bluuebunny/crossref_metadata_2025_split huggingface dataset:
MeTA studio: A cross platform, programmable IDE for computational chemist
Authors: Ganesh V. 
Published: August 2008

AbstractThe development of a cross‐platform, programmable integrated development environment (IDE), MeTA Studio, specifically tailored but not restricted to computational chemists working in the area of quantum chemistry with an emphasis on handling large molecules is presented. The IDE consists of a number of modules which include a visualizer and a programming and collaborative framework. The inbuilt viewer assists in visualizing molecules, their scalar fields, manually fragmenting a molecule, and introduces some innovative but simple techniques for handling large molecules. These include a simpleFindlanguage and simultaneous multiple camera views of the molecule. Basic tools needed to handle collaborative computing effectively are also included opening up new vistas for sharing ideas and information among computational chemists working on similar problems. MeTA Studio is an integrated programming environment that provides a rich set of application programming interfaces (APIs) which can be used to easily extend its functionality or build new applications as needed by the users. (http://code.google.com/p/metastudio/) © 2008 Wiley Periodicals, Inc. J Comput Chem 2009
Strategies to model the near‐solute solvent molecular density/polarization
Authors: Yang Pei‐Kun , Lim Carmay 
Published: August 2008

AbstractThe solvent molecular distribution significantly affects the behavior of the solute molecules and is thus important in studying many biological phenomena. It can be described by the solvent molecular density distribution, g, and the solvent electric dipole distribution, p. The g and p can be computed directly by counting the number of solvent molecules/dipoles in a microscopic volume centered at r during a simulation or indirectly from the mean force F and electrostatic field E acting on the solvent molecule at r, respectively. However, it is not clear how the g and p derived from simulations depend on the solvent molecular center or the solute charge and if the gF and pE computed from the mean force and electric field acting on the solvent molecule, respectively, could reproduce the corresponding g and p obtained by direct counting. Hence, we have computed g, p, gF, and pE using different water centers from simulations of a solute atom of varying charge solvated in TIP3P water. The results show that gF and pE can reproduce the g and p obtained using a given count center. This implies that rather than solving the coordinates of each water molecule by MD simulations, the distribution of water molecules could be indirectly obtained from analytical formulas for the mean force F and electrostatic field E acting on the solvent molecule at r. Furthermore, the dependence of the g and p distributions on the solute charge revealed provides an estimate of the change in g and p surrounding a biomolecule upon a change in its conformation. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Implementation of dynamical nucleation theory with quantum potentials
Authors: Crosby Lonnie D. , Kathmann Shawn M. , Windus Theresa L. 
Published: August 2008

AbstractA method is implemented within the context of dynamical nucleation theory in order to efficiently determine the ab initio water dimer evaporation rate constant. The drive for increased efficiency in a Monte Carlo methodology is established by the need to use relatively expensive quantum mechanical interaction potentials. A discussion is presented illustrating the theory, algorithm, and implementation of this method to the water dimer. Hartree–Fock and second order Møller–Plesset perturbation theories along with the Dang–Chang polarizable classical potential are utilized to determine the ab initio water dimer evaporation rate constant. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Screening and characterization of reactive metabolites using glutathione ethyl ester in combination with Q‐trap mass spectrometry
Authors: Wen Bo , Fitch William L. 
Published: August 2008

AbstractThe present study describes a new analytical approach for the detection and characterization of chemically reactive metabolites using glutathione ethyl ester (GSH‐EE) as the trapping agent in combination with hybrid triple quadrupole linear ion trap mass spectrometry. Polarity switching was applied between a negative precursor ion (PI) survey scan and the positive enhanced product ion (EPI) scan. The negative PI scan step was carried out monitoring the anion atm/z300, corresponding to deprotonated γ‐glutamyl‐dehydroalanyl‐glycine ethyl ester originating from the GSH‐EE moiety. Samples resulting from incubations in the presence of GSH‐EE were cleaned and concentrated by solid‐phase extraction, followed by the PI‐EPI analysis. Unambiguous identification of GSH‐EE‐trapped reactive metabolites was greatly facilitated by the unique survey scan of the anion atm/z300, which achieved less background interference, in particular, from endogenous glutathione adducts present in human liver microsomes. Further structural characterization was achieved by analyzing positive MS2spectra that featured rich fragments without mass cutoff and were acquired in the same liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analysis. The effectiveness and reliability of this approach was evaluated using a number of model compounds in human liver microsomal incubations, including acetaminophen, amodiaquine, carbamazepine, 4‐ethylphenol, imipramine and ticlopidine. In addition, iminoquinone reactive metabolites of mianserin were trapped and characterized for the first time using this method. Compared to neutral loss (NL) scanning assays using GSH as the trapping agent, the results have demonstrated superior selectivity, sensitivity, and reliability of this current approach. Copyright © 2008 John Wiley & Sons, Ltd.
Prevalence and genotype distribution of multiple human papillomavirus infection in the uterine cervix: A 7.5‐year longitudinal study in a routine cytology‐based screening population in West Germany
Authors: Kovács Krisztina , Varnai Alinda D. , Bollmann Magdolna , Bankfalvi Agnes , Szendy Marianna , Speich Norbert , Schmitt Christoph , Pajor László , Bollmann Reinhard 
Published: August 2008

AbstractThe availability of vaccines against certain HPV types and the development of broad spectrum genotyping methods have increased interest in co‐infections with different HPV types. In the present study, the prevalence and type‐specific composition of multiple HPV infections were investigated in a routine cervical screening population in West Germany both at a cross‐sectional level and longitudinally. Four hundred eighty‐nine out of 8,090 women were diagnosed with multiple HPV infections once or repeatedly. During the 7.5‐year study period, the cumulative prevalence of HPV co‐infections was 15.3% in contrast to the cross‐sectional prevalence of 3.8% at single visits. The overall cumulative prevalence within the cohort of all women screened was 6.9%. Using consensus PCR with sequencing and type‐specific PCRs, two to three HPV types were detected simultaneously, whereas broad spectrum methods detected up to seven different genotypes in one sample. Nevertheless, the most common pattern of co‐infection occurred with two to three HPV types irrespective of the age of the patient, cytology and histology of the lesions and the method used. The most common genotypes detected were HPV 16, 31, 53, 51, 52, and 66, and the most common pattern of co‐infection was double infection with HPV 16 and 31. These results show that rates and patterns of multiple HPV infections are largely dependent on the methodology used and the time interval between tests. Given the significance of HPV vaccination and its expected influence on immunized populations, it is essential to gain additional insights into the natural course and pathogenic effect of multiple HPV infection longitudinally. J. Med. Virol. 80:1814–1823, 2008. © 2008 Wiley‐Liss, Inc.
Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases of intrauterine fetal death: Association with pathological findings
Authors: Syridou Garyfallia , Spanakis Nicholas , Konstantinidou Anastasia , Piperaki Evangelia‐Theophano , Kafetzis Dimitrios , Patsouris Efstratios , Antsaklis Aris , Tsakris Athanassios 
Published: August 2008

AbstractThere are previous indications that transplacental transmission of cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and 2 (HSV‐1/2) cause fetal infections, which may lead to fetal death. In a prospective case–control study we examined the incidence of these viruses in intrauterine fetal death and their association with fetal and placenta pathological findings. Molecular assays were performed on placenta tissue extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and HSV‐1/2 genomes. Formalin‐fixed, paraffin‐embedded liver, spleen and placenta tissues of fetal death cases were evaluated histologically. Thirty‐four percent of placental specimens taken from intrauterine fetal deaths were positive for any of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV‐1/2, respectively), whereas only 6% of those taken from full term newborns were positive (P = 0.0017). No dual infection was observed. This difference was also observed when fetal deaths with a gestational age <20 weeks or a gestational age >20 weeks were compared with the controls (P = 0.025 and P = 0.0012, respectively). Intrauterine death and the control groups differed in the detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more pronounced in a gestational age >20 weeks (P = 0.03). Examination of the pathological findings among the PCR‐positive and PCR‐negative fetal deaths revealed that hydrops fetalis and chronic villitis were more common among the former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an association was detected between viral infection and fetal death, which was more pronounced in the advanced gestational age. Fetal hydrops and chronic villitis were evidently associated with viral DNA detection in cases of intrauterine death. J. Med. Virol. 80:1776–1782, 2008. © 2008 Wiley‐Liss, Inc.
Genetic disruption of cyclooxygenase‐2 does not improve histological or behavioral outcome after traumatic brain injury in mice
Authors: Ahmad Muzamil , Rose Marie E. , Vagni Vincent , Griffith Raymond P. , Dixon C. Edward , Kochanek Patrick M. , Hickey Robert W. , Graham Steven H. 
Published: August 2008

AbstractIncreasing evidence suggests a role for cyclooxygenase‐2 (COX‐2) in traumatic brain injury (TBI). In the present study, the role of COX‐2 in TBI was investigated using COX‐2 gene‐disrupted (COX‐2 null) mice and wild‐type (WT) controls that were subjected to the controlled cortical impact (CCI) model of TBI. There was increased expression of COX‐2 in ipsilateral hippocampus in WT mice subjected to CCI. CCI resulted in a significant increase in prostaglandin E2 concentrations in WT compared with COX‐2 null hippocampi. There was a significant increase in TUNEL staining of CA1 neurons 24 hr after CCI in WT, but not in COX‐2 null mice, compared with sham‐operated controls, which is consistent with a protective role for COX‐2 in the early phase of injury after TBI. However, there was no difference in lesion volume 21 days after CCI in COX‐2 null and WT mice. COX‐2 gene disruption did not alter Morris water maze performance. Taken together, these results suggest only a minor role for COX‐2 activity in determining outcome after TBI in mouse. © 2008 Wiley‐Liss, Inc.
Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell death
Authors: Ikeno Yutaka , Cheon So‐hyun , Konno Naoko , Nakamura Ayako , Kitamoto Katsuhiko , Arioka Manabu 
Published: August 2008

AbstractCultured cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing stimulation and provide an in vitro model system with which to study the effects of neurotrophic substances. Our previous results showed that secretory phospholipases A2 (sPLA2s) protect CGNs from apoptotic cell death under the nondepolarizing condition. In this study, we further analyzed the mechanism whereby sPLA2 exhibits this effect. Among the primary metabolites of sPLA2 tested, lysophosphatidylcholine (LPC), but not other lysophospholipids, remarkably rescued CGNs from apoptosis. In contrast, neither arachidonic nor oleic acids displayed neurotrophic effect. Release of LPC into the culture media occurred in response to sPLA2 treatment, and degradation or sequestration of LPC attenuated the survival‐promoting effects of sPLA2 and LPC. The neurotrophic effect of LPC required the presence of extracellular Ca2+ and L‐type Ca2+ channel activity, suggesting that Ca2+ influx across the plasma membrane is evoked by LPC. sPLA2‐ or LPC‐induced promotion of CGN survival was suppressed by inhibitors of protein kinase A and phospholipase C, suggesting that they play a role in mediating survival‐promoting signal of sPLA2. The results presented here demonstrate a novel, unexpected neurotrophin‐like effect of LPC in the central nervous system. © 2008 Wiley‐Liss, Inc.
Specific interaction between Sam68 and neuronal mRNAs: Implication for the activity‐dependent biosynthesis of elongation factor eEF1A
Authors: Grange Julien , Belly Agnès , Dupas Stéphane , Trembleau Alain , Sadoul Rémy , Goldberg Yves 
Published: August 2008

AbstractIn cultured hippocampal neurons and in adult brain, the splicing regulatory protein Sam68 is partially relocated to the somatodendritic domain and associates with dendritic polysomes. Transfer to the dendrites is activity‐dependent. We have investigated the repertoire of neuronal mRNAs to which Sam68 binds in vivo. By using coimmunoprecipitation and microarray screening techniques, Sam68 was found to associate with a number of plasticity‐related mRNA species, including Eef1a1, an activity‐responsive mRNA coding for translation elongation factor eEF1A. In cortical neuronal cultures, translation of the Eef1a1 mRNA was strongly induced by neuronal depolarisation and correlated with enhanced association of Sam68 with polysomal mRNAs. The possible function of Sam68 in Eef1a1 mRNA utilization was studied by expressing a dominant‐negative, cytoplasmic Sam68 mutant (GFP‐Sam68ΔC) in cultured hippocampal neurons. The level of eEF1A was lower in neurons expressing GFP‐Sam68ΔC than in control neurons, supporting the proposal that endogenous Sam68 may contribute to the translational efficiency of the Eef1a1 mRNA. These findings are discussed in the light of the complex, potentially crucial regulation of eEF1A biosynthesis during long‐term synaptic change. © 2008 Wiley‐Liss, Inc.
Effects of neuroglobin overexpression on mitochondrial function and oxidative stress following hypoxia/reoxygenation in cultured neurons
Authors: Liu Jianxiang , Yu Zhanyang , Guo Shuzhen , Lee Sun‐Ryung , Xing Changhong , Zhang Chenggang , Gao Yan , Nicholls David G. , Lo Eng H. , Wang Xiaoying 
Published: August 2008

AbstractNeuroglobin (Ngb) is a recently discovered tissue globin with a high affinity for oxygen that is widely and specifically expressed in neurons of vertebrate central and peripheral nervous systems. Our laboratory and others have shown Ngb overexpression can protect neurons against hypoxic/ischemic insults, but the underlying mechanisms remain poorly understood. In this study, we examined the effects of Ngb overexpression on mitochondrial function, oxidative stress, and neurotoxicity in primary cortical neurons following hypoxia/reoxygenation (H/R). Ngb‐overexpressing transgenic neurons (Ngb‐Tg) were significantly protected against H/R‐induced cell death. Rates of decline in ATP levels, MTT reduction, and mitochondrial membrane potential were significantly ameliorated in Ngb‐Tg neurons. Furthermore, Ngb overexpression reduced superoxide anion generation after H/R, whereas glutathione levels were significantly improved compared with WT controls. Taken together, these data suggest that Ngb is neuroprotective against hypoxia, in part by improving mitochondria function and decreasing oxidative stress. © 2008 Wiley‐Liss, Inc.
Differential subcellular distribution and colocalization of the microsomal and soluble epoxide hydrolases in cultured neonatal rat brain cortical astrocytes
Authors: Rawal Seema , Morisseau Christophe , Hammock Bruce D. , Shivachar Amruthesh C. 
Published: August 2008

AbstractThe microsomal epoxide hydrolase (mEH) and soluble epoxide hydrolase (sEH) enzymes exist in a variety of cells and tissues, including liver, kidney, and testis. However, very little is known about brain epoxide hydrolases. Here we report the expression, localization, and subcellular distribution of mEH and sEH in cultured neonatal rat cortical astrocytes by immunocytochemistry, subcellular fractionation, Western blotting, and radiometric enzyme assays. Our results showed a diffuse immunofluorescence pattern for mEH, which colocalized with the astroglial cytoskeletal marker glial fibrillary acidic protein (GFAP). The GFAP‐positive cells also expressed sEH, which was localized mainly in the cytoplasm, especially in and around the nucleus. Western blot analyses revealed a distinct protein band with a molecular mass of ∼50 kDa, the signal intensity of which increased about 1.5‐fold in the microsomal fraction over the whole‐cell lysate and other subcellular fractions. The polyclonal anti‐human sEH rabbit serum recognized a protein band with a molecular mass similar to that of the affinity‐purified sEH protein (∼62 kDa), the signal intensity of which increased over 1.7‐fold in the 105,000gsupernatant fraction over the cell lysate. Furthermore, the corresponding enzyme activities measured by using mEH‐ and sEH‐selective substrates generally corroborated the immunocytochemical and Western blotting data. These results suggest that rat brain cortical astrocytes differentially coexpress mEH and sEH enzymes. The differential subcellular localization of mEH and sEH may play a role in the cerebrovascular functions that are known to be affected by brain‐derived vasoactive epoxides. © 2008 Wiley‐Liss, Inc.
Chronic fluoxetine treatment improves ischemia‐induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke
Authors: Li Wen‐Lei , Cai Hui‐Hui , Wang Bin , Chen Ling , Zhou Qi‐Gang , Luo Chun‐Xia , Liu Na , Ding Xin‐Sheng , Zhu Dong‐Ya 
Published: August 2008

AbstractCognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia‐induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg−1, i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia‐induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits. © 2008 Wiley‐Liss, Inc.
Mitochondrial localization of DJ‐1 leads to enhanced neuroprotection
Authors: Junn Eunsung , Jang Won Hee , Zhao Xin , Jeong Byeong Seon , Mouradian M. Maral 
Published: August 2008

AbstractMutations in DJ‐1 (PARK7) cause recessively inherited Parkinson's disease. DJ‐1 is a multifunctional protein with antioxidant and transcription modulatory activity. Its localization in cytoplasm, mitochondria, and nucleus is recognized, but the relevance of this subcellular compartmentalization to its cytoprotective activity is not fully understood. Here we report that under basal conditions DJ‐1 is present mostly in the cytoplasm and to a lesser extent in mitochondria and nucleus of dopaminergic neuroblastoma SK‐N‐BE(2)C cells. Upon oxidant challenge, more DJ‐1 translocates to mitochondria within 3 hr and subsequently to the nucleus by 12 hr. The predominant DJ‐1 species in both mitochondria and nucleus is a dimer believed to be the functional form. Mutating cysteine 106, 53, or 46 had no impact on the translocation of DJ‐1 to mitochondria. To study the relative neuroprotective activity of DJ‐1 in mitochondria and nucleus, DJ‐1 cDNA constructs fused to the appropriate localization signal were transfected into cells. Compared with 30% protection against oxidant‐induced cell death in wild‐type DJ‐1‐transfected cells, mitochondrial targeting of DJ‐1 provided a significantly stronger (55%) cytoprotection based on lactate dehydrogenase release. Nuclear targeting of DJ‐1 preserved cells equally as well as the wild‐type protein. These observations suggest that the time frame for the translocation of DJ‐1 from the cytoplasm to mitochondria and to the nucleus following oxidative stress is quite different and that dimerized DJ‐1 in mitochondria is functional as an antioxidant not related to cysteine modification. These findings further highlight the multifaceted functions of DJ‐1 as a cytoprotector in different cellular compartments. © 2008 Wiley‐Liss, Inc.
Neuroprotective effects of erythropoietin posttreatment against kainate‐induced excitotoxicity in mixed spinal cultures
Authors: Yoo Jong Yoon , Won You Jin , Lee Jong Hwan , Kim Jong Uk , Sung In Young , Hwang Seung Jun , Kim Mi Jung , Hong Hea Nam 
Published: August 2008

AbstractAlthough the neuroprotective effects of erythropoietin (EPO) preconditioning are well known, the potential of postapplied EPO to protect neurons against excitotoxic injury has not been clearly established. Here we show that kainate (KA)‐induced excitotoxicity, which plays a key role in secondary spinal cord injury, decreased neuron survival, inhibited neurite extension, and significantly reduced the expression of erythropoietin receptors (EpoR) in cultured spinal neurons. Posttreatment with EPO for 48 hr protected neurons against KA‐induced injury, opposing KA‐induced apoptosis and promoting regrowth of motoneuron neurites. These neuroprotective effects were paralleled by a restoration of EpoR expression. The importance of the EpoR signaling pathway was demonstrated using an EpoR blocking antibody, which neutralized the neuroprotective action of EPO posttreatment and prevented EPO‐induced increases in EpoR expression. We also found that up‐regulated EpoR stimulated the Janus kinase 2 (JAK2) pathway, which is known to facilitate neuronal growth and neurite regeneration. Although EPO posttreatment modestly attenuated KA‐induced reactive gliosis in mixed neuron–glial cultures, blocking EpoR activity did not alter glial fibrillary acidic protein expression or astrocyte proliferation. In conclusion, 48 hr treatment with EPO following KA exposure induced EpoR‐dependent protection against excitotoxic injury, demonstrating that preconditioning is not a prerequisite for neuroprotection by EPO. The neuroprotective effects of EPO posttreatment were mediated by an EpoR‐dependent signaling pathway that possibly involves JAK2. The neuroprotective effect of EPO posttreatment against KA excitotoxicity appears to reflect direct effects on neurons and not indirect effects mediated by astrocytes. © 2008 Wiley‐Liss, Inc.