Dynamics and Selective Remodeling of the DNA-binding Domains of RPA

Replication protein A (RPA) coordinates important DNA metabolic events by stabilizing single-stranded DNA (ssDNA) intermediates, activating the DNA-damage response and handing off ssDNA to the appropriate downstream players. Six DNA-binding domains (DBDs) in RPA promote high-affinity binding to ssDNA yet also allow RPA displacement by lower affinity proteins. We generated fluorescent versions of Saccharomyces cerevisiae RPA and visualized the conformational dynamics of individual DBDs in the context of the full-length protein. We show that both DBD-A and DBD-D rapidly bind to and dissociate from ssDNA while RPA remains bound to ssDNA. The recombination mediator protein Rad52 selectively modulates the dynamics of DBD-D. These findings reveal how RPA-interacting proteins with lower ssDNA binding affinities can access the occluded ssDNA and remodel individual DBDs to replace RPA

Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine

<p>Abstract</p> <p>Background</p> <p>Lafutidine is a histamine H₂receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg) modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge.</p> <p>Methods</p> <p>Adult rats were treated with vehicle, lafutidine (10 – 30 mg/kg) or cimetidine (10 mg/kg), and 30 min later their stomachs were exposed to exogenous HCl (0.25 M). During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry.</p> <p>Results</p> <p>Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H₂receptor antagonist cimetidine had similar but weaker effects.</p> <p>Conclusion</p> <p>These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H₂receptor antagonists can protect the gastric mucosa from acid injury independently of their ability to suppress gastric acid secretion.</p

CHD2 variants are a risk factor for photosensitivity in epilepsy

Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2·17 × 10−5). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3·50 × 10−4). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research into human cortical excitability

Personality profiles of cultures: aggregate personality traits

Personality profiles of cultures can be operationalized as the mean trait levels of culture members. College students from 51 cultures rated an individual from their country whom they knew well (N = 12, 156). Aggregate scores on Revised NEO Personality Inventory scales generalized across age and gender groups, approximated the individual-level Five-Factor Model, and correlated with aggregate self-report personality scores and other culture-level variables. Results were not attributable to national differences in economic development or to acquiescence. Geographical differences in scale variances and mean levels were replicated, with Europeans and Americans generally scoring higher in Extraversion than Asians and Africans. Findings support the rough scalar equivalence of NEO-PI-R factors and facets across cultures, and suggest that aggregate personality profiles provide insight into cultural differences

Twitter and Teaching: to Tweet or not to Tweet?

. As increasingly more new skills are necessary for graduates entering the workplace or seeking employment, business leaders, politicians and educators suggest that if students are to succeed in today’s world, they will require 21st century skills. However, there is no single agreed-upon set of skills. We argue that social media skills are becoming ever more important for employment and society should class them as important 21st-century skills from maintaining well-rounded social media profiles to more advanced data science and analytic skills. At the same time, such a demand affects the teaching process since teachers have to acquire new knowledge about the available tools. Twitter as a microblogging platform is definitely one of the tools that is a part of 21st-century social skills. Thus, by integrating it into the teaching process, Twitter can generate new experiences for both sides, the students and the teachers. In this paper, we conduct a descriptive review of the recent literature that covers Twitter use in teaching. We reviewed results from the top 100 retrieved research results in Web of Science on Twitter and teaching in the domains of social science, science technology, and arts and humanities. We analysed the results quantitatively in terms of content, methods, and methodologies and qualitatively as the description of results found in selected papers that meet certain criteria. This paper also discusses different research departure points for use in further research of the topic

Cultural adaptation and examination of metric characteristics shirom-melamed burnout questionnaire (SMBQ) on a sample of pharmacists in Serbia

© 2018, Association of Pharmaceutical Teachers of India. All rights reserved. Introduction: Due to the nature of work in pharmacies pharmacists may occur job burnout, which can affect the quality of health services. It is necessary to use validated instruments to test the burnout. One type of instrument is Shirom-Melamed Burnout Questionnaire (SMBQ). Objective: The primary objectives of this work are: cultural adaptation and assessment metric characteristics of SMBQ in a population of pharmacists in Serbia. Alternative objective is evaluate the degree of burnout in the pharmacist population. Methods: For comparison Maslach Burnout Inventory (MBI) was used. All licensed pharmacists have received an email by the Pharmaceutical Chamber of Serbia, with a link for accessing the questionnaires. The questionnaires were completed by 514 pharmacists. Results and Discussion: Professional translators carried out the translation using translation steps like forward translation and backward translation. Were calculated following metric characteristics: α - reliability coefficient Cronbach and associates; β - the reliability of the first principal component; ψ1 - representativeness; h1 - the homogeneity (the average correlation of scale items), extent of curvature, horizontal (Skewness) and vertical (Kurtosis). Correlations between subscales are examined. Latent structure SMBQ (maximumlikelihud extraction) is examined. To select a number of factors, the method of parallel analysis was used. For calculation number of latent factors the Hull method was applied. Concurrent validity was examined by correlating the results of the questionnaire SMBQ and MBI. To confirm a one factor solution of the scale, factor analysis was used. Conclusion: All methods show that it is best to keep only one factor. SMBQ satisfies theoretical statistical criteria of reliability and validity and can be used to estimate job burnout at pharmacist population