bluuebunny/crossref_metadata_2025 huggingface dataset:
ANOTHER LOOK AT ECONOMIES OF SIZE IN CATTLE FEEDING*
Authors: Johnson Ralph D.
Published: July 2010

This article is an outgrowth of a study that failed to find any economies of size in total cost of feeding cattle. It examines a number of cattle feeding studies that reportedly found economies of size and explains why the author is not willing to accept their findings. This article is not concerned with the external economies of size that may or may not exist in cattle feeding

Cet article est le résultat ďune recherche qui n'a pas réussit à trouver de grands économics dans le prix total de ľengraissement de bétail. II examine un certain nombre ďétude sur ľengraissement de bétail que rapporterent (dit‐on) de grands economies el il explique aussi pourquoi ľauleur n'est pas prêt à accepter leurs conclusions. Cet article ne se concerne pas avec les economies de grandeur extérieur quipeuvent ou nepeuventpas exister dans ľengraissement du bétail.
CONSTITUTIONAL AND INSTITUTIONAL CONSTRAINTS IN AGRICULTURE AND AGRICULTURAL POLICY*
Authors: Richter Joseph J.
Published: July 2010

When men are committed to technology they are also committed to continual change in institutions and customs [8, p. 72].

Nowhere does the fervor for this arcadian age reach such a crescendo as it does with the odes that are dedicated to the whooping crane of the American economic scene, the ‘family farm’ [6, p. 171].
LAND VALUATION FOR TAX ASSESSMENT AND LAND USE PLANNING–THE SEARCH FOR AND USE OF APPROPRIATE MEASURES*
Authors: van Vuuren W.
Published: July 2010

This article examines the conceptual problems of measuring agricultural land values for taxation purposes and for land use planning. It is shown that prevailing market prices are often deficient. One alternative method of measuring these values is by means of the soil productivity points currently used by the Ministry of Revenue in Ontario. It is shown that the foundations on which this method is based are weak, and that many problems arise in attributing a dollar value to these points. Finally, a shadow pricing technique is suggested. It has its weaknesses in land assessment for taxation, but it has great merit in evaluating land for land use planning.

Cet article étudie les problémes possibles qui se présentent dans l'évaluation des terres agricoles pour les fins de l'im pôt et de la planification de leur utilisation. L' article indique que les prix courant ne reflètent pas la valeur réelle de ces terres. Le Ministère tin Revenu de l'Ontario propose line autre méthode de valorisation: cette d' évaleur le terrain selon sa produclivilé. L' article démontre que les raisons sur lesquelles cette methode est fondée sont faibles et que de nombreux problèmes surgissent lors de l'attribution d'une valuer monétaire à ces points d'évaltialion. Enfin, on suggère tine technique utilisant les “shadow prices', qui a des faiblesses quand il s'agit ďévaleur les terrains pour raison d'impot mais qui a de grands mérites pour leur évaluation en rue de la planification de leur utilisation.
The Use of an Innovation Possibility Frontier to Evaluate an Applied Animal Breeding Research Project
Authors: Klein K.K. , Kehrberg E.W.
Published: July 2010

This study was designed to develop and illustrate a method for evaluating individual applied research projects in agriculture. Since the individual entrepreneur must apply research results before society can benefit, a framework for project evaluation must be developed on the basis of opportunities facing him. Such a framework would permit researchers and research administrators to make sound decisions in planning, conducting, and directing their research.

A partially completed animal breeding research project was chosen to illustrate this evaluation technique. Average cost disadvantages for various crossbreeds under different input price scenarios were computed. The sensitivity of the evaluation results to tentative data was assessed.

This methodology provided encouraging results and could be employed by research teams. A researcher's prior knowledge can be incorporated to determine research areas where a higher payoff could be expected. Equally, research projects can be monitored periodically to estimate their progress toward economic goals.

L'objectif de cette étude était de développer et d'illuslrer une méthode pour l'évaluation de projets de recherche appliquée en agriculture.

Puisque chaque entrepreneur doit appliquer des résultats de recherche avam que la société ne puisse en bénéficier, il est nécessaire de mettre au point pour l'évaluation de tels projets. un cadre d'analyse se référant aux conditions auxquelles il est confronté. Un tel cadre d'analyse permettrait aux chercheurs et aux administrateurs de recherche d'effectuer de meilleures décisions dans la planification, l'exécution el I'adminislration de leurs recherches.

Un project d'élevage sur le point d'être complété a été retenu pour illustrer cette technique d'évaluation. On a calculé le coût moyen des penes pour divers croisements selon différentes hypothèses sur le prix des intrants. La sensibilité des résultats aux données préliminaires a étéévaluée.

Cette méthode a donné des résultats encourageants et pourrait être utilisée par des équipes de recherche. Les connaissances dun chercheur peuvent être utilisées pour déterminer les domaines de recherche qui présentent le plus grand intérêt. De plus, on peut contrôler périodiquement les projets de recherche afin d'apprécier leur progression vers des objectifs économiques.
The Function of the CAES Workshop: Past Performance and Suggestions for the Future
Authors: Sinclair Sol
Published: July 2010

During the quarter century that the CAES workshop has existed, it has provided agricultural economists with the opportunity to test views in open discussion and group thinking sessions. It has largely met its originally objectives, namely to provide an opportunity for intensive study of current problems, to initiate research in various areas, and to make the results of such specialized study available to a wider audience.

The workshop has been most successful when it provided discussion of a current topic of interest to the agricultural industry or professionals, was held in a location conducive to study, was held separately from any other conference, provided a readable Proceedings, and allowed sufficient time for full discussion of the topic. Recent trends to shorter meetings and to papers that read like journal articles have somewhat diminished the workshop's effectiveness, however.

L'atelier de S.C.E.R. depuis sa création, il y a 25 ans, donne aux économistes agricoles /'occasion de confronter lews opinions lors de débats ouverts et de séminaires de réflexion. II a atteint en grande partie ses objectifs initiaux, à savoir: permettre d'étudier intensément des problèmes actuels, instaurer la recherche dans des secteurs variés, faire parvenir à un plus vaste auditoire les résultats de telles études spéciatisées.

L'atelier a été des plus réussis lorsqu'il a permis de disculerd'un sujet actuel qui touchait les professionnels ou I'industrie de l'agriculture, qu'il s'est tenu dans des locaux favorables a l'étude et indépendamment de toute autre conférence, qu'il a fourni des Proceedings lisibles, enfin qu'il a alloué suffisamment de temps pour discuter pleinement d'un sujet. Pourtant, les tendances récemes à tenir des réunions plus courtes el à avoir des communications qui abusenl de termes hautement spécialisés onl quelque peu émoussé l'efficacité de l'atelier.
Rural Farmer Productivity in the Tropics: The Nigerian Experience
Authors: Ngambeki D. S. , Ikpi A. E.
Published: July 2010

The dilemma posed by the poverty and low agricultural productivity of rural farmers in tropical countries in spite of generous natural resource endowments has continuously baffled their agricultural policy makers. This paper contends that this perplexing situation has been due primarily to the omission of a crucial determinant —producer's health capital — in the usual agricultural development models applied to these countries.

This contention is analyzed through a deterministic model designed to relate rural farmers' health and the quality and level of nutrition to physical work output, farm work efficiency and rural farming profitability. To account for the full effects of all nutritional variables without encountering problems of multicollinearity and model mis‐specification, principal component analysis is used to transform these variables into a single proxy which is linearly independent of the original variables but which adequately represents them and retains their effects in the analysis.

The results are presented in four tables and show, among other things, that there is an asymmetric response inform profits with respect to being ill vis‐à‐vis being healthy because of the quality of nutrition, so that rural farmers lose farm profits much faster during sickness than they can make these profits during healthy days.

La pauvreté el la faible productivité agricole des paysans dans les pays tropicaux, bien que ces derniers soient riches en ressources naturelles, sont des dilemmes qui n'ont cessé de déconcerter les responsables en politique agricole. Cette communication affirme que cette situation déconcertante est causée avant tout par le fait qu'on néglige un determinant crucial (le capital que represénte la santé des producteurs) dans les schemas de d'eveloppement agricole que l'on applique à ces mèmes pays.

Cette thèse est analysée au moyen d'un modè le dèterministe qui met en relation la santè des paysans, la qualité et le niveau de leur alimentation avec leur rendement physique, la productivité et la rentabililé agricoles. Pour expliquer pleinemenl tous les effets des variables nutritionnelles sans se heurter aux probfemes de multicolinearité et d'erreurs de spécification dans le modele, on utilise l'analyse des composantes principalespour transformer ces variables en un seul substitut; ce dernier est lineairement indepéndant des variables originelles, mais les représente adéquatement et maintient leurs effets dans l'analyse.

Les résultats apparaissent dans quatre tableaux et montrent, entre autres, une réponse asymétrique dans les profits agricoles suivant l'ét at de santé des paysans et la qualité de leur alimentation; un paysan malade perd ses profits agricoles plus vite qu'il les acquiert quand il est bien portant.
Improvements to Market Efficiency through the Operation of the Alberta Pork Producers' Marketing Board
Authors: Leavitt S. , Hawkins M. , Veeman M.
Published: July 2010

This study evaluates the market performance of the Alberta Pork Producers' Marketing Boar J since it became the single selling agency for hogs in Alberta in 1969. Concepts of pricing and operational efficiency are applied, and comparisons made with Winnipeg, Toronto, and the average of seven U.S. markets. The effect of market information on operational and pricing efficiency is also assessed. Cost reductions in the hog marketing system are used to assess operational efficiency. Cost savings are documented and attributed to the Producers' Hog Indemnity Fund, the assembly yard system, the hog allocation system, the “cheque float mechanism.” and the hog settlement procedure. Pricing efficiency is evaluated using graphic. statistical and econometric methods. Results from these techniques are compared, among market areas, during various time periods representing policy changes by the board.

The major conclusions from this study are that the board's selling and market information procedures have improved operational efficiency. However, a firm conclusion concerning pricing efficiency cannot be made because of mixed evidence. It is recommended that other commodity interests could benefit from becoming involved in co‐operative selling through a single selling agency.

Cette étude a évalu'e le succés du marché de la régie albertaine de mise en marché du pore. Depuis 1969, e'est ia seule agence de venle des produits du pore en Alberta. Les auteurs considered ľefficacité de la détermination desprix et des operations et comparenl les marchés de Winnipeg, Toronto et une moyenne de sept marchés américains. ľinformation disponible sur le marché a étéévaluée aussi afin de déterminer son effet sur ľefficacité operalionnelle ainsi que ľefficacité du mécanisme des prix.

Les conclusions principales de cette étude sont que les procédures de vente et ďapprovisionnemenl de ľinformation sur le marché ont amélioréľefficacité operalionnelle de la régie. Cependant, à cause ďévidence mixte, une conclusion definitive concernant ľefficacité due mécanisme des prix ne peut pas étre formulée. Les auteurs recommandent que les producteurs ďautres produits de base pourraient profiler ďune participation dans la vente co‐opérative par une agence unique de vente.
An Analysis of Dynamic Economic Relationships: An Application to the U.S. Hog Market
Authors: Bessler David A.
Published: July 2010

Recent advances in multiple time‐series analysis are discussed and applied to data from the U.S. hog market. Vector‐autoregressive and moving‐average representations are derived and interpreted with respect to implied dynamic relationships among the variables.

Desprogrès récents dans l'analyse des séries temporelles multiples sont présentes el utilisés pour l'analyse des données sur le marché porcin aux Etats‐ Unis. Deux representations, la premiere vectorielle el autoregressive et la seconde moyennes mobiles, sont dérivées et interpretées selon les relations dynamiques implicites des variables.
An Economic Evaluation of Public Wheat Research and Extension Expenditures in Canada*
Authors: Zentner R.P. , Peterson W.L.
Published: July 2010

The widespread commitment of public funds to agricultural research is being questioned by administrators in governments and by the Canadian public. Questions relating to the level of public expenditure on agricultural research, the efficiency with which the resources are being allocated, and the manner in which the benefits are distributed among members of society art being asked. This study addresses these and related questions as they pertain to publicly funded wheat research activities conducted over the period 1946 to 1979‐ Two research scenarios were examined ‐ one dealing with the development of new varieties of wheat and the other dealing with all research applicable to the production of wheat. The results revealed that society has indeed benefitted substantially from public investment in wheat research. The level of social benefits averaged $49 and $143 million (measured in 1971 dollars) annually for the wheat breeding and all‐wheat research scenarios, respectively. The average annual internal rates of return earned from these public investments ranged between 30 and 39 percent. Furthermore, some evidence was presented that suggests society may, in fact, be underin‐vesting in agricultural research in the aggregate. Finally, analyses of the distribution of the benefits showed that both producers and consumers are major beneficiaries.
Financial Reporting in Agriculture: In Need of A Reliable System
Authors: Bagnall Herb , Aukes Robert
Published: July 2010

Farm managers and lenders are becoming increasingly aware of the need for thorough and accurate farm financial management.1 The current extended agricultural recession magnifies this need. Increased current loan losses and the increasing financial stress of farm operators have prompted lending institutions, government agencies and farmers to determine what has gone wrong in the area of farm financial management and, more importantly, to search out ways to reduce the frequency of farm business failure. The use of inadequate financial reporting systems is viewed as one source of the problem.
Including Inperfect Competition in Spatial Equilibrium Models: A Comnent
Authors: Yang Chin‐Wei
Published: July 2010

In a recent issue of this Journal, Nelson and McCarl proposed an interesting Cournot model with zero transportation costs and a constant marginal cost. From the well‐known first‐order condition, Nelson and McCarl derived a quadratic program with two sets of linear constraints. The purpose of this note is to show that the Nelson and McCarl formulation is not valid without some qualifications.
Economic Analysis of the Western Grain Stabilization Program
Authors: Spriggs John
Published: July 2010

The author gratefully acknowledges the financial assistance provided by the Saskatchewan Wheat Pool. However, the ideas expressed in this paper are those of the author and do not necessarily reflect the views of the Saskatchewan Wheat Pool.

On the basis of the assumptions laid out in section 2.2, the current program is projected to pay out over the prospective five‐year simulation period an amount approximately equal to what it takes in. In determining the payouts, the introduction of the new trigger mechanism is expected to make a significant, but not overwhelming contribution. Over the prospective five‐year period, the current program is expected to be actuarially sound.

The first proposed change to the current program is the adjustment of income and expenses for inflation. Such a change appears to generate much larger payouts than the current program, and to have a greater stabilization potential than the current program. However, such payouts could not be sustained by the fund as it presently operates, and it is expected that the fund would be rendered actuarially unsound. After five years, the probability of the fund being in a deficit is 93 percent. The point projection of this deficit is about $1 billion.

The second proposed change is the reduction in the number of years for averaging, from five down to three. This change appears to generate a slightly larger total payout over the simulation period. In addition, it does not appear to impact significantly on the program's actuarial soundness. The one significant feature of this change is that it appears to diminish the program's stabilization potential.

The third proposed change is the incorporation of debt interest as an expense in the determination of payouts. This change appears to generate a modestly higher total payout. Nonetheless, the fund is still expected to be actuarially sound at the end of the period, and the probability of a deficit is only 19 percent. The significant feature of this change is that the stabilization potential of the program would be enhanced.
The Measurement of Growth Rates From Time Series
Authors: Adamowicz Wiktor L. , Manning Travis W.
Published: July 2010

Growth rates are commonly used as summaries of trends in time series data. Productivity indexes, price indexes and output series are usually discussed in terms of the changing growth rates over various periods of time. Policy decisions are often based on such growth rate estimates. However, there are several techniques for measuring growth rates and depending on the nature and structure of the data, each may provide a different result. The problems of traditional measures of growth rates are discussed and some new measures and their merits are also presented. An empirical example shows the potential problems associated with some growth rate measures and presents some solutions.
The Future Role of the Farm Business Management Expert
Authors: Bauer Leonard
Published: July 2010

Farm management is a task performed only by managers of farms. It is not undertaken by those who write about it, teach it, or give advice on it. (Giles and Stansfleld 1980, 187)
Processor Pressures for Change in Pork Marketing Organizations in Ontario and in Québec
Authors: Saint‐Louis Robert
Published: July 2010

This paper reviews some of the economic and political forces that are causing processors to seek changes in pork marketing organizations in Ontario and in Québec. It is argued that those forces have been arising all at once from a very wide variety of sources, the most important of which have been structural in nature and external to the local industry. As a consequence, processors find themselves in the position of pushing strongly for further major moves towards a better vertically coordinated system of marketing slaughter hogs with perhaps new forms of chain supply risk management and lower transaction costs.

L'article traite des changements économiques et politiques qui incitent les industriels de l'abattage et de la charcuterie à revendiquer des modifications aux systèmes de mise en marché des porcs d'abattage en Ontario et au Québec. Il s'agit d'une vaste combinaison de forces, y affirme‐t‐on, qui se sont manifestées parallè lement, et dont les plus importantes sont d'ordre structurel et sont causées par des facteurs externes à l'industrie locale. Il en résulte en bout de ligne que l'industrie de la transformation porcine revendique trés fortement, dans ces provinces, l'amorce de modifications majeures aux systèmes actuels de mise en marché des porcs d'abattage. L'objectif dominant de ces industriels consiste à renforcir les liaisons de coordination verticale dans l'industrie, y inclus celles concernant la mise en marché des porcs d'abattage, sans exclure la possibilité de créer une chaîne d'approvisionnement encore plus étroitement coordonnée et au sein de laquelle les éléments de partage de risques seraient redéfinis, tout en y réduisant les coûts de transaction par animal.
An Analysis of Congestion Effects Across and Within Multiple Recreation Activities
Authors: Rollins Kimberly , Dumitras Diana , Castledine Anita
Published: July 2010

This paper uses stated and revealed preference data to quantify differential welfare impacts from changes in congestion at outdoor recreation sites that support multiple activities. The results indicate that welfare impacts from congestion vary by congestion point, site, and activity within a given site. Estimating willingness to pay (WTP) for multiple sites and activities allows for parametric testing of whether WTP varies among sites and activities. The most general implication of this study is that if one has the ability to discriminate by activity, doing so is preferable purely in terms of overall model performance. This approach is especially useful for circumstances in which visitor flows in a system of multiple use areas can be managed so as to increase net benefits associated with public lands.

Dans la présente étude, nous avons utilisé des données sur les préférences déclarées et révélées pour quantifier l'impact différentiel que des variations de congestion dans les aires d'activités récréatives multiples ont sur le bien‐être. Les résultats ont montré que l'impact différentiel de la congestion sur le bien‐être varie selon le point de congestion, l'aire et l'activité au sein d'une aire donnée. L'estimation de la volonté de payer (VDP) pour des aires et des activités multiples permet de vérifier, à l'aide d'un test paramétrique, si la VDP varie ou non entre les aires et les activités. L'implication la plus générale de cette étude est que si quelqu'un a la possibilité de discriminer selon l'activité, le fait de le faire est préférable purement si l'on considère la performance globale du modèle. Cette méthode est particulièrement utile dans les cas où l'affluence des visiteurs dans un système d'aires polyvalentes peut être gérée de sorte à accroître les avantages nets liés aux terres publiques.
The Wetland Aviary at Rheine Zoo
Authors: SALZERT WOLFGANG , JOHANN ACHIM
Published: July 2010

A walk‐through aviary opened at Rheine Zoo in 1984 was designed to simulate a wetland habitat housing egrets, ibises and spoonbills. The paper details the construction and management of the exhibit which, in addition to breeding colonies of birds, sustains appropriate flora, invertebrate and fish populations. Winter quarters and management are also described.
The Detroit Zoo Chimpanzees Pan troglodytes:: exhibit design, group composition and the process of group formation
Authors: MCDONALD SUSAN
Published: July 2010

At Detroit Zoo management staff have taken steps to promote a physically and socially sound captive Chimpanzee Pan troglodytes colony by designing and building a new exhibit based on successful models at two other zoos. A careful procedure of stepped dyadic introductions was employed to integrate 11 unfamiliar Chimpanzees into a single group of 2.9 individuals.
Abolishing obsolete legislation on crimes and criminal procedure
Authors: McBain Graham
Published: July 2010

The English criminal law has not moved with the times – nor with the increasing emphasis on human rights. Legislation still extant goes back nearly 700 years and is barely intelligible. This paper analyses antiquated criminal and criminal procedure legislation and asserts it should be repealed, being superceded by more modern enactments. It also argues for the consolidation of all criminal (and criminal procedure) legislation for the period 1313–1960 into one Act of around 300 sections. This task would not be complex.
BETWEEN CONVENTIONS: THE MEMBERS OF RESTORATION PARLIAMENTS
Authors: MORRILL JOHN
Published: July 2010

The House of Commons 166C‐1690. By Basil Duke Henning.
Neuropathy Associated with Hyperoxaluria: Improvement After Combined Renal and Liver Transplantations
Authors: Galloway Gloria , Giuliani Michael J. , Burns Dennis K. , Lacomis David
Published: July 2010

Little is known about oxaluria‐associated neuropathy, and no effective treatments have been described. We report two patients with clinically severe and progressive sensorimotor polyneuropathy associated with oxaluria. Electrodiagnostic testing and sural nerve histopathology revealed evidence of severe axon loss and demyelination. In addition, birefringent crystalline deposits were identified within endoneurial and perineurial blood vessel walls, axon cylinders, and perimysial blood vessel walls. Electron probe microscopy confirmed that calcium (consistent with calcium oxalate) was a major constituent of the crystals. Both patients had substantial improvement in neuropathic signs and symptoms after kidney and liver transplantations despite no prior improvement with hemodialysis. Our results confirm previous reports of a mixed axonal and demyelinating neuropathy with calcium oxalate deposition in association with oxaluria. In addition, our findings suggest that renal and liver transplantation may be potential treatments for the associated neuropathy.
Dementia of Frontal Type and Dementias with Subcortical Gliosis
Authors: Mann David MA
Published: July 2010

The group of Frontotemporal dementias (FTD) is composed of non‐Alzheimer forms of dementia characterized clinically by behavioural and personality change leading to apathy and mutism. The disorder is associated with a progressive atrophy of the frontal, anterior temporal and anterior parietal lobes of the brain with several types of underlying pathology. One type (frontal lobe degeneration) is characterized by a microvacuolar degeneration of the outer cortical laminae along with a mild and mainly subpial gliosis and a loss of nerve cells, mostly from layers II and III. Another type shows transcortical tissue cavitation and florid gliosis with neuronal degeneration characterized by the presence of tau and ubiquitin positive inclusion bodies and α B‐crystallin‐positive ballooned neurones: such changes have been termed ‘Pick‐type histology’, and form the basis for the modern definition of ‘Pick's disease’. The aetiological relationship between these two histological types is presently unknown. Both histologies can be differently distributed topographically throughout the brain to produce syndromes of progressive language disorder, when affecting bitemporal lobes or the left hemisphere preferentially, or progressive apraxia when parietal and motor regions are involved. Either pathology can be combined with or overlaps with that of classical motor neurone disease to produce motor neurone disease dementia. The underlying cause of FTD is unknown but genetic factors are strongly implicated. About half of cases show a previous family history of a similar disorder. In several families bearing a FTD clinical and pathological phenotype, linkage to chromosome 17 has been established but the pathology of this group appears distinctive and its relation to other forms of FTD awaits further elucidation. It is still possible that the many clinical and pathological variants of FTD may reflect different phenotypic expressions of a particular genetic change(s) at a single locus on this chromosome.
Survival of Patients with Glioblastoma Multiforme is not Influenced by Altered Expression of P16, P53, EGFR, MDM2 or Bcl‐2 Genes
Authors: Newcomb Elizabeth W. , Cohen Henry , Lee Suzanne R. , Bhalla Sandhya K. , Bloom Joanna , Hayes Roberta L. , Miller Douglas C.
Published: July 2010

Deregulated expression of one or more growth control genes including p16, p53, EGF receptor (EGFR), MDM2 or Bcl‐2 may contribute to the treatment resistance phenotype of GBM and generally poor patient survival. Clinically, GBM have been divided into two major groups defined by (1) histologic progression from a low grade tumor (“progressive” or “secondary” GBM) contrasted with (2) those which show initial clinical presentation without a prior history (“de novo” or “primary” GBM). Using molecular genetic analysis for p53 gene mutations together with immunophenotyping for overexpression of EGFR, up to four GBM variants can be distinguished, including the p53+/EGFR progressive or the p53‐/EGFR+de novo variant. We examined the survival of 80 adult patients diagnosed with astrocytic GBM stratified by age category (>40, 41–60 or 61–80) to determine whether alterations in any one given growth control gene or whether different genetic variants of GBM (progressive versus de novo) were associated with different survival outcomes. Survival testing using Kaplan‐Meier plots for GBM patients with or without altered expression of p16, p53, EGFR, MDM2 or Bcl‐2 showed no significant differences by age group or by gene expression indicating a lack of prognostic value for GBM. Also the clinical outcome among patients with GBM showed no significant differences within each age category for any GBM variant including the progressive and de novo GBM variants indicating similar biologic behavior despite different genotypes. Using a pair‐wise comparison, one‐third of the GBM with normal p16 expression showed accumulation of MDM2 protein and this association approached statistical significance (0.01 < P < 0.05) using the Bonferroni procedure. These GBM may represent a variant in which the p19ARF/MDM2/p53 pathway may be deregulated rather than the p16/cyclin D‐CDK4/Rb pathway.
Transgenic Mouse Models of Alzheimer's Disease and Amyotrophic Lateral Sclerosis
Authors: Borchelt David R. , Wong Philip C. , Sisodia Sangram S. , Price Donald L.
Published: July 2010

Over the past several years, there has been enormous progress in generating transgenic mice that model aspects of human neurodegenerative diseases. These studies build upon the efforts of molecular geneticists who have identified a number of genes that, when mutated, cause familial forms of these diseases. In this review, we focus on the mutations that cause familial forms of Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), and transgenic mouse models that develop clinical and pathological abnormalities resembling those occurring in the human diseases.
Genetic Regulatory Elements Introduced Into Neural Stem and Progenitor Cell Populations
Authors: Foster George A. , Stringer Bradley M.J.
Published: July 2010

The genetic manipulation of neural cells has advantage in both basic biology and medicine. Its utility has provided a clearer understanding of how the survival, connectivity, and chemical phenotype of neurones is regulated during, and after, embryogenesis. Much of this achievement has come from the recent generation by genetic means of reproducible and representative supplies of precursor cells which can then be analyzed in a variety of paradigms. Furthermore, advances made in the clinical use of transplantation for neurodegenerative disease have created a demand for an abundant, efficacious and safe supply of neural cells for grafting. This review describes how genetic methods, in juxtaposition to epigenetic means, have been used advantageously to achieve this goal. In particular, we detail how gene transfer techniques have been developed to enable cell immortalization, manipulation of cell differentation and commitment, and the controlled selection of cells for purification or safety purposes. In addition, it is now also possible to genetically modify antigen presentation on cell surfaces. Finally, there is detailed the transfer of therapeutic products to discrete parts of the central nervous system (CNS), using neural cells as elegant and sophisticated delivery vehicles.

In conclusion, once the epigenetic and genetic controls over neural cell production, differentiation and death have been more fully determined, providing a mixture of hard‐wired elements and more flexibly expressed characteristics becomes feasible. Optimization of the contributions and interactions of these two controlling systems should lead to improved cell supplies for neurotransplantation.
Alpha‐synuclein in Lewy Body Disease and Alzheimer's Disease
Authors: Hashimoto Makoto , Masliah Eliezer
Published: July 2010

Alzheimer's disease (AD) and Lewy body disease (LBD) are the most common causes of dementia in the elderly population. Previous studies have shown that cognitive alterations in these disorders are associated with synaptic loss. Injury and loss of synapses might be associated with altered function of synaptic proteins. Among them, recent studies have shown that abnormal aggregation and accumulation of synaptic proteins, such as α‐synuclein, might be associated with plaque formation in AD and Lewy body formation in LBD. Further reinforcing the hypothesis that α‐synuclein plays a major role in the pathogenesis of these disorders, recent work has shown that mutations that alter the conformation of this molecule are associated with familial forms of Parkinson's disease. The mechanisms by which altered function or aggregation of α‐synuclein might lead to neurodegeneration are not completely clear; however, new evidence points to a potential role for this molecule in synaptic damage and neurotoxicity via amyloid‐like fibril formation and mitochondrial dysfunction. In this manuscript we review the data linking α‐synuclein to the pathogenesis of AD and LBD.
Multiple System Atrophy: A Sporadic Synucleinopathy
Authors: Dickson Dennis W. , Lin Wen‐lang , Liu Wan‐Kyun , Yen Shu‐Hui
Published: July 2010

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized clinically by varying degrees of Parkinsonism, cerebellar ataxia and autonomic dysfunction and pathologically by degeneration in the substantia nigra, putamen, olivary nucleus, pontine nuclei and cerebellum. In addition to selective neuronal loss, iron pigment accumulation and gliosis, myelin pathology is increasingly recognized. In affected white matter, myelin displays signs of degeneration and oligodendroglia contain argyrophilic inclusion bodies, so‐called glial cytoplasmic inclusions (GCI). GCI are composed of 10–15‐nm diameter coated filaments that are immunoreactive for ubiquitin and α‐synuclein. Similar inclusions are occasionally found in neuronal cell bodies and cell processes in MSA. Given the presence of inclusion bodies composed of synuclein, it is reasonable to assume that biochemical alterations would be detected in synuclein in MSA and indeed this is the case. In MSA synuclein has biophysical properties that suggest increasing insolubility such as sedimentation in dense fractions in sucrose gradients and ready extraction into detergents and formic acid. Surprisingly, these biochemical modifications in synuclein are more widespread in the brain that the obvious pathology and suggest a fundamental molecular characteristic of the disorder. Similar neuronal, and less frequently glial, inclusions are detected in Lewy body disease, where there is also evidence for biophysical alterations in synuclein. Thus, MSA and LBD are both synucleinopathies, and they may comprise different poles of a disease spectrum that includes sporadic disorders as well as genetically determined disorders such as familial Lewy body Parkinsonism.
Low Frequency of SV40, JC and BK Polyomavirus Sequences in Human Medulloblastomas, Meningiomas and Ependymomas
Authors: Weggen Sascha , Bayer Thomas A , von Deimling Andreas , Reifenberger Guido , von Schweinitz Dietrich , Wiestler Otmar D. , Pietsch Torsten
Published: July 2010

Several reports have suggested a role for polyomaviruses in the pathogenesis of human brain tumors.This potential involvement is not conclusively resolved. For the present study, a highly sensitive PCR‐assay with fluorescence‐labelled primers was developed to search for polyomavirus sequences in human brain tumor and control DNA samples. The assay was shown to detect approximately one viral large T‐antigen (TAg) gene per 250 cells. We identified simian virus 40 (SV40)‐like sequences in 2/116 medulloblastomas, in 1/131 meningiomas, in 1/25 ependymomas and in 1/2 subependymomas. A single case of ependymoma contained SV40 VP‐1 late gene sequences. Moreover, one of the meningioma samples showed JC virus sequences. In contrast, 60 hepatoblastoma samples and 31 brain samples from schizophrenic patients were consistently negative. BK virus sequences were not detectable in any of our samples. Immunohistochemical analysis of two SV40 positive tumor biopsies failed to detect large TAg in the tumor cells. In the JC positive meningioma, immunoreactivity for the viral late gene product (VP‐1) was not observed. Our data do not entirely rule out SV40 and JC virus as an initiative agent with a hit‐and‐run mechanism. However the low frequency of virus sequences and the absence of TAg protein expression argue against a major role of these viruses in the pathogenesis of human medulloblastomas, meningiomas and ependymomas.
Expression Analysis of Ataxin‐7 mRNA and Protein in Human Brain: Evidence for a Widespread Distribution and Focal Protein Accumulation
Authors: Lindenberg Katrin S. , Yvert Gaël , Müller Klaus , Landwehrmeyer G. Bernhard
Published: July 2010

Spinocerebellar ataxia 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG‐trinucleotide repeat in the coding region of the SCA7 gene. The expansion is translated into an extended polyglutamine stretch in the protein ataxin‐7, a protein of unknown function. By Northern blot analysis expression of ataxin‐7 was detected in numerous regions of human brain and some peripheral tissues. It is unknown, however, if ataxin‐7 is enriched at sites of the SCA7 pathology. We studied the regional and cellular expression pattern of ataxin‐7 at the mRNA level by in situ hybridization histochemistry in normal human brain. Furthermore we used a monoclonal and two polyclonal antibodies raised against the normal ataxin‐7 to establish the distribution of this protein in brain, retina and peripheral organs. At the mRNA level ataxin‐7 was preferentially expressed in neurons; the regional distribution reflected neuronal packing density. Ataxin‐7 immunoreactivity (IR) was similarly widely expressed. In most neurons, ataxin‐7 IR was preferentially localized to the cytoplasmatic compartment although some nuclear ataxin‐7 IR was detected in most neurons. A more intense and more prominently nuclear ataxin‐7 IR was observed in neurons of the pons and the inferior olive, brain regions severly affected by the disease, suggesting that the subcellular localization and abundance of ataxin‐7 is regulated in a regionally specific way. Since neurons displaying more intense and more prominently nuclear ataxin‐7 IR belonged to the class of susceptible cells in SCA7, an enrichment of normal ataxin‐7 in the nuclear compartment may contribute to neurodegeneration. However not all sites of SCA7 pathology displayed a strong cytoplasmatic and nuclear immunoreactivity.
Viral Induced Demyelination
Authors: Stohlman Stephen A. , Hinton David R.
Published: July 2010

Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell‐cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral‐induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence.

Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non‐enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus‐specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the oligodendroglia or the myelin sheath; or 4) infection initiates activation of an immune response specific for either oligodendroglia or myelin components. Virus‐induced inflammation may be associated with the processing of myelin or oligodendroglial components and their presentation to the host's own T cell compartment. Alternatively, antigenic epitopes derived from the viral proteins may exhibit sufficient homology to host components that the immune response to the virus activates autoreactive T cells, i.e. molecular mimicry. Although it is not clear that each of these potential mechanisms participates in the pathogenesis of human demyelinating disease, analysis of the diverse demyelinating viral infections of both humans and rodents provides examples of many of these potential mechanisms.
Phosphorylated Map Kinase (ERK1, ERK2) Expression is Associated with Early Tau Deposition in Neurones and Glial Cells, but not with Increased Nuclear DNA Vulnerability and Cell Death, in Alzheimer Disease, Pick's Disease, Progressive Supranuclear Palsy and Corticobasal Degeneration
Authors: Ferrer I. , Blanco R. , Carmona M. , Ribera R. , Goutan E. , Puig B. , Rey M.J. , Cardozo A. , Viñals F. , Ribalta T.
Published: July 2010

Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in tau pathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double‐labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double‐labelling immunohistochemistry and in situ end‐labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation‐independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation‐independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK‐P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK‐P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK‐P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK‐P immunoreactivity is found in large numbers of tau‐positive glial cells in PSP and CBD, as seen with double‐labelling immunohistochemistry. Yet no co‐localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD.
Novel PLA2G4C Polymorphism as a Molecular Diagnostic Assay for 19q Loss in Human Gliomas
Authors: Hartmann Christian , Johnk Loki , Sasaki Hikaru , Jenkins Robert B. , Louis David N.
Published: July 2010

PLA2G4C, encoding cytosolic phospholipase A2‐γ (cPLA2‐γ), is a 17‐exon gene located on chromosome 19q13.3 within the putative glioma tumor suppressor gene region. Given the clinical importance of assessing 1p and 19q loss in human gliomas, the development of convenient and practical assays for detecting allelic loss is of considerable priority in neuro‐oncology. We report a minisatellite polymorphism in the untranslated region of exon 1, with allelic variants that have one, two or three 27‐bp repeats. The polymorphism is informative in 55.7% of a reference population, and accurately detects allelic loss of 19q in human gliomas. This novel marker offers distinct advantages for assessing 19q status in malignant gliomas. The relatively large size of the repeats allows detection of allelic variants with standard ethidium bromide‐stained agarose gels and the PLA2G4C marker is the closest polymorphism to the smallest common deletion area in the putative glioma tumor suppressor gene region. These characteristics suggest that the PLA2G4C polymorphism will be a convenient and practical assay for clinical and research evaluation of 19q status in human gliomas.
Soluble Factors Released by Virus Specific Activated Cytotoxic T‐lymphocytes Induce Apoptotic Death of Astroglioma Cell Lines
Authors: Sabri Farideh , Chiodi Francesca , Piret Jean‐Pascal , Wei Cheng‐Hong , Major Eugene , Westermark Bengt , Masucci Maria G. , Levitsky Victor
Published: July 2010

Astrocytomas and astrogliomas represent the most common types of primary tumors in human central nervous system and are associated with high mortality due to the absence of efficient therapy. Here we demonstrate that, upon antigen‐specific activation, cytotoxic T‐lymphocytes (CTLs) secrete products that inhibit proliferation and induce apoptosis in a significant proportion of astroglioma cell lines. This effect is tumor specific in that normal cultured astrocytes do not develop apoptotic changes upon exposure to supernatant of activated CTLs. Experiments with purified lym‐phokines and lymphokine specific blocking antibodies indicate that synergistic activities of tumor necrosis factor (TNF)‐α and interferon (INF)‐γ are required for the apoptosis inducing effect on some astroglioma cell lines. However, this effect appears to be dependent on additional factors produced by activated CTLs. Our results suggest that local application of factors released by activated CTLs or induction of CTL migration and activation in the tumor site may have a therapeutic effect in patients with astrogliomas.