A study of the average effect of the 3'APOB-VNTR polymorphism on lipidemic parameters could explain why the short alleles (<35 repeats) are rare in centenarians

BACKGROUND: In studies on the genetics of human aging, we observed an age-related variation of the 3'APOB-VNTR genotypic pool (alleles: Short, S, <35 repeats; Medium, M, 35–39 repeats; Long, L, >39 repeats) with the homozygous SS genotype showing a convex frequency trajectory in a healthy aging population. This genotype was rare in centenarians, thus indicating that the S alleles are unfavorable to longevity, while common in adults, thus indicating a protective role at middle age. This apparent paradox could be due to possible effects exerted by the above polymorphism on lipidemic parameters. Aim of the work was to get insights into these puzzling findings METHODS: We followed a double strategy. Firstly, we analyzed the average effects of S (α(S)), M (α(M)), and L (α(L)) alleles on lipidemic parameters in a sample of healthy people (409 subjects aged 20–102 years) recruited in Calabria (southern Italy). The (α(S)), (α(M)), and (α(L)) values were estimated by relating 3'APOB-VNTR genotypes to lipidemic parameters, after adjustment for age, sex and body mass index (multiple regression). Then, we analyzed the S alleles as susceptibility factors of Cardiovascular Atherosclerotic Disease (CD) in CD patients characterized either by low serum HDL-Cholesterol or by high serum LDL-Cholesterol (CD-H and CD-L patients, 40 and 40 subjects respectively). The Odds Ratios (OR) were computed for carriers of S alleles in CD-H and CD-L patients matched for origin, sex and age with controls extracted from the sample of healthy subjects. RESULTS: By the analysis of the healthy sample group we found that the S alleles lower the average values of serum Total Cholesterol (α(S )= -5.98 mg/dL with [-11.62 ÷ -0.74] 95% confidence interval) and LDL-Cholesterol (α(S )= -4.41 mg/dL with [-8.93 ÷ -0.20] 95% confidence interval) while the alleles M and L have no significant effect on the lipidemic phenotype. In line with these findings, the analysis of CD patients showed that the S alleles are protective as for CD-L (O.R. = 0.55 with [0.21 ÷ 0.98] 95% confidence interval) while neutral as for CD-H (O.R. = 0.75 with [0.32 ÷ 1.60] 95% confidence interval). CONCLUSION: On the whole, the S alleles would be advantageous in adults (by protecting from CD-L) while dangerous in the elderly, probably by lowering serum cholesterol below a critical threshold. This could explain the convex frequency trajectory of SS genotypes previously observed in a healthy aging population

Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle

Where Two Are Fighting, the Third Wins: Stronger Selection Facilitates Greater Polymorphism in Traits Conferring Competition-Dispersal Tradeoffs

A major conundrum in evolution is that, despite natural selection, polymorphism is still omnipresent in nature: Numerous species exhibit multiple morphs, namely several abundant values of an important trait. Polymorphism is particularly prevalent in asymmetric traits, which are beneficial to their carrier in disruptive competitive interference but at the same time bear disadvantages in other aspects, such as greater mortality or lower fecundity. Here we focus on asymmetric traits in which a better competitor disperses fewer offspring in the absence of competition. We report a general pattern in which polymorphic populations emerge when disruptive selection increases: The stronger the selection, the greater the number of morphs that evolve. This pattern is general and is insensitive to the form of the fitness function. The pattern is somewhat counterintuitive since directional selection is excepted to sharpen the trait distribution and thereby reduce its diversity (but note that similar patterns were suggested in studies that demonstrated increased biodiversity as local selection increases in ecological communities). We explain the underlying mechanism in which stronger selection drives the population towards more competitive values of the trait, which in turn reduces the population density, thereby enabling lesser competitors to stably persist with reduced need to directly compete. Thus, we believe that the pattern is more general and may apply to asymmetric traits more broadly. This robust pattern suggests a comparative, unified explanation to a variety of polymorphic traits in nature.ope

Evolution of Assortative Mating in a Population Expressing Dominance

In this article, we study the influence of dominance on the evolution of assortative mating. We perform a population-genetic analysis of a two-locus two-allele model. We consider a quantitative trait that is under a mixture of frequency-independent stabilizing selection and density- and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The trait is determined by a single (ecological) locus and expresses intermediate dominance. The second (modifier) locus determines the degree of assortative mating, which is expressed in females only. Assortative mating is based on similarities in the quantitative trait (‘magic trait’ model). Analytical conditions for the invasion of assortment modifiers are derived in the limit of weak selection and weak assortment. For the full model, extensive numerical iterations are performed to study the global dynamics. This allows us to gain a better understanding of the interaction of the different selective forces. Remarkably, depending on the size of modifier effects, dominance can have different effects on the evolution of assortment. We show that dominance hinders the evolution of assortment if modifier effects are small, but promotes it if modifier effects are large. These findings differ from those in previous work based on adaptive dynamics

A novel nucleo-cytoplasmic hybrid clone formed via androgenesis in polyploid gibel carp

<p>Abstract</p> <p>Background</p> <p>Unisexual vertebrates have been demonstrated to reproduce by gynogenesis, hybridogenesis, parthenogenesis, or kleptogenesis, however, it is uncertain how the reproduction mode contributes to the clonal diversity. Recently, polyploid gibel carp has been revealed to possess coexisting dual modes of unisexual gynogenesis and sexual reproduction and to have numerous various clones. Using sexual reproduction mating between clone D female and clone A male and subsequent 7 generation multiplying of unisexual gynogenesis, we have created a novel clone strain with more than several hundred millions of individuals. Here, we attempt to identify genetic background of the novel clone and to explore the significant implication for clonal diversity contribution.</p> <p>Methods</p> <p>Several nuclear genome markers and one cytoplasmic marker, the mitochondrial genome sequence, were used to identify the genetic organization of the randomly sampled individuals from different generations of the novel clone.</p> <p>Results</p> <p>Chromosome number, <it>Cot</it>-1 repetitive DNA banded karyotype, microsatellite patterns, AFLP profiles and transferrin alleles uniformly indicated that nuclear genome of the novel clone is identical to that of clone A, and significantly different from that of clone D. However, the cytoplasmic marker, its complete mtDNA genome sequence, is same to that of clone D, and different from that of clone A.</p> <p>Conclusions</p> <p>The present data indicate that the novel clone is a nucleo-cytoplasmic hybrid between the known clones A and D, because it originates from the offspring of gonochoristic sexual reproduction mating between clone D female and clone A male, and contains an entire nuclear genome from the paternal clone A and a mtDNA genome (cytoplasm) from the maternal clone D. It is suggested to arise via androgenesis by a mechanism of ploidy doubling of clone A sperm in clone D ooplasm through inhibiting the first mitotic division. Significantly, the selected nucleo-cytoplasmic hybrid female still maintains its gynogenetic ability. Based on the present and previous findings, we discuss the association of rapid genetic changes and high genetic diversity with various ploidy levels and multiple reproduction modes in several unisexual and sexual complexes of vertebrates and even other invertebrates.</p

A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk

Background This review provides a reappraisal of the potential effects of dairy foods, including dairy fats, on cardiovascular disease (CVD)/coronary heart disease (CHD) risk. Commodities and foods containing saturated fats are of particular focus as current public dietary recommendations are directed toward reducing the intake of saturated fats as a means to improve the overall health of the population. A conference of scientists from different perspectives of dietary fat and health was convened in order to consider the scientific basis for these recommendations. Aims This review and summary of the conference focus on four key areas related to the biology of dairy foods and fats and their potential impact on human health: (a) the effect of dairy foods on CVD in prospective cohort studies; (b) the impact of dairy fat on plasma lipid risk factors for CVD; (c) the effects of dairy fat on non-lipid risk factors for CVD; and (d) the role of dairy products as essential contributors of micronutrients in reference food patterns for the elderly. Conclusions Despite the contribution of dairy products to the saturated fatty acid composition of the diet, and given the diversity of dairy foods of widely differing composition, there is no clear evidence that dairy food consumption is consistently associated with a higher risk of CVD. Thus, recommendations to reduce dairy food consumption irrespective of the nature of the dairy product should be made with cautionJ. Bruce German, Robert A. Gibson, Ronald M. Krauss, Paul Nestel, Benoît Lamarche, Wija A. van Staveren, Jan M. Steijns, Lisette C. P. G. M. de Groot, Adam L. Lock and Frédéric Destaillat

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Physical activity, sedentary time and gain in overall and central body fat: 7-year follow-up of the ProActive trial cohort.

OBJECTIVE: The objective of this study is to examine the independent associations of time spent in moderate-to-vigorous physical activity (MVPA) and sedentary (SED-time), with total and abdominal body fat (BF), and the bidirectionality of these associations in adults at high risk of type 2 diabetes. DESIGN AND SUBJECTS: We measured MVPA (min per day) and SED-time (h per day) by accelerometry, and indices of total (body weight, fat mass (FM), BF% and FM index) and abdominal BF (waist circumference (WC)) using standard procedures in 231 adults (41.3 ± 6.4 years) with parental history of type 2 diabetes (ProActive UK) at baseline, 1-year and 7-year follow-up. Mixed effects models were used to quantify the independent associations (expressed as standardised β-coefficients (95% confidence interval (CI))) of MVPA and SED-time with fat indices, using data from all three time points. All models were adjusted for age, sex, intervention arm, monitor wear time, follow-up time, smoking status, socioeconomic status and MVPA/SED-time. RESULTS: MVPA was inversely and independently associated with all indices of total BF (for example, 1 s.d. higher MVPA was associated with a reduction in FM, β = -0.09 (95% CI: -0.14, -0.04) s.d.) and abdominal BF (for example, WC: β = -0.07 (-0.12, -0.02)). Similarly, higher fat indices were independently associated with a reduction in MVPA (for example, WC: β = -0.25 (-0.36, -0.15); FM: β = -0.27 (-0.36, -0.18)). SED-time was positively and independently associated with most fat indices (for example, WC: β = 0.03 (-0.04, 0.09); FM: β = 0.10 (0.03, 0.17)). Higher values of all fat indices independently predicted longer SED-time (for example, WC: β = 0.10 (0.02, 0.18), FM: β = 0.15 (0.07, 0.22)). CONCLUSIONS: The associations of MVPA and SED-time with total and abdominal BF are bidirectional and independent among individuals at high risk for type 2 diabetes. The association between BF and MVPA is stronger than the reciprocal association, highlighting the importance of considering BF as a determinant of decreasing activity and a potential consequence. Promoting more MVPA and less SED-time may reduce total and abdominal BF