bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Small Molecule Deubiquitinase Inhibitor Increases Localization of Inducible Nitric Oxide Synthase to the Macrophage Phagosome and Enhances Bacterial Killing
Authors: Burkholder Kristin M. , Perry Jeffrey W. , Wobus Christiane E. , Donato Nicholas J. , Showalter Hollis D. , Kapuria Vaibhav , O'Riordan Mary X. D. 
Published: September 2011

ABSTRACTMacrophages are key mediators of antimicrobial defense and innate immunity. Innate intracellular defense mechanisms can be rapidly regulated at the posttranslational level by the coordinated addition and removal of ubiquitin by ubiquitin ligases and deubiquitinases (DUBs). While ubiquitin ligases have been extensively studied, the contribution of DUBs to macrophage innate immune function is incompletely defined. We therefore employed a small molecule DUB inhibitor, WP1130, to probe the role of DUBs in the macrophage response to bacterial infection. Treatment of activated bone marrow-derived macrophages (BMM) with WP1130 significantly augmented killing of the intracellular bacterial pathogenListeria monocytogenes. WP1130 also induced killing of phagosome-restricted bacteria, implicating a bactericidal mechanism associated with the phagosome, such as the inducible nitric oxide synthase (iNOS). WP1130 had a minimal antimicrobial effect in macrophages lacking iNOS, indicating that iNOS is an effector mechanism for WP1130-mediated bacterial killing. Although overall iNOS levels were not notably different, we found that WP1130 significantly increased colocalization of iNOS with theListeria-containing phagosome during infection. Taken together, our data indicate that the deubiquitinase inhibitor WP1130 increases bacterial killing in macrophages by enhancing iNOS localization to the phagosome and suggest a potential role for ubiquitin regulation in iNOS trafficking.
Genome Sequence of Anaerophaga sp. Strain HS1, a Novel, Moderately Thermophilic, Strictly Anaerobic Bacterium Isolated from Hot Spring Sediment
Authors: Gao Zhaoming , Liu Xin , Ruan Lingwei 
Published: September 2011

ABSTRACT

Anaerophaga
sp. strain HS1 was isolated from offshore hot spring sediment in Xiamen, China. It was identified as a novel, moderately thermophilic, strictly anaerobic bacterium affiliated with the family
Marinilabiaceae
and showed xylanase activity. Here, we describe the 3.88-Mb draft genome sequence of
Anaerophaga
sp. strain HS1 and the annotation analysis of related xylanase genes.
Complete Genome Sequence of the Agarase-Producing Marine Bacterium Strain S89, Representing a Novel Species of the Genus Alteromonas
Authors: Oh Chulhong , Zoysa Mahanama De , Kwon Young-Kyung , Heo Soo-Jin , Affan Abu , Jung Won-Kyo , Park Heung-Sik , Lee Jehee , Son Seung-Kyu , Yoon Kon-Tak , Kang Do-Hyung 
Published: September 2011

ABSTRACT

We report here the annotated genome sequence of the marine bacterium
Alteromonas
sp. S89 and the identification of six genes coding for agar-degrading enzymes. The sequenced
Alteromonas
sp. S89 genome is composed of a 3,864,871-bp circular chromosome that includes 3,236 complete open reading frames.
Effectiveness and safety of the A-H1N1 vaccine in children: a hospital-based case–control study
Authors:   Italian Multicenter Study Group for Drug and Vaccine Safety in Children
Published: September 2011

ObjectiveTo verify whether vaccination against the A-H1N1 virus in the paediatric population was effective in preventing the occurrence of influenza-like illness (ILI) or was associated with adverse events of special interest.Design, setting and patientsA case–control analysis was performed as part of surveillance of children hospitalised through the emergency departments of eight paediatric hospitals/wards for ILI, neurological disorders, non-infectious muco-cutaneous diseases and vasculitis, thrombocytopaenia and gastroduodenal lesions.ResultsAmong 736 children enrolled from November 2009 to August 2010, only 25 had been vaccinated with the pandemic vaccine. Out of 268 children admitted for a diagnosis compatible with the adverse events of special interest, six had received the A-H1N1 vaccine, although none of the adverse events occurred within the predefined risk windows. Only 35 children out of 244 admitted with a diagnosis of ILI underwent laboratory testing: 11 were positive and 24 negative for the A-H1N1 virus. None of the A-H1N1 positive children had received the pandemic vaccine. The OR of ILI associated with any influenza vaccination was 0.9 (95% CI 0.1 to 5.5).ConclusionsThe study provides additional information on the benefit–risk profile of the pandemic vaccine. No sign of risk associated with the influenza A-H1N1 vaccine used in Italy was found, although several limitations were observed: in Italy, pandemic vaccination coverage was low, the epidemic was almost over by mid December 2009 and the A-H1N1 laboratory test was performed only during the epidemic phase (in <10% of children). This study supports the importance of the existing network of hospitals for the evaluation of signals relevant to new vaccines and drugs.
Role of the Arabian Sea Warm Pool on the Precipitation Characteristics during the Monsoon Onset Period
Authors: Sijikumar S. , Rajeev K. 
Published: September 2011

Abstract
Regional distribution of precipitation during the onset phase of the Indian summer monsoon (15 May–15 June) shows distinct patterns in the years 2009 and 2010, with the latter having considerably more precipitation over the southeast Arabian Sea (AS) and the west coast of peninsular India. During these years, the location and regional extent of the warm pool in the AS are also distinct. In 2009, the warm pool core is located in the equatorial region, whereas in 2010 it spreads to a wide region of the AS. Sensitivity experiments with different SST forcings have been carried out using the Weather Research and Forecasting (WRF) model to understand the influence of the AS warm pool on the monsoon onset precipitation characteristics. Simulations with actual SSTs in the AS and climatological SSTs elsewhere are able to reproduce the distinct behavior of the monsoon onset precipitation observed during 2009 and 2010. These simulations show suppressed convection over the central and northern AS in 2009, while warmer SSTs in the AS favor enhanced convection during 2010 combined with a sharp contrast in the moisture transport. The strong intrusion of drier air from the north AS effectively confines the moist air mass from the south, causing a net transport of moisture toward the southwest coast of peninsular India and leads to positive anomalies in precipitation over the region in 2010. However, during 2009, the drier air from the north mixes rather easily over the AS, which suppress the convection.
Regulation of the BRCA1 gene by an SRC3/53BP1 complex
Authors: Corkery Dale , Thillainadesan Gobi , Coughlan Niamh , Mohan Ryan D , Isovic Majdina , Tini Marc , Torchia Joseph 
Published: September 2011

Abstract

Background
Steroid Receptor coactivator 3(SRC3) is an oncogene and a member of the SRC family of nuclear receptor coactivator proteins that mediate the transcriptional effects of nuclear hormone receptors as well as other transcription factors.

Results
We have used protein purification and mass spectrometry to identify the 53BP1 tumour suppressor as a novel SRC3-associated protein. Copurification was demonstrated using multiple antibodies, and was not dependent on DNA damage suggesting that SRC3 is not directly involved in the DNA damage response. However using chromatin immunoprecipitation(ChIP) and siRNA knockdown, we have demonstrated that both SRC3 and 53BP1 co-occupy the same region of the BRCA1 promoter and both are required for BRCA1 expression in HeLa cells.

Conclusions
Our results suggest that both 53BP1 and SRC3 have a common function that converge at the BRCA1 promoter and possibly other genes important for DNA repair and genomic stability.
Integrating GPCR-specific information with full text articles
Authors: Vroling Bas , Thorne David , McDermott Philip , Attwood Teresa K , Vriend Gert , Pettifer Steve 
Published: September 2011

Abstract

Background
With the continued growth in the volume both of experimental G protein-coupled receptor (GPCR) data and of the related peer-reviewed literature, the ability of GPCR researchers to keep up-to-date is becoming increasingly curtailed.

Results
We present work that integrates the biological data and annotations in the GPCR information system (GPCRDB) with next-generation methods for intelligently exploring, visualising and interacting with the scientific articles used to disseminate them. This solution automatically retrieves relevant information from GPCRDB and displays it both within and as an adjunct to an article.

Conclusions
This approach allows researchers to extract more knowledge more swiftly from literature. Importantly, it allows reinterpretation of data in articles published before GPCR structure data became widely available, thereby rescuing these valuable data from long-dormant sources.
Increase in serotype 19A prevalence and amoxicillin non-susceptibility among paediatric Streptococcus pneumoniae isolates from middle ear fluid in a passive laboratory-based surveillance in Spain, 1997-2009
Authors: Fenoll Asunción , Aguilar Lorenzo , Vicioso Maria-Dolores , Gimenez Maria-Jose , Robledo Olga , Granizo Juan-Jose 
Published: September 2011

Abstract

Background
Conjugate vaccines, such as the 7-valent conjugate vaccine (PCV7), alter serotype nasopharyngeal carriage, potentially increasing cases of otitis media by non-vaccine serotypes.

Methods
All paediatric middle ear fluid (MEF) isolates received in the Spanish Reference Laboratory for Pneumococci through a passive, laboratory-based surveillance system from January 1997 to June 2009 were analysed. Data from 1997 to 2000 were pooled as pre-vaccination period. Trends over time were explored by linear regression analysis.

Results
A total of 2,077 isolates were analysed: 855 belonging to PCV7 serotypes, 466 to serotype 19A, 215 to serotype 3, 89 to serotype 6A and 452 to other serotypes (< 40 isolates each). Over time, there has been a decreasing trend for PCV7 serotypes (R2 = 0.944; p < 0.001, with significant decreasing trends for serotypes 19F, 14, 23F and 9V), and increasing trends for serotype 19A (R2 = 0.901; p < 0.001), serotype 3 (R2 = 0.463; p = 0.030) and other non-PCV7 serotypes (R2 = 0.877; p < 0.001), but not for serotype 6A (R2 = 0.311; p = 0.094). Considering all isolates, amoxicillin non-susceptibility showed an increasing trend (R2 = 0.528; p = 0.017). Regarding serotype 19A, increasing trends in non-susceptibility to penicillin (R2 = 0.726; p = 0.001), amoxicillin (R2 = 0.804; p < 0.001), cefotaxime (R2 = 0.546; p = 0.005) and erythromycin (R2 = 0.546; p = 0.009) were found, with amoxicillin non-susceptibility firstly detected in 2003 (7.4%) and increasing up to 38.0% in 2009. In PCV7 serotypes (which prevalence decreased from 70.7% during 1997-2000 to 10.6% in 2009) amoxicillin non-susceptibility rates showed an increasing trend (R2 = 0.702; p = 0.002). However, overall, amoxicillin non-susceptibility (≈25% in 2008-9) could be mainly attributed to serotype 19A (> 35% isolates) since PCV7 strains represented < 11% of total clinical isolates.

Conclusions
In contrast to reports on invasive pneumococcal strains, in MEF isolates the reduction in the prevalence of PCV7 serotypes was not associated with decreases in penicillin/erythromycin non-susceptibility. The high prevalence of serotype 19A among paediatric MEF isolates and the amoxicillin non-susceptibility found in this serotype are worrisome since amoxicillin is the most common antibiotic used in the treatment of acute otitis media. These data suggest that non-PCV7 serotypes (mainly serotype 19A followed by serotypes 3 and 6A) are important etiological agents of acute otitis media and support the added value of the broader coverage of the new 13-valent conjugate vaccine.
Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of Escherichia coli O157:H7-infected BALB/c mice
Authors: Rahal Elias A , Kazzi Natalie , Sabra Ahmad , Abdelnoor Alexander M , Matar Ghassan M 
Published: September 2011

Abstract

Background
Treatment of Escherichia coli O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy.

Methods
The utility of decreasing Shiga toxin gene expression in E. coli O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated in vitro using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of E. coli O157:H7-infected BALB/c mice was also monitored.

Results
Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating E. coli O157:H7 in vitro with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins from E. coli O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with E. coli O157:H7 was observed in those treated with the in vivo MIC equivalent dose of rifampicin followed by the in vivo MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone.

Conclusions
The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating E. coli O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing E. coli strains.
Response to dexamethasone is glucose-sensitive in multiple myeloma cell lines
Authors: Friday Ellen , Ledet Johnathan , Turturro Francesco 
Published: September 2011

Abstract

Background
Hyperglycemia is among the major side effects of dexamethasone (DEX). Glucose or glucocorticoid (GC) regulates the expression of thioredoxin-interacting protein (TXNIP) that controls the production of reactive oxygen species (ROS) through the modulation of thioredoxin (TRX) activity.

Methods
Multiple myeloma (MM) cells were grown in 5 or 20 mM/L glucose with or without 25 μM DEX. Semiquantitative reverse transcription-PCR (RT-PCR) was used to assess TXNIP RNA expression in response to glucose and DEX. ROS were detected by 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA). TRX activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorbtion and used to calculate the DEX IC50 in 20 mM/L glucose using the Chou's dose effect equation.

Results
TXNIP RNA level responded to glucose or DEX with the same order of magnitude ARH77 > NCIH929 > U266B1 in these cells. MC/CAR cells were resistant to the regulation. ROS level increased concurrently with reduced TRX activity. Surprisingly glucose increased TRX activity in MC/CAR cells keeping ROS level low. DEX and glucose were lacking the expected additive effect on TXNIP RNA regulation when used concurrently in sensitive cells. ROS level was significantly lower when DEX was used in conditions of hyperglycemia in ARH77/NCIH9292 cells but not in U266B1 cells. Dex-IC50 increased 10-fold when the dose response effect of DEX was evaluated with glucose in ARH && and MC/Car cells

Conclusions
Our study shows for the first time that glucose or DEX regulates important components of ROS production through TXNIP modulation or direct interference with TRX activity in MM cells. We show that glucose modulates the activity of DEX through ROS regualtion in MM cells. A better understanding of these pathways may help in improving the efficacy and reducing the toxicity of DEX, a drug still highly used in the treatment of MM. Our study also set the ground to study the relevance of the metabolic milieu in affecting drug response and toxicity in diabetic versus non-diabetic patients with MM.
Platelet glycoprotein Ibα is an important mediator of ischemic stroke in mice
Authors: De Meyer Simon F , Schwarz Tobias , Schatzberg Daphne , Wagner Denisa D 
Published: September 2011

Abstract

Background
Platelets play an important role in ischemic stroke. GPIbα is a major platelet receptor that is critical for platelet adhesion to exposed subendothelial matrix components at sites of vascular damage.

Methods
In this study, we used transgenic mice in which the extracellular part of GPIbα is replaced by human interleukin 4-receptor (GPIbα/IL4Rα). We observed normal brain vasculature in these mice. We compared infarct size in GPIbα/IL4Rα and wild-type (WT) mice 23 hours after 1-hour transient middle cerebral artery occlusion (tMCAO). In addition, the functional outcome was evaluated using a modified Bederson score.

Results
We found a significantly smaller infarct size in GPIbα/IL4Rα mice compared to WT mice (38.0 ± 6.5 mm3 vs. 74.2 ± 8.6 mm3, p < 0.001). The decrease in infarct size was functionally relevant as indicated by a significantly better functional Bederson score in GPIbα/IL4Rα mice compared to WT animals (1.3 ± 0.4 vs. 2.7 ± 0.3, p < 0.05).

Conclusions
Our data illustrate and further confirm the important role of platelet GPIbα in ischemic stroke, suggesting that targeted inhibition of this receptor may open new avenues in stroke treatment.
The Tat-dependent protein translocation pathway
Authors: Hou Bo , Brüser Thomas 
Published: September 2011

AbstractThe twin-arginine translocation (Tat) pathway is found in bacteria, archaea, and plant chloroplasts, where it is dedicated to the transmembrane transport of fully folded proteins. These proteins contain N-terminal signal peptides with a specific Tat-system binding motif that is recognized by the transport machinery. In contrast to other protein transport systems, the Tat system consists of multiple copies of only two or three usually small (∼8–30 kDa) membrane proteins that oligomerize to two large complexes that transiently interact during translocation. Only one of these complexes includes a polytopic membrane protein, TatC. The other complex consists of TatA. Tat systems of plants, proteobacteria, and several other phyla contain a third component, TatB. TatB is evolutionarily and structurally related to TatA and usually forms tight complexes with TatC. Minimal two-component Tat systems lacking TatB are found in many bacterial and archaeal phyla. They consist of a ‘bifunctional’ TatA that also covers TatB functionalities, and a TatC. Recent insights into the structure and interactions of the Tat proteins have various important implications.
The Chinese ambivalence to humor: Views from undergraduates in Hong Kong and China
Authors: Yue Xiao Dong 
Published: September 2011

AbstractThis paper proposes that Chinese people have traditionally been ambivalent about humor in the following three manners: (1) they tend to value humor but consider themselves to lack humor; (2) being humorous is not associated with being an orthodox Chinese; (3) humor is important but not for everyone. The paper also proposes that the Chinese ambivalence toward humor is largely due to an appreciation-despising complex about humor that is deep-rooted in Chinese culture. To verify this, this author conducted a survey study among a sample of 337 undergraduates in Hong Kong and Huhehot. Results show that (1) participants all rated highly on importance of humor but low on perception of self humor; (2) male students considered themselves to be more humorous than female students; (3) the top ten important characteristics for humor are fundamentally different from the top ten characteristics important for Chinese personality; (4) perception of humor is more positive than that of the Chinese personality. The paper concludes with a discussion of the psycho-social implications of the present findings on studies and enhancement of humor in Chinese society as well on some thoughts on further directions of research.
Modeling and Simulation of Film and Transitional Boiling Processes on a Metallic Cylinder During Quenching
Authors: Stark Paul , Fritsching Udo 
Published: September 2011

Abstract
A multiphase flow and heat transfer model is used to simulate the flow field and the heat transfer process of a metal specimen located in a flow during the quenching process. The applied bubble crowd model is able to investigate the separate boiling phases within one single numerical model approach. Simulation results are discussed for the quenching of a circular cylinder in a facing water flow. The initial flow velocity and the wall superheat (at temperatures above and below the Leidenfrost point) are varied to investigate their influence on the vapor formation and on the local as well as the averaged heat transfer rates. Characteristic differences between the heat transfer on the different surfaces of the cylinder due to their orientation in the flow field are discussed.
Effects of Genetic Susceptibility for Type 2 Diabetes on the Evolution of Glucose Homeostasis Traits Before and After Diabetes Diagnosis
Authors: Gautier Alain , Roussel Ronan , Lange Céline , Piguel Xavier , Cauchi Stéphane , Vol Sylviane , Froguel Philippe , Balkau Beverley , Bonnet Fabrice 
Published: September 2011

OBJECTIVE
To assess the impact of genetic susceptibility on evolution toward type 2 diabetes (T2D) by analyzing time trajectories of fasting glucose, glycated hemoglobin (HbA1c), insulin sensitivity (homeostasis model assessment [HOMA2%S]), and β-cell secretion (HOMA2%B) in a large nondiabetic cohort. We also examined whether baseline HbA1c modified the effect of genetic predisposition on the time trajectories.

RESEARCH DESIGN AND METHODS
Time trajectories were drawn in 4,744 participants from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort based on samples collected every 3 years over a 9-year follow-up. Trajectories were analyzed according to the TCF7L2 common variant, a family history of T2D, and a combination of at-risk alleles from nine T2D-associated genes.

RESULTS
There was a marked decrease in HOMA2%B in parallel to a steep increase in HbA1c over the 3 years before incident diabetes, which was not influenced by genetic predisposition when considered alone. However, after the onset of T2D, the TCF7L2 at-risk variant was associated with a greater decrease in HOMA2%B. There was a joint effect of a family history of T2D with the presence of the TCF7L2 risk allele with a greater rise in HbA1c conferred by the coexistence of a family history and the T risk allele. An HbA1c ≥5.7% at baseline was associated with a greater increase in both glycemia and HbA1c levels in the presence of a combination of diabetes at-risk alleles.

CONCLUSIONS
After incident T2D, TCF7L2 at-risk variants were associated with a faster decrease in β-cell function compared with those with the CC genotype. There was a joint effect of family history of T2D and TCF7L2 risk variant on the rise in glycemia and the decrease in insulin secretion at the end of follow-up, suggesting the joint influence of the combination of diabetes genetic predisposition with familial factors on the evolution of glycemia over time.
Clinical Evaluation of DIAGNOdent in Detection of Occlusal Caries in Newly Erupted Noncavitated First Permanent Molars in Caries-Active Children
Authors: Duruturk L , Çiftçi A , Baharoğlu S , Öztuna D 
Published: September 2011

Clinical RelevanceThis paper indicates that DIAGNOdent readings are not reliable for the detection of early occlusal caries in young permanent teeth.