22 research outputs found
Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases
Background: The secondary structure and complexity of mRNA influences its
accessibility to regulatory molecules (proteins, micro-RNAs), its stability and
its level of expression. The mobile elements of the RNA sequence, the wobble
bases, are expected to regulate the formation of structures encompassing coding
sequences.
Results: The sequence/folding energy (FE) relationship was studied by
statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found
that the FE (dG) associated with coding sequences is significant and negative
(407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able
to form structures. However, the FE has only a small free component, less than
10% of the total. The contribution of the 1st and 3rd codon bases to the FE is
larger than the contribution of the 2nd (central) bases. It is possible to
achieve a ~ 4-fold change in FE by altering the wobble bases in synonymous
codons. The sequence/FE relationship can be described with a simple algorithm,
and the total FE can be predicted solely from the sequence composition of the
nucleic acid. The contributions of different synonymous codons to the FE are
additive and one codon cannot replace another. The accumulated contributions of
synonymous codons of an amino acid to the total folding energy of an mRNA is
strongly correlated to the relative amount of that amino acid in the translated
protein.
Conclusion: Synonymous codons are not interchangable with regard to their
role in determining the mRNA FE and the relative amounts of amino acids in the
translated protein, even if they are indistinguishable in respect of amino acid
coding.Comment: 14 pages including 6 figures and 1 tabl
Endomyocardial Fibrosis: Still a Mystery after 60 Years
The pathologist Jack N. P. Davies identified endomyocardial fibrosis in Uganda in 1947. Since that time, reports of this restrictive cardiomyopathy have come from other parts of tropical Africa, South Asia, and South America. In Kampala, the disease accounts for 20% of heart disease patients referred for echocardiography. We conducted a systematic review of research on the epidemiology and etiology of endomyocardial fibrosis. We relied primarily on articles in the MEDLINE database with either “endomyocardial fibrosis” or “endomyocardial sclerosis” in the title. The volume of publications on endomyocardial fibrosis has declined since the 1980s. Despite several hypotheses regarding cause, no account of the etiology of this disease has yet fully explained its unique geographical distribution
Baseline Morbidity in 2,990 Adult African Volunteers Recruited to Characterize Laboratory Reference Intervals for Future HIV Vaccine Clinical Trials
BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons
Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review.
BACKGROUND: Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. METHODS: A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. FINDINGS: This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. CONCLUSIONS: There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease.This work was funded by the National Institute for Health and Care Excellence (NICE), invitation to tender reference DDER 42013, and supported by the National Institute for Health Research School for Public Health Research. The scope of the work was defined by NICE and the protocol was agreed with NICE prior to the start of work. The funders had no role in data analysis, preparation of the manuscript or decision to publish.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014440