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101.
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103.
Masayasu Naito Ursula Hainz Ute E. Burkhardt Buyin Fu Deborah Ahove Kristen E. Stevenson Mohini Rajasagi Baogong Zhu Anselmo Alonso Elizabeth Witten Ken-ichi Matsuoka Donna Neuberg Jonathan S. Duke-Cohan Catherine J. Wu Gordon J. Freeman 《Cancer immunology, immunotherapy : CII》2013,62(2):347-357
CD40L has a well-established role in enhancing the immunostimulatory capacity of normal and malignant B cells, but a formulation suitable for clinical use has not been widely available. Like other TNF family members, in vivo and in vitro activity of CD40L requires a homotrimeric configuration, and growing evidence suggests that bioactivity depends on higher-order clustering of CD40. We generated a novel formulation of human recombinant CD40L (CD40L-Tri) in which the CD40L extracellular domain and a trimerization motif are connected by a long flexible peptide linker. We demonstrate that CD40L-Tri significantly expands normal CD19+ B cells by over 20- to 30-fold over 14 days and induces B cells to become highly immunostimulatory antigen-presenting cells (APCs). Consistent with these results, CD40L-Tri-activated B cells could effectively stimulate antigen-specific T responses (against the influenza M1 peptide) from normal volunteers. In addition, CD40L-Tri could induce malignant B cells to become effective APCs, such that tumor-directed immune responses could be probed. Together, our studies demonstrate the potent immune-stimulatory effects of CD40L-Tri on B cells that enable their expansion of antigen-specific human T cells. The potent bioactivity of CD40L-Tri is related to its ability to self-multimerize, which may be facilitated by its long peptide linker. 相似文献
104.
Carmen García-Ibarbia Jesús Delgado-Calle Iñigo Casafont Javier Velasco Jana Arozamena María I. Pérez-Núñez María A. Alonso María T. Berciano Fernando Ortiz José L. Pérez-Castrillón Agustín F. Fernández Mario F. Fraga María T. Zarrabeitia José A. Riancho 《Gene》2013
We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic and epigenetic mechanisms involved. 相似文献
105.
Elaine T. Lim Soumya Raychaudhuri Stephan J. Sanders Christine Stevens Aniko Sabo Daniel G. MacArthur Benjamin M. Neale Andrew Kirby Douglas M. Ruderfer Menachem Fromer Monkol Lek Li Liu Jason Flannick Stephan Ripke Uma Nagaswamy Donna Muzny Jeffrey G. Reid Alicia Hawes Mark J. Daly 《Neuron》2013,77(2):235-242
106.
Adela García‐Martín Alicia Acitores Marta Maycas María L. Villanueva‐Peñacarrillo Pedro Esbrit 《Journal of cellular biochemistry》2013,114(6):1404-1413
Parathyroid hormone‐related protein (PTHrP) stimulates osteoblastic function through its N‐ and C‐terminal domains. Since the osteogenic action of the latter domain appears to depend at least in part on its interaction with the vascular endothelial growth factor (VEGF) system, we aimed to explore the putative mechanism underlying this interaction in osteoblasts. Using native conditions for protein extraction and immunoblotting, we found that both PTHrP (107–139) and the shorter PTHrP (107–111) peptide (known as osteostatin), at 100 nM, promoted the appearance of a VEGF receptor (VEGFR) 2 protein band of apparent Mr. wt. 230 kDa, which likely represents its activation by dimer formation, in mouse osteoblastic MC3T3‐E1 cells. Moreover, osteostatin (100 nM) maximally increased VEGFR2 phosphorylation at Tyr‐1059 within 5–10 min in both MC3T3‐E1 and rat osteoblastic osteosarcoma UMR‐106 cells. This phosphorylation elicited by osteostatin appears to be VEGF‐independent, but prevented by the VEGFR2 activation inhibitor SU1498 and also by the Src kinase inhibitors SU6656 and PP1. Furthermore, osteostatin induced phosphorylation of Src, extracellular signal‐regulated kinase (ERK) and Akt with a similar time course to that observed for VEGFR2 activation in these osteoblastic cells. This osteostatin‐dependent induction of ERK and Akt activation was abrogated by SU6656. Up‐regulation of VEGF and osteoprotegerin gene expression as well as the pro‐survival effect induced by osteostatin treatment were all prevented by both SU1498 and SU6656 in these osteoblastic cells. Collectively, these findings demonstrate that the osteostatin domain of C‐terminal PTHrP phosphorylates VEGFR2 through Src activation, which represents a mechanism for modulating osteoblastic function. J. Cell. Biochem. 114: 1404–1413, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
107.
Isabel Marques Antonio José Díaz‐Pérez José Ángel López‐Rodríguez Victoria Mirones Ana Sus Félix Llamas Alicia Alonso Ernesto Pérez‐Collazos Juan Viruel Elvira Sahuquillo Maria Del Carmen Sancho Benjamin Komac José Antonio Manso José Gabriel Segarra‐Moragues David Draper Luis Villar Pilar Catalán 《Botanical journal of the Linnean Society. Linnean Society of London》2013,173(4):676-706
The Iberian mountain spiny fescues are a reticulate group of five diploid grass taxa consisting of three parental species and two putative hybrids: F. × souliei (F. eskia × F. quadriflora) and F. × picoeuropeana (F. eskia × F. gautieri). Phenotypic and molecular studies were conducted with the aim of determining the taxonomic boundaries and genetic relationships of the five taxa and disentangling the origins of the two hybrids. Statistical analyses of 31 selected phenotypic traits were conducted on individuals from 159 populations and on nine type specimens. Molecular analyses of random amplified polymorphic DNA (RAPD) markers were performed on 29 populations. The phenotypic analyses detected significant differences between the five taxa and demonstrated the overall intermediacy of the F. × picoeuropeana and F. × souliei between their respective parents. The RAPD analysis corroborated the genetic differentiation of F. eskia, F. gautieri and F. quadriflora and the intermediate nature of the two hybrids; however, they also detected genetic variation within F. × picoeuropeana. These results suggest distinct origins for F. × picoeuropeana in the Cantabrian and Pyrenean mountains, with the sporadic Pyrenean populations having potentially resulted from recent hybridizations and the stabilized Cantabrian ones from older events followed by potential displacements of the parents. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 173 , 676–706. 相似文献
108.
M. L. Merroun N. Ben Omar E. Alonso J. M. Arias M. T. GonzÁlez-MuÑoz 《Geomicrobiology journal》2013,30(2):183-192
This paper deals with silver sorption to Myxococcus xanthus biomass. The dry biomass of this microorganism is shown to be a good sorbent for the recovery of silver present at low solution concentrations. Between initial silver concentrations of 2 and 0.05 mM, the percentage of accumulation ranges from 8.12% to 75% of the total silver present in the solution. Transmission electron microscopy study of M. xanthus wet biomass after silver accumulation shows the sorption within the extracellular polysaccharide, on the cell wall, and in the cytoplasm. The presence of silver deposits in the cytoplasm indicates that at least two mechanisms are involved in silver sorption by this bacterium biomass. First, silver was bound to the cell surface and extracellular polysaccharide, and second, a silver intracellular deposition process took place. The higher amount of silver deposits in the extracellular polysaccharide, present abundantly in M. xanthus cells, explains the capacity of this bacterium to bind silver efficiently. The results obtained indicate that the removal of silver by M. xanthus from the diluted solutions could be used in recycling this valuable metal. One interesting observation of this investigation is the crystalline form, possibly as chlorargyrite, in which the silver deposits are found in the M. xanthus cells. 相似文献
109.
Ramanagouda Ramanagoudr-Bhojappa Shubeena Chib Alicia K. Byrd Suja Aarattuthodiyil Manjula Pandey Smita S. Patel Kevin D. Raney 《The Journal of biological chemistry》2013,288(22):16185-16195
Kinetic analysis of the DNA unwinding and translocation activities of helicases is necessary for characterization of the biochemical mechanism(s) for this class of enzymes. Saccharomyces cerevisiae Pif1 helicase was characterized using presteady state kinetics to determine rates of DNA unwinding, displacement of streptavidin from biotinylated DNA, translocation on single-stranded DNA (ssDNA), and ATP hydrolysis activities. Unwinding of substrates containing varying duplex lengths was fit globally to a model for stepwise unwinding and resulted in an unwinding rate of ∼75 bp/s and a kinetic step size of 1 base pair. Pif1 is capable of displacing streptavidin from biotinylated oligonucleotides with a linear increase in the rates as the length of the oligonucleotides increased. The rate of translocation on ssDNA was determined by measuring dissociation from varying lengths of ssDNA and is essentially the same as the rate of unwinding of dsDNA, making Pif1 an active helicase. The ATPase activity of Pif1 on ssDNA was determined using fluorescently labeled phosphate-binding protein to measure the rate of phosphate release. The quantity of phosphate released corresponds to a chemical efficiency of 0.84 ATP/nucleotides translocated. Hence, when all of the kinetic data are considered, Pif1 appears to move along DNA in single nucleotide or base pair steps, powered by hydrolysis of 1 molecule of ATP. 相似文献
110.
Rafael Bielza Galindo Alejandro Ortiz Espada Estefanía Arias Muñana Rocío Velasco Guzmán de Lázaro Asunción Mora Casado Ricardo Moreno Martín Blanca Tapia Salinas Javier Escalera Alonso Jorge Gómez Cerezo 《Revista espa?ola de geriatría y gerontología》2013