bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis
Authors: Jobe Shawn M. , Wilson Katina M. , Leo Lorie , Raimondi Alejandro , Molkentin Jeffery D. , Lentz Steven R. , Di Paola Jorge 
Published: November 2007

Abstract
Many of the cellular responses that occur in activated platelets resemble events that take place following activation of cell-death pathways in nucleated cells. We tested the hypothesis that formation of the mitochondrial permeability transition pore (MPTP), a key signaling event during cell death, also plays a critical role in platelet activation. Stimulation of murine platelets with thrombin plus the glycoprotein VI agonist convulxin resulted in a rapid loss of mitochondrial transmembrane potential (Δψm) in a subpopulation of activated platelets. In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine platelet activation responses were altered. CypD-deficient platelets exhibited defects in phosphatidylserine externalization, high-level surface fibrinogen retention, membrane vesiculation, and procoagulant activity. Also, in CypD-deficient platelet-rich plasma, clot retraction was altered. Stimulation with thrombin plus H2O2, a known activator of MPTP formation, also increased high-level surface fibrinogen retention, phosphatidylserine externalization, and platelet procoagulant activity in a CypD-dependent manner. In a model of carotid artery photochemical injury, thrombosis was markedly accelerated in CypD-deficient mice. These results implicate CypD and the MPTP as critical regulators of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating arterial thrombosis.
Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia
Authors: Kosaka Yoshiyuki , Yagasaki Hiroshi , Sano Kimihiko , Kobayashi Ryoji , Ayukawa Hiroshi , Kaneko Takashi , Yabe Hiromasa , Tsuchida Masahiro , Mugishima Hideo , Ohara Akira , Morimoto Akira , Otsuka Yoshitoshi , Ohga Shouichi , Bessho Fumio , Nakahata Tatsutoshi , Tsukimoto Ichiro , Kojima Seiji 
Published: November 2007

Abstract
We conducted a prospective multicenter study to compare the efficacy of repeated immunosuppressive therapy (IST) with stem-cell transplantation (SCT) from an alternative donor in children with acquired aplastic anemia (AA) who failed to respond to an initial course of IST. Patients with severe (n = 86) and very severe disease (n = 119) received initial IST consisting of antithymocyte globulin (ATG) and cyclosporine. Sixty patients failed to respond to IST after 6 months from the initial IST and were eligible for second-line treatment. Among them, 21 patients lacking suitable donors received a second course of IST. Three patients developed an anaphylactoid reaction to ATG and could not complete the second IST. A trilineage response was seen in only 2 of 18 (11%) evaluable patients after 6 months. Thirty-one patients received SCT from an alternative donor. At 5 years from the initiation of second-line therapy, the estimated failure-free survival (FFS), defined as survival with response, was 83.9% (± 16.1%, SD) in the SCT group compared with 9.5% (± 9.0%) in the IST group (P = .001). These results suggest that SCT from an alternative donor offers a better chance of FFS than a second IST in patients not responding to an initial IST.
The Modifier of hemostasis (Mh) locus on chromosome 4 controls in vivo hemostasis of Gp6−/− mice
Authors: Cheli Yann , Jensen Deborah , Marchese Patrizia , Habart David , Wiltshire Tim , Cooke Michael , Fernandez José A. , Ware Jerry , Ruggeri Zaverio M. , Kunicki Thomas J. 
Published: November 2007

Abstract
Platelet glycoprotein VI (GPVI) is a key receptor for collagens that mediates the propagation of platelet attachment and activation. Targeted disruption of the murine gene Gp6 on a mixed 129 × 1/SvJ × C57BL/6J background causes the expected defects in collagen-dependent platelet responses in vitro. The extent of this dysfunction in all Gp6−/− mice is uniform and is not affected by genetic background. However, the same Gp6−/− mice exhibit 2 diametrically opposed phenotypes in vivo. In some mice, tail bleeding times are extremely prolonged, and thrombus formation in an in vivo carotid artery ferric chloride-injury model is significantly impaired. In other littermates, tail bleeding times are within the range of wild-type mice, and in vivo thrombus formation is indistinguishable from that of control mice. Directed intercrosses revealed that these phenotypes are heritable, and a genome-wide single-nucleotide polymorphism scan revealed the most significant linkage to a single locus (8 megabases) on chromosome 4 (logarithm of the odds [LOD] score = 6.9, P < .0001) that we designate Modifier of hemostasis (Mh). Our results indicate that one or more modifier genes in Mh control the extent to which in vivo platelet thrombus formation is disrupted by the absence of platelet GPVI.
COPD patients' ability to follow exercise influences short-term outcomes of rehabilitation
Authors: Puhan M. A. , Schünemann H. J. , Buesching G. , vanOort E. , Spaar A. , Frey M. 
Published: November 2007

Chronic obstructive pulmonary disease (COPD) patients with limited ability to follow exercise protocols may receive smaller benefits from rehabilitation. The association between the ability to follow exercise protocols and short-term outcomes of rehabilitation was assessed in COPD patients.As a measure of the ability to follow exercise protocols, the number of major breaks lasting ≥1 min was determined in 98 COPD patients during supervised exercise sessions. The benefits from rehabilitation were compared between patients with, on average, more than one and one or fewer major breaks per session.Patients with one or fewer major breaks per session showed significantly greater improvements in exercise capacity (between-groups difference of 38 m for 6-min walking distance, 22.1 W for short-time maximum exercise capacity (steep ramp test) and 5.5 W for maximum exercise capacity). Quality of life also tended to be better in patients with one or fewer major breaks per session, but the differences were nonsignificant (adjusted between-groups difference in Chronic Respiratory Disease Questionnaire total score of 0.14).Limited ability to follow exercise protocols is associated with smaller benefits of rehabilitation. This finding highlights the importance of choosing tolerable exercise protocols for chronic obstructive pulmonary disease patients.
Local immunodiagnosis of pulmonary tuberculosis by enzyme-linked immunospot
Authors: Jafari C. , Ernst M. , Strassburg A. , Greinert U. , Kalsdorf B. , Kirsten D. , Lange C. 
Published: November 2007

Lymphocytes are crucial in the immune defence againstMycobacterium tuberculosis(MTB) infection. The aim of the present study was to ascertain whether or not MTB-specific lymphocytes are selectively compartmentalised in the lungs of patients with minimal active pulmonary tuberculosis (PTB).Patients with smear-negative MTB-culture-confirmed PTB were prospectively recruited. Differential cell counts, immunophenotyping with monoclonal antibodies directed against the cell surface markers CD4, CD8, CD4CD45RA, CD4CD45R0, CD38, human leukocyte antigen DR, CD19, CD3, CD57 and CD16 and MTB-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) mononuclear cells with 6-kDa early secretory antigenic target and culture filtrate protein 10 were performed.Among 12 patients with culture-confirmed smear-negative PTB, no differences were found in the distribution of total CD4 or CD8 T-cells in peripheral blood or BAL fluid (BALF). Activated human leukocyte antigen-DR-positive cells, as well as memory CD4CD45R0-positive T-cells, were expanded among cells of the BALF. Compared with a group of control patients with alternative pulmonary pathologies, there was no significant difference in lymphocyte subpopulations. However, 6-kDa early secretory antigenic target- and culture filtrate protein 10-specific lymphocytes were more concentrated, with a median BALF:peripheral blood ratio of 9.9 and 8.9, respectively, in patients with PTB.Mycobacterium tuberculosis-specific T-cells are highly selectively compartmentalised at the site of infection in active pulmonary tuberculosis.
Validation and comparison of reference equations for the 6-min walk distance test
Authors: Cote C. G. , Casanova C. , Marín J. M. , Lopez M. V. , Pinto-Plata V. , de Oca M. M. , Dordelly L. J. , Nekach H. , Celli B. R. 
Published: November 2007

Exercise impairment as measured by the 6-min walk distance (6MWD) test afflicts many patients with chronic obstructive pulmonary disease (COPD) and is known to predict mortality. Reference equations for the 6MWD in adults have been published but not yet validated.The present authors prospectively followed 1,379 COPD patients for 55±30 months and tested the predictive value of the baseline 6MWD in metres, the 6MWD work (kg·m−1) and as a percentage of predicted values the 6MWD in meters according to two reference equations. All-cause mortality was the validating outcome. The best threshold values were identified for each of the tests using receiver operating characteristic (ROC) curves.The threshold values obtained were: 350 m for the 6MWD, 25,000 kg·m−1for the 6MWD work, and 67 and 54% predicted for the two reference equations.All modalities of the testing were similar at predicting COPD mortality and correlated well with the 6MWD test.In conclusion, all modalities of testing predict mortality in chronic obstructive pulmonary disease equally well. In the 6-min walk distance test, a value <350 m is associated with increased mortality and should be regarded as abnormal.
Palliative and end-of-life care for patients with severe COPD
Authors: Curtis J. R. 
Published: November 2007

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. For many patients, maximal therapy for COPD produces only modest or incomplete relief of disabling symptoms and these symptoms result in a significantly reduced quality of life.Despite the high morbidity and mortality associated with severe COPD, many patients receive inadequate palliative care. There are several reasons for this. First, patient–physician communication about palliative and end-of-life care is infrequent and often of poor quality. Secondly, the uncertainty in predicting prognosis for patients with COPD makes communication about end-of-life care more difficult. Consequently, patients and their families frequently do not understand that severe COPD is often a progressive and terminal illness.The purpose of the present review is to summarise recent research regarding palliative and end-of-life care for patients with COPD. Recent studies provide insight and guidance into ways to improve communication about end-of-life care and thereby improve the quality of palliative and end-of-life care the patients receive. Two areas that may influence the quality of care are also highlighted: 1) the role of anxiety and depression, common problems for patients with COPD; and 2) the importance of advance care planning.Improving communication represents an important opportunity for the improvement of the quality of palliative and end-of-life care received by these patients.
Longitudinal lung function decline and wood dust exposure in the furniture industry
Authors: Jacobsen G. , Schlünssen V. , Schaumburg I. , Taudorf E. , Sigsgaard T. 
Published: November 2007

The aim of the present study was to investigate the relationship between change in lung function and cumulative exposure to wood dust.In total, 1,112 woodworkers (927 males, 185 females) and 235 reference workers (104 males, 185 females) participated in a 6-yr longitudinal study. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), height and weight were measured, and questionnaire data on respiratory symptoms, wood dust exposure and smoking habits were collected. Cumulative inhalable wood dust exposure was assessed using a study-specific job exposure matrix and exposure time.The median (range) for cumulative wood dust exposure was 3.75 (0–7.55) mg·year·m−3. A dose–response relationship between cumulative wood dust exposure and percent annual decrease in FEV1was suggested for female workers. This was confirmed in a linear regression model adjusted for confounders, including smoking, height and age. An additional difference of -14.50 mL·yr−1and −27.97 mL·yr−1was revealed for females exposed to 3.75–4.71 mg·yr·m−3or to >4.71 mg·yr·m−3, respectively, compared with non-/low-exposed females. For females, a positive trend between wood dust exposure and the cumulative incidence proportion of FEV1/FVC <70% was suggested.In conclusion, in the present low-exposed cohort, female woodworkers had an accelerated decline in lung function, which may be clinically relevant.
The role of IFN-γ in regulation of IFN-γ-inducible protein 10 (IP-10) expression in lung epithelial cell and peripheral blood mononuclear cell co-cultures
Authors: Torvinen Maria , Campwala Hinnah , Kilty Iain 
Published: November 2007

AbstractBackgroundInterferons play a critical role in regulating both the innate and adaptive immune responses. Previous reports have shown increased levels of IFN-γ, IFN-γ-inducing IL-12 and IFN-γ-inducible chemokine IP-10 in patients with chronic obstructive pulmonary disease (COPD).MethodsThe present study focuses on the regulation of the IP-10 secretion in co-cultures of lung epithelial cells and peripheral blood mononuclear cells (PBMCs).ResultsNo IP-10 secretion was detected in cells cultured alone, whereas a significant increase in IP-10 levels was observed in epithelial cell/PBMC co-cultures. Furthermore, the results show that interactions between lung epithelial cells, lymphocytes and monocytes are needed for basal IP-10 secretion. Interestingly, we have also shown that incubation with IL-12 can induce an IFN-γ independent increase in IP-10 levels in co-cultures. Furthermore, inhibition studies supported the suggestion that different intracellular pathways are responsible of IFN-γ and IL-12 mediated IP-10 secretion.ConclusionThese studies demonstrate a novel diversity in IFN-γ/IL-12 pathways, showing that the IP-10 expression in co-cultures is regulated by multiple factors, such as intercellular interactions in addition to IFN-γ and IL-12 levels. These results may be valuable in designing novel strategies to antagonize IP-10 mediated immunological reactions and chemotactic effects on T cells.
Identifications of conserved 7-mers in 3'-UTRs and microRNAs in Drosophila
Authors: Gu Jin , Fu Hu , Zhang Xuegong , Li Yanda 
Published: November 2007

Abstract

Background
MicroRNAs (miRNAs) are a class of endogenous regulatory small RNAs which play an important role in posttranscriptional regulations by targeting mRNAs for cleavage or translational repression. The base-pairing between the 5'-end of miRNA and the target mRNA 3'-UTRs is essential for the miRNA:mRNA recognition. Recent studies show that many seed matches in 3'-UTRs, which are fully complementary to miRNA 5'-ends, are highly conserved. Based on these features, a two-stage strategy can be implemented to achieve the de novo identification of miRNAs by requiring the complete base-pairing between the 5'-end of miRNA candidates and the potential seed matches in 3'-UTRs.

Results
We presented a new method, which combined multiple pairwise conservation information, to identify the frequently-occurred and conserved 7-mers in 3'-UTRs. A pairwise conservation score (PCS) was introduced to describe the conservation of all 7-mers in 3'-UTRs between any two Drosophila species. Using PCSs computed from 6 pairs of flies, we developed a support vector machine (SVM) classifier ensemble, named Cons-SVM and identified 689 conserved 7-mers including 63 seed matches covering 32 out of 38 known miRNA families in the reference dataset. In the second stage, we searched for 90 nt conserved stem-loop regions containing the complementary sequences to the identified 7-mers and used the previously published miRNA prediction software to analyze these stem-loops. We predicted 47 miRNA candidates in the genome-wide screen.

Conclusion
Cons-SVM takes advantage of the independent evolutionary information from the 6 pairs of flies and shows high sensitivity in identifying seed matches in 3'-UTRs. Combining the multiple pairwise conservation information by the machine learning approach, we finally identified 47 miRNA candidates in D. melanogaster.
Nodal signaling is required for closure of the anterior neural tube in zebrafish
Authors: Aquilina-Beck Allisan , Ilagan Kristine , Liu Qin , Liang Jennifer O 
Published: November 2007

Abstract

Background
Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish.

Results
We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish.

Conclusion
This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.
Computational RNomics of Drosophilids
Authors: Rose Dominic , Hackermüller Jörg , Washietl Stefan , Reiche Kristin , Hertel Jana , Findeiß Sven , Stadler Peter F , Prohaska Sonja J 
Published: November 2007

Abstract

Background
Recent experimental and computational studies have provided overwhelming evidence for a plethora of diverse transcripts that are unrelated to protein-coding genes. One subclass consists of those RNAs that require distinctive secondary structure motifs to exert their biological function and hence exhibit distinctive patterns of sequence conservation characteristic for positive selection on RNA secondary structure.
The deep-sequencing of 12 drosophilid species coordinated by the NHGRI provides an ideal data set of comparative computational approaches to determine those genomic loci that code for evolutionarily conserved RNA motifs. This class of loci includes the majority of the known small ncRNAs as well as structured RNA motifs in mRNAs. We report here on a genome-wide survey using RNAz.

Results
We obtain 16 000 high quality predictions among which we recover the majority of the known ncRNAs. Taking a pessimistically estimated false discovery rate of 40% into account, this implies that at least some ten thousand loci in the Drosophila genome show the hallmarks of stabilizing selection action of RNA structure, and hence are most likely functional at the RNA level. A subset of RNAz predictions overlapping with TRF1 and BRF binding sites [Isogai et al., EMBO J. 26: 79–89 (2007)], which are plausible candidates of Pol III transcripts, have been studied in more detail. Among these sequences we identify several "clusters" of ncRNA candidates with striking structural similarities.

Conclusion
The statistical evaluation of the RNAz predictions in comparison with a similar analysis of vertebrate genomes [Washietl et al., Nat. Biotech. 23: 1383–1390 (2005)] shows that qualitatively similar fractions of structured RNAs are found in introns, UTRs, and intergenic regions. The intergenic RNA structures, however, are concentrated much more closely around known protein-coding loci, suggesting that flies have significantly smaller complement of independent structured ncRNAs compared to mammals.
Analysis of Schistosoma mansoni genes shared with Deuterostomia and with possible roles in host interactions
Authors: Venancio Thiago M , DeMarco Ricardo , Almeida Giulliana T , Oliveira Katia C , Setubal João C , Verjovski-Almeida Sergio 
Published: November 2007

Abstract

Background:

Schistosoma mansoni is a blood helminth parasite that causes schistosomiasis, a disease that affects 200 million people in the world. Many orthologs of known mammalian genes have been discovered in this parasite and evidence is accumulating that some of these genes encode proteins linked to signaling pathways in the parasite that appear to be involved with growth or development, suggesting a complex co-evolutionary process.

Results:
In this work we found 427 genes conserved in the Deuterostomia group that have orthologs in S. mansoni and no members in any nematodes and insects so far sequenced. Among these genes we have identified In sulin I nduced G ene (INSIG), I nterferon R egulatory F actor (IRF) and vasohibin orthologs, known to be involved in mammals in mevalonate metabolism, immune response and angiogenesis control, respectively. We have chosen these three genes for a more detailed characterization, which included extension of their cloned messages to obtain full-length sequences. Interestingly, SmINSIG showed a 10-fold higher expression in adult females as opposed to males, in accordance with its possible role in regulating egg production. SmIRF has a DNA binding domain, a tryptophan-rich N-terminal region and several predicted phosphorylation sites, usually important for IRF activity. Fourteen different alternatively spliced forms of the S. mansoni vasohibin (SmVASL) gene were detected that encode seven different protein isoforms including one with a complete C-terminal end, and other isoforms with shorter C-terminal portions. Using S. mansoni homologs, we have employed a parsimonious rationale to compute the total gene losses/gains in nematodes, arthropods and deuterostomes under either the Coelomata or the Ecdysozoa evolutionary hypotheses; our results show a lower losses/gains number under the latter hypothesis.

Conclusion:
The genes discussed which are conserved between S. mansoni and deuterostomes, probably have an ancient origin and were lost in Ecdysozoa, being still present in Lophotrochozoa. Given their known functions in Deuterostomia, it is possible that some of them have been co-opted to perform functions related (directly or indirectly) to host adaptation or interaction with host signaling processes.