Preferences for and comprehension of original and readability-adapted materials

Running title: Preferences and comprehensionIncludes bibliographical references (leaves 41-42)Performed pursuant to contract no. 400-81-0030 of the National Institute of Educatio

Disruption of the GDP-mannose synthesis pathway in Streptomyces coelicolor results in antibiotic hyper-susceptible phenotypes

Actinomycete bacteria use polyprenol phosphate mannose as a lipid linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. We showed recently that strains of Streptomyces coelicolor with mutations in the gene ppm1 encoding polyprenol phosphate mannose synthase were both resistant to phage φC31 and have greatly increased susceptibility to antibiotics that mostly act on cell wall biogenesis. Here we show that mutations in the genes encoding enzymes that act upstream of Ppm1 in the polyprenol phosphate mannose synthesis pathway can also confer phage resistance and antibiotic hyper-susceptibility. GDP-mannose is a substrate for Ppm1 and is synthesised by GDP-mannose pyrophosphorylase (GMP; ManC) which uses GTP and mannose-1-phosphate as substrates. Phosphomannomutase (PMM; ManB) converts mannose-6-phosphate to mannose-1-phosphate. S. coelicolor strains with knocked down GMP activity or with a mutation in sco3028 encoding PMM acquire phenotypes that resemble those of the ppm1-mutants i.e. φC31 resistant and susceptible to antibiotics. Differences in the phenotypes of the strains were observed, however. While the ppm1-strains have a small colony phenotype, the sco3028 :: Tn5062 mutants had an extremely small colony phenotype indicative of an even greater growth defect. Moreover we were unable to generate a strain in which GMP activity encoded by sco3039 and sco4238 is completely knocked out, indicating that GMP is also an important enzyme for growth. Possibly GDP-mannose is at a metabolic branch point that supplies alternative nucleotide sugar donors

Optimization Of Detergent-Mediated Reconstitution Of Influenza A M2 Protein Into Proteoliposomes

We report the optimization of detergent-mediated reconstitution of an integral membrane-bound protein, full-length influenza M2 protein, by direct insertion into detergent-saturated liposomes. Detergent-mediated reconstitution is an important method for preparing proteoliposomes for studying membrane proteins, and must be optimized for each combination of protein and membrane constituents used. The purpose of the reconstitution was to prepare samples for site-directed spin-labeling electron paramagnetic resonance (SDSL-EPR) studies. Our goals in optimizing the protocol were to minimize the amount of detergent used, reduce overall proteoliposome preparation time, and confirm the removal of all detergent. The liposomes were comprised of (1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) and 1-palmitoyl-2-oleyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG), and the detergent octylglucoside (OG) was used for reconstitution. Rigorous physical characterization was applied to optimize each step of the reconstitution process. We used dynamic light scattering (DLS) to determine the amount of OG needed to saturate the preformed liposomes. During detergent removal by absorption with Bio-Beads, we quantified the detergent concentration by means of a colorimetric assay, thereby determining the number of Bio-Bead additions needed to remove all detergent from the final proteoliposomes. We found that the overnight Bio-Bead incubation used in previously published protocols can be omitted, reducing the time needed for reconstitution. We also monitored the size distribution of the proteoliposomes with DLS, confirming that the size distribution remains essentially constant throughout the reconstitution process

Effects of memory load and distraction on performance and event-related slow potentials in a visuospatial working memory task

Brain electrical activity related to working memory was recorded at 15 scalp electrodes during a visuospatial delayed response task. Participants (N = 18) touched the remembered position of a target on a computer screen after either a 1 or 8 sec delay. These memory trials were compared to sensory trials in which the target remained present throughout the delay and response periods. Distracter stimuli identical to the target were briefly presented during the delay on 30% of trials. Responses were less accurate in memory than sensory trials, especially after the long delay. During the delay slow potentials developed that were significantly more negative in memory than sensory trials. The difference between memory and sensory trials was greater at anterior than posterior electrodes. On trials with distracters, the slow potentials generated by memory trials showed further enhancement of negativity whereas there were minimal effects on accuracy of performance. The results provide evidence that engagement of visuospatial working memory generates slow wave negativity with a timing and distribution consistent with frontal activation. Enhanced brain activity associated with working memory is required to maintain performance in the presence of distraction. © 1997 by the Massachusetts Institute of Technolog

Sea Level Rise and City-Level Climate Action.

BACKGROUND: Climate change is the greatest threat to global health in the 21st century. Rising sea levels are one particularly concerning manifestation of this and many of the world’s largest cities are vulnerable to sea level rise (SLR). Thus, urban climate adaptation and mitigation policies are increasingly important to protect population health. OBJECTIVES: This study aimed to determine whether being at risk of SLR was associated with city-level climate action. It also aimed to assess the wider drivers of climate action in cities, in order to guide ongoing efforts to motivate climate action, assess public health preparedness and identify research gaps. METHODS: This is an ecological cross-sectional study using secondary data from CDP, the Urban Climate Change Research Network (UCCRN), World Bank, United Nations Cities and EM-DAT (Emergency Events Database). The study population consisted of 517 cities who participated in CDP’s 2019 Cities Survey. Multivariable logistic regression was utilized to assess the relationship between risk of SLR and city-level climate action, and secondly, to assess the wider determinants of city-level climate action. RESULTS: There was evidence of crude associations between risk of SLR and three outcome variables representing city-level climate action. However, after adjusting for confounding variables, these crude associations disappeared. World region, national income status and urban population were shown to be stronger predictors of city-level climate action. CONCLUSION: It is concerning for population health that there is no association demonstrated between risk of SLR and climate action. This could indicate a lack of awareness of the risks posed by SLR within urban governance. To fulfil their health protection responsibilities, it is essential that public health professionals take a leading role in advocating for climate action

Generation of spatially coherent light at extreme ultraviolet wavelengths

Includes bibliographical references (page 378).We present spatial coherence measurements of extreme ultraviolet (EUV) light generated through the process of high-harmonic up-conversion of a femtosecond laser. With a phase-matched hollow-fiber geometry, the generated beam was found to exhibit essentially full spatial coherence. The coherence of this laser-like EUV source was shown by recording Gabor holograms of small objects. This work demonstrates the capability to perform EUV holography with a tabletop experimental setup. Such an EUV source, with low divergence and high spatial coherence, can be used for experiments involving high-precision metrology, inspection of optical components for EUV lithography, and microscopy and holography with nanometer resolution. Furthermore, the short time duration of the EUV radiation (a few femtoseconds) will enable EUV microscopy and holography to be performed with ultrahigh time resolution

Co-expression and prognostic significance of putative CSC markers CD44, CD133, wild-type EGFR and EGFRvIII in metastatic colorectal cancer

The presence of colorectal cancer stem cells (CSCs) have been associated with tumour initiation and resistance to therapy. This study investigated the co-expression and prognostic significance of the CSCs biomarkers CD44 and CD133 with wild-type EGFR (wtEGFR) and EGFRvIII in colorectal cancer (CRC). The expression of these biomarkers were determined in tumours from 70 patients with metastatic CRC by immunohistochemistry, and in a panel of human CRC cell lines, and their variants with acquired-resistance to EGFR inhibitors, by flow cytometry. The expression of CD44, CD133, wtEGFR and EGFRvIII were present in 17%, 23%, 26% and 13% of cases and the co-expression of CD44/CD133 with wtEGFR and EGFRvIII were present in 9% and 3% of the cases respectively. Only co-expression of CSCs/EGFRvIII (P = 0.037), and amphiregulin (P = 0.017) were associated with worse overall survival. Interestingly, disease-free survival was improved in BTC expressing patients (P = 0.025). In vitro CD133 expression and its co-expression with CD44 were associated with primary-resistance to irinotecan and acquired-resistance to anti-EGFR inhibitors respectively. Our results suggest co-expression of CSCs and EGFRvIII could be potential biomarkers of worse overall survival and resistance to therapy in patients with mCRC and warrants further validation in a larger cohort

Genus β human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study

Objective To investigate the association between genus β human papillomaviruses and the incidence of non-melanocytic skin cancer in the general population

Use of a Community Center Primary Care Clinic and Subsequent Emergency Department Visits among Unhoused Women

Funding/Support: Dr Stewart was supported by grants T32AI007044 and K23MH124466 from the National Institutes of Health (NIH), and Dr Stadeli was supported by training grant T32DK070555 from the NIH. The use of REDCap (Research Electronic Data Capture) software (Vanderbilt University) was supported by grants UL1TR002319, KL2TR002317, and TL1TR002318 from the Institute of Translational Health Science and from the National Center for Advancing Translational Sciences/NIH. The Safe. Healthy. Empowered (SHE) Clinic pilot program was supported by grants from Lahai Health for the period of April 1, 2018 through March 31, 2019, and by the City of Seattle Human Services Department. A mobile van owned and operated by Puget Sound Christian Clinic was used in the study.This cohort study evaluates the association between use of a community center primary care clinic and subsequent nonemergent emergency department (ED) visits by unhoused women who exchange sex and inject drugs.Peer reviewe