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

Nonjudgmental Acceptance: Associations With Substance-Related Cue Reactivity in Adults With Substance Use Disorders and Posttraumatic Stress

The present investigation examined the predictive utility of nonjudgmental acceptance, a facet of mindfulness defined as the ability to remain aware and nonevaluative about internal experience, in terms of substance-related cue reactivity among adults with substance use disorders (SUD) and posttraumatic stress (PTS) symptomatology. We hypothesized that higher nonjudgmental acceptance, indexed via self-report, would predict higher levels of self-reported control over oneself and safety \u27in the moment\u27, broadly, and lower levels of substance-related craving in response to substance script cues. Effects were expected after subtracting reactivity to neutral script cues from each outcome rating. PTS severity was included as a covariate. The sample was comprised of 53 adults (48.1% women; 75.9% African American; 74.1% with past-month PTSD) with substance dependence per DSM-IV and at least four symptoms of PTSD per DSM-5. Higher baseline nonjudgmental acceptance predicted greater safety and control in response to substance cues; no effects were found for craving. These experimental laboratory results elucidate the potential clinical utility of mindfulness-based interventions in bolstering recovery from addiction among adults with SUD/PTS by fostering safety and control in response to substance cues

Electrophysiological Responses to Emotional and Cocaine Cues Reveal Individual Neuroaffective Profiles in Cocaine Users

Smokers with stronger neuroaffective responses to drug-related cues compared to non-drug-related pleasant images (C\u3eP) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P\u3eC). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n=43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. For each picture category, we computed the amplitude of the late positive potential (LPP), an event-related potential component that reflects motivational relevance. k-means clustering classified participants based on their LPP responses. In line with what has been observed in smokers, clustering participants using LPP responses revealed the presence of two groups: one with larger LPPs to pleasant images compared to cocaine images (P\u3eC) and one group with larger LPPs to cocaine images compared to pleasant images (C\u3eP). Individuals with the C\u3eP reactivity profile also had higher attentional bias toward drug cues. The two groups did not differ on demographic and drug use characteristics, however individuals with the C\u3eP profile reported lower distress tolerance, higher anhedonia, and higher posttraumatic stress symptoms compared to the P\u3eC group. This is the first study to report the presence of these neuroaffective profiles in individuals with CUD, indicating that this pattern may cut across addiction populations

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

We present spatial coherence measurements of extreme-ultraviolet light generated using the process of high-harmonic upconversion of a femtosecond laser. Using a phase-matched hollow-fiber geometry, the generated beam is found to exhibit essentially full spatial coherence. The coherence of this laser-like EUV source is demonstrated by recording Gabor holograms of small objects. This work demonstrates the capability to do EUV holography using a tabletop experimental setup. Such an EUV source, with low divergence and high spatial coherence, can be used for experiments such as high-precision metrology, inspection of optical components for EUV lithography (1), and for microscopy and holography (2) 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.Comment: 16 pages, 4 figure

Posttraumatic Stress Symptom Clusters Differentially Predict Late Positive Potential to Cocaine Imagery Cues in Trauma-Exposed Adults With Cocaine Use Disorder

BACKGROUND: While studies have investigated the effects of posttraumatic stress disorder (PTSD) symptoms on substance use, information on these associations in the context of drug cue reactivity is lacking, which can provide meaningful information about risk for relapse. The current study assessed the associations between PTSD symptom clusters and reactivity to cues in trauma-exposed adults with cocaine use disorder. METHODS: We recorded electroencephalogram on 52 trauma-exposed participants (M RESULTS: Linear mixed modeling indicated that higher NACM symptomatology was associated with higher LPPs to cocaine cues and higher arousal/reactivity was associated with lower LPPs to cocaine cues. CONCLUSIONS: These results highlight the potential clinical utility of the LPP in assessing drug cue reactivity in trauma-exposed adults with substance use disorder