Fitness of Escherichia coli during Urinary Tract Infection Requires Gluconeogenesis and the TCA Cycle

Microbial pathogenesis studies traditionally encompass dissection of virulence properties such as the bacterium's ability to elaborate toxins, adhere to and invade host cells, cause tissue damage, or otherwise disrupt normal host immune and cellular functions. In contrast, bacterial metabolism during infection has only been recently appreciated to contribute to persistence as much as their virulence properties. In this study, we used comparative proteomics to investigate the expression of uropathogenic Escherichia coli (UPEC) cytoplasmic proteins during growth in the urinary tract environment and systematic disruption of central metabolic pathways to better understand bacterial metabolism during infection. Using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and tandem mass spectrometry, it was found that UPEC differentially expresses 84 cytoplasmic proteins between growth in LB medium and growth in human urine (P<0.005). Proteins induced during growth in urine included those involved in the import of short peptides and enzymes required for the transport and catabolism of sialic acid, gluconate, and the pentose sugars xylose and arabinose. Proteins required for the biosynthesis of arginine and serine along with the enzyme agmatinase that is used to produce the polyamine putrescine were also up-regulated in urine. To complement these data, we constructed mutants in these genes and created mutants defective in each central metabolic pathway and tested the relative fitness of these UPEC mutants in vivo in an infection model. Import of peptides, gluconeogenesis, and the tricarboxylic acid cycle are required for E. coli fitness during urinary tract infection while glycolysis, both the non-oxidative and oxidative branches of the pentose phosphate pathway, and the Entner-Doudoroff pathway were dispensable in vivo. These findings suggest that peptides and amino acids are the primary carbon source for E. coli during infection of the urinary tract. Because anaplerosis, or using central pathways to replenish metabolic intermediates, is required for UPEC fitness in vivo, we propose that central metabolic pathways of bacteria could be considered critical components of virulence for pathogenic microbes

The Putative Liquid-Liquid Transition is a Liquid-Solid Transition in Atomistic Models of Water

We use numerical simulation to examine the possibility of a reversible liquid-liquid transition in supercooled water and related systems. In particular, for two atomistic models of water, we have computed free energies as functions of multiple order parameters, where one is density and another distinguishes crystal from liquid. For a range of temperatures and pressures, separate free energy basins for liquid and crystal are found, conditions of phase coexistence between these phases are demonstrated, and time scales for equilibration are determined. We find that at no range of temperatures and pressures is there more than a single liquid basin, even at conditions where amorphous behavior is unstable with respect to the crystal. We find a similar result for a related model of silicon. This result excludes the possibility of the proposed liquid-liquid critical point for the models we have studied. Further, we argue that behaviors others have attributed to a liquid-liquid transition in water and related systems are in fact reflections of transitions between liquid and crystal

Selective Cholinergic Depletion in Medial Septum Leads to Impaired Long Term Potentiation and Glutamatergic Synaptic Currents in the Hippocampus

Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Why do work sampling studies in construction? The case of plumbing work in Scandiavia

Purpose– The purpose of this paper is to identify reasons for doing work sampling studies in processes performed by temporary organisations. Specific questions consider if the technique can be used for measuring productivity and if it can be used to compare performances over time.Design/methodology/approach– A work sampling study of plumbing work in eight construction projects is compared with a similar study performed 20 years earlier. Interviews are made in order to find out how the work conditions have developed over time.Findings– Work sampling studies are of little value for measuring productivity as well as for comparing performances over time. One reason is that the conditions vary to a high extent from one situation to another. Another reason is that working conditions undergo significant development over time. On the other hand, the authors experience that data from work sampling studies are of high relevance for discussions on improvement opportunities among workers as well as among corporate managers

Why do work sampling studies in construction? The case of plumbing work in Scandiavia

Purpose– The purpose of this paper is to identify reasons for doing work sampling studies in processes performed by temporary organisations. Specific questions consider if the technique can be used for measuring productivity and if it can be used to compare performances over time.Design/methodology/approach– A work sampling study of plumbing work in eight construction projects is compared with a similar study performed 20 years earlier. Interviews are made in order to find out how the work conditions have developed over time.Findings– Work sampling studies are of little value for measuring productivity as well as for comparing performances over time. One reason is that the conditions vary to a high extent from one situation to another. Another reason is that working conditions undergo significant development over time. On the other hand, the authors experience that data from work sampling studies are of high relevance for discussions on improvement opportunities among workers as well as among corporate managers

31 recommendations for increased profit - reducing waste

Those companies and organizations that wish to ensure long-term profitability must successively decrease resource use in both product development and in product usage. Primarily, it is waste that must be reduced, i.e. the consumption of resources that do not add to customer value or to the organization. Waste is widespread in all operations. Even in well-functioning processes, more than half of the resource consumption can be classified as waste. One obstacle to waste elimination is that most waste is hidden. Thus, executives, middle management and specialists must prioritize efforts to uncover the waste in their operations.Building and construction activities consist of a complex system of decisions, components, organizations and processes that must be coordinated. There are therefore many explanations as to why waste arises, or does not. Based on a series of discussions with experienced builders, consultants, contractors and materials providers, five main groups of factors that characterize effective operations were found. In this report these factors are illustrated in the form of a “value pyramid”. A holistic view of long-term customer benefits is the apex of the pyramid. Structure, competence, leadership and culture act as the driving forces at each corner of the pyramid’s foundation. Should one of the corners gives way, then the pyramid risks toppling over.With the value pyramid as support, 31 recommendations for what should be done to reduce waste are presented. These are aimed at standardizing the product from an overall perspective (five recommendations), defining and standardizing processes (ten recommendations), developing the organization and its competence (seven recommendations), disciplining management (five recommendations), and driving continuous improvement work (four recommendations). Reducing uncertainties and increasing effective time utilization are the red threads, as the Swedes would say, that run through all the recommendations.Everyone who uses resources has a responsibility to reduce waste. By systematically monitoring one’s own use of time, one can gain insights that will help improve one’s work situation. However, the burden of initiating and driving improvements overall obviously lies with management. How this should be done depends on the nature and purpose of the activities as well as on the organization’s capabilities. It is to manage this progress and achieve profitability that managers are appointed. It is in the interest of all enterprises and organizations to develop the ability and an interest to detect and understand what work/task is value adding what is not. This ability will provide possibilities to develop new competitive advantages and new business concepts