bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redox Balance via Lactate Dehydrogenase Is Important for Multiple Stress Resistance and Virulence in Enterococcus faecalis
Authors: Rana Nosheen Fatima , Sauvageot Nicolas , Laplace Jean-Marie , Bao YinYin , Nes Ingolf , Rincé Alain , Posteraro Brunella , Sanguinetti Maurizio , Hartke Axel 
Published: May 2013

ABSTRACT

Enterococcus faecalis
is a highly stress resistant opportunistic pathogen. The intrinsic ruggedness of this bacterium is supposed to be the basis of its capacity to colonize the hostile environments of hospitals and to cause several kinds of infections. We show in this work that general resistance to very different environmental stresses depends on the ability of
E. faecalis
to maintain redox balance via lactate dehydrogenase (LDH). Furthermore, LDH-deficient mutants are less successful than the wild type at colonizing host organs in a murine model of systemic infection. Taken together, our results, as well as those previously published for
Staphylococcus aureus
(A. R. Richardson, S. J. Libby, and F. C. Fang, Science 319:1672–1676, 2008), identify LDH as an attractive drug target. These drugs may have additional applications, as in the fight against glycopeptide antibiotic-resistant bacteria and even cancer.
Sleep Disruption Among Older Men and Risk of Prostate Cancer
Authors: Sigurdardottir Lara G. , Valdimarsdottir Unnur A. , Mucci Lorelei A. , Fall Katja , Rider Jennifer R. , Schernhammer Eva , Czeisler Charles A. , Launer Lenore , Harris Tamara , Stampfer Meir J. , Gudnason Vilmundur , Lockley Steven W. 
Published: May 2013

Abstract
Background: Although positive associations have consistently been reported between sleep disruption and breast cancer, less is known about its potential role in prostate cancer.
Methods: Within the prospective AGES-Reykjavik cohort study, we followed 2,102 men recruited in 2002–2006 until the end of 2009. Participants answered questions on sleep disruption. Information on the occurrence of prostate cancer was obtained through record linkages across the Icelandic Cancer Registry. We used Cox regression models with 95% confidence intervals (CI) to estimate HRs of prostate cancer by symptoms of sleep disruption.
Results: During follow-up, 135 men (6.4%) were diagnosed with prostate cancer. Compared with men without sleep disruption, those with problems falling and staying asleep were at significantly increased risk of prostate cancer [HR, 1.7 (95% CI, 1.0–2.9) and 2.1 (95% CI, 1.2–3.7)], respectively, with increasing sleep disruption severity. When restricted to advanced prostate cancer (≥ stage T3 or lethal disease), these associations became even stronger [HR 2.1 (95% CI, 0.7–6.2) and 3.2 (95% CI, 1.1–9.7)]. The results did not change after excluding from the analyses men who woke up during the night, indicative of nocturia, suggesting limited risk of reverse association.
Conclusions: Our data suggest that certain aspects of sleep disruption may confer an increased risk of prostate cancer and call for additional, larger studies with longer follow-up times.
Impact: Prostate cancer is one of the leading public health concerns in men; if confirmed in future studies, the association between sleep disruption and prostate cancer risk may open new avenues for prevention. Cancer Epidemiol Biomarkers Prev; 22(5); 872–9. ©2013 AACR.
A NOTCH3 Transcriptional Module Induces Cell Motility in Neuroblastoma
Authors: van Nes Johan , Chan Alvin , van Groningen Tim , van Sluis Peter , Koster Jan , Versteeg Rogier 
Published: May 2013

Abstract
Purpose: Neuroblastoma is a childhood tumor of the peripheral sympathetic nervous system with an often lethal outcome due to metastatic disease. Migration and epithelial–mesenchymal transitions have been implicated in metastasis but they are hardly investigated in neuroblastoma.
Experimental Design: Cell migration of 16 neuroblastoma cell lines was quantified in Transwell migration assays. Gene expression profiling was used to derive a migration signature, which was applied to classify samples in a neuroblastoma tumor series. Differential expression of transcription factors was analyzed in the subsets. NOTCH3 was prioritized, and inducible transgene expression studies in cell lines were used to establish whether it functions as a master switch for motility.
Results: We identified a 36-gene expression signature that predicts cell migration. This signature was used to analyse expression profiles of 88 neuroblastoma tumors and identified a group with distant metastases and a poor prognosis. This group also expressed a known mesenchymal gene signature established in glioblastoma. Neuroblastomas recognized by the motility and mesenchymal signatures strongly expressed genes of the NOTCH pathway. Inducible expression of a NOTCH intracellular (NOTCH3-IC) transgene conferred a highly motile phenotype to neuroblastoma cells. NOTCH3-IC strongly induced expression of motility- and mesenchymal marker genes. Many of these genes were significantly coexpressed with NOTCH3 in neuroblastoma, as well as colon, kidney, ovary, and breast tumor series.
Conclusion: The NOTCH3 transcription factor is a master regulator of motility in neuroblastoma. A subset of neuroblastoma with high expression of NOTCH3 and its downstream-regulated genes has mesenchymal characteristics, increased incidence of metastases, and a poor prognosis. Clin Cancer Res; 19(13); 3485–94. ©2013 AACR.
Subcapital Oblique Osteotomy for Correction of Bunionette Deformity
Authors: Cooper Minton Truitt , Coughlin Michael J. 
Published: May 2013

Background: Many procedures have been described for correction of bunionette deformity. For symptomatic type I deformity, the authors have routinely performed a subcapital oblique osteotomy of the fifth metatarsal. The purpose of this study was to report the medium-term results of this procedure. Methods: This is a retrospective review of patients who underwent subcapital oblique osteotomy for correction of type I bunionette deformity. Patients were evaluated radiographically and clinically. Sixteen feet in 14 patients were available at final follow-up. Results: At a mean 2.9-year follow-up, 88% of patients had good or excellent clinical result, 88% of patients had no limitation in activity, and mean pain score on a visual analog scale was 1.6 out of 10. Radiographically, a statistical difference was found when we compared the preoperative and 6-week follow-up fifth metatarsophalangeal angle; however, no statistical difference was found in the fourth to fifth intermetatarsal angle at any time or in comparison of the preoperative and final follow-up fifth metatarsophalangeal angles. Conclusion: We found the subcapital oblique osteotomy of the fifth metatarsal to provide reliable clinical results for correction of painful type I bunionette deformity. Level of Evidence: Level IV, retrospective case series.
Recent progress toward epigenetic therapies: the example of mixed lineage leukemia
Authors: Neff Tobias , Armstrong Scott A. 
Published: May 2013

AbstractThe importance of epigenetic gene regulatory mechanisms in normal and cancer development is increasingly evident. Genome-wide analyses have revealed the mutation, deletion, and dysregulated expression of chromatin-modifying enzymes in a number of cancers, including hematologic malignancies. Genome-wide studies of DNA methylation and histone modifications are beginning to reveal the landscape of cancer-specific chromatin patterns. In parallel, recent genetic loss-of-function studies in murine models are demonstrating functional involvement of chromatin-modifying enzymes in malignant cell proliferation and self-renewal. Paradoxically, the same chromatin modifiers can, depending on cancer type, be either hyperactive or inactivated. Increasingly, cross talk between epigenetic pathways is being identified. Leukemias carrying MLL rearrangements are quintessential cancers driven by dysregulated epigenetic mechanisms in which fusion proteins containing N-terminal sequences of MLL require few or perhaps no additional mutations to cause human leukemia. Here, we review how recent progress in the field of epigenetics opens potential mechanism-based therapeutic avenues.
EBV-positive diffuse large B-cell lymphoma of the elderly
Authors: Ok Chi Young , Papathomas Thomas G. , Medeiros L. Jeffrey , Young Ken H. 
Published: May 2013

Abstract
Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008 World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in patients >50 years of age and in whom there is no known immunodeficiency or history of lymphoma. These tumors are more common in Asia but also occur in North America and Europe at a low frequency. These neoplasms exhibit a morphologic continuum, from polymorphous to monomorphous, but morphologic features do not correlate with prognosis as all patients have a clinically aggressive course. Most EBV-positive DLBCL of the elderly patients have an activated B-cell immunophenotype and are characterized by prominent nuclear factor-κB activation. Cytogenetic complexity is usually low. In this review, we comprehensively delineate the data emerging from analyses of EBV latency program, microRNA-mediated EBV viral oncogenesis, functional genomics of EBV and its biology, and differential diagnosis challenge for EBV-positive DLBCL of the elderly. It is hoped that the improved understanding of these tumors will lead to the development of novel therapeutic approaches, enhance the effectiveness of clinical trials, and improve prognosis.
Gene-based single nucleotide polymorphism discovery in bovine muscle using next-generation transcriptomic sequencing
Authors: Djari Anis , Esquerré Diane , Weiss Bernard , Martins Frédéric , Meersseman Cédric , Boussaha Mekki , Klopp Christophe , Rocha Dominique 
Published: May 2013

Abstract

Background
Genetic information based on molecular markers has increasingly being used in cattle breeding improvement programmes, as a mean to improve conventionally phenotypic selection. Advances in molecular genetics have led to the identification of several genetic markers associated with genes affecting economic traits. Until recently, the identification of the causative genetic variants involved in the phenotypes of interest has remained a difficult task. The advent of novel sequencing technologies now offers a new opportunity for the identification of such variants. Despite sequencing costs plummeting, sequencing whole-genomes or large targeted regions is still too expensive for most laboratories. A transcriptomic-based sequencing approach offers a cheaper alternative to identify a large number of polymorphisms and possibly to discover causative variants. In the present study, we performed a gene-based single nucleotide polymorphism (SNP) discovery analysis in bovine Longissimus thoraci, using RNA-Seq. To our knowledge, this represents the first study done in bovine muscle.

Results
Messenger RNAs from Longissimus thoraci from three Limousin bull calves were subjected to high-throughput sequencing. Approximately 36–46 million paired-end reads were obtained per library. A total of 19,752 transcripts were identified and 34,376 different SNPs were detected. Fifty-five percent of the SNPs were found in coding regions and ~22% resulted in an amino acid change. Applying a very stringent SNP quality threshold, we detected 8,407 different high-confidence SNPs, 18% of which are non synonymous coding SNPs. To analyse the accuracy of RNA-Seq technology for SNP detection, 48 SNPs were selected for validation by genotyping. No discrepancies were observed when using the highest SNP probability threshold. To test the usefulness of the identified SNPs, the 48 selected SNPs were assessed by genotyping 93 bovine samples, representing mostly the nine major breeds used in France. Principal component analysis indicates a clear separation between the nine populations.

Conclusions
The RNA-Seq data and the collection of newly discovered coding SNPs improve the genomic resources available for cattle, especially for beef breeds. The large amount of variation present in genes expressed in Limousin Longissimus thoracis, especially the large number of non synonymous coding SNPs, may prove useful to study the mechanisms underlying the genetic variability of meat quality traits.
Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis
Authors: Zhao Guanghui , Zhou Aihua , Lv Gang , Meng Min , Sun Min , Bai Yang , Han Yali , Wang Lin , Zhou Huaiyu , Cong Hua , Zhao Qunli , Zhu Xing-Quan , He Shenyi 
Published: May 2013

Abstract

Background

Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii. The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii.

Methods
Using bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines.

Results
TgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection.

Conclusions

T. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines.
Five years of malaria control in the continental region, Equatorial Guinea
Authors: Rehman Andrea M , Mann Andrea G , Schwabe Christopher , Reddy Michael R , Roncon Gomes Irina , Slotman Michel A , Yellott Lee , Matias Abrahan , Caccone Adalgisa , Nseng Nchama Gloria , Kleinschmidt Immo 
Published: May 2013

Abstract

Background
A successful malaria control programme began in 2004 on Bioko Island, Equatorial Guinea. From 2007, the same multiple malaria interventions, though reduced in scope for funding reasons, were introduced to the four mainland provinces of Equatorial Guinea (the continental region) aiming to recreate Bioko’s success. Two provinces received long-lasting insecticidal nets (LLINs) and two provinces received biannual indoor residual spraying (IRS). Enhanced case management and communications were introduced throughout.

Methods
Estimates of intervention coverage and indicators of malaria transmission for 2007 to 2011 were derived from annual malaria indicator surveys (MIS). Results were complemented by health information system (HIS) and entomological data. The personal protection offered by LLINs and IRS against Plasmodium falciparum infection was estimated with logistic regression.

Results
The estimated proportion of children aged 1–4 using either an LLIN the previous night or living in a house sprayed in the last six months was 23% in 2007 and 42% in 2011. The estimated prevalence of P. falciparum in children aged 1–4 was 68% (N=1,770; 95% confidence interval [CI]: 58-76%) in 2007 and 52% (N=1,602; 95% CI: 44-61%) in 2011. Children 1–4 years had lower prevalence if they used an LLIN the previous night (N=1,124, 56%; adjusted odds ratio [aOR] 0.64, 95% CI: 0.55-0.74) or if they lived in a sprayed house (N=1,150, 57%; aOR 0.80, 95% CI: 0.62-1.03) compared to children with neither intervention (N=4,131, 66%, reference group). The minority of children who both used an LLIN and lived in a sprayed house had the lowest prevalence of infection (N=171, 45%; aOR 0.52, 95% CI: 0.35-0.78). High site-level intervention coverage did not always correlate with lower site-level P. falciparum prevalence. The malaria season peaked in either June or July, not necessarily coinciding with MIS data collection.

Conclusions
Though moderate impact was achieved after five years of vector control, case management, and communications, prevalence remained high due to an inability to sufficiently scale-up coverage with either IRS or LLINs. Both LLINs and IRS provided individual protection, but greater protection was afforded to children who benefitted from both.
Expression of HPV16 E5 down-modulates the TGFbeta signaling pathway
Authors: French Deborah , Belleudi Francesca , Mauro Maria Vittoria , Mazzetta Francesca , Raffa Salvatore , Fabiano Vincenza , Frega Antonio , Torrisi Maria Rosaria 
Published: May 2013

Abstract

Background
Infection with high-risk human papillomavirus (HR-HPV) genotypes, mainly HPV16 and HPV18, is a major risk factor for cervical cancer and responsible for its progression. While the transforming role of the HPV E6 and E7 proteins is more characterized, the molecular mechanisms of the oncogenic activity of the E5 product are still only partially understood, but appear to involve deregulation of growth factor receptor expression. Since the signaling of the transforming growth factor beta (TGFbeta) is known to play crucial roles in the epithelial carcinogenesis, aim of this study was to investigate if HPV16 E5 would modulate the TGF-BRII expression and TGFbeta/Smad signaling.

Findings
The HPV16 E5 mRNA expression pattern was variable in low-grade squamous intraepithelial lesions (LSIL), while homogeneously reduced in high-grade lesions (HSIL). Parallel analysis of TGFBRII mRNA showed that the receptor transcript levels were also variable in LSILs and inversely related to those of the viral protein. In vitro quantitation of the TGFBRII mRNA and protein in human keratinocytes expressing 16E5 in a dose-dependent and time-dependent manner showed a progressive down-modulation of the receptor. Phosphorylation of Smad2 and nuclear translocation of Smad4 were also decreased in E5-expressing cells stimulated with TGFbeta1.

Conclusions
Taken together our results indicate that HPV16 E5 expression is able to attenuate the TGFbeta1/Smad signaling and propose that this loss of signal transduction, leading to destabilization of the epithelial homeostasis at very early stages of viral infection, may represent a crucial mechanism of promotion of the HPV-mediated cervical carcinogenesis.
Signal transduction in primary human T lymphocytes in altered gravity – results of the MASER-12 suborbital space flight mission
Authors: Tauber Svantje , Hauschild Swantje , Crescio Claudia , Secchi Christian , Paulsen Katrin , Pantaleo Antonella , Saba Angela , Buttron Isabell , Thiel Cora Sandra , Cogoli Augusto , Pippia Proto , Ullrich Oliver 
Published: May 2013

AbstractWe investigated the influence of altered gravity on key proteins of T cell activation during the MASER-12 ballistic suborbital rocket mission of the European Space Agency (ESA) and the Swedish Space Cooperation (SSC) at ESRANGE Space Center (Kiruna, Sweden). We quantified components of the T cell receptor, the membrane proximal signaling, MAPK-signaling, IL-2R, histone modifications and the cytoskeleton in non-activated and in ConA/CD28-activated primary human T lymphocytes. The hypergravity phase during the launch resulted in a downregulation of the IL-2 and CD3 receptor and reduction of tyrosine phosphorylation, p44/42-MAPK phosphorylation and histone H3 acetylation, whereas LAT phosphorylation was increased. Compared to the baseline situation at the point of entry into the microgravity phase, CD3 and IL-2 receptor expression at the surface of non-activated T cells were reduced after 6 min microgravity. Importantly, p44/42-MAPK-phosphorylation was also reduced after 6 min microgravity compared to the 1g ground controls, but also in direct comparison between the in-flight μg and the 1g group. In activated T cells, the reduced CD3 and IL-2 receptor expression at the baseline situation recovered significantly during in-flight 1g conditions, but not during microgravity conditions. Beta-tubulin increased significantly after onset of microgravity until the end of the microgravity phase, but not in the in-flight 1g condition. This study suggests that key proteins of T cell signal modules are not severely disturbed in microgravity. Instead, it can be supposed that the strong T cell inhibiting signal occurs downstream from membrane proximal signaling, such as at the transcriptional level as described recently. However, the MASER-12 experiment could identify signal molecules, which are sensitive to altered gravity, and indicates that gravity is obviously not only a requirement for transcriptional processes as described before, but also for specific phosphorylation / dephosphorylation of signal molecules and surface receptor dynamics.
Self-reported sitting time is not associated with incidence of cardiovascular disease in a population-based cohort of mid-aged women
Authors: Herber-Gast Gerrie-Cor M , Jackson Caroline A , Mishra Gita D , Brown Wendy J 
Published: May 2013

Abstract

Background
In Westernised societies adults are increasingly spending many hours each day in sedentary, low energy expenditure activities such as sitting. Although there is growing evidence on the relationship between television/screen time and increased cardiovascular disease mortality, very little is known about the association between total sitting time (in different domains) and cardiovascular disease incidence. We investigated this in a population-based cohort of mid-aged women in Australia.

Findings
Data were from 6154 participants in the 1946–51 birth cohort of the Australian Longitudinal Study on Women’s Health who were free of cardiovascular disease at baseline. Survival analysis was used to determine the association between self-reported sitting time and cardiovascular disease incidence, determined through hospital diagnoses and cause of death data. During a mean (± SD) follow-up time of 9.9 ± 1.2 years, 177 cases of cardiovascular disease occurred. Mean sitting time (± SD) was 5.4 ± 2.6 hours a day. Sitting time was not associated with incident cardiovascular disease (adjusted hazard ratio 0.97, 95% CI 0.92 to 1.03). We found no interaction between physical activity and sitting time and cardiovascular disease.

Conclusions
In mid-aged women sitting time does not appear to be associated with cardiovascular disease incidence. These findings are contrary to expectations, given the growing evidence of a relationship between sitting time and cardiovascular disease mortality. Research in this area is scarce and additional studies are needed to confirm or refute these findings.