bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABAergic striatal neurons exhibit caspase‐independent, mitochondrially mediated programmed cell death
Authors: Diwakarla Shanti , Mercer Linda D. , Kardashsyan Liubov , Chu Percy W. Y. , Shin Yea Seul , Lau Chew L. , Hughes Maria L. R. , Nagley Phillip , Beart Philip M. 
Published: April 2009

AbstractGABAergic striatal neurons are compromised in basal ganglia pathologies and we analysed how insult nature determined their patterns of injury and recruitment of the intrinsic mitochondrial pathway during programmed cell death (PCD). Stressors affecting targets implicated in striatal neurodegeneration [3‐morpholinylsydnoneimine (SIN‐1), 3‐nitropropionic acid (3‐NP), NMDA, 3,5‐dihydroxyphenylglycine (DHPG), and staurosporine (STS)] were compared in cultured GABAergic neurons from murine striatum by analyzing the progression of injury and its correlation with mitochondrial involvement, the redistribution of intermembrane space (IMS) proteins, and patterns of protease activation. Stressors produced PCD exhibiting slow‐onset kinetics with time‐dependent annexin‐V labeling and eventual DNA fragmentation. IMS proteins including cytochromecwere differentially distributed, although stressors except STS produced early redistribution of apoptosis‐inducing factor and Omi, suggestive of early recruitment of both caspase‐dependent and caspase‐independent signaling. In general, Bax mobilization to mitochondria appeared to promote IMS protein redistribution. Caspase 3 activation was prominent after STS, whereas NMDA and SIN‐1 produced mainly calpain activation, and 3‐NP and DHPG elicited a mixed profile of protease activation. PCD and redistribution of IMS proteins in striatal GABAergic neurons were canonical and insult‐dependent, reflecting differential interplay between the caspase cascade and alternate cell death pathways.
Acute changes in intermediary metabolism in cerebellum and contralateral hemisphere following middle cerebral artery occlusion in rat
Authors: Håberg Asta K. , Qu Hong , Sonnewald Ursula 
Published: April 2009

AbstractFocal ischemia leads to functional deafferentation of regions connected to the ischemic area via fiber tracts. Using i.v. administration of 13C‐labeled glucose and acetate combined with ex vivo13C MR spectroscopy and HPLC of brain extracts we identify the effect of middle cerebral artery occlusion (MCAO) on neurotransmitter synthesis and turnover, and on neuro‐astrocytic interactions in the non‐ischemic cerebellum and in contralesional lateral caudoputamen plus lower parietal cortex (LPC), and upper frontoparietal cortex (UFPCx) in the rat after 30, 60, 120 and 240 min of ischemia. In all regions, there was a significant persisting loss of glutamate, and in LCP and UFPCx also of glutamine, but only in LCP was GABA reduced at all times. Metabolism and blood flow were uncoupled in all regions. In cerebellum, glucose metabolism as well as utilization of intermediates derived from astrocytic tricarboxylic acid cycle activity were significantly decreased at all times in both glutamatergic and GABAergic neurons. In LCP and UFPCx, there were normal or increased enrichment in glutamate and GABA from glucose. Glutamate derived from astrocytic acetate metabolism was increased, but GABA synthesis from acetate was initially impaired. The results showed that both the type of afferent connection, i.e., glutamatergic and/or GABAergic, and local cytoarchitecture, determined the effect MCAO had on metabolic activity in the non‐ischemic regions. In conclusion, it was primarily excitatory input into non‐ischemic regions that was affected by MCAO, perhaps enabling resetting of the excitatory/inhibitory balance, aiding reshaping of the receptive fields and thus facilitating recovery.
Inhibition of the alpha‐ketoglutarate dehydrogenase‐mediated reactive oxygen species generation by lipoic acid
Authors: Ambrus Attila , Tretter László , Adam‐Vizi Vera 
Published: April 2009

AbstractDihydrolipoamide dehydrogenase (LADH) is a flavo‐enzyme that serves as a subunit of α‐ketoglutarate dehydrogenase complex (α‐KGDHC). Reactive oxygen species (ROS) generation by α‐KGDHC has been assigned to LADH (E3 subunit) and explained by the diaphorase activity of E3. Dysfunctions of α‐KGDHC and concurrent ROS production have been implicated in neurodegeneration, ischemia‐reperfusion, and other pathological conditions. In this work we investigated the in‐depth details of ROS generation by isolated LADH and α‐KGDHC. We found a parallel generation of superoxide and hydrogen peroxide by the E3 subunit of α‐KGDHC which could be blocked by lipoic acid (LA) acting on a site upstream of the E3 subunit. The pathologically relevant ROS generation (at high NADH/NAD+ ratio and low pH) in the reverse mode of α‐KGDHC could also be inhibited by LA. Our results contradict the previously proposed mechanism for pH‐dependent ROS generation by LADH, showing no disassembling of the E3 functional homodimer at acidic pH using a physiologically relevant method for the examination. It is also suggested that LA could be beneficial in reducing the cell damage related to excessive ROS generation under pathological conditions.
The turnover of the H3 deuterons from (2‐13C) glutamate and (2‐13C) glutamine reveals subcellular trafficking in the brain of partially deuterated rats
Authors: Cerdán Sebastián , Sierra Alejandra , Fonseca Luis L. , Ballesteros Paloma , Rodrigues Tiago B. 
Published: April 2009

AbstractWe investigated by 13C NMR the turnover of the H3 deuterons of (2‐13C) glutamate and (2‐13C) glutamine in the brain of partially deuterated rats. Adult animals (150–200 g) fed ad libitum received 50%2H2O or tap water 9 days before infusing (1‐13C) glucose or (2‐13C) acetate for 5, 10, 15, 30, 60, or 90 min. The brains were then funnel‐frozen and acid extracts were prepared and analyzed by high‐resolution 13C NMR. The deuteration of one or the two H3 hydrogens of (2‐13C) glutamate or glutamine resulted in single (−0.07 ppm) or double (−0.14 ppm) isotopic shifts upfield of the corresponding C2 perprotonated resonance, demonstrating two sequential deuteration steps. The faster monodeuteration generated 3R or 3S (2‐13C, 3‐2H) glutamate or glutamine through the alternate activities of cerebral aconitase or isocitrate dehydrogenase, respectively. The slower process produced bideuterated (2‐13C, 3,3′‐2H2) glutamate or glutamine through the consecutive activity of both enzymes. The kinetics of deuteration was fitted to a Michaelis–Menten model including the apparent Km′ and Vmax′ values for the observed deuterations. Our results revealed different kinetic constants for the alternate and consecutive deuterations, suggesting that these processes were caused by the different cytosolic or mitochondrial isoforms of aconitase and isocitrate dehydrogenase, respectively. The deuterations of (2‐13C) glutamate or glutamine followed also different kinetics from (1‐13C) glucose or (2‐13C) acetate, revealing distinct deuteration environments in the neuronal or glial compartments.
Ischemia activates JNK/c‐Jun/AP‐1 pathway to up‐regulate 14‐3‐3γ in astrocyte
Authors: Dong Yan , Liu Hua Dong , Zhao Rui , Yang Chun Zhang , Chen Xiao Qian , Wang Xin Hong , Lau Lok Ting , Chen Jianguo , Yu Albert Cheung Hoi 
Published: April 2009

AbstractIschemia occurs in the brain as the result of stroke and other related injuries and few therapies are effective. If more is understood then potential treatments could be investigated. It was previously reported that 14‐3‐3γ could be up‐regulated by ischemia in astrocyte to protect cells from ischemia‐induced apoptosis. In this study, we attempted to uncover the mechanism responsible for this 14‐3‐3γ up‐regulation in primary culture of astrocytes under ischemic‐like conditions. It was found that in vitro ischemia may activate PI3K/Akt and MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). Only SP600125 could inhibit the ischemia‐induced 14‐3‐3γ up‐regulation in astrocytes. At the same time, we observed an ischemia‐induced nuclear translocation of p‐c‐Jun, a major downstream component of JNK. Inhibition of AP‐1 with curcumin also inhibited 14‐3‐3γ up‐regulation indicating that ischemia‐induced up‐regulation of 14‐3‐3γ in astrocyte involves activation of the JNK/p‐c‐Jun/AP‐1 pathway.
Differential gene expression in LPS/IFNγ activated microglia and macrophages: in vitro versus in vivo
Authors: Schmid Christoph D. , Melchior Benoit , Masek Kokoechat , Puntambekar Shweta S. , Danielson Patria E. , Lo David D. , Gregor Sutcliffe J. , Carson Monica J. 
Published: April 2009

AbstractTwo different macrophage populations contribute to CNS neuroinflammation: CNS‐resident microglia and CNS‐infiltrating peripheral macrophages. Markers distinguishing these two populations in tissue sections have not been identified. Therefore, we compared gene expression between LPS (lipopolysaccharide)/interferon (IFN)γ‐treated microglia from neonatal mixed glial cultures and similarly treated peritoneal macrophages. Fifteen molecules were identified by quantative PCR (qPCR) as being enriched from 2‐fold to 250‐fold in cultured neonatal microglia when compared with peritoneal macrophages. Only three of these molecules (C1qA, Trem2, and CXCL14) were found by qPCR to be also enriched in adult microglia isolated from LPS/IFNγ‐injected CNS when compared with infiltrating peripheral macrophages from the same CNS. The discrepancy between the in vitro and in vivo qPCR data sets was primarily because of induced expression of the ‘microglial’ molecules (such as the tolerance associated transcript, Tmem176b) in CNS‐infiltrating macrophages. Bioinformatic analysis of the ∼19000 mRNAs detected by TOGA gene profiling confirmed that LPS/IFNγ‐activated microglia isolated from adult CNS displayed greater similarity in total gene expression to CNS‐infiltrating macrophages than to microglia isolated from unmanipulated healthy adult CNS. In situ hybridization analysis revealed that nearly all microglia expressed high levels of C1qA, while subsets of microglia expressed Trem2 and CXCL14. Expression of C1qA and Trem2 was limited to microglia, while large numbers of GABA+ neurons expressed CXCL14. These data suggest that (i) CNS‐resident microglia are heterogeneous and thus a universal microglia‐specific marker may not exist; (ii) the CNS micro‐environment plays significant roles in determining the phenotypes of both CNS‐resident microglia and CNS‐infiltrating macrophages; (iii) the CNS microenvironment may contribute to immune privilege by inducing macrophage expression of anti‐inflammatory molecules.
The brain‐specific protein, p42IP4(ADAP 1) is localized in mitochondria and involved in regulation of mitochondrial Ca2+
Authors: Galvita Anastasia , Grachev Dmitry , Azarashvili Tamara , Baburina Yulia , Krestinina Olga , Stricker Rolf , Reiser Georg 
Published: April 2009

AbstractIn brain, p42IP4(centaurin‐α1; recently named ADAP 1, which signifies ADP ribosylation factor GTPase activating protein with dual PH domains 1, within the large family of Arf‐GTPase activating proteins) is mainly expressed in neurons. p42IP4operates as a dual receptor recognising two second messengers, the soluble inositol(1,3,4,5)tetrakisphosphate and the lipid phosphatidylinositol(3,4,5)trisphosphate. We show here for the first time that p42IP4is localized in mitochondria, isolated from rat brain and from cells transfected with p42IP4. In rat brain mitochondria we additionally found interaction of p42IP4with 2′, 3′‐cyclic nucleotide 3′‐phosphodiesterase and α‐tubulin by pull‐down binding assay and by immunoprecipitation. In mitochondria from Chinese hamster ovary cells, p42IP4is predominantly associated with the intermembrane space and the inner membrane. This localization of p42IP4indicates that p42IP4might have a still unknown mitochondrial function. We studied whether p42IP4is involved in Ca2+‐induced permeability transition pore opening, which is important in mitochondrial events leading to programmed cell death. We used mouse neuroblastoma cells as a model for the functional studies of p42IP4in mitochondria. In mitochondria isolated from p42IP4‐transfected mouse neuroblastoma cells, over‐expression of p42IP4significantly decreased Ca2+capacity and lag time for Ca2+retention. Thus, we suggest that p42IP4is involved in the regulation of Ca2+transport in mitochondria. We propose that p42IP4promotes Ca2+‐induced permeability transition pore opening and thus destabilizes mitochondria.
Practicalities of participation in urban IWRM: Perspectives of wastewater management in two cities in Sri Lanka and Bangladesh
Authors: Evans Alexandra , Varma Samyuktha 
Published: April 2009

Abstract As the demand for water in cities increases, the quantity of wastewater being produced is growing at a phenomenal rate. If resources are to be managed effectively, a new paradigm is required for urban wastewater management. This paper reviews the initial findings of a participatory action planning process for managing wastewater for agricultural use. It finds that such processes need considerable facilitation, capacity building and knowledge sharing, but that if a plan can be devised that meets the needs of the stakeholders, even if some compromise is required, then certain stakeholders are likely to take responsibility for specific aspects. This may not meet the entire integrated water resources management (IWRM) vision of the plan but provided the plan is developed in such a way that incremental implementation will be beneficial then this will produce some success and may stimulate further cooperation.
Local IWRM organizations for groundwater regulation: The experiences of the Aquifer Management Councils (COTAS) in Guanajuato, Mexico
Authors: Wester Philippus , Hoogesteger Jaime , Vincent Linden 
Published: April 2009

Abstract Evidence of groundwater management by aquifer users emerging under Integrated Water Resources Management (IWRM) initiatives is presented, by analyzing the Consejos Técnicos de Aguas (COTAS; Technical Water Councils or Aquifer Management Councils) in the state of Guanajuato, Mexico, established between 1998 and 2000 by the Guanajuato State Water Commission (CEAG). Two contrasting models influenced this attempt to promote user self‐regulation of groundwater extractions: locally autonomous aquifer organizations with powers to regulate groundwater extractions versus aquifer organizations with advisory powers only. The COTAS were conceived as locally autonomous IWRM organizations consisting of all aquifer users that would work together to reduce groundwater over‐extraction and stabilize aquifer levels, at a later stage. CEAG followed an expedient IWRM approach to develop the COTAS, setting achievable targets for their development and explicitly focusing on active stakeholder participation. The article shows that, due to struggles between the state and federal levels, the COTAS have become advisory bodies that have not led to reductions in groundwater extractions. It concludes that achieving user self‐regulation of groundwater extractions requires a fuller delegation of responsibilities to the COTAS which would not be possible without addressing the institutional struggles over water governance at the state and federal levels.
Harvesting of rainwater and brooklets water to increase mountain agricultural productivity: A case study from a dry valley of southwestern China
Authors: Wu Yang , Tang Ya , Huang Chengmin 
Published: April 2009

Abstract In semi‐arid valleys of southwestern China, seasonal shortage of water is the major contributing factor to low and unstable crop yield. Harvesting of both rainwater and brooklets water in the semi‐arid valleys of Ningnan county of Sichuan Province has brought about considerable economic and environmental change. Brooklet water is collected throughout the year but mainly during the rainy season in a series of ponds while rainwater is harvested in underground tanks constructed on road side or land boundaries with only a small opening above ground to save limited cropland. Increased water availability has promoted cultivation of sugarcane, tobacco, and mulberry, and increased per unit area yield of food crops. Sericulture, sugarcane and tobacco have become three important sources of farmers’ income. The water harvesting has contributed considerably to increased rural income, poverty reduction, reduced soil erosion and improvement in overall environment. Government has played a key role in planning and implementation of water harvesting programmes. Financial support of government and clear ownership of water harvesting facilities are critical for the success of the programme. Application of similar water harvesting techniques in other areas with similar biophysical conditions would contribute to enhancing the rural economy and alleviating poverty.
Gene expression profile of Huh‐7 cells expressing hepatitis C virus genotype 1b or 3a core proteins
Authors: Pazienza Valerio , Clément Sophie , Pugnale Paolo , Conzelmann Stéphanie , Pascarella Stéphanie , Mangia Alessandra , Negro Francesco 
Published: April 2009

AbstractBackground: The liver disease expression in chronic hepatitis C patients is variable and may partially depend on the sequence of the infecting viral genotype.Aim: To identify some hepatitis C virus (HCV) genotype‐specific virus–host interactions potentially leading to clinically significant consequences.Methods: We compared the gene expression profile of Huh‐7 cells transiently expressing the core protein of HCV genotype 1b and 3a using microarray technology.Results: Thirty‐two genes were overexpressed in Huh‐7 transfected with the HCV genotype 1b core protein and 57 genes in cells transfected with the genotype 3a core protein. On the other hand, we found 20 genes downregulated by core 1b and 31 genes by core 3a. These included genes involved in lipid transport and metabolism, cell cycle, immune response and insulin signalling.Conclusion: The expression of HCV core proteins of different genotypes leads to a specific gene expression profile. This may account for the variable disease expression associated with HCV infection.
Ultrasound‐guided treatments under low acoustic power contrast harmonic imaging for hepatocellular carcinomas undetected by B‐mode ultrasonography
Authors: Maruyama Hitoshi , Takahashi Masanori , Ishibashi Hiroyuki , Okugawa Hidehiro , Okabe Shinichiro , Yoshikawa Masaharu , Yokosuka Osamu 
Published: April 2009

AbstractBackground/Aims: The aim was to examine the efficacy of contrast‐enhanced ultrasound (US) with Sonazoid™ to demonstrate ultrasonically unrecognizable hypervascular hepatocellular carcinoma (HCC) and apply percutaneous US‐guided treatments.Methods: The subjects of this prospective study were 44 cirrhotic patients with 55 hypervascular lesions (12.7±4.5 mm) found by contrast‐enhanced computed tomography but unrecognized by non‐contrast US. Contrast‐enhanced US was performed to demonstrate these hepatic lesions after an intravenous injection of Sonazoid™ (0.0075 ml/kg). The sonograms in both the early phase (for 1 min after injection) and the late phase (5–10 min after) were taken in the harmonic imaging mode under a low mechanical index (0.24–0.3).Results: Fifty‐three lesions were demonstrated by contrast‐enhanced US, 52 with positive enhancement in the early phase and 44 with negative enhancement in the late phase. Percutaneous US‐guided treatments were successfully performed for 42 lesions (ethanol injection in 20 and radiofrequency ablation in 22) in 32 patients with reference to contrast‐enhanced US findings. Six patients were treated by transarterial chemoembolization alone because they had more than three lesions in the liver. In the remaining seven lesions in six patients, six were diagnosed as non‐HCC lesions: five with vascular abnormalities such as arterioportal or arteriovenous communication and the other one with benign lesion in alcoholic liver disease. These six lesions and one HCC lesion with severe liver damage were followed up without any treatment.Conclusions: As the detectability of ultrasonically unrecognizable hypervascular HCC improved by contrast‐enhanced US with Sonazoid™, a wider application of percutaneous US‐guided treatments may be possible.
ABCB4 sequence variations in young adults with cholesterol gallstone disease
Authors: Nakken Karl Esten , Labori Knut Jørgen , Rødningen Olaug K. , Nakken Sigve , Berge Knut E. , Eiklid Kristin , Ræder Morten G. 
Published: April 2009

AbstractBackground and Aims: Mutations in the gene encoding the ABCB4 [adenosine triphosphate (ATP)‐binding cassette, sub‐family B (MDR/TAP), member 4] transporter lower phosphatidylcholine output into bile and contribute to cholesterol gallstone formation by decreasing the solubility of cholesterol in bile. Mutations in ABCB4 have been identified in patients with low phospholipid‐associated cholelithiasis. The aim of the present study was to determine the types and frequencies of ABCB4 mutations in cholecystectomized patients aged <40 years.Patients and methods: Hundred and four patients (mean age 30.6 years, range 12–39) were included in the study and the ABCB4 gene was sequenced. The frequency of missense mutations found in the patient material was measured in 95 healthy controls. The potential functional implications of the ABCB4 missense variations were assessed by computerized analysis (BLOSUM62 and Grantham substitution matrices, polymorphism phenotyping and sorting intolerant from tolerant).Results: One patient was heterozygous for a frameshift mutation (c.1399_1400ins10/p.Y467F fsX25). Another patient was heterozygous for a nonsense mutation (c.3136C>T/p.R1046X). These two mutations are considered detrimental to ABCB4 protein function. In addition, six missense mutations were found in the ABCB4 gene, and three of these were only present in patients.Conclusion: In our study, <2% of young gallstone patients were found to be heterozygous for detrimental ABCB4 mutations. The functional implication of several missense mutations remains to be clarified. Thus, mutations in the ABCB4 gene are a rare cause of gallstone disease.
Radiotracer imaging studies in hepatic encephalopathy: ISHEN practice guidelines
Authors: Berding Georg , Banati Richard B. , Buchert Ralph , Chierichetti Franca , Grover Vijay P. B. , Kato Akinobu , Keiding Susanne , Taylor‐Robinson Simon D. 
Published: April 2009

AbstractThere is lack of consensus on radiotracer usage in hepatic encephalopathy (HE). We have focused our attention on three main areas: (i) radiotracer imaging in animal models of HE, (ii) methodological issues of radiotracer imaging in HE and (iii) radiotracer imaging studies on the pathophysiology and (new) therapies in HE. We suggest the following: 1. Positron emission tomography (PET) and single photon emission computed tomography lend themselves to the study of animal models of HE, but the models that are suitable depend on the specific research question. Magnetic resonance imaging (MRI) may be a useful alternative technique. 2. Owing to the cost of the technique, there is a need for multicentre human PET studies to overcome the problem of underpowered small studies being undertaken in individual research centres. There should be a unified PET protocol with central, anonymised data analysis in one centre, using validated methodology, on behalf of all participating centres. Such studies would be useful for the assessment of early intervention in patients with subtle neuropsychiatric symptoms, or for clarification of the effect of liver transplantation on HE. 3. While radiotracer imaging modalities remain useful research tools for the study of pathogenesis and for the assessment of treatment effects, there is no consensus on the use of imaging in routine clinical practice for diagnosis and prognosis. The most promising objective tools appear to be magnetic resonance spectroscopy (MRS) and volumetric MRI, which can be performed in multiple centres without the difficulties that radiotracer imaging entail.