucleases: TspGWI, TaqII, TspDTI, and Tth111II.

Results
Here we describe cloning, mutagenesis and analysis of the prototype TspGWI enzyme that recognises the 5'-ACGGA-3' site and cleaves 11/9 nt downstream. We cloned, expressed, and mutagenised the tspgwi gene and investigated the properties of its product, the bifunctional TspGWI restriction/modification enzyme. Since TspGWI does not cleave DNA completely, a cloning method was devised, based on amino acid sequencing of internal proteolytic fragments. The deduced amino acid sequence of the enzyme shares significant sequence similarity with another representative of the Thermus sp. family – TaqII. Interestingly, these enzymes recognise similar, yet different sequences in the DNA. Both enzymes cleave DNA at the same distance, but differ in their ability to cleave single sites and in the requirement of S-adenosylmethionine as an allosteric activator for cleavage. Both the restriction endonuclease (REase) and methyltransferase (MTase) activities of wild type (wt) TspGWI (either recombinant or isolated from Thermus sp.) are dependent on the presence of divalent cations.

Conclusion
TspGWI is a bifunctional protein comprising a tandem arrangement of Type I-like domains; particularly noticeable is the central HsdM-like module comprising a helical domain and a highly conserved S-adenosylmethionine-binding/catalytic MTase domain, containing DPAVGTG and NPPY motifs. TspGWI also possesses an N-terminal PD-(D/E)XK nuclease domain related to the corresponding domains in HsdR subunits, but lacks the ATP-dependent translocase module of the HsdR subunit and the additional domains that are involved in subunit-subunit interactions in Type I systems. The MTase and REase activities of TspGWI are autonomous and can be uncoupled. Structurally and functionally, the TspGWI protomer appears to be a streamlined 'half' of a Type I enzyme.
Elongation factor eEF1B modulates functions of the release factors eRF1 and eRF3 and the efficiency of translation termination in yeast
Authors: Valouev Igor A , Fominov Gleb V , Sokolova Elizaveta E , Smirnov Vladimir N , Ter-Avanesyan Michael D 
Published: June 2009

Abstract

Background
Termination of translation in eukaryotes is controlled by two interacting polypeptide chain release factors, eRF1 and eRF3. While eRF1 recognizes nonsense codons, eRF3 facilitates polypeptide chain release from the ribosome in a GTP-dependent manner. Besides termination, both release factors have essential, but poorly characterized functions outside of translation.

Results
To characterize further the functions of yeast eRF1 and eRF3, a genetic screen for their novel partner proteins was performed. As a result, the genes for γ (TEF4 and TEF3/CAM1) and α (TEF5/EFB1) subunits of the translation elongation factor eEF1B, known to catalyze the exchange of bound GDP for GTP on eEF1A, were revealed. These genes act as dosage suppressors of a synthetic growth defect caused by some mutations in the SUP45 and SUP35 genes encoding eRF1 and eRF3, respectively. Extra copies of TEF5 and TEF3 can also suppress the temperature sensitivity of some sup45 and sup35 mutants and reduce nonsense codon readthrough caused by these omnipotent suppressors. Besides, overproduction of eEF1Bα reduces nonsense codon readthrough in the strain carrying suppressor tRNA. Such effects were not shown for extra copies of TEF2, which encodes eEF1A, thus indicating that they were not due to eEF1A activation.

Conclusion
The data obtained demonstrate involvement of the translation elongation factor eEF1B in modulating the functions of translation termination factors and suggest its possible role in GDP for GTP exchange on eRF3.
In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain
Authors: Ratai Eva-Maria , Pilkenton Sarah J , Greco Jane B , Lentz Margaret R , Bombardier Jeffrey P , Turk Katherine W , He Julian , Joo Chan-Gyu , Lee Vallent , Westmoreland Susan , Halpern Elkan , Lackner Andrew A , González R Gilberto 
Published: June 2009

Abstract

Background

In vivo proton magnetic resonance spectroscopy (1H-MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection.

Results
Changes in the N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), creatine (Cr) and glutamine/glutamate (Glx) resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi). At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions.

Conclusion
These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.
Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease
Authors: Jaiswal Manoj Kumar , Zech Wolf-Dieter , Goos Miriam , Leutbecher Christine , Ferri Alberto , Zippelius Annette , Carrì Maria Teresa , Nau Roland , Keller Bernhard U 
Published: June 2009

Abstract

Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN) in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS) and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD) imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS.

Results
To gain insights into the molecular mechanisms of SOD1G93A associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage – dependent cytosolic Ca2+ elevations and mitochondria – controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5YWT) and G93A (SH-SY5YG93A) expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation.

Conclusion
In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells an established cellular model of ALS. The primary goals of this paper are (1) method development, and (2) screening for deficits in mutant cells on the single cell level. On the technological level, our method promises to serve as a valuable tool to identify mitochondrial and Ca2+-related defects during G93A-mediated MN degeneration. In addition, our experiments support a model where a specialized interplay between cytosolic calcium profiles and mitochondrial mechanisms contribute to the selective degeneration of neurons in ALS.
The HaDREB2 transcription factor enhances basal thermotolerance and longevity of seeds through functional interaction with HaHSFA9
Authors: Almoguera Concepción , Prieto-Dapena Pilar , Díaz-Martín Juan , Espinosa José M , Carranco Raúl , Jordano Juan 
Published: June 2009

Abstract

Background
Transcription factor HaDREB2 was identified in sunflower (Helianthus annuus L.) as a drought-responsive element-binding factor 2 (DREB2) with unique properties. HaDREB2 and the sunflower Heat Shock Factor A9 (HaHSFA9) co-activated the Hahsp17.6G1 promoter in sunflower embryos. Both factors could be involved in transcriptional co-activation of additional small heat stress protein (sHSP) promoters, and thus contribute to the HaHSFA9-mediated enhancement of longevity and basal thermotolerance of seeds.

Results
We found that overexpression of HaDREB2 in seeds did not enhance longevity. This was deduced from assays of basal thermotolerance and controlled seed-deterioration, which were performed with transgenic tobacco. Furthermore, the constitutive overexpression of HaDREB2 did not increase thermotolerance in seedlings or result in the accumulation of HSPs at normal growth temperatures. In contrast, when HaDREB2 and HaHSFA9 were conjointly overexpressed in seeds, we observed positive effects on seed longevity, beyond those observed with overexpression of HaHSFA9 alone. Such additional effects are accompanied by a subtle enhancement of the accumulation of subsets of sHSPs belonging to the CI and CII cytosolic classes.

Conclusion
Our results reveal the functional interdependency of HaDREB2 and HaHSFA9 in seeds. HaDREB2 differs from other previously characterized DREB2 factors in plants in terms of its unique functional interaction with the seed-specific HaHSFA9 factor. No functional interaction between HaDREB2 and HaHSFA9 was observed when both factors were conjointly overexpressed in vegetative tissues. We therefore suggest that additional, seed-specific factors, or protein modifications, could be required for the functional interaction between HaDREB2 and HaHSFA9.
Characterization and structural analysis of wild type and a non-abscission mutant at the development funiculus (Def) locus in Pisum sativum L
Authors: Ayeh Kwadwo Owusu , Lee YeonKyeong , Ambrose Mike J , Hvoslef-Eide Anne Kathrine 
Published: June 2009

AbstractBackgroundIn pea seeds (Pisum sativumL.), theDeflocus defines an abscission event where the seed separates from the funicle through the intervening hilum region at maturity. A spontaneous mutation at this locus results in the seed failing to abscise from the funicle as occurs in wild type peas. In this work, structural differences between wild type peas that developed a distinct abscission zone (AZ) between the funicle and the seed coat and non-abscissiondefmutant were characterized.ResultsA clear abscission event was observed in wild type pea seeds that were associated with a distinct double palisade layers at the junction between the seed coat and funicle. Generally, mature seeds fully developed an AZ, which was not present in young wild type seeds. The AZ was formed exactly below the counter palisade layer. In contrast, the palisade layers at the junction of the seed coat and funicle were completely absent in thedefmutant pea seeds and the cells in this region were seen to be extensions of surrounding parenchymatous cells.ConclusionTheDefwild type developed a distinct AZ associated with palisade layer and counterpalisade layer at the junction of the seed coat and funicle while thedefmutant pea seed showed non-abscission and an absence of the double palisade layers in the same region. We conclude that the presence of the double palisade layer in the hilum of the wild type pea seeds plays an important structural role in AZ formation by delimiting the specific region between the seed coat and the funicle and may play a structural role in the AZ formation and subsequent detachment of the seed from the funicle.
Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care
Authors: Leathem Claire S , Cupples Margaret E , Byrne Mary C , O'Malley Mary , Houlihan Ailish , Murphy Andrew W , Smith Susan M 
Published: June 2009

AbstractBackgroundRecruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers' and participants' experiences of its implementation and to inform future strategies to maximise recruitment and retention.MethodsIn total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection.ResultsWe achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners' contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention.ConclusionRecruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.Trial registrationISRCTN24081411
Timing of surgical antibiotic prophylaxis administration: Complexities of analysis
Authors: Cartmill Carrie , Lingard Lorelei , Regehr Glenn , Espin Sherry , Bohnen John , Baker Ross , Rotstein Lorne 
Published: June 2009

Abstract

Background
The timing of prophylactic antibiotic administration is a patient safety outcome that is recurrently tracked and reported. The interpretation of these data has important implications for patient safety practices. However, diverse data collection methods and approaches to analysis impede knowledge building in this field. This paper makes explicit several challenges to quantifying the timing of prophylactic antibiotics that we encountered during a recent study and offers a suggested protocol for resolving these challenges.

Challenges
Two clear challenges manifested during the data extraction process: the actual classification of antibiotic timing, and the additional complication of multiple antibiotic regimens with different timing classifications in a single case. A formalized protocol was developed for dealing with incomplete, ambiguous and unclear documentation. A hierarchical coding system was implemented for managing cases with multiple antibiotic regimens.

Interpretation
Researchers who are tracking prophylactic antibiotic timing as an outcome measure should be aware that documentation of antibiotic timing in the patient chart is frequently incomplete and unclear, and these inconsistencies should be accounted for in analyses. We have developed a systematic method for dealing with specific problematic patterns encountered in the data. We propose that the general adoption of a systematic approach to analysis of this type of data will allow for cross-study comparisons and ensure that interpretation of results is on the basis of timing practices rather than documentation practices.