bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of glial‐derived matrix molecules, especially chondroitin sulfates, on neurite growth and survival of cultured mouse embryonic motoneurons
Authors: Klausmeyer Alice , Conrad Rebecca , Faissner Andreas , Wiese Stefan 
Published: December 2010

AbstractMechanisms controlling neuronal survival and regeneration play an important role during development, after birth, and under lesion conditions. Isolated embryonic mouse motoneurons have been a useful tool for studying such basic mechanisms. These cultured motoneurons depend on extracellular matrix (ECM) molecules, which are potent mediators of survival and axonal growth and guidance in the CNS and in vitro, exhibiting either attractive or repellent guidance cues. Additionally, ECM proteoglycans and glycoproteins are components of the glial scar acting as a growth barrier for regenerating axons. Compared with CNS axon outgrowth, less is known about the cues that guide motoneurons toward their peripheral targets. Because we are interested in the effects of glial‐derived chondroitin sulfate proteoglycans (CSPGs), we have worked out a model system for investigating the influences of glial‐derived matrix molecules on motoneuron outgrowth and survival. We used cultured embryonic mouse motoneurons to investigate axon growth effects of matrix molecules produced by the glial‐derived cell lines A7, Neu7, and Oli‐neu primary astrocytes as wellas the immortalized Schwann cell line IMS32. The results indicate that molecules of the ECM, especially chondroitin sulfates, play an important role as axon growth‐promoting cues. We could demonstrate a modifying effect of the matrix components on motoneuron survival and caspase3‐induced apoptosis. © 2010 Wiley‐Liss, Inc.
Characterization of kinases involved in the phosphorylation of aggregated α‐synuclein
Authors: Waxman Elisa A. , Giasson Benoit I. 
Published: December 2010

Abstractα‐Synuclein (α‐syn) is the major component of pathological inclusions characteristic of several neurodegenerative disorders, such as Parkinson's disease. The major posttranslational modification of α‐syn is phosphorylation at S129, and previous studies estimate that approximately 90% of α‐syn in proteinaceous, pathological inclusions is phosphorylated at this site. α‐Syn can be phosphorylated by polo‐like kinases (PLKs) 1–3 and casein kinases (CK) 1 and 2; however, the kinases associated with the hyperphosphorylation of aggregated α‐syn are still under debate. Using a high‐efficiency cellular model of α‐syn aggregate formation, we found that selective inhibitors for CK2 and PLKs each partially inhibited S129 phosphorylation of soluble (nonaggregated) α‐syn, but only PLK inhibitors modestly attenuated the phosphorylation of aggregated α‐syn. In addition, none of the kinase inhibitors used had a substantial effect on the propensity of α‐syn to aggregate. Overexpression of all PLKs promoted robust phosphorylation of soluble α‐syn, but none altered the propensity of α‐syn to aggregate. Overexpression of only PLK2 increased phosphorylation of aggregated α‐syn at S129, which likely is due to increased phosphorylation of soluble α‐syn, which then was incorporated into aggregates. Overexpression of PLK1 and treatment with BI2536 resulted in a significant reduction of phosphorylated, aggregated α‐syn protein, beyond that of BI2536 treatment alone. These studies suggest that phosphorylation of α‐syn is independent of α‐syn aggregate formation, that PLK1 is involved in the phosphorylation of aggregated α‐syn at S129 in this system, and that mechanisms resulting in hyperphosphorylation of aggregated α‐syn appear to be independent of those responsible for the phosphorylation of soluble α‐syn. © 2010 Wiley‐Liss, Inc.
Expression of macrophage inflammatory protein‐1α and monocyte chemoattractant protein‐1 in glioma‐infiltrating microglia: Involvement of ATP and P2X7receptor
Authors: Fang Kuan‐Min , Wang Ying‐Lan , Huang Ming‐Chao , Sun Synthia H. , Cheng Henrich , Tzeng Shun‐Fen 
Published: December 2010

AbstractChemokines can be produced by gliomas, which mediate the infiltration of microglia, a characteristic feature of glioma‐associated neuropathogenesis. ATP that is released at a high level from glioma has been reported to play a regulatory role in chemokine production in cultured glioma cells. The objective of this study was to define the potential role of extracellular ATP in the regulation of macrophage inflammatory protein‐1α (MIP‐1α) and monocyte chemoattractant protein‐1(MCP‐1) expression in glioma‐associated microglia/macrophages. The results showed that Iba1+and ED1+microglia existed in the tumor at 3 and 7 day after injection of C6 glioma cells into the rat cerebral cortex (dpi). ED1+microglia/macrophages or Iba1+microglia in the glioma were also colocalized to MIP‐1α‐ and MCP‐1‐expressing cells. In vitro study indicated that treatment with ATP and BzATP (an agonist for ATP ionotropic receptor P2X7R) caused an increase in the intracellular levels of microglial MIP‐1α and MCP‐1. By using an extracellular Ca2+chelator (EGTA) and P2X7R antagonists, oxidized ATP (oxATP) and brilliant blue G (BBG), we demonstrated that BzATP‐induced production of MIP‐1α and MCP‐1 levels was due to P2X7R activation and Ca2+‐dependent regulation. Coadministration of C6 glioma cells and oxATP into the rat cerebral cortex resulted in a reduction of MIP‐1α‐ and MCP‐1‐expressing microglia/macrophages. We suggest, based on the results from in vivo and in vitro studies, that a massive amount of ATP molecules released in the glioma tumor site may act as the regulator with P2X7R signaling that increases MIP‐1α and MCP‐1 expression in tumor‐infiltrating microglia/macrophages. © 2010 Wiley‐Liss, Inc.
Changes in growth hormone (GH), GH receptor, and GH signal transduction in hippocampus of congenital hypothyroid rats
Authors: Tang Huiqin , Zhang Yu , Yu Xiaomei , Song Jian , Xu Chengshi , Wan Yu 
Published: December 2010

AbstractRecent studies have shown that, like thyroid hormone (TH), growth hormone (GH) plays a critical role in development of the brain. However, it is still unclear whether the functions of the two hormones are locally orchestrated in the brain or whether TH has a permissive effect on GH in the central nervous system as it does in the periphery. To address this question, the present study investigated the changes in local expression of GH and GH receptor (GHR) and the activity of GH signaling molecules in the hippocampus of congenitally hypothyroid (CHT) rats. As demonstrated by morphometric measurements and the Y‐maze test, CHT rats had decreased neurons and weaker Nissl staining in the stratum pyramidal/granule in the hippocampus and a reduced acquisition of safe place recognition memory. Analyses of QPCR and Western blot revealed a substantially decreased hippocampal expression of GH and GHR, accompanied by a corresponding decrease in phosphorylation of JAK2 and STAT5 in the CHT rats. These changes were, at least in part, corrected by systemic supplement of T3. The findings provide the first direct evidence suggesting that the functional autocrine and paracrine regulation of GH in the CNS is orchestrated by TH. © 2010 Wiley‐Liss, Inc.
Fragile X mice: Reduced long‐term potentiation and N‐Methyl‐D‐Aspartate receptor‐mediated neurotransmission in dentate gyrus
Authors: Yun Sung Hwan , Trommer Barbara L. 
Published: December 2010

AbstractFragile X syndrome (FXS) is a monogenic mental retardation syndrome that frequently includes autism. The Fmr1‐knockout (Fmr1‐KO) mouse, like FXS‐affected individuals, lacks the fragile X mental retardation protein (FMRP) and models autism as well as FXS. Limited human data and several mouse models have implicated the hippocampal dentate gyrus (DG) in autism. We therefore investigated whether the Fmr1‐KO mouse exhibited functional changes in DG. We found diminished medial perforant path‐granule cell long‐term potentiation (LTP), complementing previous investigations of synaptic plasticity in Fmr1‐KO demonstrating impaired LTP in CA1, neocortex, and amygdala and exaggerated long‐term depression in CA1. We also found that peak amplitude of NMDA receptor‐mediated excitatory postsynaptic currents (EPSCs) was smaller in Fmr1‐KO than control. AMPA receptor‐mediated EPSCs were comparable in the two strains, yielding a lower NMDA/AMPA ratio in Fmr1‐KO mice and suggesting one mechanism by which absent FMRP might contribute to diminished LTP. The clinical hallmarks of autism include both excessive adherence to patterns and impaired detection of socially important patterns. The DG has a putative role in pattern separation (for time, space, and features) that has been attributed to granule cell number, firing rates, adult neurogenesis, and even perforant path LTP. DG also contributes to pattern completion in CA3 via its mossy fiber efferents, whose terminals include abundant FMRP in “fragile X granules.” Together with the present data, these observations suggest that DG is a candidate region for further investigation in autism and that the Fmr1‐KO model may be particularly apt. © 2010 Wiley‐Liss, Inc.
Small‐molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells
Authors: Morizane Asuka , Doi Daisuke , Kikuchi Tetsuhiro , Nishimura Kaneyasu , Takahashi Jun 
Published: December 2010

AbstractThe balance of bone morphogenic protein (BMP), transforming growth factor‐β (TGFβ)/activin/nodal, and Wnt signals regulates the early lineage segregation of human embryonic stem cells (ESCs). Here we demonstrate that a combination of small‐molecule inhibitors of BMP (Dorsomorphin) and TGFβ/activin/nodal (SB431542) signals promotes highly efficient neural induction from both human ESCs and induced pluripotent stem cells (iPSCs). The combination of small molecules had effects on both cell survival and purity of neural differentiation, under conditions of stromal (PA6) cell coculture and feeder‐free floating aggregation culture, for all seven pluripotent stem cell lines that we studied, including three ESC and four iPSC lines. Small molecule compounds are stable and cost effective, so our findings provide a promising strategy for controlled production of neurons in regenerative medicine. © 2010 Wiley‐Liss, Inc.
Differential treatment within sports teams, leader–member (coach–player) exchange quality, team atmosphere, and team performance
Authors: van Breukelen Wim , van der Leeden Rien , Wesselius Wendy , Hoes Madelien 
Published: December 2010

SummaryUsing the leader–member exchange (LMX) theory as a theoretical framework, the present study focused on the occurrence of differential treatment by leaders on social and task‐related issues within teams. It was investigated whether team members' perceptions of the frequency and degree of social and task‐related differential treatment by the leader were associated with their evaluation of team atmosphere and team performance, in addition to the effects of the quality of their own working relationship with the leader (LMX quality). The context of this study consisted of interdependent sports teams. The participants were 605 players belonging to 69 amateur sports teams playing various team sports such as soccer, hockey, and basketball. Social differential treatment was negatively associated with team atmosphere and unrelated to team performance. In addition, it was found that the two forms of task‐related differential treatment included in this study were unrelated to team atmosphere and were differently associated with team performance. The results are discussed with reference to the existing leadership literature. Copyright © 2010 John Wiley & Sons, Ltd.
Noninvasive detection of brainstem and spinal cord axonal degeneration in an amyotrophic lateral sclerosis mouse model
Authors: Kim Joong Hee , Wu Tzy‐Haw , Budde Matthew D. , Lee Jin‐Moo , Song Sheng‐Kwei 
Published: December 2010

AbstractDegeneration of motor neurons and their associated axons is a hallmark of amyotrophic lateral sclerosis, but reliable noninvasive lesion detection is lacking. In vivo diffusion tensor imaging was performed to evaluate neurodegeneration in the brainstem and cervical spinal cord of wild‐type and G93A‐SOD1 transgenic mice, an animal model of amyotrophic lateral sclerosis. A statistically significant reduction in the apparent diffusion coefficient was observed in the motor nuclei VII and XII of G93A‐SOD1 transgenic mice relative to wild‐type mice. No significant difference in diffusion anisotropy was observed in dorsal white or gray matter in cervical and lumbar segments of the spinal cord. In contrast, statistically significant decreases in axial diffusivity (diffusivity parallel to the axis of the spinal cord) and apparent diffusion coefficient were found in the ventrolateral white matter of G93A‐SOD1 mice in both the cervical and lumbar spinal cord. The reduction in axial diffusivity, suggestive of axonal injury, in the white matter of the spinal cord of G93A‐SOD1 mice was verified by immunostaining with nonphosphorylated neurofilament. The present study demonstrates that in vivo diffusion tensor imaging‐derived axial diffusivity may be used to accurately evaluate axonal degeneration in an animal model of amyotrophic lateral sclerosis. Copyright © 2010 John Wiley & Sons, Ltd.
Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia
Authors: Lund Bendik , Åsberg Ann , Heyman Mats , Kanerva Jukka , Harila‐Saari Arja , Hasle Henrik , Söderhäll Stefan , Jónsson Ólafur Gisli , Lydersen Stian , Schmiegelow Kjeld ,   On behalf of the Nordic Society of Paediatric Haematology and Oncology (NOPHO)
Published: December 2010

AbstractBackgroundIn spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2–4% of patients still die from treatment related complications.ProcedureWe investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL‐92 and ALL‐2000 protocols. Fifty‐five TRDs were identified among the 1,645 ALL‐92 patients and 33 among the 1,090 ALL‐2000 patients.ResultsThere was no significant difference in the incidence of TRDs between the two protocols (3.4% vs. 3.2%). Five patients died before initiation of therapy (0.2%), and the overall subsequent risk of induction death and death in first complete remission (CR1) was 1.2% and 1.8%, respectively. Infections were the major cause of death comprising 72% of all cases including 9 deaths from Pseudomonas aeruginosa and 11 deaths from fungal infections. Other causes of death included bleeding or thrombosis (eight patients), tumour burden related toxicities (seven patients) and organ toxicity (seven patients). Female gender (hazard ratio (HR): 2.2, 95% confidence interval (95% CI): 1.4–3.4), high white blood cell count (≥200 × 109/L) at diagnosis (HR: 3.5, 95% CI: 1.7–7.1), T‐cell disease (HR: 1.9, 95% CI: 1.01–3.7), Down syndrome (HR: 7.3, 95% CI: 3.6–14.9) and haematopoietic stem cell transplantation in CR1 (HR: 8.0, 95% CI: 3.3–19.5) were identified as independent risk factors for TRD.ConclusionSeveral TRDs were potentially preventable and future efforts should be directed towards patients at risk. Pediatr Blood Cancer 2011;56:551–559. © 2010 Wiley‐Liss, Inc.
Reaction of bicyclo[2.2.1]hept‐5‐ene‐endo‐2‐ylmethylamine and nitrophenyl glycidyl ethers
Authors: Kasyan Liliya I. , Prid'ma Stanislav A. , Palchikov Vitaliy A. , Karat Leonid D. , Turov Alexandr V. , Isayev Olexandr 
Published: December 2010

AbstractReactions of 2‐nitro‐, 4‐nitro‐ and 2,4‐dinitrophenylglycidyl ethers with bicyclo[2.2.1]hept‐5‐ene‐endo‐2‐ylmethylamine in isopropanol have been studied. The mixtures of products were chromatographed on silica gel and eluted with ether or ether/2‐propanol (1:1), the structures of individual products have been confirmed by IR spectra, NMR 1H, 13C spectra, using experiments that involve homonuclear and heteronuclear scalar coupling interactions (COSY, TOCSY, HMQC, HMBC), and mass spectrometry. Amino alcohols as the major products of regioselective aminolysis of epoxides (according to the Krasusky rule) have been obtained. The minor products were the compounds with two hydroxyalkyl fragments at the nitrogen atom. In case of dinitrophenylglycidyl ether, it was the minor product of aryl nucleophilic substitution (SNAr). The abnormal course of aminolysis has been confirmed by the results of quantum‐chemical calculations of activation barries and Free Gibbs energies of the competitive reactions of epoxides (at the B3LYP/6‐311 + G(d,p) level of theory). Copyright © 2010 John Wiley & Sons, Ltd.
Synthesis and characterization of new copolyacrylates containing porphyrin units as pendant groups and their use as sensors
Authors: Dattilo S. , Mineo P. , Scamporrino E. , Spina E. , Vitalini D. 
Published: December 2010

AbstractNovel copolyacrylates containing various molar ratios of 5,10,15‐tri[p‐(9‐methoxy‐triethylenoxy)phenyl]‐20‐(p‐acryloxyphenyl)porphyrin units in the chains have been synthesized, and their chemical structure was determined by NMR and MALDI‐TOF mass spectrometry. Sensing response of the synthesized copolymers has been tested for trifluoroacetic and hydrochloric acids and nitrogen dioxide analytes. The reported sensing data indicate that porphyrin units are interacting with analytes in a reversible fashion. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Self‐assembly of di‐ and triblock PEG‐pentavaline amphiphiles
Authors: Hwang Elizabeth E. , Wilson‐Hill Taylor R. , Ahn Ji Won , Platt Andrew P. , Rutledge Katherine E. , Goh Sarah L. 
Published: December 2010

AbstractNanoparticles formed from amphiphilic block copolymers can be used as drug delivery vehicles for hydrophilic therapeutics. Poly(ethylene glycol) (PEG)‐peptide copolymers were investigated for their self‐assembling properties and as consequent potential delivery systems. Mono‐ and dihydroxy PEGs were functionalized with a pentavaline sequence bearing Fmoc end groups. The molecular weight of the PEG component was varied to evaluate copolymer size and block number. These di‐ and tri‐block copolymers readily self‐assemble in aqueous solution with critical aggregation concentrations (CACs) of 0.46–16.29 μM. At concentrations above the CAC, copolymer solutions form spherical assemblies. Dynamic light scattering studies indicate these aggregates have a broad size distribution, with average diameters between 33 and 127 nm. The copolymers are comprised β‐conformations that are stable up to 80 °C, as observed by circular dichroism. This peptide secondary structure is retained in solutions up to 50% MeOH as well. The triblock copolymers proved to be the most stable, with copolymers synthesized from 10 kDa PEG having the most stable particles. Loading of carboxyfluorescein at 2–5 mol % shows that these copolymers have the potential to encapsulate hydrophilic drugs for delivery applications. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Block‐brush copolymers via ROMP and sequential double click reaction strategy
Authors: Dag Aydan , Sahin Hatice , Durmaz Hakan , Hizal Gurkan , Tunca Umit 
Published: December 2010

AbstractWe report an efficient way, sequential double click reactions, for the preparation of brush copolymers with AB block‐brush architectures containing polyoxanorbornene (poly (ONB)) backbone and poly(ε‐caprolactone) (PCL), poly(methyl methacrylate) (PMMA) or poly(tert‐butyl acrylate) (PtBA) side chains: poly(ONB‐g‐PMMA)‐b‐poly(ONB‐g‐PCL) and poly(ONB‐g‐PtBA)‐b‐poly(ONB‐g‐PCL). The living ROMP of ONB affords the synthesis of well‐defined poly(ONB‐anthracene)20‐b‐poly (ONB‐azide)5 block copolymer with anthryl and azide pendant groups. Subsequently, well‐defined linear alkyne end‐functionalized PCL (PCL‐alkyne), maleimide end‐functionalized PMMA (PMMA‐MI) and PtBA‐MI were introduced onto the block copolymer via sequential azide‐alkyne and Diels‐Alder click reactions, thus yielding block‐brush copolymers. The molecular weight of block‐brush copolymers was measured via triple detection GPC (TD‐GPC) introducing the experimentally calculated dn/dc values to the software. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Structural determinants of ligand imprinting: A molecular dynamics simulation study of subtilisin in aqueous and apolar solvents
Authors: Lousa Diana , Baptista António M. , Soares Cláudio M. 
Published: December 2010

AbstractThe phenomenon known as “ligand imprinting” or “ligand‐induced enzyme memory” was first reported in 1988, when Russell and Klibanov observed that lyophilizing subtilisin in the presence of competitive inhibitors (that were subsequently removed) could significantly enhance its activity in an apolar solvent. (Russell and Klibanov, J Biol Chem 1988;263:11624‐11626). They further observed that this enhancement did not occur when similar assays were carried out in water. Herein, we shed light on the molecular determinants of ligand imprinting using a molecular dynamics (MD) approach. To simulate the effect of placing an enzyme in the presence of a ligand before its lyophilization, an inhibitor was docked in the active site of subtilisin and 20 ns MD simulations in water were performed. The ligand was then removed and the resulting structure was used for subsequent MD runs using hexane and water as solvents. As a control, the same simulation setup was applied using the structure of subtilisin in the absence of the inhibitor. We observed that the ligand maintains the active site in an open conformation and that this configuration is retained after the removal of the inhibitor, when the simulations are carried out in hexane. In agreement with experimental findings, the structural configuration induced by the ligand is lost when the simulations take place in water. Our analysis of fluctuations indicates that this behavior is a result of the decreased flexibility displayed by enzymes in an apolar solvent, relatively to the aqueous situation.
Conserved core of amyloid fibrils of wild type and A30P mutant α‐synuclein
Authors: Cho Min‐Kyu , Kim Hai‐Young , Fernandez Claudio O. , Becker Stefan , Zweckstetter Markus 
Published: December 2010

AbstractThe major component of neural inclusions that are the pathological hallmark of Parkinson's disease are amyloid fibrils of the protein α‐synuclein (aS). Here we investigated if the disease‐related mutation A30P not only modulates the kinetics of aS aggregation, but also alters the structure of amyloid fibrils. To this end we optimized the method of quenched hydrogen/deuterium exchange coupled to NMR spectroscopy and performed two‐dimensional proton‐detected high‐resolution magic angle spinning experiments. The combined data indicate that the A30P mutation does not cause changes in the number, location and overall arrangement of β‐strands in amyloid fibrils of aS. At the same time, several residues within the fibrillar core retain nano‐second dynamics. We conclude that the increased pathogenicity related to the familial A30P mutation is unlikely to be caused by a mutation‐induced change in the conformation of aS aggregates.