TransCom 3 experimental protocol

July 2000.Includes bibliographical references.Sponsored by NSF award OCE-9900310, and NOAA NA67RJ0152 Amend. 30

A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic

Background Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin. Methodology/Principal Findings High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters. Targeted gene knockouts confirmed the role of these clusters in biosynthesis of the two separate components, pseudomonic acid and the pyrrothine, and identified a putative amide synthetase that joins them together. Feeding mupirocin to a mutant unable to make the endogenous pseudomonic acid created a novel hybrid with the pyrrothine via “mutasynthesis” that allows inhibition of mupirocin-resistant isoleucyl-tRNA synthetase, the mupirocin target. A mutant defective in pyrrothine biosynthesis was also able to incorporate alternative amine substrates. Conclusions/Significance Plasmid pTML1 provides a paradigm for combining independent antibiotic biosynthetic pathways or using mutasynthesis to develop a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA

Severe climate change risks to food security and nutrition

This paper discusses severe risks to food security and nutrition that are linked to ongoing and projected climate change, particularly climate and weather extremes in global warming, drought, flooding, and precipitation. We specifically consider the impacts on populations vulnerable to food insecurity and malnutrition due to lower income, lower access to nutritious food, or social discrimination. The paper defines climate-related “severe risk” in the context of food security and nutrition, using a combination of criteria, including the magnitude and likelihood of adverse consequences, the timing of the risk and the ability to reduce the risk. Severe climate change risks to food security and nutrition are those which result, with high likelihood, in pervasive and persistent food insecurity and malnutrition for millions of people, have the potential for cascading effects beyond the food systems, and against which we have limited ability to prevent or fully respond. The paper uses internationally agreed definitions of risks to food security and nutrition to describe the magnitude of adverse consequences. Moreover, the paper assesses the conditions under which climate change-induced risks to food security and nutrition could become severe based on findings in the literature using different climate change scenarios and shared socioeconomic pathways. Finally, the paper proposes adaptation options, including institutional management and governance actions, that could be taken now to prevent or reduce the severe climate risks to future human food security and nutrition

Musculoskeletal shoulder pain: Home exercise frequency and adherence to appointments are not mediators of outcome

Objective: To investigate whether appointment adherence and frequency of home exercises mediates the association of baseline i) pain self-efficacy (PSE) or ii) patient expectation of recovery, with outcome at 6 months.Design: Multicentre longitudinal cohort study. Methods: Six-month outcome data (SPADI, QuickDASH) were provided by 810 of 1030 recruited participants. Daily frequency of home exercises over 6 weeks, were expressed as the proportion of days exercises were completed. Measures of adherence included proportion of appointments attended and completing a course of physiotherapy. Mediation analyses were conducted using Baron and Kennys’ four-step method, and for continuous variables, testing the indirect effect using a non-parametric version of Sobel’s test. Results: Appointment adherence, completing a course of physiotherapy and frequency of home exercise did not mediate the relationship between PSE or patient expectation with 6 months SPADI or QuickDASH. Higher PSE was significantly associated with appointment adherence and completing a course of physiotherapy. Patient expectation was significantly associated with frequency of home exercise. However, none of the hypothesised mediators had a significant effect on outcome. Conclusion: Appointment adherence and higher frequency of home exercise do not appear to be the mechanisms by which high PSE or expectation of recovery predict a good outcome. This study was not designed to address the effectiveness of a home exercise programme for which no conclusions should be drawn. However, our results do support the need for a greater emphasis on the assessment and incorporation of techniques to facilitate high pain self-efficacy and expectation of recovery

The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders

Research data management as a “wicked problem”

Purpose – The purpose of this paper is to explore the usefulness of the concept to thinking about Research Data Management (RDM). The concept of “wicked problems” seeks to differentiate very complex, intractable challenges from tamer issues where approaches to problem solving are well-understood. Design/methodology/approach – The paper is based on and co-authored by a collaboration of practitioners from libraries, information technology and research administration, with facilitators from the Sheffield Information School. Participants worked together in two-day-long workshops to understand the wicked problem concept and advice on leadership in wicked problem contexts. Findings – Participants concurred that RDM had many features of a wicked problem and most of Grint’s advice on leadership for wicked problems also resonated. Some elements of the issue were simple; participants were optimistic about improving the situation over time. Participants were resistant to the more negative or fatalistic connotations of the phrase “wicked problem”. Viewing RDM as a wicked problem is an interesting way of looking at it as a challenge for support professionals. Practical implications – The notion of a wicked problem is a generative concept that can be usefully added to professional vocabulary. Originality/value – The paper captures an in-depth response from practitioners to the notion of wicked problems as a lens for examining RDM

Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313, KADY, Lokk, MyraDee, Stagni, and StepMih

Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster

Garotas de loja, história social e teoria social [Shop Girls, Social History and Social Theory]

Shop workers, most of them women, have made up a significant proportion of Britain’s labour force since the 1850s but we still know relatively little about their history. This article argues that there has been a systematic neglect of one of the largest sectors of female employment by historians and investigates why this might be. It suggests that this neglect is connected to framings of work that have overlooked the service sector as a whole as well as to a continuing unease with the consumer society’s transformation of social life. One element of that transformation was the rise of new forms of aesthetic, emotional and sexualised labour. Certain kinds of ‘shop girls’ embodied these in spectacular fashion. As a result, they became enduring icons of mass consumption, simultaneously dismissed as passive cultural dupes or punished as powerful agents of cultural destruction. This article interweaves the social history of everyday shop workers with shifting representations of the ‘shop girl’, from Victorian music hall parodies, through modernist social theory, to the bizarre bombing of the Biba boutique in London by the Angry Brigade on May Day 1971. It concludes that progressive historians have much to gain by reclaiming these workers and the service economy that they helped create

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe