bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury
Authors: de Visser Yvonne P , Walther Frans J , Laghmani El Houari , Boersma Hester , van der Laarse Arnoud , Wagenaar Gerry TM 
Published: April 2009

Abstract

Background
Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD), a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome.

Methods
Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously) and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue.

Results
Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day) significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH).

Conclusion
Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary inflammatory response, fibrin deposition and RVH, and stimulates alveolarization. Initiation of sildenafil treatment after hyperoxic lung injury and continued during room air recovery improves alveolarization and restores pulmonary angiogenesis and RVH in experimental BPD.
Modeling post-transcriptional regulation activity of small non-coding RNAs in Escherichia coli
Authors: Wang Rui-Sheng , Jin Guangxu , Zhang Xiang-Sun , Chen Luonan 
Published: April 2009

AbstractBackgroundTranscriptional regulation is a fundamental process in biological systems, where transcription factors (TFs) have been revealed to play crucial roles. In recent years, in addition to TFs, an increasing number of non-coding RNAs (ncRNAs) have been shown to mediate post-transcriptional processes and regulate many critical pathways in both prokaryotes and eukaryotes. On the other hand, with more and more high-throughput biological data becoming available, it is possible and imperative to quantitatively study gene regulation in a systematic and detailed manner.ResultsMost existing studies for inferring transcriptional regulatory interactions and the activity of TFs ignore the possible post-transcriptional effects of ncRNAs. In this work, we propose a novel framework to infer the activity of regulators including both TFs and ncRNAs by exploring the expression profiles of target genes and (post)transcriptional regulatory relationships. We model the integrated regulatory system by a set of biochemical reactions which lead to a log-bilinear problem. The inference process is achieved by an iterative algorithm, in which two linear programming models are efficiently solved. In contrast to available related studies, the effects of ncRNAs on transcription process are considered in this work, and thus more reasonable and accurate reconstruction can be expected. In addition, the approach is suitable for large-scale problems from the viewpoint of computation. Experiments on two synthesized data sets and a model system ofEscherichia coli(E. coli) carbon source transition from glucose to acetate illustrate the effectiveness of our model and algorithm.ConclusionOur results show that incorporating the post-transcriptional regulation of ncRNAs into system model can mine the hidden effects from the regulation activity of TFs in transcription processes and thus can uncover the biological mechanisms in gene regulation in a more accurate manner. The software for the algorithm in this paper is available upon request.
LC-MS/MS-based proteome profiling in Daphnia pulex and Daphnia longicephala: the Daphnia pulex genome database as a key for high throughput proteomics in Daphnia
Authors: Fröhlich Thomas , Arnold Georg J , Fritsch Rainer , Mayr Tobias , Laforsch Christian 
Published: April 2009

AbstractBackgroundDaphniids, commonly known as waterfleas, serve as important model systems for ecology, evolution and the environmental sciences. The sequencing and annotation of theDaphnia pulexgenome both open future avenues of research on this model organism. As proteomics is not only essential to our understanding of cell function, and is also a powerful validation tool for predicted genes in genome annotation projects, a first proteomic dataset is presented in this article.ResultsA comprehensive set of 701,274 peptide tandem-mass-spectra, derived fromDaphnia pulex, was generated, which lead to the identification of 531 proteins. To measure the impact of theDaphnia pulexfiltered models database for mass spectrometry basedDaphniaprotein identification, this result was compared with results obtained with the Swiss-Prot and theDrosophila melanogasterdatabase. To further validate the utility of theDaphnia pulexdatabase for research on otherDaphniaspecies, additional 407,778 peptide tandem-mass-spectra, obtained fromDaphnia longicephala, were generated and evaluated, leading to the identification of 317 proteins.ConclusionPeptides identified in our approach provide the first experimental evidence for the translation of a broad variety of predicted coding regions within theDaphniagenome. Furthermore it could be demonstrated that identification ofDaphnia longicephalaproteins using theDaphnia pulexprotein database is feasible but shows a slightly reduced identification rate. Data provided in this article clearly demonstrates that theDaphniagenome database is the key for mass spectrometry based high throughput proteomics inDaphnia.
Simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza
Authors: Kelso Joel K , Milne George J , Kelly Heath 
Published: April 2009

Abstract

Background
Social distancing interventions such as school closure and prohibition of public gatherings are present in pandemic influenza preparedness plans. Predicting the effectiveness of intervention strategies in a pandemic is difficult. In the absence of other evidence, computer simulation can be used to help policy makers plan for a potential future influenza pandemic. We conducted simulations of a small community to determine the magnitude and timing of activation that would be necessary for social distancing interventions to arrest a future pandemic.

Methods
We used a detailed, individual-based model of a real community with a population of approximately 30,000. We simulated the effect of four social distancing interventions: school closure, increased isolation of symptomatic individuals in their household, workplace nonattendance, and reduction of contact in the wider community. We simulated each of the intervention measures in isolation and in several combinations; and examined the effect of delays in the activation of interventions on the final and daily attack rates.

Results
For an epidemic with an R0 value of 1.5, a combination of all four social distancing measures could reduce the final attack rate from 33% to below 10% if introduced within 6 weeks from the introduction of the first case. In contrast, for an R0 of 2.5 these measures must be introduced within 2 weeks of the first case to achieve a similar reduction; delays of 2, 3 and 4 weeks resulted in final attack rates of 7%, 21% and 45% respectively. For an R0 of 3.5 the combination of all four measures could reduce the final attack rate from 73% to 16%, but only if introduced without delay; delays of 1, 2 or 3 weeks resulted in final attack rates of 19%, 35% or 63% respectively. For the higher R0 values no single measure has a significant impact on attack rates.

Conclusion
Our results suggest a critical role of social distancing in the potential control of a future pandemic and indicate that such interventions are capable of arresting influenza epidemic development, but only if they are used in combination, activated without delay and maintained for a relatively long period.
Nonattendance in pediatric pulmonary clinics: an ambulatory survey
Authors: Goldbart Aviv D , Dreiher Jacob , Vardy Daniel A , Alkrinawi Soliman , Cohen Arnon D 
Published: April 2009

AbstractBackgroundNonattendance for scheduled appointments disturbs the effective management of pediatric pulmonary clinics. We hypothesized that the reasons for non-attendance and the necessary solutions might be different in pediatric pulmonary medicine than in other pediatric fields. We therefore investigated the factors associated with nonattendance this field in order to devise a corrective strategy.MethodsThe effect of age, gender, ethnic origin, waiting time for an appointment and the timing of appointments during the day on nonattendance proportion were assessed. Chi-square tests were used to analyze statistically significant differences of categorical variables. Logistic regression models were used for multivariate analysis.ResultsA total of 1190 pediatric pulmonology clinic visits in a 21 month period were included in the study. The overall proportion of nonattendance was 30.6%. Nonattendance was 23.8% when there was a short waiting time for an appointment (1–7 days) and 36.3% when there was a long waiting time (8 days and above) (p-value < 0.001). Nonattendance was 28.7% between 8 a.m. to 3 p.m. and 37.5% after 3 p.m. (p = 0.007). Jewish rural patients had 15.4% nonattendance, Jewish urban patients had 31.2% nonattendance and Bedouin patients had 32.9% nonattendance (p < 0.004). Age and gender were not significantly associated with nonattendance proportions. A multivariate logistic regression model demonstrated that the waiting time for an appointment, time of the day, and the patients' origin was significantly associated with nonattendance.ConclusionThe factors associated with nonattendance in pediatric pulmonary clinics include the length of waiting time for an appointment, the hour of the appointment within the day and the origin of the patient.
The association between back pain and trunk posture of workers in a special school for the severe handicaps
Authors: Wong Kelvin CH , Lee Raymond YW , Yeung Simon S 
Published: April 2009

Abstract

Background
The present study aims to determine the time spent in different static trunk postures during a typical working day of workers in a special school for the severe handicaps.

Methods
Eighteen workers with low back pain (LBP) and fifteen asymptomatic workers were recruited. A cross-sectional design was employed to study the time spent in different static trunk postures which was recorded by a biaxial accelerometer attached to the T12 level of the back of the subjects.

Results
The results of ANCOVA revealed that subjects with LBP spent significantly longer percentage of time in static trunk posture when compared to normal (p < 0.05). It was also shown that they spent significantly longer time in trunk flexion for more than 10° (p < 0.0125).

Conclusion
An innovative method has been developed for continuous tracking of spinal posture, and this has potential for widespread applications in the workplace. The findings of the present investigation suggest that teachers in special schools are at increased risk of getting LBP. In order to minimise such risk, frequent postural change and awareness of work posture are recommended.
Acetaldehyde and hexanaldehyde from cultured white cells
Authors: Shin Hye-Won , Umber Brandon J , Meinardi Simone , Leu Szu-Yun , Zaldivar Frank , Blake Donald R , Cooper Dan M 
Published: April 2009

AbstractBackgroundNoninvasive detection of innate immune function such as the accumulation of neutrophils remains a challenge in many areas of clinical medicine. We hypothesized that granulocytes could generate volatile organic compounds.MethodsTo begin to test this, we developed a bioreactor and analytical GC-MS system to accurately identify and quantify gases in trace concentrations (parts per billion) emitted solely from cell/media culture. A human promyelocytic leukemia cell line, HL60, frequently used to assess neutrophil function, was grown in serum-free medium.ResultsHL60 cells released acetaldehyde and hexanaldehyde in a time-dependent manner. The mean ± SD concentration of acetaldehyde in the headspace above the cultured cells following 4-, 24- and 48-h incubation was 157 ± 13 ppbv, 490 ± 99 ppbv, 698 ± 87 ppbv. For hexanaldehyde these values were 1 ± 0.3 ppbv, 8 ± 2 ppbv, and 11 ± 2 ppbv. In addition, our experimental system permitted us to identify confounding trace gas contaminants such as styrene.ConclusionThis study demonstrates that human immune cells known to mimic the function of innate immune cells, like neutrophils, produce volatile gases that can be measuredin vitroin trace amounts.
Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis
Authors: Sarma Jayasri Das , Ciric Bogoljub , Marek Ryan , Sadhukhan Sanjoy , Caruso Michael L , Shafagh Jasmine , Fitzgerald Denise C , Shindler Kenneth S , Rostami AM 
Published: April 2009

AbstractBackgroundInterleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.MethodsEAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA.ResultsHere we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RAin vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA.ConclusionIL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions.
Regulation of Chk1
Authors: Tapia-Alveal Claudia , Calonge Teresa M , O'Connell Matthew J 
Published: April 2009

Abstract
Chk1 is a serine/threonine protein kinase that is the effector of the G2 DNA damage checkpoint. Chk1 homologs have a highly conserved N-terminal kinase domain, and a less conserved C-terminal regulatory domain of ~200 residues. In response to a variety of genomic lesions, a number of proteins collaborate to activate Chk1, which in turn ensures that the mitotic cyclin-dependent kinase Cdc2 remains in an inactive state until DNA repair is completed. Chk1 activation requires the phosphorylation of residues in the C-terminal domain, and this is catalyzed by the ATR protein kinase. How phosphorylation of the C-terminal regulatory domain activates the N-terminal kinase domain has not been elucidated, though some studies have suggested that this phosphorylation relieves an inhibitory intramolecular interaction between the N- and C-termini. However, recent studies in the fission yeast Schizosaccharomyces pombe have revealed that there is more to Chk1 regulation than this auto-inhibition model, and we review these findings and their implication to the biology of this genome integrity determinant.
Application of serum proteomics to the Women's Health Initiative conjugated equine estrogens trial reveals a multitude of effects relevant to clinical findings
Authors: Katayama Hiroyuki , Paczesny Sophie , Prentice Ross , Aragaki Aaron , Faca Vitor M , Pitteri Sharon J , Zhang Qing , Wang Hong , Silva Melissa , Kennedy Jacob , Rossouw Jacques , Jackson Rebecca , Hsia Judith , Chlebowski Rowan , Manson JoAnn , Hanash Samir 
Published: April 2009

Abstract
Background
The availability of serum collections from the Women's Health Initiative (WHI) conjugated equine estrogens (CEE) randomized controlled trial provides an opportunity to test the potential of in-depth quantitative proteomics to uncover changes in the serum proteome related to CEE and to assess their relevance to trial findings, including elevations in the risk of stroke and venous thromboembolism and a reduction in fractures.

Methods
Five independent large scale quantitative proteomics analyses were performed, each comparing a set of pooled serum samples collected from 10 subjects, 1 year following initiation of CEE at 0.625 mg/d, relative to their baseline pool. A subset of proteins that exhibited increased levels with CEE by quantitative proteomics was selected for validation studies.

Results
Of 611 proteins quantified based on differential stable isotope labeling, the levels of 116 (19%) were changed after 1 year of CEE (nominal P < 0.05), while 64 of these had estimated false discovery rates <0.05. Most of the changed proteins were not previously known to be affected by CEE and had relevance to processes that included coagulation, metabolism, osteogenesis, inflammation, and blood pressure maintenance. To validate quantitative proteomic data, 14 proteins were selected for ELISA. Findings for ten - IGF1, IGFBP4, IGFBP1, IGFBP2, F10, AHSG, GC, CP, MMP2, and PROZ - were confirmed in the initial set of 50 subjects and further validated in an independent set of 50 additional subjects who received CEE.

Conclusions
CEE affected a substantial fraction of the serum proteome, including proteins with relevance to findings from the WHI CEE trial related to cardiovascular disease and fracture.

Clinical Trials Registration
ClinicalTrials.gov identifier: NCT00000611
The membrane expression of Neisseria meningitidis adhesin A (NadA) increases the proimmune effects of MenB OMVs on human macrophages, compared with NadA– OMVs, without further stimulating their proinflammatory activity on circulating monocytes
Authors: Tavano Regina , Franzoso Susanna , Cecchini Paola , Cartocci Elena , Oriente Francesca , Aricò Beatrice , Papini Emanuele 
Published: April 2009

Abstract
Anti-Meningococcus B vaccine candidate stimulates macrophages.
Hypervirulent MenB causing fatal human infections frequently display the oligomeric-coiled coil adhesin NadA, a 45-kDa intrinsic outer membrane protein implicated in binding to and invasion of respiratory epithelial cells. A recombinant soluble mutant lacking the 10-kDa COOH terminal membrane domain (NadAΔ351–405) also activates human monocytes/macrophages/DCs. As NadA is physiologically released during sepsis as part of OMVs, in this study, we tested the hypothesis that NadA+ OMVs have an enhanced or modified proinflammatory/proimmune action compared with NadA– OMVs. To do this we investigated the activity of purified free NadAΔ351–405 and of OMVs from MenB and Escherichia coli strains, expressing or not full-length NadA. NadAΔ351–405 stimulated monocytes and macrophages to secrete cytokines (IL-1β, TNF-α, IL-6, IL-12p40, IL-12p70, IL-10) and chemokines (IL-8, MIP-1α, MCP-1, RANTES), and full-length NadA improved MenB OMV activity, preferentially on macrophages, and only increased cytokine release. NadAΔ351–405 induced the lymphocyte costimulant CD80 in monocytes and macrophages, and NadA+ OMVs induced a wider set of molecules supporting antigen presentation (CD80, CD86, HLA-DR, and ICAM-1) more efficiently than NadA– OMVs only in macrophages. Moreover, membrane NadA effects, unlike NadAΔ351–405 ones, were much less IFN-γ-sensitive. The activity of NadA-positive E. coli OMVs was similar to that of control OMVs. NadA in MenB OMVs acted at adhesin concentrations ∼106 times lower than those required to stimulate cells with free NadAΔ351–405.
A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction
Authors: Chan Mabel M P , Cheung Benny K W , Li James C B , Chan Lally L Y , Lau Allan S Y 
Published: April 2009

Abstract
GSK3 regulation of inflammation is targeted by mycobacterial for evasion of immunity resulting in IL-10 induction in the host.
Mtb dysregulates monocyte/macrophage functions to produce a large amount of the immunosuppressive cytokine IL-10. An important function of IL-10 in promoting Mtb survival is the suppression of antigen presentation of monocytes/macrophages to T cells. This dampens the host immune responses and provides an opportunity for immune evasion. GSK3 has been shown to control the balance between pro- and anti-inflammatory cytokine productions. Here, we investigated whether GSK3 regulates IL-10 expression and mediates a protective role upon live mycobacterial challenge using BCG as a model. Our results showed that BCG increased Akt phosphorylation and inhibited GSK3 activity, resulting in increased IL-10 production. We confirmed further that suppression of GSK3 activities by a specific chemical inhibitor strongly enhanced BCG-induced IL-10 production. We also showed that IL-10 secreted by BCG-infected human PBMo was a major suppressor of subsequent IFN-γ production by PBMC and HLA-DR expression on PBMo in response to BCG. Neutralization of PBMo-secreted IL-10 by anti-IL-10 antibodies restored the IFN-γ production and HLA-DR surface expression. Taken together, GSK3 negatively regulates mycobacteria-induced IL-10 production in human PBMo. The kinase may play a role in restoring IFN-γ secretions and subsequent antigen presentation in response to mycobacterial infection. In conclusion, our results suggest a significant role for GSK3 in guarding against mycobacterial evasion of immunity via IL-10 induction in the host.