Genetic and environmental melanoma models in fish

Experimental animal models are extremely valuable for the study of human diseases, especially those with underlying genetic components. The exploitation of various animal models, from fruitflies to mice, has led to major advances in our understanding of the etiologies of many diseases, including cancer. Cutaneous malignant melanoma is a form of cancer for which both environmental insult (i.e., UV) and hereditary predisposition are major causative factors. Fish melanoma models have been used in studies of both spontaneous and induced melanoma formation. Genetic hybrids between platyfish and swordtails, different species of the genus Xiphophorus, have been studied since the 1920s to identify genetic determinants of pigmentation and melanoma formation. Recently, transgenesis has been used to develop zebrafish and medaka models for melanoma research. This review will provide a historical perspective on the use of fish models in melanoma research, and an updated summary of current and prospective studies using these unique experimental systems

Poison sedge can kill stock

POISON SEDGE was first suspected of being toxic to livestock in Western Australia nearly 80 years ago. Sudden deaths of sheep grazing areas on which poison sedge grew have been reported from many regions from Geraldton to Scott River. This article reports a case of poisoning in the field, and the experimental reproduction of poison sedge toxicity in pen-fed sheep

Direct Interaction of PP2A Phosphatase with GABAB Receptors Alters Functional Signaling

Addictive drugs usurp the brain's intrinsic mechanism for reward, leading to compulsive and destructive behaviors. In the ventral tegmental area (VTA), the center of the brain's reward circuit, GABAergic neurons control the excitability of dopamine (DA) projection neurons and are the site of initial psychostimulant-dependent changes in signaling. Previous work established that cocaine/methamphetamine exposure increases protein phosphatase 2A (PP2A) activity, which dephosphorylates the GABABR2 subunit, promotes internalization of the GABAB receptor (GABABR) and leads to smaller GABABR-activated G-protein-gated inwardly rectifying potassium (GIRK) currents in VTA GABA neurons. How the actions of PP2A become selective for a particular signaling pathway is poorly understood. Here, we demonstrate that PP2A can associate directly with a short peptide sequence in the C terminal domain of the GABABR1 subunit, and that GABABRs and PP2A are in close proximity in rodent neurons (mouse/rat; mixed sexes). We show that this PP2A-GABABR interaction can be regulated by intracellular Ca2+ Finally, a peptide that potentially reduces recruitment of PP2A to GABABRs and thereby limits receptor dephosphorylation increases the magnitude of baclofen-induced GIRK currents. Thus, limiting PP2A-dependent dephosphorylation of GABABRs may be a useful strategy to increase receptor signaling for treating diseases.SIGNIFICANCE STATEMENT Dysregulation of GABAB receptors (GABABRs) underlies altered neurotransmission in many neurological disorders. Protein phosphatase 2A (PP2A) is involved in dephosphorylating and subsequent internalization of GABABRs in models of addiction and depression. Here, we provide new evidence that PP2A B55 regulatory subunit interacts directly with a small region of the C-terminal domain of the GABABR1 subunit, and that this interaction is sensitive to intracellular Ca2+ We demonstrate that a short peptide corresponding to the PP2A interaction site on GABABR1 competes for PP2A binding, enhances phosphorylation GABABR2 S783, and affects functional signaling through GIRK channels. Our study highlights how targeting PP2A dependent dephosphorylation of GABABRs may provide a specific strategy to modulate GABABR signaling in disease conditions

Exact Solution of Two-Species Ballistic Annihilation with General Pair-Reaction Probability

The reaction process $A+B->C$ is modelled for ballistic reactants on an infinite line with particle velocities $v_A=c$ and $v_B=-c$ and initially segregated conditions, i.e. all A particles to the left and all B particles to the right of the origin. Previous, models of ballistic annihilation have particles that always react on contact, i.e. pair-reaction probability $p=1$. The evolution of such systems are wholly determined by the initial distribution of particles and therefore do not have a stochastic dynamics. However, in this paper the generalisation is made to $p<1$, allowing particles to pass through each other without necessarily reacting. In this way, the A and B particle domains overlap to form a fluctuating, finite-sized reaction zone where the product C is created. Fluctuations are also included in the currents of A and B particles entering the overlap region, thereby inducing a stochastic motion of the reaction zone as a whole. These two types of fluctuations, in the reactions and particle currents, are characterised by the `intrinsic reaction rate', seen in a single system, and the `extrinsic reaction rate', seen in an average over many systems. The intrinsic and extrinsic behaviours are examined and compared to the case of isotropically diffusing reactants.Comment: 22 pages, 2 figures, typos correcte

Investigation of fiber/matrix adhesion: test speed and specimen shape effects in the cylinder test

The cylinder test, developed from the microdroplet test, was adapted to assess the interfacial adhesion strength between fiber and matrix. The sensitivity of cylinder test to pull-out speed and specimen geometry was measured. It was established that the effect of test speed can be described as a superposition of two opposite, simultaneous effects which have been modeled mathematically by fitting two parameter Weibull curves on the measured datas. Effects of the cylinder size and its geometrical relation on the measured strength values have been analyzed by finite element method. It was concluded that the geometry has a direct influence on the stress formation. Based on the results achieved, recommendations were given on how to perform the novel single fiber cylinder test