Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells

BACKGROUND: All human immunodeficiency virus (HIV-1) uses a host tRNA(Lys,3 )as the primer for reverse transcription. The tRNA(Lys,3 )is bound to a region on the HIV-1 genome, the primer-binding site (PBS), that is complementary to the 18 terminal nucleotides of tRNA(Lys,3). How HIV-1 selects the tRNA from the intracellular milieu is unresolved. RESULTS: HIV-1 tRNA primer selection has been investigated using viruses in which the primer-binding site (PBS) and a sequence within U5 were altered so as to be complementary to tRNA(Met), tRNA(Pro )or tRNA(Ile). Analysis of the replication of these viruses in human peripheral blood mononuclear cells (PBMC) revealed preferences for the selection of certain tRNAs. HIV-1 with the PBS altered to be complementary to tRNA(Met), with and without the additional mutation in U5 to be complementary to the anticodon of tRNA(Met), stably maintains the PBS complementary to tRNA(Met )following extended in vitro culture in PBMC. In contrast, viruses with either the PBS or PBS and U5 mutated to be complementary to tRNA(Ile )were unstable during in vitro replication in PBMC and reverted to utilize tRNA(Lys,3). Viruses with the PBS altered to be complementary to tRNA(Pro )replicated in PBMC but reverted to use tRNA(Lys,3); viruses with mutations in both the U5 and PBS complementary to tRNA(Pro )maintained this PBS, yet replicated poorly in PBMC. CONCLUSION: The results of these studies demonstrate that HIV-1 has preferences for selection of certain tRNAs for high-level replication in PBMC

Footballers' Image Rights in the New Media Age

Image rights, broadly defined as the commercial appropriation of someone's personality, including indices of their image, voice, name and signature, have become increasingly important in the political economy of media sport. A range of legal, economic and political arguments have developed in the UK as to what image rights actually are, their legal efficacy and their potential impact on developments in the long-standing relationship between sport and the media. This paper focuses on the problematic definition of the term in the UK context and how it relates to certain economic and commercial transformations in British football. Using the English Premier League and the ‘celebrity footballer’ David Beckham as its primary focus, the paper traces the rise of image rights clauses in player contracts. This process is analysed in the context of rapid and dramatic change in the media coverage of the sport. The paper focuses on the growing legal complexities of protecting star images in relation to the Internet and the wider issues of football, fandom and popular culture

Heme metabolism genes Downregulated in COPD Cachexia.

IntroductionCachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.MethodsWe analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (< 20 kg/m2) and 1/3 criteria: decreased muscle strength (six-minute walk distance < 350 m), anemia (hemoglobin < 12 g/dl), and low fat-free mass index (FFMI) (< 15 kg/m2 among women and < 17 kg/m2 among men) in COPDGene. In ECLIPSE, cachexia was defined as weight-loss > 5% in the past 12 months or low BMI and 3/5 criteria: decreased muscle strength, anorexia, abnormal biochemistry (anemia or high c-reactive protein (> 5 mg/l)), fatigue, and low FFMI. Differential gene expression was assessed between cachectic and non-cachectic subjects, adjusting for age, sex, white blood cell counts, and technical covariates. Gene set enrichment analysis was performed using MSigDB.ResultsThe prevalence of COPD cachexia was 13.7% in COPDGene and 7.9% in ECLIPSE. Fourteen genes were differentially downregulated in cachectic versus non-cachectic COPD patients in COPDGene (FDR < 0.05) and ECLIPSE (FDR < 0.05).DiscussionSeveral replicated genes regulating heme metabolism were downregulated among participants with COPD cachexia. Impaired heme biosynthesis may contribute to cachexia development through free-iron buildup and oxidative tissue damage

Pioglitazone use in Australia and the United Kingdom following drug safety advisories on bladder cancer risk: An interrupted time series study

Purpose: National regulators in Australia and the United Kingdom issued safety advisories on the association between pioglitazone use and bladder cancer in July 2011. The Australian advisory noted that males were at higher risk of bladder cancer than females, while the UK advisory highlighted a new recommendation, suggest careful consideration in the elderly due to increasing risk with age. This study examined whether these differences in the advisories had different age- and sex-based impacts in each country. Methods: Interrupted time series analysis was used to compare pioglitazone use (prescriptions/100000 population) in Australia and the United Kingdom for the 24 months before and 11 months after the July 2011 safety advisories (study period July 2009–June 2012). Separate models were used to compare use by sex and age group (≥65 years vs. <65 years) in each country. Results: Pioglitazone use fell in Australia (17%) and the United Kingdom (24%) following the safety advisories. Use of pioglitazone fell more for males (18%) than females (16%) in Australia, and more for females (25%) than males (23%) in the United Kingdom; however, neither difference was statistically significant (Australia p = 0.445, United Kingdom p = 0.462). Pioglitazone use fell to a similar extent among older people than younger people in the United Kingdom (23% vs. 26%, p = 0.354), and did not differ between age groups in Australia (both 18%, p = 0.772). Conclusions: The results indicate that differences in the Australian and UK safety advisories resulted in substantial reductions in pioglitazone use at the population level in both countries, however, differences by sub-groups were not observed

Walking the walk: a phenomenological study of long distance walking

Evidence suggests that regular walking can elicit significant psychological benefits although little evidence exists concerning long distance walking. The purpose of this study was to provide detailed accounts of the experiences of long distance walkers. Phenomenological interviews were conducted with six long distance walkers. Data were transcribed verbatim before researchers independently analyzed the transcripts. Participants reported a cumulative effect with positive feelings increasing throughout the duration of the walk. Long distance walking elicited positive emotions, reduced the effects of life-stress, and promoted an increased sense of well-being and personal growth. Results are aligned to theories and concepts from positive psychology

B806: Performance Evaluations of Potato Clones and Varieties in the Northeastern States 1984

Cooperative potato clone and variety trials were conducted at 32 locations to determine field performance of selected clones and varieties grown under soil, climatic, and cultural management common to the potato growing areas of 12 cooperating states and the Province of New Brunswick, Canada. A few locations also evaluated storage and processing behavior of selected clones and varieties. These tests are contributions to Regional Project NE107 entitled, Breeding and Evaluation of New Potato Clones for the Northeast. The primary objective of this project is to determine clone performance and stability over a wide range of soil, climate, and cultural conditions.https://digitalcommons.library.umaine.edu/aes_bulletin/1117/thumbnail.jp

B801: Performance Evaluations of Potato Clones and Varieties in the Northeastern States 1983

Cooperative potato clone and variety trials were conducted at 23 locations to determine field, storage, and processing behavior of selected clones and varieties grown under soil, climatic, and cultural management common to the potato growing areas of 13 cooperating states and the Province of New Brunswick, Canada. These tests are all contributions to Regional Project NE107 entitled, Breeding and Evaluation of New Potato Clones for the Northeast. The primary objective of this project is to determine clone stability over a wide range of soil, climate, and cultural conditions.https://digitalcommons.library.umaine.edu/aes_bulletin/1119/thumbnail.jp

A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg−1 day−1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR