bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARCS-Motif: discovering correlated motifs from unaligned biological sequences
Authors: Zhang Shijie , Su Wei , Yang Jiong 
Published: December 2008

Abstract
Motivation: The goal of motif discovery is to detect novel, unknown, and important signals from biology sequences. In most models, the importance of a motif is equal to the sum of the similarity of every single position. In 2006, Song et al. introduced Aggregated Related Column Score (ARCS) measure which includes correlation information to the evaluation of motif importance. The paper showed that the ARCS measure is superior to other measures. Due to the complicated nature of the ARCS motif model, we cannot directly apply existing sequential motif discovery methods to find motifs with high ARCS values.
Results: This article presents a novel mining algorithm, ARCSMotif, to discover related sequential motifs in biological sequences. ARCS-Motif is applied to 400 PROSITE datasets and compared with five alternative methods (CONSENSUS, Gibbs sampler, MEME, SPLASH and DIALIGN-TX). ARCS-Motif outperforms all the methods in accuracy, and most of the methods in efficiency. Although SPLASH has better efficiency than ARCS-Motif, ARCS-Motif has much better accuracy than SPLASH. On average, ARCS-Motif is able to produce the motifs which are at least 10% better than the best of the alternative methods. Among the 400 PROSITE datasets, ARCS-Motif produces the best motifs for more than 200 families. Other than SPLASH, the execution time of ARCS-Motif is less than a third of that of the fastest alternative method and its execution time grows at the slowest rate with respect to the number of sequences and the average sequence among all methods.
Availability: Software: http://beijing.case.edu/ARCS_Motif/ARCS_Motif; Results: http://beijing.case.edu/ARCS_Motif
Contact: jiong.yang@case.edu
PASTAA: identifying transcription factors associated with sets of co-regulated genes
Authors: Roider Helge G. , Manke Thomas , O'Keeffe Sean , Vingron Martin , Haas Stefan A. 
Published: December 2008

Abstract
Motivation: A major challenge in regulatory genomics is the identification of associations between functional categories of genes (e.g. tissues, metabolic pathways) and their regulating transcription factors (TFs). While, for a limited number of categories, the regulating TFs are already known, still for many functional categories the responsible factors remain to be elucidated.
Results: We put forward a novel method (PASTAA) for detecting transcriptions factors associated with functional categories, which utilizes the prediction of binding affinities of a TF to promoters. This binding strength information is compared to the likelihood of membership of the corresponding genes in the functional category under study. Coherence between the two ranked datasets is seen as an indicator of association between a TF and the category. PASTAA is applied primarily to the determination of TFs driving tissue-specific expression. We show that PASTAA is capable of recovering many TFs acting tissue specifically and, in addition, provides novel associations so far not detected by alternative methods. The application of PASTAA to detect TFs involved in the regulation of tissue-specific gene expression revealed a remarkable number of experimentally supported associations. The validated success for various datasets implies that PASTAA can directly be applied for the detection of TFs associated with newly derived gene sets.
Availability: The PASTAA source code as well as a corresponding web interface is freely available at http://trap.molgen.mpg.de
Contact: roider@molgen.mpg.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Better bioinformatics through usability analysis
Authors: Bolchini Davide , Finkelstein Anthony , Perrone Vito , Nagl Sylvia 
Published: December 2008

Abstract
Motivation: Improving the usability of bioinformatics resources enables researchers to find, interact with, share, compare and manipulate important information more effectively and efficiently. It thus enables researchers to gain improved insights into biological processes with the potential, ultimately, of yielding new scientific results. Usability ‘barriers’ can pose significant obstacles to a satisfactory user experience and force researchers to spend unnecessary time and effort to complete their tasks. The number of online biological databases available is growing and there is an expanding community of diverse users. In this context there is an increasing need to ensure the highest standards of usability.
Results: Using ‘state-of-the-art’ usability evaluation methods, we have identified and characterized a sample of usability issues potentially relevant to web bioinformatics resources, in general. These specifically concern the design of the navigation and search mechanisms available to the user. The usability issues we have discovered in our substantial case studies are undermining the ability of users to find the information they need in their daily research activities. In addition to characterizing these issues, specific recommendations for improvements are proposed leveraging proven practices from web and usability engineering. The methods and approach we exemplify can be readily adopted by the developers of bioinformatics resources.
Contact: dbolchin@iupui.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Glycan family analysis for deducing N-glycan topology from single MS
Authors: Goldberg David , Bern Marshall , North Simon J. , Haslam Stuart M. , Dell Anne 
Published: December 2008

Abstract
Motivation: In the past few years, mass spectrometry (MS) has emerged as the premier tool for identification and quantification of biological molecules such as peptides and glycans. There are two basic strategies: single-MS, which uses a single round of mass analysis, and MS/MS (or higher order MSn), which adds one or more additional rounds of mass analysis, interspersed with fragmentation steps. Single-MS offers higher throughput, broader mass coverage and more direct quantitation, but generally much weaker identification. Single-MS, however, does work fairly well for the case of N-glycan identification, which are more constrained than other biological polymers. We previously demonstrated single-MS identification of N-glycans to the level of ‘cartoons’ (monosaccharide composition and topology) by a system that incorporates an expert's detailed knowledge of the biological sample. In this article, we explore the possibility of ab initio single-MS N-glycan identification, with the goal of extending single-MS, or primarily-single-MS, identification to non-expert users, novel conditions and unstudied tissues.
Results: We propose and test three cartoon-assignment algorithms that make inferences informed by biological knowledge about glycan synthesis. To test the algorithms, we used 71 single-MS spectra from a variety of tissues and organisms, containing more than 2800 manually annotated peaks. The most successful of the algorithms computes the most richly connected subgraph within a ‘cartoon graph’. This algorithm uniquely assigns the correct cartoon to more than half of the peaks in 41 out of the 71 spectra.
Contact: goldberg@parc.com
Supplementary information: Supplementary data are available at Bioinformatics online.
SIMoNe: Statistical Inference for MOdular NEtworks
Authors: Chiquet Julien , Smith Alexander , Grasseau Gilles , Matias Catherine , Ambroise Christophe 
Published: December 2008

AbstractSummary: The R package SIMoNe (Statistical Inference for MOdular NEtworks) enables inference of gene-regulatory networks based on partial correlation coefficients from microarray experiments. Modelling gene expression data with a Gaussian graphical model (hereafter GGM), the algorithm estimates non-zero entries of the concentration matrix, in a sparse and possibly high-dimensional setting. Its originality lies in the fact that it searches for a latent modular structure to drive the inference procedure through adaptive penalization of the concentration matrix.Availability: Under the GNU General Public Licence at http://cran.r-project.org/web/packages/simone/Contact: julien.chiquet@genopole.cnrs.fr
Peroxisomal ATP Import Is Essential for Seedling Development inArabidopsis thaliana
Authors: Linka Nicole , Theodoulou Frederica L. , Haslam Richard P. , Linka Marc , Napier Jonathan A. , Neuhaus H. Ekkehard , Weber Andreas P.M. 
Published: December 2008

AbstractSeveral recent proteomic studies of plant peroxisomes indicate that the peroxisomal matrix harbors multiple ATP-dependent enzymes and chaperones. However, it is unknown whether plant peroxisomes are able to produce ATP by substrate-level phosphorylation or whether external ATP fuels the energy-dependent reactions within peroxisomes. The existence of transport proteins that supply plant peroxisomes with energy for fatty acid oxidation and other ATP-dependent processes has not previously been demonstrated. Here, we describe two Arabidopsis thaliana genes that encode peroxisomal adenine nucleotide carriers, PNC1 and PNC2. Both proteins, when fused to enhanced yellow fluorescent protein, are targeted to peroxisomes. Complementation of a yeast mutant deficient in peroxisomal ATP import and in vitro transport assays using recombinant transporter proteins revealed that PNC1 and PNC2 catalyze the counterexchange of ATP with ADP or AMP. Transgenic Arabidopsis lines repressing both PNC genes were generated using ethanol-inducible RNA interference. A detailed analysis of these plants showed that an impaired peroxisomal ATP import inhibits fatty acid breakdown during early seedling growth and other β-oxidation reactions, such as auxin biosynthesis. We show conclusively that PNC1 and PNC2 are essential for supplying peroxisomes with ATP, indicating that no other ATP generating systems exist inside plant peroxisomes.
Survival of male breast cancer patients: Population‐based cohort study
Authors: Thalib Lukman , Hall Per 
Published: December 2008

Little information is available on the survival of male breast cancer patients because the disease is extremely rare in men. Moreover, previous reports on the prognosis of male breast cancer have been conflicting. We took advantage of a number of large, nationwide registries in Sweden to evaluate the prognostic value of sex in breast cancer patients. A population‐based cohort of 269 male and 30 011 female breast cancer patients born after 1935 and diagnosed with primary breast cancer between 1970 and 1997 was generated by linking a number of Swedish registries, including the Swedish Cancer Registry, the Cause of Death Registry, the Swedish Generation Registry, and the Registry of Population and Population Changes. We used this cohort to quantify the association between the sex of the patient and breast cancer‐specific mortality, using the Cox proportional hazards. The sex of the patient did not significantly influence the prognosis of breast cancer. Adjusting for age at diagnosis and calendar period did not alter the results. Nor did the results change when the analyses were repeated for all causes of morality. Our study, one of the largest to date, failed to find evidence to support the proposed association between the sex of breast cancer patients and survival. Given the previous reports, which advocated that male breast cancer patients have poorer survival and need aggressive treatment strategies, our findings are reassuring and clinically very important. (Cancer Sci 2009; 100: 292–295)
The combined effect of SNP‐marker and phenotype attributes in genome‐wide association studies
Authors: Chan E. K. F. , Hawken R. , Reverter A. 
Published: December 2008

SummaryThe last decade has seen rapid improvements in high‐throughput single nucleotide polymorphism (SNP) genotyping technologies that have consequently made genome‐wide association studies (GWAS) possible. With tens to hundreds of thousands of SNP markers being tested simultaneously in GWAS, it is imperative to appropriately pre‐process, or filter out, those SNPs that may lead to false associations. This paper explores the relationships between various SNP genotype and phenotype attributes and their effects on false associations. We show that (i) uniformly distributed ordinal data as well as binary data are more easily influenced, though not necessarily negatively, by differences in various SNP attributes compared with normally distributed data; (ii) filtering SNPs on minor allele frequency (MAF) and extent of Hardy–Weinberg equilibrium (HWE) deviation has little effect on the overall false positive rate; (iii) in some cases, filtering on MAF only serves to exclude SNPs from the analysis without reduction of the overall proportion of false associations; and (iv) HWE, MAF and heterozygosity are all dependent on minor genotype frequency, a newly proposed measure for genotype integrity.
Statin treatment in a cohort of 20 212 men and women in Norway according to cardiovascular risk factors and level of education
Authors: Selmer Randi , Sakshaug Solveig , Skurtveit Svetlana , Furu Kari , Tverdal Aage 
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Use of statins reduces cardiovascular morbidity and mortality.• Little is known about educational inequalities in use of statins. WHAT THIS STUDY ADDS • In Norway in patients with no history of cardiovascular disease or diabetes, start of statin treatment was not associated with educational level after adjustment for cardiovascular risk factors.• In patients with a history of cardiovascular disease or diabetes, especially highly educated women tended to start statin treatment more often than women of low educational level.• Persistence of statin treatment did not vary by educational level.AIMS To study the influence of patients' education and cardiovascular risk factors on the probability of statin treatment.METHODS A prospective cohort study of participants in regional health surveys in Norway 2000–2002 with statin use recorded in the Norwegian Prescription Database 2004–2006 as outcome measure. Information on history of cardiovascular disease (CVD) and diabetes, lipid levels, blood pressure, use of cardiovascular drugs, body mass index, family history, smoking, physical activity, marital status and place of residence was obtained at baseline. A total of 20 212 men and women aged 40–41, 45–46 and 59–61 years who reported never use of statins were included. Educational level was retrieved from Statistics Norway. Adjusted relative risks (RR) were estimated by Poisson regression.RESULTS Whereas 655 participants reported a history of CVD or diabetes, 19 557 reported no such history. In the non‐CVD/diabetes group 1620 persons (8%) became statin users and 222 persons (34%) in the CVD/diabetes group. RR of becoming a statin user for high vs. low education increased from 0.64 [95% confidence interval (CI) 0.55, 0.73] to 0.91 (95% CI 0.79, 1.05) after adjustment in the non‐CVD/diabetes group and from 0.94 (95% CI 0.70, 1.26) to 1.35 (95% CI 1.00, 1.81) in the CVD/diabetes group.CONCLUSIONS Patients with no history of CVD/diabetes were prescribed statins according to cardiovascular risk independent of education. There was a tendency to a higher probability of statin treatment among highly educated compared with people of lower educational level in the group with a history of CVD or diabetes, after adjustment for other CVD risk factors, particularly in women.
Clinical Immunology Review Series: An approach to the patient with allergy in childhood
Authors: Sporik R , Henderson J , Hourihane J O'B 
Published: December 2008

SummaryARTICLES PUBLISHED IN THIS CLINICAL IMMUNOLOGY REVIEW SERIESallergy in childhood, allergy diagnosis by use of the clinical immunology laboratory, anaphylaxis, angioedema, management of pulmonary disease in primary antibody deficiency, recurrent infections in childhood, recurrent infections in adulthood, recurrent oro-genital ulceration, recurrent superficial abscesses, SLE and Sjögren's syndrome, urticaria, vasculitis/CTDAllergic conditions are common, with asthma being the most common chronic illness in childhood in most developed countries. Some 80% of asthmatic children are sensitized to aeroallergens, usually indoor animal dander and house dust mite. Some 80% of asthmatics also have rhinitis. Rhinitis and eczema receive less medical attention than asthma, but they can cause long-term morbidity and have substantial direct and indirect economic costs. Food allergy and anaphylaxis are increasingly recognised and are usually easily diagnosed and managed. Clinicians can use in vivo and in vitro measurements of allergen-specific immunoglobulin E to better time reintroduction of implicated foods. Specific parenteral and sublingual immunotherapy is widely practiced internationally but is uncommon in the UK. It may alter the natural history of aeroallergen reactive diseases in the upper and lower airways. Specific oral tolerance induction represents the current cutting edge in clinical allergy research. It remands resource intensive at present and cannot be adopted into routine clinical practice at this time.
Reduced circulating CD4+CD25+ cell populations in haemorrhagic fever with renal syndrome
Authors: Zhu L Y , Chi L J , Wang X , Zhou H 
Published: December 2008

Summary
Immunopathological mechanisms are speculated to underlie haemorrhagic fever with renal syndrome (HFRS) caused by Hantaviruses. CD4+CD25+ T regulatory cells (Tregs), a subset of CD4+ T cells, expressed high levels of CD25 and the forkhead box transcription factor P3 (FoxP3), plays an important role in the down-regulation of various immune responses. Therefore, we hypothesized that in patients with HFRS the immunopathology could be, at least in part, the result of an inefficient control of pathogenic effector T cells by Tregs. The number of Tregs was determined by flow cytometry according to their characteristic CD4+CD25high membrane phenotype. The functional characterization of Tregs was analysed by suppression of proliferation and secretion of cytokines by co-cultured effector CD4+CD25- T cells. FoxP3 mRNA level was assessed by quantitative real-time polymerase chain reaction. We observed that CD4+CD25high cells of patients with HFRS showed a conventional phenotype. Furthermore, acute-stage patients with HFRS exhibited significantly reduced numbers of peripheral Tregs compared with healthy donors, and marked improvement was observed in convalescent-phase patients. The frequency of Tregs was correlated positively with platelet count, and was correlated negatively with blood urea nitrogen, serum creatinine and serum aspartate aminotransferase. On the other hand, Tregs from both healthy individuals and patients with HFRS exhibited equal FoxP3 expression of mRNA, and their ability to suppress the proliferation and cytokine secretion of CD4+ effector T cells was unimpaired in HFRS patients.
Accumulation of DNA damage in Antarctic mosses: correlations with ultraviolet‐B radiation, temperature and turf water content vary among species
Authors: TURNBULL JOHANNA D. , ROBINSON SHARON A. 
Published: December 2008

AbstractThe susceptibility of three East Antarctic moss species to UV‐B radiation was examined by measuring accumulation of cyclobutane pyrimidine dimers under natural sunlight during the austral summer season of 2002/03. The 2002/03 season was characterized by unusually low springtime ozone depletion and as such our results likely underestimate the DNA damage possible in a more typical UV‐B radiation season. Despite this all three species accumulated significant DNA photoproducts. We also found a positive association between photoproduct accumulation and incident UV‐B radiation in the two cosmopolitan species, Bryum pseudotriquetrum and Ceratodon purpureus, with more DNA damage in samples collected early in the season compared with later in the summer. For B. pseudotriquetrum, negative associations were also observed between photoproduct accumulation and both turf water content and the 10‐day mean air temperature. Photoproduct accumulation in the endemic species Schistidium antarctici was similarly high across the season and no significant association with environmental variables was found. Our results are consistent with the two cosmopolitan species having somewhat higher UV‐B‐screening capabilities and possibly more efficient mechanisms for repairing DNA damage than the endemic S. antarctici.
Quantitative aspects of heterogeneity in soil organic matter dynamics in a cool‐temperate Japanese beech forest: a radiocarbon‐based approach
Authors: KOARASHI JUN , ATARASHI‐ANDOH MARIKO , ISHIZUKA SHIGEHIRO , MIURA SATORU , SAITO TAKESHI , HIRAI KEIZO 
Published: December 2008

AbstractSoil is the largest carbon reservoir in terrestrial ecosystems; it stores twice as much carbon as the atmosphere. It is well documented that global warming can lead to accelerated microbial decomposition of soil organic carbon (SOC) and enhance the release of CO2 from the soil to the atmosphere; however, the magnitude and timing of this effect remain highly uncertain due to a lack of quantitative data concerning the heterogeneity of SOC biodegradability. Therefore, we sought to identify SOC pools with respect to their specific mean residence times (MRTs), to use those SOC pools to partition soil respiration sources, and to estimate the potential response of the pools to warming. We collected surface soil and litter samples from a cool‐temperate deciduous forest in Japan, chemically separated the samples into SOC fractions, estimated their MRTs based on radiocarbon (14C) isotope measurements, and used the data to construct a model representing the soil as a complex of six SOC pools with different MRT ranges. We estimate that a minor, fast‐cycling SOC pool with an MRT of less than 10 years (corresponding to the O horizon and recognizable plant leaf fragments in the A1 horizon) is responsible for 73% of annual heterotrophic respiration and 44% of total soil respiration. However, the predicted response of these pools to warming demonstrates that the rate of SOC loss from the fast‐cycling SOC pool diminishes quickly (within several decades) because of limited substrate availability. In contrast, warming will continue to accelerate SOC loss from slow‐cycling pools with MRTs of 20–200 years over the next century. Although using a 14C‐based approach has drawbacks, these estimates provide quantitative insights into the potential importance of slow‐cycling SOC dynamics for the prediction of positive feedback to climate change.