bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversification of Clonal Complex 5 Methicillin-Resistant Staphylococcus aureus Strains (Rhine-Hesse Clone) within Germany
Authors: Schulte Berit , Bierbaum Gabriele , Pohl Konstanze , Goerke Christiane , Wolz Christiane 
Published: November 2012

ABSTRACT

Since 1995, a methicillin-resistant
Staphylococcus aureus
(MRSA) clone has spread in southern Germany. The strain was assigned to the Rhine-Hesse pulsed-field gel electrophoresis (PFGE) type by the staphylococcal reference center and was highly similar to epidemic clones known to belong to clonal complex 5 (CC5; USA100) based on multilocus sequence typing (MLST). Here we analyzed a defined collection of strains assigned to the Rhine-Hesse/USA100 PFGE type. Using sequence-based typing methods (MLST,
spa
), the isolates were divided into two distinct clusters, ST5 and its single-locus variant ST225. These two lineages are not distinguishable by PFGE or phage typing. Most of the ST5 isolates were derived from patients and volunteers from the Tübingen area in southwest Germany, whereas the ST225 isolates were mostly from other locations in Germany. The locally restricted ST5 isolates were shown to contain different SSC
mec
islands and exhibited different antibiotic resistance profiles. In contrast, the ST225 isolates form a highly homogenous group and are emerging all over Germany. The two lineages are clearly distinguishable by their phage content and
spa
type: ST5 strains from Tübingen are characterized by a Sa7int phage that carries the virulence gene
sak
, which codes for staphylokinase, and ST225 isolates are characterized by a Sa1int phage. In conclusion, based on sequence typing and phage content, CC5 strains can be subdivided into two distinct lineages with different epidemicities.
Three-Way Comparison of BBL CHROMagar MRSA II, MRSA
Select
, and Spectra MRSA for Detection of Methicillin-Resistant Staphylococcus aureus Isolates in Nasal Surveillance Cultures
Authors: Denys Gerald A. , Renzi Pamela B. , Koch Kim M. , Wissel Carol M. 
Published: November 2012

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a major cause of hospital-acquired and life-threatening infections. Active surveillance programs for MRSA utilize either molecular or culture-based methods. A prospective study was performed to compare the performance of selective and differential chromogenic media, BBL CHROMagar MRSA II (CMRSA II; BD Diagnostics, Sparks, MD), MRSA
Select
(Bio-Rad Laboratories, Redmond, WA), and Spectra MRSA (Remel, Lenexa, KS), for the detection of MRSA in nasal swab specimens. A total of 515 compliant remnant nasal swab specimens were sequentially used to inoculate BBL Trypticase soy agar with 5% sheep blood (TSA II) and each chromogenic medium. After 24 h of incubation, colony color reactions and morphology on chromogenic media were compared to suspicious colonies on nonselective TSA II. MRSA on TSA II was confirmed by Gram staining, a coagulase test, and a cefoxitin disk test. The overall prevalence of MRSA and methicillin-susceptible
S. aureus
(MSSA) on TSA II was 12.4% (64/515) and 9.7% (50/515), respectively. When each chromogenic medium was compared to the standard culture method, the sensitivity and specificity, respectively, were as follows: CMRSA II, 87.7% and 98.6%; MRSA
Select
, 89.0% and 93.4%; and Spectra MRSA, 83.6% and 92.1%. The positive predictive values were highest for CMRSA II (91.4%), followed by MRSA
Select
(69.1%) and Spectra MRSA (63.5%). False-positive results on chromogenic media were mainly due to color interpretation. The negative predictive values for all three media were greater than 97%. In conclusion, CMRSA II gave the best overall results for detecting MRSA from nasal specimens.
Sensitivity and Specificity of
In Situ
Hybridization for Diagnosis of Cutaneous Infection by Leishmania infantum in Dogs
Authors: Menezes Rodrigo C. , Figueiredo Fabiano B. , Wise Annabel G. , Madeira Maria F. , Oliveira Raquel V. C. , Schubach Tânia M. P. , Kiupel Matti , Langohr Ingeborg M. 
Published: November 2012

ABSTRACT

An accurate diagnosis of infection by
Leishmania infantum
in dogs is fundamental for the control of zoonotic visceral leishmaniasis (VL). Histopathology (HP) and immunohistochemistry (IHC) are frequently used for the histological diagnosis of
L. infantum
in dogs but have shown limited accuracy. To improve the sensitivity and specificity of the histological diagnosis of VL, we evaluated automated
in situ
hybridization (ISH) using a generic probe for
Leishmania
and a specific probe for
L. infantum
in surgical skin biopsy specimens of dogs. The ISH results were compared with those of HP and IHC, using parasitological culture as the reference standard. Skin samples from 51 dogs with cutaneous
L. infantum
infection and 51 noninfected dogs were randomly selected from samples of dogs from various cities in Brazil where canine VL is endemic. These samples were processed for parasitological culture, HP, IHC, and ISH using both probes. The sensitivities of ISH using the specific probe, ISH using the generic probe, IHC, and HP were, respectively, 74.5%, 70.6%, 69.5%, and 57.6%. The specificity of both ISH probes tested was 100%, and there was no cross-hybridization of the generic and specific probes with selected pathogenic fungi and protozoa. The specific probe discriminated
L. infantum
from the other species of
Leishmania
that infect dogs in the New World. ISH is highly sensitive and specific for the diagnosis of
L. infantum
in histologic samples of skin from infected dogs and can be used on routine biopsy material to make a diagnosis of leishmaniasis.
Sonication versus Vortexing of Implants for Diagnosis of Prosthetic Joint Infection
Authors: Portillo María Eugenia , Salvadó Margarita , Trampuz Andrej , Plasencia Virginia , Rodriguez-Villasante María , Sorli Lluisa , Puig Lluis , Horcajada Juan Pablo 
Published: November 2012

ABSTRACT

Biofilm removal efficacy of vortexing alone was compared with the standard vortexing-sonication procedure. Among 135 removed prostheses, 35 were diagnosed with infection and 100 with aseptic failure. At a cutoff of ≥50 CFU/ml, sonication was more sensitive than vortexing (60% versus 40%,
P
= 0.151), while the specificity was 99% for both methods.
The Replication Defect of ICP0-Null Mutant Herpes Simplex Virus 1 Can Be Largely Complemented by the Combined Activities of Human Cytomegalovirus Proteins IE1 and pp71
Authors: Everett Roger D. , Bell Adam J. , Lu Yongxu , Orr Anne 
Published: November 2012

ABSTRACT
Herpes simplex virus 1 (HSV-1) immediate-early protein ICP0 is required for efficient lytic infection and productive reactivation from latency and induces derepression of quiescent viral genomes. Despite being unrelated at the sequence level, ICP0 and human cytomegalovirus proteins IE1 and pp71 share some functional similarities in their abilities to counteract antiviral restriction mediated by components of cellular nuclear structures known as ND10. To investigate the extent to which IE1 and pp71 might substitute for ICP0, cell lines were developed that express either IE1 or pp71, or both together, in an inducible manner. We found that pp71 dissociated the hDaxx-ATRX complex and inhibited accumulation of these proteins at sites juxtaposed to HSV-1 genomes but had no effect on the promyelocytic leukemia protein (PML) or Sp100. IE1 caused loss of the small ubiquitin-like modifier (SUMO)-conjugated forms of PML and Sp100 and inhibited the recruitment of these proteins to HSV-1 genome foci but had little effect on hDaxx or ATRX in these assays. Both IE1 and pp71 stimulated ICP0-null mutant plaque formation, but neither to the extent achieved by ICP0. The combination of IE1 and pp71, however, inhibited recruitment of all ND10 proteins to viral genome foci, stimulated ICP0-null mutant HSV-1 plaque formation to near wild-type levels, and efficiently induced derepression of quiescent HSV-1 genomes. These results suggest that ND10-related intrinsic resistance results from the additive effects of several ND10 components and that the effects of IE1 and pp71 on subsets of these components combine to mirror the overall activities of ICP0.
Human T Cell Leukemia Virus Type 2 Tax-Mediated NF-κB Activation Involves a Mechanism Independent of Tax Conjugation to Ubiquitin and SUMO
Authors: Journo Chloé , Bonnet Amandine , Favre-Bonvin Arnaud , Turpin Jocelyn , Vinera Jennifer , Côté Emilie , Chevalier Sébastien Alain , Kfoury Youmna , Bazarbachi Ali , Pique Claudine , Mahieux Renaud 
Published: November 2012

ABSTRACT
Permanent activation of the NF-κB pathway by the human T cell leukemia virus type 1 (HTLV-1) Tax (Tax1) viral transactivator is a key event in the process of HTLV-1-induced T lymphocyte immortalization and leukemogenesis. Although encoding a Tax transactivator (Tax2) that activates the canonical NF-κB pathway, HTLV-2 does not cause leukemia. These distinct pathological outcomes might be related, at least in part, to distinct NF-κB activation mechanisms. Tax1 has been shown to be both ubiquitinated and SUMOylated, and these two modifications were originally proposed to be required for Tax1-mediated NF-κB activation. Tax1 ubiquitination allows recruitment of the IKK-γ/NEMO regulatory subunit of the IKK complex together with Tax1 into centrosome/Golgi-associated cytoplasmic structures, followed by activation of the IKK complex and RelA/p65 nuclear translocation. Herein, we compared the ubiquitination, SUMOylation, and acetylation patterns of Tax2 and Tax1. We show that, in contrast to Tax1, Tax2 conjugation to endogenous ubiquitin and SUMO is barely detectable while both proteins are acetylated. Importantly, Tax2 is neither polyubiquitinated on lysine residues nor ubiquitinated on its N-terminal residue. Consistent with these observations, Tax2 conjugation to ubiquitin and Tax2-mediated NF-κB activation is not affected by overexpression of the E2 conjugating enzyme Ubc13. We further demonstrate that a nonubiquitinable, non-SUMOylable, and nonacetylable Tax2 mutant retains a significant ability to activate transcription from a NF-κB-dependent promoter after partial activation of the IKK complex and induction of RelA/p65 nuclear translocation. Finally, we also show that Tax2 does not interact with TRAF6, a protein that was shown to positively regulate Tax1-mediated activation of the NF-κB pathway.
Nucleolar Trafficking of the Mouse Mammary Tumor Virus Gag Protein Induced by Interaction with Ribosomal Protein L9
Authors: Beyer Andrea R. , Bann Darrin V. , Rice Breanna , Pultz Ingrid S. , Kane Melissa , Goff Stephen P. , Golovkina Tatyana V. , Parent Leslie J. 
Published: November 2012

ABSTRACT
The mouse mammary tumor virus (MMTV) Gag protein directs the assembly in the cytoplasm of immature viral capsids, which subsequently bud from the plasma membranes of infected cells. MMTV Gag localizes to discrete cytoplasmic foci in mouse mammary epithelial cells, consistent with the formation of cytosolic capsids. Unexpectedly, we also observed an accumulation of Gag in the nucleoli of infected cells derived from mammary gland tumors. To detect Gag-interacting proteins that might influence its subcellular localization, a yeast two-hybrid screen was performed. Ribosomal protein L9 (RPL9 or L9), an essential component of the large ribosomal subunit and a putative tumor suppressor, was identified as a Gag binding partner. Overexpression of L9 in cells expressing the MMTV(C3H) provirus resulted in specific, robust accumulation of Gag in nucleoli. Förster resonance energy transfer (FRET) and coimmunoprecipitation analyses demonstrated that Gag and L9 interact within the nucleolus, and the CA domain was the major site of interaction. In addition, the isolated NC domain of Gag localized to the nucleolus, suggesting that it contains a nucleolar localization signal (NoLS). To determine whether L9 plays a role in virus assembly, small interfering RNA (siRNA)-mediated knockdown was performed. Although Gag expression was not reduced with L9 knockdown, virus production was significantly impaired. Thus, our data support the hypothesis that efficient MMTV particle assembly is dependent upon the interaction of Gag and L9 in the nucleoli of infected cells.
Heat stress, health and well-being: findings from a large national cohort of Thai adults
Authors: Tawatsupa Benjawan , Yiengprugsawan Vasoontara , Kjellstrom Tord , Seubsman Sam-ang , Sleigh Adrian ,   the Thai Cohort Study Team
Published: November 2012

ObjectivesThis study aims to examine the association between self-reported heat stress interference with daily activities (sleeping, work, travel, housework and exercise) and three graded-holistic health and well-being outcomes (energy, emotions and life satisfaction).DesignA cross-sectional study.SettingThe setting is tropical and developing countries as Thailand, where high temperature and high humidity are common, particularly during the hottest seasons.ParticipantsThis study is based on an ongoing national Thai Cohort Study of distance-learning open-university adult students (N=60 569) established in 2005 to study the health-risk transition.Primary and secondary outcome measuresHealth impacts from heat stress in our study are categorised as physical health impacts (energy levels), mental health impacts (emotions) and well-being (life satisfaction). For each health and well-being outcome we report ORs and 95% CIs using multinomial logistic regression adjusting for a wide array of potential confounders.ResultsNegative health and well-being outcomes (low-energy level, emotional problems and low life satisfaction) associated with increasing frequency of heat stress interfering with daily activities. Adjusted ORs for emotional problems were between 1.5 and 4.8 and in general worse than energy level (between 1.31 and 2.91) and life satisfaction (between 1.10 and 2.49). The worst health outcomes were when heat interfered with sleeping, followed by interference with daily travel, work, housework and exercise.ConclusionsIn tropical Thailand there already are substantial heat stress impacts on health and well-being. Increasing temperatures from climate change plus the ageing and urbanisation of the population could significantly worsen the situation. There is a need to improve public health surveillance and public awareness regarding the risks of heat stress in daily life.
Remagnetization and chemical alteration of sedimentary rocks
Authors: Elmore R. D. , Muxworthy A. R. , Aldana M. 
Published: November 2012

Abstract
Chemical remagnetization is a very common phenomenon in sedimentary rocks and developing a greater understanding of the mechanisms has several benefits. Acquisition of a secondary magnetization is usually tangible evidence of a diagenetic event that can be dated by isolation of the chemical remanent magnetization and comparison of the pole position to the apparent polar wander path. This can be important because diagenetic investigations are frequently limited by the difficulty in constraining the time frames in which most past events have occurred. Remagnetization can commonly obscure a primary magnetization; developing a better understanding of remagnetization could improve our ability to uncover primary magnetizations. Many chemical remagnetization mechanisms have been proposed, including those associated with chemical alteration by a number of different fluids (orogenic, basinal and hydrocarbons), burial diagenetic processes (clay diagenesis and maturation of organic matter) or other processes. This paper summarizes our current knowledge of these chemical remagnetization mechanisms, with a focus on examples where there is a connection with chemical alteration.
An Integrated Genomic Screen Identifies LDHB as an Essential Gene for Triple-Negative Breast Cancer
Authors: McCleland Mark L. , Adler Adam S. , Shang Yonglei , Hunsaker Thomas , Truong Tom , Peterson David , Torres Eric , Li Li , Haley Benjamin , Stephan Jean-Philippe , Belvin Marcia , Hatzivassiliou Georgia , Blackwood Elizabeth M. , Corson Laura , Evangelista Marie , Zha Jiping , Firestein Ron 
Published: November 2012

Abstract
Breast cancer has been redefined into three clinically relevant subclasses: (i) estrogen/progesterone receptor positive (ER+/PR+), (ii) HER2/ERRB2 positive, and (iii) those lacking expression of all three markers (triple negative or basal-like). While targeted therapies for ER+/PR+ and HER2+ tumors have revolutionized patient treatment and increased lifespan, an urgent need exists for identifying novel targets for triple-negative breast cancers. Here, we used integrative genomic analysis to identify candidate oncogenes in triple-negative breast tumors and assess their function through loss of function screening. Using this approach, we identify lactate dehydrogenase B (LDHB), a component of glycolytic metabolism, as an essential gene in triple-negative breast cancer. Loss of LDHB abrogated cell proliferation in vitro and arrested tumor growth in fully formed tumors in vivo. We find that LDHB and other related glycolysis genes are specifically upregulated in basal-like/triple-negative breast cancers as compared with other subtypes, suggesting that these tumors are distinctly glycolytic. Consistent with this, triple-negative breast cancer cell lines were more dependent on glycolysis for growth than luminal cell lines. Finally, we find that patients with breast cancer and high LDHB expression in their tumors had a poor clinical outcome. While previous studies have focused on the ubiquitous role of LDHA in tumor metabolism and growth, our data reveal that LDHB is upregulated and required only in certain cancer genotypes. These findings suggest that targeting LDHB or other components of lactate metabolism would be of clinical benefit in triple-negative breast cancer. Cancer Res; 72(22); 5812–23. ©2012 AACR.
An Integrated Genome-Wide Approach to Discover Tumor-Specific Antigens as Potential Immunologic and Clinical Targets in Cancer
Authors: Xu Qing-Wen , Zhao Wei , Wang Yue , Sartor Maureen A. , Han Dong-Mei , Deng Jixin , Ponnala Rakesh , Yang Jiang-Ying , Zhang Qing-Yun , Liao Guo-Qing , Qu Yi-Mei , Li Lu , Liu Fang-Fang , Zhao Hong-Mei , Yin Yan-Hui , Chen Wei-Feng , Zhang Yu , Wang Xiao-Song 
Published: November 2012

Abstract
Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G–based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets. Cancer Res; 72(24); 6351–61. ©2012 AACR.
PD-1–Expressing Tumor-Infiltrating T Cells Are a Favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer
Authors: Badoual Cécile , Hans Stéphane , Merillon Nathalie , Van Ryswick Cordélia , Ravel Patrice , Benhamouda Nadine , Levionnois Emeline , Nizard Mevyn , Si-Mohamed Ali , Besnier Nicolas , Gey Alain , Rotem-Yehudar Rinat , Pere Hélène , Tran Thi , Guerin Coralie L. , Chauvat Anne , Dransart Estelle , Alanio Cécile , Albert Sebastien , Barry Beatrix , Sandoval Federico , Quintin-Colonna Françoise , Bruneval Patrick , Fridman Wolf H. , Lemoine Francois M. , Oudard Stephane , Johannes Ludger , Olive Daniel , Brasnu Daniel , Tartour Eric 
Published: November 2012

Abstract
Head and neck cancers positive for human papillomavirus (HPV) have a more favorable clinical outcome than HPV-negative cancers, but it is unknown why this is the case. We hypothesized that prognosis was affected by intrinsic features of HPV-infected tumor cells or differences in host immune response. In this study, we focused on a comparison of regulatory Foxp3+ T cells and programmed death-1 (PD-1)+ T cells in the microenvironment of tumors that were positive or negative for HPV, in two groups that were matched for various clinical and biologic parameters. HPV-positive head and neck cancers were more heavily infiltrated by regulatory T cells and PD-1+ T cells and the levels of PD-1+ cells were positively correlated with a favorable clinical outcome. In explaining this paradoxical result, we showed that these PD-1+ T cells expressed activation markers and were functional after blockade of the PD-1–PD-L1 axis in vitro. Approximately 50% of PD-1+ tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. In mice, administration of a cancer vaccine increased PD-1 on T cells with concomitant tumor regression. In this setting, PD-1 blockade synergized with vaccine in eliciting antitumor efficacy. Our findings prompt a need to revisit the significance of PD-1–infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade. Cancer Res; 73(1); 128–38. ©2012 AACR.
Development of [11C]erlotinib Positron Emission Tomography for In Vivo Evaluation of EGF Receptor Mutational Status
Authors: Bahce Idris , Smit Egbert F. , Lubberink Mark , van der Veldt Astrid A. M. , Yaqub Maqsood , Windhorst Albert D. , Schuit Robert C. , Thunnissen Erik , Heideman Daniëlle A. M. , Postmus Pieter E. , Lammertsma Adriaan A. , Hendrikse N. Harry 
Published: November 2012

Abstract
Purpose: To evaluate whether, in patients with non–small cell lung carcinoma (NSCLC), tumor uptake of [11C]erlotinib can be quantified and imaged using positron emission tomography and to assess whether the level of tracer uptake corresponds with the presence of activating tumor EGF receptor (EGFR) mutations.
Experimental Design: Ten patients with NSCLCs, five with an EGFR exon 19 deletion, and five without were scanned twice (test retest) on the same day with an interval of at least 4 hours. Each scanning procedure included a low-dose computed tomographic scan, a 10-minute dynamic [15O]H2O scan, and a 1-hour dynamic [11C]erlotinib scan. Data were analyzed using full tracer kinetic modeling. EGFR expression was evaluated using immunohistochemistry.
Results: The quantitative measure of [11C]erlotinib uptake, that is, volume of distribution (VT), was significantly higher in tumors with activating mutations, that is, all with exon 19 deletions (median VT, 1.76; range, 1.25–2.93), than in those without activating mutations (median VT, 1.06; range, 0.67–1.22) for both test and retest data (P = 0.014 and P = 0.009, respectively). Good reproducibility of [11C]erlotinib VT was seen (intraclass correlation coefficient = 0.88). Intergroup differences in [11C]erlotinib uptake were not correlated with EGFR expression levels, nor tumor blood flow.
Conclusion: [11C]erlotinib VT was significantly higher in NSCLCs tumors with EGFR exon 19 deletions. Clin Cancer Res; 19(1); 183–93. ©2012 AACR.