Nephron number, hypertension, renal disease, and renal failure

Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension. The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or multihit models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility. Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the Barker hypothesis, which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9). The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.

Family structure and age at menarche: A children-of-twins approach

Girls who grow up in households with an unrelated adult male reach menarche earlier than peers, a finding hypothesized to be an evolutionary strategy for families under stress. The authors tested the alternative hypothesis that nonrandom selection into stepfathering due to shared environmental and/or genetic predispositions creates a spurious relation between stepfathering and early menarche. Using the unique controls for genetic and shared environmental experiences offered by the children-of-twins design, the authors found that cousins discordant for stepfathering did not differ in age of menarche. Moreover, controlling for mother's age of menarche eliminated differences in menarcheal age associated with stepfathering in unrelated girls. These findings strongly suggest selection, and not causation, accounts for the relationship between stepfathering and early menarche.

Cognitive modelling and the behaviour genetics of reading

While it is well known that reading is highly heritable, less has been understood about the bases of these genetic influences. In this paper, we review the research that we have been conducting in recent years to examine genetic and environmental influences on the particular reading processes specified in the dual-route cognitive model of reading. We argue that a detailed understanding of the role of genetic factors in reading acquisition requires the delineation and measurement of precise phenotypes, derived from well-articulated models of the reading process. We report evidence for independent genetic influences on the lexical and nonlexical reading processes represented in the dual-route model, based on studies of children with particular subtypes of dyslexia, and on univariate and multivariate genetic modelling of reading performance in the normally reading population.

A framework for the study of genetic variation in migratory behaviour

Evolutionary change results from selection acting on genetic variation. For migration to be successful, many different aspects of an animal's physiology and behaviour need to function in a co-coordinated way. Changes in one migratory trait are therefore likely to be accompanied by changes in other migratory and life-history traits. At present, we have some knowledge of the pressures that operate at the various stages of migration, but we know very little about the extent of genetic variation in various aspects of the migratory syndrome. As a consequence, our ability to predict which species is capable of what kind of evolutionary change, and at which rate, is limited. Here, we review how our evolutionary understanding of migration may benefit from taking a quantitative-genetic approach and present a framework for studying the causes of phenotypic variation. We review past research, that has mainly studied single migratory traits in captive birds, and discuss how this work could be extended to study genetic variation in the wild and to account for genetic correlations and correlated selection. In the future, reaction-norm approaches may become very important, as they allow the study of genetic and environmental effects on phenotypic expression within a single framework, as well as of their interactions. We advocate making more use of repeated measurements on single individuals to study the causes of among-individual variation in the wild, as they are easier to obtain than data on relatives and can provide valuable information for identifying and selecting traits. This approach will be particularly informative if it involves systematic testing of individuals under different environmental conditions. We propose extending this research agenda by using optimality models to predict levels of variation and covariation among traits and constraints. This may help us to select traits in which we might expect genetic variation, and to identify the most informative environmental axes. We also recommend an expansion of the passerine model, as this model does not apply to birds, like geese, where cultural transmission of spatio-temporal information is an important determinant of migration patterns and their variation.

Biological, antigenic and phylogenetic characterization of the flavivirus Alfuy

Alfuy virus (ALFV) is classified as a subtype of the flavivirus Murray Valley encephalitis virus (MVEV); however, despite preliminary reports of antigenic and ecological similarities with MVEV, ALFV has not been associated with human disease. Here, it was shown that ALFV is at least 10(4)-fold less neuroinvasive than MVEV after peripheral inoculation of 3-week-old Swiss outbred mice, but ALFV demonstrates similar neurovirulence. In addition, it was shown that ALFV is partially attenuated in mice that are deficient in alpha/beta interferon responses, in contrast to MVEV which is uniformly lethal in these mice. To assess the antigenic relationship between these viruses, a panel of monoclonal antibodies was tested for the ability to bind to ALFV and MVEV in ELISA. Although the majority of monoclonal antibodies recognized both viruses, confirming their antigenic similarity, several discriminating antibodies were identified. Finally, the entire genome of the prototype strain of ALFV (MRM3929) was sequenced and phylogenetically analysed. Nucleotide (73%) and amino acid sequence (83 %) identity between ALFV and IMVEV confirmed previous reports of their close relationship. Several nucleotide and amino acid deletions and/or substitutions with putative functional significance were identified in ALFV, including the abolition of a conserved glycosylation site in the envelope protein and the deletion of the terminal dinucleotide 5'-CUOH-3' found in all other members of the genus. These findings confirm previous reports that ALFV is closely related to IMVEV, but also highlights significant antigenic, genetic and phenotypic divergence from MVEV. Accordingly, the data suggest that ALFV is a distinct species within the serogroup Japanese encephalitis virus.

Mapping the emergence of heart disease in a black, urban population in Africa: The Heart of Soweto Study

Background: There is increasing evidence that many populations in the developing world are in epidemiologic transition with the subsequent emergence of more affluent disease states. The Heart of Soweto Study will systematically investigate the emergence of heart disease (HD) in a large urban population in South Africa. Methods: Part of the conurbation of Johannesburg, South Africa, Soweto is a predominantly Black African community of I million individuals. During an initial two year period, all individuals presenting to the local Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic and diagnostic coding data in those with pre-established HD will form an abbreviated clinical registry of > 12,000 prevalent cases. Similarly, socio-demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in newly diagnosed patients will form a more detailed clinical registry of > 5000 incident cases. Sub-studies of the relationship between HIV status and H D and the optimal management of chronic heart failure will also be performed. Results: These data will provide a unique insight into the causes and consequences of a broad spectrum of HD-related conditions in a developing world community in epidemiologic transition. Initially documented Population rates, in addition to detailed examinations of the underlying risk factors and causes of HD-related morbidity/mortality will provide an important platform for future stages of the study: a community-based, population screening program and culturally specific primary and secondary programs of care. Conclusion: There is an urgent need to systematically track the emergence of HD in the developing world. Initially involving more than 15,000 individuals, the unique Heart of Soweto Study has the potential to provide a wealth of information in this regard. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Planted forests and biodiversity

Expansion of planted forests and intensification of their management has raised concerns among forest managers and the public over the implications of these trends for sustainable production and conservation of forest biological diversity. We review the current state of knowledge on the impacts of plantation forestry on genetic and species diversity at different spatial scales and discuss the economic and ecological implications of biodiversity management within plantation stands and landscapes. Managing plantations to produce goods such as timber while also enhancing ecological services such as biodiversity involves tradeoffs, which can be made only with a clear understanding of the ecological context of plantations in the broader landscape and agreement among stakeholders on the desired balance of goods and ecological services from plantations.

Strong and weak lifespan extension: What is most feasible and likely?

Recent advances in biomedical science indicate that it may eventually be possible to intervene in the biological process of human ageing. This paper overviews the current state of the science of lifespan extension and promising future directions. It is uncertain whether 'strong' lifespan extension - the extension of human life beyond the maximum 122 years so far observed - will become a reality. It is more likely that cumulative effects of numerous scientific and biomedical advances in the treatment of common disease will produce 'weak' lifespan extension - the extension of average life expectancy. The practical application of molecular, genetic and nanomaterials research may also lead to advances in life expectancy. It is not too early to begin to consider the policy implications of either form of lifespan extension.

Longitudinal Genetic Analysis of Plasma Lipids

The consensus from published studies is that plasma lipids are each influenced by genetic factors, and that this contributes to genetic variation in risk of cardiovascular disease. Heritability estimates for lipids and lipoproteins are in the range .48 to .87, when measured once per study participant. However, this ignores the confounding effects of biological variation measurement error and ageing, and a truer assessment of genetic effects on cardiovascular risk may be obtained from analysis of longitudinal twin or family data. We have analyzed information on plasma high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides, from 415 adult twins who provided blood on two to five occasions over 10 to 17 years. Multivariate modeling of genetic and environmental contributions to variation within and across occasions was used to assess the extent to which genetic and environmental factors have long-term effects on plasma lipids. Results indicated that more than one genetic factor influenced HDL and LDL components of cholesterol, and triglycerides over time in all studies. Nonshared environmental factors did not have significant long-term effects except for HDL. We conclude that when heritability of lipid risk factors is estimated on only one occasion, the existence of biological variation and measurement errors leads to underestimation of the importance of genetic factors as a cause of variation in long-term risk within the population. In addition our data suggest that different genes may affect the risk profile at different ages.

Heritability and Stability of Resting Blood Pressure in Australian Twins

In Australian twins participating in three different studies (1979-1996), the contribution of genetic and environmental influences to variation in resting systolic (SBP) and diastolic blood pressure (DBP) was studied. The sample consisted of 368 monozygotic and 335 dizygotic twin pairs with measurements for both individuals. Blood pressure measurements in two studies were available for 115 complete twin pairs, and 49 twin pairs had measurements in three studies. This allowed assessment of blood pressure tracking over an average period of 12 years in the age range of 23 to 45 years. Multivariate analyses showed significant heritability (h(2)) of blood pressure in all studies (SBP h(2) = 19%-56%, DBP h(2) = 37%-52%). In addition, the analyses showed that the blood pressure tracking was explained by the same set of genetic factors. These results replicate an earlier finding in Dutch twins that also showed stability of the contribution of genetic factors to blood pressure tracking.

Genetic Influences on Exercise Participation in 37.051 Twin Pairs from Seven Countries

Background A sedentary lifestyle remains a major threat to health in contemporary societies. To get more insight in the relative contribution of genetic and environmental influences on individual differences in exercise participation, twin samples from seven countries participating in the GenomEUtwin project were used. Methodology Self-reported data on leisure time exercise behavior from Australia, Denmark, Finland, Norway, the Netherlands, Sweden and United Kingdom were used to create a comparable index of exercise participation in each country (60 minutes weekly at a minimum intensity of four metabolic equivalents). Principal Findings Modest geographical variation in exercise participation was revealed in 85,198 subjects, aged 19–40 years. Modeling of monozygotic and dizygotic twin resemblance showed that genetic effects play an important role in explaining individual differences in exercise participation in each country. Shared environmental effects played no role except for Norwegian males. Heritability of exercise participation in males and females was similar and ranged from 48% to 71% (excluding Norwegian males). Conclusions Genetic variation is important in individual exercise behavior and may involve genes influencing the acute mood effects of exercise, high exercise ability, high weight loss ability, and personality. This collaborative study suggests that attempts to find genes influencing exercise participation can pool exercise data across multiple countries and different instruments

An electrical heart model incorporating real geometry and motion

Abstract—This paper describes an electrical model of the ventricles incorporating real geometry and motion. Cardiac geometry and motion is obtained from segmentations of multipleslice MRI time sequences. A static heart model developed previously is deformed to match the observed geometry using a novel shape registration algorithm. The resulting electrocardiograms and body surface potential maps are compared to a static simulation in the resting heart. These results demonstrate that introducing motion into the cardiac model modifies the ECG during the T wave at peak contraction of the ventricles.

Mapping mosquito breeding habitats (water) under mangrove canopy: contribution from airborne thermal scanning

Proceedings of the 11th Australasian Remote Sensing and Photogrammetry Conference