bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward accurate relative energy predictions of the bioactive conformation of drugs
Authors: Butler Keith T. , Luque F. Javier , Barril Xavier
Published: August 2008

Quantifying the relative energy of a ligand in its target‐bound state (i.e. the bioactive conformation) is essential to understand the process of molecular recognition, to optimize the potency of bioactive molecules and to increase the accuracy of structure‐based drug design methods. This is, nevertheless, seriously hampered by two interrelated issues, namely the difficulty in carrying out an exhaustive sampling of the conformational space and the shortcomings of the energy functions, usually based on parametric methods of limited accuracy. Matters are further complicated by the experimental uncertainty on the atomic coordinates, which precludes a univocal definition of the bioactive conformation. In this article we investigate the relative energy of bioactive conformations introducing two major improvements over previous studies: the use sophisticated QM‐based methods to take into account both the internal energy of the ligand and the solvation effect, and the application of physically meaningful constraints to refine the bioactive conformation. On a set of 99 drug‐like molecules, we find that, contrary to previous observations, two thirds of bioactive conformations lie within 0.5 kcal mol−1 of a local minimum, with penalties above 2.0kcal mol−1 being generally attributable to structural determination inaccuracies. The methodology herein described opens the door to obtain quantitative estimates of the energy of bioactive conformations and can be used both as an aid in refining crystallographic structures and as a tool in drug discovery. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009
MeTA studio: A cross platform, programmable IDE for computational chemist
Authors: Ganesh V.
Published: August 2008

The 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

The 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

A 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

The 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

The 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

There 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

Increasing 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

Cultured 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

In 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

Neuroglobin (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

The 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

Cognitive 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

Mutations 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

Although 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.
Regulation of protein kinases and coregulatory interplay of S‐100β and serotonin transporter on serotonin levels in diabetic rat brain
Authors: Ramakrishnan R. , Sheeladevi R. , Namasivayam A.
Published: August 2008

Protein kinases are critical component in the regulation of signal transduction pathways, including neurotransmitters. Our previous studies have shown that serotonin (5‐HT) altered under diabetic condition was accompanied by alterations of protein kinase C‐α (PKC‐α) and CaMKII, and those alterations were reversed after insulin administration. The current study showed that alloxan‐induced diabetic animals revealed hyperglycemia and was associated with an increase in the content of 5‐HT, PKC‐α expression and PKC activity (P< 0.05) simultaneously in striatum (ST), midbrain (MB), pons medulla (PM), cerebellum (CB), and cerebral cortex (CCX) from 7 days to 60 days. Although the 5‐HT levels in hippocampus (HC) and hypothalamus (HT) were not altered, the PKC‐α expression and PKC activity showed increases (P< 0.05) in level in HC. Insulin administration reversed all these changes to a normal level. In contrast, the in vitro study has shown that the 5‐HT levels correlated with PKC‐α expressions as well as PKC activity (P< 0.05) only in ST, MB, and CB either after induction with phorbol 12‐myristate 13‐acetate (PMA) or blocking with chelerythrine, whereas PM and CCX remained elevated (P< 0.05), implying a regulatory role for PKC‐α only in ST, MB, and CB. However, our consecutive studies have shown that the 5‐HT level in PM was regulated by p38‐mitogen‐activated protein kinase (p38‐MAPK) both in vivo and in vitro, whereas the 5‐HT level in CCX was coregulated by S‐100β by protein–protein interaction with serotonin transporter (SERT) via 8‐bromoadenosine 3′,5′‐cyclic monophosphate sodium salt (8‐Br‐cAMP)‐induced cAMP/PKAII pathway(s). © 2008 Wiley‐Liss, Inc.
1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one inhibits neurite outgrowth and causes neurite retraction in PC12 cells independently of soluble guanylyl cyclase
Authors: Lee Han Gil , Kim So Young , Kim Du Sik , Seo Su Ryeon , Lee Syng‐Ill , Shin Dong Min , De Smet Patrick , Seo Jeong Taeg
Published: August 2008

The effect of the potent soluble guanylyl cyclase (sGC) inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) on neurite outgrowth and retraction was investigated in PC12 cells and SH‐SY5Y human neuroblastoma cells. ODQ inhibited neurite outgrowth and triggered neurite retraction in the cells stimulated with nerve growth factor (NGF), staurosporine, or Y‐27632. The nitric oxide (NO) scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethyl‐imidazoline‐1‐oxyl‐3‐oxide (PTIO) had little effect on neurite outgrowth induced by Y‐27632 or staurosporine. In the presence of ODQ, treatment of the cells with the cell‐permeable cGMP analogue 8‐bromo‐cGMP failed to retrigger Y‐27632‐ and staurosporine‐induced neurite outgrowth. Furthermore, the depletion of sGC by RNA interference failed to prevent Y‐27632‐ and staurosporine‐induced neurite outgrowth. These results indicate that the NO/sGC/cGMP signaling cascade is not critically involved in ODQ‐induced neurite remodeling. The MEK inhibitor PD98059 did not inhibit neurite outgrowth, and Y‐27632 and staurosporine did not induce ERK phosphorylation, suggesting that the inhibitory effect of ODQ on neurite outgrowth is independent of the ERK signaling pathway. In contrast, pretreatment with dithionite or a hemin‐glutathione mixture reversed the inhibitory effect of ODQ on Y‐27632‐ and staurosporine‐induced neurite outgrowth, indicating that ODQ might act on an intracellular redox‐sensitive molecule. We conclude that ODQ inhibits Y‐27632‐ and staurosporine‐induced neurite outgrowth and triggers neurite retraction in an sGC‐independent manner in neuronal cells and suggest that oxidation of unidentified redox‐sensitive protein could be responsible for these effects. © 2008 Wiley‐Liss, Inc.
Validation of reference genes for normalization of real‐time quantitative RT‐PCR data in traumatic brain injury
Authors: Cook Naomi L. , Vink Robert , Donkin James J. , van den Heuvel Corinna
Published: August 2008

Careful validation of reference genes used for the normalization of real‐time RT‐PCR data is required to obtain accurate results regarding gene expression. We evaluated the stability of seven commonly used reference genes in the cerebral cortex and hippocampus of rats 3 days following traumatic brain injury (TBI). HPRT, SDHA, and GUSB were found to be the most stable reference genes in the cerebral cortex, whereas B2MG, TBP, and GAPDH were the most stable in the hippocampus. The use of three reference genes was determined to be the optimal number for accurate normalization of data. To illustrate this point, when our gene of interest, substance P (SP), was normalized against the three most stable reference genes in both brain areas, we found no significant difference between injured and uninjured rats at the 3‐day time point. However, when our SP data were normalized to each reference gene individually, SP mRNA level was highly variable depending on the reference gene chosen. The results of the present study highlight the importance of validating reference genes to be used for real‐time RT‐PCR analysis. The use of the most stable reference genes presented here will allow more accurate normalization of gene expression data in TBI. © 2008 Wiley‐Liss, Inc.
Effect of fencing, artificial seeding and abandonment on vegetation composition and dynamics of ‘black soil land’ in the headwaters of the Yangtze and the Yellow Rivers of the Qinghai‐Tibetan Plateau
Authors: Shang Z. H. , Ma Y. S. , Long R. J. , Ding L. M.
Published: August 2008

Rangeland management can affect plant diversity and plant functional groups of native grassland communities. To improve pasture for livestock grazing from the existing poisonous and ruderal vegetation in the ‘black soil land’ grassland in the headwaters of the Yangtze and the Yellow Rivers (HAYYR) of the Qinghai‐Tibetan Plateau, three treatments (fencing‐FT, artificial seeding with local grasses‐ST and abandonment‐AT) were applied during a 5‐year period (2000–2005). Plant diversity and groups (sedges, grasses and dwarf shrubs) in the treated plots were compared with non‐treated control plots. Results showed that (1) FT promoted an increase in forbs species, but there was no change in the other plant functional groups; (2) with ST, species richness of forbs decreased but grass species increased indicating that sowing local grasses could change plant composition of black soil land in the short‐term, and increase the proportion of grasses and, thus, forage for grazing and (3) AT, after plowing, was similar to CK plots, with forbs being the dominant plant functional group for the 5 years. In conclusion, the goal to alter black soil land cover from poisonous and ruderal plants to more useful plants for livestock grazing by either fencing, artificial seeding or abandonment was not successful in the long term. Copyright © 2008 John Wiley & Sons, Ltd.
A Capelli type theorem for multiplicative convolutions of polynomials
Authors: Bonciocat Anca Iuliana , Ciprian Bonciocat Nicolae
Published: August 2008

We prove a Capelli type theorem on the canonical decomposition for multiplicative convolutions of polynomials. We derive then some irreducibility criteria for convolutions of polynomials in several variables over a given field. The irreducibility conditions are expressed only in terms of the degrees of the polynomials in convolution, the degrees of their coefficients, and the degrees of some suitable divisors of the resulting leading coefficient. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Property (quasi‐α) and the denseness of norm attaining mappings
Authors: Choi Yun Sung , Song Hyun Gwi
Published: August 2008

We introduce property (quasi ‐α), which implies property (A) defined by Lindenstrauss [10] and whose dual property is property (quasi‐β) [2]. We consider relations between this property and other sufficient conditions for property (A), and study the denseness of norm attaining mappings under the conditions of these properties. In particular, if each of the Banach spaces Xk , 1 ≤ k ≤ n – 1, has property (quasi‐α) and Xn has property (A), then the projective tensor product X1 ··· Xn has property (A). (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stability criterion for second order linear impulsive differential equations with periodic coefficients
Authors: Guseinov G. Sh. , Zafer A.
Published: August 2008

In this paper we obtain instability and stability criteria for second order linear impulsive differential equations with periodic coefficients. Further, a Lyapunov type inequality is also established. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A distributional limit law for the continued fraction digit sum
Authors: Kesseböhmer Marc , Slassi Mehdi
Published: August 2008

We consider the continued fraction digits as random variables measured with respect to Lebesgue measure. The logarithmically scaled and normalised fluctuation process of the digit sums converges strongly distributional to a random variable uniformly distributed on the unit interval. For this process normalised linearly we determine a large deviation asymptotic. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On Hill's operator with a matrix potential
Authors: Veliev O. A.
Published: August 2008

In this article we obtain asymptotic formulas for eigenvalues and eigenfunctions of the self‐adjoint operator generated by a system of Sturm–Liouville equations with summable coefficients and quasiperiodic boundary conditions. Then using these asymptotic formulas, we find conditions on the potential for which the number of gaps in the spectrum of the Hill's operator with matrix potential is finite. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Macromol. Rapid Commun. 16/2008
Authors: Zhou Xuechang , Li Junfang , Wu Chi , Zheng Bo
Published: August 2008

Back Cover: A microfluidic platform was developed for loading, concentrating and studying the aqueous solution of poly(N–isopropylacrylamide) in a microchamber. The phase diagram of the polymer solution was successfully constructed, as can be seen on the back cover picture. Further details can be found in the article by X. Zhou, J. Li, C. Wu, and B. Zheng* on page 1363.
Biosynthesis of Multi‐Component Polyhydroxyalkanoates by the Bacterium Wautersia eutropha
Authors: Volova Tatiana G. , Kalacheva Galina S. , Steinbüchel Alexander
Published: August 2008

The study addresses the effect of different conditions of carbon nutrition on synthesis of polyhydroxyalkanoates by the bacterium Wautersia eutropha. In experiments with two wild type strains (H16 and B5786), it has been first found that under mixotrophic growth conditions – CO2 + co‐substrate (alkanoic acids) – bacteria can synthesize multi‐component PHAs, consisting of short‐ and medium‐chain‐length monomers with carbon chains containing 4 to 8 atoms. It has been shown that PHA composition is determined by the type of the co‐substrate. Fatty acids with odd number of carbons induce bacteria to synthesize four‐ and five‐component PHAs with hydroxybutyrate, hydroxyvalerate as major monomers and hydroxyhexanoate, hydroxyheptanoate and hydroxyoctanoate as minor, occasionally occurring, ones. Fatty acids with even number of carbons induce synthesis of not only their respective monomers (hydroxyhexanoate and hydroxyoctanoate) but also hydroxyvalerate, making possible synthesis of four‐component PHAs, containing hydroxybutyrate and hydroxyhexanoate as major components (up to 18 mol%). A family of short‐ and medium‐chain‐length four‐ and five‐component PHAs were synthesized and their physicochemical properties examined.
Isolation of PHA–Producing Bacteria from Date Syrup Waste
Authors: Ataei Seyed Ahmad , Vasheghani‐Farahani Ebrahim , Shojaosadati Seyed Abbas , Tehrani Hossein Abdul
Published: August 2008

Since the major problem associated with the industrial production of Polyhydroxyalkanoates (PHAs) is their high production cost, this study was carried out using date syrup as the major carbon source to decrease the production cost and also help to supply other nutrient requirements. To isolate PHA–producing bacteria for this purpose, microorganisms were isolated from the syrup waste of a local date factory. These purified colonies were screened for intracellular granules by staining with Sudan Black. The positive‐staining strains were grown for production of PHAs in 5% date syrup as carbon source supplemented with mineral salt medium. The culture was incubated at 30 °C with shaking at 140 rpm for 60 h. Among positively stained bacteria, the best PHA producers were selected on the basis of cell growth, cell dry weight, PHA content and the monomer composition of PHA. One of them could utilize date syrup for growth and produce the homopolymer of Polyhydroxybutyrate (PHB) with a cell density of about 5.1 g/L and maximum concentration of PHB equal to 3.6 g/L which is 71% of cell dry weight. Another one produces copolymer of Poly (hydroxybutyrate‐hydroxyvalerate) in date syrup media with a maximum concentration of 2.2 g/L containing 10 wt % valerate in shake flask cultivation.
Luminous Bacteria as Producers of Polyhydroxyalkanoates
Authors: Boyandin Anatoly , Kalacheva Galina S. , Medvedeva Svetlana , Rodicheva Emma , Volova Tatiana G.
Published: August 2008

The study addresses the ability of luminous bacteria of different taxa (Photobacterium leiognathi, Photobacterium phosphoreum, Vibrio harveyi, Vibrio fischeri) to synthesize polyesters of hydrocarbon acids (polyhydroxyalkanoates, PHAs) as storage macromolecules. The screened strains widely varied in their PHA productivity. Conditions for attaining high polymer yields (including two‐ and three‐component polymers) in batch culture have been determined. The attained polymer yields reached 40‐70% of dry cell biomass. The results suggest a conclusion that luminous microorganisms can be considered as producers of multi‐component PHAs.
Brush Type Copolymers of Poly(3‐hydroxybutyrate) and Poly(3‐hydroxyoctanoate) with Same Vinyl Monomers via “Grafting From” Technique by Using Atom Transfer Radical Polymerization Method
Authors: Arslan Hülya , Yeşilyurt Nazlı , Hazer Baki
Published: August 2008

Brush type graft copolymers of poly(3‐hydroxybutyrate) (PHB) and poly(3‐hydroxyoctanoate) (PHO) with methylmethacrylate, (MMA), styrene, (S), and n‐butylmethacrylate, (n‐BuMA) were obtained by using Atom Transfer Radical Polymerization Method, (ATRP), via “grafting from” technique. Firstly PHB and PHO were chlorinated by passing chlorine gas through their solution in CHCl3/CCl4 (75/25 v/v) mixture and CCl4, respectively, in order to prepare chlorinated PHB, PHB‐Cl, and chlorinated PHO, PHO‐Cl, with different chlorine contents. The determination of the chlorine content in chlorinated poly(3‐hydroxyalkanoate) (PHA‐Cl) was performed by the Volhard Method. Then ATRP of vinyl monomers was initiated by using PHA‐Cl as macroinitiators in the presence of cuprous chloride (CuCl)/2,2′‐bipyridine complex as catalyst, at 90 °C in order to obtain brushes containing PHAs. The polymer brushes were fractionated by fractional precipitation methods and the γ values calculated from the ratio of the volume of nonsolvent (methanol) and the volume of solvent (chloroform) of brushes varied between 0.82 and 6.50 depending on the composition of brushes. The polymer products were characterized by gel permeation chromatography (GPC), 1H NMR, FTIR, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques.
Comparative Study of PHA Degradation in Natural Reservoirs Having Various Types of Ecosystems
Authors: Voinova Olga , Gladyshev Michail , Volova Tatiana G.
Published: August 2008

The kinetics of polyhydroxyalkanoate (PHA) degradation in natural environment in two water reservoirs having various ecological characteristics was studied. It was shown that biodegradation of polymer essentially depends on the environment temperature and inorganic composition of water. The processes of polymer degradation under aerobic and anaerobic conditions were compared. The polymer degradation was slower under anaerobic conditions.
Influence of Enzymatic Degradation on Physical Properties of Poly(ε‐caprolactone) Films and Sponges
Authors: Vidaurre Ana , Dueñas José M. Meseguer , Estellés Jorge Más , Cortázar Isabel Castilla
Published: August 2008

The effect of enzymatic degradation on poly(ε‐caprolactone) (PCL) films and sponges was investigated at 37 °C using Pseudomonas lipase. Film samples were prepared by the solution casting method, while sponges were obtained by the freeze extraction method. The porosity was 17 and 60% respectively. Weight loss, morphology, crystallinity and mechanical properties were studied. The kinetic study on the enzymatic degradation of PCL porous samples depends on porosity, suggesting that degradation took place on the surface, not suffering bulk degradation. The non‐dependence on crystallinity indicates that degradation occurred in both phases, amorphous and crystalline, at the same time.
An Atomistic Modeling and Quantum Mechanical Approach to the Hydrolytic Degradation of Aliphatic Polyesters
Authors: Entrialgo‐Castaño María , Salvucci Anthony E. , Lendlein Andreas , Hofmann Dieter
Published: August 2008

This paper reports computational simulations at two different scales employed to investigate the hydrolytic degradation of two homopolyesters: polyglycolide, PGA and poly(L‐lactide), PLLA. Atomistic bulk models were used to investigate the dry and various hydrated states of the two systems. In addition, the first moments of contact between the polymers and water were studied employing atomistic interface models. A higher affinity of water to polyglycolide in comparison with poly(L‐lactide) was observed, while diffusion of water was found to be lower in the first polymer. Quantum chemical calculations for the first step of the water‐assisted hydrolysis revealed a higher resistance to hydrolytical scission of the L‐lactyl units in comparison to glycolyl units.
Biomedical Investigations of Biodegradable PHAs
Authors: Shishatskaya Ekaterina I.
Published: August 2008

This work is a review of the results of biomedical studies of polymer devices (films, fibers, microparticles, 3D implants) made from resorbable PHAs synthesized by the bacterium Wautersia (Ralstonia) eutropha B5786, using the technology developed at the Institute of Biophysics of the Siberian Branch of the Russian Academy of Sciences. Two types of PHAs – polyhydroxybutyrate (PHB) and a hydroxybutyrate/hydroxyvalerate copolymer (PHB/PHV) – have been proven to be biocompatible in vitro in cultures of fibroblasts, endothelial cells, hepatocytes, and osteoblasts, and in short‐ and long‐duration experiments on animals. Polymer films and membranes have been found to be usable as scaffolds for functioning cells and monofilament suture fibers – for stitching muscular‐fascial wounds and in abdominal surgery. Ectopic bone formation assay and experiments with the model of segmental osteotomy showed that 3D PHB and PHB/HA implants can be used for reparative osteogenesis. The paper reports beneficial results of using polymers to repair bone defects in oral surgery.
In Vivo Justification of Using Endobiliary Stents Made of Polyhydroxyalkanoates
Authors: Markelova N.M. , Shishatskaya E.I. , Vinnik Y.S. , Cherdantsev D.V. , Beletskiy I.I. , Kuznetsov M.N. , Zykova L.D.
Published: August 2008

Treatment of patients with mechanical jaundice (MJ) has been one of the topical problems of current medicine. The fraction of patients having MJ of oncologic character that can undergo radical surgery does not exceed 25–30%. A way out of such situation is to use minimally invasive endobiliary interventions, the main type of which is endoprosthesis replacement of bile duct lumens. The aim of the work was to study the biological properties of the experimental models of polymer stents made of PHA for endobiliary prosthetics and to investigate the biological properties of PHA suture material for forming of biliary‐enteric anastomoses (cholecystoduodenostomy). Experiments were performed on 20 adult mongrel dogs, weighing 10–12 kg. The animals were divided to three groups: the negative control group (intact animals); the positive control group (the animals with implanted endobiliary silicon stents); and the experimental group (the animals with the PHA stents). The animals were monitored for 100 days. The clinical blood analysis was made before the operation, on day 7, 30, 60 and 100 days. During autopsy the presence of exudate, commissural process in the free abdominal cavity and subhepatic spatium, the appearance of choledoch where the prosthesis was located, as well as the appearance of cholecystoenterostomy, liver and duodenum. We did not found any signs of inflammation, cicatrical changes were estimated in the free abdominal cavity and subhepatic spatium. All implanted PHA stents were at their initial places of implantation. After the end of the experiment inflammatory reaction and anastomositis were absent. Macroscopic changes of liver and duodenum were also not detected. Liver function did not have any pathological deviations. These positive results give grounds to conclude that application of PHA as endobiliary stents in reconstructive surgery of bile passages and as suture material is a promising technology.