Using electrostatic potentials to predict DNA-binding sites on DNA-binding proteins

A method to detect DNA-binding sites on the surface of a protein structure is important for functional annotation. This work describes the analysis of residue patches on the surface of DNA-binding proteins and the development of a method of predicting DNA-binding sites using a single feature of these surface patches. Surface patches and the DNA-binding sites were initially analysed for accessibility, electrostatic potential, residue propensity, hydrophobicity and residue conservation. From this, it was observed that the DNA-binding sites were, in general, amongst the top 10% of patches with the largest positive electrostatic scores. This knowledge led to the development of a prediction method in which patches of surface residues were selected such that they excluded residues with negative electrostatic scores. This method was used to make predictions for a data set of 56 non-homologous DNA-binding proteins. Correct predictions made for 68% of the data set

The Courage to Change: Striving for Magnet Hospital Recognition

In the ever-changing environment of health care, good leaders are of utmost importance to the effective functioning of the hospital. Leadership in the hospital setting requires innovativeness and courage. This means the passion to discover, create and experience the unknown. Until recently why some hospitals attract and retain good nurses while others do not was unknown. The magnet hospital concept identified attributes that supported the professional practice of nursing which, in turn increased nurse recruitment and retention. The objective of this study was to compare Chief Nursing Officer (CNO) and Chief Executive Officer (CEO) perceptions of their innovativeness and leadership preferences in magnet hospitals and matched non-magnet hospitals as well as differences in the perceived organizational effectiveness. This study was a survey-based cross-sectional, non-experimental study. The basic statistical design for testing the hypotheses was a 2 (Chief Officer type: CNO vs. CEO) x 2 (hospital type: magnet vs. non-magnet) mixed design ANOVA. A web-based survey supported the collection of leadership attributes, innovativeness, and perceived organizational effectiveness as well as obtained demographic information. The two major findings were the predicted staff status (CNO vs. CEO) by hospital type (magnet vs. non-magnet) interactions for innovativeness and the leadership practice of “enabling.” The pattern of results suggests that most CNOs and some CEOs use innovative approaches and have the skills to develop co-operative relationships and teams. Magnet CNOs demonstrated the highest scores. This study supports the American Nurses Credentialing Center\u27s emphasis on the role of the CNO in adopting magnet standards and strategies. Further research on the “magnet CNO effect” is encouraged

Immunological and electrophoretic studies on dog alkaline phosphates with particular reference to serum.

An investigation was carried out to determine the tissue of origin of serum alkaline phosphatase in normal dogs and in dogs treated with the insecticide dieldrin. The work involved comparisons between tissue and serum alkaline phosphatases on the basis of immunological and electrophoretic properties. Alkaline phosphatases from dog liver, kidney, intestine and bone were separable by electrophoretic pattern on polyacrylamide gel, except for some overlapping between bone and renal bands. By electrophoretic analysis, liver appeared to be the major source of serum alkaline phosphatase in both normal and hyperphosphatasemic sera from dieldrin treated dogs. Rabbit antiserum to dog intestinal alkaline phosphatase was used to demonstrate phosphatase of intestinal origin in some dog sera. The presence of this additional serum enzyme was not related to administration of dieldrin. The work was extended to an investigation of the origin of alkaline phosphatase in dog urine. Urinary phosphatase differed electrophoretically and immunologically from that of the kidney and showed some similarity to bladder alkaline phosphatase. Alkaline phosphatase from dog intestinal mucosa was shown to differ from phosphatases extractable from the predominant bacterial flora of dog duodenum and faeces. Immunofluorescence was used to demonstrate alkaline phosphatase on the outer surface of intestinal villi

Using structural motifs to identify proteins with DNA binding function

This work describes a method for predicting DNA binding function from structure using 3-dimensional templates. Proteins that bind DNA using small contiguous helix¿turn¿helix (HTH) motifs comprise a significant number of all DNA-binding proteins. A structural template library of seven HTH motifs has been created from non-homologous DNA-binding proteins in the Protein Data Bank. The templates were used to scan complete protein structures using an algorithm that calculated the root mean squared deviation (rmsd) for the optimal superposition of each template on each structure, based on Ca backbone coordinates. Distributions of rmsd values for known HTH-containing proteins (true hits) and non-HTH proteins (false hits) were calculated. A threshold value of 1.6 Å rmsd was selected that gave a true hit rate of 88.4% and a false positive rate of 0.7%. The false positive rate was further reduced to 0.5% by introducing an accessible surface area threshold value of 990 Å2 per HTH motif. The template library and the validated thresholds were used to make predictions for target proteins from a structural genomics project

Mars atmospheric escape and isotopic fractionation: Synthesis of data and models

The present Mars atmosphere is relatively thin and cold. It is not at all like that which is presumed to have been responsible for the formation of valley networks and the heavy erosion of craters during the earliest epochs of martian history. An important goal of Mars exploration is to try to understand the properties of the early atmosphere, the initial inventory of volatiles at the planet's surface, the processes by which the atmosphere and climate have evolved over time, and the current location of volatiles presumed to have been in the atmosphere in the earlier times. The current status of understanding of the escape of volatiles to space over geologic time and the resulting fractionation of isotopes of stable atoms remaining in the atmosphere are described, and a scenario for volatile abundance and evolution that is consistent with the available information on the escape and fractionation of each species is constructed. In particular, the evolution of hydrogen, carbon, oxygen, and nitrogen, as contained in atmospheric (and non-atmospheric) water, carbon dioxide, and molecular nitrogen, is examined

“We’re, like, the Most Unhealthy People in the Country”: Employing an Equity Lens to Reduce Barriers to Healthy Food Access in Rural Appalachia

Introduction Obesity disproportionately affects rural communities, and Appalachia has some of the highest obesity rates in the nation. Successful policy, systems, and environmental (PSE) interventions to reduce obesity must reflect the circumstances of the population. We used a health equity lens to identify barriers and facilitators for healthy food access in Martin County, Kentucky, to design interventions responsive to social, cultural, and historical contexts. Methods We conducted 5 focus groups in Martin County, Kentucky, in fall 2019 to obtain perspectives on the local food system and gauge acceptability of PSE interventions. We used grounded theory to identify perceived barriers and facilitators for healthy eating. Results Thirty-four adults (27 women; median age, 46 years) participated in 5 groups. One prominent theme was declining interest in farming; many participants believed this decline was generational. One participant noted, “Most of my adult male relatives worked in the coal mines, and they worked 6 days a week. . . . My grandpa had the garden, but then my dad’s generation is the one quit gardening.” Another shared, “You would probably have to have someone to teach [gardening].” Instead of enhancing farmers markets, participants suggested building community capacity for home gardens to increase vegetable consumption. Conclusion Our findings demonstrate the importance of obtaining community input on the development of PSE interventions to mitigate inequities in obesity. Although farmers market interventions were deemed not feasible, other solutions to enhance access to produce were identified. Developers of community-responsive PSE interventions to improve healthy eating in rural, food-insecure locations should consider using an equity-oriented prevention framework to ensure acceptable interventions

Patterns of Natural and Human-Caused Mortality Factors of a Rare Forest Carnivore, the Fisher (Pekania pennanti) in California.

Wildlife populations of conservation concern are limited in distribution, population size and persistence by various factors, including mortality. The fisher (Pekania pennanti), a North American mid-sized carnivore whose range in the western Pacific United States has retracted considerably in the past century, was proposed for threatened status protection in late 2014 under the United States Endangered Species Act by the United States Fish and Wildlife Service in its West Coast Distinct Population Segment. We investigated mortality in 167 fishers from two genetically and geographically distinct sub-populations in California within this West Coast Distinct Population Segment using a combination of gross necropsy, histology, toxicology and molecular methods. Overall, predation (70%), natural disease (16%), toxicant poisoning (10%) and, less commonly, vehicular strike (2%) and other anthropogenic causes (2%) were causes of mortality observed. We documented both an increase in mortality to (57% increase) and exposure (6%) from pesticides in fishers in just the past three years, highlighting further that toxicants from marijuana cultivation still pose a threat. Additionally, exposure to multiple rodenticides significantly increased the likelihood of mortality from rodenticide poisoning. Poisoning was significantly more common in male than female fishers and was 7 times more likely than disease to kill males. Based on necropsy findings, suspected causes of mortality based on field evidence alone tended to underestimate the frequency of disease-related mortalities. This study is the first comprehensive investigation of mortality causes of fishers and provides essential information to assist in the conservation of this species

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer : Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial

Background The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence. Materials and methods Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests. Results 334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]). Conclusions Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC