bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is susceptibility to tuberculosis acquired or inherited?
Authors: Schurr E. 
Published: January 2007

Abstract.Tuberculosis is an ongoing major public health problem on a global scale. One of the striking features of the disease is that only an estimated 10% of immunocompetent persons infected by the causative pathogen Mycobacterium tuberculosis will develop clinical signs of disease. This well‐established epidemiological observation has prompted an intense search for the factors that trigger advancement of infection to disease in the small proportion of susceptible individuals. Central to this search is the questions if tuberculosis patients are inherently susceptible to the disease or if disease development is promoted by specific environmental factors. It is known that genetic and non‐genetic factors of both the bacterium and the host have impact on the host response to M. tuberculosis. Yet, little is known about the interaction of these different factors and the resulting impact on disease development. Recent work suggests that in addition to common host susceptibility genes a second group of susceptibility loci exists the action of which strongly depends on the individual's clinical and exposure history. The latter genes may have a very strong effect on promoting advancement from infection to disease only in specific epidemiological settings. These findings suggest that a more detailed knowledge of gene–environment interactions in tuberculosis is necessary to understand why a small proportion of individuals are susceptible to the disease whilst the majority of humans are naturally resistant to tuberculosis.
Enhanced anxiety, depressive‐like behaviour and impaired recognition memory in mice with reduced expression of the vesicular glutamate transporter 1 (VGLUT1)
Authors: Tordera R. M. , Totterdell S. , Wojcik S. M. , Brose N. , Elizalde N. , Lasheras B. , Del Rio J. 
Published: January 2007

AbstractThree isoforms of a vesicular glutamate transporter (VGLUT1–3) have been identified. Of these, VGLUT1 is the major isoform in the cerebral cortex and hippocampus where it is selectively located on synaptic vesicles of excitatory glutamatergic terminals. Variations in VGLUT1 expression levels have a major impact on the efficacy of glutamate synaptic transmission. Given evidence linking alterations in glutamate neurotransmission to various neuropsychiatric disorders, we investigated the possible influence of a down‐regulation of VGLUT1 transporter on anxiety, depressive‐like behaviour and learning. The behavioural phenotype of VGLUT1‐heterozygous mice (C57BL/6) was compared to wild‐type (WT) littermates. Moreover, VGLUT1–3 expression, hippocampal excitatory terminal ultrastructure and neurochemical phenotype were analysed. VGLUT1‐heterozygous mice displayed normal spontaneous locomotor activity, increased anxiety in the light–dark exploration test and depressive‐like behaviour in the forced swimming test: no differences were shown in the elevated plus‐maze model of anxiety. In the novel object recognition test, VGLUT1+/– mice showed normal short‐term but impaired long‐term memory. Spatial memory in the Morris water maze was unaffected. Western blot analysis confirmed that VGLUT1 heterozygotes expressed half the amount of transporter compared to WT. In addition, a reduction in the reserve pool of synaptic vesicles of hippocampal excitatory terminals and a 35–45% reduction in GABA in the frontal cortex and the hippocampus were observed in the mutant mice. These observations suggest that a VGLUT1‐mediated presynaptic alteration of the glutamatergic synapses, in specific brain regions, leads to a behavioural phenotype resembling certain aspects of psychiatric and cognitive disorders.
‘Policies Don't Protect People, It's How They Are Implemented’: Policy and Practice in Protecting People with Learning Disabilities from Abuse
Authors: Northway Ruth , Davies Rachel , Mansell Ian , Jenkins Robert 
Published: January 2007

Abstract Recent years have seen the development of policy guidance documents in both Wales and England relating to the protection of vulnerable adults from abuse. This policy guidance does, however, require translation into policies at the local level and that these policies are then implemented in day‐to‐day practice. This article reports some of the findings of a two‐year study that examined the development and implementation of such policies in services for people with learning disabilities within Wales. Data were gathered by means of a survey of service providers from across Wales and also via focus groups held with direct care staff and those with a responsibility for investigating alleged abuse. Positive developments include a commitment to multi‐disciplinary working, increased clarity and consistency, and greater awareness. Less positive aspects include the potential for policy ‘overload’ and a feeling that, while there is awareness of the existence of vulnerable adults policies, knowledge of their content may be more limited. Recommendations are made for the development of policy, practice and research.
Realizing the Literate Traveller
Authors: Cartwright William E , Williams Bob , Pettit Chris 
Published: January 2007

AbstractA current research project is addressing the problem of finding appropriate geographical information by developing a (geo)information realization resource based upon the concepts of the Literate Traveller. It has as its main goal to provide tools for geographical knowledge building and exploration, by providing conventional spatial information plus geographical interpretation and appreciation artifacts. These artifacts are delivered in an interactive multimedia environment. This research examines the formulation of an initial prototype component to assist in providing geographical knowledge. The prototype is based on a study site in Townsville, Australia, and is being used as a vehicle to explore enhanced spatial information provision through the use of rich media. The research examines new ways to prospect for, discover and disseminate spatial knowledge within an intelligence‐briefing context. The paper reports on the concepts behind the design of the application developed for the test site, and presents initial findings from the early evaluation of the prototype.
Towards a Coherent Statistical Framework for Dense Deformable Template Estimation
Authors: Allassonnière S. , Amit Y. , Trouvé A. 
Published: January 2007

SummaryThe problem of estimating probabilistic deformable template models in the field of computer vision or of probabilistic atlases in the field of computational anatomy has not yet received a coherent statistical formulation and remains a challenge. We provide a careful definition and analysis of a well-defined statistical model based on dense deformable templates for grey level images of deformable objects. We propose a rigorous Bayesian framework for which we prove asymptotic consistency of the maximum a posteriori estimate and which leads to an effective iterative estimation algorithm of the geometric and photometric parameters in the small sample setting. The model is extended to mixtures of finite numbers of such components leading to a fine description of the photometric and geometric variations of an object class. We illustrate some of the ideas with images of handwritten digits and apply the estimated models to classification through maximum likelihood.
The shape of the hominoid proximal femur: a geometric morphometric analysis
Authors: Harmon Elizabeth H. 
Published: January 2007

AbstractAs part of the hip joint, the proximal femur is an integral locomotor component. Although a link between locomotion and the morphology of some aspects of the proximal femur has been identified, inclusive shapes of this element have not been compared among behaviourally heterogeneous hominoids. Previous analyses have partitioned complex proximal femoral morphology into discrete features (e.g. head, neck, greater trochanter) to facilitate conventional linear measurements. In this study, three‐dimensional geometric morphometrics are used to examine the shape of the proximal femur in hominoids to determine whether femoral shape co‐varies with locomotor category. Fourteen landmarks are recorded on adult femora of Homo, Pan, Gorilla, Pongo and Hylobates. Generalized Procrustes analysis (GPA) is used to adjust for position, orientation and scale among landmark configurations. Principal components analysis is used to collapse and compare variation in residuals from GPA, and thin‐plate spline analysis is used to visualize shape change among taxa. The results indicate that knucklewalking African apes are similar to one another in femoral shape, whereas the more suspensory Asian apes diverge from the African ape pattern. The shape of the human and orangutan proximal femur converge, a result that is best explained in terms of the distinct requirements for locomotion in each group. These findings suggest that the shape of the proximal femur is brought about primarily by locomotor behaviour.
Internalization of PrP106–126 by the formyl‐peptide‐receptor‐like‐1 in glial cells
Authors: Brandenburg Lars‐Ove , Koch Thomas , Sievers Jobst , Lucius Ralph 
Published: January 2007

AbstractRecent studies suggest that the formyl‐peptide‐receptor‐like‐1 (FPRL1) plays an essential role in inflammatory responses in the host defence mechanisms and neurodegenerative disorders. Furthermore, it may be involved in proinflammatory processes of prion diseases. However, little is known about the induction and regulation of PrP106–126‐induced receptor endocytosis. We have thus analysed whether PrP106–126 increases the activity of phospholipase D (PLD) via FPRL1, an enzyme involved in the regulation of the secretion, endocytosis and receptor signalling, in glial cells. PLD activity was determined using a transphosphatidylation assay and the internalization of PrP106–126, and FPRL1 was assessed by fluorescence microscopy and quantified by ELISA. We could show that PLD is activated by PrP106–126 both in astrocytes and microglia, and moreover that PrP106–126 is rapidly internalized via FPRL1 in astrocytes and microglia cells. The determination of receptor activity by extracellular signal‐regulated kinases 1/2 phosphorylation and cAMP level measurement verified the PrP106–126‐induced activation of FPRL1. FPRL1‐mediated PrP106–126 uptake was blocked by the receptor antagonist chenodeoxycholic acid. These studies indicate the involvement of FPRL1‐mediated cellular signalling in PrP106–126‐endocytosis and may allow the development of therapeutic agents interfering with prion uptake and/or PLD function, using either PLD or the FPRL1 as a possible pharmaceutical target.
Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein
Authors: Grünblatt Edna , Salkovic‐Petrisic Melita , Osmanovic Jelena , Riederer Peter , Hoyer Siegfried 
Published: January 2007

AbstractThe intracerebroventricular (icv) application of streptozotocin (STZ) in low dosage was used in 3‐month‐old rats to explore brain insulin system dysfunction. Three months following STZ icv treatment, the expression of insulin‐1 and ‐2 mRNA was significantly reduced to 11% in hippocampus and to 28% in frontoparietal cerebral cortex, respectively. Insulin receptor (IR) mRNA expression decreased significantly in frontoparietal cerebral cortex and hippocampus (16% and 33% of control). At the protein/activity level, different abnormalities of protein tyrosine kinase activity (increase in hippocampus), total IR β‐subunit (decrease in hypothalamus) and phosphorylated IR tyrosine residues (increase) became apparent. The STZ‐induced disturbance in learning and memory capacities was not abolished by icv application of glucose transport inhibitors known to prevent STZ‐induced diabetes mellitus. The discrepancy between reduced IR gene expression and increase in both phosphorylated IR tyrosine residues/protein tyrosine kinase activity may indicate imbalance between phosphorylation/dephosphorylation of the IR β‐subunit causing its dysfunction. These abnormalities may point to a complex brain insulin system dysfunction after STZ icv application, which may lead to an increase in hyperphosphorylated tau‐protein concentration. Brain insulin system dysfunction is discussed as possible pathological core in the generation of hyperphosphorylated tau protein as a morphological marker of sporadic Alzheimer’s disease.
Isolation and characterization of LCHN: a novel factor induced by transient global ischemia in the adult rat hippocampus
Authors: Zhang Guangming , Jung Benjamin P. , Ho Warren , Jugloff Denis G. M. , Cheung Herman H. , Gurd James W. , Wallace M. Christopher , Eubanks James H. 
Published: January 2007

AbstractUsing mRNA differential display to identify cerebral ischemia‐responsive mRNAs, we isolated and cloned a cDNA derived from a novel gene, that has been designated LCHN. Antisense mRNA in situ hybridization and immunoblotting confirmed LCHN expression to be induced in the rat hippocampus following transient forebrain ischemia. The deduced amino acid sequence of the novel LCHN cDNA contains an open reading frame of 455 amino acids, encoding a protein with a predicted molecular mass of approximately 51 kDa. Although LCHN is highly conserved between rat, mouse, and human, the deduced amino acid sequence of LCHN does not possess significant homology to other known genes. LCHN immunoreactivity is detected within the somatodendritic compartment of neurons, is also present on dendritic growth cones, but is not detected on astrocytes. The induction of LCHN in the hippocampus following ischemic injury may have functional consequences, as the ectopic over‐expression of LCHN generated neurons with longer and more branched axons and dendrites. Taken together, these data suggest that LCHN could play a role in neuritogenesis, as well as in neuronal recovery and/or restructuring in the hippocampus following transient cerebral ischemia.
Nitric oxide synthase inhibitors modulate nerve growth factor‐mediated regulation of amyloid precursor protein expression in PC12 cells
Authors: Binnington Janet C. , Kalisch Bettina E. 
Published: January 2007

AbstractNerve growth factor (NGF) can regulate nitric oxide synthase (NOS) expression and nitric oxide (NO) can modulate NGF‐mediated neurotrophic responses. In this study, the role of NO in NGF‐stimulated amyloid precursor protein (APP) levels was studied. PC12 cells were treated with either the non‐selective NOS inhibitor Nω‐nitro‐L‐arginine methylester (L‐NAME) or the inducible NOS selective inhibitor s‐methylisothiourea (S‐MIU), and the effect on NGF‐mediated increases in APP expression was determined. NGF significantly increased total APP protein levels following 96 h of treatment and this increase was prevented in cells pre‐treated with S‐MIU. Pre‐treatment of cells with actinomycin D also blocked this NGF‐mediated induction of APP, indicating de novo protein synthesis is necessary. Treatment with NGF increased APP promoter activity; however, this increase was only partially inhibited by pre‐treatment with S‐MIU and was increased in the presence of L‐NAME. This suggests that NO may be modulating other aspects of APP expression in addition to transcription. Inhibition of NGF signaling pathways was also investigated using inhibitors of mitogen‐activated protein (MAP) kinase (U0126), Akt (LY294002) and protein kinase C (PKC; U73122 and bisindolylmaleimide 1 (BIS‐1)) activation. Inhibition of each of these pathways prevented NGF‐mediated increases in APP protein expression; however, only BIS‐1 attenuated NGF‐mediated increases in promoter activation. This study indicates that NO is involved in the NGF‐mediated regulation of APP, in part at the level of APP transcription and could involve the modulation of NGF signal transduction pathways.
DNA barcoding of Neotropical bats: species identification and discovery within Guyana
Authors: CLARE ELIZABETH L. , LIM BURTON K. , ENGSTROM MARK D. , EGER JUDITH L. , HEBERT PAUL D. N. 
Published: January 2007

AbstractSequence diversity in the cytochrome c oxidase subunit 1 gene has been shown to be an effective tool for species identification and discovery in various groups of animals, but has not been extensively tested in mammals. We address this gap by examining the performance of DNA barcodes in the discrimination of 87 species of bats from Guyana. Eighty‐one of these species showed both low intraspecific variation (mean = 0.60%), and clear sequence divergence from their congeners (mean = 7.80%), while the other six showed deeply divergent intraspecific lineages suggesting that they represent species complexes. Although further work is needed to examine patterns of sequence diversity at a broader geographical scale, the present study validates the effectiveness of barcoding for the identification of regional bat assemblages, even highly diverse tropical faunas.
Intraindividual comparison of human radial and internal thoracic arteries in vitro and the effect of preoperative calcium blocker therapy
Authors: Grapow Martin T.R. , Reineke David C. , Kern Thomas , Antona Carlo , Gelpi Guido , Santoli Eduardo , Zerkowski Hans‐Reinhard , Carrel Thierry P. , Müller‐Schweinitzer Else 
Published: January 2007

AbstractThe patency rate of radial artery (RA) conduits is considerably lower than that of internal thoracic artery (ITA) grafts and the evidence suggests that this is due to a clinically suspected higher incidence of vasospasm. The aim of this study was, therefore, to compare intraindividually the pharmacological reactivity of RA with that of ITA. Both RA and ITA were taken from the same patients and investigated in parallel. Changes in tone were monitored isometrically on ring preparations from both arteries in organ baths with modified Krebs–Henseleit solution containing 1.25 mm calcium chloride at 1 g passive preload. In intraindividual comparisons maximal receptor‐mediated contractile responses to noradrenaline and endothelin‐1 and endothelium‐dependent acetylcholine‐induced relaxant responses revealed no differences between both arteries. By contrast, depolarization‐induced contractions to potassium chloride (KCl) appeared to be significantly higher in RA than in ITA. Further analysis, however, revealed that this difference was due to preoperative calcium entry blocker (Ca2+eB) therapy. Compared with control tissues, maximal responses to KCl were significantly attenuated in the ITA but unchanged in RA when arteries were obtained from patients with preoperative Ca2+eB therapy. The present results suggested that functional responses to pharmacological stimuli of both RA and ITA were quite similar. Preoperative Ca2+eB therapy, however, attenuated markedly responses to KCl of the ITA leaving those of RA unchanged. These results, demonstrating a lower sensitivity to Ca2+eB of RA, therefore suggested that in addition to Ca2+eB other classes of drug may be more effective at reducing the propensity of RA conduits to vasospasm.
The effect of modulation ofγ‐glutamyl transpeptidase and nitric oxide synthase activity on GSH homeostasis in HepG2 cells
Authors: Kwiecień Inga , Rokita Hanna , Lorenc‐Koci Elżbieta , Sokolowska Maria , Włodek Lidia 
Published: January 2007

AbstractHigh glutathione (GSH) level and elevatedγ‐glutamyl transpeptidase (γGT) activity are hallmarks of tumor cells. Toxicity of drugs and radiation to the cells is largely dependent on the level of thiols. In the present studies, we attempted to inhibitγGT activity in human hepatoblastoma (HepG2) cells to examine whether the administration ofγGT inhibitors, acivicin (AC) and 1,2,3,4‐tetrahydroisoquinoline (TIQ) influences cell proliferation and enhances cytostatic action of doxorubicin (DOX) and cisplatin (CP) on HepG2 cells. The effects of these inhibitors were determined by 1‐(4,5‐dimethylthiazol‐2‐yl)‐3,5‐diphenylformazan (MTT), BrdU and lactate dehydrogenase (LDH) tests and by estimation of GSH level. Additionally, we investigated the changes in caspase‐3 activity, which is a marker of apoptosis. The obtained results showed that theγGT inhibitors introduced to the medium alone elicited cytotoxic effect, which was accompanied by an increase in GSH level in the cells. TIQ concomitantly increased caspase‐3 activity. Doxorubicin and CP proved to be cytotoxic, and both inhibitors augmented this effect. As well DOX as CP radically decreased GSH levels, whereasγGT inhibitors had diverse effects. Therefore, the obtained results confirm thatγGT inhibitors can enhance pharmacological action of DOX and CP, which may permit clinicians to decrease their doses thereby alleviating side effects. Aminoguanidine (nitric oxide synthase inhibitor) given alone was little cytotoxic to HepG2 cells, while its introduction to the medium together with DOX and CP significantly increased their cytotoxicity. Aminoguanidine on its own did not show any effect on GSH level in HepG2 cells, but markedly and significantly elevated its concentration when added in combination with CP but not with DOX. This indicates that when CP was used as a cytostatic, GSH level rose after treatment with its combination with both AC and aminoguanidine.
Comparative effects of two type I interferons, human IFN‐α and ovine IFN‐τ on indoleamine‐2,3‐dioxygenase in primary cultures of human macrophages
Authors: Maneglier Benjamin , Rogez‐Kreuz Christine , Spreux‐Varoquaux Odile , Malleret Benoit , Thérond Patrice , Samah Boubekeur , Drouet Isabelle , Dormont Dominique , Advenier Charles , Clayette Pascal 
Published: January 2007

AbstractType I interferons (IFNs) are widely used to treat viral diseases. Depressive symptoms and suicide attempts are common neuropsychiatric side‐effects during treatment with type I IFNs. Activation of indoleamine‐2,3‐dioxygenase (IDO), the first and rate‐limiting enzyme of the kynurenine pathway by IFNs, leads to an increase in tryptophan (Trp) catabolism. Low levels of Trp lead to decrease of serotonin synthesis, which is likely to be related to the depressive symptoms. Ovine type I interferon‐tau (IFN‐τ) has a more potent antiretroviral effect and is less toxic than human type I IFN‐α. Effects of IFN‐τ and IFN‐α on IDO expression and activity in primary cultures of human macrophages were compared in parallel to those of IFN‐γ, considered as one of the most potent IDO inducer. We found that both IFN‐α and IFN‐τ were poor inducers of IDO compared with IFN‐γ. However, IDO activation was slightly and significantly lower with ovine IFN‐τ than human IFN‐α, suggesting that ovine IFN‐τ might have a lower impact on serotoninergic pathway compared with human IFN‐α.