bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress
Authors: Li Hualing , Ren Changhong , Shi Jinping , Hang Xingyi , Zhang Feilong , Gao Yan , Wu Yonghong , Xu Langlai , Chen Changsheng , Zhang Chenggang 
Published: September 2010

Abstract

Background
The nematode Caenorhabditis elegans is both sensitive and tolerant to hypoxic stress, particularly when the evolutionarily conserved hypoxia response pathway HIF-1/EGL-9/VHL is involved. Hypoxia-induced changes in the expression of a number of genes have been analyzed using whole genome microarrays in C. elegans, but the changes at the protein level in response to hypoxic stress still remain unclear.

Results
Here, we utilized a quantitative proteomic approach to evaluate changes in the expression patterns of proteins during the early response to hypoxia in C. elegans. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to compare the proteomic maps of wild type C. elegans strain N2 under a 4-h hypoxia treatment (0.2% oxygen) and under normoxia (control). A subsequent analysis by MALDI-TOF-TOF-MS revealed nineteen protein spots that were differentially expressed. Nine of the protein spots were significantly upregulated, and ten were downregulated upon hypoxic stress. Three of the upregulated proteins were involved in cytoskeletal function (LEV-11, MLC-1, ACT-4), while another three upregulated (ATP-2, ATP-5, VHA-8) were ATP synthases functionally related to energy metabolism. Four ribosomal proteins (RPL-7, RPL-8, RPL-21, RPS-8) were downregulated, indicating a decrease in the level of protein translation upon hypoxic stress. The overexpression of tropomyosin (LEV-11) was further validated by Western blot. In addition, the mutant strain of lev-11(x12) also showed a hypoxia-sensitive phenotype in subsequent analyses, confirming the proteomic findings.

Conclusions
Taken together, our data suggest that altered protein expression, structural protein remodeling, and the reduction of translation might play important roles in the early response to oxygen deprivation in C. elegans, and this information will help broaden our knowledge on the mechanism of hypoxia response.
Overestimation of physical activity level is associated with lower BMI: a cross-sectional analysis
Authors: Watkinson Clare , van Sluijs Esther MF , Sutton Stephen , Hardeman Wendy , Corder Kirsten , Griffin Simon J 
Published: September 2010

Abstract

Background
Poor recognition of physical inactivity may be an important barrier to healthy behaviour change, but little is known about this phenomenon. We aimed to characterize a high-risk population according to the discrepancies between objective and self-rated physical activity (PA), defined as awareness.

Methods
An exploratory cross-sectional analysis of PA awareness using baseline data collected from 365 ProActive participants between 2001 and 2003 in East Anglia, England. Self-rated PA was defined as 'active' or 'inactive' (assessed via questionnaire). Objective PA was defined according to achievement of guideline activity levels (≥30 minutes or <30 minutes spent at least moderate intensity PA, assessed by heart rate monitoring). Four awareness groups were created: 'Realistic Actives', 'Realistic Inactives', 'Overestimators' and 'Underestimators'. Logistic regression was used to assess associations between awareness group and 17 personal, social and biological correlates.

Results
63.3% of participants (N = 231) were inactive according to objective measurement. Of these, 45.9% rated themselves as active ('Overestimators'). In a multiple logistic regression model adjusted for age and smoking, males (OR = 2.11, 95% CI = 1.12, 3.98), those with lower BMI (OR = 0.89, 95% CI = 0.84, 0.95), younger age at completion of full-time education (OR = 0.83, 95% CI = 0.74, 0.93) and higher general health perception (OR = 1.02 CI = 1.00, 1.04) were more likely to overestimate their PA.

Conclusions
Overestimation of PA is associated with favourable indicators of relative slimness and general health. Feedback about PA levels could help reverse misperceptions.
Modulation of polymorphonuclear neutrophil functions by astrocytes
Authors: Xie Luokun , Poteet Ethan C , Li Wenjun , Scott Amanda E , Liu Ran , Wen Yi , Ghorpade Anuja , Simpkins James W , Yang Shao-Hua 
Published: September 2010

AbstractBackgroundNeuroinflammation is a complex process involving cells from the immune system and the central nerve system (CNS). Polymorphonuclear neutrophils (PMN) are the most abundant class of white blood cells, and typically the first type of leukocyte recruited to sites of inflammation. In the CNS, astrocytes are the most abundant glial cell population and participate in the local innate immune response triggered by a variety of insults. In the present study, we investigated the impacts of astrocytes on PMN function.MethodsPrimary astrocyte cultures were derived from postnatal C57BL/6 mice and primary neutrophils were isolated from 8 to 12 weeks old C57BL/6 mice. PMNs respiratory burst was analyzed by H2DCFDA assay. For phagocytosis assay, neutrophils were incubated with FITC-labeled E. coli and the phagocytosis of E coli was determined by flow cytometer. PMNs degranulation was determined by myeloperoxidase assay. Cytokine expression was determined by real-time PCR. To determine the involvement of different signaling pathway, protein lysates were prepared and western blots were conducted to assess the activation of Akt, Erk1/2, and p38.ResultsUsing ex vivo neutrophils and primary astrocyte cultures, our study demonstrated that astrocytes differentially regulate neutrophil functions, depending upon whether the interactions between the two cell types are direct or indirect. Upon direct cell-cell contact, astrocytes attenuate neutrophil apoptosis, respiratory bust, and degranulation, while enhancing neutrophil phagocytic capability and pro-inflammatory cytokine expression. Through indirect interaction with neutrophils, astrocytes attenuate apoptosis and enhance necrosis in neutrophils, augment neutrophil phagocytosis and respiratory burst, and inhibit neutrophil degranulation. In addition, astrocytes could augment Akt, Erk1/2, and p38 activation in neutrophils.ConclusionsAstrocytes differentially regulate neutrophil functions through direct or indirect interactions between the two cell types. The diversified actions of astrocytes on neutrophils might provide protection against potential microbial infections given compromised blood-brain barrier integrity under certain neuropathological conditions. The complex actions of astrocytes on neutrophils could provide further insight to harness the inflammatory response to promote CNS repair.
Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction
Authors: van der Schaaf René J , Claessen Bimmer E , Hoebers Loes P , Verouden Niels J , Koolen Jacques J , Suttorp Maarten J , Barbato Emanuele , Bax Matthijs , Strauss Bradley H , Olivecrona Göran K , Tuseth Vegard , Glogar Dietmar , Råmunddal Truls , Tijssen Jan G , Piek Jan J , Henriques José PS ,   EXPLORE investigators
Published: September 2010

Abstract

Background
In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.

Methods/Design
The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.

Discussion
The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.

Trial registration
trialregister.nl NTR1108.
Use of anchorchip-time-of-flight spectrometry technology to screen tumor biomarker proteins in serum for small cell lung cancer
Authors: Du Jie , Yang Shuanying , Lin Xiuli , Bu Lina , Nan Yandong , Huo Shufen , Shang Wenli 
Published: September 2010

Abstract

Background
The purpose of this study is to discover potential biomarkers in serum for the detection of small cell lung cancer (SCLC).

Methods
74 serum samples including 30 from SCLC patients and 44 from healthy controls were analyzed using ClinProt system combined with matrix-assisted laser desorption/ionization time-of-flight masss spectrometry (MALDI-TOF-MS). ClinProt software and genetic algorithm analysis selected a panel of serum markers that most efficiently predicted which patients had SCLC.

Results
The diagnostic pattern combined with 5 potential biomarkers could differentiate SCLC patients from healthy persons, with a sensitivity of 90%, specificity of 97.73%. Remarkably, 88.89% of stage I/II patients were accurately assigned to SCLC.

Conclusions
Anchorchip-time-of-flight spectrometry technology will provide a highly accurate approach for discovering new biomarkers for the detection of SCLC.
A yeast's eye view of mammalian reproduction: cross-species gene co-expression in meiotic prophase
Authors: Li Yunfei , Lam Ka-sum , Dasgupta Nairanjana , Ye Ping 
Published: September 2010

Abstract

Background
Meiotic prophase is a critical stage in sexual reproduction. Aberrant chromosome recombination during this stage is a leading cause of human miscarriages and birth defects. However, due to the experimental intractability of mammalian gonads, only a very limited number of meiotic genes have been characterized. Here we aim to identify novel meiotic genes important in human reproduction through computational mining of cross-species and cross-sex time-series expression data from budding yeast, mouse postnatal testis, mouse embryonic ovary, and human fetal ovary.

Results
Orthologous gene pairs were ranked by order statistics according to their co-expression profiles across species, allowing us to infer conserved meiotic genes despite obvious differences in cellular synchronicity and composition in organisms. We demonstrated that conserved co-expression networks could successfully recover known meiotic genes, including homologous recombination genes, chromatin cohesion genes, and genes regulating meiotic entry. We also showed that conserved co-expression pairs exhibit functional connections, as evidenced by the annotation similarity in Gene Ontology and overlap with physical interactions. More importantly, we predicted six new meiotic genes through their co-expression linkages with known meiotic genes, and subsequently used the genetically more amenable yeast system for experimental validation. The deletion mutants of all six genes showed sporulation defects, equivalent to a 100% validation rate.

Conclusions
We identified evolutionarily conserved gene modules in meiotic prophase by integrating cross-species and cross-sex expression profiles from budding yeast, mouse, and human. Our co-expression linkage analyses confirmed known meiotic genes and identified several novel genes that might be critical players in meiosis in multiple species. These results demonstrate that our approach is highly efficient to discover evolutionarily conserved novel meiotic genes, and yeast can serve as a valuable model system for investigating mammalian meiotic prophase.
Evaluation of the bacterial diversity of Pressure ulcers using bTEFAP pyrosequencing
Authors: Smith Drake M , Snow David E , Rees Eric , Zischkau Ann M , Hanson J Delton , Wolcott Randall D , Sun Yan , White Jennifer , Kumar Shashi , Dowd Scot E 
Published: September 2010

Abstract

Background
Decubitus ulcers, also known as bedsores or pressure ulcers, affect millions of hospitalized patients each year. The microflora of chronic wounds such as ulcers most commonly exist in the biofilm phenotype and have been known to significantly impair normal healing trajectories.

Methods
Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP), a universal bacterial identification method, was used to identify bacterial populations in 49 decubitus ulcers. Diversity estimators were utilized and wound community compositions analyzed in relation to metadata such as Age, race, gender, and comorbidities.

Results
Decubitus ulcers are shown to be polymicrobial in nature with no single bacterium exclusively colonizing the wounds. The microbial community among such ulcers is highly variable. While there are between 3 and 10 primary populations in each wound there can be hundreds of different species present many of which are in trace amounts. There is no clearly significant differences in the microbial ecology of decubitus ulcer in relation to metadata except when considering diabetes. The microbial populations and composition in the decubitus ulcers of diabetics may be significantly different from the communities in non-diabetics.

Conclusions
Based upon the continued elucidation of chronic wound bioburdens as polymicrobial infections, it is recommended that, in addition to traditional biofilm-based wound care strategies, an antimicrobial/antibiofilm treatment program can be tailored to each patient's respective wound microflora.
Genome-wide analysis of mRNA decay patterns during early Drosophiladevelopment
Authors: Thomsen Stefan , Anders Simon , Janga Sarath Chandra , Huber Wolfgang , Alonso Claudio R 
Published: September 2010

Abstract
Background
The modulation of mRNA levels across tissues and time is key for the establishment and operation of the developmental programs that transform the fertilized egg into a fully formed embryo. Although the developmental mechanisms leading to differential mRNA synthesis are heavily investigated, comparatively little attention is given to the processes of mRNA degradation and how these relate to the molecular programs controlling development.

Results
Here we combine timed collection of Drosophila embryos and unfertilized eggs with genome-wide microarray technology to determine the degradation patterns of all mRNAs present during early fruit fly development. Our work studies the kinetics of mRNA decay, the contributions of maternally and zygotically encoded factors to mRNA degradation, and the ways in which mRNA decay profiles relate to gene function, mRNA localization patterns, translation rates and protein turnover. We also detect cis-regulatory sequences enriched in transcripts with common degradation patterns and propose several proteins and microRNAs as developmental regulators of mRNA decay during early fruit fly development. Finally, we experimentally validate the effects of a subset of cis-regulatory sequences and trans-regulators in vivo.

Conclusions
Our work advances the current understanding of the processes controlling mRNA degradation during early Drosophila development, taking us one step closer to the understanding of mRNA decay processes in all animals. Our data also provide a valuable resource for further experimental and computational studies investigating the process of mRNA decay.
Hepatitis C Virus Seromarkers and Subsequent Risk of Hepatocellular Carcinoma: Long-Term Predictors From a Community-Based Cohort Study
Authors: Mei-Hsuan Lee , Yang Hwai-I , Lu Sheng-Nan , Jen Chin-Lan , Yeh Shiou-Hwei , Liu Chun-Jen , Chen Pei-Jer , You San-Lin , Wang Li-Yu , Chen Wei J. , Chen Chien-Jen 
Published: September 2010

Purpose Hepatitis C virus (HCV) contributes to one third of hepatocellular carcinoma cases worldwide. Long-term predictors for HCV-related hepatocellular carcinoma are essential for early intervention. Serum HCV RNA and ALT levels and HCV genotype were assessed for their predictability of hepatocellular carcinoma risk. Methods A prospective cohort of 925 participants positive for antibodies against HCV and age 30 to 65 years was recruited and followed from 1991 to 2006. Serum HCV RNA and ALT levels and HCV genotypes at enrollment and during follow-up were examined. Newly developed hepatocellular carcinoma was identified by health examination and computerized linkage with national cancer registration and death certification profiles. Multivariate adjusted hazard ratios with 95% CIs were estimated using Cox regression models. Results Fifty-five participants newly developed hepatocellular carcinoma during 8,476 person-years of follow-up, giving an incidence rate of 648.9 per 100,000 person-years. The cumulative hepatocellular carcinoma risk increased from 1.1% for HCV RNA seronegative status to 6.4% for low HCV RNA levels and to 14.7% for high HCV RNA levels (P < .001). The cumulative risk also increased with elevated serum ALT levels from 1.7% for persistently ≤ 15 U/L to 4.2% for ever more than 15 U/L but never more than 45 U/L and to 13.8% for ALT ever ≥ 45 U/L (P < .001). Having HCV genotype 1 was associated with a higher cumulative hepatocellular carcinoma risk (12.6%) than not having HCV genotype 1 (4.5%; P < .001). Conclusion Elevated serum levels of HCV RNA and ALT and HCV genotype 1 infection are independent risk predictors of hepatocellular carcinoma. These findings have strong implications for the management of chronic HCV.
Factors for Hematopoietic Toxicity of Carboplatin: Refining the Targeting of Carboplatin Systemic Exposure
Authors: Schmitt Antonin , Gladieff Laurence , Laffont Céline M. , Evrard Alexandre , Boyer Jean-Christophe , Lansiaux Amélie , Bobin-Dubigeon Christine , Etienne-Grimaldi Marie-Christine , Boisdron-Celle Michèle , Mousseau Mireille , Pinguet Frédéric , Floquet Anne , Billaud Eliane M. , Durdux Catherine , Le Guellec Chantal , Mazières Julien , Lafont Thierry , Ollivier Florent , Concordet Didier , Chatelut Etienne 
Published: September 2010

Purpose Area under the curve (AUC) dosing is routinely carried out for carboplatin, but the chosen target AUC values remain largely empirical. This multicenter pharmacokinetic-pharmacodynamic (PK-PD) study was performed to determine the covariates involved in the interindividual variability of carboplatin hematotoxicity that should be considered when choosing individual target AUCs. Patients and Methods Three hundred eighty-three patients received carboplatin as part of established regimens. A semi-physiologic population PK-PD model was applied to describe separately the time course of absolute neutrophil and platelet counts using NONMEM software. The plasma ultrafiltrable carboplatin concentration (CCarbo) was assumed to inhibit the proliferation of blood cell precursors through a linear model: drug effect = slope × CCarbo. The slope corresponds to the patients' sensitivity to carboplatin hematotoxicity. The relationships between the patients' sensitivity to the neutropenic or thrombopenic effects of carboplatin and various covariates, including associated chemotherapies, demographic, biologic, and pharmacogenetic data, were studied. Results The sensitivity of carboplatin-induced thrombocytopenia decreased in the case of concomitant paclitaxel chemotherapy (slope decreased by 24%), whereas it increased with coadministration of etoposide and gemcitabine (slope increased by 45% and 133%, respectively). For neutropenia, the sensitivity increased when carboplatin was combined with other cytotoxics (slope increased by 76%). Conclusion This study provides useful information to clinicians to better estimate the hematopoietic toxicity of carboplatin and thus choose more rationally carboplatin target AUCs as a function of pretreatment or concomitantly administered chemotherapies. For example, an AUC of 5 mg/mL · min is associated with a risk of grade 3 or 4 thrombocytopenia of 2% in combination with paclitaxel versus 38% with gemcitabine in a non-pretreated patient.
Best Supportive Care Compared With Chemotherapy for Unresectable Gall Bladder Cancer: A Randomized Controlled Study
Authors: Sharma Atul , Dwary Amit Dutt , Mohanti Bidhu Kalyan , Deo Surya V. , Pal Sujoy , Sreenivas Vishnu , Raina Vinod , Shukla Nootan Kumar , Thulkar Sanjay , Garg Pramod , Chaudhary Surendra Pal 
Published: September 2010

Purpose We designed this study to evaluate efficacy of modified gemcitabine and oxaliplatin (mGEMOX) over best supportive care (BSC) or fluorouracil (FU) and folinic acid (FA) in unresectable gall bladder cancer (GBC). Patients and Methods Patients with unresectable GBC were enrolled for single center randomized study. Arm A, BSC; arm B, FU 425 mg/m2 and FA 20 mg/m2 intravenous (IV) bolus weekly for 30 weeks (FUFA); arm C, gemcitabine 900 mg/m2 and oxaliplatin 80 mg/m2 IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles. Eighty-one patients were randomly assigned, arms A (n = 27), B (n = 28), and C (n = 26). Results Complete response plus partial response in the three groups was 0 (0%), four (14.3%), and eight (30.8%) respectively (P < .001). Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy. One patient in the mGEMOX arm had complete pathologic response. Median overall survival (OS) was 4.5, 4.6, and 9.5 months for the BSC, FUFA, and mGEMOX arms (P = .039), respectively. Progression-free survival (PFS) was 2.8, 3.5, and 8.5 months for the three groups (P < .001). There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis, which was more prevalent in mGEMOX arm (P = .04). Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression. Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics. Conclusion This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.