University of Auckland

About: University of Auckland is a education organization based out in Auckland, New Zealand. It is known for research contribution in the topics: Population & Context (language use). The organization has 28049 authors who have published 77706 publications receiving 2689366 citations. The organization is also known as: The University of Auckland & Auckland University College.

Bayesian Evolutionary Analysis with BEAST

Abstract: What are the models used in phylogenetic analysis and what exactly is involved in Bayesian evolutionary analysis using Markov chain Monte Carlo (MCMC) methods? How can you choose and apply these models, which parameterisations and priors make sense, and how can you diagnose Bayesian MCMC when things go wrong? These are just a few of the questions answered in this comprehensive overview of Bayesian approaches to phylogenetics. This practical guide:Addresses the theoretical aspects of the field Advises on how to prepare and perform phylogenetic analysisHelps with interpreting analyses and visualisation of phylogeniesDescribes the software architecture Helps developing BEAST 2.2 extensions to allow these models to be extended further.With an accompanying website providing example files and tutorials (http://beast2.org/), this one-stop reference to applying the latest phylogenetic models in BEAST 2 will provide essential guidance for all users – from those using phylogenetic tools, to computational biologists and Bayesian statisticians.

Paracetamol (Acetaminophen): mechanisms of action

Abstract: Paracetamol has a central analgesic effect that is mediated through activation of descending serotonergic pathways. Debate exists about its primary site of action, which may be inhibition of prostaglandin (PG) synthesis or through an active metabolite influencing cannabinoid receptors. Prostaglandin H(2) synthetase (PGHS) is the enzyme responsible for metabolism of arachidonic acid to the unstable PGH(2). The two major forms of this enzyme are the constitutive PGHS-1 and the inducible PGHS-2. PGHS comprises of two sites: a cyclooxygenase (COX) site and a peroxidase (POX) site. The conversion of arachidonic acid to PGG(2) is dependent on a tyrosine-385 radical at the COX site. Formation of a ferryl protoporphyrin IX radical cation from the reducing agent Fe(3+) at the POX site is essential for conversion of tyrosine-385 to its radical form. Paracetamol acts as a reducing cosubstrate on the POX site and lessens availability of the ferryl protoporphyrin IX radical cation. This effect can be reduced in the presence of hydroperoxide-generating lipoxygenase enzymes within the cell (peroxide tone) or by swamping the POX site with substrate such as PGG(2). Peroxide tone and swamping explain lack of peripheral analgesic effect, platelet effect, and anti-inflammatory effect by paracetamol. Alternatively, paracetamol effects may be mediated by an active metabolite (p-aminophenol). p-Aminophenol is conjugated with arachidonic acid by fatty acid amide hydrolase to form AM404. AM404 exerts effect through cannabinoid receptors. It may also work through PGHS, particularly in areas of the brain with high concentrations of fatty acid amide hydrolase.

On the biological basis of human laterality: I. Evidence for a maturational left–right gradient

Abstract: In this paper, we consider human handedness and cerebral lateralization in a general biological context, and attempt to arrive at some conclusions common to the growth of human laterality and of other structural asymmetries. We suggest that many asymmetries appear to be under the influence of a left-right maturational gradient, which often seems to favor earlier or more rapid development on the left than on the right. If the leading side is damaged or restricted, this gradient may be reversed so that growth occurs with the opposite polarity. A mechanism of this sort appears to underlie the phenomenon of situs inversus viscerum et cordis , and the same principle may help explain the equipotentiality of the two sides of the human brain with respect to the representation of language in the early years of life. However we must also suppose that the leading side normally exerts an inhibitory influence on the lagging side, for otherwise one would expect language ultimately to develop in both halves of the brain. Examples of an inhibitory influence of this kind can also be found in other biological asymmetries; for instance, in the crab Alpheus heterochelis , one claw is normally greatly enlarged relative to the other, but if the larger claw is removed the smaller one is apparently released from its inhibitory influence and grows larger. This last example is particularly interesting because it suggests a mechanism comparable to that proposed by Annett to account for the distribution of handedness in the human population. She argued, in effect, that there is a “right shift” factor among the majority of the population, but that among a minority who lack this factor handedness is determined at random. If it is supposed that cerebral lateralization is also determined at random among this recessive minority, the model can be extended to provide a reasonable fit to the data on the correlation between handedness and cerebral lateralization. However this genetic model (or any other) still fails to account for the near-binomial distribution of handedness among twins and among nontwin siblings. We suggest that right-handedness and leftcerebral dominance for language are manifestations of an underlying gradient which is probably coded in the cytoplasm rather than in the genes. We must leave open the question as to whether departures from this pattern are due to a recessive gene which effectively cancels the asymmetry to environmental influences, or to both genetic and cytoplasmic factors.

The Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone Decreases Bone Formation and Bone Mineral Density in Healthy Postmenopausal Women: A Randomized, Controlled Trial

Abstract: Context: Thiazolidinediones, which are peroxisome proliferator-activated receptor-γ agonists, are widely prescribed to patients with disorders characterized by insulin resistance. Preclinical studies suggest that peroxisome proliferator-activated receptor-γ signaling negatively regulates bone formation and bone density. Human data on the skeletal effects of thiazolidinediones are currently available only from observational studies. Objective: The objective of the study was to determine whether rosiglitazone, a thiazolidinedione, inhibits bone formation. Design: The study was a 14-wk randomized, double-blind, placebo-controlled trial. Setting: The study was conducted in the general community. Patients: Fifty healthy, postmenopausal women participated in the study. Intervention: Intervention was rosiglitazone 8 mg/d. Main Outcome Measures: The primary end point was biochemical markers of bone formation, and secondary end points were a bone resorption marker and bone mineral density. Results: The osteoblast ...