bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID
Authors: Sauer Aisha V. , Brigida Immacolata , Carriglio Nicola , Jofra Hernandez Raisa , Scaramuzza Samantha , Clavenna Daniela , Sanvito Francesca , Poliani Pietro L. , Gagliani Nicola , Carlucci Filippo , Tabucchi Antonella , Roncarolo Maria Grazia , Traggiai Elisabetta , Villa Anna , Aiuti Alessandro 
Published: December 2011

AbstractAdenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)–mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA–treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA−/− Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA–treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA–treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID. Trials were registered at www.clinicaltrials.gov as NCT00598481/NCT00599781.
The acute effect of budesonide/formoterol in COPD: a multi-slice computed tomography and lung function study
Authors: De Backer Lieve A. , Vos Wim , De Backer Jan , Van Holsbeke Cedric , Vinchurkar Samir , De Backer Wilfried 
Published: December 2011

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of chronic obstructive pulmonary disease (COPD) does not always match with other clinical disease descriptors such as exacerbation frequency and quality of life, indicating that forced expiratory volume in 1 s (FEV1) is not a perfect descriptor of the disease. The aim of this study was to find out whether changes in airway geometry after inhalation of the most commonly used inhalation therapy in severe COPD can more adequately be described with an image-based approach than with spirometry.10 COPD GOLD stage III patients were assessed in a double-blind crossover study. Airway volumes were analysed using segmentation of multi-slice computed tomography (MSCT) images; airway resistance was determined using computational fluid dynamics (CFD).Distal airway volume significantly increased (p=0.011) in patients 4 h after receiving a budesonide/formoterol combination from 9.6±4.67 cm3to 10.14±4.81 cm3. Also CFD-determined airway resistance significantly decreased (p=0.047) from 0.051±0.021 kPa·s·L−1to 0.043±0.019 kPa·s·L−1. None of the lung function parameters showed a significant change. Only functional residual capacity (FRC) showed a trend to decline (p=0.056). Only the image-based parameters were able to predict the visit at which the combination product was administered.This study showed that imaging is a sensitive, complementary tool to describe changes in airway structure.
Metabolic profiling detects biomarkers of protein degradation in COPD patients
Authors: Ubhi Baljit K. , Riley John H. , Shaw Paul A. , Lomas David A. , Tal-Singer Ruth , MacNee William , Griffin Julian L. , Connor Susan C. 
Published: December 2011

There is a paucity of biomarkers for chronic obstructive pulmonary disease (COPD). Metabolomics were applied to a defined COPD patient cohort from the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points). Results were correlated with accepted biomarkers for the disease.Baseline control serum (n=66) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II (n=70), III (n=64) and IV (n=44) COPD patients were analysed by proton nuclear magnetic resonance (1H NMR). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to confirm amino acid changes detected by1H NMR. Data were correlated with body composition, emphysema and systemic inflammation.1H NMR identified decreased lipoproteins,N,N-dimethylglycine, and increased glutamine, phenylalanine, 3-methylhistidine and ketone bodies in COPD patients with decreased branched-chain amino acids (BCAAs) observed in GOLD stage IV patients. BCAAs, their degradation products, 3-methylhistidine, ketone bodies, and triglycerides were correlated negatively with cachexia and positively with systemic inflammation. Emphysema patients also displayed decreased serum creatine, glycine andN,N-dimethylglycine. LC-MS/MS confirmed1H NMR findings relating to BCAAs, glutamine and 3-methylhistidine in GOLD stage IV patients.NMR-based metabolomics characterised COPD patients based on systemic effects and lung function parameters. Increased protein turnover occurred in all COPD patients with increased protein degradation in individuals with emphysema and cachexia.
Validation of the English Severe Respiratory Insufficiency Questionnaire
Authors: Ghosh Dipansu , Rzehak Peter , Elliott Mark W. , Windisch Wolfram 
Published: December 2011

Assessment of health-related quality of life in patients with respiratory failure on home ventilation requires appropriate and highly specific measurement tools. We attempt to validate the English version of the Severe Respiratory Insufficiency Questionnaire (SRI).Psychometric properties of the SRI in 152 patients established on home ventilation were assessed.Cronbach’s alpha ranged between 0.77 and 0.89 for the seven subscales and and was 0.93 for the summary scale. Principal components analysis revealed a one-factor solution for four and two factors for three subscales. Confirmatory factor analysis revealed a two-factor solution for six subscales, but these factors were dependent on each other. One factor was extracted out of the subscales confirming one summary scale accounting for 70% of the total variance. Correlation analysis between scales of the SRI and the Medical Outcome Study 36-item short-form health survey demonstrated highest correlations between comparable subscales. Chronic obstructive pulmonary disease patients had lower summary scale scores than patients with restrictive chest wall diseases, neuromuscular disorders and obesity hypoventilation syndrome.The English SRI has high internal consistency reliability, clearly established construct and concurrent validity, and is capable of differentiating between different diseases. It is now validated for use in research involving patients receiving home ventilation.
Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD?
Authors: Guenette Jordan A. , Webb Katherine A. , O’Donnell Denis E. 
Published: December 2011

Dynamic hyperinflation (DH) during exercise occurs in most but not all patients with advanced chronic obstructive pulmonary disease (COPD). It is not known whether the presence or absence of DH has implications for dyspnoea and exercise tolerance. Therefore, we compared detailed ventilatory and sensory responses to exercise in hyperinflators and nonhyperinflators with moderate-to-severe COPD.Nonhyperinflators (n=65) were retrospectively identified from a sample of 427 patients and case-matched to a group of hyperinflators (n=65) based on sex, age, body mass index and % predicted forced expiratory volume in 1 s. Resting pulmonary function and constant work rate cycle exercise responses were compared.Hyperinflators decreased inspiratory capacity (IC) from rest to peak exercise by 0.46±0.24 L whereas the nonhyperinflators increased IC by 0.10±0.15 L (p<0.0001). There were no significant group differences in endurance time (9.11±5.98versus8.87±5.24 min) or dyspnoea intensity for any given time or ventilation. An inflection in tidal volumeversusventilation occurred in the majority of nonhyperinflators (n=61) and hyperinflators (n=62) at a similar time and ventilation. Mechanical constraints on tidal volume expansion and the attendant rise in dyspnoea intensity were similar in both groups.Dyspnoea intensity during exercise was associated with progressive mechanical constraints on tidal volume expansion regardless of the presence of DH.
Fuzzy Hyers-Ulam stability of an additive functional equation
Authors: Kenary Hassan Azadi , Rezaei Hamid , Ghaffaripour Anoshiravan , Talebzadeh Saedeh , Park Choonkil , Lee Jung Rye 
Published: December 2011

Abstract
In this paper, using the fixed point and direct methods, we prove the Hyers-Ulam stability of the following additive functional equation

2
f

x
+
y
+
z

2

=
f

x

+
f

y

+
f

z

in fuzzy normed spaces.

Mathematics Subject Classification (2010): 39B22; 39B52; 39B82; 46S10; 47S10; 46S40.
Vaccination of influenza a virus decreases transmission rates in pigs
Authors: Romagosa Anna , Allerson Matt , Gramer Marie , Joo Han Soo , Deen John , Detmer Susan , Torremorell Montserrat 
Published: December 2011

AbstractLimited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R) of infection (i.e. the number of secondary infections caused by an infectious individual) using a deterministic Susceptible-Infectious-Recovered (SIR) model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i) non-vaccinated (NV), (ii) vaccinated with a heterologous vaccine (HE), and (iii) vaccinated with a homologous inactivated vaccine (HO). The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference betweenRestimates was observed between vaccinated and non-vaccinated pigs (p< 0.05). A statistically significant reduction in transmission was observed in the vaccinated groups whereR(95%CI) was 1 (0.39-2.09) and 0 for the HE and the HO groups respectively, compared to anRovalue of 10.66 (6.57-16.46) in NV pigs (p< 0.05). Transmission in the HE group was delayed and variable when compared to the NV group and transmission could not be detected in the HO group. Results from this study indicate that influenza vaccines can be used to decrease susceptibility to influenza infection and decrease influenza transmission.
Morphometic analysis of TCGA glioblastoma multiforme
Authors: Chang Hang , Fontenay Gerald V , Han Ju , Cong Ge , Baehner Frederick L , Gray Joe W , Spellman Paul T , Parvin Bahram 
Published: December 2011

AbstractBackgroundOur goals are to develop a computational histopathology pipeline for characterizing tumor types that are being generated by The Cancer Genome Atlas (TCGA) for genomic association. TCGA is a national collaborative program where different tumor types are being collected, and each tumor is being characterized using a variety of genome-wide platforms. Here, we have developed a tumor-centric analytical pipeline to process tissue sections stained with hematoxylin and eosin (H&E) for visualization and cell-by-cell quantitative analysis. Thus far, analysis is limited to Glioblastoma Multiforme (GBM) and kidney renal clear cell carcinoma tissue sections. The final results are being distributed for subtyping and linking the histology sections to the genomic data.ResultsA computational pipeline has been designed to continuously update a local image database, with limited clinical information, from an NIH repository. Each image is partitioned into blocks, where each cell in the block is characterized through a multidimensional representation (e.g., nuclear size, cellularity). A subset of morphometric indices, representing potential underlying biological processes, can then be selected for subtyping and genomic association. Simultaneously, these subtypes can also be predictive of the outcome as a result of clinical treatments. Using the cellularity index and nuclear size, the computational pipeline has revealed five subtypes, and one subtype, corresponding to the extreme high cellularity, has shown to be a predictor of survival as a result of a more aggressive therapeutic regime. Further association of this subtype with the corresponding gene expression data has identified enrichment of (i) the immune response and AP-1 signaling pathways, and (ii) IFNG, TGFB1, PKC, Cytokine, and MAPK14 hubs.ConclusionWhile subtyping is often performed with genome-wide molecular data, we have shown that it can also be applied to categorizing histology sections. Accordingly, we have identified a subtype that is a predictor of the outcome as a result of a therapeutic regime. Computed representation has become publicly available through our Web site.
Retinoic acid is a key regulatory switch determining the difference between lung and thyroid fates in Xenopus laevis
Authors: Wang Jean H , Deimling Steven J , D'Alessandro Nicole E , Zhao Lin , Possmayer Fred , Drysdale Thomas A 
Published: December 2011

Abstract

Background
The lung and thyroid are derived from the anterior endoderm. Retinoic acid and Fgf signalling are known to be essential for development of the lung in mouse but little is known on how the lung and thyroid are specified in Xenopus.

Results
If either retinoic acid or Fgf signalling is inhibited, there is no differentiation of the lung as assayed by expression of sftpb. There is no change in expression of thyroid gland markers when retinoic acid signalling is blocked after gastrulation and when Fgf signalling is inhibited there is a short window of time where pax2 expression is inhibited but expression of other markers is unaffected. If exogenous retinoic acid is given to the embryo between embryonic stages 20 and 26, the presumptive thyroid expresses sftpb and sftpc, specific markers of lung differentiation and expression of key thyroid transcription factors is lost. When the presumptive thyroid is transplanted into the posterior embryo, it also expresses sftpb, although pax2 expression is not blocked.

Conclusions
After gastrulation, retinoic acid is required for lung but not thyroid differentiation in Xenopus while Fgf signalling is needed for lung but only for early expression of pax2 in the thyroid. Exposure to retinoic acid can cause the presumptive thyroid to switch to a lung developmental program.
Mechanisms of intron gain and loss in Drosophila
Authors: Yenerall Paul , Krupa Bradlee , Zhou Leming 
Published: December 2011

Abstract

Background
It is widely accepted that orthologous genes have lost or gained introns throughout evolution. However, the specific mechanisms that generate these changes have proved elusive. Introns are known to affect nearly every level of gene expression. Therefore, understanding their mechanism of evolution after their initial fixation in eukaryotes is pertinent to understanding the means by which organisms develop greater regulation and complexity.

Results
To investigate possible mechanisms of intron gain and loss, we identified 189 intron gain and 297 intron loss events among 11 Drosophila species. We then investigated these events for signatures of previously proposed mechanisms of intron gain and loss. This work constitutes the first comprehensive study into the specific mechanisms that may generate intron gains and losses in Drosophila. We report evidence of intron gain via transposon insertion; the first intron loss that may have occurred via non-homologous end joining; intron gains via the repair of a double strand break; evidence of intron sliding; and evidence that internal or 5' introns may not frequently be deleted via the self-priming of reverse transcription during mRNA-mediated intron loss. Our data also suggest that the transcription process may promote or result in intron gain.

Conclusion
Our findings support the occurrence of intron gain via transposon insertion, repair of double strand breaks, as well as intron loss via non-homologous end joining. Furthermore, our data suggest that intron gain may be enabled by or due to transcription, and we shed further light on the exact mechanism of mRNA-mediated intron loss.
Interspecific variation of calls in clownfishes: degree of similarity in closely related species
Authors: Colleye Orphal , Vandewalle Pierre , Lanterbecq Déborah , Lecchini David , Parmentier Eric 
Published: December 2011

Abstract

Background
Clownfishes are colorful coral reef fishes living in groups in association with sea anemones throughout the Indo-Pacific Ocean. Within their small societies, size hierarchy determines which fish have access to reproduction. These fishes are also prolific callers whose aggressive sounds seem to play an important role in the social hierarchy. Agonistic interactions being involved in daily behaviour suggest how acoustic communication might play an important role in clownfish group. Sounds were recorded and compared in fourteen clownfish species (some of which have never been recorded before) to evaluate the potential role of acoustic communication as an evolutionary driving force.

Results
Surprisingly, the relationship between fish size and both dominant frequency and pulse duration is not only species-specific; all the specimens of the 14 species are situated on exactly the same slope, which means the size of any Amphiprion can be predicted by both acoustic features. The number of pulses broadly overlaps among species, whereas the pulse period displays the most variation even if it shows overlap among sympatric species. Sound comparisons between three species (A. akallopisos, A. ocellaris and A. frenatus) having different types of teeth and body shape do not show differences neither in the acoustic waveform nor in the power spectrum.

Conclusion
Significant overlap in acoustic features demonstrates that the sound-producing mechanism is highly conservative among species. Differences in the calls of some species are due to size dimorphism and the sound variation might be in this case a by-product. This morphological constraint does not permit a consideration of acoustic communication as the main driving force in the diversification of clownfishes. Moreover, calls are not produced to find mate and consequently are less subject to variations due to partner preference, which restricts the constraints of diversification. Calls are produced to reach and defend the competition to mate access. However, differences in the pulse period between cohabiting species show that, in some case, sounds can help to differentiate the species, to prevent competition between cohabiting species and to promote the diversification of taxa.
Detecting the symplesiomorphy trap: a multigene phylogenetic analysis of terebelliform annelids
Authors: Zhong Min , Hansen Benjamin , Nesnidal Maximilian , Golombek Anja , Halanych Kenneth M , Struck Torsten H 
Published: December 2011

AbstractBackgroundFor phylogenetic reconstructions, conflict in signal is a potential problem for tree reconstruction. For instance, molecular data from different cellular components, such as the mitochondrion and nucleus, may be inconsistent with each other. Mammalian studies provide one such case of conflict where mitochondrial data, which display compositional biases, support the Marsupionta hypothesis, but nuclear data confirm the Theria hypothesis. Most observations of compositional biases in tree reconstruction have focused on lineages with different composition than the majority of the lineages under analysis. However in some situations, the position of taxa that lack compositional bias may be influenced rather than the position of taxa that possess compositional bias. This situation is due to apparent symplesiomorphic characters and known as "the symplesiomorphy trap".ResultsHerein, we report an example of the sympleisomorphy trap and how to detect it. Worms within Terebelliformia (sensu Rouse & Pleijel 2001) are mainly tube-dwelling annelids comprising five 'families': Alvinellidae, Ampharetidae, Terebellidae, Trichobranchidae and Pectinariidae. Using mitochondrial genomic data, as well as data from the nuclear 18S, 28S rDNA and elongation factor-1α genes, we revealed incongruence between mitochondrial and nuclear data regarding the placement of Trichobranchidae. Mitochondrial data favored a sister relationship between Terebellidae and Trichobranchidae, but nuclear data placed Trichobranchidae as sister to an Ampharetidae/Alvinellidae clade. Both positions have been proposed based on morphological data.ConclusionsOur investigation revealed that mitochondrial data of Ampharetidae and Alvinellidae exhibited strong compositional biases. However, these biases resulted in a misplacement of Trichobranchidae, rather than Alvinellidae and Ampharetidae. Herein, we document that Trichobranchidae was apparently caught in the symplesiomorphy trap suggesting that in certain situations even homologies can be misleading.
Expression QTL mapping in regulatory and helper T cells from the BXD family of strains reveals novel cell-specific genes, gene-gene interactions and candidate genes for auto-immune disease
Authors: Alberts Rudi , Chen Hairong , Pommerenke Claudia , Smit August B , Spijker Sabine , Williams Robert W , Geffers Robert , Bruder Dunja , Schughart Klaus 
Published: December 2011

AbstractBackgroundRegulatory T cells (Tregs) play an essential role in the control of the immune response. Treg cells represent important targets for therapeutic interventions of the immune system. Therefore, it will be very important to understand in more detail which genes are specifically activated in Treg cells versus T helper (Th) cells, and which gene regulatory circuits may be involved in specifying and maintaining Treg cell homeostasis.ResultsWe isolated Treg and Th cells from a genetically diverse family of 31 BXD type recombinant inbred strains and the fully inbred parental strains of this family--C57BL/6J and DBA/2J. Subsequently genome-wide gene expression studies were performed from the isolated Treg and Th cells. A comparative analysis of the transcriptomes of these cell populations allowed us to identify many novel differentially expressed genes. Analysis of cis- and trans-expression Quantitative Trait Loci (eQTLs) highlighted common and unique regulatory mechanisms that are active in the two cell types. Trans-eQTL regions were found for the Treg functional genesNrp1, Stat3andIkzf4. Analyses of the respective QTL intervals suggested several candidate genes that may be involved in regulating these genes in Treg cells. Similarly, possible candidate genes were found which may regulate the expression ofF2rl1, Ctla4, Klrb1f. In addition, we identified a focused group of candidate genes that may be important for the maintenance of self-tolerance and the prevention of allergy.ConclusionsVariation of expression across the strains allowed us to find many novel gene-interaction networks in both T cell subsets. In addition, these two data sets enabled us to identify many differentially expressed genes and to nominate candidate genes that may have important functions for the maintenance of self-tolerance and the prevention of allergy.