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Institution

Kettering University

EducationFlint, Michigan, United States
About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.
Topics: RNA, Antigen, DNA, Cancer, Population


Papers
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Journal ArticleDOI
TL;DR: It is established that En1/2 are fundamental components of the genetic pathways that pattern the two intersecting coordinate systems of the Cb, morphological divisions and the molecular code.
Abstract: Underlying the seemingly uniform cellular composition of the adult mammalian cerebellum (Cb) are striking parasagittal stripes of gene expression along the medial-lateral (ML) axis that are organized with respect to the lobules that divide the Cb along the anterior-posterior (AP) axis. Although there is a clear correlation between the organization of gene expression stripes and Cb activity patterns, little is known about the genetic pathways that determine the intrinsic stripe molecular code. Here we establish that ML molecular code patterning is highly dependent on two homeobox transcription factors, Engrailed1 (En1) and En2, both of which are also required for patterning the lobules. Gene expression analysis of an allelic series of En1/2 mutant mice that have an intact Purkinje cell layer revealed severe patterning defects using three known components of the ML molecular code and a new marker of Hsp25 negative stripes (Neurofilament heavy chain, Nfh). Importantly, the complementary expression of ZebrinII/PhospholipaseC beta4 and Hsp25/Nfh changes in unison in each mutant. Furthermore, each En gene has unique as well as overlapping functions in patterning the ML molecular code and each En protein has dominant functions in different AP domains (subsets of lobules). Remarkably, in En1/2 mutants with almost normal foliation, ML molecular code patterning is severely disrupted. Thus, independent mechanisms that use En1/2 must pattern foliation and spatial gene expression separately. Our studies reveal that En1/2 are fundamental components of the genetic pathways that pattern the two intersecting coordinate systems of the Cb, morphological divisions and the molecular code.

86 citations

Journal ArticleDOI
TL;DR: These findings imply an intimate evolutionary relationship between the poxvirus and bacterial type IB enzymes, and they engender a scheme for the evolution of topoisomerase IB and tyrosine recombinases from a common ancestral strand transferase in the bacterial domain.
Abstract: We report that diverse species of bacteria encode a type IB DNA topoisomerase that resembles vaccinia virus topoisomerase. Deinococcus radiodurans topoisomerase IB (DraTopIB), an exemplary member of this family, relaxes supercoiled DNA in the absence of a divalent cation or ATP. DraTopIB has a compact size (346 aa) and is a monomer in solution. Mutational analysis shows that the active site of DraTopIB is composed of the same constellation of catalytic side chains as the vaccinia enzyme. Sequence comparisons and limited proteolysis suggest that their folds are conserved. These findings imply an intimate evolutionary relationship between the poxvirus and bacterial type IB enzymes, and they engender a scheme for the evolution of topoisomerase IB and tyrosine recombinases from a common ancestral strand transferase in the bacterial domain. Remarkably, bacteria that possess topoisomerase IB appear to lack DNA topoisomerase III.

85 citations

Journal ArticleDOI
TL;DR: Subunit heterodimerization is necessary, but not sufficient, for full methyltransferase activity, and a mutation of vicinal positions His-682-Tyr-683 that specifically affects catalytic activity but not subunit interaction implicates these residues as constituents of the active site.

85 citations

Journal ArticleDOI
TL;DR: The Kit receptor functions in hematopoiesis, lymphocyte development, gastrointestinal tract motility, melanogenesis, and gametogenesis and Kit-mediated PI 3-kinase signaling and Src kinase family signaling is highly specific for different cellular contexts in vivo.
Abstract: The Kit receptor functions in hematopoiesis, lymphocyte development, gastrointestinal tract motility, melanogenesis, and gametogenesis. To investigate the roles of different Kit signaling pathways in vivo, we have generated knock-in mice in which docking sites for PI 3-kinase (KitY719) or Src kinase (KitY567) have been mutated. Whereas steady-state hematopoiesis is normal in KitY719F/Y719F and KitY567F/Y567F mice, lymphopoiesis is affected differentially. The KitY567F mutation, but not the KitY719F mutation, blocks pro T cell and pro B cell development in an age-dependent manner. Thus, the Src family kinase, but not the PI 3-kinase docking site in Kit, mediates a critical signal for lymphocyte development. In agreement with these results, treatment of normal mice with the Kit tyrosine kinase inhibitor imatinib (Gleevec®) leads to deficits in pro T and pro B cell development, similar to those seen in KitY567F/Y567F and KitW/W mice. The two mutations do not affect embryonic gametogenesis but the KitY719F mutation blocks spermatogenesis at the spermatogonial stages and in contrast the KitY567F mutation does not affect this process. Therefore, Kit-mediated PI 3-kinase signaling and Src kinase family signaling is highly specific for different cellular contexts in vivo.

85 citations

Journal ArticleDOI
TL;DR: It is speculated that noncyclic photosynthetic electron flow is an environmental sensor which causes stomata to remain open in light.
Abstract: A new procedure is reported for high-yield isolation of guard cell protoplasts from Vicia faba L. Delayed light emission and P700 content plus absorption and fluorescence emission spectra of these protoplast extracts are reported. It is concluded that both photosystems are present. The presence of photosystem II and the absence of the reductive-step enzyme of the Calvin-Benson Cycle (Outlaw WH Jr, J Manchester, CH DiCamelli, DD Randall, B Rapp, GM Veith 1979 Proc Natl Acad Sci USA 76: 6371-6375) in a cell has no precedent in the literature. It is speculated that noncyclic photosynthetic electron flow is an environmental sensor which causes stomata to remain open in light.

85 citations


Authors

Showing all 6853 results

NameH-indexPapersCitations
Joan Massagué189408149951
Chris Sander178713233287
Timothy A. Springer167669122421
Murray F. Brennan16192597087
Charles M. Rice15456183812
Lloyd J. Old152775101377
Howard I. Scher151944101737
Paul Tempst14830989225
Pier Paolo Pandolfi14652988334
Barton F. Haynes14491179014
Jedd D. Wolchok140713123336
James P. Allison13748383336
Harold E. Varmus13749676320
Scott W. Lowe13439689376
David S. Klimstra13356461682
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20238
202216
2021211
2020234
2019204
2018225