Canine Neurodegenerative Diseases: A Bridge from Bench to Health for Humans and their Companions

Translational Vision and Neuroscience Research PanelSpontaneous neurologic diseases are common in dogs and frequently there is a genetic predisposition. Advances in canine genomics and the nature of pure-bred dog populations make it possible to efficiently map and sequence the genes responsible. In contrast to transgenic rodent models, investigations into spontaneous canine disease start with a recognized disease process and work from there to the contribution of genetics to that disease. Thus there is never a question whether the findings will be relevant to real world disease since that is where we start. Once a disease has been characterized and the genes responsible identified, either the clinical population or a research colony can be utilized to investigate the pathogenesis of disease or to conduct therapeutic trials. The larger size and complexity of the brain in dogs compared with rodents can make the canine model more predictive of outcome in human trials in modalities such as gene, stem cell, or enzyme replacement therapies. The Comparative Neurology Program at the University of Missouri, College of Veterinary Medicine has applied this approach to identify the genes responsible for numerous developmental and degenerative diseases of the nervous system. These include seizures disorders, inborn errors of metabolism, amyotrophic lateral sclerosis, and parkinsonism; and we continue to identify new diseases regularly through our clinical practice and our relationship with other veterinary neurologist and neurosurgeons throughout the world

Progress in visibility modeling

December 1992.Includes bibliographical references.The cross section for total scattering by a cluster of spheres is derived from an integration, over a closed spherical surface, of the scattered Poynting flux associated with the different pairs of spheres in the ensemble. With the use of the addition theorem for vector spherical harmonics, the integral can be evaluated analytically. The pair-wise cross sections can be rearranged into an expression for the scattering cross section of sphere aggregates which is analogous to that obtained from Lorenz-Mie theory for a single sphere. This latter formulation, however, is more difficult to treat numerically than is the summation over pair-wise cross sections. The cross section for total scattering by a cluster of spheres thus derived is applied to a study of the effects of scavenging and aggregation on the specific absorption of carbon. Results are presented for polarization- and orientation-dependent absorption cross sections of sulfate haze elements and cloud droplets with small carbon grains (spheres) attached to their surfaces. Soot typically occurs as aggregates of carbon spherules. In order to address the validity of certain assumptions that are made in the analysis of such structures by fractal theory, comparisons between the absorption cross sections of free carbon, linear chains, and tightly clumped carbon spheres are also provided. Monte Carlo integration of the radiative transfer equation is the technique most easily adapted to complex scattering geometries. It is demonstrated that the multidimensional integrals can be evaluated more accurately and more efficiently with quasi Monte Carlo integration and that the convergence of the multiple scattering series can be accelerated by estimating the rate of decay of the tail of the series. Each of these techniques has been found to be robust and applicable to scattering with any geometry.Research supported by DOE DE-FG02-90ER61067 & NPSNOAA-NPS-NA90RAH00077

A Comparison of Two Intervention Strategies on the Academic Performance of Student-Athletes

The purpose of this study was to determine the effect of the Model Student Tutor Program (MSTP) when compared with the traditional study table on the academic performance of football players at the University of Wisconsin-LaCrosse as measured by grades acquired in selected courses. The subjects for this study consisted of eighty-one football players from a Division Ill program, the University of Wisconsin-La Crosse, in the fall semester of 1989. Participants registered in Biology 100 were randomly assigned to one of three groups: one group receiving peer tutoring, one group assigned to the traditional study table, and a control group. Participants registered in 100 level English and history were randomly assigned to one of three groups: one group receiving peer tutoring, one group assigned to the traditional study table, and a control group. Neither of the control groups received the academic intervention. ACT (composite, English, and science) scores were tested for pre-disposing differences. Three hypotheses were developed. The first hypothesis stated that there will be no significant difference in the grades of football players based on the type of intervention for literature-based courses. The second hypothesis stated that there will be no significant difference in the grades of football players, based on the type of intervention for science-based courses. The third hypothesis stated that there will be no significant difference in the grades of football players based on the type of intervention used across course content. Based on the results of an ANOVA, the first hypothesis was rejected while the second and third hypotheses were retained. There was a significant difference between the study table and control group for literature courses. Neither peer tutoring nor study table was significantly effective in improving the performance of football players in science-based classes. It could not be shown that study table or peer tutoring would be more effective if one had to choose between interventions regardless of course content

Role for polo-like kinase 4 in mediation of cytokinesis.

The mitotic protein polo-like kinase 4 (PLK4) plays a critical role in centrosome duplication for cell division. By using immunofluorescence, we confirm that PLK4 is localized to centrosomes. In addition, we find that phospho-PLK4 (pPLK4) is cleaved and distributed to kinetochores (metaphase and anaphase), spindle midzone/cleavage furrow (anaphase and telophase), and midbody (cytokinesis) during cell division in immortalized epithelial cells as well as breast, ovarian, and colorectal cancer cells. The distribution of pPLK4 midzone/cleavage furrow and midbody positions pPLK4 to play a functional role in cytokinesis. Indeed, we found that inhibition of PLK4 kinase activity with a small-molecule inhibitor, CFI-400945, prevents translocation to the spindle midzone/cleavage furrow and prevents cellular abscission, leading to the generation of cells with polyploidy, increased numbers of duplicated centrosomes, and vulnerability to anaphase or mitotic catastrophe. The regulatory role of PLK4 in cytokinesis makes it a potential target for therapeutic intervention in appropriately selected cancers

A Missense Mutation in Canine CLN6 in an Australian Shepherd with Neuronal Ceroid Lipofuscinosis

The childhood neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases that are progressive and ultimately fatal. An Australian Shepherd that exhibited a progressive neurological disorder with signs similar to human NCL was evaluated. The cerebral cortex, cerebellum, and retina were found to contain massive accumulations of autofluorescent inclusions characteristic of the NCLs. Nucleotide sequence analysis of DNA from the affected dog identified a T to C variant (c.829T>C) in exon 7 of CLN6. Mutations in the human ortholog underlie a late-infantile form of NCL in humans. The T-to-C transition results in a tryptophan to arginine amino acid change in the predicted protein sequence. Tryptophans occur at homologous positions in the CLN6 proteins from all 13 other vertebrates evaluated. The c.829T>C transition is a strong candidate for the causative mutation in this NCL-affected dog. Dogs with this mutation could serve as a model for the analogous human disorder

An Archaeological Survey on the Xoxocotlan Piedmont, Oaxaca, Mexico

Surface survey on the piedmont near the present village of Xoxocotlan, Oaxaca, Mexico, has revealed the pattern of prehistoric settlement around an irrigation canal that distributed water from a dammed reservoir located on the flanks of Monte Alban. Intensive systematic collection techniques have permitted quantitative statements to be made about the density of occupation and the contribution of the irrigation system to the food supply of Monte Alban