bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human T cells expressing affinity-matured TCR display accelerated responses but fail to recognize low density of MHC-peptide antigen
Authors: Thomas Sharyn , Xue Shao-An , Bangham Charles R. M. , Jakobsen Bent K. , Morris Emma C. , Stauss Hans J. 
Published: May 2011

AbstractWe have tested whether affinity-matured TCRs that retain peptide specificity improve the ability of primary human CD8+ T cells to mount antigen-specific responses. We found that TCR affinity correlated with the speed of T-cell responses. High affinity TCR–antigen interactions rapidly initiated T-cell responses, but low affinity TCR/antigen interactions required longer time periods to elicit the same responses. Within the “natural” affinity range, increased TCR-to-antigen affinity correlated with improved ability of T cells to recognize low concentration of antigen. However, affinity-matured TCR with 700-fold enhanced affinity for MHC-to-antigen required 100-fold higher antigen-density to initiate T-cell responses than did wild-type TCR. Using modified peptides to reduce the affinity of TCR-to-antigen interaction, we demonstrate that affinity-matured TCRs are not defective, being superior to wild-type TCR in recognizing low concentration of modified peptides. These data indicate that enhancing TCR affinity can accelerate the speed of T-cell activation and reduce the ability to recognize low density of MHC-to-peptide antigen. We predict that future studies of the human T-cell repertoire will reveal 2 types of low avidity T cells: fast and slow responders, with high-affinity and low-affinity TCR, respectively.
Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers
Authors: Papaioannou Andriana I , Loukides Stelios , Minas Markos , Kontogianni Konstantina , Bakakos Petros , Gourgoulianis Konstantinos I , Alchanatis Manos , Papiris Spyros , Kostikas Konstantinos 
Published: May 2011

Abstract
Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status.
EBC was collected from 161 patients with stable COPD and 112 controls (current and ex-smokers). EBC pH was measured after Argon deaeration and all subjects underwent pulmonary function testing.
EBC pH was lower in COPD patients compared to controls [7.21 (7.02, 7.44) vs. 7.50 (7.40, 7.66); p < 0.001] and ex-smokers with COPD had lower EBC pH compared to current smokers [7.16 (6.89, 7.36) vs 7.24 (7.09, 7.54), p = 0.03]. In ex-smokers with COPD, EBC pH was lower in patients with GOLD stage III and IV compared to patients with stage I disease (p = 0.026 and 0.004 respectively). No differences were observed among current smokers with different disease severity. EBC pH levels in ex-smokers were associated with static hyperinflation (as expressed by IC/TLC ratio), air trapping (as expressed by RV/TLC ratio) and diffusing capacity for carbon monoxide, whereas no associations were observed in current smokers.
Endogenous airway acidification is related to disease severity and to parameters expressing hyperinflation and air trapping in ex-smokers with COPD. The possible role of EBC pH in COPD needs to be further evaluated in longitudinal studies.
The biomedical discourse relation bank
Authors: Prasad Rashmi , McRoy Susan , Frid Nadya , Joshi Aravind , Yu Hong 
Published: May 2011

AbstractBackgroundIdentification of discourse relations, such as causal and contrastive relations, between situations mentioned in text is an important task for biomedical text-mining. A biomedical text corpus annotated with discourse relations would be very useful for developing and evaluating methods for biomedical discourse processing. However, little effort has been made to develop such an annotated resource.ResultsWe have developed the Biomedical Discourse Relation Bank (BioDRB), in which we have annotated explicit and implicit discourse relations in 24 open-access full-text biomedical articles from the GENIA corpus. Guidelines for the annotation were adapted from the Penn Discourse TreeBank (PDTB), which has discourse relations annotated over open-domain news articles. We introduced new conventions and modifications to the sense classification. We report reliable inter-annotator agreement of over 80% for all sub-tasks. Experiments for identifying the sense of explicit discourse connectives show the connective itself as a highly reliable indicator for coarse sense classification (accuracy 90.9% and F1 score 0.89). These results are comparable to results obtained with the same classifier on the PDTB data. With more refined sense classification, there is degradation in performance (accuracy 69.2% and F1 score 0.28), mainly due to sparsity in the data. The size of the corpus was found to be sufficient for identifying the sense of explicit connectives, with classifier performance stabilizing at about 1900 training instances. Finally, the classifier performs poorly when trained on PDTB and tested on BioDRB (accuracy 54.5% and F1 score 0.57).ConclusionOur work shows that discourse relations can be reliably annotated in biomedical text. Coarse sense disambiguation of explicit connectives can be done with high reliability by using just the connective as a feature, but more refined sense classification requires either richer features or more annotated data. The poor performance of a classifier trained in the open domain and tested in the biomedical domain suggests significant differences in the semantic usage of connectives across these domains, and provides robust evidence for a biomedical sublanguage for discourse and the need to develop a specialized biomedical discourse annotated corpus. The results of our cross-domain experiments are consistent with related work on identifying connectives in BioDRB.
Mapping the distribution of packing topologies within protein interiors shows predominant preference for specific packing motifs
Authors: Basu Sankar , Bhattacharyya Dhananjay , Banerjee Rahul 
Published: May 2011

Abstract

Background
Mapping protein primary sequences to their three dimensional folds referred to as the 'second genetic code' remains an unsolved scientific problem. A crucial part of the problem concerns the geometrical specificity in side chain association leading to densely packed protein cores, a hallmark of correctly folded native structures. Thus, any model of packing within proteins should constitute an indispensable component of protein folding and design.

Results
In this study an attempt has been made to find, characterize and classify recurring patterns in the packing of side chain atoms within a protein which sustains its native fold. The interaction of side chain atoms within the protein core has been represented as a contact network based on the surface complementarity and overlap between associating side chain surfaces. Some network topologies definitely appear to be preferred and they have been termed 'packing motifs', analogous to super secondary structures in proteins. Study of the distribution of these motifs reveals the ubiquitous presence of typical smaller graphs, which appear to get linked or coalesce to give larger graphs, reminiscent of the nucleation-condensation model in protein folding. One such frequently occurring motif, also envisaged as the unit of clustering, the three residue clique was invariably found in regions of dense packing. Finally, topological measures based on surface contact networks appeared to be effective in discriminating sequences native to a specific fold amongst a set of decoys.

Conclusions
Out of innumerable topological possibilities, only a finite number of specific packing motifs are actually realized in proteins. This small number of motifs could serve as a basis set in the construction of larger networks. Of these, the triplet clique exhibits distinct preference both in terms of composition and geometry.
GiSAO.db: a database for ageing research
Authors: Hofer Edith , Laschober Gerhard T , Hackl Matthias , Thallinger Gerhard G , Lepperdinger Günter , Grillari Johannes , Jansen-Dürr Pidder , Trajanoski Zlatko 
Published: May 2011

Abstract

Background
Age-related gene expression patterns of Homo sapiens as well as of model organisms such as Mus musculus, Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster are a basis for understanding the genetic mechanisms of ageing. For an effective analysis and interpretation of expression profiles it is necessary to store and manage huge amounts of data in an organized way, so that these data can be accessed and processed easily.

Description
GiSAO.db (Genes involved in senescence, apoptosis and oxidative stress database) is a web-based database system for storing and retrieving ageing-related experimental data. Expression data of genes and miRNAs, annotation data like gene identifiers and GO terms, orthologs data and data of follow-up experiments are stored in the database. A user-friendly web application provides access to the stored data. KEGG pathways were incorporated and links to external databases augment the information in GiSAO.db. Search functions facilitate retrieval of data which can also be exported for further processing.

Conclusions
We have developed a centralized database that is very well suited for the management of data for ageing research. The database can be accessed at https://gisao.genome.tugraz.at and all the stored data can be viewed with a guest account.
Transcriptomic assessment of resistance to effects of an aryl hydrocarbon receptor (AHR) agonist in embryos of Atlantic killifish (Fundulus heteroclitus) from a marine Superfund site
Authors: Oleksiak Marjorie F , Karchner Sibel I , Jenny Matthew J , Franks Diana G , Mark Welch David B , Hahn Mark E 
Published: May 2011

Abstract

Background
Populations of Atlantic killifish (Fundulus heteroclitus) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway. The resistance is accompanied by reduced sensitivity to induction of cytochrome P450 1A (CYP1A), a widely used biomarker of aromatic hydrocarbon exposure and effect, but whether the reduced sensitivity is specific to CYP1A or reflects a genome-wide reduction in responsiveness to all AHR-mediated changes in gene expression is unknown. We compared gene expression profiles and the response to 3,3',4,4',5-pentachlorobiphenyl (PCB-126) exposure in embryos (5 and 10 dpf) and larvae (15 dpf) from F. heteroclitus populations inhabiting the New Bedford Harbor, Massachusetts (NBH) Superfund site (PCB-resistant) and a reference site, Scorton Creek, Massachusetts (SC; PCB-sensitive).

Results
Analysis using a 7,000-gene cDNA array revealed striking differences in responsiveness to PCB-126 between the populations; the differences occur at all three stages examined. There was a sizeable set of PCB-responsive genes in the sensitive SC population, a much smaller set of PCB-responsive genes in NBH fish, and few similarities in PCB-responsive genes between the two populations. Most of the array results were confirmed, and additional PCB-regulated genes identified, by RNA-Seq (deep pyrosequencing).

Conclusions
The results suggest that NBH fish possess a gene regulatory defect that is not specific to one target gene such as CYP1A but rather lies in a regulatory pathway that controls the transcriptional response of multiple genes to PCB exposure. The results are consistent with genome-wide disruption of AHR-dependent signaling in NBH fish.
Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus
Authors: Dean Scott N , Bishop Barney M , van Hoek Monique L 
Published: May 2011

AbstractBackgroundChronic, infected wounds typically contain multiple genera of bacteria, includingStaphylococcus aureus, many of which are strong biofilm formers. Bacterial biofilms are thought to be a direct impediment to wound healing. New therapies that focus on a biofilm approach may improve the recovery and healing rate for infected wounds. In this study, cathelicidins and related short, synthetic peptides were tested for their anti-microbial effectiveness as well as their ability to inhibit the ability ofS. aureusto form biofilms.ResultsThe helical human cathelicidin LL-37 was tested againstS. aureus, and was found to exhibit effective anti-microbial, anti-attachment as well as anti-biofilm activity at concentrations in the low μg/ml range. The effect of peptide chirality and associated protease-resistance was explored through the use of an all-D amino acid peptide, D-LL-37, and in turn compared to scrambled LL-37. Helical cathelicidins have been identified in other animals such as the Chinese cobra,Naja atra(NA-CATH). We previously identified an 11-residue imperfectly repeated pattern (ATRA motif) within the sequence of NA-CATH. A series of short peptides (ATRA-1, -2, -1A), as well as a synthetic peptide, NA-CATH:ATRA1-ATRA1, were designed to explore the significance of the conserved residues within the ATRA motif for anti-microbial activity. The CD spectrum of NA-CATH and NA-CATH:ATRA1-ATRA1 revealed the structural properties of these peptides and suggested that helicity may factor into their anti-microbial and anti-biofilm activities.ConclusionsThe NA-CATH:ATRA1-ATRA1 peptide inhibits the production of biofilm byS. aureusin the presence of salt, exhibiting anti-biofilm activity at lower peptide concentrations than NA-CATH, LL-37 and D-LL-37; and demonstrates low cytoxicity against host cells but does not affect bacterial attachment. The peptides utilized in this anti-biofilm approach may provide templates for a new group of anti-microbials and potential future topical therapeutics for treating chronic wound infections.
Functional characterization of the ER stress induced X-box-binding protein-1 (Xbp-1) in the porcine system
Authors: Zhang Jin-Yu , Lee Kyu-Sun , Kim Ji-Su , Song Bong-Seok , Jin Dong-Il , Koo Deog-Bon , Yu Kweon 
Published: May 2011

AbstractBackgroundThe unfolded protein response (UPR) is an evolutionary conserved adaptive reaction for increasing cell survival under endoplasmic reticulum (ER) stress conditions. X-box-binding protein-1 (Xbp1) is a key transcription factor of UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The UPR induced by ER stress was extensively studied in diseases linked to protein misfolding and aggregations. However, in the porcine system, genes in the UPR pathway were not investigated. In this study, we isolated and characterized the porcineXbp1(pXbp1) gene in ER stress using porcine embryonic fibroblast (PEF) cells and porcine organs. ER stress was induced by the treatment of tunicamycin and cell viability was investigated by the MTT assay. For cloning and analyzing the expression pattern ofpXbp1, RT-PCR analysis and Western blot were used. Knock-down ofpXbp1was performed by the siRNA-mediated gene silencing.ResultsWe found that thepXbp1mRNA was the subject of the IRE1α-mediated unconventional splicing by ER stress. Knock-down ofpXbp1enhanced ER stress-mediated cell death in PEF cells. In adult organs,pXbp1mRNA and protein were expressed and the spliced forms were detected.ConclusionsIt was first found that the UPR mechanisms and the function of pXbp1 in the porcine system. These results indicate that pXbp1 plays an important role during the ER stress response like other animal systems and open a new opportunity for examining the UPR pathway in the porcine model system.
Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial)
Authors: Brevoord Daniel , Hollmann Markus W , De Hert Stefan G , van Dongen Eric HPA , Heijnen Bram GADH , de Bruin Anton , Tolenaar Noortje , Schlack Wolfgang S , Weber Nina C , Dijkgraaf Marcel GW , de Groot Joris R , de Mol Bas AJM , Driessen Antoine HG , Momeni Mona , Wouters Patrick , Bouchez Stefaan , Hofland Jan , Lüthen Christan , Meijer-Treschan Tanja A , Pannen Benedikt H , Preckel Benedikt 
Published: May 2011

Abstract

Background
Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome.

Methods/design
This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year.
Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%.

Discussion
The RICO-trial (the effect of Remote Ischemic Conditioning on atrial fibrillation and Outcome) is a randomized controlled multicenter trial, designed to investigate whether remote ischemic pre- and/or post-conditioning of the arm reduce the incidence of AF following CABG surgery.

Trial registration
ClinicalTrials.gov under NCT01107184.
To screen or not to screen for peripheral arterial disease in subjects aged 80 and over in primary health care: a cross-sectional analysis from the BELFRAIL study
Authors: Bergiers Stein , Vaes Bert , Degryse Jan 
Published: May 2011

Abstract

Background
Peripheral arterial disease (PAD) is common in older people. An ankle-brachial index (ABI) < 0.9 can be used as an indicator of PAD. Patients with low ABI have increased mortality and a higher risk of serious cardiovascular morbidity. However, because 80% of the patients are asymptomatic, PAD remains unrecognised in a large group of patients. The aims of this study were 1) to examine the prevalence of reduced ABI in subjects aged 80 and over, 2) to determine the diagnostic accuracy of the medical history and clinical examination for reduced ABI and 3) to investigate the difference in functioning and physical activity between patients with and without reduced ABI.

Methods
A cross-sectional study embedded within the BELFRAIL study. A general practitioner (GP) centre, located in Hoeilaart, Belgium, recruited 239 patients aged 80 or older. Only three criteria for exclusion were used: urgent medical need, palliative situation and known serious dementia. The GP recorded the medical history and performed a clinical examination. The clinical research assistant performed an extensive examination including Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Activities of Daily Living (ADL), Tinetti test and the LASA Physical Activity Questionnaire (LAPAQ). ABI was measured using an automatic oscillometric appliance.

Results
In 40% of patients, a reduced ABI was found. Cardiovascular risk factors were unable to identify patients with low ABI. A negative correlation was found between the number of cardiovascular morbidities and ABI. Cardiovascular morbidity had a sensitivity of 65.7% (95% CI 53.4-76.7) and a specificity of 48.6% (95% CI 38.7-58.5). Palpation of the peripheral arteries showed the highest negative predictive value (77.7% (95% CI 71.8-82.9)). The LAPAQ score was significantly lower in the group with reduced ABI.

Conclusion
The prevalence of PAD is very high in patients aged 80 and over in general practice. The clinical examination, cardiovascular risk factors and the presence of cardiovascular morbidity were not able to identify patients with a low ABI. A screening strategy for PAD by determining ABI could be considered if effective interventions for those aged 80 and over with a low ABI become available through future research.
Seroprevalence of transfusion-transmissible infections and evaluation of the pre-donation screening performance at the Provincial Hospital of Tete, Mozambique
Authors: Stokx Jocelijn , Gillet Philippe , De Weggheleire Anja , Casas Esther C , Maendaenda Rosa , Beulane Adelino J , Jani Ilhes V , Kidane Solon , Mosse Carla D , Jacobs Jan , Bottieau Emmanuel 
Published: May 2011

AbstractBackgroundThe World Health Organization recommends universal and quality-controlled screening of blood donations for the major transfusion-transmissible infections (TTIs): human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis. The study objectives were to determine the seroprevalence of these TTIs among blood donors at the Provincial Hospital of Tete, Mozambique, and to assess the local pre-donation screening performance.MethodsAll consenting voluntary and replacement candidate blood donors were consecutively included from February to May 2009. Sera of all candidates, independent of deferral by questionnaire, were submitted to screening with quality-assured rapid or simple assays for HIV, HBV surface antigen (HBsAg), HCV and syphilis. Assays locally used by the blood bank for HBV and syphilis screening were run in parallel to quality-assured external assays supplied during the study, and all discordant samples were submitted to confirmation testing in reference laboratories in Mozambique and Belgium.ResultsOf 750 consenting candidates (50.5% of voluntary donors), 71 (9.5%) were deferred by the questionnaire, including 38 specifically because of risk behavior for TTI. Of the 679 non-deferred candidates, 127 (18.7%) had serological confirmation of at least one TTI, with a lower prevalence in voluntary than in replacement donors (15.2% versus 22.4%, p = 0.016). Seroprevalence of HIV, HBsAg and syphilis infections was 8.5%, 10.6 % and 1.2%. No confirmed HCV infection was found. Seroprevalence of TTIs was similar in the 38 candidates deferred for TTI risk as in the non-deferred group, except for HBsAg (26.3 % versus 10.6 %; p = 0.005). The local assays used for HBV and syphilis had sensitivities of 98.4% and 100% and specificities of 80.4% and 98.8% respectively. This resulted in the rejection of 110 of the 679 blood donations (16.2%) because of false positive results.ConclusionsThe seroprevalence of TTIs after questionnaire screening is high in Tete, Mozambique, but HCV infection does not appear as a major issue. The questionnaire did not exclude effectively HIV-infected donor candidates, while the locally used assays led to unnecessary rejection of many safe donations. A contextualized questionnaire and consistent use of quality-assured assays would considerably improve the current screening procedure for blood donation.