Bayesian molecular dating: opening up the black box

Molecular dating analyses allow evolutionary timescales to be estimated from genetic data, offering an unprecedented capacity for investigating the evolutionary past of all species. These methods require us to make assumptions about the relationship between genetic change and evolutionary time, often referred to as a ‘molecular clock’. Although initially regarded with scepticism, molecular dating has now been adopted in many areas of biology. This broad uptake has been due partly to the development of Bayesian methods that allow complex aspects of molecular evolution, such as variation in rates of change across lineages, to be taken into account. But in order to do this, Bayesian dating methods rely on a range of assumptions about the evolutionary process, which vary in their degree of biological realism and empirical support. These assumptions can have substantial impacts on the estimates produced by molecular dating analyses. The aim of this review is to open the ‘black box’ of Bayesian molecular dating and have a look at the machinery inside. We explain the components of these dating methods, the important decisions that researchers must make in their analyses, and the factors that need to be considered when interpreting results. We illustrate the effects that the choices of different models and priors can have on the outcome of the analysis, and suggest ways to explore these impacts. We describe some major research directions that may improve the reliability of Bayesian dating. The goal of our review is to help researchers to make informed choices when using Bayesian phylogenetic methods to estimate evolutionary rates and timescales.     

Photoperiodic induction of diapause: opening the black box

Abstract.  Over several decades, formal experiments measuring diapause responses to variable light inputs have indicated that photoperiodic time measurement in insects is accomplished either by a nonoscillatory 'hourglass-like' mechanism or by oscillatory components of the circadian system. Although both are possible given the present state of our knowledge, a substantial body of evidence strongly suggests that night-length measurement is a function of the circadian system, and that 'hourglass-like' clocks are manifestations of damping circadian components. The two types of time measurement, 'hourglass' and circadian, are therefore parts of a spectrum of mechanisms differing in their damping coefficients. If this view is correct, it may follow that genes and proteins involved in circadian timing are also involved in photoperiodism, although additional genes, or known 'clock' genes used in novel ways, may also play a part. This review outlines the experimental evidence for the oscillator clock theory of photoperiodism and suggests ways in which further progress may be made.     

Neuroeconomics

This paper introduces an emerging transdisciplinary field known as neuroeconomics. Neuroeconomics uses neuroscientific measurement techniques to investigate how decisions are made. First, I present a basic overview of neuroanatomy and explain how brain activity is measured. I then survey findings from the neuroeconomics literature on acquiring rewards and avoiding losses, learning, choice under risk and ambiguity, delay of gratification, the role of emotions in decision-making, strategic decisions and social decisions. I conclude by identifying new directions that neuroeconomics is taking, including applications to public policy and law.     

Neuroeconomics: the shadow of the future

Humans and other animals tend to disregard future benefits and costs when choosing between immediate and delayed gratification. This tendency can lead to the choice of options that are not in one's own long-term interest. A new study looks at the neurophysiological basis of this self-defeating behavior.     

Neuroeconomics of suicide

Suicidal behavior is a leading cause of injury and death worldwide. Suicide has been associated with psychiatric illnesses such as depression and schizophrenia, as well as economic uncertainty, and social/cultural factors. This study proposes a neuroeconomic framework of suicide. Neuroeconomic parameters (e.g., risk-attitude, probability weighting, time discounting in intertemporal choice, and loss aversion) are predicted to be related to suicidal behavior. Neurobiological and neuroendocrinological substrates such as serotonin, dopamine, cortisol (HPA axis), nitric oxide, serum cholesterol, epinephrine, norepinephrine, gonadal hormones (e.g., estradiol and progesterone), dehydroepiandrosterone (DHEA) in brain regiouns such as the orbitofrontal/dorsolateral prefrontal cortex and limbic regions (e.g., the amygdala) may supposedly be related to the neuroeconomic parameters modulating the risk of suicide. The present framework puts foundations for "molecular neuroeconomics" of decision-making processes underlying suicidal behavior.     

Introduction. Neuroeconomics: the promise and the profit

Neuroeconomics investigates the neural mechanisms underlying decisions about rewarding or punishing outcomes ('economic' decisions). It combines the knowledge about the behavioural phenomena of economic decisions with the mechanistic explanatory power of neuroscience. Thus, it is about the neurobiological foundations of economic decision making. It is hoped that by 'opening the box' we can understand how decisions about gains and losses are directed by the brain of the individual decision maker. Perhaps we can even learn why some decisions are apparently paradoxical or pathological. The knowledge could be used to create situations that avoid suboptimal decisions and harm.     

Experimental analysis of soft‐tissue fossilization: opening the black box

Taphonomic experiments provide important insights into fossils that preserve the remains of decay‐prone soft tissues, tissues that are usually degraded and lost prior to fossilization. These fossils are among the most scientifically valuable evidence of ancient life on Earth, giving us a view into the past that is much less biased and incomplete than the picture provided by skeletal remains alone. Although the value of taphonomic experiments is beyond doubt, a lack of clarity regarding their purpose and limitations, and ambiguity in the use of terminology, are hampering progress. Here we distinguish between processes that promote information retention and those that promote information loss, in order to clarify the distinction between fossilization and preservation. Recognizing distinct processes of decay, mineralization and maturation, the sequence in which they act, and the potential for interactions, has important consequences for analysis of fossils, and for the design of taphonomic experiments. The purpose of well‐designed taphonomic experiments is generally to understand decay, maturation and preservation individually, thus limiting the number of variables involved. Much work remains to be done, but these methodologically reductionist foundations will allow researchers to build towards more complex taphonomic experiments and a more holistic understanding and analysis of the interactions between decay, maturation and preservation in the fossilization of non‐biomineralized remains. Our focus must remain on the key issue of understanding what exceptionally preserved fossils reveal about the history of biodiversity and evolution, rather than on debating the scope and value of an experimental approach.     

Detecting short tandem repeats from genome data: opening the software black box

Short tandem repeats, specifically microsatellites, are widely used genetic markers, associated with human genetic diseases, and play an important role in various regulatory mechanisms and evolution. Despite their importance, much is yet unknown about their mutational dynamics. The increasing availability of genome data has led to several in silico studies of microsatellite evolution which have produced a vast range of algorithms and software for tandem repeat detection. Documentation of these tools is often sparse, or provided in a format that is impenetrable to most biologists without informatics background. This article introduces the major concepts behind repeat detecting software essential for informed tool selection. We reflect on issues such as parameter settings and program bias, as well as redundancy filtering and efficiency using examples from the currently available range of programs, to provide an integrated comparison and practical guide to microsatellite detecting programs.     

Life history in a model system: opening the black box with Arabidopsis thaliana

A broad research programme in Arabidopsis thaliana has provided estimates of selection on specific alleles in specific contexts, and identified geographic patterns of alleles in genes linked to timing of flowering. A closely related field has successfully captured many key axes of the evolution of timing of flowering in other monocarpic species through statistical and demographic modelling of large empirical databases. There has as yet been no synthesis between these two fields. Here we examine ways in which the two fields inform each other, and how this synergy will shape our knowledge of life-history evolution as a whole.     

Gene expression profiling: opening the black box of plant ecosystem responses to global change

The use of genomic techniques to address ecological questions is emerging as the field of genomic ecology. Experimentation under environmentally realistic conditions to investigate the molecular response of plants to meaningful changes in growth conditions and ecological interactions is the defining feature of genomic ecology. Because the impact of global change factors on plant performance are mediated by direct effects at the molecular, biochemical, and physiological scales, gene expression analysis promises important advances in understanding factors that have previously been consigned to the 'black box' of unknown mechanism. Various tools and approaches are available for assessing gene expression in model and nonmodel species as part of global change biology studies. Each approach has its own unique advantages and constraints. A first generation of genomic ecology studies in managed ecosystems and mesocosms have provided a testbed for the approach and have begun to reveal how the experimental design and data analysis of gene expression studies can be tailored for use in an ecological context.     

Biology in a gray box: targeting the emergent properties of protein complexes: 2011 Yale Chemical Biology Symposium

At the 2011 Yale Chemical Biology Symposium, Jason Gestwicki presented a novel yet intuitive approach to drug screening. This method, which he termed "gray box" screening, targets protein complexes that have been reconstituted in vitro. Therefore, the gray box screen can achieve greater phenotypic complexity than biochemical assays but avoids the need for target identification that follows cell-based assays. Dr. Gestwicki's research group was able to use the gray box screen to identify myricetin as an inhibitor of the DnaK-DnaJ chaperone complex. This review will discuss Dr. Gestwicki's approach to identifying DnaK-DnaJ inhibitors as well as where the gray box screen fits among traditional techniques in drug discovery.     

Neuroeconomics in parasitoids: computing accurately with a minute brain

In the so‐called ‘patch problem’, at any given moment, the forager must decide whether to leave the current patch or to remain there and continue foraging. Optimal foraging theory and subsequent theoretical works have identified theoretical optimal policies governing this decision. In a stochastic environment, the Bayesian framework has proved to be effective. A set of mechanistic proximal mechanisms explaining how parasitoid wasps may take decisions has been proposed. These mechanisms are based in on changes in the degree of motivation to continue foraging during a particular foraging episode. Using a simple, straightforward model, we show here that the psychological mechanism proposed mimics precisely the theoretical Bayesian solution, provided that motivation displays exponential decay, rather than the linear pattern of decay initially assumed. Changes in motivation thus function as a sort of analogue computer, and may be seen as more than purely heuristic rules of thumb. This link between psychological processes and ultimate optimisation places foraging theory in the domain of neuroeconomics.     

Inhibition of jaw opening reflexes by stimulation of the central gray matter and raphe nuclei in cats

The effect of stimulation of the mesencephalic central gray matter and raphe nuclei on jaw opening reflexes evoked by excitation of high-threshold (dental pulp) and low-threshold (A-alpha) fibers of the infraorbital nerve afferents was studied in cats anesthetized with chloralose and pentobarbital. The jaw opening reflex evoked by stimulation of the dental pulp was shown to be effectively suppressed by conditioning stimulation of the central gray matter and raphe nuclei. The reflex evoked by stimulation of low-threshold infraorbital nerve afferents also was depressed (but less deeply and for a shorter period than the reflex evoked by stimulation of the dental pulp) during stimulation of the raphe nuclei and caudal zone of the central gray matter, but was unchanged after stimulation of the points located in the rostral zone of the central gray matter. Application of single stimuli or bursts of five stimuli with a frequency of 100 Hz had no effect on the reflexes studied. Short-term stimulation with a burst of 10–20 stimuli with a following frequency of 200–400 Hz led to inhibition of the reflexes, which lasted 450–1000 msec. Long-term stimulation of the central gray matter and raphe nuclei for 30 sec with a frequency of 50 Hz caused inhibition of jaw opening reflexes evoked by stimulation of both high- and low-threshold afferents for 60 min. Impulses from the central gray matter and raphe nuclei thus have a mainly inhibitory action on the jaw opening reflex evoked by stimulation of high-threshold afferents, but they act less effectively on the reflex evoked by stimulation of low-thres-hold afferents. The duration of inhibition depends essentially on the parameters of stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 374–387, May–June, 1984.