bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowth
Authors: Alfa Ronald W. , Tuszynski Mark H. , Blesch Armin 
Published: April 2009

AbstractNervous system growth factor gene delivery can promote axonal growth and prevent cell death in animal models of CNS trauma and neurodegenerative diseases. The ability to regulate growth factor expression or signaling pathways downstream from growth factor receptors remains a desirable goal for in vivo gene transfer. To achieve precise pharmacological modulation of neurotrophin activity, we have generated a chimeric trkA receptor (ItrkA) by fusing the entire intracellular domain of the trkA high‐affinity NGF receptor to two intracellular, modified FK506 binding domains for the synthetic small molecule dimerization ligand AP20187. Rat PC12 cells were transduced with lentiviral vectors containing ItrkA and green fluorescent protein (GFP; via an internal ribosome entry site). Treatment of ItrkA‐expressing PC12 cells with AP20187 induced neurite outgrowth and differentiation in a time‐ and dose‐dependent fashion, with a half‐maximal response at a concentration of 1 nM AP20187. Seventy percent of cells responded to AP20187 by day 3. Western blots demonstrated that AP20187 treatment resulted in phosphorylation of Erk1/2 and Akt in ItrkA‐transduced PC12 cells but not in nontransduced, naïve cells. Phosphorylation levels were comparable to levels obtained with 50 ng/ml nerve growth factor (NGF). In addition, ItrkA lentiviral transduction of primary E15 dorsal root ganglion neurons significantly increased neurite growth three‐ to fourfold in the presence of AP20187 compared with control GFP transduced and naïve neurons. These results demonstrate that small ligand‐induced dimerization of the intracellular domain of trkA can efficiently simulate the biological activity of NGF and provide a means to regulate intracellular neurotrophin receptor signaling. © 2009 Wiley‐Liss, Inc.
The two‐hydrophobic domain tertiary structure of reticulon proteins is critical for modulation of β‐secretase BACE1
Authors: Kume Hideaki , Murayama Kiyoko S. , Araki Wataru 
Published: April 2009

Abstractβ‐Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is a membrane‐bound protease that is essential for the production of β‐amyloid protein (Aβ). Given the crucial role of Aβ accumulation in Alzheimer's disease (AD), inhibition of BACE1 activity may represent a feasible therapeutic strategy in the treatment of AD. Recently, we and others identified reticulon 3 (RTN3) and reticulon 4‐B/C (RTN4‐B/C or Nogo‐B/C) as membrane proteins that interact with BACE1 and inhibit its ability to produce Aβ. In this study, we employed various mutants of RTN3 and RTN4‐C and C. elegans RTN to investigate the molecular mechanisms by which RTNs regulate BACE1. We found that RTN3 mutants lacking the N‐terminal or C‐terminal or loop domain as well as a RTN4‐C mutant lacking the C‐terminal domain bound to BACE1 comparably to wild‐type RTN3 and RTN4‐C. Furthermore, overexpression of wild‐type RTN3, RTN4‐C, and these RTN mutants similarly reduced Aβ40 and Aβ42 secretion by cells expressing Swedish mutant APP. C. elegans RTN, which has low homology to human RTNs, also interacted with BACE1 and inhibited Aβ secretion. In contrast, two RTN3 mutants containing deletions of the first or second potential transmembrane domains and an RTN3 swap mutant of the second transmembrane domain bound BACE1 but failed to inhibit Aβ secretion. Collectively, these results suggest that the two‐transmembrane‐domain tertiary structure of RTN proteins is critical for the ability of RTNs to modulate BACE1 activity, whereas N‐terminal, C‐terminal and loop regions are not essential for this function. © 2009 Wiley‐Liss, Inc.
Identification of major S‐nitrosylated proteins in murine experimental autoimmune encephalomyelitis
Authors: Bizzozero Oscar A. , Zheng Jianzheng 
Published: April 2009

AbstractNitrosative stress has been implicated in the pathophysiology of several CNS disorders, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). We have recently shown that protein nitrosothiols (PrSNOs) accumulate in the brain of MS patients, and there is indirect evidence that PrSNO levels are also increased in EAE. In this study we sought to identify the major PrSNOs in the spinal cord of EAE animals prepared by active immunization of C57/BL6 mice with MOG35–55 peptide. For this purpose, PrSNOs from control and EAE mice at various disease stages were derivatized with HPDP‐biotin, and the biotinylated proteins were isolated with streptavidin‐agarose. Proteins from total and streptavidin‐bound fractions were then analyzed by Western blotting using antibodies against the major S‐nitrosylated substrates of CNS tissue. With this approach we found that the proportion of S‐nitrosylated neurofilament proteins, NMDA receptors, α/β‐tubulin, β‐actin, and GAPDH is increased in EAE. Other potential substrates either were not S‐nitrosylated in vivo (HCN3, HSP‐72, CRMP‐2, γ‐actin, calbindin) or their S‐nitrosylation levels were unaltered in EAE (Na/K ATPase, hexokinase, glycogen phosphorylase). We also discovered that neuronal specific enolase is the major S‐nitrosylated protein in acute EAE. Given that S‐nitrosylation affects protein function, it is likely that the observed changes are significant to the pathophysiology of inflammatory demyelination. © 2009 Wiley‐Liss, Inc.
Specificity of the second messenger pathways involved in basic fibroblast growth factor‐induced survival and neurite growth in chick ciliary ganglion neurons
Authors: Gilardino Alessandra , Farcito Silvia , Zamburlin Pollyanna , Audisio Chiara , Lovisolo Davide 
Published: April 2009

AbstractBasic fibroblast growth factor (bFGF) exerts multiple neurotrophic actions on cultured neurons from the ciliary ganglion of chick embryo, among them promotion of neuronal survival and of neurite outgrowth. To understand the specificity of the signal transduction cascades involved in the control of these processes, we used pharmacological inhibitors of the three main effectors known to act downstream of the bFGF receptor (FGFR): phospholipase Cγ (PLCγ), mitogen‐activated protein kinase (MAPK), and phosphatidylinositol 3‐kinase (PI3‐K). Neuronal survival was assessed at 24 and 48 hr; neurite growth was analyzed both on dissociated neurons and on explants of whole ganglia. Our data show that only the PI3‐K pathway is involved in the survival‐promoting effect of bFGF; on the other hand, all three effectors converge on the enhancement of neurite outgrowth, both on isolated neurons and in whole ganglia. © 2009 Wiley‐Liss, Inc.
Air temperature changes in the arctic from 1801 to 1920
Authors: Przybylak Rajmund , Vízi Zsuzsanna , Wyszyński Przemysław 
Published: April 2009

AbstractIn this paper, the results of an investigation into the thermal conditions in the Arctic in the period from 1801 to 1920 are presented. For this ‘early instrumental’ period limited meteorological data exist. Generally, the first meteorological stations in the Arctic were established in the second half of the 19th century and almost all of them were located in the coastal parts of Greenland. In order to get at least a rough idea of thermal conditions in the Arctic in the study period, data from different land and marine expeditions were collected. A total of 118 temperature series of monthly means have been gathered. Although the area and time periods covered by the data are variable, it is still possible to describe the general character of the temperature conditions.The results show that the areally averaged Arctic temperature in the early instrumental period was 0.8 °C lower than the next 60‐year period (1861–1920). In comparison to present‐day conditions, winter and autumn were significantly colder (winter by 1.6 °C and autumn by 0.9 °C) than were summer (colder by 0.4 °C) and spring (colder by only 0.2 °C). The air temperature in the real Arctic during the first International Polar Year (IPY) was, on average, colder than today by 1.0–1.5 °C. Winter was exceptionally cold with the average temperature being lower by more than 3 °C in all months except February. On the other hand, spring (March–May) was slightly warmer than today, and April was exceptionally warm (1.1 °C above present norm).The temperature differences calculated between historical and modern mean monthly temperatures show that majority of them lie within one standard deviation (SD) from present long‐term mean. Thus, it means that the climate in the early instrumental period was not as cold as some proxy data suggest. Copyright © 2009 Royal Meteorological Society
Downscaling hydroclimatic changes over the Western US based on CAM subgrid scheme and WRF regional climate simulations
Authors: Qian Yun , Ghan Steven J. , Leung L. Ruby 
Published: April 2009

AbstractThis study examines two dynamical downscaling methods, a subgrid parameterization and a regional climate model, to compare their impacts on simulating orographic precipitation and surface hydrology in mountain regions. A global climate model was first applied at 1° × 1.25° grid resolution with a subgrid orographic precipitation scheme. The global simulations were then used to drive a regional climate model at 15‐km grid resolution over the Western United States. By comparing the global and regional simulations for two 10‐year periods, 1993–2003 and 2039–2049, this study assesses the two downscaling methods in the context of simulating both the present climate and climate change signals, and the implications of the relatively short simulation length to investigate differences in current and future climate simulated by the models are discussed.The model results show that improving the representation of surface topography through higher spatial resolution or a subgrid method has a large impact on the simulations. Both the subgrid scheme and the regional model significantly improved the simulation of snowpack in the mountains. The spatial distributions of precipitation and snowpack are generally consistent between the subgrid and regional simulations, since they were driven by the same large‐scale circulation from the global simulations. However, because rain‐shadow effects are not represented in the subgrid scheme, the regional simulations produced much more realistic spatial variability in precipitation and snowpack than the subgrid simulations in narrow mountain ranges.In the climate change experiments, both downscaling procedures preserved the large‐scale patterns of temperature and precipitation changes in the global simulations. However, the regional simulations show larger changes in precipitation and snowpack along the coastal mountains than the subgrid simulations. This is attributed to the fact that the regional model explicitly simulates the interactions of atmospheric circulation and the underlying topography, so changes in wind directions with respect to the orientations of the mountains may lead to changes in orographic precipitation that cannot be explained by changes in atmospheric temperature and moisture alone. Hence differences between the precipitation changes simulated by the regional model and the subgrid method are larger in narrow mountains such as the Cascades and the Sierra Nevada because the subgrid method does not account for the influence of mountain orientations at the subgrid scale. As precipitation is an important driver of surface hydrological processes, differences between the precipitation changes simulated by the two methods lead to important differences in the surface hydrological processes under climate change. Copyright © 2009 Royal Meteorological Society
Additive effects of hyperbaric oxygen and platelet‐derived growth factor‐BB in chondrocyte transplantation via up‐regulation expression of platelet‐derived growth factor‐β receptor
Authors: Yuan Li‐Jen , Niu Chi‐Chien , Lin Song‐Shu , Chan Yi‐Sheng , Yang Chuen‐Yung , Chen Wen‐Jer , Ueng Steve W.N. 
Published: April 2009

AbstractThe present study investigated the effects of hyperbaric oxygen (HBO) and platelet‐derived growth factor‐BB (PDGF‐BB) in chondrocyte transplantation. In vitro, chondrocytes were treated with HBO, PDGF‐BB, and HBO combined with PDGF‐BB (H+P). Cell growth was analyzed using cell counting, MTT assay, and FACS analysis. mRNA expression of the PDGF‐α receptor (PDGFR‐α) and β receptor (PDGFR‐β) was detected by RT‐PCR. Protein expression of PDGFR‐β was detected by Western blotting. In vivo, chondrocytes and PDGF‐BB were suspended in alginate as a transplantation system. Cartilage defects were grafted with this system and with or without HBO treatment. Released PDGF‐BB concentration was quantified by ELISA. After 8 weeks, animals were sacrificed and the repaired tissues were examined. In vitro data suggested that each treatment increased cell growth via the up‐regulated mRNA expression of PDGFR‐α and increased cell accumulation in the S‐phase. The H+P treatment was more additive in cell growth and in mRNA and protein expression of PDGFR‐β than HBO or PDGF‐BB. In vivo results suggested that PDGF‐BB delivery lasted for more than 5 weeks. Scoring results showed that each treatment significantly increased the cartilage repair. Safranin‐O and type II collagen staining confirmed the hyaline‐like cartilage regeneration in the repaired tissues. In situ up‐regulation of PDGFR‐β expression partially explains the additive effect of H+P treatment in cartilage repair. Accordingly, H+P offers a potential treatment method for cartilage repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1439–1446, 2009
Drilling and microfracture lead to different bone structure and necrosis during bone‐marrow stimulation for cartilage repair
Authors: Chen Hongmei , Sun Jun , Hoemann Caroline D. , Lascau‐Coman Viorica , Ouyang Wei , McKee Marc D. , Shive Matthew S. , Buschmann Michael D. 
Published: April 2009

AbstractBone marrow stimulation is performed using several surgical techniques that have not been systematically compared or optimized for a desired cartilage repair outcome. In this study, we investigated acute osteochondral characteristics following microfracture and comparing to drilling in a mature rabbit model of cartilage repair. Microfracture holes were made to a depth of 2 mm and drill holes to either 2 mm or 6 mm under cooled irrigation. Animals were sacrificed 1 day postoperatively and subchondral bone assessed by histology and micro‐CT. We confirmed one hypothesis that microfracture produces fractured and compacted bone around holes, essentially sealing them off from viable bone marrow and potentially impeding repair. In contrast, drilling cleanly removed bone from the holes to provide access channels to marrow stroma. Our second hypothesis that drilling would cause greater osteocyte death than microfracture due to heat necrosis was not substantiated, because more empty osteocyte lacunae were associated with microfracture than drilling, probably due to shearing and crushing of adjacent bone. Drilling deeper to 6 mm versus 2 mm penetrated the epiphyseal scar in this model and led to greater subchondral hematoma. Our study revealed distinct differences between microfracture and drilling for acute subchondral bone structure and osteocyte necrosis. Additional ongoing studies suggest these differences significantly affect long‐term cartilage repair outcome. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1432–1438, 2009
Adsorbed states of substituted α‐aminophosphinic acids on a silver electrode surface: comparison with a colloidal silver substrate
Authors: Podstawka Edyta , Kudelski Andrzej , Dra̧g M. , Oleksyszyn J. , Proniewicz Leonard M. 
Published: April 2009

AbstractWe investigated the interfacial structures of various aromatic (each compound contains one or two phenyls) di‐α‐amino (L1–L3) and α‐amino‐α‐hydroxyphosphinic (L4–L6) acids immobilized onto an electrochemically roughened silver electrode surface in an aqueous solution using surface‐enhanced Raman scattering (SERS). These structures were compared to those on a colloidal silver surface to determine the relationship between adsorption strength and geometry. The presence of an enhanced ν19a ring band in the SERS spectra of L6, L2, and L3 on the electrode indicated that the benzene rings of those molecules interact with the electrode surface through localized CC bond(s). We observed significant band broadening of the benzene ring modes for all α‐hydroxyphosphinic acids on both substrates, except for L1 deposited onto the electrode surface. This suggests the possibility of direct interaction between the ring and Ag, although the benzene ring–surface π overlap is weaker for the colloidal silver than for the Ag electrode. The downward shift in wavenumber and alternations in the enhancement of a ν12 ring band indicate a general increase of tilt angle on both silver substrates in the order L3 < L4 < L5 < L6. The altered enhancement of the bands due to the vibrations of the NH2 and OPO fragments, a finding observed on both silver substrates, strongly suggests that the groups interact with different strength and geometry with these substrates. Copyright © 2009 John Wiley & Sons, Ltd.
Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: The rotterdam experience
Authors: van Meerten E. , van der Gaast A. , Tilanus H.W. , Poley J.W. , Muller K. , van Dekken H. 
Published: April 2009

AbstractMultimodality treatment is increasingly used in the treatment for esophageal cancer. We determined the tumor regression grade after preoperative chemoradiation and correlated the effect of specific pathologic and clinical findings to overall survival. For this purpose esophageal biopsies and surgical specimens of 67 patients treated with neoadjuvant paclitaxel and carboplatin concurrent with radiotherapy were reviewed. Neoadjuvant chemoradiotherapy led to a significant downstaging. Complete tumor regression was found in 24% of the patients resulting in a trend towards better survival. It was found more frequently in poorly differentiated tumors. Patients with pre‐treatment nodal involvement, assessed by endoscopic ultrasound, had a significantly worse survival compared to patients without. Contrastingly, this was not found for post‐treatment nodal involvement, as determined by pathological examination, speculating that survival is more determined by (submicroscopic) distant disease, than by locoregional tumor cells. J. Surg. Oncol. 2009;100:32–37. © 2009 Wiley‐Liss, Inc.
Expression of extracellular matrix molecules in brain metastasis
Authors: Yoshida Seiichi , Takahashi Hideaki 
Published: April 2009

AbstractBackground and ObjectivesThe objectives of this study were to investigate the role of growth factors and matrix metalloproteinases in the brain metastasis.MethodsTumors from 40 patients with brain metastasis (30 lung cancer, 10 breast cancer) were studied to investigate the expression‐patterns of EGFR, MT1‐MMP, MMP7, and CD44 using the immunostaining and RT ‐PCR analysis.ResultsEGFR immunostaining was detected in 92% (23/25) and 70% (7/10) of brain metastasis from lung adenocarcinoma and breast cancer, respectively. MT1‐MMP immunostaining was also detected in 80% (20/25) and 50% (5/10) of brain metastasis from lung adenocarcinoma and breast cancer, respectively. EGFR mRNA was detected in 83.3% (25/30) and 70% (7/10) of brain metastasis from lung cancer and breast cancer, respectively. MT1‐MMP mRNA was detected in 73.3% (22/30) specimens of brain metastasis from lung cancer, and only 13.3% (4/30) specimens of these patients expressed MMP7 mRNA.ConclusionsThe high expression of EGFR and MT1‐MMP indicates that a extracellular matrix remodeling may be playing an important role in brain metastasis. J. Surg. Oncol. 2009;100:65–68. © 2009 Wiley‐Liss, Inc.
Medicinal chemistry and therapeutic potential of muscarinic M3 antagonists
Authors: Peretto Ilaria , Petrillo Paola , Imbimbo Bruno P. 
Published: April 2009

AbstractMuscarinic acetylcholine receptors belong to the G‐protein‐coupled receptors family. Currently five different receptor subtypes have been identified and cloned. M3 receptor subtypes are coupled to Gqfamily proteins and increase phosphatidyl inositol hydrolysis and calcium release from internal stores. They are widely distributed both in the central nervous system and in the periphery. At the central level, M3 receptor subtypes are involved in modulation of neurotransmitter release, temperature homeostasis, and food intake, while in the periphery they induce smooth muscle contraction, gland secretion, indirect relaxation of vascular smooth muscle, and miosis. The main therapeutic applications of M3 antagonists include overactive bladder (OAB), chronic obstructive pulmonary disease (COPD), and pain‐predominant irritable bowel syndrome (IBS). The introduction of selective M3 antagonists has not improved clinical efficacy compared with the old non‐selective antimuscarinics but has reduced the rate of adverse events mediated by the blockade of cardiac M2 receptors (tachycardia) and central M1 receptors (cognitive impairment). Improved tolerability has been obtained also with controlled release or with inhaled formulations. However, there is still a need for safer M3 antagonists for the treatment of COPD and better‐tolerated and more effective compounds for the therapy of OAB. New selective muscarinic M3 antagonists currently in early discovery and under development have been designed to address these issues. However, as M3 receptors are widely located in various tissues including salivary glands, gut smooth muscles, iris, and ciliary muscles, further clinical improvements may derive from the discovery and the development of new compounds with tissue rather than muscarinic receptor subtype selectivity. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 6, 867–902, 2009
Supermicrosurgical lymphaticovenular anastomosis and lymphaticovenous implantation for treatment of unilateral lower extremity lymphedema
Authors: Demirtas Yener , Ozturk Nuray , Yapici Oktay , Topalan Murat 
Published: April 2009

AbstractRecent supermicrosurgical techniques have developed the possibility for vascular anastomosis of smaller vessels and it is now safe and sound to perform precise anastomoses between lymphatics and venules. Reported here is the 2 years experience on supermicrosurgical lymphaticovenular anastomosis and/or lymphaticovenous implantation combined with a nonoperative physical therapy for treatment of lower extremity lymphedema. Microlymphatic surgery was performed in 42 patients with unilateral lower extremity lymphedema. Thirty patients were women and 12 were men with a mean age of 34. Lymphaticovenular anastomoses were performed in 37 patients with an average of 2.5 anastomoses per patient, and lymphaticovenous implantations were made in 36 patients with an average of 2.4 implantations per patient. The lymphatics that were larger than 0.3 mm were anastomosed to venules with supermicrosurgical technique. Lymphaticovenous implantation technique was used for thinner lymphatics in a particular incision. Postoperatively, 18 patients used continuous compressive garments, 9 patients used garments but discontinued after 6 months, and no compression was used in 9 patients. The results of surgery were assessed both clinically with volume measurements and by lymphoscintigraphy and were classified as good, moderate, or ineffective. The mean decrease in the volume of the edema was 59.3% at an average follow‐up of 11.8 months. Six outcomes were classified as ineffective, eight outcomes as moderate, and 28 outcomes as good. Supermicrosurgical lymphaticovenular anastomosis and/or lymphaticovenous implantation seems to be highly beneficial, especially in the early stages of peripheral lymphedema and may be offered as the treatment of choice in selected patients. © 2009 Wiley‐Liss, Inc. Microsurgery 2009.