bluuebunny/crossref_metadata_2025 huggingface dataset:
Information Sharing in Food Supply Chains
Authors: Mohtadi Hamid
Published: July 2010

Information sharing among firms within many industries accounts for a substantial part of the gains from information technology adoption in these industries. In this paper we examine the determinants of information sharing between retailers and their suppliers, in the food industry supply chain. Using a data set known as the Super Market Panel Data gathered by the University of Minnesota's Food Industry Center, the behavior of food retailers is examined in their adoption of information sharing technologies that facilitate vertical exchange of information with suppliers. Evidence supports the hypothesis that retail firms with larger number of suppliers are more inclined to share, rather than to withhold, information. Prior theoretical work suggests that this happens because retail firms with large number of suppliers are less concerned about opportunistic behavior of suppliers from the misuse of retailer information by the supplier. We also find that self‐distribution chains are more inclined to share information. Finally, the structure of the market plays an interesting role in the type of information sharing platforms that the retailers adopt.

Dans de nombreux secteurs, l'échange d'information entre entreprises représente une part substantielle des gains issus de l'adoption des technologies de l'information. Dans le présent article, nous avons examiné les déterminants de l'échange d'information entre les détaillants de la chaîne d'approvisionnement alimentaire et leurs fournisseurs. À l'aide de l'ensemble de données Supermarket Panel Data, établi par le Food Industry Center de l'University of Minnesota, nous avons examiné le comportement des détaillants en alimentation quant à l'adoption des technologies d'échange d'information facilitant l'échange d'information vertical avec les fournisseurs. Les observations appuient l'hypothèse selon laquelle les détaillants qui comptent de nombreux fournisseurs sont plus disposés àéchanger qu’à retenir l'information. D'après des études théoriques antérieures, cette situation serait attribuable au fait que les détaillants qui comptent de nombreux fournisseurs sont moins préoccupés par le comportement opportuniste de fournisseurs qui utiliseraient de façon malveillante de l'information sur le détaillant. Nous avons également observé que les chaînes d'autodistribution étaient plus enclines àéchanger de l'information. Finalement, la structure du marché joue un rôle intéressant dans le type de plateformes d'échange d'information qu’adoptent les détaillants.
IDENTIFICATION OF BACTERIA FROM UNCOOKED ARK SHELLS BY USING SHERLOCK MICROBIAL IDENTIFICATION SYSTEM AND 16S rRNA SEQUENCE ANALYSIS
Authors: SU XIURONG , CHEN YAN , LIU BING , SONG YIYIN
Published: July 2010

Seven bacteria strains were isolated from fresh uncooked ark shells and were subsequently identified by their unique fatty acid profile using Sherlock Microbial Identification System (MIS). Identification with MIS followed the manufacturer's instruction except for 2.7% NaCl supplement in culture medium because these halophilic bacteria do not grow well on the standard trypticase soy broth agar medium. Results obtained from MIS were verified by 16S rRNA sequence analysis. Based on the sequence of 16S rRNA gene, SB1 was Vibrio alginolyticus, SB3 was Vibrio parahaemolyticus, SB2 was Pseudoalteromonas haloplanktis, AS1 was Vibrio furnissii, TG1 was Vibrio mediterranei, TG2 was Bacillus circulans, and TG3 was Pseudomonas fluorescens. The results obtained from 16S rRNA sequence analysis were consistent with those obtained from MIS. These results suggested that both methods can be applied for routine identification of bacteria isolated from fresh seafood to ensure that the consumption of uncooked ark shells is safe.

PRACTICAL APPLICATIONS

Uncooked seafood mainly includes fresh mollusks and processed products such as crab paste and Bullacta exarata. They are popular with lots of customers as they are not only delicious, but also rich in nutrients. However, it is a pity that bacteria were commonly found in uncooked seafood primarily because of its special edible way, uncooking. As a result of this, foodborne disease caused by uncooked seafood occurred frequently. In this article, the author did research on bacterial community in uncooked seafood to provide evidence for food safety and quality control.
The New Zealand Penguin Conservation Assessment and Management Plan: implications for conservation partnerships
Authors: ELLIS SUSIE
Published: July 2010

One of the processes recently introduced for assessing management of wild and captive populations is the Conservation Assessment and Management Plan. A CAMP workshop was held in August 1992 to develop a conservation strategy for 11 taxa of New Zealand penguins. Each taxon was reviewed to assess threats and to develop preliminary recommendations for research and management of wild and captive populations. In this paper emphasis is laid on the part which could be played by captive management, both in making space available for the most threatened taxa and in the use of captive propagation techniques to aid the recovery of species in the wild.
Black stork Ciconia nigra: management in Europe
Authors: KING CATHERINE E.
Published: July 2010

A Black stork Ciconia nigra management survey undertaken in 1993 indicated that several variables, including nest type, enclosure mates, cage dimensions, whether the cage is covered and flight status of the birds may be factors in reproductive success. Predation was the primary cause of mortality, with trauma and intraspecific killings also being major causes of death. Reproduction could probably be improved and mortality reduced by taking these factors into consideration when designing Black stork enclosures. A number of Black storks are held singly and are unsexed; sexing and pairing of birds would almost certainly also improve Black stork breeding success in Europe.
Breeding the Spix's macaw Cyanopsitta spixii: at Loro Parque, Tenerife
Authors: SILVA TONY
Published: July 2010

The Spix's macaw Cyanopsitta spixii is a monotypic bird endemic to north‐eastern Brazil. In the late 1980s only a single individual was known to survive in Brazil and the species was, for all practical purposes, extinct in the wild, although at that time there were at least 17 birds in captivity. In 1992 two chicks hatched at Loro Parque, Tenerife, and both were taken for hand‐rearing. This paper gives details on growth and development of one chick until weaning.
Management and early development of infant behaviour in the White‐crowned mangabey: Cercocebus torquatus lunulatus at the Paris Menagerie
Authors: SCHLEE MARSHA A. , LABEJOF LISE P.
Published: July 2010

Since 1973 the Paris Menagerie has maintained a group of White‐crowned mangabey Cercocebus torquatus lunulatus. Between 1977 and 1992 35 young were born and a number of these were hand‐ or mother‐reared successfully. Development of behaviour of a mother‐reared infant was observed and recorded over a three‐month period in 1989.
Triangular Contests and Caucus Rhetoric at the 1885 General Election*
Authors: OWEN JAMES
Published: July 2010

This article explores the role played by late‐Victorian political associations during parliamentary election campaigns. The central hypothesis is that party organisation, known popularly as the ‘caucus’, is best understood as a rhetorical device used by politicians and the press to gain legitimacy in the new context created by an expanded and quasi‐democratic electorate. The hypothesis is tested by examining the 1885 general election campaigns in Nottingham West and Sheffield Central. Both constituencies witnessed a triangular contest whereby an ‘additional’ candidate, standing on a radical platform, entered the campaign and pursued a distinctly ‘anti‐caucus’ agenda that was aimed primarily at the local Liberal Party Association. The manner in which the ‘caucus’ issue was articulated by all sides involved throws new light on the role played by party organisation during this period. While all sides described their association in a way that both defended and asserted its legitimacy, they equally used ‘anti‐caucus’ rhetoric to diminish the credibility of their opponent's organisation, even though they were emulating the deeds they were denouncing. Indeed, it was those within official Liberalism that indulged in the most virulent ‘anti‐caucus’ rhetoric. Thus, it is suggested that, with regard to the attitude of radicals towards official Liberalism, this ‘anti‐caucus’ rhetoric reflected not a real popular resistance against party organisation or ‘party’, but simply intense competition and imitation between rival ‘caucuses’.
A Pocket Borough? Reformed Politics in Ripon, 1832–67
Authors: MARKUS MICHAEL
Published: July 2010

This article examines the political history of the parliamentary borough of Ripon between the Great Reform Act of 1832 and the Second Reform Act of 1867. It challenges the notion that Ripon remained a ‘pocket borough’ during this era; rather, the Reform Act rendered Ripon's politics much more open, vibrant and participatory than they had been during the ‘unreformed’ era. In demonstrating this, the article calls into question the alleged prevalence of ‘pocket boroughs’ in the reformed era.
Identification of the End Stage of Scrapie Using Infected Neural Grafts
Authors: Brandner Sebastian , Isenmann Stefan , Kühne Guido , Aguzzi Adriano
Published: July 2010

Although the formal pathogenesis of spongiform encephalopathies has been described in detail, it is not known whether the infectious agent targets primarily neurons, glial cells, or both. To address this question, we have transplanted transgenic embryonic neural tissue overexpressing PrPc into the forebrain of Prnp ‐knockout mice, and infected it with scrapie prions. After infection, grafts developed severe spongiform encephalopathy. As the infected hosts were not clinically affected, we were able to prolong the experiment and to assess changes in the graft over periods of time, which vastly exceeded the normal life span of scrapie‐infected mice. Sequential contrast‐enhanced magnetic resonance imaging (MRI) revealed progressive impairment of blood‐brain barrier properties in infected grafts. However, loss of astrocytes was not observed. Subtotal neuronal loss occurred during the progression of the disease in the grafts, reactive astrocytes persisted until the terminal stage of disease. We conclude that scrapie encephalopathy primarily leads to neuronal death, while degeneration of astrocytes does not occur. Functional impairment of the blood‐brain barrier suggests involvement of astrocytes and endothelial cells in the pathological process.
Cellular Pathology of Lysosomal Storage Disorders
Authors: Walkley Steven U.
Published: July 2010

Lysosomal storage disorders are rare, inborn errors of metabolism characterized by intralysosomal accumulation of unmetabolized compounds. The brain is commonly a central focus of the disease process and children and animals affected by these disorders often exhibit progressively severe neurological abnormalities. Although most storage diseases result from loss of activity of a single enzyme responsible for a single catabolic step in a single organelle, the lysosome, the overall features of the resulting disease belies this simple beginning. These are enormously complex disorders with metabolic and functional consequences that go far beyond the lysosome and impact both soma‐dendritic and axonal domains of neurons in highly neuron type‐specific ways. Cellular pathological changes include growth of ectopic dendrites and new synaptic connections and formation of enlargements in axons far distant from the lysosomal defect. Other storage diseases exhibit neuron death, also occurring in a cell‐selective manner. The functional links between known molecular genetic and enzyme defects and changes in neuronal integrity remain largely unknown. Future studies on the biology of lysosomal storage diseases affecting the brain can be anticipated to provide insights not only into these pathogenic mechanisms, but also into the role of lysosomes and related organelles in normal neuron function.
Distribution of Brain HIV Load in AIDS
Authors: Wiley Clayton A. , Soontornniyomkij Virawudh , Radhakrishnan Lakshmi , Masliah Eliezer , Mellors John , Hermann Steve A. , Dailey Peter , Achim Cristian L.
Published: July 2010

Approximately one quarter of patients with AIDS develop severe cognitive deficits called HIV‐associated dementia complex (ADC). There is some controversy regarding the importance of viral load in mediating neurologic disease. With the advent of sensitive, quantitative and reproducible RNA assays for HIV load in plasma and CSF, we quantified viral load in brains from 10 autopsied HIV‐infected subjects and 2 non‐infected controls. The new quantitative HIV RNA assays showed general agreement with previously used semi‐quantitative immunocytochemical assessments of HIV envelope protein, and were performed without professional subjective interpretation. All cases with very high levels of HIV in the CSF, had high overall levels in the brain, suggesting that CSF viral loads exceeding 106 copies per mL may be a surrogate marker of high viral load in the brain. Levels of virus in the spleen showed no clear association with those found in the brain. HIV RNA was not uniformly distributed throughout the brain. Selective regions, including basal ganglia and hippocampus, showed higher levels of virus than the cerebellar cortex and mid‐frontal cortical gray matter. Assessment of overall brain viral load requires careful attention to regional quantitation.
Establishing a Pathological Diagnosis in Degenerative Dementias
Authors: Lowe James , FRCPath DM
Published: July 2010

While clinicopathological studies have confirmed that Alzheimer's disease (AD) is the most common neurodegenerative cause of dementia, these same studies have also revealed that other degenerative pathologies account for a significant proportion of patients with cognitive decline. Because pathological assessment of non‐Alzheimer neurodegenerative diseases now demands routine use of a costly panel of immunohistochemical techniques a scheme for staged examination of brain tissue has been developed. This scheme is weighted to initially screen out cases of Alzheimer's disease, dementia with Lewy bodies and vascular dementia using conventional staining methods and established diagnostic protocols, bringing in immunochemical techniques to discriminate between non‐Alzheimer degenerative dementias. Diagnosis of pathologies causing the clinical syndrome of frontotemporal dementia can be ascertained using conventional staining supplemented by immunochemical detection of ubiquitin, tau protein and α B crystallin. The diagnosis of prion disease is reliably confirmed by immunohistochemical detection of prion protein. This morphological assessment complements emerging genetic insights into many of these neurodegenerative diseases.
Molecular Pathology of Fatal Familial Insomnia
Authors: Parchi Piero , Petersen Robert B. , Chen Shu G. , Autilio‐Gambetti L. , Capellari Sabina , Monari Lucia , Cortelli Pietro , Montagna Pasquale , Lugaresi Elio , Gambetti Pierluigi
Published: July 2010

Fatal familial insomnia (FFI) is linked to a mutation at codon 178 of the prion protein gene, coupled with the methionine codon at position 129, the site of a methionine/valine polymorphism. The D178N mutation coupled with the 129 valine codon is linked to a subtype of Creutzfeldt‐Jakob disease (CJD178) with a different phenotype. Two protease resistant fragments of the pathogenic PrP (PrPres), which differ in molecular mass, are associated with FFI and CJD178, respectively, suggesting that the two PrPres have different conformations and hence they produce different disease phenotypes. FFI transmission experiments, which show that the endogenous PrPres recovered in affected syngenic mice specifically replicates the molecular mass of the FFI PrPres inoculated and is associated with a phenotype distinct from that of the CJD178 inoculated mice, support this idea. The second distinctive feature of the FFI PrPres is the underrepresentation of the unglycosylated PrPresform. Cell models indicate that the underrepresentation of this PrPres form results from the PrP dys‐metabolism caused by the D178N mutation and not from the preferential conversion of the glycosylated forms. Codon 129 on the normal allele further modifies the FFI phenotype determining patient subpopulations of 129 homozygotes and heterozygotes: disease duration is generally shorter, insomnia more severe and histopathology more restricted to the thalamus in the homozygotes than in the heterozygotes The allelic origin of PrPres fails to explain this finding since in both cases FFI PrPres is expressed only by the mutant allele. Despite remarkable advances, many issues remain unsolved precluding full understanding of the FFI pathogenesis.
Severe, Early and Selective Loss of a Subpopulation of GABAergic Inhibitory Neurons in Experimental Transmissible Spongiform Encephalopathies
Authors: Guentchev Marin , Groschup Martin H. , Kordek Radzislaw , Liberski Pawel P. , Budka Herbert
Published: July 2010

Little is known about the pathogenetic basis of characteristic symptoms in transmissible spongiform encephalopathies (TSEs) such as myoclonus and characteristic EEG hyperactivity. We investigated the GABAergic system and its subpopulations in mice inoculated with experimental scrapie (ME7, RML, 22A strains) and Creutzfeldt‐Jakob disease (CJD; Fujisaki strain), to study damage to inhibitory neurons. Since recent studies have shown electrophysiological changes in prion protein (PrP) knockout mice, we also studied mice lacking or overexpressing the PrP gene. Antibodies against glutamic acid decarboxylase (GAD), parvalbumin (PV), calbindin (CB), and calretinin (CR) were used to stain GABAergic neurons, and isolectin‐B4 to stain perineuronal nets around PV+ neurons. In scrapie infected mice, cortical PV+ neurons were severely reduced while CB+ and CR+ neurons were well preserved. In CJD inoculated mice, loss of PV+ neurons was severe and occurred very early after inoculation. PrP‐/‐ and tg20 mice showed normal appearance of PV, CB, CR, GAD+ neurons and their neuropil, and of isolectin‐B4+ perineuronal nets. The early, severe and selective loss of cortical PV+ neurons in experimental scrapie and CJD suggest selective loss of PV+ GABAergic neurons as important event during disease development, possibly as one basis of excitatory symptoms in TSEs.
HHV‐8/KSHV is Not Associated with AIDS‐Related Primary Central Nervous System Lymphoma
Authors: Antinori Andrea , Larocca Luigi M. , Fassone Lucia , Cattani Paola , Capello Daniela , Cingolani Antonella , Saglio Giuseppe , Fadda Giovanni , Gaidano Gianluca , Ortona Luigi
Published: July 2010

Primary central nervous system lymphoma (PCNSL) is a major complication of the late stages of human immunodeficiency virus (HIV) disease. Epstein Barr virus (EBV) infection is the only genetic lesion consistently associated with this neoplasia. Recently, it has been proposed that the pathogenesis of AIDS‐related PCNSL (AIDS‐PCNSL) may be associated with infection by human herpesvirus‐8/Kaposi's sarcoma associated herpesvirus (HHV‐8/KSHV), although at present such association remains controversial. In order to conclusively assess the link between HHV‐8/KSHV infection and AIDS‐PCNSL, we performed a comprehensive study based on multiple molecular assays on cerebral tissues and cerebrospinal fluid (CSF) as well as specific immunologic assays on patients’ sera. A well characterized panel of 33 Italian patients with AIDS‐PCNSL and 13 controls with other HIV‐related brain focal diseases from the same geographical area was analyzed. No signs of HHV‐8/KSHV infection were detected in cerebral tissues by single‐step PCR. Cerebral tissues of all AIDS‐PCNSL scored negative for HHV‐8/KSHV DNA sequences also by nested PCR, with the exception of one single patient who was simultaneously affected by Kaposi's sarcoma. All CSF samples analyzed were consistently devoid of HHV‐8/KSHV sequences by molecular assays. By serologic assays, detecting both latent and lytic HHV‐8/KSHV antigens, a specific immunoreactivity was observed in 16/33 (48%) AIDS‐PCNSL and in 6/13 (46%) controls (P=0.88). A significant correlation with HHV‐8/KSHV serum reactivity was seen with a homosexual route of HIV transmission (P=0.018), but not with the presence of AIDS‐PCNSL. The results of our analysis conclusively assess that HHV‐8/KSHV infection is not a feature of AIDS‐PCNSL.
Paraneoplastic Neurologic Syndromes: Pathogenesis and Physiopathology
Authors: Dalmau Josep , Gultekin Humayun S. , Posner Jerome B.
Published: July 2010

Since 1965 when the first paraneoplastic antineuronal antibody was reported by Wilkinson and Zeromski (55), the number of immunological responses detected in association with paraneoplastic syndromes of the nervous system has steadily increased. These responses are characterized by the presence of antineuronal antibodies in serum and CSF and/or infiltrates of T‐cells in the tumor and nervous system. A few syndromes are mediated by antibodies; they include those resulting from dysfunction of the neuromuscular junction at the pre‐ or post‐synaptic level (Lambert‐Eaton myasthenic syndrome, myasthenia gravis) or ion channel dysfunction in the peripheral nervous system (i.e, Voltage‐gated potassium channel and neuromyotonia). In most other paraneoplastic syndromes, including those involving the central nervous system, the pathogenic role of highly specific antineuronal antibodies (anti‐Hu, anti‐Yo, etc) has not been established; nevertheless these antibodies should be regarded as useful markers of specific paraneoplastic syndromes and tumors. Moreover, there is increasing evidence that in some of these syndromes T‐cell mediated mechanisms can cause the neurologic dysfunction and contribute to tumor rejection. Some paraneoplastic syndromes are caused by the tumor secretion of antibodies (macroglobulinemia and MAG antibodies), hormones, and cytokines. In other instances, the tumor may compete with the nervous system for an essential substrate (glucose, tryptophan) and result in neurologic dysfunction.
The Neurobiology of Schwann Cells
Authors: Mirsky Rhona , Jessen Kristjan R
Published: July 2010

This selective review of Schwann cell biology focuses on questions relating to the origins, development and differentiation of Schwann cells and the signals that control these processes. The importance of neuregulins and their receptors in controlling Schwann cell precursor survival and generation of Schwann cells, and the role of these molecules in Schwann cell biology is addressed. The reciprocal signalling between peripheral glial cells and neurons in development and adult life revealed in recent years is highlighted, and the profound change in survival regulation from neuron‐dependent Schwann cell precursors to adult Schwann cells that depend on autocrine survival signals is discussed. Besides providing neuronal and autocrine signals, Schwann cells signal to mesenchymal cells and influence the development of the connective tissue sheaths of peripheral nerves. The importance of Desert Hedgehog in this process is described. The control of gene expression during Schwann cell development and differentiation by transcription factors is reviewed. Knockout of Oct‐6 and Krox‐20 leads to delay or absence of myelination, and these results are related to morphological or physiological observations on knockout or mutation of myelin‐related genes. Finally, the relationship between selected extracellular matrix components, integrins and the cytoskeleton is explored and related to disease.
Neurotrophic Factors in Peripheral Neuropathies: Therapeutic Implications
Authors: Apfel Stuart C.
Published: July 2010

Neurotrophic factors are proteins which promote the survival of specific neuronal populations. Many have other physiological effects on neurons such as inducing morphological differentiation, enhancing nerve regeneration, stimulating neurotransmitter expression, and otherwise altering the physiological characteristics of neurons. These properties suggest that neurotrophic factors are highly promising as potential therapeutic agents for neurological disease.

Neurotrophic factors will most likely be applied to the peripheral nervous system initially, since there are fewer problems for large proteins to gain access to peripheral neurons. Many of the most intensively studied factors are active in the peripheral nervous system. These include the neurotrophins (nerve growth factor, brain derived neurotrophic factor, neu‐rotrophin‐3, neurotrophin‐4/5), the insulin like growth factors, ciliary neurotrophic factor, and glial cell derived neurotrophic factor and its related proteins. The biology of these factors and their receptors in the peripheral nervous system is reviewed here. We also review data suggesting that abnormal availability of some factors may contribute towards the pathogenesis of certain types of peripheral neuropathy. Finally, the pre‐clinical data suggesting that individual factors might be effective in treating neuropathy is reviewed, along with data relating to possible side effects of neurotrophic factor therapy. Several factors have already entered clinical trials with variable success. The data from these trials is reviewed as well
Characteristic Chromosomal Imbalances in Primary Central Nervous System Lymphomas of the Diffuse Large B‐Cell Type
Authors: Weber Tillmann , Weber Ruthild G. , Kaulich Kerstin , Actor Bertrand , Meyer‐Puttlitz Birgit , Lampel Stefan , Büschges Rainer , Weigel Ralf , Deckert‐Schlüter Martina , Schmiedek Peter , Reifenberger Guido , Lichter Peter
Published: July 2010

We performed a genome wide screening for genomic alterations on a series of 19 sporadic primary central nervous system lymphomas (PCNSL) of the diffuse large B‐cell type by comparative genomic hybridization (CGH). The tumors were additionally analyzed for amplification and rearrangement of the BCL2 gene at 18q21 as well as for mutation of the recently cloned BCL10 gene at 1p22. Eighteen tumors showed genomic imbalances on CGH analysis. On average, 2.1 losses and 4.7 gains were detected per tumor. The chromosome arm most frequently affected by losses of genomic material was 6q (47%) with a commonly deleted region mapping to 6q21‐q22. The most frequent gains involved chromosome arms 12q (63%), 18q and 22q (37% each), as well as 1q, 9q, 11q, 12p, 16p and 17q (26% each). High‐level amplifications were mapped to 9p23‐p24 (1 tumor) and to 18q21‐q23 (2 tumors). However, PCR‐based analysis, Southern blot analysis and high‐resolution matrix‐CGH of the BCL2 gene revealed neither evidence for amplification nor for genetic rearrangement. Mutational analysis of BCL10 in 16 PCNSL identified four distinct sequence polymorphisms but no mutation. Taken together, our data do not support a role of BCL2 rearrangement/ amplification and BCL10 mutation in PCNSL but indicate a number of novel chromosomal regions that likely carry yet unknown tumor suppressor genes or proto‐oncogenes involved in the pathogenesis of these tumors.
Diagnostic Protein Expression in Human Muscle Biopsies
Authors: Bornemann Antje , Anderson Louise V. B.
Published: July 2010

Using immunohistochemistry in diagnosing neuromuscular diseases is meant to enhance the diagnostic yield in two ways. The first application aims at visualizing molecules which are developmentally, neurally, and/or immunologically regulated and not expressed by normal muscle. They are upregulated in pathological conditions and may help assign a given muscular biopsy to one of the main diagnostic entities (muscular dystrophies, inflammatory myopathy, neurogenic atrophy). In the past, muscle‐specific molecules with a defined expression pattern during fetal myogenesis served as antigens, with the rationale that the developmental program was switched on in new fibers. Recently, myofibers in diseased muscle are thought of as targets of stimuli which are released by macrophages in muscular dystrophy, by lymphocytes in inflammatory myopathies, or by a lesioned peripheral nerve in neurogenic atrophies. This has somewhat blurred the borders between the diagnostic groups, for certain molecules, e.g. cytokines, may be upregulated after experimental necrotization, denervation, and also in inflammatory myopathies. In the second part of this review we summarise the experiences of a Centre in the North of England that specialises in the diagnosis and clinical support of patients with muscular dystrophy. Emphasis is placed on the use of protein expression to guide mutation analysis, particularly in the limb‐girdle muscular dystrophies (a group of diseases that are very difficult to differentiate on clinical grounds alone). We confirm that genetic analysis is essential to corroborate the results of protein analysis in certain conditions (particularly in calpainopathy). However, we conclude that analysing biopsies for abnormal protein expression is very useful in aiding the decision between alternative diagnoses.
Northern Epilepsy: A Novel Form of Neuronal Ceroid‐Lipofuscinosis
Authors: Herva Riitta , Tyynelä Jaana , Hirvasniemi Aune , Syrjäkallio‐Ylitalo Marja , Haltia Matti
Published: July 2010

Northern epilepsy is an autosomal recessive childhood onset epilepsy syndrome, clinically characterized by generalized tonic‐clonic seizures with onset at 5 to 10 years of age and subsequent slowly progressive mental deterioration. The patients may reach 50 or 60 years of age. A mutation responsible for the disease has recently been identified in a novel gene on chromosome 8p23, encoding a putative membrane protein with an unknown function. The present study, based on three autopsied patients, is the first neuropathological analysis of the disease, and showed intraneuronal accumulation of cytoplasmic autofluorescent granules. The granules were strongly stained by the Luxol fast blue, periodic acid‐Schiff, and Sudan black B methods in paraffin sections, and were immunoreactive for subunit c of the mitochondrial ATP synthase and sphingolipid activator proteins A and D. The intraneuronal storage was highly selective: the third layer of the isocortex and the hippocampal CA2, CA3, and CA4 sectors were severely affected, while other layers of the isocortex, the CA1 sector, and the cerebellar cortex were only minimally involved. The membrane‐bound storage cytosomes showed a curvilinear ultrastructure with admixture of some granular components. Western blotting and N‐terminal sequence analysis of purified storage material identified subunit c as the major component. These findings establish Northern epilepsy as a new form of neuronal ceroid‐lipofuscinosis with an exceptionally protracted course.
Bag‐1 and Bcl‐2 Gene Transfer in Malignant Glioma: Modulation of Cell Cycle Regulation and Apoptosis
Authors: Roth Wilfried , Grimmel Cornelia , Rieger Lorenz , Strik Herwig , Takayama Shinichi , Krajewski Stanislaw , Meyermann Richard , Dichgans Johannes , Reed John C. , Weller Michael
Published: July 2010

Bag‐1 is a heat shock 70 kDa (Hsp70)‐binding protein that can collaborate with Bcl‐2 in suppressing apoptosis under some conditions. Here, we report that 11 of 12 human glioma cell lines express Bag‐1 protein in vitro. Moreover, 15 of 19 human glioblastomas expressed Bag‐1 as assessed by immunohistochemistry in primary tumor specimens. To examine the biological effects of Bag‐1 in glioma cells, we expressed Bag‐1 or Bcl‐2 transgenes in 2 human malignant glioma cell lines, LN‐18 and LN‐229. Bag‐1 significantly slowed glioma cell growth and reduced clonogenicity of both cell lines in vitro. Coexpressed Bcl‐2 abrogated these effects of Bag‐1. Intracranial LN‐229 glioma xenografts implanted into nude mice revealed a substantial growth advantage afforded by Bcl‐2. Bag‐1 had no such effect, either in the absence or presence of Bcl‐2. Upon serum starvation in vitro, Bcl‐2 prevented cell death whereas Bag‐1 did not. Both Bcl‐2 and Bag‐1 slowed proliferation of serum‐starved cells when expressed alone. Importantly, coexpression of Bcl‐2 and Bag‐1 provided a distinct growth advantage under conditions of serum starvation that is probably the result of (i) the death‐preventing activity of Bcl‐2 and (ii) the property of Bag‐1 to overcome a Bcl‐2‐mediated enhancement of exit from the cell cycle. In contrast to these Bcl‐2/Bag‐1 interactions observed under serum starvation conditions, Bag‐1 did not further enhance the strong protection from staurosporine‐, CD95 (Fas/Apo1) ligand‐, Apo2 ligand (TRAIL)‐ or chemotherapeutic drug‐induced apoptosis afforded by Bcl‐2. Taken together, these results indicate a role for Bag‐1/Bcl‐2 interactions in providing a survival advantage to cancer cells in a deprived microenvironment that may be characteristic of ischemic/hypoxic tumors such as human glioblastoma multiforme, and suggest that Bcl‐2/Bag‐1 interactions also modulate cell proliferation.
Astroblastoma: Clinicopathologic Features and Chromosomal Abnormalities Defined by Comparative Genomic Hybridization
Authors: Brat Daniel J. , Hirose Yuichi , Cohen Kenneth J. , Feuerstein Burt G. , Burger Peter C.
Published: July 2010

Astroblastomas are uncommon brain tumors whose classification and histogenesis have been debated. Precise criteria for diagnosis have been described only recently, but have not found wide acceptance. We report the clinical, radiographic, and histopathologic features of 20 astroblastomas, and the chromosomal alterations in seven cases as detected by comparative genomic hybridization (CGH). The tumors occurred both in children and young adults (average age, 14 years), most often as well circumscribed, peripheral, cerebral hemispheric masses. Radiographically, the lesions were contrastenhancing and solid, often with a cystic component. All were characterized histologically by astroblastic pseudorosettes, and most displayed prominent perivascular hyalinization, regional hyaline changes, and pushing borders in regard to adjacent brain. Tumor cells were strongly immunoreactive for S‐100 protein, GFAP, and vimentin. Staining for EMA was focal. Ten of 20 astroblastomas were classified as “well differentiated” and 10 were classified as “malignant,” largely on the basis of hypercellular zones with increased mitotic indices, vascular proliferation, and necrosis with pseudopalisading. All 10 well differentiated lesions and 8 of 10 malignant lesions were completely resected. None of the well differentiated astroblastomas recurred within the limited follow‐up period. Three malignant astroblastomas recurred, including two incompletely resected tumors, and one that had been totally resected. One patient died of disease following recurrence. The most frequent chromosomal alterations detected by CGH were gains of chromosome arm 20q (4/7 tumors) and chromosome 19 (3/7). The combination of these gains occurred in three, including two well differentiated and one malignant astroblastoma. Other alterations noted in two tumors each were losses on 9q, 10, and X. These chromosomal alterations are not typical of ependymoma or infiltrating astrocytic neoplasms, and suggest that astroblastomas may have a characteristic cytogenetic profile in addition to their distinctive clinical, radiographic, and histopathologic features.
Lewy Bodies in Alzheimer's Disease: A Neuropathological Review of 145 Cases Using α‐Synuclein Immunohistochemistry
Authors: Hamilton Ronald L.
Published: July 2010

Antibodies to α‐synuclein (AS) now provide a sensitive and specific method for the detection of Lewy bodies (LBs) and their use will allow a more accurate determination of the prevalence of LBs in Alzheimer's Disease (AD). Studies using AS immunohistochemistry (IHC) have found LBs in the amygdala of over 60% early onset familial AD and in 50% of Down's syndrome patients with AD, however, no studies have reported the use of AS IHC to detect LBs in a large cohort of sporadic AD. This study examined 145 sporadic AD cases diagnosed using CERAD criteria from 1995–1999 for the presence of LBs using AS IHC. AS IHC detected LBs in 88/145 (60.7%) of sporadic AD cases. Similarly, LBs were found in 56.8% of the 95 cases fulfilling the more stringent NIA‐RI criteria for the diagnosis of AD (Braak stage 5–6). In all cases with LBs, the amygdala was involved and LBs were always most numerous in this area, however, in some cases LBs in the substantia nigra were rare or not present. In conclusion, this study found that AS IHC detects LBs in the majority of sporadic AD cases and that the amygdala is the most commonly affected region.
Antibody Association with a Novel Model for Primary Progressive Multiple Sclerosis: Induction of Relapsing‐Remitting and Progressive Forms of EAE in H2S Mouse Strains
Authors: Tsunoda Ikuo , Kuang Li‐Qing , Theil Diethilde J. , Fujinami Robert S.
Published: July 2010

Multiple sclerosis (MS) can be divided into 4 clinical forms: relapsing‐remitting (RR), primary progressive (PP), secondary progressive (SP), and progressive relapsing (PR). Since PP‐MS is notably different from the other forms of MS, both clinically and pathologically, the question arises whether PP‐MS is immunologically similar to the other forms. The pathogenesis of the PP‐MS remains unclear, partly due to a lack of highly relevant animal models. Using an encephalitogenic peptide from myelin oligodendrocyte glycoprotein (MOG)92–106, we have established animal models that mimic different forms of MS in 2 strains of H‐2s mice, SJL/J and A.SW. We induced experimental allergic encephalomyelitis (EAE) using MOG92‐106 in the presence or absence of supplemental Bordetella pertussis (BP). Although, SJL/J mice developed RR‐EAE whether BP was given or not, A.SW mice developed PP‐EAE without BP and SP‐EAE with BP. Histologically, SJL/J mice developed mild demyelinating disease with T cell infiltration, while A.SW mice developed large areas of plaque‐like demyelination with immunoglobulin deposition and neutrophil infiltration, but with minimal T cell infiltration. In A.SW mice without BP, high titer serum anti‐MOG antibody was detected and the anti‐MOG IgG2a/IgG1 ratio correlated with survival times of mice. We hypothesized that, in A.SW mice, a Th2 response favors production of myelinotoxic antibodies, leading to progressive forms with early death. Our new models indicate that a single encephalitogen could induce either RR‐, PP‐, or SP‐ forms of demyelinating disease in hosts with immunologically different humoral immune responses.
The Role of Mitochondria in the Pathogenesis of Neurodegenerative Diseases
Authors: Manfredim Giovanni , Beal M. Flint
Published: July 2010

A growing body of evidence indicates that mitochondrial dysfunction may play an important role in the pathogenesis of many neurodegenerative disorders. Because mitochondrial metabolism is not only the principal source of high energy intermediates, but also of free radicals, it has been suggested that inherited or acquired mitochondrial defects could be the cause of neuronal degeneration as a consequence of energy defects and oxidative damage. Mitochondrial respiratory chain dysfunction has been reported in association with primary mitochondrial DNA abnormalities, and also as a consequence of mutations in nuclear genes directly involved in mitochondrial functions, such as SURF1, frataxin, and paraplegin.

Defects of oxidative phosphorylation and increased free radical production have also been observed in diseases that are not due to primary mitochondrial abnormalities. In these cases, the mitochondrial dysfunction is likely to be an epiphenomenon, which, nevertheless, could be of importance in precipitating a cascade of events leading to cell death. In either case, understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could be important for the development of therapeutic strategies in these disorders.
Galectins Are Differentially Expressed in Supratentorial Pilocytic Astrocytomas, Astrocytomas, Anaplastic Astrocytomas and Glioblastomas, and Significantly Modulate Tumor Astrocyte Migration
Authors: Camby Isabelle , Belot Nathalie , Rorive Sandrine , Lefranc Florence , Maurage Claude‐Alain , Lahm Harald , Kaltner Herbert , Hadari Yaron , Ruchoux Marie‐Magdeleine , Brotchi Jacques , Zick Ehiel , Salmon Isabelle , Gabius Hans‐Joachim , Kiss Robert
Published: July 2010

Galectins, a family of mammalian lectins with specificity to β‐galactosides, are involved in growth‐regulatory mechanisms and cell adhesion. A relationship is assumed to exist between the levels of expression of galectins and the level of malignancy in human gliomas. A comparative study of this aspect in the same series of clinical samples is required to prove this hypothesis. Using computer‐assisted microscopy, we quantitatively characterized by immunohistochemistry the levels of expression of galectins‐1, ‐3 and‐8 in 116 human astrocytic tumors of grades I to IV. Extent of transcription of galectins‐1, ‐3, and ‐8 genes was investigated in 8 human glioblastoma cell lines by means of RT‐PCR techniques. Three of these cell lines were grafted into the brains of nude mice in order to characterize in vivo the galectins‐1, ‐3 and ‐8 expression in relation to the patterns of the tumor invasion of the brain. The role of galectin‐1, ‐3 and ‐8 in tumor astrocyte migration was quantitatively determined in vitro by means of computer‐assisted phase‐contrast videomicroscopy. The data indicate that the levels of galectin‐1 and galectin‐3 expression significantly change during the progression of malignancy in human astrocytic tumors, while that of galectin‐8 remains unchanged. These three galectins are involved in tumor astrocyte invasion of the brain parenchyma since their levels of expression are higher in the invasive parts of xenografted glioblastomas than in their less invasive parts. Galectin‐3, galectin‐1, and to a lesser extent galectin‐8, markedly stimulate glioblastoma cell migration in vitro. Since bands for the transcripts of human galectins‐2, ‐4 and ‐9 were apparently less frequent and intense in the 8 human glioblastoma cell lines, this system provides an excellent model to assign defined roles to individual galectins and delineate overlapping and distinct functional aspects.
Clonal Analysis in Glioblastoma with Epithelial Differentiation
Authors: Mueller Wolf , Lass Ulrike , Herms Jochen , Kuchelmeister Klaus , Bergmann Markus , von Deimling Andreas
Published: July 2010

Epithelial differentiation in glioblastomas (GBM) may be associated with circumscribed growth and focal keratin expression resembling carcinoma metastasis. Therefore these rare lesions can pose a diagnostic problem suggesting coincidental occurrence of two separate neoplasms. However molecular analysis should succeed in establishing a common origin of seemingly unrelated tumor samples. Five GBMs exhibiting epithelial differentiation were microdissected and analyzed for mutations in the TP53 gene. SSCP analysis of exons 5–8 was followed by direct sequencing of aberrantly migrating fragments. TP53 mutations were identified in tumors from two of five patients. A G → T transversion in codon 176 was detected in a tumor, initially diagnosed as metastases of unknown origin, however, a later autopsy revealed GBM. In this lesion, the mutation was observed in both, areas of astrocytic differentiation and areas of epithelial differentiation. One tumor diagnosed as GBM with epithelial differentiation carried C→T transition in codon 211 in both, areas of astrocytic and epithelial differentiation. Thus, molecular analysis proved clonality in two GBMs with epithelial differentiation, thereby excluding a collision tumor. The present data support the concept of clonal origin of these morphologically heterogeneous lesions.
Human Herpesvirus Latency
Authors: Cohrs Randall J. , Gilden Donald H.
Published: July 2010

Herpesviruses are among the most successful human pathogens. In healthy individuals, primary infection is most often inapparent. After primary infection, the virus becomes latent in ganglia or blood mononuclear cells. Three major subfamilies of herpesviruses have been identified based on similar growth characteristics, genomic structure, and tissue predilection. Each herpesvirus has evolved its own unique ecological niche within the host that allows the maintenance of latency over the life of the individual (e.g. the adaptation to specific cell types in establishing latent infection and the mechanisms, including expression of different sets of genes, by which the virus remains latent). Neurotropic alpha‐herpesviruses become latent in dorsal root ganglia and reactivate to produce epidermal ulceration, either localized (herpes simplex types 1 and 2) or spread over several dermatomes (varicalla‐zoster virus). Human cytomegalovirus, the prototype beta‐herpesvirus, establishes latency in bone marrow‐derived myeloid progenitor cells. Reactivation of latent virus is especially serious in transplant recipients and AIDS patients. Lymphotropic gammaher‐pesviruses (Epstein‐Barr virus) reside latent in resting B cells and reactivate to produce various neurologic complications. This review highlights the alphaherpesvirus, specifically herpes simplex virus type 1 and varicella‐zoster virus, and describes the characteristics of latent infection.
The Clinical Course of Experimental Autoimmune Encephalomyelitis is Associated with a Profound and Sustained Transcriptional Activation of the Genes Encoding Toll‐like Receptor 2 and CD14 in the Mouse CNS
Authors: Zekki Hakima , Feinstein Douglas L. , Rivest Serge
Published: July 2010

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune demyelinating disease commonly used to model the pathogenetic mechanisms involved in multiple sclerosis (MS). In this study, we examined the effects of immunization with the myelin oligodendrocyte glycoprotein MOG35–55 on the expression of molecules of the innate immune system, namely toll‐like receptor 2 (TLR2) and CD14. Expression of the mRNA encoding TLR2 increased in the choroid plexus, the leptomeninges and within few isolated cells in the CNS parenchyma 4 to 8 days after immunization with MOG. At day 10, the signal spread across the meninges, few perivas‐cular regions and over isolated groups of parenchy‐mal cells. Three weeks after the MOG treatment, at which time animals showed severe clinical symptoms, a robust expression of both TLR2 and CD14 transcripts occurred in barrier‐associated structures, as well as parenchymal elements of the spinal cord, and within numerous regions of the brain including, the medulla, cerebellum and the cortex. Dual labeling provided the anatomical evidence that microglia/macrophages were positive for TLR2 in the brain of EAE mice. The regions that exhibited chronic expression of TLR2 and CD14 were also associated with an increase in NF‐KB activity and transcriptional activation of genes encoding numerous proinflammatory molecules. The present data provide evidence that receptors of the pathogen‐associated molecular patterns are strongly induced in the CNS of EAE mice, further reinforcing the concept that the innate immune system plays a determinant role in this autoimmune demyelinating disease.