bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein tyrosine nitration in rat brain is associated with raft proteins, flotillin‐1 and α‐tubulin: effect of biological aging
Authors: Dremina Elena S. , Sharov Victor S. , Schöneich Christian 
Published: June 2005

AbstractProtein 3‐nitrotyrosine (3‐NY) immunoreactivity of rat brain homogenate was localized to a ca. 50 kDa protein band by western blot (WB) analysis. The nitrated proteins were localized to the raft fraction obtained by centrifugation of the homogenate in a sucrose density gradient, which contained specific raft markers such as flotillin‐1 and caveolin‐1. Purification of the nitrated raft proteins either by a combination of reversed‐phase high‐performance liquid chromatography (HPLC) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS–PAGE) or by immunoprecipitation (IP) with protein‐ and modification‐specific antibodies coupled to WB and HPLC‐electrospray ionization‐tandem mass spectrometry (ESI–‐MS/MS) analysis allowed us to identify two proteins modified by 3‐NY: flotillin‐1 and α‐tubulin. Both α‐ and β‐tubulin were detected in the rat brain raft fraction as abundant proteins, which co‐immunoprecipitate with flotillin‐1 and caveolin‐1. Importantly, some protein–protein interactions in rafts were disrupted in 3‐NY‐containing proteins, e.g. caveolin‐1 was dissociated from a complex with flotillin‐1 and α‐tubulin. The analysis of age dependencies did not show any significant change in protein nitration and expression of flotillin‐1 and α‐tubulin, but a decrease in the brain caveolin‐1 level for old (34 months) versus young (6 months) rats. The putative mechanism of nitric oxide synthase (NOS) activity regulation by the level of caveolin expression and raft protein–protein interactions is discussed.
Direct visualization of mitochondrial zinc accumulation reveals uniporter‐dependent and ‐independent transport mechanisms
Authors: Malaiyandi Latha M. , Vergun Olga , Dineley Kirk E. , Reynolds Ian J. 
Published: June 2005

AbstractCurrent evidence suggests that zinc kills neurons by disrupting energy production, specifically by inhibiting mitochondrial function. However it is unclear if the inhibitory effect requires zinc accumulation, and if so, precisely how zinc enters mitochondria. Here, using fluorescence microscopy to visualize individual rat brain mitochondria, we detected matrix zinc uptake using the fluorophore FluoZin‐3. Fluorescence increased rapidly in mitochondria treated with micromolar free zinc, and was quickly returned to baseline by membrane permeant chelation. Zinc uptake occurred through the calcium uniporter, because depolarization or uniporter blockade reduced fluorescence changes. However, increased fluorescence under these conditions suggests that zinc can enter through a uniporter‐independent pathway. Fluorescence steadily declined over time and was unaffected by acidification or phosphate depletion, suggesting that zinc precipitation is not a mechanism for reducing matrix zinc. Uniporter blockade with ruthenium red also did not change the rate of zinc loss. Instead, zinc appears to exit the matrix through a novel efflux pathway not yet identified. Interestingly, dye‐loaded mitochondria showed no fluorescence increase after treatment with strong oxidants, arguing against oxidant‐labile intra‐mitochondrial zinc pools. This study is the first to directly demonstrate zinc accumulation in individual mitochondria and provides insight about mechanisms mediating mitochondrial zinc uptake and efflux.
Modification by the tissue plasminogen activator–plasmin system of morphine‐induced dopamine release and hyperlocomotion, but not anti‐nociceptive effect in mice
Authors: Nagai Taku , Kamei Hiroyuki , Ito Mina , Hashimoto Kazuki , Takuma Kazuhiro , Nabeshima Toshitaka , Yamada Kiyofumi 
Published: June 2005

AbstractThe extracellular serine protease tissue plasminogen activator (tPA) that converts plasminogen into plasmin is abundantly expressed throughout the central nervous system. We have recently demonstrated that the tPA–plasmin system participates in the rewarding and locomotor‐stimulating effects of morphine by acutely regulating morphine‐induced dopamine release in the nucleus accumbens (NAc). In the present study, we examined the effects of microinjections of plasminogen activator inhibitor‐1 (PAI‐1), tPA or plasmin into the NAc on morphine‐induced dopamine release, hyperlocomotion and anti‐nociceptive effects in ICR mice. A single morphine treatment resulted in an increase in protein levels of PAI‐1 in the NAc. Microinjection of PAI‐1 into the NAc dose‐dependently reduced morphine‐induced dopamine release and hyperlocomotion. In contrast, microinjection of tPA into the NAc significantly potentiated morphine‐induced dopamine release and hyperlocomotion without affecting basal levels. Furthermore, microinjection of plasmin enhanced morphine‐induced dopamine release, but did not modify the hyperlocomotion induced by morphine. The intracerebroventricular injection of PAI‐1, tPA and plasmin at high doses had no effect on the anti‐nociceptive effects of morphine. These results suggest that the tPA–plasmin system is involved in the regulation of morphine‐induced dopamine release and dopamine‐dependent behaviors but not the anti‐nociceptive effects of morphine.
NT3 inhibits FGF2‐induced neural progenitor cell proliferation via the PI3K/GSK3 pathway
Authors: Jin Lu , Hu Xinhua , Feng Linyin 
Published: June 2005

AbstractNeurotrophin 3 (NT3), a member of the neurotrophin family, antagonizes the proliferative effect of fibroblast growth factor 2 (FGF2) on cortical precursors. However, the mechanism by which NT3 inhibits FGF2‐induced neural progenitor (NP) cell proliferation is unclear. Here, using an FGF2‐dependent rat neurosphere culture system, we found that NT3 inhibits both FGF2‐induced neurosphere growth and bromodeoxyuridine (BrdU) incorporation in a dose‐dependent manner. U0126, a mitogen‐activated protein kinase kinase 1/2 (MEK1/2) inhibitor, and LY294002, a phosphatidylinositol 3‐kinase (PI3K) inhibitor, both inhibited FGF2‐induced BrdU incorporation, suggesting that the extracellular signal‐regulated kinase1/2 (ERK1/2) and PI3K pathways are required for FGF2‐induced NP cell proliferation. NT3 significantly inhibited FGF2‐induced phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β), a downstream kinase of Akt, whereas phosphorylation of ERK1/2 was unaffected. The inhibitory effect of NT3 on FGF2‐induced NP cell proliferation was abolished by LY294002, and treatment with SB216763, a specific GSK3 inhibitor, antagonized the NT3 effect, rescuing both neurosphere growth and BrdU incorporation. Moreover, experiments with anti‐NT3 antibody revealed that endogenous NT3 also plays a role in inhibiting FGF2‐induced NP cell proliferation, and that anti‐NT3 antibody enhanced phospho‐Akt and phospho‐GSK3β levels in the presence of FGF2. These findings indicate that FGF2‐induced NP cell proliferation is inhibited by NT3 via the PI3K/GSK3 pathway.
The critical role of calpain versus caspase activation in excitotoxic injury induced by nitric oxide
Authors: Volbracht Christiane , Chua Boon Tin , Ng Chee Peng , Bahr Ben A. , Hong Wanjin , Li Peng 
Published: June 2005

AbstractThe pathogenesis of various acute and chronic neurodegenerative disorders has been linked to excitotoxic processes and excess generation of nitric oxide. We investigated the deleterious effects of calpain activation in nitric oxide‐elicited neuronal apoptosis. In this model, nitric oxide triggers apoptosis of murine cerebellar granule cells by an excitotoxic mechanism requiring glutamate exocytosis and receptor‐mediated intracellular calcium overload. Here, we found that calcium‐dependent cysteine proteases, calpains, were activated early in apoptosis of cerebellar granule cells exposed to nitric oxide. Release of the proapoptogenic factors cytochrome c and apoptosis‐inducing factor from mitochondria preceded neuronal death. However, caspases‐3 was not activated. We observed that procaspase‐9 was cleaved by calpains to proteolytically inactive fragments. Inhibition of calpains by different synthetic calpain inhibitors or by adenovirally mediated expression of the calpastatin inhibitory domain prevented mitochondrial release of cytochrome c and apoptosis‐inducing factor, calpain‐specific proteolysis and neuronal apoptosis. We conclude that (i) signal transduction pathways exist that prevent the entry of neurons into a caspase‐dependent death after mitochondrial release of cytochrome c and (ii) that calpain activation links nitric oxide‐triggered excitotoxic events with the execution of caspase‐independent apoptosis in neurons.
Enhanced expression and shedding of the transmembrane chemokine CXCL16 by reactive astrocytes and glioma cells
Authors: Ludwig Andreas , Schulte Alexander , Schnack Cathrin , Hundhausen Christian , Reiss Karina , Brodway Neil , Held‐Feindt Janka , Mentlein Rolf 
Published: June 2005

AbstractThe transmembrane chemokine CXCL16 is expressed by dendritic and vascular cells and mediates chemotaxis and adhesion of activated T cells via the chemokine receptor CXCR6/Bonzo. Here we describe the expression and shedding of this chemokine by glioma cells in situ and in vitro. By quantitative RT‐PCR and immunohistochemistry, we show that CXCL16 is highly expressed in human gliomas, while expression in normal brain is low and mainly restricted to brain vascular endothelial cells. In cultivated human glioma cells as well as in activated mouse astroglial cells, CXCL16 mRNA and protein is constitutively expressed and further up‐regulated by tumour necrosis factor α (TNFα) and interferon‐γ (IFNγ). CXCL16 is continuously released from glial cells by proteolytic cleavage which is rapidly enhanced by stimulation with phorbol‐12‐myristate‐13‐acetate (PMA). As shown by inhibitor studies, two distinct members of the disintegrin‐like metalloproteinase family ADAM10 and 17 are involved in the constitutive and PMA‐induced shedding of glial CXCL16. In addition to the chemokine, its receptor CXCR6 could be detected by quantitative RT‐PCR in human glioma tissue, cultivated murine astrocytes and at a lower level in microglial cells. Functionally, recombinant soluble CXCL16 enhanced proliferation of CXCR6‐positive murine astroglial and microglial cells. Thus, the transmembrane chemokine CXCL16 is expressed in the brain by malignant and inflamed astroglial cells, shed to a soluble form and targets not only activated T cells but also glial cells themselves.
The membrane‐associated progesterone‐binding protein 25‐Dx is expressed in brain regions involved in water homeostasis and is up‐regulated after traumatic brain injury
Authors: Meffre Delphine , Delespierre Brigitte , Gouézou Monique , Leclerc Philippe , Vinson Gavin P. , Schumacher Michael , Stein Donald G. , Guennoun Rachida 
Published: June 2005

AbstractAfter traumatic brain injury, progesterone has important neuroprotective effects in the nervous system. There is better functional outcome and less oedema formation in pseudopregnant rat females (high levels of endogenous progesterone) than in males. In addition to intracellular progesterone receptors, membrane binding sites of the hormone such as 25‐Dx may also be involved in neuroprotection. In the present study we investigated the distribution of the membrane‐associated progesterone‐binding protein 25‐Dx in rat brain. Immunohistochemical analysis showed that 25‐Dx is particularly abundant in the hypothalamic area, circumventricular organs, and ependymal cells of the lateral walls of the third and lateral ventricles. A strong signal was also detected in the meninges. Double immunofluorescence immunolabelling and confocal microscopy showed that 25‐Dx is co‐expressed with vasopressin in neurones of the paraventricular, supraoptic and retrochiasmatic nuclei. Levels of 25‐Dx expression were higher in pseudopregnant females than in males. After traumatic brain injury, 25‐Dx expression was up‐regulated in neurones and induced in astrocytes, which play an important role in regulating water and ion homeostasis. The expression of 25‐Dx in structures involved in CSF production (choroid plexus) and in osmoregulation (circumventricular organs, hypothalamus and meninges), and its up‐regulation after brain damage, point to a novel and potentially important role of this progesterone‐binding protein in the maintenance of water homeostasis after traumatic brain injury.
Α genetic fusion construct between the tetanus toxin C fragment and the lysosomal acid hydrolase β‐glucuronidase expresses a bifunctional protein with enhanced secretion and neuronal uptake
Authors: Jiang Kanli , Watson Deborah J. , Wolfe John H. 
Published: June 2005

AbstractThe neurotropic atoxic fragment of tetanus toxin has been used as a carrier for transporting macromolecules into neurons but all studies to date have tested cytosolic proteins. In this study we investigated the effect of a genetic addition of the tetanus toxin C fragment sequence to a lysosomal enzyme which contains a signal sequence for insertion into the membrane‐bound compartment and must be extensively modified in the endoplasmic reticulum (ER) and Golgi to attain functionality. In‐frame fusion constructs between the atoxic C fragment and β‐glucuronidase were compared with the wild‐type enzyme for: (i) enzymatic activity; (ii) heat stability; (iii) pH dependence; (iv) specific activity; (v) apparent molecular mass and (vi) receptor‐mediated uptake by fibroblasts and neurons. The modified proteins had biochemical properties similar to wild‐type enzyme but exhibited different enzyme secretion profiles. Addition of the secreted fusion enzyme to cultures of primary neurons showed significantly increased neuronal uptake of the modified protein compared with the wild‐type, demonstrating the bifunctionality of the chimeric molecule.
Comparison between fundamental and second‐harmonic imaging echocardiography for calculation of left ventricular mass in children
Authors: Dencker M. , Thorsson O. , Wollmer P. 
Published: June 2005

SummaryIn adults, calculation of left ventricular mass (LVM) has been shown to give higher values when based on M‐mode measurements obtained by the second‐harmonic imaging (SHI) technique than with the older fundamental imaging (FI) technique. No information is available in paediatric subjects. This study, therefore, compares LVM calculated from measurements obtained with SHI and FI in 14 children, aged 6·9–13·0 years. M‐mode tracings were obtained in accordance with American Society of Echocardiography (ASE) recommendations. Three experienced sonographers performed measurements on each subject with both SHI and FI. The mean value was used in all calculations. LVM was calculated according to ASE convention and indexed by body surface area. LVM mean values were 58·9 ± 9·7 g m−2 for SHI and 57·8 ± 8·2 g m−2 for FI (P = 0·45). This preliminary study in a small group of paediatric subjects demonstrates no systematic differences between FI and SHI modalities in the calculation of LVM. The likely explanation is that the left ventricular endocardial border is usually well visualized with SHI as well as with FI in children.
Psychological Aspects of Weekend Headache Sufferers in Comparison with Migraine Patients
Authors: Nattero Giovanni , De Lorenzo Cristina , Biale Lucia , Allais Gianni , Torre Eugenio , Ancona Mario 
Published: June 2005

SYNOPSISSometimes the relaxation after stress may trigger a migraine attack. This is the principle that underlies that particular variant of migraine called “weekend headache”.We hypothesize the presence in weekend headache prone subjects of a particular psychological background, different from that of common migraine sufferers. In order to detect possible differences supporting our hypothesis, we studied 104 new outpatients: 46 patients suffering from headache only on weekends (23 males and 23 females) and 58 matched common migraineurs (26 males and 32 females) with no weekend predilection.The psychological assessment was performed using the following psychometric tools: MMPI, BDI, STAI X1‐X2 . A clinical assessment of each patient was also carried out. Significant differences were found after statistically analyzing the test results. Most of the MMPI scales were found to be more elevated in both male and female weekend headache sufferers. From a clinical point of view, the weekend headache attacks proved to be similar to those of common migraine, but with a significantly higher incidence of concomitant symptoms.Our study confirms the important role that psychological factors play in the pathogenesis and clinical development of migraine and leads us to conclude that a psychic tension component is associated with the vascular one in weekend headache.
Treatment of a Cluster Headache Patient in a Hyperbaric Chamber
Authors: Weiss Larry D. , Ramasastry Sai S. , Eidelman Benjamin H. 
Published: June 2005

SYNOPSISA patient with severe cluster headaches was treated in a hyperbaric chamber on two occasions. Her symptoms had been refractory to other treatment modalities including conventional oxygen therapy. On both occasions her pain was promptly relieved while breathing 100% oxygen at two atmospheres of pressure. This is the first known reported case of a cluster headache treated with hyperbaric oxygen. A prospective study is needed to substantiate the efficacy of this treatment modality for cluster headaches.
Low Brain Magnesium in Migraine
Authors: Ramadan N.M. , Halvorson H. , Vande‐Linde A. , Levine Steven R. , Helpern J.A. , Welch K.M.A. 
Published: June 2005

SYNOPSISBrain magnesium was measured in migraine patients and control subjects using in vivo 31‐Phosphorus Nuclear Magnetic Resonance Spectroscopy. pMg and pH were calculated from the chemical shifts between Pi, PCr and ATP signals. Magnesium levels were low during a migraine attack without changes in pH. We hypothesize that low brain magnesium is an important factor in the mechanism of the migraine attack.
A Controlled Study of Visual Symptoms and Eye Strain Factors in Chronic Headache
Authors: Vincent Arnaud J.P. , Spierings Egilius L.H. , Messinger Harley B. 
Published: June 2005

SYNOPSISIn a questionnaire survey we determined the prevalence of visual symptoms and eye strain factors in a group of chronic headache sufferers as compared with age‐ and sex‐matched controls. The visual symptoms studied were those not pecific for headache, i.e., sensitivity to light and blurred vision. Sensitivity to light in the absence of headache was reported by 27.8% of controls and 44.7% of headache sufferers (p<0.05). The latter figure increased to 71.3% when headache was actually present (p<0.001). Blurred vision occurred in 13.5% of controls and 7.4% of headache sufferers (not significant). In the presence of headache, the latter figure increased to 44.7% (p< 0.01).Of the eye strain factors studied, bright light was reported to precipitate headache in 29.3% and to aggravate it in 73.4%. For reading, these figures were 16.0% and 55.3%, respectively; for working at the computer screen, 14.5% and 31.3%; and for watching television, 6.4% and 27.7%. We conclude that visual symptoms are more common in chronic headache and eye strain factors more important than is generally recognized.
Investigation of Environmental Factors in Pediatric Headache
Authors: Budd Karen S. , Kedesdy Jurgen H. 
Published: June 2005

SYNOPSISThis study assessed the environmental conditions surrounding headache for a clinical sample of 38pediatric headache patients. A parent rating questionnaire, the Children's Headache Assessment Scale(CHAS), was developed and pilot tested as a means of identifying particular environmental events or situations impacting on children's headaches. CHAS items are organized into six functional categories (Stress Antecedents, Physical Antecedents, Attention Consequences, Escape Consequences, Coping Responses, and Medication Use) potentially related to headache activity. Patents filled out the CHAS at an intake evaluation for behavioral medicine treatment, and parents of children who completed treatment filled out another CHAS after therapy. Results showed that the frequency of specific CHAS items varied widely both within and between functional categories, suggesting that headache is affected by a variety of situational factors, some of which are common across many children and others of which are pertinent only for a small proportion of children. The results further suggest that the environmental conditions of headache are open to change by behavioral medicine treatment. In the present study, items reflecting social attention to headache, interference of headache with school attendance, and use of relaxation procedures changed after treatment. The potential value of the CHAS for treatment planning is discussed.
Leadership and Economic Theories of Nonprofit Organizations
Authors: Wallis Joseph , Dollery Brian 
Published: June 2005

AbstractEconomic theories of nonprofit organizations (NPOs) have modified standard economic assumptions to explain altruism and nonprofit entrepreneurship but have neglected their dependence on leadership due to the traditional reluctance of economists to consider phenomena associated with preference change. The relevance of Hermalin's (1998) model of leadership by example and Casson's (1991) theory of leadership through moral manipulation are considered within an NPO context where leaders seek to influence stakeholder commitments to the organization's quest. The propositions Elster (1998) advanced with regard to the relationship between the emotions and decision making are then applied in a theory that explains how NPO leaders can develop a culture of hope that maintains the quality control and product differentiation advantages claimed for these organizations. It is argued that policymakers should consider the dependence of NPOs on the quality of leadership when choosing the organizational mechanism for social service delivery.
Beyond Gratz and Grutter: Prospects for Affirmative Action in the Aftermath of the Supreme Court's Michigan Decisions
Authors: Elliott Euel W. , Ewoh Andrew I. E. 
Published: June 2005

AbstractThis article explores the meaning of the Supreme Court's Michigan decisions and their implications for higher education in the judicial, political, and social–cultural context. It concludes that the complex and dynamic interplay of judicial policymaking, politics and public opinion, and demographic changes could have important consequences, including unanticipated ones, in the years ahead.