67 research outputs found

    A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer

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    Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS–driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, whereas the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression. SIGNIFICANCE: Our high-throughput and high-resolution analysis of tumor suppression uncovered novel genetic determinants of oncogenic KRAS–driven lung cancer initiation, overall growth, and exceptional growth. This taxonomy is consistent with changing constraints during the life history of cancer and highlights the value of quantitative in vivo genetic analyses in autochthonous cancer models

    The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study.

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    BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug-resistant organisms in healthcare settings worldwide, but little is known about MRSA transmission outside of acute healthcare settings especially in Asia. We describe the methods for a prospective longitudinal study of MRSA prevalence and transmission. METHODS: MRSA-colonized individuals were identified from MRSA admission screening at two tertiary hospitals and recruited together with their household contacts. Participants submitted self-collected nasal, axilla and groin (NAG) swabs by mail for MRSA culture at baseline and monthly thereafter for 6 months. A comparison group of households of MRSA-negative patients provided swab samples at one time point. In a validation sub-study, separate swabs from each site were collected from randomly selected individuals, to compare MRSA detection rates between swab sites, and between samples collected by participants versus those collected by trained research staff. Information on each participant's demographic information, medical status and medical history, past healthcare facilities usage and contacts, and personal interactions with others were collected using a self-administered questionnaire. DISCUSSION/CONCLUSION: Understanding the dynamics of MRSA persistence and transmission in the community is crucial to devising and evaluating successful MRSA control strategies. Close contact with MRSA colonized patients may to be important for MRSA persistence in the community; evidence from this study on the extent of community MRSA could inform the development of household- or community-based interventions to reduce MRSA colonization of close contacts and subsequent re-introduction of MRSA into healthcare settings. Analysis of longitudinal data using whole-genome sequencing will yield further information regarding MRSA transmission within households, with significant implications for MRSA infection control outside acute hospital settings

    A comparison of methods to assess the antimicrobial activity of nanoparticle combinations on bacterial cells

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    Copyright: © 2018 Bankier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.BACKGROUND: Bacterial cell quantification after exposure to antimicrobial compounds varies widely throughout industry and healthcare. Numerous methods are employed to quantify these antimicrobial effects. With increasing demand for new preventative methods for disease control, we aimed to compare and assess common analytical methods used to determine antimicrobial effects of novel nanoparticle combinations on two different pathogens. METHODS: Plate counts of total viable cells, flow cytometry (LIVE/DEAD BacLight viability assay) and qPCR (viability qPCR) were used to assess the antimicrobial activity of engineered nanoparticle combinations (NPCs) on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria at different concentrations (0.05, 0.10 and 0.25 w/v%). Results were analysed using linear models to assess the effectiveness of different treatments. RESULTS: Strong antimicrobial effects of the three NPCs (AMNP0-2) on both pathogens could be quantified using the plate count method and flow cytometry. The plate count method showed a high log reduction (>8-log) for bacteria exposed to high NPC concentrations. We found similar antimicrobial results using the flow cytometry live/dead assay. Viability qPCR analysis of antimicrobial activity could not be quantified due to interference of NPCs with qPCR amplification. CONCLUSION: Flow cytometry was determined to be the best method to measure antimicrobial activity of the novel NPCs due to high-throughput, rapid and quantifiable results.Peer reviewe

    Maternal atrial fibrillation after sequential use of nifedipine and atosiban for treatment of preterm labor: case report

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    Effect on human attention of exposure to the electromagnetic field emitted by mobile phones

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    This study examined the effect of exposure to the electromagnetic field emitted by mobile phones on human attention. Three measures of attention were administered to 72 teenagers, 37 of whom were mobile phone users. The results showed that the mobile phone users performed better on one of the three measures of attention than did the non-mobile phone users. The results suggest that exposure to the electromagnetic field emitted by mobile phones may have a mild facilitating effect on attention functions, which is consistent with previous observations that exposure to the electromagnetic field has a facilitating effect on cognitive processing. The possibility that mobile phone users may be naturally better at multiple tasking tasks was discussed. © 2001 Lippincott Williams & Wilkins.link_to_subscribed_fulltex

    Effect on human attention of exposure to the electromagnetic field emitted by mobile phones

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    This study examined the effect of exposure to the electromagnetic field emitted by mobile phones on human attention. Three measures of attention were administered to 72 teenagers, 37 of whom were mobile phone users. The results showed that the mobile phone users performed better on one of the three measures of attention than did the non-mobile phone users. The results suggest that exposure to the electromagnetic field emitted by mobile phones may have a mild facilitating effect on attention functions, which is consistent with previous observations that exposure to the electromagnetic field has a facilitating effect on cognitive processing. The possibility that mobile phone users may be naturally better at multiple tasking tasks was discussed. © 2001 Lippincott Williams & Wilkins.link_to_subscribed_fulltex
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