Application of qPCR Technologies in Stormwater Source Tracking and Determination of Host Contributions of Fecal Indicator Bacteria

2012 S.C. Water Resources Conference - Exploring Opportunities for Collaborative Water Research, Policy and Managemen

Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock

During heat shock and other proteotoxic stresses, cells regulate multiple steps in gene expression in order to globally repress protein synthesis and selectively upregulate stress response proteins. Splicing of several mRNAs is known to be inhibited during heat stress, often meditated by SRp38, but the extent and specificity of this effect have remained unclear. Here, we examined splicing regulation genome-wide during heat shock in mouse fibroblasts. We observed widespread retention of introns in transcripts from ~1,700 genes, which were enriched for tRNA synthetase, nuclear pore, and spliceosome functions. Transcripts with retained introns were largely nuclear and untranslated. However, a group of 580+ genes biased for oxidation reduction and protein folding functions continued to be efficiently spliced. Interestingly, these unaffected transcripts are mostly cotranscriptionally spliced under both normal and stress conditions, whereas splicing-inhibited transcripts are mostly spliced posttranscriptionally. Altogether, our data demonstrate widespread repression of splicing in the mammalian heat stress response, disproportionately affecting posttranscriptionally spliced genes.Weizmann Institute of Science (Postdoctoral Award for Advancing Women in Science)European Molecular Biology Organization (Long-term Fellowship)Machiah FoundationNational Science Foundation (U.S.) (Grant 0821391)National Institutes of Health (U.S.

Widespread Regulation of Translation by Elongation Pausing in Heat Shock

Global repression of protein synthesis is a hallmark of the cellular stress response and has been attributed primarily to inhibition of translation initiation, although this mechanism may not always explain the full extent of repression. Here, using ribosome footprinting, we show that 2 hr of severe heat stress triggers global pausing of translation elongation at around codon 65 on most mRNAs in both mouse and human cells. The genome-wide nature of the phenomenon, its location, and features of protein N termini suggested the involvement of ribosome-associated chaperones. After severe heat shock, Hsp70’s interactions with the translational machinery were markedly altered and its association with ribosomes was reduced. Pretreatment with mild heat stress or overexpression of Hsp70 protected cells from heat shock-induced elongation pausing, while inhibition of Hsp70 activity triggered elongation pausing without heat stress. Our findings suggest that regulation of translation elongation in general, and by chaperones in particular, represents a major component of cellular stress responses.National Institute of General Medical Sciences (U.S.) (NIGMS fellowship number F32GM095060)Machiah FoundationEuropean Molecular Biology Organization (EMBO long-term fellowship)Weitzmann Institute of Science (National Postdoctoral Award Program for Advancing Women in Science

BrewDog: business growth for punks!

This case study tells an atypical entrepreneurship story about two men and a dog. It explores the rapid growth of the phenomenon that is BrewDog plc - a company situated in the remote north-east of Scotland. What makes this case special is that the business, set up in 2007 by two university graduates in their early twenties with limited experience of the brewing industry, is now trading as a plc. From the outset they deliberately chose a strategy that flew in the face of accepted orthodoxy in the brewing industry. To industry experts, it made little sense because the remote Aberdeenshire town of Fraserburgh, with its peripheral location, would surely be the last place any rational individual would seek to start a new brewery. The story of how James Watt and Martin Dickie did so is uplifting and inspirational

Understanding the relative valuation of research impact: a best-worst scaling experiment of the general public and biomedical and health researchers

Objectives: (1) To test the use of Best Worst Scaling (BWS) experiments in valuing different types of biomedical and health research impact, and (2) to explore how different types of research impact are valued by different stakeholder groups. Design: Survey-based BWS experiment and discrete choice modelling. Setting: United Kingdom. Participants: Current and recent UK Medical Research Council grant holders and a representative sample of the general public recruited from an online panel. Results: In relation to the study’s two objectives: (1) We demonstrate the application of BWS methodology in the quantitative assessment and valuation of research impact. (2) The general public and researchers provided similar valuations for research impacts such as improved life expectancy, job creation and reduced health costs, but there was less agreement between the groups on other impacts, including commercial capacity development, training and dissemination. Conclusion: This is the second time that a discrete choice experiment has been used to assess how the general public and researchers value different types of research impact, and the first time that BWS has been used to elicit these choices. While the two groups value different research impacts in different ways, we note that where they agree, this is generally about matters that are seemingly more important and associated with wider social benefit, rather than impacts occurring within the research system. These findings are a first step in exploring how the beneficiaries and producers of research value different kinds of impact, an important consideration given the growing emphasis on funding and assessing research on the basis of (potential) impact. Future research should refine and replicate both the current study and that of Miller et al. (2013) in other countries and disciplines. Strength

Acute respiratory effects on workers exposed to metalworking fluid aerosols in an automotive transmission plant

Exposure to metalworking fluids has been linked to modest cross-shift reductions in FEV 1 and occupational asthma. To identify responsible agents, we measured personal exposures to thoracic particulate (TP), viable plus nonviable thoracic bacteria (BAC), and vapor phase nicotine (VPN) (as a surrogate for tobacco particulate) among 83 machinists exposed to soluble oils and 46 dry assemblers working in an automotive transmission machining plant using biocides infrequently. The participants completed interviews and performed pre- and postshift spirometry on Monday and Thursday of the same week in each of three rounds of data collection (June 1992, January 1993, June 1993). Generalized estimating equations were used to combine information across rounds in multiple regression models of cross-shift and cross-week changes in forced expiratory volume, I second (FEV 1 ) and forced vital capacity (FVC). Mean seniority was 19 years among machinists. Mean personal TP levels were 0.41 mg/m 3 in machinists and 0.13 mg/m 3 in assemblers. Six of the 83 machinists and none of the 46 assemblers experienced a greater than 19% cross-shift decrement in FEV 1 or FVC at least once (p = .07). In regression models using either TP or BAC, among subjects with lower baseline (Monday preshift) FEV 1 /FVC ratios, increasing exposure was significantly associated with increasing cross-shift decrements in FEV 1 and FVC in linear models, and with increased likelihood of a 10% or greater cross-shift decrement in FEV 1 or FVC in logistic models. Adjustment of TP for VPN did not affect models significantly. We conclude that clinically important cross-shift decrements in pulmonary function are associated with exposure to metalworking fluid aerosols within a high-seniority population. Am. J. Ind. Med. 31:510–524, 1997. © 1997 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34816/1/4_ftp.pd

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

BGEM: An In Situ Hybridization Database of Gene Expression in the Embryonic and Adult Mouse Nervous System

This article describes an open-access gene expression database analyzed for more than 2,000 genes on mouse nervous system tissue in the coronal, sagittal, and transverse orientation representing multiple developmental ages

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur 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 creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]