bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential mechanisms contributing to sulfatide depletion at the earliest clinically recognizable stage of Alzheimer’s disease: a tale of shotgun lipidomics
Authors: Han Xianlin 
Published: November 2007

AbstractShotgun lipidomics is a rapidly developing technology, which identifies and quantifies individual lipid molecular species directly from lipid extracts of biological samples. Alterations in lipid molecular species in the brain induced by neurodegenerative diseases, such as Alzheimer’s disease (AD) could provide fundamental clues to disease pathogenesis. To date, the cause(s) leading to AD pathogenesis are still unknown and apolipoprotein E (apoE) allele 4 is the only known major risk factor for this devastating disease. By utilizing shotgun lipidomics, we have recently shown that a substantial and specific depletion of sulfatide (a class of specialized myelin sphingolipids) is present in postmortem brains from subjects at the earliest clinically recognizable stage of AD. In subsequent studies to identify the biochemical mechanisms underlying sulfatide depletion at this very mild stage of AD, we have found that apoE is associated with sulfatide transport and mediates sulfatide homeostasis in the nervous system through lipoprotein metabolism pathways and that alterations in apoE‐mediated sulfatide trafficking can lead to sulfatide depletion in the brain. Thus, a working model related to the potential biochemical mechanisms underlying sulfatide depletion in AD can be derived based on these results. Collectively, the results obtained from lipidomic analyses of brain samples provide important insights into the biochemical mechanisms underlying AD pathogenesis.
Regulation of axonal development by plasma membrane gangliosides
Authors: Abad‐Rodriguez José , Robotti Andrea 
Published: November 2007

AbstractGangliosides present in the plasma membrane participate in fundamental processes during neuronal development. From the determination and the outgrowth of the axon, to the growth inhibitory activity produced after CNS injury, local interconversion of these glycosphingolipids regulate actin dynamics in a spatially restricted manner by modulating membrane receptors and their downstream signaling pathways. Here, we will review the possible mechanisms underlying these modulations and the potential importance of gangliosides and ganglioside‐transforming enzymes as therapeutic targets.
Alzheimer’s disease: the lipid connection
Authors: Hartmann Tobias , Kuchenbecker Johannna , Grimm Marcus O. W. 
Published: November 2007

AbstractAlzheimer’s disease is the most common neurodegenerative disorder. This short review summarizes the current knowledge about the role of lipids, especially cholesterol, sphingolipids, plasmalogens, and polyunsaturated fatty acids in Alzheimer’s disease etiology, pathogenesis, risk‐factors, prevention, treatment, and the function of the amyloid precursor protein and the amyloid peptides in lipid homeostasis.
Dissecting polysialic acid and NCAM functions in brain development
Authors: Hildebrandt Herbert , Mühlenhoff Martina , Weinhold Birgit , Gerardy‐Schahn Rita 
Published: November 2007

AbstractThe unique modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is tightly associated with nervous system development and plasticity. The prevailing view that this large carbohydrate polymer acts as an anti‐adhesive factor seems straightforward at first sight. However, during almost 25 years of polySia research it became increasingly clear that the impact of polySia on cell surface interactions can not be explained by one unifying mechanism. Recent progress in the generation of mouse models, which partially or completely lack polySia due to ablation of one or both of the two polySia synthesizing enzymes, provides novel insights into the function of this unique post‐translational modification. The present review is focused on a phenotype comparison between the newly established mouse strains which combine polySia‐deficiency with normal NCAM expression and the well‐characterized NCAM negative mouse model. Analysis of shared and individual phenotypes allows a clear distinction between NCAM and polySia functions and revealed that polySia plays a vital role as a specific control element of NCAM‐mediated interactions.
Glycosylation of glycolipids in the Golgi complex
Authors: Maccioni Hugo J. F. 
Published: November 2007

AbstractGangliosides are a family of glycolipids characterized by containing a variable number of sialic acid residues. Nearly, all animal cells contain at least some class of ganglioside in their membranes, but membranes from the CNS are characterized by their high content of these lipids. The synthesis of the oligosaccharide moiety of glycolipids is carried out in the Golgi complex. In this study, I will discuss the cellular and molecular basis of the organization of the glycosylating machinery in the Golgi complex, with particular attention to the mutual relationships, sub‐Golgi localization, and intracellular trafficking of glycolipid glycosyltransferases, and to their relationships with the corresponding glycolipid acceptors and sugar nucleotide donors. I will also discuss how the organization of the glycosylating machinery in the Golgi may adapt to events controlling glycolipid expression.
Gangliosides as targets for autoimmune injury to the nervous system
Authors: Willison Hugh J. 
Published: November 2007

AbstractImmune responses directed towards gangliosides and their microbial mimics are important mediators of several subtypes of acute post‐infectious autoimmune neuropathy, collectively referred to as the Guillain–Barré syndromes. In this diverse group of paralytic syndromes, the immunopathology is in a proportion of cases characterised by anti‐ganglioside antibody deposits, accompanied by inflammatory destruction of both axonal and glial components within the PNS. By gaining an understanding of the immunological mechanisms underlying these pathological pathways, it should be possible to select the correct targets for therapeutic intervention. Recent years has seen particular progress in our understanding of the basis for, and immunological consequences of molecular mimicry between gangliosides and microbial glycans, the relationships between ganglioside antibody specificity and different clinical phenotypes of GBS, the pathological basis for antibody‐mediated nerve injury and the testing of intervention strategies in pre‐clinical models. The focus of this mini‐review is to provide a brief background to this field, summarise a selection of recent highlights focused on our own research, identify areas of outstanding knowledge and present data that supports novel therapeutic approaches based on the latest experimental findings.
Lipid raft heterogeneity: an enigma
Authors: Mishra Sudha , Joshi Preeti G. 
Published: November 2007

AbstractGlycosphingolipids (GSLs) and glycoproteins are ubiquitous components of mammalian cell membranes. GSLs are especially enriched in the nervous system and significantly contribute to membrane organization and a variety of cellular functions. Current body of evidence suggests that GSLs along with cholesterol are enriched in discrete membrane domains that associate specific proteins. Current notion of membrane organization is that, the GSL–cholesterol‐enriched membrane domains known as ‘lipid rafts’ float in the phospholipid‐enriched bulk of the membrane and regulate the cell signaling by facilitating the lipid–protein/protein–protein interactions. The sizeable literature accumulated during the last decade has provided some insight into the organization and function of rafts; however, they still remain perplexing. In recent years, an appealing concept of lipid raft heterogeneity has emerged. GSL‐ and glycosylphosphatidylinositol‐anchored proteins are considered as the crucial pivots of heterogeneous rafts. This review deals with the enigma of organizational and functional heterogeneity of lipid rafts and discusses the dynamic coalescence of heterogeneous rafts during signaling that can explain the specificity of raft‐regulated cellular signaling events.
GM1 in the nuclear envelope regulates nuclear calcium through association with a nuclear sodium‐calcium exchanger
Authors: Ledeen Robert , Wu Gusheng 
Published: November 2007

AbstractThe inner membrane of the nuclear envelope (NE) of neurons and other cells has been shown to contain GM1 tightly associated with a Na+/Ca2+ exchanger (NCX) whose activity it potentiates in mediating transfer of Ca2+ from nucleoplasm to the NE lumen. This is consistent with localization of the NCX/GM1 complex in the inner membrane of the NE. NCXs of the plasma membrane, in contrast, appear to bind GM1 much less avidly. This is believed due to different isoforms of NCX in the two membranes, and a difference in topology of NCX relative to GM1. A cytoprotective function for nuclear NCX/GM1 was suggested in the observation that cultured neurons from mice lacking GM1 (GM2/GD2 synthase knockout) were vulnerable to Ca2+‐induced apoptosis. These neurons in culture were rescued to some extent by GM1 but more effectively by LIGA‐20, a membrane‐permeant derivative of GM1 that entered the NE. Further indication came from a study of the mutant mice, which were highly susceptible to kainate‐induced seizures and could be rescued by LIGA‐20. This correlated with the ability of LIGA‐20 to cross the blood–brain barrier, enter brain cells, insert into the NE, and potentiate nuclear NCX.
Metalloproteases and γ‐secretase: new membrane partners regulating p75 neurotrophin receptor signaling?
Authors: Bronfman Francisca C. 
Published: November 2007

AbstractSignaling by the p75 neurotrophin receptor (p75) has been implicated in diverse neuronal responses, including the control of neuronal survival versus death and axonal regeneration and growth cone collapse, involving p75 in different neuropathological conditions. There are different levels of complexity regulating p75‐mediated signaling. First, p75 can interact with different ligands and co‐receptors in the plasma membrane, forming tripartite complexes, whose activation result in different cellular outcomes. Moreover, it was recently described that trafficking capacities of p75 in neurons are regulating, in addition to p75 downstream interactions, also the sequential cleavage of p75. The proteolytical processing of p75 involves, first, a shedding event that releases a membrane‐bound carboxiterminal fragment (p75‐CTF), followed by a γ‐secretase mediated cleavage, generating a soluble intracellular domain (p75‐ICD) with signaling capabilities. The first shedding event, generating a p75‐CTF, is the key step to regulating the production of p75‐ICD, and although the generation of p75‐ICD is important for both p75‐mediated control of neuronal survival and the control of neurite outgrowth, little is known how both cleavage events are regulated. In this review, we argue that both sheddases and γ‐secretase are key membrane components regulating p75‐mediated signaling transduction; therefore, further attention should be paid to their roles as p75 signaling regulators.
Lactosylceramide: a lipid second messenger in neuroinflammatory disease
Authors: Won Je‐Seong , Singh Avtar K. , Singh Inderjit 
Published: November 2007

AbstractInflammatory disease plays a critical role in the pathogenesis of many neurological disorders. Astrogliosis and induction of pro‐inflammatory mediators such as chemokines, cytokines and inducible nitric oxide synthase (iNOS) are the ‘hallmarks’ of inflammatory disease. Increased activity of lactosylceramide (LacCer) synthase and increased synthesis of LacCer during glial proliferation, and induction of pro‐inflammatory cytokines and iNOS suggests a role for LacCer in these cellular signaling pathways. Studies using complementary techniques of inhibitors and antisense reported that inhibition of LacCer synthesis inhibits glial proliferation, as well as the induction of pro‐inflammatory mediators (cytokines and iNOS). This inhibition was bypassed by exogenous LacCer, but not by other related lipids (e.g. glucosylceramide, galactocerebroside, GD1, GM1), indicating a role for LacCer in inflammatory signaling pathways. Furthermore, inhibition of glial proliferation and induction of inflammatory mediators by antisense to Ras GTPase, PI3Kinase and inhibitors of mitogen‐activated protein kinase indicate the participation of the phosphoinositide 3‐kinase (PI3Kinas)/Ras/mitogen‐activated protein kinase/nuclear factor‐κB (NF‐κB) signaling pathways in LacCer‐mediated inflammatory events thus exposing additional targets for therapeutics for inflammatory disease conditions.
The N‐glycan profile of mouse myelin, a specialized central nervous system membrane
Authors: Ishii Akihiro , Ikenaka Kazuhiro , Pfeiffer Steven E. 
Published: November 2007

AbstractUnderstanding the rich complement of sugar chains found in cellular membranes is impeded by the complexity of cell types and membrane diversity. To overcome this, we have analyzed the N‐linked sugar chain composition of the glycoproteins of CNS myelin, an elaboration of the plasma membranes of oligodendrocytes (OLs) that result in a multilamellar wrapping of neuronal axons, facilitating nerve conduction with dramatic savings of space and energy. Due to an usually high lipid to protein ratio, myelin can be separated readily from other heavier membranes on sucrose gradients and further fractionated into subdomains related to myelin structure and function, including compact myelin and myelin‐associated axolemmal membrane (Menon et al. 2003). We analyzed these fractions for N‐linked sugar chains, using 2D HPLC following hydrazinolysis and pyridylamination. Our results indicate that compared with total brain homogenate, the amount of N‐glycans is 1.3‐fold higher in the myelin‐associated axolemmal membranes, but it is 0.5‐fold less in CM. M5 [Manα1–3((Manα1–3)(Manα1–6)Manα1–6)Manβ1–4GlcNAcβ1–4GlcNAc] is the most abundant sugar chain in total brain homogenate, compact myelin, and myelin‐associated axolemma, constituting ∼20% of sugar chains. Although the types of sugar chains are similar among the fractions, their expression levels vary significantly. In addition to high mannose type oligosaccharides, the core fucosylated, biantennary N‐glycans with bisecting N‐acetylglucosamine (GlcNAc) residue, A2G1(3)FB [Galβ1–4GlcNAcβ1–2Manα1–3(GlcNAcβ1–2Manα1–6)(GlcNAcβ1–4)Manβ1–4GlcNAcβ1–4(Fucα1–6)GlcNAc], A2G1(6)FB [GlcNAcβ1–2Manα1–3(Galβ1–4GlcNAcβ1–2Manα1–6)(GlcNAcβ1–4)Manβ1–4GlcNAcβ1–4 (Fucα1–6)GlcNAc] and BA‐1 [Manα1–3(GlcNAcβ1–2Manα1–6)(GlcNAcβ1–4)Manβ1–4GlcNAcβ1–4(Fucα1–6)GlcNAc], and A1(6)G0F [Manα1–3(GlcNAcβ1–2Manα1–6)Manβ1–4GlcNAcβ1–4(Fucα1–6) GlcNAc] are also present in relatively large proportions in compact myelin. We suggest that these differences may be related to myelin‐axolemmal function.
Isolation and characterization of 12 dinucleotide microsatellite loci in the anadromous fish Osmerus eperlanus (L.)
Authors: TAYLOR A. N. , TAYLOR M. I. , MCCARTHY I. D. , BEAUMONT A. R. 
Published: November 2007

AbstractA subtractive hybridization method was used to isolate 12 dinucleotide microsatellite loci for the anadromous European smelt, Osmerus eperlanus (L.). Three to 17 (mean 8.08) alleles per locus were identified in the two populations screened, and observed heterozygosity ranged from 0.067 to 0.933. Loci in both populations showed significant deviations from Hardy–Weinberg expected frequencies. These 12 loci provide a good basis for investigation of O. eperlanus population structure.
Highly polymorphic microsatellite loci for the Gran Canarian skink (Chalcides sexlineatus) and their applicability in other Canarian Chalcides
Authors: SUÁREZ N. M. , BLOOR P. , BROWN R. P. , PESTANO J. 
Published: November 2007

AbstractThe scincid lizard Chalcides sexlineatus is endemic to the island of Gran Canaria, within which it shows a pronounced phylogeographical pattern. Understanding the maintenance of this pattern requires knowledge of nuclear DNA structuring. Eleven polymorphic tetranucleotide microsatellite loci were isolated from a library constructed from genomic DNA enriched for AAAG repeat sequence. The number of alleles per locus ranged from 12 to 19, and expected heterozygosities spanned from 0.738 to 0.933 (n = 30). The majority of these could be cross‐amplified in other endemic Canarian Chalcides. The loci will be used to investigate gene flow between the principal mitochondrial clades within C. sexlineatus.
ON THE INFORMATIONAL EFFECT OF SHORT‐SALES CONSTRAINTS: EVIDENCE FROM THE TOKYO STOCK EXCHANGE
Authors: Isaka Naoto 
Published: November 2007

AbstractUsing a database of stock lending fees for Japanese centralized margin transactions, I show that short‐sales constraints reduce the adjustment speed of stock prices to negative information before the announcements of revised earnings forecasts disclosed by firms in the Tokyo Stock Exchange from July 1998 to December 2001. I find that the cumulative abnormal returns (CARs) of the stocks with high short‐sales costs are insensitive to negative information on pre‐announcement days, but the CARs of these stocks become significantly lower than the CARs of the stocks with low short‐sales costs when the announcements reveal negative information to the public.
FURTHER EVIDENCE ON INSIDER TRADING AND THE MERITS OF SECURITIES CLASS ACTIONS
Authors: Iqbal Zahid , Shetty Shekar , Wang Kun 
Published: November 2007

AbstractTo provide further evidence on the merits of securities class actions, we examine insider transactions immediately before and during the class period, using a larger and newer data set. We show that insiders reduce their stock sales by an abnormal amount immediately before the class period. Alternative measures of insider transactions and analysis of data before the enactment of the Private Securities Litigation Reform Act of 1995 provide consistent results. These new findings indicate that class actions, on average, have merit. Our data also reestablish a previous empirical result that there is no abnormal selling during the class period.
Intranasal Granulocyte-Macrophage Colony-Stimulating Factor Reduces theAspergillusBurden in an Immunosuppressed Murine Model of Pulmonary Aspergillosis
Authors: Quezada Gerardo , Koshkina Nadezhda V. , Zweidler-McKay Patrick , Zhou Zichao , Kontoyiannis Dimitrios P. , Kleinerman Eugenie S. 
Published: November 2007

ABSTRACTWe demonstrated that intranasal granulocyte-macrophage colony-stimulating factor given to immunosuppressed mice infected with pulmonary aspergillosis resulted in a sixfold reduction in the lung fungal burden compared to the result for saline-treated mice (P= 0.045). These data suggest that lung-targeted immunotherapy may be complementary to antifungal agents and may improve patient responses.
Pharmacokinetics and Pharmacodynamics of Piperaquine in a Murine Malaria Model
Authors: Moore Brioni R. , Batty Kevin T. , Andrzejewski Christopher , Jago Jeffrey D. , Page-Sharp Madhu , Ilett Kenneth F. 
Published: November 2007

ABSTRACT

Piperaquine (PQ) is an important partner in antimalarial treatment strategies. However, there is a paucity of detailed preclinical and pharmacokinetic data to link PQ serum concentrations and toxicity or efficacy. The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of PQ in a murine malaria treatment model. The study comprised three arms. (i) PQ pharmacokinetic parameters were determined in healthy and malaria-infected mice (90 mg/kg PQ phosphate [PQP]). (ii) For determination of single-dose pharmacodynamics, Swiss mice were inoculated with
Plasmodium berghei
parasites and given PQP (10, 30, or 90 mg/kg intraperitoneally) at 2 to 5% starting parasitemia. After 60 days, the 90-mg/kg PQP group was reinoculated with
P. berghei
. (iii) Combination efficacy was investigated at doses of 10 mg/kg PQP and 30 mg/kg dihydroartemisinin (DHA). The median survival times were 4, 10, and 54 days for 0, 10, and 30 mg/kg PQP, respectively. All mice given 90 mg/kg PQP survived beyond 60 days, with a mean parasitemia of <1% before and after reinoculation. The nadir for DHA plus PQP was significantly lower (22-fold ± 12-fold) than the initial parasitemia for the individual drugs (DHA, 12-fold ± 5-fold; PQP, 13-fold ± 3-fold;
P
= 0.007 [analysis of variance]). The elimination half-lives of PQ in healthy and infected mice were 18 and 16 days, respectively, and the extrapolated residual PQ concentration at 60 days (<10 μg/liter) was ineffective at suppressing
P. berghei
infection. PQ has a potent antimalarial effect after single-dose treatment, and its efficacy was enhanced by combination with DHA.
Environmental Determinants of the Occurrence and Distribution of
Vibrio parahaemolyticus
in the Rias of Galicia, Spain
Authors: Martinez-Urtaza Jaime , Lozano-Leon Antonio , Varela-Pet Jose , Trinanes Joaquin , Pazos Yolanda , Garcia-Martin Oscar 
Published: November 2007

ABSTRACT

Infections associated with
Vibrio parahaemolyticus
on the coast of Galicia (in northwestern Spain) were reported to be linked to large outbreaks of illness during 1999 and 2000. Little information is available about the ecological factors that influence the emergence of
V. parahaemolyticus
infections in this temperate region. We carried out a 3-year study to investigate the occurrence and distribution of
V. parahaemolyticus
at 26 sites located in the four main rias of Galicia in association with environmental and oceanographic variables.
V. parahaemolyticus
was detected in all the areas investigated and throughout the complete period of study with an overall incidence of 12.5%. Salinity was the primary factor governing the temporal and spatial distribution of
V. parahaemolyticus
, whereas seawater temperature had a secondary effect and only modulated the abundance in periods and areas of reduced salinities. Higher occurrence of
V. parahaemolyticus
was observed during periods of lower salinity in autumn, with a total of 61 positive samples (18%) and a mean density of 1,234 most probable number/100 g.
V. parahaemolyticus
was primarily detected in areas of reduced salinity close to freshwater discharge points, where it was found in up to 45% of the samples. Characterization of the isolates obtained from the study resulted in the first identification of two pathogenic
tdh
-positive strains of
V. parahaemolyticus
recovered from the marine environment in Galicia. These isolates showed serotypes identical to and DNA profiles indistinguishable from those of the clinical clone of
V. parahaemolyticus
dominant in infections in Spain in the last 10 years.