40 research outputs found
One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas
Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate
Metabolic flux analysis and the NAD(P)H/NAD(P) + ratios in chemostat cultures of Azotobacter vinelandii
Azotobacter vinelandii is a bacterium that produces alginate and polyhydroxybutyrate (P3HB); however, the role of NAD(P)H/NAD(P) + ratios on the metabolic fluxes through biosynthesis pathways of these biopolymers remains unknown. The aim of this study was to evaluate the NAD(P)H/NAD(P) + ratios and the metabolic fluxes involved in alginate and P3HB biosynthesis, under oxygen-limiting and non-limiting oxygen conditions. The results reveal that changes in the oxygen availability have an important effect on the metabolic fluxes and intracellular NADPH/NADP + ratio, showing that at the lowest OTR (2.4 mmol L −1 h −1), the flux through the tricarboxylic acid (TCA) cycle decreased 27.6-fold, but the flux through the P3HB biosynthesis increased 6.6-fold in contrast to the cultures without oxygen limitation (OTR = 14.6 mmol L −1 h −1). This was consistent with the increase in the level of transcription of phbB and the P3HB biosynthesis. In addition, under conditions without oxygen limitation, there was an increase in the carbon uptake rate (twofold), as well as in the flux through the pentose phosphate (PP) pathway (4.8-fold), compared to the condition of 2.4 mmol L −1 h −1. At the highest OTR condition, a decrease in the NADPH/NADP + ratio of threefold was observed, probably as a response to the high respiration rate induced by the respiratory protection of the nitrogenase under diazotrophic conditions, correlating with a high expression of the uncoupled respiratory chain genes (ndhII and cydA) and induction of the expression of the genes encoding the nitrogenase complex (nifH). We have demonstrated that changes in oxygen availability affect the internal redox state of the cell and carbon metabolic fluxes. This also has a strong impact on the TCA cycle and PP pathway as well as on alginate and P3HB biosynthetic fluxes
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Physician-patient communication in rheumatology: a systematic review
The nature of physician–patient interaction can have a significant impact on patient outcomes through information-sharing and disease-specific education that can enhance patients’ active involvement in their care. The aim of this systematic review was to examine all the empirical evidence pertaining to aspects of physician–patient communication and its impact on patient outcomes. A systematic search of five electronic databases (MEDLINE, PsycINFO, EMBASE, CINAHL, and Web of Science) was undertaken from earliest record to December 2016. Studies were eligible if they: (1) included adult participants (18 years or over) with a diagnosis of a rheumatic condition; (2) were of quantitative, qualitative or mixed methods design; (4) were surveys, observational and interventional studies; (5) were published in the English language; and (6) reported findings on either various physician–patient communication aspects alone or in combination with physical and psychological outcomes. Searches identified 455 papers. Following full-text retrieval and assessment for eligibility and quality, ten studies were included in the review; six quantitative, one mixed methods, and three qualitative papers. Higher levels of trust in the physician and active patient participation in the medical consultation were linked to lower disease activity, better global health, less organ damage accrual, greater treatment satisfaction with fewer side effects from the medication, more positive beliefs about control over the disease, and about current and future health. Future research could focus on the design and implementation of interventions incorporating communications skills and patient-education training
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults
Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity
Unmaking public housing towers: the role of lifts and stairs in the demolition of a Puerto Rican project
Through the case of a Puerto Rican public housing project, Las Gladiolas, this article argues that demolitions should be understood as long-term physical and emotional processes of home un making. It focuses on the diverse appearances of lifts and stairs in public housing representations, residents' everyday life, memories, and legal arguments to tell a nuanced story about their meaning and materiality in the un making of home. Drawing together strands from critical geographies of architecture, geographies of home, and emotional geographies, these internal building technologies are approached as active mediators in the way personal and communal life was negotiated and remembered, as well as in the anti-displacement struggle unfolding in the final throes of the buildings' existence. The loss of home through long-term deterioration and displacement is situated in its historical and cultural context, since the island's public housing trajectory has been continually framed by dominant national aspirations of homeownership