bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cell migration protein Grb7 associates with transcriptional regulator FHL2 in a Grb7 phosphorylation‐dependent manner
Authors: Siamakpour‐Reihani Sharareh , Argiros Haroula J. , Wilmeth Lori J. , Haas L. Lowell , Peterson Tabitha A. , Johnson Dennis L. , Shuster Charles Brad , Lyons Barbara A. 
Published: October 2008

AbstractGrb7 is an adaptor molecule that can mediate signal transduction from multiple cell surface receptors to various downstream signaling pathways. Grb7, along with Grb10 and Grb14, make up the Grb7 protein family. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor tyrosine kinase (RTK), erbB2, are overexpressed in 20–30% of breast cancers. Grb7 overexpression has been linked to enhanced cell migration and metastasis, though the participants in these pathways have not been determined. In this study, we report that Grb7 interacts with four and half lim domains isoform 2 (FHL2), a transcription regulator with an important role in oncogenesis, including breast cancer. Additionally, in yeast 2‐hybrid (Y2H) assays, we show that the interaction is specific to the Grb7 RA and PH domains. We have also demonstrated that full‐length (FL) Grb7 and FHL2 interact in mammalian cells and that Grb7 must be tyrosine phosphorylated for this interaction to occur. Immunofluorescent microscopy demonstrates possible co‐localization of Grb7 and FHL2. A model with supporting NMR evidence of Grb7 autoinhibition is proposed. Copyright © 2008 John Wiley & Sons, Ltd.
Interaction between the CBM of Cel9A from Thermobifida fusca and cellulose fibers
Authors: Oliveira Osmair V. , Freitas Luiz C. G. , Straatsma T. P. , Lins Roberto D. 
Published: October 2008

AbstractMolecular docking and molecular dynamics (MD) simulations were used to investigate the binding of a cellodextrin chain in a crystal‐like conformation to the carbohydrate‐binding module (CBM) of Cel9A from Thermobifida fusca. The fiber was found to bind to the CBM in a single and well‐defined configuration in‐line with the catalytic cleft, supporting the hypothesis that this CBM plays a role in the catalysis by feeding the catalytic domain (CD) with a polysaccharide chain. The results also expand the current known list of residues involved in the binding. The polysaccharide‐protein attachment is shown to be mediated by five amine/amide‐containing residues. E478 and E559 were found not to interact directly with the sugar chain; instead they seem to be responsible to stabilize the binding motif via hydrogen bonds. Copyright © 2008 John Wiley & Sons, Ltd.
Structural characterization of in vitro rat liver microsomal metabolites of antihistamine desloratadine using LTQ‐Orbitrap hybrid mass spectrometer in combination with online hydrogen/deuterium exchange HR‐LC/MS
Authors: Chen Guodong , Daaro Ibrahim , Pramanik Birendra N. , Piwinski John J. 
Published: October 2008

AbstractIn vitro drug metabolism study is an integral part of drug discovery process. In this report, we have described the application of LTQ‐Orbitrap hybrid mass spectrometer in conjunction with online hydrogen (H)/deuterium (D) exchange high resolution (HR)‐LC/MS for structural characterization of in vitro rat liver microsomal metabolites of antihistamine desloratadine. Five metabolites M1M5 have been identified, including three hydroxylated metabolites M1M3, one N‐oxide M4 and one uncommon aromatized N‐oxide M5. Accurate mass data have been obtained in both full scan and MSn mode support assignments of metabolite structures with reported mass errors less than 3 ppm. Online H/D exchange HR‐LC/MS experiments provide additional evidence in differentiating hydroxylated metabolites from N‐oxides. This study demonstrates the effectiveness of this approach in structural characterization of drug metabolites. Copyright © 2008 John Wiley & Sons, Ltd.
Stimulation of choline acetyltransferase by C3d, a neural cell adhesion molecule ligand
Authors: Burgess Alison , Saini Saumya , Weng Ying‐Qi , Aubert Isabelle 
Published: October 2008

AbstractSeptal cholinergic neurons project to the hippocampus and release acetylcholine, a neurotransmitter involved in learning and memory. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing acetylcholine. Promoting ChAT activity and acetylcholine release can lead to new treatments for neurodegenerative diseases with cholinergic deficits, such as Alzheimer's disease. We present evidence that the synthetic molecule C3d, which is a peptide mimetic of the neural cell adhesion molecule (NCAM), promotes ChAT activity in cultures of rat embryonic septal neurons. Our data demonstrate that ChAT activity triggered by C3d is dependent on the fibroblast growth factor receptor (FGFR) and the mitogen‐activated protein kinase (MAPK) pathway. C3d did not affect the number of cholinergic neurons in culture, indicating that NCAM homophilic binding enhances ChAT activity, without affecting cholinergic cell survival. In conclusion, the NCAM mimetic peptide C3d promotes ChAT activity in septal neurons through FGFR and MAPK. These findings are relevant to the design of new strategies aimed at stimulating cholinergic function and improving cognition in disorders such as Alzheimer's disease. © 2008 Wiley‐Liss, Inc.
Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury
Authors: Lee Mee‐Young , Chen Lei , Toborek Michal 
Published: October 2008

AbstractPrimary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. In the present study, we hypothesized that the altered expression of nitric oxide synthase (NOS) may contribute to these effects. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in spinal cord injury (SCI). Therefore, the aim of the present study was to evaluate whether the administration of nicotine can influence expression of inducible NOS (iNOS) and/or neuronal NOS (nNOS) in injured spinal cords. Adult male Long‐Evans rats were subjected to a moderate contusion model of SCI and received a single intraperitoneal injection of either saline or nicotine (0.35, 3.5, or 7 mg/kg) 2 hr after trauma. SCI dramatically increased iNOS (but not nNOS) mRNA and protein levels in microglial cells in the thoracic and lumbar regions of spinal cords. iNOS overexpression resulted in increased nitrotyrosine formation, decreased number of NeuN (neuronal nuclei)–immunoreactive cells, and up‐regulation of inflammatory genes. Most importantly, these effects were markedly attenuated by nicotine acting via a receptor‐mediated mechanism. These data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma. © 2008 Wiley‐Liss, Inc.
Oxidative stress promotes proliferation and dedifferentiation of retina glial cells in vitro
Authors: Abrahan Carolina E. , Insua M. Fernanda , Politi Luis E. , German O. Lorena , Rotstein Nora P. 
Published: October 2008

AbstractOxidative damage is involved in triggering neuronal death in several retinal neurodegenerative diseases. The recent finding of stem cells in the retina suggests that both preventing neuronal death and replacing lost neurons might be useful strategies for treating these diseases. We have previously shown that oxidative stress induces apoptosis in cultured retinal neurons. We now investigated the response of Müller cells, proposed as retina stem cells, to this damage. Treatment of glial cell cultures prepared from rat retinas with the oxidant paraquat (PQ) did not induce glial cell apoptosis. Instead, PQ promoted their rapid dedifferentiation and proliferation. PQ decreased expression of a marker of differentiated glial cells, simultaneously increasing the expression of smooth muscle actin, shown to increase with glial dedifferentiation, the levels of cell‐cycle markers, and the number of glial cells in the cultures. In addition, glial cells protected neurons in coculture from apoptosis induced by PQ and H2O2. In pure neuronal cultures, PQ induced apoptosis of photoreceptors and amacrine neurons, simultaneously decreasing the percentage of neurons preserving mitochondrial membrane potential; coculturing neurons with glial cells completely prevented PQ‐induced apoptosis and preserved mitochondrial potential in both neuronal types. These results demonstrate that oxidative damage activated different responses in Müller glial cells; they rapidly dedifferentiated and enhanced their proliferation, concurrently preventing neuronal apoptosis. Glial cells might not only preserve neuronal survival but also activate their cell cycle in order to provide a pool of new progenitor cells that might eventually be manipulated to preserve retinal functionality. © 2008 Wiley‐Liss, Inc.
A Na+/Ca2+exchanger isoform, NCX1, is involved in retinal cell death afterN‐methyl‐D‐aspartate injection and ischemia–reperfusion
Authors: Inokuchi Y. , Shimazawa M. , Nakajima Y. , Komuro I. , Matsuda T. , Baba A. , Araie M. , Kita S. , Iwamoto T. , Hara H. 
Published: October 2008

AbstractWe investigated the expression of Na+/Ca2+exchanger (NCX) and the functional role of NCX in retinal damage by using NCX1‐heterozygous deficient mice (NCX1+/−) and SEA0400 (2‐[4‐[(2,5‐difluorophenyl)methoxy] phenoxy]‐5‐ethoxyaniline), a selective NCX inhibitor in vivo. We also examined the role of NCX in oxygen–glucose deprivation (OGD) stress with a retinal ganglion cell line (RGC‐5) cell culture in vitro. The expression of NCX1 was confirmed and entirely localized in retina by immunoblotting and immunohistochemistry, respectively. NCX1+/−mice possessed significant protection against retinal damage induced by intravitreal injection ofN‐methyl‐D‐aspartate (NMDA). SEA0400 at 3 and 10 mg/kg significantly reduced NMDA‐ or high intraocular pressure–induced retinal cell damage in mice. Furthermore, SEA0400 reduced the number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick‐end labeling)‐positive cells and the expression of phosphorylated mitogen‐activated protein kinases (ERK1/2, JNK, p38) induced by NMDA injection. In RGC‐5, SEA0400 at 0.3 and 1 μM significantly inhibited OGD‐induced cell damage. OGD‐induced cell damage was aggravated by ouabain (a Na+,K+‐ATPase inhibitor) at 100 μM, and this increased damage was significantly reduced by SEA0400 at 1 μM. In conclusion, these results suggest that NCX1 may play a role in retinal cell death induced by NMDA and ischemia–reperfusion. © 2008 Wiley‐Liss, Inc.
The fate of transplanted xenogeneic bone marrow‐derived stem cells in rat intervertebral discs
Authors: Wei Aiqun , Tao Helen , Chung Sylvia A. , Brisby Helena , Ma David D. , Diwan Ashish D. 
Published: October 2008

AbstractIntervertebral disc degeneration is a major cause and a risk factor for chronic low back pain. The potential of using stem cells to treat disc degeneration has been raised. The aims of our study were to assess whether xenogeneic bone‐marrow derived stem cells could survive in a rat disc degeneration model and to determine which cell types, if any, survived and differentiated into disc‐like cells. Human bone‐marrow derived CD34+ (hematopoietic progenitor cells) and CD34− (nonhematopoietic progenitor cells, including mesenchymal stem cells) cells were isolated, fluorescent‐labeled, and injected into rat coccygeal discs. The rats were sacrificed at day 1, 10, 21, and 42. Treated discs were examined by histological and immunostaining techniques and compared to control discs. The survival of transplanted cells was further confirmed with a human nuclear specific marker. Fluorescent labeled CD34− cells were detected until day 42 in the nucleus pulposus of the injected discs. After 3 weeks these cells had differentiated into cells expressing chondrocytic phenotype (Collagen II and Sox‐9). In contrast, the fluorescent labeled CD34+ cells could not be detected after day 21. No fluorescence‐positive cells were detected in the noninjected control discs. Further, no inflammatory cells infiltrated the nucleus pulposus, even though these animals had not received immunosuppressive treatment. Our data provide evidence that transplanted human BM CD34− cells survived and differentiated within the relative immune privileged nucleus pulposus of intervertebral disc degeneration. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:374–379, 2009
Enhancement of posterolateral lumbar spine fusion using low‐dose rhBMP‐2 and cultured marrow stromal cells
Authors: Fu Tsai‐Sheng , Chen Wen‐Jer , Chen Lih‐Huei , Lin Song‐Shu , Liu Shih‐Jung , Ueng Steve W.N. 
Published: October 2008

AbstractWe tested the hypothesis that the dose of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) required to induce spine fusion can be reduced by combination with mesenchymal stem cells (MSCs). Twenty‐four adult rabbits underwent posterolateral intertransverse fusion at the L4–L5 level. The animals were divided into four groups based on the implant material: autologous iliac graft, Alginate‐MSCs composite, Alginate‐BMP‐2‐MSCs composite, and Alginate‐BMP‐2 composite. After 16 weeks, the rabbits were euthanized for radiographic examination, manual palpation, biomechanical testing, and histology. Radiographic union of 12 intertransverse fusion areas for the autogenous iliac graft, Alginate‐MSCs, Alginate‐BMP‐2‐MSCs, and Alginate‐BMP‐2 groups was 11, 8, 11, and 0, respectively. Moreover, manual palpation of six fusion segments in each subgroup found solid union to be 6, 1, 5, and 0, respectively. The average torques at failure of the first three groups were 2278 ± 135, 1943 ± 140, and 2334 ± 187 N‐mm, respectively. The failure torque did not differ significantly between the autograft and Alginate‐BMP‐2‐MSCs groups; both groups were significantly higher than the Alginate‐MSCs group. The results indicate that MSCs delivered with in vitro cellular doses of rhBMP‐2 are more osteoinductive than MSCs without rhBMP‐2. In combination with MSCs, a low dose (2.5 µg) of rh‐BMP‐2 could enhance bone formation and posterolateral spine fusion success in the rabbit model. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:380–384, 2009
Identifying scapholunate ligamentous injury
Authors: Werner Frederick W. , Wang Haoyu , Short Walter H. , Sutton Levi G. , Rosenbaum Paula F. 
Published: October 2008

AbstractThe first purpose of this study was to develop a noninvasive clinical tool that could predict whether the scapholunate interosseous ligament and other secondary stabilizing ligaments are injured in the presence of suspected scapholunate instability. The second purpose of this study was to determine which of those ligaments or ligament groups have been injured. Kinematic and three‐dimensional (3D) meaurements from 62 cadaver wrists moved in a wrist joint motion simulator were used to develop various neural network predictive models. One group of models was based on angular changes in scaphoid and lunate motion before and after ligament sectioning (representing scapholunate instability). A second group of models was based on changes in the minimum distance between the scaphoid and lunate as well as other 3D gap measurements. The models, based on the scaphoid and lunate angular data, could predict with a 93% accuracy rate whether the wrist ligaments were intact. These models could also predict whether it was the dorsal ligaments or the volar ligaments that were sectioned 84% of the time. The models worked best using data with the wrist in 10 to 30 degrees of wrist flexion. The viability of a CT‐based predictive model has been demonstrated by obtaining high prediction rates, sensitivity, specificity, and kappa statistic values. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:394–399, 2009
High levels of glucosamine–chondroitin sulfate can alter the cyclic preload and acute overload responses of chondral explants
Authors: Wei Feng , Haut Roger C. 
Published: October 2008

AbstractA recent study by our laboratory showed that 14 days of low intensity, intermittent cyclic preloading of chondral explants elevated the concentration of proteoglycans (PGs) to cause a mechanical stiffening of the explants prior to an acute overload and limit the extent of tissue damage. Longer term loading to 21 days resulted in tissue degradation prior to the acute traumatic event and excessive damage from an acute overload. Previous studies by others showed that bathing chondral explants in a supplement of glucosamine–chondroitin sulfate (glcN‐CS) upregulated the synthesis of tissue PGs, particularly in stressed tissue, and the supplement served as an anti‐inflammatory agent. Our current hypothesis was that the supplementation of culture media with a high concentration of glcN‐CS would upregulate the production of tissue PG and limit or mitigate long‐term degradation of chondral explants under cyclic preloading and limit tissue damage in an acute overload. We showed that, in the presence of supplement, cyclic preloading significantly increased tissue PG content and matrix modulus by about 65 and 300%, respectively, at 21 days, resulting in a reduction of matrix damage and cell death following an acute overload. These data show a biological action of high concentrations of this supplement and its effect on the mechanical properties in this in vitro model. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:353–359, 2009
How age impairs the response of the neuromuscular junction to nerve transection and repair: An experimental study in rats
Authors: Apel Peter J. , Alton Timothy , Northam Casey , Ma Jianjun , Callahan Michael , Sonntag William E. , Li Zhongyu 
Published: October 2008

AbstractAge is the most important predictor of clinical outcome after peripheral nerve injury. The stability of the neuromuscular junction (NMJ) after denervation is thought to be central to neuromuscular recovery. Stability is characterized by maintenance of the motor endplate and mRNA upregulation of the constituent nicotinic acetylcholinergic receptor (nAChR) subtypes and the muscle regulatory factors (MRFs). The purpose of this study was to determine the effect of age on the recovery and stability of the postsynaptic NMJ after peripheral nerve injury. Young and aged rats underwent transection and repair of the tibial nerve. At 1, 2, 4, 8, or 16 weeks following transection, the gastrocnemius was examined for electrical recovery, NMJ fragmentation and endplate area, mRNA, and protein levels of the MRFs and nAChR subtypes. After nerve injury, aged NMJ exhibited significant fragmentation and loss of motor endplate area while the young NMJ remained relatively stable. Concomitantly, age impaired peak upregulation of the MRFs and nAChRs. However, expression of γ‐nAChR and myogenin after nerve injury was not affected by age. These data support the claim that upregulation of the nAChRs and MRFs may play an important role in maintaining NMJ stability following nerve transection and repair. Furthermore, expression of γ‐nAChR and myogenin does not appear to prevent age‐related NMJ fragmentation and loss of endplate area after nerve injury. These impairments of the aged NMJ response to injury may contribute to the poor neuromuscular recovery seen after nerve injury in this population. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:385–393, 2009
Healing ligament mechanical properties are improved by repair with interpositional allografts but not by concomitant treatment with hyaluronic acid
Authors: Thornton Gail M. , Shao Xinxin , Kuchison Marielle E. , Marchuk Linda L. , Shrive Nigel G. , Frank Cyril B. 
Published: October 2008

AbstractHealing ligaments have inferior mechanical properties compared to normal ligaments during early healing intervals. The purpose of this study was to investigate if in vivo ligament repair with an interpositional allograft and treatment with hyaluronic acid (HA) would improve the mechanical properties of a medial collateral ligament (MCL) healing from a gap injury. Twenty rabbits were assigned equally to either a donor or recipient group. A gap injury of the MCL was created in both hindlimbs of 10 recipient animals. The right hindlimb was treated with allograft plus HA while the left hindlimb was treated with allograft only. Low‐load and high‐load mechanical properties, including laxity, relaxation and failure, and histology were evaluated after 6 weeks of healing. Mechanical results were compared to previously published normal MCL and MCL gap scar data. MCL allografts had greater initial force during cyclic relaxation testing and maximum force during failure testing than MCL scars, but were weaker than normal MCLs. Failure stress was the only parameter to demonstrate a statistically significant effect of treatment with HA on the allografts. However, the failure stress of the HA‐treated MCL allografts was not different than MCL scars and was less than normal MCLs. In conclusion, interpositional allografts could enhance some mechanical properties of ligament healing but HA, in the way we applied it, did not produce an obvious improvement. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:400–407, 2009
Customer access and competitive certainty: performance effects in Swedish foreign subsidiaries
Authors: Pehrsson Anders 
Published: October 2008

Abstract

This article extends our understanding of performance effects of expansion barriers in different strategy contexts relevant to industrial firms. Effects of perceived obstacles to customer access are studied, and competitive certainty is acknowledged since barriers to a large extent originate from business strategies of competitors.

The study explores patterns using data from subsidiaries of Swedish manufacturing firms in Germany, the United Kingdom, and the United States. For units with a narrow product/market scope, the direct performance effects of customer access obstacles and competitive certainty are negative.

On the other hand, in the narrow context competitive certainty moderates the relationship between customer access obstacles and performance, and this implicates a positive effect. There are no significant effects in the context of a broad product/market scope.

Performance effects of barriers are, thus, more complicated than previously thought, and we need to pay attention to perceived competitive certainty and the strategy context.

Copyright © 2008 John Wiley & Sons, Ltd.