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Using Multivariate Statistics

So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

In this book, Andrew Harvey sets out to provide a unified and comprehensive theory of structural time series models. Unlike the traditional ARIMA models, structural time series models consist explicitly of unobserved components, such as trends and seasonals, which have a direct interpretation. As a result the model selection methodology associated with structural models is much closer to econometric methodology. The link with econometrics is made even closer by the natural way in which the models can be extended to include explanatory variables and to cope with multivariate time series. From the technical point of view, state space models and the Kalman filter play a key role in the statistical treatment of structural time series models. The book includes a detailed treatment of the Kalman filter. This technique was originally developed in control engineering, but is becoming increasingly important in fields such as economics and operations research. This book is concerned primarily with modelling economic and social time series, and with addressing the special problems which the treatment of such series poses. The properties of the models and the methodological techniques used to select them are illustrated with various applications. These range from the modellling of trends and cycles in US macroeconomic time series to to an evaluation of the effects of seat belt legislation in the UK.

Forecasting, Structural Time Series Models and the Kalman Filter

Analysis of emotional response patterns for adolescent stepsons using P-technique factor analysis

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Transmitter Release Deficits at the Neuromuscular Synapse of Mice with Mutations in the Cav2.1 (α1A) Subunit of the P/Q-Type Ca2+ Channel

Heart failure (HF) is a global pandemic with significant mortality and morbidity. Despite current medications, 50% of individuals die within 5 years of diagnosis. Of these deaths, 30-50% will be a result of sudden cardiac death from ventricular arrhythmias. This review discusses two stress-induced mechanisms, phosphorylation from chronic β-adrenoceptor (β-AR) stimulation and thiol modifications from oxidative stress, and how they modulate the cardiac ryanodine receptor type 2 (RyR2) and foster an arrhythmogenic phenotype. Calcium (Ca2+) is the ubiquitous secondary messenger of excitation-contraction coupling and provides a common pathway for contractile dysfunction and arrhythmia genesis. In a healthy heart, Ca2+ is released from the sarcoplasmic reticulum (SR) by RyR2. The open probability of RyR2 is under the dynamic influence of co-proteins, ions, and kinases that are in strict balance to ensure normal physiological functioning. In HF, chronic β-AR activity and production of reactive oxygen species and reactive nitrogen species provide two stress-induced mechanisms uncoupling RyR2 control, resulting in pathological diastolic SR Ca2+ leak. This increased cytosolic [Ca2+] promotes Ca2+ extrusion via the local Na+/Ca2+ exchanger, resulting in net sarcolemmal depolarization, delayed after depolarization and ventricular arrhythmia. Experimental models researching oxidative stress and phosphorylation have aimed to identify how post-translational modifications to the RyR2 macromolecular complex, and the associated Na+/Ca2+ cycling proteins, result in pathological Ca2+ handling and diastolic leak. However, the causative molecular changes remain controversial and undefined. Through understanding the molecular mechanisms that produce an arrhythmic phenotype, novel therapeutic targets to treat HF and prevent its malignant course can be identified.

Understanding How Phosphorylation and Redox Modifications Regulate Cardiac Ryanodine Receptor Type 2 Activity to Produce an Arrhythmogenic Phenotype in Advanced Heart Failure.

Peter C. M. Molenaar

Papers

Analysis of emotional response patterns for adolescent stepsons using P-technique factor analysis

Transmitter Release Deficits at the Neuromuscular Synapse of Mice with Mutations in the Cav2.1 (α1A) Subunit of the P/Q-Type Ca2+ Channel

Understanding How Phosphorylation and Redox Modifications Regulate Cardiac Ryanodine Receptor Type 2 Activity to Produce an Arrhythmogenic Phenotype in Advanced Heart Failure.

Stochastic maximum likelihood mean and cross-spectrum structure modelling in neuro-magnetic source estimation

The Detection Of Genotype-Environment Interaction In Longitudinal Genetic Models