bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory role of DC‐derived osteopontin in systemic allergen sensitization
Authors: Kurokawa Masatsugu , Konno Satoshi , Takahashi Ayumu , Plunkett Beverly , Rittling Susan R. , Matsui Yutaka , Kon Shigeyuki , Morimoto Junko , Uede Toshimitsu , Matsukura Satoshi , Kokubu Fumio , Adachi Mitsuru , Nishimura Masaharu , Huang Shau‐Ku 
Published: October 2009

AbstractOsteopontin (OPN) is a secreted phosphoglycoprotein with a wide range of functions, and is involved in various pathophysiological conditions. However, the role of OPN in IgE and Th2‐associated allergic responses remains incompletely defined. The aim of this study was to elucidate the role of OPN in systemic allergen sensitization in mice. When compared with OPN+/+ mice, significantly increased levels of OVA‐induced IgE were found in OPN−/− mice. OPN−/− DC demonstrated an increased capacity to enhance Th2 cytokine production in CD4+ T cells from sensitized OPN+/+ mice. Furthermore, significantly reduced levels of IL‐12p70 expression were seen in LPS‐stimulated OPN−/− DC as compared with the WT DC, and the reduction was reversible by the addition of recombinant OPN (rOPN). rOPN was able to suppress OVA‐induced IL‐13 production in the cultures of CD4 and OPN−/− DC, but this inhibitory activity was neutralized by the addition of anti‐IL‐12 Ab. In addition, administration of rOPN in vivo suppressed OVA‐specific IgE production; however, this suppressive effect was abrogated in IL‐12‐deficient mice. These results indicate that DC‐derived OPN plays a regulatory role in the development of systemic allergen sensitization, which is mediated, at least in part, through the production of endogenous IL‐12.
Flt3 ligand–receptor interaction is important for maintenance of early thymic progenitor numbers in steady‐state thymopoiesis
Authors: Kenins Linda , Gill Jason W. , Holländer Georg A. , Wodnar‐Filipowicz Aleksandra 
Published: October 2009

AbstractT‐cell production throughout life depends on efficient colonization and intrathymic expansion of BM‐derived hematopoietic precursors. After irradiation‐induced thymic damage, thymic recovery is facilitated by Flt3 ligand (FL), expressed by perivascular fibroblasts surrounding the thymic entry site of Flt3 receptor‐positive progenitor cells. Whether intrathymic FL–Flt3 interactions play a role in steady‐state replenishment of T cells remains unknown. Here, using competitive BM transplantation studies and fetal thymic organ cultures we demonstrated the continued numerical advantage of Flt3+intrathymic T‐cell precursors. Sub‐kidney capsule thymic transplantation experiments, in which WT and FL−/−thymic lobes were grafted into FL−/−recipients, revealed that FL expression by the thymic microenvironment plays a role in steady‐state thymopoiesis. The deficiency of the most immature thymic T‐cell precursors correlated to upregulation of FL by thymic MTS15+fibroblasts, suggesting that the number of Flt3+progenitor cells may regulate the thymic expression of this cytokine. Together, these results show that FL expression by thymic stromal fibroblasts interacting with Flt3+T‐cell progenitors is important for the physiological maintenance of early T‐cell development.
Gr‐1 antibody induces STAT signaling, macrophage marker expression and abrogation of myeloid‐derived suppressor cell activity in BM cells
Authors: Ribechini Eliana , Leenen Pieter J. M. , Lutz Manfred B. 
Published: October 2009

AbstractThe Gr‐1 (RB6‐8C5) Ab binds with high affinity to mouse Ly‐6G molecules and to a lower extent to Ly‐6C and has been widely used for cell depletion in infected or tumor‐bearing mice. Here we found that Gr‐1 treatment of BM cells in vitro and in vivo showed no depleting effects. The epitope recognized by the Gr‐1 Ab overlapped with Ly‐6G (1A8 Ab) but not Ly‐6C (ER‐MP20 Ab). In vitro the Gr‐1 Ab transmitted signals via STAT‐1, STAT‐3 and STAT‐5 into BM cells, similar to GM‐CSF. In healthy mice injected with the Gr‐1 Ab, the Ab remained attached to the surface of myeloid cells for at least four days. Gr‐1 Ab induced myeloid cell expansion, upregulation of macrophage markers, but not the DC marker CD11c. Suppressor activity of two distinct Gr‐1high and Gr‐1low expressing BM‐myeloid‐derived suppressor cell subsets was transiently ablated by Gr‐1 Ab injection. Depleting effects of Gr‐1 Ab could only be observed on inflammatory Ly‐6CintLy‐6Ghigh neutrophils from the peritoneal cavity, which occurred via apoptosis and was associated with the absence of Mcl‐1 expression. Together, Gr‐1 Ab induces signals leading to myelopoiesis and affects myeloid‐derived suppressor cell activity, suggesting functional roles for Ly‐6C/G molecules in macrophage differentiation and neutrophil apoptosis.
The Th17 cytokine IL‐22 induces IL‐20 production in keratinocytes: A novel immunological cascade with potential relevance in psoriasis
Authors: Wolk Kerstin , Witte Ellen , Warszawska Katarzyna , Schulze‐Tanzil Gundula , Witte Katrin , Philipp Sandra , Kunz Stefanie , Döcke Wolf‐Dietrich , Asadullah Khusru , Volk Hans‐Dieter , Sterry Wolfram , Sabat Robert 
Published: October 2009

AbstractPsoriasis is a common chronic skin disease. Recent studies demonstrated that IL‐20 and IL‐22, cytokines produced by keratinocytes and T cells, respectively, both inhibit keratinocyte terminal differentiation and induce psoriasis‐like epidermis alterations. Here, we investigated the relationship between these mediators. Although IL‐20 was not able to regulate IL‐22 production, IL‐22 induced IL‐20 mRNA and protein in human keratinocytes. However, IL‐22 had only a minimal effect, if any, on IL‐19 and IL‐26. Cutaneous IL‐20 was also elevated in mice following IL‐22 application. Accordingly, some of IL‐22's effects on differentiation‐regulating genes were partially mediated by an endogenous, secreted protein and attenuated by anti‐IL‐20 Ab. Like IL‐22, IL‐17A and TNF‐α induced IL‐20 in keratinocytes, whereas IFN‐γ and IL‐20 itself did not. Furthermore, IL‐17A and TNF‐α individually strengthened the IL‐22‐induced IL‐20 production. In lesional skin of psoriasis patients, highly elevated IL‐20 levels strongly correlated with IL‐22, and to a lesser extent, with IL‐17A and TNF‐α. As previously shown for IL‐22, IL‐20 blood levels correlated with the disease severity, although with a lower significance. This study demonstrates that a T‐cell mediator induces a tissue cell mediator with similar effects to its own and therefore suggests the existence of a novel type of pathogenetic cascade.
CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells
Authors: Haas Jan D. , González Frano H. Malinarich , Schmitz Susanne , Chennupati Vijaykumar , Föhse Lisa , Kremmer Elisabeth , Förster Reinhold , Prinz Immo 
Published: October 2009

Abstractγδ T cells are a potent source of innate IL‐17A and IFN‐γ, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24low CD44high effector γδ T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ γδ T cells produced IL‐17A, while NK1.1+ γδ T cells were efficient producers of IFN‐γ but not of IL‐17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ γδ T cells. Accordingly, both γδ T‐cell subsets were rare in gut‐associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL‐17A and IFN‐γ in response to TCR‐specific and TCR‐independent stimuli. IL‐12 and IL‐18 induced IFN‐γ and IL‐23 induced IL‐17A production by NK1.1+ or CCR6+ γδ T cells, respectively. Importantly, we show that CCR6+ γδ T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL‐17A‐producing γδ T cells derive from less TCR‐dependent selection events than IFN‐γ‐producing NK1.1+ γδ T cells.
The Diene Effect: The Design, Development, and Mechanistic Investigation of Metal‐Catalyzed Diene‐yne, Diene‐ene, and Diene‐allene [2+2+1] Cycloaddition Reactions
Authors: Croatt Mitchell P. , Wender Paul A. 
Published: October 2009

AbstractMetal‐catalyzed diene‐yne, diene‐ene, and diene‐allene [2+2+1] cycloaddition reactions provide new methods for the facile construction of highly functionalized five‐membered rings. These reactions can be conducted with a variety of substrate substitution patterns and functional groups and often in the absence of solvent. The special reactivity of dienes, a key to enabling or enhancing the effectiveness of the [2+2+1] and other reactions, is significantly different from that of alkynes, alkenes, or allenes. For example, the [2+2+1] reaction of a diene‐yne is accelerated compared to that of the corresponding ene‐yne. An even more dramatic “diene effect” is found with diene‐enes and diene‐allenes. While bis‐enes and ene‐allenes are not reported to yield [2+2+1] cycloadducts, the related diene‐enes and diene‐allenes undergo efficient [2+2+1] cycloadditions, providing new routes to cyclopentanones and alkylidenecyclopentanones. Mechanistic studies suggest that the unique reactivity observed with dienes arises from their participation in the putative rate‐determining reductive elimination step by providing an additional energy‐lowering coordination site for the transition metal catalyst.
Targeted radionuclide therapy in head and neck cancer
Authors: Nestor Marika V. 
Published: October 2009

AbstractThere is great potential for targeted radionuclide therapy (TRT) in the treatment of head and neck cancer. In recent years, developments in fields such as antigen screening, protein engineering, and cancer biology have facilitated the rational design of targeted pharmaceuticals, with monoclonal antibodies forming the most rapidly expanding category. TRT may be a promising way to improve targeted treatment, especially in head and neck cancer, because of the intrinsic radiosensitivity of this tumor type. TRT may also provide a good foundation on which to build rational biologic combination therapies. In the next few years the use of TRT may offer new opportunities for further improvement of the therapeutic ratio that potentially may obviate or reduce the need for conventional cytotoxics. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Morbidity and mortality of thyroidectomy for substernal goiter
Authors: Abboud Bassam , Sleilaty Ghassan , Mallak Nadine , Abou Zeid Hicham , Tabchy Bassam 
Published: October 2009

AbstractBackgroundOur objective was to evaluate morbidity and mortality of thyroidectomy in substernal goiters and identify patients at risk for these events.MethodsThe medical records of 127 patients with substernal goiters were retrospectively reviewed.ResultsThe most common preoperative symptom was shortness of breath (48%). 13% of the 127 patients were asymptomatic. Preoperative imaging identified tracheal deviation in 69% and tracheal compression in 41% of the cases. Substernal goiters were resected via a cervical approach in 100% of the cases. Six patients (5%) had postoperative hoarseness, 1 had permanent vocal cord paralysis, and 19 (15%) had transient postoperative hypocalcemia. The mortality and permanent hypoparathyroidism were null. Patients with postoperative complications had larger goiters and were more likely to have tracheal compression.ConclusionsThyroid resection via a cervical approach for substernal goiters is associated with low rate of morbidity and no mortality. Patients with large tumors and tracheal compression are more likely to develop postoperative complications. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
MicroRNA‐15b represents an independent prognostic parameter and is correlated with tumor cell proliferation and apoptosis in malignant melanoma
Authors: Satzger Imke , Mattern Anika , Kuettler Uta , Weinspach Dirk , Voelker Bernward , Kapp Alexander , Gutzmer Ralf 
Published: October 2009

AbstractMicroRNAs (miRNAs) are small noncoding RNAs (∼22 bp) that posttranscriptionally regulate gene expression. MiRNAs possess oncogenic or tumor suppressor activity in various tumors but little is known about miRNA expression pattern in malignant melanoma. We determined the expression level of 16 potentially relevant miRNAs (miR‐15a, miR‐15b, miR‐16, miR‐34a, miR‐210, let‐7I, miR‐23a, miR‐23b, miR‐24, miR‐27a, miR‐27b, miR‐100, miR‐137, miR‐222, miR‐373‐1, miR‐373*) by real‐time PCR in 6 preparations of normal melanocytes vs. 10 melanoma cell lines and in formalin fixed paraffin embedded tissue of 11 melanocytic nevi versus 16 melanomas. MiR‐15b and miR‐210 were significantly upregulated, miR‐34a was significantly downregulated in melanomas compared with melanocytic nevi. These 3 miRNAs were analyzed in a total of 128 primary melanomas from patients with detailed clinical follow‐up information. High expression of miR‐15b (but not miR‐210 upregulation and miR‐34a downregulation) was significantly associated with poor recurrence free survival and overall survival by univariate Kaplan‐Meier and multivariate Cox analyses. Downregulation of miR‐15b in two melanoma cell lines with high miR‐15b expression by transfection with anti‐miR‐15b siRNA was associated with reduced tumor cell proliferation, whereas apoptosis was increased. In summary, miRNA expression levels show distinct differences comparing benign and malignant melanocytic cell proliferations and can provide independent prognostic informations. MiR‐15b appears to represent a particular important miRNA in melanoma that is associated with poor prognosis and tumorigenesis.
Expression and subcellular localization of myogenic regulatory factors during the differentiation of skeletal muscle C2C12 myoblasts
Authors: Ferri Paola , Barbieri Elena , Burattini Sabrina , Guescini Michele , D'Emilio Alessandra , Biagiotti Laura , Del Grande Paolo , De Luca Antonio , Stocchi Vilberto , Falcieri Elisabetta 
Published: October 2009

AbstractIt is known that the MyoD family members (MyoD, Myf5, myogenin, and MRF4) play a pivotal role in the complex mechanism of skeletal muscle cell differentiation. However, fragmentary information on transcription factor‐specific regulation is available and data on their post‐transcriptional and post‐translational behavior are still missing. In this work, we combined mRNA and protein expression analysis with their subcellular localization. Each myogenic regulator factor (MRF) revealed a specific mRNA trend and a protein quantitative analysis not overlapping, suggesting the presence of post‐transcriptional mechanisms. In addition, each MRF showed a specific behavior in situ, characterized by a differentiation stage‐dependent localization suggestive of a post‐translational regulation also. Consistently with their transcriptional activity, immunogold electron microscopy data revealed MRFs distribution in interchromatin domains. Our results showed a MyoD and Myf5 contrasting expression profile in proliferating myoblasts, as well as myogenin and MRF4 opposite distribution in the terminally differentiated myotubes. Interestingly, MRFs expression and subcellular localization analysis during C2C12 cell differentiation stages showed two main MRFs regulation mechanisms: (i) the protein half‐life regulation to modulate the differentiation stage‐dependent transcriptional activity and (ii) the cytoplasmic retention, as a translocation process, to inhibit the transcriptional activity. Therefore, our results exhibit that MRFs nucleo‐cytoplasmic trafficking is involved in muscle differentiation and suggest that, besides the MRFs expression level, also MRFs subcellular localization, related to their functional activity, plays a key role as a regulatory step in transcriptional control mechanisms. J. Cell. Biochem. 108: 1302–1317, 2009. © 2009 Wiley‐Liss, Inc.
GSKIP, an inhibitor of GSK3β, mediates the N‐cadherin/β‐catenin pool in the differentiation of SH‐SY5Y cells
Authors: Lin Ching‐Chih , Chou Chia‐Hua , Howng Shen‐Long , Hsu Chia‐Yi , Hwang Chi‐Ching , Wang Chihuei , Hsu Ching‐Mei , Hong Yi‐Ren 
Published: October 2009

AbstractEmerging evidence has shown that GSK3β plays a pivotal role in regulating the specification of axons and dendrites. Our previous study has shown a novel GSK3β interaction protein (GSKIP) able to negatively regulate GSK3β in Wnt signaling pathway. To further characterize how GSKIP functions in neurons, human neuroblastoma SH‐SY5Y cells treated with retinoic acid (RA) to differentiate to neuron‐like cells was used as a model. Overexpression of GSKIP prevents neurite outgrowth in SH‐SY5Y cells. GSKIP may affect GSK3β activity on neurite outgrowth by inhibiting the specific phosphorylation of tau (ser396). GSKIP also increases β‐catenin in the nucleus and raises the level of cyclin D1 to promote cell‐cycle progression in SH‐SY5Y cells. Additionally, overexpression of GSKIP downregulates N‐cadherin expression, resulting in decreased recruitment of β‐catenin. Moreover, depletion of β‐catenin by small interfering RNA, neurite outgrowth is blocked in SH‐SY5Y cells. Altogether, we propose a model to show that GSKIP regulates the functional interplay of the GSK3β/β‐catenin, β‐catenin/cyclin D1, and β‐catenin/N‐cadherin pool during RA signaling in SH‐SY5Y cells. J. Cell. Biochem. 108: 1325–1336, 2009. © 2009 Wiley‐Liss, Inc.
PDEF is a negative regulator of colon cancer cell growth and migration
Authors: Moussa Omar , Turner David P. , Feldman Ron J. , Sementchenko Victor I. , McCarragher Brent D. , Desouki Mohamed M. , Fraig Mostafa , Watson Dennis K. 
Published: October 2009

AbstractETS is a family of transcriptional regulators with functions in most biological processes. Dysregulated ETS factor function leads to altered expression of multiple genes that play critical roles in many of the processes required for cancer progression. While the Ets family gene, prostate‐derived ETS factor (PDEF), is expressed in epithelial tissues including prostate, breast, and colon, PDEF protein expression has been found to be reduced or lost during prostate and breast cancer progression. The goal of this study was to examine the expression and biologic impact of altered PDEF expression in colon cancer. PDEF mRNA and protein are not detectable in several colon‐cancer‐derived cell lines. Re‐expression of PDEF in colon cancer cells inhibits growth and migration. Growth affects are due to altered cellular proliferation, indicated by increased altered cell population in G1 and S phases of the cell cycle, as well as increased apoptosis. Relevant to its modulation of growth and migration phenotypes, PDEF expression resulted in altered expression of genes with established roles in cell cycle, motility, and invasion. Furthermore, chromatin immunoprecipitation studies show that p21 and urokinase plasminogen activator (uPA) are direct PDEF transcriptional targets. While non‐tumor colon epithelium expresses PDEF mRNA and protein, the majority of tumors showed decreased mRNA and/or protein expression. In human tumor tissue samples, PDEF expression was inversely correlated with the expression levels of uPA. Collectively, the data support the model that PDEF is a negative regulator of tumor progression by modulating the expression of growth and migration promoting genes. J. Cell. Biochem. 108: 1389–1398, 2009. © 2009 Wiley‐Liss, Inc.
Intramolecular electronic communication in a dimethylaminoazobenzene–fullerene C60 dyad: An experimental and TD‐DFT study
Authors: Senthil Kumar K. , Patnaik Archita 
Published: October 2009

AbstractAn electronically push–pull type dimethylaminoazobenzene–fullerene C60 hybrid was designed and synthesized by tailoring N,N‐dimethylaniline as an electron donating auxochrome that intensified charge density on the β‐azonitrogen, and on N‐methylfulleropyrrolidine (NMFP) as an electron acceptor at the 4 and 4′ positions of the azobenzene moiety, respectively. The absorption and charge transfer behavior of the hybrid donor‐bridge‐acceptor dyad were studied experimentally and by performing TD‐DFT calculations. The TD‐DFT predicted charge transfer interactions of the dyad ranging from 747 to 601 nm were experimentally observed in the UV‐vis spectra at 721 nm in toluene and dichloromethane. A 149 mV anodic shift in the first reduction potential of the NN group of the dyad in comparison with the model aminoazobenzene derivative further supported the phenomenon. Analysis of the charge transfer band through the orbital picture revealed charge displacement from the n(NN) (nonbonding) and π (NN) type orbitals centered on the donor part to the purely fullerene centered LUMOs and LUMO+n orbitals, delocalized over the entire molecule. The imposed electronic perturbations on the aminoazobenzene moiety upon coupling it with C60 were analyzed by comparing the TD‐DFT predicted and experimentally observed electronic transition energies of the dyad with the model compounds, NMFP and (E)‐N,N‐dimethyl‐4‐(p‐tolyldiazenyl)aniline (AZNME). The n(NN) → π*(NN) and π(NN) → π*(NN) transitions of the dyad were bathochromically shifted with a significant charge transfer character. The shifting of π(NN) → π*(NN) excitation energy closer to the n → π*(NN) in comparison with the model aminoazobenzene emphasized the predominant existence of charge separated quinonoid‐like ground state electronic structure. Increasing solvent polarity introduced hyperchromic effect in the π(NN) → π*(NN) electronic transition at the expense of transitions involved with benzenic states, and the extent of intensity borrowing was quantified adopting the Gaussian deconvolution method. On a comparative scale, the predicted excitation energies were in reasonable agreement with the observed values, demonstrating the efficiency of TD‐DFT in predicting the localized and the charge transfer nature of transitions involved with large electronically asymmetric molecules with HOMO and LUMO centered on different parts of the molecular framework. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Small maximal matchings of random cubic graphs
Authors: Assiyatun H. , Duckworth W. 
Published: October 2009

AbstractWe consider the expected size of a smallest maximal matching of cubic graphs. Firstly, we present a randomized greedy algorithm for finding a small maximal matching of cubic graphs. We analyze the average‐case performance of this heuristic on random n‐vertex cubic graphs using differential equations. In this way, we prove that the expected size of the maximal matching returned by the algorithm is asymptotically almost surely (a.a.s.) less than 0.34623n. We also give an existence proof which shows that the size of a smallest maximal matching of a random n‐vertex cubic graph is a.a.s. less than 0.3214n. It is known that the size of a smallest maximal matching of a random n‐vertex cubic graph is a.a.s. larger than 0.3158n. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 293–323, 2009