The demographic transition: are we any closer to an evolutionary explanation?

The radical shift in human reproduction in the late 19th century, known as the demographic transition, constitutes a major challenge to evolutionary approaches to human behaviour. Why would people ever choose to limit their reproduction voluntarily when, at the peak of the Industrial Revolution, resources were apparently so plentiful? Can the transition be attributed to standard life history tradeoffs, is it a consequence of cultural evolutionary processes, or is it simply a maladaptive outcome of novel and environmental social conditions? Empirical analyses and new models suggest that reproductive decision making might be driven by a human psychology designed by natural selection to maximize material wealth. If this is the case, the mechanisms governing fertility and parental investment are likely to respond to modern conditions with a fertility level much lower than that that would maximize fitness.     

Neurochemical dementia diagnostics in Alzheimer's disease: where are we now and where are we going?

Neurochemical dementia diagnostics (NDD) is a routine laboratory tool used in the diagnostic process for patients with neurodegenerative disorders, such as Alzheimer's disease. Currently, two groups of biomarkers analyzed in the cerebrospinal fluid are considered - namely amyloid-β peptides and Tau proteins - along with the hyperphosphorylated forms of the latter (pTau). Current directions in the development of NDD include the following: search for novel biomarkers with improved analytical or diagnostic performance; optimization of the analysis of the biomarkers already available (e.g., by improved quality control and interlaboratory comparison of results); applications of novel technologies enabling better management of patient samples; and search for biomarkers in the blood. This article presents the state-of-the-art in the field of cerebrospinal fluid-based NDD, and also summarizes some of the hypotheses of how the future development of NDD tools might look.     

Naturally SIV-infected sooty mangabeys: are we closer to understanding why they do not develop AIDS?

Simian immunodeficiency viruses (SIV) infection of sooty mangabey (SM) monkeys (Cercocebus atys), a natural host species, does not induce CD4+ T cell depletion and acquired immunodeficiency syndrome (AIDS) despite chronic high levels of virus replication. In contrast, SIV infection of non-natural host species, such as rhesus macaques (RM), induces a disease that closely resembles AIDS in humans. The mechanisms underlying the lack of disease progression in SIV-infected SMs are incompletely understood, but certainly reflect a complex evolutionary adaptation whereby the host immune system is not significantly damaged by the highly replicating virus. It is now widely recognized that a better understanding of these mechanisms may provide clues to the pathogenesis of immunodeficiency in HIV-infected humans. In this article I discuss five different hypotheses that may account for the non-pathogenic course of infection in SIV-infected SMs and briefly review the available data supporting each of these hypotheses.     

Engineering plants with increased disease resistance: what are we going to express?

To engineer plants with increased and durable disease resistance using transgenic technologies we must address two questions. First, what gene or genes do we want to express to improve disease resistance, and second, how are we going to express these genes so that crop yields are actually increased? Emerging technologies are providing us with a plethora of candidate genes that might lead to enhanced crop protection through genetic engineering. These genes can come from plants, from pathogens or from other organisms and several strategies for their manipulation show promise. Here, we discuss recent advances and consider future perspectives for producing plants with durable disease resistance.     

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual’s blood pressure, the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection, and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases.

Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. While there are only few proteomic studies specifically addressing human primary hypertension, there are more data available in hypertensive disorders in pregnancy, such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches.

Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardized large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases.     

Gynodioecy to dioecy: are we there yet?

Background

The ‘gynodioecy–dioecy pathway’ is considered to be one of the most important evolutionary routes from hermaphroditism to separate sexes (dioecy). Despite a large accumulation of evidence for female seed fertility advantages in gynodioecious species (females and hermaphrodites coexist) in support of the first step in the gynodioecy–dioecy pathway, we still have very little evidence for the second step, i.e. the transition from gynodioecy to dioecy.

Scope

We review the literature to evaluate whether basic predictions by theory are supported. To establish whether females'' seed fertility advantage and frequencies are sufficient to favour the invasion of males, we review these for species along the gynodioecy–dioecy pathway published in the last 5 years. We then review the empirical evidence for predictions deriving from the second step, i.e. hermaphrodites'' male fertility increases with female frequency, selection favours greater male fertility in hermaphrodites in gynodioecious species, and, where males and hermaphrodites coexist with females (subdioecy), males have greater male fertility than hermaphrodites. We review how genetic control and certain ecological features (pollen limitation, selfing, plasticity in sex expression and antagonists) influence the trajectory of a population along the gynodioecy–dioecy pathway.

Conclusions

Females tend to have greater seed fertility advantages over hermaphrodites where the two coexist, and this advantage is positively correlated with female frequency across species, as predicted by theory. A limited number of studies in subdioecious species have demonstrated that males have an advantage over hermaphrodites, as also predicted by theory. However, less evidence exists for phenotypic selection to increase male traits of hermaphrodites or for increasing male function of hermaphrodites in populations with high female frequency. A few key case studies underline the importance of examining multiple components of male fertility and the roles of pollen limitation, selfing and plasticity, when evaluating advantages. We conclude that we do not yet have a full understanding of the transition from gynodioecy to dioecy.     

Engineering plants with increased disease resistance: how are we going to express it?

Precise control of transgene expression is pivotal to the engineering of plants with increased disease resistance. Many early attempts to boost disease resistance used constitutive overexpression of defence components but frequently this resulted in poor quality plants. It is now clear that the extensive cellular reprogramming associated with defence will reduce yields if uncontrolled defence reactions are activated in uninfected cells. Therefore, for many strategies pathogen-inducible promoters might be the most useful as they limit the cost of resistance by restricting expression to infection sites. Although progress to date has been hindered by a lack of suitable promoters, new research should reveal more potentially useful native promoters. Additionally, the first steps towards 'designer' synthetic promoters have proved encouraging.     

Validation of three-dimensional conduction models using experimental mapping: are we getting closer?

The anisotropic material properties, irregular geometry, and specialized conduction system of the heart all affect the three-dimensional (3D) spread of electrical activation. A limited number of research groups have tried accounting for these features in 3D conduction models to investigate more thoroughly their observations of cardiac electrical activity in 3D experimental preparations. The full potential of these large scale conduction models, however, has not been realized because of a lack of quantitative validation with experiment. Such validation is critical in order to use the models to predict the electrical response of the myocardium to drugs or electrical stimulation. In this paper, a quantitative, experimental validation of paced activation in a 3D conduction model of a 3 cm × 3 cm × 1 cm section of the ventricular wall is presented. Epicardial and intramural pacing stimuli were applied in the center of a 528 channel electrode plaque sutured to the left ventricle in dogs. Unipolar electrograms were recorded at 2 kHz during and after pacing. Fiber directions within the tissue below the electrodes were estimated histologically and from pace-mapping. Simulated epicardial electrograms were computed for surface paced beats using our 3D bidomain model of the mapped tissue volume incorporating the measured fiber directions. Extracellular potentials and isochronal maps resulting from paced activations in both model and experiment were directly compared. Preliminary results demonstrate that our 3D model reproduces qualitatively such key features of the experimental data as electrogram morphologies and epicardial conduction velocities. Though quantitative agreement between model and experiment was only moderate, the validation approach described herein is an essential first step in assessing the predictive capability of present day conduction models.     

Do we need theory to study disease? Lessons from cancer research and their implications for mental illness

This article applies general ideas from contemporary philosophy of science--chief among them that much good science proceeds without theories and laws--to the science of medicine. I claim that traditional philosophical debates over the nature of disease make demands on medicine that are mistaken. I demonstrate this philosophical error by applying the perspective of the philosophy of science to understanding the nature of disease in two concrete cases, cancer and depression. I first argue that cancer research produces various kinds of piecemeal causal explanation and does so without any well-developed theory of normal and malignant functioning, despite the rhetoric of some leading cancer researchers. I then defuse doubts about the scientific status of psychiatry, by demonstrating that it is not necessary to have a theory of normal functioning in order to understand and treat depression.     

Abnormal cervical smears: are we in for an epidemic?

A retrospective study was conducted to examine the pattern of a disturbing increase in abnormal cervical smears in one health district. Past records over fifteen years (1965-79) were analysed to produce pick up rates according to age, screening state, severity of lesion, and area of residence. Main findings included an increased pick up rate in unscreened (5.8 to 12.9/1000 smears) and screened (0.9 to 3.6/1000 smears) women. The order of increase was proportionately much higher in women under 40 years. The only significant epidemiological variable in the catchment area was a substantial population increase, overweighted by the younger age groups. The principal conclusion of the study was that the increased pick up rates of abnormal cervical smears in the district reflected a true increase in the incidence of premalignant lesions of the cervix. Screening efforts aided by computerisation should be examined nationwide in order to reach high risk groups and thus try to prevent an increase in carcinoma of the cervix.     

Genetic counselling and testing for susceptibility to breast,ovarian and colon cancer: where are we today?

Recent advances in our understanding of the genetic characteristics of cancer will change approaches to genetic screening and counselling. Cancer results from multiple, cumulative mutations in genes that regulate cell replication and differentiation. In familial cancer a germ-line mutation is passed on in an autosomal dominant pattern, but cancer will develop in people who inherit the defect only if other mutations also occur in susceptible somatic cells. The tumour-suppressor gene known as BRCA1 is thought to affect half of those families who have an inherited breast cancer syndrome and most families with a breast and ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in surveillance genes that protect DNA from the spontaneous errors that occur during cell division. Because there are no outcome data on which to base practice guidelines for genetic screening or management of asymptomatic carriers in families at risk, testing should be restricted to research settings.