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Small multidrug resistance (SMR) transporters are key players in the defense of multidrug-resistant pathogens to toxins and other homeostasis-perturbing compounds. However, recent evidence demonstrates that EmrE, an SMR from Escherichia coli and a model for understanding transport, can also induce susceptibility to some compounds by drug-gated proton leak. This runs down the ∆pH component of the proton-motive force (PMF), reducing the viability of the affected bacteria. Proton leak may provide an unexplored drug target distinct from the targets of most known antibiotics. Activating proton leak requires an SMR to be merely present, rather than be the primary resistance mechanism, and dissipates the energy source for many other efflux pumps. PAsmr, an EmrE homolog from Pseudomonas aeruginosa , transports many EmrE substrates in cells and purified systems. We hypothesized that PAsmr, like EmrE, may confer susceptibility to some compounds via drug-gated proton leak. Growth assays of E. coli expressing PAsmr displayed substrate-dependent resistance and susceptibility phenotypes, and in vitro solid-supported membrane electrophysiology experiments revealed that PAsmr performs both antiport and substrate-gated proton uniport, demonstrating the same functional promiscuity observed in EmrE. Growth assays of P. aeruginosa strain PA14 demonstrated that PAsmr contributes resistance to some antimicrobial compounds, but no growth defect is observed with susceptibility substrates, suggesting P. aeruginosa can compensate for the proton leak occurring through PAsmr. These phenotypic differences between P. aeruginosa and E. coli advance our understanding of the underlying resistance mechanisms in P. aeruginosa and prompt further investigation into the role that SMRs play in antibiotic resistance in pathogens., Importance: Small multidrug resistance (SMR) transporters are a class of efflux pumps found in many pathogens, although their contributions to antibiotic resistance are not fully understood. We hypothesize that these transporters may confer not only resistance but also susceptibility, by dissipating the proton-motive force. This means to use an SMR transporter as a target; it merely needs to be present (as opposed to being the primary resistance mechanism). Here, we test this hypothesis with an SMR transporter found in Pseudomonas aeruginosa and find that it can perform both antiport (conferring resistance) and substrate-gated proton leak. Proton leak is detrimental to growth in Escherichia coli but not P. aeruginosa , suggesting that P. aeruginosa responds differently to or can altogether prevent ∆pH dissipation., Competing Interests: The authors declare no conflict of interest.

Spot form net blotch, caused by Pyrenophora teres f. maculata, is a major foliar disease of barley worldwide. Knowledge of the pathogen's genetic diversity and population structure is critical for a better understanding of inherent evolutionary capacity and for the development of sustainable disease management strategies. Genome-wide, single nucleotide polymorphism data of 254 Australian isolates revealed genotypic diversity and an absence of population structure, either between states, or between fields and cultivars in different agro-ecological zones. This indicates there is little geographical isolation or cultivar directional selection and that the pathogen is highly mobile across the continent. However, two cryptic genotypic groups were found only in Western Australia, predominantly associated with genes involved in fungicide resistance. The findings in this study are discussed in the context of current cultivar resistance and the pathogen's adaptive potential., Competing Interests: Conflicts of interest statement The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Genetics Society of America.)

Key Message: QTL for tan spot resistance were mapped on wheat chromosomes 1A and 2A. Lines were developed with resistance alleles at these loci and at the tsn1 locus on chromosome 5B. These lines expressed significantly higher resistance than the parent with tsn1 only. Tan spot (syn. yellow spot and yellow leaf spot) caused by Pyrenophora tritici-repentis is an important foliar disease of wheat in Australia. Few resistance genes have been mapped in Australian germplasm and only one, known as tsn1 located on chromosome 5B, is known in Australian breeding programs. This gene confers insensitivity to the fungal effector ToxA. The main aim of this study was to map novel resistance loci in two populations: Calingiri/Wyalkatchem, which is fixed for the ToxA-insensitivity allele tsn1, and IGW2574/Annuello, which is fixed for the ToxA-sensitivity allele Tsn1. A second aim was to combine new loci with tsn1 to develop lines with improved resistance. Tan spot severity was evaluated at various growth stages and in multiple environments. Symptom severity traits exhibited quantitative variation. The most significant quantitative trait loci (QTL) were detected on chromosomes 2A and 1A. The QTL on 2A explained up to 29.2% of the genotypic variation in the Calingiri/Wyalkatchem population with the resistance allele contributed by Wyalkatchem. The QTL on 1A explained up to 28.1% of the genotypic variation in the IGW2574/Annuello population with the resistance allele contributed by Annuello. The resistance alleles at both QTL were successfully combined with tsn1 to develop lines that express significantly better resistance at both seedling and adult plant stages than Calingiri which has tsn1 only.

Despite the global transition to overnutrition, stunting affected approximately 159 million children worldwide in 2014, while an estimated 50 million children were wasted. India is an important front in the fight against malnutrition and is grappling with the coexistence of undernutrition, overnutrition, and micronutrient deficiencies. This report summarizes discussions on trends in malnutrition in India, its evolution in the context of economic growth, intrahousehold aspects, infant and young child feeding practices, women's status, maternal nutrition, and nutrition policymaking. The discussion focuses on a review of trends in malnutrition and dietary intakes in India in the context of economic change over the past four decades, identification of household dynamics affecting food choices and their consequences for family nutritional status in India, and effective malnutrition prevention and treatment interventions and programs in India and associated policy challenges., (© 2017 New York Academy of Sciences.)

Nutrition is affected by numerous environmental and societal causes. This paper starts with a simple framework based on three domains: nutritional quality, economic viability, and environmental sustainability, and calls for an integrated approach in research to simultaneously account for all three. It highlights limitations in the current understanding of each domain, and how they influence one another. Five research topics are identified: measuring the three domains (nutritional quality, economic viability, environmental sustainability); modeling across disciplines; furthering the analysis of food systems in relation to the three domains; connecting climate change and variability to nutritional quality; and increasing attention to inequities among population groups in relation to the three domains. For an integrated approach to be developed, there is a need to identify and disseminate available metrics, modeling techniques, and tools to researchers, practitioners, and policy makers. This is a first step so that a systems approach that takes into account potential environmental and economic trade-offs becomes the norm in analyzing nutrition and food-security patterns. Such an approach will help fill critical knowledge gaps and will guide researchers seeking to define and address specific research questions in nutrition in their wider socioeconomic and environmental contexts., (© 2014 New York Academy of Sciences.)

Gastrointestinal dysfunction remains a major cause of morbidity and mortality. Indeed, gastrointestinal (GI) motility in health and disease remains an area of productive research with over 1,400 published animal studies in just the last 5 years. Numerous techniques have been developed for quantifying smooth muscle activity of the stomach, small intestine, and colon. In vitro and ex vivo techniques offer powerful tools for mechanistic studies of GI function, but outside the context of the integrated systems inherent to an intact organism. Typically, measuring in vivo smooth muscle contractions of the stomach has involved an anesthetized preparation coupled with the introduction of a surgically placed pressure sensor, a static pressure load such as a mildly inflated balloon or by distending the stomach with fluid under barostatically-controlled feedback. Yet many of these approaches present unique disadvantages regarding both the interpretation of results as well as applicability for in vivo use in conscious experimental animal models. The use of dual element strain gages that have been affixed to the serosal surface of the GI tract has offered numerous experimental advantages, which may continue to outweigh the disadvantages. Since these gages are not commercially available, this video presentation provides a detailed, step-by-step guide to the fabrication of the current design of these gages. The strain gage described in this protocol is a design for recording gastric motility in rats. This design has been modified for recording smooth muscle activity along the entire GI tract and requires only subtle variation in the overall fabrication. Representative data from the entire GI tract are included as well as discussion of analysis methods, data interpretation and presentation.

Fortification is the purposeful addition of vitamins and minerals to foods during their industrial processing, as a way to improve the nutrition and health of populations who consume these foods. Twelve countries have mandatory maize (Zea mays subsp. Mays) flour or meal fortification. The World Health Organization (WHO) is updating evidence-informed guidelines for the fortification of staple foods in public health, including the fortification of maize flour and corn meal with iron and other micronutrients. Although there is limited experience with fortification of maize, mass fortification of maize flour with at least iron has been practiced for many years in several countries in the Americas and Africa: Brazil, Costa Rica, El Salvador, Kenya, Mexico, Nigeria, Rwanda, South Africa, Tanzania, Uganda, the United States, and Venezuela. The WHO, in collaboration with the Sackler Institute for Nutrition Science and the Flour Fortification Initiative (FFI), convened a consultation on technical considerations for fortification of maize flour and corn meal in public health in New York, New York on April 8-9, 2013 to provide input into the guideline-development process and to discuss technical considerations of the fortification processes for maize flour and corn meal., (© 2014 New York Academy of Sciences. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

The responses of 95 barley lines and cultivars to spot form of net blotch (SFNB) caused by Pyrenophora teres f. maculata were analyzed as seedlings and adults in Australia and Canada. Cluster analyses revealed complex reaction responses. Only 2 lines (Esperance Orge 289 and TR3189) were resistant to all isolates at the seedling stage, whereas 15 lines and cultivars (81-82/033, Arimont, BYDV-018, CBSS97M00855T-B2-M1-Y1-M2-Y-1M-0Y, CI9776, Keel, Sloop, Torrens, TR326, VB0111, Yarra, VB0229, WI-2477, WI2553, and Wisconsin Pedigree) were resistant toward the two Canadian isolates and mixture of Australian isolates at the adult stages. In Australian field experiments, the effectiveness of SFNB resistance in three barley cultivars (Barque, Cowabbie, and Schooner) and one breeding line (VB9104) with a different source of resistance was tested. Barque, which possessed a resistance gene that provided complete resistance to SFNB, was the most effective and showed no effect on grain yield or quality in the presence of inoculum. Generally, cultivars with seedling or adult resistance had less disease and better grain quality than the susceptible control, Dash, but they were not as effective as Barque. A preliminary differential set of 19 barley lines and cultivars for P. teres f. maculata is proposed.