Staphylococcus aureus with reduced susceptibility to vancomycin isolated from a patient with fatal bacteremia.

A Staphylococcus aureus isolate with reduced susceptibility to vancomycin was obtained from a dialysis patient with a fatal case of bacteremia. Comparison of the isolate with two methicillin-resistant S. aureus (MRSA) isolated obtained from the same patient 4 months earlier suggests that the S. aureus with reduced susceptibility to vancomycin emerged from the MRSA strain with which the patient was infected. Atypical phenotypic characteristics, including weak or negative latex-agglutination test results, weak or negative-slide coagulase test results, heterogeneous morphologic features, slow rate of growth, and vancomycin susceptibility (by disk diffusion test) were observed

The bovine nasal fungal community and associations with bovine respiratory disease

IntroductionEffective identification and treatment of bovine respiratory disease (BRD) is an ongoing health and economic issue for the dairy and beef cattle industries. Bacteria pathogens Pasteurellamultocida, Mycoplasmabovis, Mannheimia haemolytica, and Histophilus somni and the virus Bovine herpesvirus-1 (BHV-1), Bovine parainfluenza-3 virus (BPIV-3), Bovine respiratory syncytial virus (BRSV), Bovine adenovirus 3 (BAdV3), bovine coronavirus (BoCV) and Bovine viral diarrhea virus (BVDV) have commonly been identified in BRD cattle; however, no studies have investigated the fungal community and how it may also relate to BRD.MethodsThe objective of this study was to understand if the nasal mycobiome differs between a BRD-affected (n = 56) and visually healthy (n = 73) Holstein steers. Fungal nasal community was determined by using Internal Transcribed Spacer (ITS) sequencing.ResultsThe phyla, Ascomycota and Basidiomycota, and the genera, Trichosporon and Issatchenkia, were the most abundant among all animals, regardless of health status. We identified differences between healthy and BRD animals in abundance of Trichosporon and Issatchenkia orientalis at a sub-species level that could be a potential indicator of BRD. No differences were observed in the nasal fungal alpha and beta diversity between BRD and healthy animals. However, the fungal community structure was affected based on season, specifically when comparing samples collected in the summer to the winter season. We then performed a random forest model, based on the fungal community and abundance of the BRD-pathobionts (qPCR data generated from a previous study using the same animals), to classify healthy and BRD animals and determine the agreement with visual diagnosis. Classification of BRD or healthy animals using ITS sequencing was low and agreed with the visual diagnosis with an accuracy of 51.9%. A portion of the ITS-predicted BRD animals were not predicted based on the abundance of BRD pathobionts. Lastly, fungal and bacterial co-occurrence were more common in BRD animals than healthy animals.DiscussionThe results from this novel study provide a baseline understanding of the fungal diversity and composition in the nasal cavity of BRD and healthy animals, upon which future interaction studies, including other nasal microbiome members to further understand and accurately diagnose BRD, can be designed

Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia

Mesenchymal cell populations contribute to microenvironments regulating stem cells and the growth of malignant cells. Osteolineage cells participate in the hematopoietic stem cell niche. Here, we report that deletion of the miRNA processing endonuclease Dicer1 selectively in mesenchymal osteoprogenitors induces markedly disordered hematopoiesis. Hematopoietic changes affected multiple lineages recapitulating key features of human myelodysplastic syndrome (MDS) including the development of acute myelogenous leukemia. These changes were microenvironment dependent and induced by specific cells in the osteolineage. Dicer1−/− osteoprogenitors expressed reduced levels of Sbds, the gene mutated in the human bone marrow failure and leukemia predisposition Shwachman-Bodian-Diamond Syndrome. Deletion of Sbds in osteoprogenitors largely phenocopied Dicer1 deletion. These data demonstrate that differentiation stage-specific perturbations in osteolineage cells can induce complex hematological disorders and indicate the central role individual cellular elements of ‘estroma’ can play in tissue homeostasis. They reveal that primary changes in the hematopoietic microenvironment can initiate secondary neoplastic disease

From Ideal to Practice and Back Again: Beginning Teachers Teaching for Social Justice

The five authors of this article designed a multicase study to follow recent graduates of an elementary preservice teacher education program into their beginning teaching placements and explore the ways in which they enacted social justice curricula. The authors highlight the stories of three beginning teachers, honoring the plurality of their conceptions of social justice teaching and the resiliency they exhibited in translating social justice ideals into viable pedagogy. They also discuss the struggles the teachers faced when enacting social justice curricula and the tenuous connection they perceived between their conceptions and their practices. The authors emphasize that such struggles are inevitable and end the article with recommendations for ways in which teacher educators can prepare beginning teachers for the uncertain journey of teaching for social justice

Consequences of various landscape-scale ecosystem management strategies and fire cycles on age-class structure and harvest in boreal forests

At the landscape scale, one of the key indicators of sustainable forest management is the age-class distribution of stands, since it provides a coarse synopsis of habitat potential, structural complexity, and stand volume, and it is directly modified by timber extraction and wildfire. To explore the consequences of several landscape-scale boreal forest management strategies on age-class structure in the Mauricie region of Quebec, we used spatially explicit simulation modelling. Our study investigated three different harvesting strategies (the one currently practiced and two different strategies to maintain late seral stands) and interactions between fire and harvesting on stand age-class distribution. We found that the legacy of initial forested age structure and its spatial configuration can pose short- (<50 years) to medium-term (150-300 years) challenges to balancing wood supply and ecological objectives. Also, ongoing disturbance by fire, even at relatively long cycles in relation to historic levels, can further constrain the achievement of both timber and biodiversity goals. For example, when fire was combined with management, harvest shortfalls occurred in all scenarios with a fire cycle of 100 years and most scenarios with a fire cycle of 150 years. Even a fire cycle of 500 years led to a reduction in older forest when its maintenance was not a primary constraint. Our results highlight the need to consider the broad-scale effects of natural disturbance when developing ecosystem management policies and the importance of prioritizing objectives when planning for multiple resource use

Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Introduction Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. Objectives We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. Methods A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p\0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not. Conclusion High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation

Immunotherapy with MVA-BN®-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells

MVA-BN®-HER2 is a new candidate immunotherapy designed for the treatment of HER-2-positive breast cancer. Here, we demonstrate that a single treatment with MVA-BN®-HER2 exerts potent anti-tumor efficacy in a murine model of experimental pulmonary metastasis. This anti-tumor efficacy occurred despite a strong tumor-mediated immunosuppressive environment characterized by a high frequency of regulatory T cells (Treg) in the lungs of tumor-bearing mice. Immunogenicity studies showed that treatment with MVA-BN®-HER2 induced strongly Th1-dominated HER-2-specific antibody and T-cell responses. MVA-BN®-HER2-induced anti-tumor activity was characterized by an increased infiltration of lungs with highly activated, HER-2-specific, CD8+CD11c+ T cells accompanied by a decrease in the frequency of Treg cells in the lung, resulting in a significantly increased ratio of effector T cells to Treg cells. In contrast, administration of HER2 protein formulated in Complete Freund’s Adjuvant (CFA) induced a strongly Th2-biased immune response to HER-2. However, this did not lead to significant infiltration of the tumor-bearing lungs by CD8+ T cells or the decrease in the frequency of Treg cells nor did it result in anti-tumor efficacy. In vivo depletion of CD8+ cells confirmed that CD8 T cells were required for the anti-tumor activity of MVA-BN®-HER2. Furthermore, depletion of CD4+ or CD25+ cells demonstrated that tumor-induced Treg cells promoted tumor growth and that CD4 effector cells also contribute to MVA-BN®-HER2-mediated anti-tumor efficacy. Taken together, our data demonstrate that treatment with MVA-BN®-HER2 controls tumor growth through mechanisms including the induction of Th1-biased HER-2-specific immune responses and the control of tumor-mediated immunosuppression

p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production

Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production

Direct application of compound-specific radiocarbon analysis of leaf waxes to establish lacustrine sediment chronology

Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Paleolimnology 39 (2008): 43-60, doi:10.1007/s10933-007-9094-1.This study demonstrates use of compound-specific radiocarbon analysis (CSRA) for dating Holocene lacustrine sediments from carbonate-hosted Ordy Pond, Oahu, Hawaii. Long-chain odd-numbered normal alkanes (n-alkanes), biomarkers characteristic of terrestrial higher plants, were ubiquitous in Ordy Pond sediments. The δ13C of individual n-alkanes ranged from −29.9 to −25.5‰, within the expected range for n-alkanes synthesized by land plants using the C3 or C4 carbon fixation pathway. The 14C ages of n-alkanes determined by CSRA showed remarkably good agreement with 14C dates of rare plant macrofossils obtained from nearby sedimentary horizons. In general, CSRA of n-alkanes successfully refined the age-control of the sediments. The sum of n-alkanes in each sample produced 70–170 μg of carbon (C), however, greater age errors were confirmed for samples containing less than 80 μg of C. The 14C age of n-alkanes from one particular sedimentary horizon was 4,155 years older than the value expected from the refined age-control, resulting in an apparent and arguable age discrepancy. Several lines of evidence suggest that this particular sample was contaminated by introduction of 14C-free C during preparative capillary gas chromatography. This study simultaneously highlighted the promising potential of CSRA for paleo-applications and the risks of contamination associated with micro-scale 14C measurement of individual organic compounds.This project was funded by Petroleum Research Fund (PRF #40088-ACS) and in part by Sigma Xi, The Scientific Research Society (Grants in aid of research, 2003)