bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propionibacterium acnes
and
Staphylococcus epidermidis
Isolated from Refractory Endodontic Lesions Are Opportunistic Pathogens
Authors: Niazi Sadia A. , Clarke Douglas , Do Thuy , Gilbert Steven C. , Mannocci Francesco , Beighton David 
Published: August 2010

ABSTRACT

The predominant cultivable microbiota from 20 refractory endodontic lesions (9 with abscesses and 11 without abscesses) were determined, and
Propionibacterium acnes
and
Staphylococcus epidermidis
were among the most predominant organisms. The number of species identified from lesions with abscesses (14.1 ± 2.6) was significantly greater (
P
< 0.001) than the number from lesions without abscesses (7.4 ± 5.9). Comparison of perioral isolates using repetitive extragenic palindromic PCR of the same species from the same subjects demonstrated that the endodontic and skin populations were significantly different. The
P. acnes
isolates were typed on the basis of
recA
gene sequence comparison, and only three types (types I, II, and III) were identified among 125 isolates examined. However, we found that type I (type IA and IB) isolates were primarily isolated from the skin, while types II and III were significantly more likely to be isolated from the endodontic lesions (
P
< 10
−10
). We found that the robustness of the
recA
phylotypes was not strong by comparing the partial gene sequences of six putative virulence determinants, PAmce, PAp60, PA-25957, PA-5541, PA-21293, and PA-4687. The resulting neighbor-joining trees were incongruent, and significant (phi test;
P
= 2.2 × 10
−7
) evidence of recombination was demonstrated, with significant phylogenetic heterogeneity being apparent within the clusters.
P. acnes
and
S. epidermidis
isolated from refractory endodontic infections, with or without periapical abscesses, are likely to be nosocomial infections.
Herbaspirillum
Species Bacteremia in a Pediatric Oncology Patient
Authors: Ziga Edward D. , Druley Todd , Carey-Ann Burnham D. 
Published: August 2010

ABSTRACT

Herbaspirillum
species, an organism commonly found in soil, has only recently been linked to disease in humans. We report
Herbaspirillum
bacteremia in a 2-year-old female patient following a hematopoietic stem cell transplant for relapsed acute lymphoblastic leukemia.
Characterization of Vancomycin-Resistant
Enterococcus faecium
Isolated from Swine in Three Michigan Counties
Authors: Donabedian Susan M. , Perri Mary Beth , Abdujamilova Nodira , Gordoncillo Mary Joy , Naqvi Amir , Reyes Katherine C. , Zervos Marcus J. , Bartlett Paul 
Published: August 2010

ABSTRACT

Vancomycin-resistant enterococci are a major cause of nosocomial infections but are rarely found in humans in the community and have not been identified in food animals in the United States. We evaluated a total of 360 fecal specimens from humans and their animals being raised for exhibit at three county fairs in Michigan. Fecal samples from 158 humans, 55 swine, 50 cattle, 25 horses, 57 sheep, 14 goats, and 1 llama were obtained and plated onto Enterococcosel agar containing 16 μg/ml of vancomycin. Vancomycin-resistant
Enterococcus faecium
(VREF) was isolated from six pigs but not from humans or any animal other than pigs. All six VREF isolates had a MIC to vancomycin of ≥256 μg/ml and contained the
vanA
gene. Pulsed-field gel electrophoresis (PFGE) patterns of the six VREF isolates were ≥80% similar. Multilocus sequence typing (MLST) revealed sequence type 5 (ST5) (
n
= 2), ST6 (
n
= 3), and ST185 (
n
= 1), which are
E. faecium
sequence types belonging to clonal complex 5 (CC5). These findings show the dissemination of VREF strains among pigs in three Michigan counties. This is the first report of VRE found in food animals in the United States.
Compromised Spindle Assembly Checkpoint due to Altered Expression of Ubch10 and Cdc20 in Human Papillomavirus Type 16 E6- and E7-Expressing Keratinocytes
Authors: Patel Daksha , McCance Dennis J. 
Published: August 2010

ABSTRACT

Cells expressing human papillomavirus type 16 (HPV-16) E6 and E7 proteins exhibit deregulation of G
2
/M genes, allowing bypass of DNA damage arrest signals. Normally, cells with DNA damage that override the G
2
damage checkpoint would precociously enter mitosis and ultimately face mitotic catastrophe and apoptotic cell death. However, E6/E7-expressing cells (E6/E7 cells) have the ability to enter and exit mitosis in the presence of DNA damage and continue with the next round of the cell cycle. Little is known about the mechanism that allows these cells to gain entry into and exit from mitosis. Here, we show that in the presence of DNA damage, E6/E7 cells have elevated levels of cyclin B, which would allow entry into mitosis. Also, as required for exit from mitosis, cyclin B is degraded in these cells, permitting initiation of the next round of DNA synthesis and cell cycle progression. Proteasomal degradation of cyclin B by anaphase-promoting complex/cyclosome (APC/C) is, in part, due to elevated levels of the E2-conjugating enzyme, Ubch10, and the substrate recognition protein, Cdc20, of APC/C. Also, in E6/E7 cells with DNA damage, while Cdc20 is complexed with BubR1, indicating an active checkpoint, it is also present in complexes free of BubR1, presumably allowing APC/C activity and slippage through the checkpoint.
Environmental Sources of Scrapie Prions
Authors: Maddison Ben C. , Baker Claire A. , Terry Linda A. , Bellworthy Susan J. , Thorne Leigh , Rees Helen C. , Gough Kevin C. 
Published: August 2010

ABSTRACT
Ovine scrapie and cervine chronic wasting disease show considerable horizontal transmission. Here we report that a scrapie-affected sheep farm has a widespread environmental contamination with prions. Prions were amplified by protein-misfolding cyclic amplification (sPMCA) from seven of nine environmental swab samples taken, including those from metal, plastic, and wooden surfaces. Sheep had been removed from the areas from which the swabs were taken up to 20 days prior to sampling, indicating that prions persist for at least that long. These data implicate inanimate objects as environmental reservoirs for prion infectivity that are likely to contribute to facile disease transmission.
Human Cytomegalovirus Induces the Endoplasmic Reticulum Chaperone BiP through Increased Transcription and Activation of Translation by Using the BiP Internal Ribosome Entry Site
Authors: Buchkovich Nicholas J. , Yu Yongjun , Pierciey Francis J. , Alwine James C. 
Published: August 2010

ABSTRACT
The endoplasmic reticulum (ER) chaperone BiP (immunoglobulin binding protein) plays a major role in the control of the unfolded protein response. We have previously shown that BiP levels are dramatically increased during human cytomegalovirus (HCMV) infection, where BiP performs unique roles in viral assembly and egress. We show that BiP mRNA levels increase during infection due to activation of the BiP promoter by the major immediate-early (MIE) proteins. The BiP promoter, like other ER stress-activated promoters, contains endoplasmic reticulum stress elements (ERSEs), which are activated by unfolded protein response (UPR)-induced transcription factors. However, these elements are not needed for MIE protein-mediated transcriptional activation; thus, a virus-specific transcriptional activation mechanism is used. Transcriptional activation results in only a 3- to 4-fold increase in BiP mRNA, suggesting that additional mechanisms for BiP production are utilized. The BiP mRNA contains an internal ribosome entry site (IRES) which increases the level of BiP mRNA translation. We show that utilization of the BiP IRES is dramatically increased in HCMV-infected cells. Utilization of the BiP IRES can be activated by the La autoantigen, also called Sjögren's syndrome antigen B (SSB). We show that SSB/La levels are significantly increased during HCMV infection, and SSB/La depletion causes the loss of BiP IRES utilization and lowers endogenous BiP levels in infected cells. Our data show that BiP levels increase in HCMV-infected cells through the combination of increased BiP gene transcription mediated by the MIE proteins and increased BiP mRNA translation due to SSB/La-induced utilization of the BiP IRES.
Oseltamivir-Resistant Variants of the 2009 Pandemic H1N1 Influenza A Virus Are Not Attenuated in the Guinea Pig and Ferret Transmission Models
Authors: Seibert Christopher W. , Kaminski Michael , Philipp Jennifer , Rubbenstroth Dennis , Albrecht Randy A. , Schwalm Folker , Stertz Silke , Medina Rafael A. , Kochs Georg , García-Sastre Adolfo , Staeheli Peter , Palese Peter 
Published: August 2010

ABSTRACT

Oseltamivir is routinely used worldwide for the treatment of severe influenza A virus infection, and should drug-resistant pandemic 2009 H1N1 viruses become widespread, this potent defense strategy might fail. Oseltamivir-resistant variants of the pandemic 2009 H1N1 influenza A virus have been detected in a substantial number of patients, but to date, the mutant viruses have not moved into circulation in the general population. It is not known whether the resistance mutations in viral neuraminidase (NA) reduce viral fitness. We addressed this question by studying transmission of oseltamivir-resistant mutants derived from two different isolates of the pandemic H1N1 virus in both the guinea pig and ferret transmission models.
In vitro
, the virus readily acquired a single histidine-to-tyrosine mutation at position 275 (H275Y) in viral neuraminidase when serially passaged in cell culture with increasing concentrations of oseltamivir. This mutation conferred a high degree of resistance to oseltamivir but not zanamivir. Unexpectedly, in guinea pigs and ferrets, the fitness of viruses with the H275Y point mutation was not detectably impaired, and both wild-type and mutant viruses were transmitted equally well from animals that were initially inoculated with 1:1 virus mixtures to naïve contacts. In contrast, a reassortant virus containing an oseltamivir-resistant seasonal NA in the pandemic H1N1 background showed decreased transmission efficiency and fitness in the guinea pig model. Our data suggest that the currently circulating pandemic 2009 H1N1 virus has a high potential to acquire drug resistance without losing fitness.
Murine Coronavirus Receptors Are Differentially Expressed in the Central Nervous System and Play Virus Strain-Dependent Roles in Neuronal Spread
Authors: Bender Susan J. , Phillips Judith M. , Scott Erin P. , Weiss Susan R. 
Published: August 2010

ABSTRACTCoronavirus infection of the murine central nervous system (CNS) provides a model for studies of viral encephalitis and demyelinating disease. Mouse hepatitis virus (MHV) neurotropism varies by strain: MHV-A59 causes mild encephalomyelitis and demyelination, while the highly neurovirulent strain JHM.SD (MHV-4) causes fatal encephalitis with extensive neuronal spread of virus. In addition, while neurons are the predominant CNS cell type infectedin vivo, the canonical receptor for MHV, the carcinoembryonic antigen family member CEACAM1a, has been demonstrated only on endothelial cells and microglia. In order to investigate whether CEACAM1a is also expressed in other cell types,ceacam1amRNA expression was quantified in murine tissues and primary cells. As expected, among CNS cell types, microglia expressed the highest levels ofceacam1a, but lower levels were also detected in oligodendrocytes, astrocytes, and neurons. Given the low levels of neuronal expression ofceacam1a, primary neurons from wild-type andceacam1aknockout mice were inoculated with MHV to determine the extent to which CEACAM1a-independent infection might contribute to CNS infection. While both A59 and JHM.SD infected small numbers ofceacam1aknockout neurons, only JHM.SD spread efficiently to adjacent cells in the absence of CEACAM1a. Quantification of mRNA for theceacam1a-related genesceacam2andpsg16(bCEA), which encode proposed alternative MHV receptors, revealed lowceacam2expression in microglia and oligodendrocytes andpsg16expression exclusively in neurons; however, only CEACAM2 mediated infection in human 293T cells. Therefore, neither CEACAM2 nor PSG16 is likely to be an MHV receptor on neurons, and the mechanism for CEACAM1a-independent neuronal spread of JHM.SD remains unknown.
Economical Evolution: Microbes Reduce the Synthetic Cost of Extracellular Proteins
Authors: Smith Daniel R. , Chapman Matthew R. 
Published: August 2010

ABSTRACT

Protein evolution is not simply a race toward improved function. Because organisms compete for limited resources, fitness is also affected by the relative economy of an organism’s proteome. Indeed, many abundant proteins contain relatively high percentages of amino acids that are metabolically less taxing for the cell to make, thus reducing cellular cost. However, not all abundant proteins are economical, and many economical proteins are not particularly abundant. Here we examined protein composition and found that the relative synthetic cost of amino acids constrains the composition of microbial extracellular proteins. In
Escherichia coli
, extracellular proteins contain, on average, fewer energetically expensive amino acids independent of their abundance, length, function, or structure. Economic pressures have strategically shaped the amino acid composition of multicomponent surface appendages, such as flagella, curli, and type I pili, and extracellular enzymes, including type III effector proteins and secreted serine proteases. Furthermore,
in silico
analysis of
Pseudomonas syringae
,
Mycobacterium tuberculosis
,
Saccharomyces cerevisiae
, and over 25 other microbes spanning a wide range of GC content revealed a broad bias toward more economical amino acids in extracellular proteins. The synthesis of any protein, especially those rich in expensive aromatic amino acids, represents a significant investment. Because extracellular proteins are lost to the environment and not recycled like other cellular proteins, they present a greater burden on the cell, as their amino acids cannot be reutilized during translation. We hypothesize that evolution has optimized extracellular proteins to reduce their synthetic burden on the cell.

IMPORTANCE
Microbes secrete proteins to perform essential interactions with their environment, such as motility, pathogenesis, biofilm formation, and resource acquisition. However, because microbes generally lack protein import systems, secretion is often a one-way street. Consequently, secreted proteins are less likely to be recycled by the cell due to environmental loss. We demonstrate that evolution has in turn selected these extracellular proteins for increased economy at the level of their amino acid composition. Compared to their cellular counterparts, extracellular proteins have fewer synthetically expensive amino acids and more inexpensive amino acids. The resulting bias lessens the loss of cellular resources due to secretion. Furthermore, this economical bias was observed regardless of the abundance, length, structure, or function of extracellular proteins. Thus, it appears that economy may address the compositional bias seen in many extracellular proteins and deliver further insight into the forces driving their evolution.
Return-to-work interventions integrated into cancer care: a systematic review
Authors: Tamminga S J , de Boer A G E M , Verbeek J H A M , Frings-Dresen M H W 
Published: August 2010

ObjectivesThe purpose of this study was to review the literature on the content of interventions focusing on return to work, employment status, or work retention in patients with cancer. Furthermore, the effect of the interventions on return to work was assessed in studies reporting return to work.MethodsA literature search was conducted using the databases MEDLINE, PsycINFO, EMBASE and CINAHL. Articles that described a work-directed intervention focusing on return to work, employment status, or work retention in patients with cancer were included. The content of the work-directed part of the interventions was assessed based on two criteria for content analysis: 1. does the setting fit the shared care model of cancer survivor care? 2. Does the intervention target work ability and physical workload? For studies reporting return-to-work outcomes, the return-to-work rates were assessed. For studies that used a control group the ORs and the 95% CIs were calculated.ResultsTwenty-three articles describing 19 interventions met the inclusion criteria. Seven studies reported return-to-work outcomes of which four used a control group. Only three interventions aimed primarily at enhancing return to work or employment status. The most frequently reported work-directed components were encouragement, education or advice about work or work-related subjects (68%), vocational or occupational training (21%), or work accommodations (11%). One intervention fit the shared care model of cancer survivor care and five interventions enhanced work ability or decreased physical workload. The rate of return to work ranged from 37% to 89%. In one of the four controlled studies the intervention increased return to work significantly and in the other studies the results were insignificant.ConclusionsOnly few interventions are primarily aimed at enhancing return to work in patients with cancer and most do not fit the shared care model involving integrated cancer care. Future studies should be developed with well-structured work-directed components that should be evaluated in randomised controlled trials.
Connecting world youth with tobacco brands: YouTube and the internet policy vacuum on Web 2.0
Authors: Elkin Lucy , Thomson George , Wilson Nick 
Published: August 2010

BackgroundThe internet is an ideal forum for tobacco marketing, as it is largely unregulated and there is no global governing body for controlling content. Nevertheless, tobacco companies deny advertising on the internet.ObjectiveTo assess the extent and nature of English language videos available on the Web 2.0 domain ‘YouTube’ that contain tobacco brand images or words.MethodsThe authors conducted a YouTube search using five leading non-Chinese cigarette brands worldwide. The themes and content of up to 40 of the most viewed videos returned for each search were analysed: a total of 163 videos.ResultsA majority of the 163 tobacco brand-related videos analysed (71.2%, 95% CI 63.9 to 77.7) had pro-tobacco content, versus a small minority (3.7%) having anti-tobacco content (95% CI 1.4 to 7.8). Most of these videos contained tobacco brand content (70.6%), the brand name in the title (71.2%) or smoking imagery content (50.9%). One pro-smoking music video had been viewed over 2 million times. The four most prominent themes of the videos were celebrity/movies, sports, music and ‘archive’, the first three of which represent themes of interest to a youth audience.ConclusionsPro-tobacco videos have a significant presence on YouTube, consistent with indirect marketing activity by tobacco companies or their proxies. Since content may be removed from YouTube if it is found to breach copyright or if it contains offensive material, there is scope for the public and health organisations to request the removal of pro-tobacco content containing copyright or offensive material. Governments should also consider implementing Framework Convention on Tobacco Control requirements on the internet, to further reduce such pro-tobacco content.
Aberrant Silencing of Cancer-Related Genes by CpG Hypermethylation Occurs Independently of Their Spatial Organization in the Nucleus
Authors: Easwaran Hariharan P. , Van Neste Leander , Cope Leslie , Sen Subhojit , Mohammad Helai P. , Pageau Gayle J. , Lawrence Jeanne B. , Herman James G. , Schuebel Kornel E. , Baylin Stephen B. 
Published: August 2010

Abstract
Aberrant promoter DNA-hypermethylation and repressive chromatin constitutes a frequent mechanism of gene inactivation in cancer. There is great interest in dissecting the mechanisms underlying this abnormal silencing. Studies have shown changes in the nuclear organization of chromatin in tumor cells as well as the association of aberrant methylation with long-range silencing of neighboring genes. Furthermore, certain tumors show a high incidence of promoter methylation termed as the CpG island methylator phenotype. Here, we have analyzed the role of nuclear chromatin architecture for genes in hypermethylated inactive versus nonmethylated active states and its relation with long-range silencing and CpG island methylator phenotype. Using combined immunostaining for active/repressive chromatin marks and fluorescence in situ hybridization in colorectal cancer cell lines, we show that aberrant silencing of these genes occurs without requirement for their being positioned at heterochromatic domains. Importantly, hypermethylation, even when associated with long-range epigenetic silencing of neighboring genes, occurs independent of their euchromatic or heterochromatic location. Together, these results indicate that, in cancer, extensive changes around promoter chromatin of individual genes or gene clusters could potentially occur locally without preference for nuclear position and/or causing repositioning. These findings have important implications for understanding relationships between nuclear organization and gene expression patterns in cancer. Cancer Res; 70(20); 8015–24. ©2010 AACR.
Folotyn (Pralatrexate Injection) for the Treatment of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma: U.S. Food and Drug Administration Drug Approval Summary
Authors: Malik Shakun M. , Liu Ke , Qiang Xu , Sridhara Rajeshwari , Tang Shenghui , McGuinn W. David , Verbois S. Leigh , Marathe Anshu , Williams Gene M. , Bullock Julie , Tornoe Christoffer , Lin Sue Ching , Ocheltree Terrance , Vialpando Milinda , Kacuba Alice , Justice Robert , Pazdur Richard 
Published: August 2010

Abstract
Purpose: On September 24, 2009, the U.S. Food and Drug Administration granted accelerated approval for Folotyn (pralatrexate injection, Allos Therapeutics, Inc.) as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL); it is the first drug approved for this indication.
Experimental Design: This review was based on study PDX-008, a phase II, single-arm, nonrandomized, open-label, international, multicenter trial, designed to evaluate the safety and efficacy of pralatrexate when administered concurrently with vitamin B12 and folic acid supplementation in patients with relapsed or refractory PTCL.
Results: The overall response rate was 27% in 109 evaluable patients [95% confidence interval (CI), 19–36%]. Twelve percent of 109 evaluable patients (95% CI, 7–20%)] had a response duration of ≥14 weeks. Six of these 13 patients achieved a complete response, and one patient had complete response unconfirmed. The most common grade 3 and 4 toxicities were thrombocytopenia, mucositis, and neutropenia.
Conclusion: This accelerated approval was based on a response rate that is reasonably likely to predict clinical benefit in this heavily pretreated patient population with this rare disease. The applicant has committed to conducting postmarketing clinical trials to assess clinical benefit. The recommended starting dose of pralatrexate in patients with relapsed or refractory PTCL is 30 mg/m2 via intravenous push over 3 to 5 min weekly for 6 weeks followed by a one-week rest (one cycle). Intramuscular injection of 1 mg vitamin B12 should be administered every 8 to 10 weeks along with 1.0 mg folic acid given orally once a day. Clin Cancer Res; 16(20); 4921–7. ©2010 AACR.