Influenza Polymerase Activity Correlates with the Strength of Interaction between Nucleoprotein and PB2 through the Host-Specific Residue K/E627

The ribonucleoprotein (RNP) complex is the essential transcription-replication machinery of the influenza virus. It is composed of the trimeric polymerase (PA, PB1 and PB2), nucleoprotein (NP) and RNA. Elucidating the molecular mechanisms of RNP assembly is central to our understanding of the control of viral transcription and replication and the dependence of these processes on the host cell. In this report, we show, by RNP reconstitution assays and co-immunoprecipitation, that the interaction between NP and polymerase is crucial for the function of the RNP. The functional association of NP and polymerase involves the C-terminal ‘627’ domain of PB2 and it requires NP arginine-150 and either lysine-627 or arginine-630 of PB2. Using surface plasmon resonance, we demonstrate that the interaction between NP and PB2 takes place without the involvement of RNA. At 33, 37 and 41°C in mammalian cells, more positive charges at aa. 627 and 630 of PB2 lead to stronger NP-polymerase interaction, which directly correlates with the higher RNP activity. In conclusion, our study provides new information on the NP-PB2 interaction and shows that the strength of NP-polymerase interaction and the resulting RNP activity are promoted by the positive charges at aa. 627 and 630 of PB2

Weight loss in individuals with metabolic syndrome given DASH diet counseling when provided a low sodium vegetable juice: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights.</p> <p>Objective</p> <p>To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure).</p> <p>A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress.</p> <p>Methods</p> <p>A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks.</p> <p>Results</p> <p>There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05).</p> <p>Conclusion</p> <p>The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.</p

The immediate and long-term effects of exercise and patient education on physical, functional, and quality-of-life outcome measures after single-level lumbar microdiscectomy: a randomized controlled trial protocol

BACKGROUND: Low back pain remains a costly quality-of-life-related health problem. Microdiscectomy is often the surgical procedure of choice for a symptomatic, single-level, lumbar disc herniation in younger and middle-aged adults. The question of whether a post-microdiscectomy exercise program enhances function, quality of life, and disability status has not been systematically explored. Thus, the overall purpose of this study is to assess immediate and long-term outcomes of an exercise program, developed at University of Southern California (USC), targeting the trunk and lower extremities (USC Spine Exercise Program) for persons who have undergone a single-level microdiscectomy for the first time. METHODS/DESIGN: One hundred individuals between the ages of 18 and 60 who consent to undergo lumbar microdiscectomy will be recruited to participate in this study. Subjects will be randomly assigned to one of two groups: 1) one session of back care education, or 2) a back care education session followed by the 12-week USC Spine Exercise Program. The outcome examiners (evaluators), as well as the data managers, will be blinded to group allocation. Education will consist of a one-hour "one-on-one" session with the intervention therapist, guided by an educational booklet specifically designed for post-microdiscectomy care. This session will occur four to six weeks after surgery. The USC Spine Exercise Program consists of two parts: back extensor strength and endurance, and mat and upright therapeutic exercises. This exercise program is goal-oriented, performance-based, and periodized. It will begin two to three days after the education session, and will occur three times a week for 12 weeks. Primary outcome measures include the Oswestry Disability Questionnaire, Roland-Morris Disability Questionnaire, SF-36(® )quality of life assessment, Subjective Quality of Life Scale, 50-foot Walk, Repeated Sit-to-Stand, and a modified Sorensen test. The outcome measures in the study will be assessed before and after the 12-week post-surgical intervention program. Long-term follow up assessments will occur every six months beginning one year after surgery and ending five years after surgery. Immediate and long-term effects will be assessed using repeated measures multivariate analysis of variance (MANOVA). If significant interactions are found, one-way ANOVAs will be performed followed by post-hoc testing to determine statistically significant pairwise comparisons. DISCUSSION: We have presented the rationale and design for a randomized controlled trial evaluating the effectiveness of a treatment regimen for people who have undergone a single-level lumbar microdiscectomy

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe