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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 shown that, although Drosophila melanogaster miRNA* species are less abundant than their partners, they are often present at physiologically relevant levels and can associate with Argonaute proteins, suggesting an important mechanism that diversifies miRNA function during evolution.
Abstract: During microRNA (miRNA) biogenesis, one strand of a ∼21–22-nucleotide RNA duplex is preferentially selected for entry into a silencing complex. The other strand, known as the miRNA* species, has typically been assumed to be a carrier strand. Here we show that, although Drosophila melanogaster miRNA* species are less abundant than their partners, they are often present at physiologically relevant levels and can associate with Argonaute proteins. Comparative genomic analyses revealed that >40% of miRNA* sequences resist nucleotide divergence across Drosophilid evolution, and at least half of these well-conserved miRNA* species select for conserved 3′ untranslated region seed matches well above background noise. Finally, we validated the inhibitory activity of miRNA* species in both cultured cells and transgenic animals. These data broaden the reach of the miRNA regulatory network and suggest an important mechanism that diversifies miRNA function during evolution.

538 citations

Journal ArticleDOI
TL;DR: GVHD is associated with significant shifts in the composition of the intestinal microbiota in human and mouse models; manipulating the microbiota can alter the severity of GVHD in mice.
Abstract: Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.

532 citations

Journal ArticleDOI
TL;DR: It is shown that NCS cells plated at clonal density give rise to multiple neural crest lineages and the availability of unlimited numbers of human N CS cells offers new opportunities for studies of neural crest development and for efforts to model and treat neural crest–related disorders.
Abstract: Vertebrate neural crest development depends on pluripotent, migratory precursor cells. Although avian and murine neural crest stem (NCS) cells have been identified, the isolation of human NCS cells has remained elusive. Here we report the derivation of NCS cells from human embryonic stem cells at the neural rosette stage. We show that NCS cells plated at clonal density give rise to multiple neural crest lineages. The human NCS cells can be propagated in vitro and directed toward peripheral nervous system lineages (peripheral neurons, Schwann cells) and mesenchymal lineages (smooth muscle, adipogenic, osteogenic and chondrogenic cells). Transplantation of human NCS cells into the developing chick embryo and adult mouse hosts demonstrates survival, migration and differentiation compatible with neural crest identity. The availability of unlimited numbers of human NCS cells offers new opportunities for studies of neural crest development and for efforts to model and treat neural crest-related disorders.

530 citations

Journal ArticleDOI
TL;DR: This Review focuses on the comparison of the different strategies to assemble the bicyclo[3.2.1]octane core, to introduce the bridgehead quaternary C20 to form the pyrrolidine moiety, to construct the oxindole residue, and to close the tetrahydropyran ring en route to gelsemine.
Abstract: Gelsemine and 21-oxogelsemine have been synthesized through several routes. This Review focuses on the comparison of the different strategies to assemble the bicyclo[3.2.1]octane core, to introduce the bridgehead quaternary C20 to form the pyrrolidine moiety, to construct the oxindole residue, and to close the tetrahydropyran ring en route to gelsemine.

529 citations

Journal ArticleDOI
TL;DR: This method discriminates the specimen-related scattered background from signal fluorescence, thereby removing out-of-focus light and optimizing the contrast of in-focus structures, and provides rapid control of the illumination pattern, exceptional imaging quality and high imaging speeds.
Abstract: The combination of digital scanned laser light sheet microscopy and incoherent structured illumination allows intrinsic removal of scattered background fluorescence from the desired fluorescent signal. This provides substantial advantages for imaging nontransparent organisms and allowed reconstruction of a fly digital embryo from a developing Drosophila embryo.

529 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