bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redistribution of Sphingosine 1-Phosphate by Sphingosine Kinase 2 Contributes to Lymphopenia
Authors: Sensken Sven-Christian , Bode Constantin , Nagarajan Manju , Peest Ulrike , Pabst Oliver , Gräler Markus H. 
Published: March 2010

Abstract
Sphingosine kinases (SKs) 1 and 2 produce high concentrations of sphingosine 1-phosphate (S1P) in blood and lymph. In contrast, S1P concentrations in lymphoid tissues are kept low by the S1P-degrading activity of the S1P-lyase. These differences in S1P concentrations drive lymphocyte circulation. Inhibition of the S1P-lyase prevents lymphocyte egress and causes lymphopenia because of increased S1P levels in lymphoid tissues. In this study, we investigated the source of this accumulating S1P in lymphoid tissues by using SK2-deficient (SK2−/−) mice. In contrast to wild-type mice, SK2−/− mice exhibited attenuated lymphopenia after S1P-lyase inhibition by 4-deoxypyridoxine (DOP). Consistently, S1P concentrations were only modestly increased in lymphoid tissues of SK2−/− mice compared with a significantly higher increase in wild-type mice after DOP treatment. Low S1P concentrations in lymphoid tissues of DOP-treated SK2−/− mice were accompanied by higher S1P concentrations in blood, suggesting that SK2−/− mice display defective S1P transport from blood into lymphoid tissues. To investigate this potential new role of SK2, RBCs loaded with traceable C17-S1P were transfused into wild-type and SK2−/− mice, resulting in much higher C17-S1P concentrations in blood of SK2−/− mice compared with wild-type mice 2 h after transfusion. Moreover, cocultures of RBCs with mouse splenocytes and endothelial cells demonstrated that SK2 regulated cellular uptake of S1P from RBCs. Collectively, our data suggest that S1P in lymphoid tissues derives from blood and point to an essential role of SK2 in S1P transport.
Attenuation of PI3K/Akt-Mediated Tumorigenic Signals through PTEN Activation by DNA Vaccine-Induced Anti-ErbB2 Antibodies
Authors: Porzia Alessandra , Lanzardo Stefania , Citti Arianna , Cavallo Federica , Forni Guido , Santoni Angela , Galandrini Ricciarda , Paolini Rossella 
Published: March 2010

Abstract
By studying BALB/c mice deficient in immune components, we show that the protective immunity to rat ErbB2+ tumors rests on the Ab response elicited by the electroporation of a DNA vaccine encoding the extracellular and transmembrane domains of rat ErbB2. In vivo, the adoptive transfer of vaccine-elicited anti-rat ErbB2 Abs protected against a challenge of rat ErbB2+ carcinoma cells (TUBO cells). In vitro, such Abs inhibited TUBO cell growth by impairing cell cycle progression and inducing apoptosis. To correlate intrinsic mechanisms of Ab action with their tumor-inhibitory potential, first we showed that TUBO cells constitutively express phosphorylated transgenic ErbB2/autochthonous ErbB3 heterodimers and exhibit a basal level of Akt phosphorylation, suggesting a constitutive activation of the PI3K/Akt pathway. Treatment with anti-ErbB2 Abs caused a drastic reduction in the basal level of Akt phosphorylation in the absence of an impairment of PI3K enzymatic activity. Notably, the same Ab treatment induced an increase in PTEN phosphatase activity that correlated with a reduced PTEN phosphorylation. In conclusion, vaccine-induced anti-ErbB2 Abs directly affected the transformed phenotype of rat ErbB2+ tumors by impairing ErbB2-mediated PI3K/Akt signaling.
Mathematical Modeling of Chimeric TCR Triggering Predicts the Magnitude of Target Lysis and Its Impairment by TCR Downmodulation
Authors: James Scott E. , Greenberg Philip D. , Jensen Michael C. , Lin Yukang , Wang Jinjuan , Budde Lihua E. , Till Brian G. , Raubitschek Andrew A. , Forman Stephen J. , Press Oliver W. 
Published: March 2010

Abstract
We investigated relationships among chimeric TCR (cTCR) expression density, target Ag density, and cTCR triggering to predict lysis of target cells by cTCR+ CD8+ T human cells as a function of Ag density. Triggering of cTCR and canonical TCR by Ag could be quantified by the same mathematical equation, but cTCR represented a special case in which serial triggering was abrogated. The magnitude of target lysis could be predicted as a function of cTCR triggering, and the predicted minimum cTCR density required for maximal target lysis by CD20-specific cTCR was experimentally tested. cTCR density below ∼20,000 cTCR/cell impaired target lysis, but increasing cTCR expression above this density did not improve target lysis or Ag sensitivity. cTCR downmodulation to densities below this critical minimum by interaction with Ag-expressing targets limited the sequential lysis of targets in a manner that could be predicted based on the number of cTCRs remaining. In contrast, acute inhibition of lysis of primary, intended targets (e.g., leukemic B cells) due to the presence of an excess of secondary targets (e.g., normal B cells) was dependent on the Ag density of the secondary target but occurred at Ag densities insufficient to promote significant cTCR downmodulation, suggesting a role for functional exhaustion rather than insufficient cTCR density. This suggests increasing cTCR density above a critical threshold may enhance sequential lysis of intended targets in isolation, but will not overcome the functional exhaustion of cTCR+ T cells encountered in the presence of secondary targets with high Ag density.
Toxin-Coupled MHC Class I Tetramers Can Specifically Ablate Autoreactive CD8+ T Cells and Delay Diabetes in Nonobese Diabetic Mice
Authors: Vincent Benjamin G. , Young Ellen F. , Buntzman Adam S. , Stevens Rosemary , Kepler Thomas B. , Tisch Roland M. , Frelinger Jeffrey A. , Hess Paul R. 
Published: March 2010

Abstract
There is compelling evidence that self-reactive CD8+ T cells are a major factor in development and progression of type 1 diabetes in animals and humans. Hence, great effort has been expended to define the specificity of autoimmune CD8+ T cells and to alter their responses. Much work has focused on tolerization of T cells using proteins or peptides. A weakness in this approach is that residual autoreactive T cells may be activated and exacerbate disease. In this report, we use a novel approach, toxin-coupled MHC class I tetramers. Used for some time to identify Ag-specific cells, in this study, we use that same property to delete the Ag-specific cells. We show that saporin-coupled tetramers can delete islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-reactive T cells in vitro and in vivo. Sequence analysis of TCRβ-chains of IGRP+ cells reveals the repertoire complexity in the islets is markedly decreased as NOD mice age and significantly altered in toxic tetramer-treated NOD mice. Further tetramer+ T cells in the islets are almost completely deleted, and, surprisingly, loss of tetramer+ T cells in the islets is long lasting. Finally, we show deletion at 8 wk of age of IGRP+ CD8+ T cells, but not dystophia myotonica kinase- or insulin B-reactive cells, significantly delays diabetes in NOD mice.
Organic Ligands Made Porous: Magnetic and Catalytic Properties of Transition Metals Coordinated to the Surfaces of Mesoporous Organosilica
Authors: Kuschel Andreas , Luka Martin , Wessig Martin , Drescher Malte , Fonin Mikhail , Kiliani Gillian , Polarz Sebastian 
Published: March 2010

AbstractInorganic solids with porosity on the mesoscale possess a high internal surface area and a well‐accessible pore system. Therefore, it is a relevant task to equip the surfaces of such materials with a maximum density of various organic functional groups. Among these functions it is the capability of coordinating to metal species as a ligand that is of extraordinary importance in many areas, for example, in catalysis. This paper describes how prominent ligands containing donor functions such as carboxylic, thio, chelating, or amine groups can be obtained in the form of nanoporous organosilica materials. The coordination of metal centers such as CoII, MnII, VIV, or PtIV is studied in detail. The magnetic properties of the corresponding materials and some applications in catalysis are reported. A quantitative determination of the surface density of donor atoms by distance measurements using EPR spectroscopy is shown.
Template‐Directed Liquid ALD Growth of TiO2 Nanotube Arrays: Properties and Potential in Photovoltaic Devices
Authors: Foong Thelese R. B. , Shen Yaodong , Hu Xiao , Sellinger Alan 
Published: March 2010

AbstractDense and well‐aligned arrays of TiO2 nanotubes extending from various substrates are successfully fabricated via a new liquid‐phase atomic layer deposition (LALD) in nanoporous anodic alumina (AAO) templates followed by alumina dissolution. The facile and versatile process circumvents the need for vacuum conditions critical in traditional gas‐phase ALD and yet confers ALD‐like deposition rates of 1.6–2.2 Å cycle−1, rendering smooth conformal nanotube walls that surpass those achievable by sol–gel and Ti‐anodizing techniques. The nanotube dimensions can be tuned, with most robust structures being 150–400 nm tall, 60–70 nm in diameter with 5–20 nm thick walls. The viability of TiO2 nanotube arrays deposited on indium tin oxide (ITO)–glass electrodes for application in model hybrid poly(3‐hexylthiophene) (P3HT):TiO2 solar cells is studied. The results achieved provide platforms and research directions for further advancements.
Developing standard approaches for recording and assessing river hydromorphology: the role of the European Committee for Standardization (CEN)
Authors: Boon Philip J. , Holmes Nigel T.H. , Raven Paul J. 
Published: March 2010

Abstract 1. Over the last 20 years the concept of ‘freshwater quality’ has expanded to incorporate a range of physical, chemical, hydromorphological and biological characteristics. In Europe, this process has been given greater impetus by the EC Water Framework Directive (WFD) and the requirement for Member States to assess and monitor a comprehensive suite of freshwater features. 2. Assessments of river hydromorphology are needed not only for implementing the WFD but also for nature conservation purposes, such as monitoring the condition of Special Areas of Conservation under the EC Habitats Directive and helping in the management and restoration of rivers. At present there are few detailed methods available in Europe for assessing river hydromorphology, and standard approaches are urgently required. 3. The European Committee for Standardization (CEN) works to promote voluntary technical harmonization in Europe in conjunction with worldwide bodies and its European partners. The production of a CEN standard for assessing the hydromorphological features of rivers began in September 1999 and culminated in the production of EN 14614 in November 2004. 4. EN 14614 is a ‘guidance standard’ that provides a framework of general principles and sets out which aspects of river hydromorphology should be assessed, how to plan and conduct field surveys, how results should be interpreted and presented, and ways of applying quality assurance procedures. 5. A second CEN standard on river hydromorphology has recently been published. Using simple scoring systems, this will enable the extent of hydromorphological modification to river channels, banks, riparian zones and floodplains to be recorded and assessed consistently. 6. CEN standards encourage European collaboration and provide a framework which other countries can use to develop their own assessment methods. However, ways need to be found to streamline the process of standardization and to ensure that published standards influence the work of researchers, environmental regulators and policy makers. Copyright © 2010 John Wiley & Sons, Ltd.
Expression of VEGF‐C and VEGF‐D as Significant Markers for Assessment of Lymphangiogenesis and Lymph Node Metastasis in Non‐Small Cell Lung Cancer
Authors: Feng Yukuan , Wang Wei , Hu Jing , Ma Jing , Zhang Yafang , Zhang Jianguo 
Published: March 2010

AbstractVascular endothelial growth factor (VEGF)‐C and VEGF‐D induce lymphangiogenesis through activation of VEGF receptor 3 (VEGFR‐3) and have been implicated in tumor spread to the lymphatic system. Lymph node dissemination critically determines clinical outcome and therapeutic options of patients with non‐small cell lung cancer (NSCLC). However, the relationship of VEGF‐C, VEGF‐D, and lymph node metastasis in cancers, including NSCLC, is still controversial. To evaluate the relationship between lymphangiogenesis and lymph node metastasis, the expression of VEGF‐C and VEGF‐D in NSCLC tumors were detected by immunohistochemistry and quantitative real‐time polymerase chain reaction (QRT‐PCR). QRT‐PCR revealed that in marginal region VEGF‐C and VEGF‐D mRNA was significantly higher than in tumor center, and VEGF‐D mRNA was also higher than that in peritumoral lung tissue. Immunohistochemically, we observed the same heterogeneous expression of VEGF‐C and VEGF‐D proteins. The group with high expression of VEGF‐C and VEGF‐D in marginal region had a higher incidence of lymph node metastasis compared with the group with low expression. Furthermore, the group with high expression of VEGF‐D in marginal region had a higher incidence of lymphatic invasion. The group with high peritumoral lymphatic vessel density (LVD) had higher expression of VEGF‐C and VEGF‐D mRNA compared with the group with low peritumoral LVD. Our studies suggested that the expression of VEGF‐C and VEGF‐D at invasive edge was significantly associated with lymph node metastasis or lymphatic invasion in patients with NSCLC and may be involved in regulation of lymphangiogenesis and lymph node metastasis in NSCLC. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Evaluation of rhBMP‐2 and Natural Latex as Potential Osteogenic Proteins in Critical Size Defects by Histomorphometric Methods
Authors: Issa João Paulo Mardegan , Defino Helton Luiz Aparecido , Netto Joaquim Coutinho , Volpon José Batista , Regalo Simone Cecílio Hallak , Iyomasa Mamie Mizusaki , Siéssere Selma , Tiossi Rodrigo 
Published: March 2010

AbstractThis in vivo study evaluated the osteogenic potential of two proteins, recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and a protein extracted from natural latex (Hevea brasiliensis, P‐1), and compared their effects on bone defects when combined with a carrier or a collagen gelatin. Eighty‐four (84) Wistar rats were divided into two groups, with and without the use of collagen gelatin, and each of these were divided into six treatment groups of seven animals each. The treatment groups were: (1) 5 μg of pure rhBMP‐2; (2) 5 μg of rhBMP‐2/monoolein gel; (3) pure monoolein gel; (4) 5 μg of pure P‐1; (5) 5 μg of P‐1/monoolein gel; (6) critical bone defect control. The animals were anesthetized and a 6 mm diameter critical bone defect was made in the left posterior region of the parietal bone. Animals were submitted to intracardiac perfusion after 4 weeks and the calvaria tissue was removed for histomorphometric analysis. In this experimental study, it was concluded that rhBMP‐2 allowed greater new bone formation than P‐1 protein and this process was more effective when the bone defect was covered with collagen gelatin (P < 0.05). Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Ultramicroscopic Examination of the Ovine Tonsillar Epithelia
Authors: Casteleyn Christophe , Cornelissen Maria , Simoens Paul , Van Den Broeck Wim 
Published: March 2010

AbstractAs solid morphological knowledge of ovine tonsillar epithelia might contribute to a better understanding of the pathogenesis of several diseases including prion diseases, the epithelia of all tonsils of 7 one‐year‐old Texel sheep were examined using scanning and transmission electron microscopy. Major parts of the pharyngeal and tubal tonsils were covered by pseudostratified columnar ciliated epithelia that were interrupted by patches of epithelium containing cells with densely packed microfolds or microvilli, and cells with both microvilli and cilia. Smaller parts were covered by either flattened polygonal cells with densely packed microvilli or microfolds, squamous epithelial cells, or patches of reticular epithelium. The palatine and paraepiglottic tonsils were mainly lined by squamous epithelial cells with apical microplicae or short knobs. Additionally, regions of reticular epithelium containing epithelial cells with apical microvilli were seen. The lingual tonsil was uniformly covered by a keratinized squamous epithelium and devoid of microvillous cells and patches of reticular epithelium. The rostral half of the tonsil of the soft palate was lined by a pseudostratified columnar ciliated epithelium with characteristics of the pharyngeal and tubal tonsils. The epithelium of the caudal part resembled the epithelia of the palatine and paraepiglottic tonsils. Putative M cells, mainly characterized by apical microvilli or microfolds and a close association with lymphoid cells, seem manifestly present on the nasopharyngeal tonsils. The reticular epithelium of the palatine and paraepiglottic tonsils also harbor cells with small apical microvilli. The exact nature of these presumptive M cells should, however, be elucidated in functional studies. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Expression of Muscle Segment Homeobox Genes in the Developing Myocardium
Authors: Boogerd Cornelis J.J. , Moorman Antoon F.M. , Barnett Phil 
Published: March 2010

AbstractMsx1 and Msx2 are essential for the development of many organs. In the heart, they act redundantly in development of the cardiac cushions. Additionally, Msx2 is expressed in the developing conduction system. However, the exact expression of Msx1 has not been established. We show that Msx1 is expressed in the cardiac cushions, but not in the myocardium. In Msx2‐null mice, Msx1 is not ectopically expressed in the myocardium. The absence of myocardial defects in the Msx2 knock‐out can therefore not be attributed to a redundant action of Msx1 in the myocardium. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Distribution Analysis of Deacetylase SIRT1 in Rodent and Human Nervous Systems
Authors: Zakhary Sherry M. , Ayubcha Diana , Dileo Jeffery N. , Jose Riya , Leheste Joerg R. , Horowitz Judith M. , Torres German 
Published: March 2010

AbstractSirtuins function with other biogenic molecules to promote adaptation to caloric restriction in a broad spectrum of eukaryotic species. Sirtuin pathways also converge in the mammalian brain where they appear to protect neurons from nutrient stress. However, few anatomical studies on sirtuins (e.g., SIRT1) are available, particularly those detailing the spatial distribution and subcellular localization pattern of SIRT1 in the brain parenchyma. Here, we report the characterization of a panel of SIRT1‐specific antibodies within rodent (i.e., rat and mouse) and human central nervous systems. Immunocytochemical and Western blot analyses indicate that the subcellular localization of SIRT1 is predominantly nuclear throughout the rodent brain and spinal cord. A similar subcellular distribution pattern of SIRT1 was detected in human central nervous system material. SIRT1 is ubiquitously present in areas of the brain especially susceptible to age‐related neurodegenerative states (e.g., the prefrontal cortex, hippocampus and basal ganglia). Further, we show no apparent species‐specific differences in the subcellular localization pattern of rodent versus human SIRT1. Finally, we identify the chemical phenotype of SIRT1‐containing neurons in a number of brain sites that are strongly compromised by aging. These data provide additional and important anatomical findings for the role of SIRT1 in the mammalian brain and suggest that SIRT1 pathways are broadly distributed in neurons most susceptible to senescence injury. Activating endogenous sirtuin pathways may, therefore, offer a therapeutic approach to delay and/or treat human age‐related diseases. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Interleukin‐2 Enhances Dendritic Development and Spinogenesis in Cultured Hippocampal Neurons
Authors: Shen Yi , Liu Shuang‐Shuang , Zhan Min‐Ye , Luo Jian‐Hong , Zhu Li‐Jun 
Published: March 2010

AbstractIn this study, we investigated the effects of interleukin‐2 (IL‐2) on dendritic filopodia, dendritic arborization, and spine maturation during the development of cultured rat hippocampal neurons. The cultured hippocampal neurons were transfected with F‐GFP (farnesylated enhanced green fluorescent protein) at DIV5 to display the subtle structure of dendrites, and were then treated with IL‐2 at various concentrations for different time before living cell image observation. We found that both the dendritic arborization and the length of dendrites per neuron at DIV7, DIV10, and DIV14 were increased under IL‐2 treatment in a dose‐dependent manner, and the strongest IL‐2 effects on both dendritic number and length were observed at DIV7. Also, there was a significant increase in the mobility of dendritic filopodia in neurons at DIV7 treated with 10 ng/mL IL‐2 for 48 hr from DIV5. In addition, IL‐2 caused an increase in spine density of neurons at DIV14 either treated with IL‐2 from DIV5 to DIV7 or from DIV5 to DIV14, but did not affect neurons treated from DIV12 to DIV14. These results indicate that IL‐2 affects the dendritic development and spinogenesis of cultured hippocampal neurons, especially during the early developmental stage. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Identification and Expression Analysis of a Novel CW‐Type Zinc Finger Protein MORC2 in Cancer Cells
Authors: Wang Gui‐Ling , Wang Chun‐Yu , Cai Xin‐Ze , Chen Wei , Wang Xiao‐Hui , Li Feng 
Published: March 2010

AbstractMicrorchidia2 (MORC2) is a member of the MORC protein family that is localized to both the nucleus and cytoplasm when transiently expressed in gastric cancer cells. We identified and analyzed the functional domains of MORC2, which has specific unique structural characteristics compared to the other MORC proteins. Our data showed that nuclear localization signals (NLS) of MORC2 was mainly dependent on the NLS amino acids (aa) 657–781 and cytoplasmic localization of MORC2 was attributed to the nuclear export signal (NES) aa 481–657. Moreover, the NLS appears to predominate over the NES in the localization of full‐length human MORC2 indicating that MORC2 is localized mainly in the nucleus. Our results also demonstrated that the NLS (aa 657–781) and proline‐rich domain within MORC2 C‐terminus were required for the transcriptional repressive role in cancer cells. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Possible Mechanisms of Trichosanthin‐Induced Apoptosis of Tumor Cells
Authors: Li Meng , Li Xiang , Li Ji‐Cheng 
Published: March 2010

AbstractTrichosanthin (TCS) is a type I ribosome‐inactivating protein that is isolated from the root tubers of the Chinese medicinal herb Trichosanthes kirilowii Maximowicz. TCS has been used as an abortifacient for 1,500 years in China because of its high toxicity on trophoblasts. Over the past 20 years, TCS has been the subject of much research because of its potential antitumor activities. Many reports have revealed that TCS is cytotoxic in a variety of tumor cell lines in vitro and in vivo. Monoclonal antibody‐conjugated TCS could enhance its antitumor efficacy; thus, TCS is considered to be a potential biological agent for cancer treatment. TCS is able to inhibit protein synthesis and consequently induce necrosis. Recent studies have demonstrated that TCS does indeed induce apoptosis in several tumor cell lines. Although TCS‐induced apoptosis of tumor cell lines is now well known, the underlying mechanisms remain to be elucidated. The purpose of this review was to investigate the effects of TCS and its possible mechanisms of action, based on published literature and the results of our own studies. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.