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Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with nearly 100% of patients ultimately succumbing to the disease. Median patient survival is 15 months, and no standard of care currently exists for recurrent cases. Glioma stem cells (GSCs), a rare and highly aggressive subpopulation of cells within these tumors, have recently emerged as drivers of tumor initiation and recurrence, and a growing body of evidence suggests that they must be completely eradicated todoi:10.1021/acs.molpharmaceut.8b00707 pmid:30260647 pmcid:PMC6469355 fatcat:w2nu5uog2zh6zk7wvzrew4dkf4
more »... event relapse. Toward this goal, we have developed polyethylenimine-wrapped spherical nucleic acid nanoparticles (PEI-SNAs) targeting Gli1, a transcription factor within the Hedgehog signaling pathway that is crucial for the maintenance of GSCs. Here, we demonstrate that Gli1 PEI-SNAs bind scavenger receptors on GBM cells to undergo endocytosis in a caveolae/lipid raft/dynamin-dependent manner. They further achieve ∼30% silencing of tumor-promoting Hedgehog pathway genes and downstream target genes that promote the aggressive, chemoresistant phenotype of GBM. This produces a 30% decrease in proliferation that correlates with a robust onset of GBM cell senescence as well as an ∼60% decrease in metabolic activity with or without cotreatment with temozolomide (TMZ), the frontline chemotherapy for GBM. Most importantly, Gli1 PEI-SNAs impair the self-renewal capacity of GBM cells as indicated by a 30-40% reduction in the expression of stemness genes and further impair the formation of stem-like neurospheres. They also substantially improve neurosphere chemosensitivity as demonstrated by a 2-fold increase in the fraction of cells undergoing apoptosis in response to low doses of TMZ. These results underscore the potential for siRNA therapeutics targeting Gli1 to reduce GBM resistance to therapy and warrant further development of PEI-SNAs and Gli1-targeted therapies to alleviate drug resistance and recurrence for GBM patients.
Computational assignment of function to proteins with no known homologs is still an unsolved problem. We have created a novel, function-based approach to protein annotation and discovery called D-SPACE (Deep Semantic Protein Annotation Classification and Exploration), comprised of a multi-task, multi-label deep neural network trained on over 70 million proteins. Distinct from homology and motif-based methods, D-SPACE encodes proteins in high-dimensional representations (embeddings), allowingdoi:10.1101/365965 fatcat:kf4ivxlrurh4lmpx3pcugpn764
more »... accurate assignment of over 180,000 labels for 13 distinct tasks. The embedding representation enables fast searches for functionally related proteins, including homologs undetectable by traditional approaches. D-SPACE annotates all 109 million proteins in UniProt in under 35 hours on a single computer and searches the entirety of these in seconds. D-SPACE further quantifies the relative functional effect of mutations, facilitating rapid in silico mutagenesis for protein engineering applications. D-SPACE incorporates protein annotation, search, and other exploratory efforts into a single cohesive model.
AbstractThe domestic pig (Sus scrofa) is important both as a food source and as a biomedical model with high anatomical and immunological similarity to humans. The draft reference genome (Sscrofa10.2) represents a purebred female pig from a commercial pork production breed (Duroc), and was established using older clone-based sequencing methods. The Sscrofa10.2 assembly was incomplete and unresolved redundancies, short range order and orientation errors and associated misassembled genes limiteddoi:10.1101/668921 fatcat:k4bclu6iovdodndojtnhdgqnhu
more »... ts utility. We present two genome assemblies created with more recent long read technologies and a whole genome shotgun strategy, one for the same Duroc female (Sscrofa11.1) and one for an outbred, composite breed male animal commonly used for commercial pork production (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy compared to the earlier reference, and the availability of two independent assemblies provided an opportunity to identify large-scale variants and to error-check the accuracy of representation of the genome. We propose that the improved Duroc breed assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.
Background The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model given its similarity in size, anatomy, physiology, metabolism, pathology, and pharmacology to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete, and unresolved redundancies, short-range order and orientation errors, and associated misassembled genes limited its utility. Results We present 2doi:10.1093/gigascience/giaa051 pmid:32543654 pmcid:PMC7448572 fatcat:75gn5f2hfzeqnclwumqnonttsm
more »... ted highly contiguous chromosome-level genome assemblies created with more recent long-read technologies and a whole-genome shotgun strategy, 1 for the same Duroc female (Sscrofa11.1) and 1 for an outbred, composite-breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. Conclusions These highly contiguous assemblies plus annotation of a further 11 short-read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.
The Journal of Aesthetics and Art Criticism
Hale, J. Douglas, Dept. of Art, Arizona State U., Tempe, Ariz. Hall, Mrs. Ariel, The Pony Barn, Woodfin Lane off State St., Marblehead, Mass. Hallman, Ralph J., 357 N. ... Michael J., 16350 S. W. Phantom Bluff Rd., Oswego, Ore Friedrich, Carl J., Harvard U., Cambridge 38, Mass. Frye, Robert, 811 N. Grant Ave., Indianapolis 1, Ind. Fulton, J. ...
Peace Research Abstracts Journal
Christopher, 240986 Collins, Clay, 241002 Collins, Rebecca L., 241141 Colonomos, Ariel, 240990, 241193 Connolly, Ellis, 240853 Connolly, Laura S., 240844 Constantine, Madonna G., 241102 Cooper, Andrew ... Lauren E., 241071 Hall, Susan R., 241062 Hamblen, Jessica L., 241160 Hammer, Nikolaus, 241014 Haimmerli, August, 240977 Hammersley, Rachel, 240955 Hammond, Kenneth R., 240917 Hanley, Andrew Mike, 240840 Hannum ...
Julia, 4577 Hannum, Thomas E., 6126 Hansen, Duncan N., 6462 Hanson, Bruce R., 6037 Hansson, Robert O., 5494 Harding, Britta, 5594 Hare, A. ... A., 4755, 4972 Goodglass, Harold, 5730 Goodman, Allan C., 4843, 4857 Goodrick, Charles L., 4875 Goodson, Felix E., 4575 Goodwin, Frederick K., 5999 Goodwin, Marilyn S., 5352 Gordin, Ariel et al, 5023 Gordon ...
., 24546 Rose, Jonathan, 24649 Rose, Julia Hannum, 24696 Rose, Suzanna, 2 Rosen, Craig S Rosen, Irwin C., Rosen, Marc A., 22 Rosenberg, R. ... ., 23122, 24573 Rosenheck, Robert, 24391 Rosenthal, Robert, 22257 Rosenzweig, Pierre, 22783 Roésler, Ariel, 24394 R6Bner, Patricia, 23591 Rosnow, Ralph L., 22257 Rosofsky, Wendie, 24532 Ross, Brian H., ...
The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model given its similarity in size, anatomy, physiology, metabolism, pathology, and pharmacology to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete, and unresolved redundancies, short-range order and orientation errors, and associated misassembled genes limited its utility. Results: We present 2 annotateddoi:10.17863/cam.65263 fatcat:e7peygud7ncfvhisr57cifkh54
more »... contiguous chromosome-level genome assemblies created with more recent long-read technologies and a whole-genome shotgun strategy, 1 for the same Duroc female (Sscrofa11.1) and 1 for an outbred, composite-breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. Conclusions: These highly contiguous assemblies plus annotation of a further 11 short-read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.
David’s Lane Schenectady, New York MENGARINI, ARIEL ALDACE ANTEO 225 W. 86 Street New York 24, New York MILLER, JASON 147 East 50th Street New York 22, New York MonkE, J. ... Prichard Place Fort Knox, Kentucky GOLDNER, RICHARD DAN 41001 Seven Mile Road Northville, Michigan GOLDSTEIN, NORMAN PHILIP 10117 Gates Avenue Silver Spring, Maryland GorRDON, KENNETH HICKOK, JR. 23 Hannum ...doi:10.1097/00005053-195501000-00014 fatcat:orkhfezffbbcficvdv7nf3vhcq
Hannum ; Secretary and Treasurer, H. H. Syl- vester; Trustees, N. D. Freeman, Joshua Snow, J. H. Dyer; Re- gatta Committee, E. N. Young, Alexander McKenzie, Thomas Lowe, Joseph A. West, James A. ... J. Y. C.; Secretary, Henry Woods, N. Y.C.; J. H. Kreymeyer, P. Y. C.; Andrew Brush, E. Y.C.; J. A. Weaver, C. Y. C.; A. J. Prime, Y. Y. C. re THE CANOE REGATTAS. ...
Marcial Pons, Madrid, 2014, pp. 143-147. 19 Cita de stuart miLL, J., recogida por hannum, H., «Rethinking Self-Determination», Virginia Journal of International Law, 34, no. 1 (1993), p. 3. ... J., El Derecho Internacional en la encrucijada. ...doi:10.15581/010.32.259-295 fatcat:eppdztpcfzfgnbntvpesbfbc2i
Am J Clin Nutr. 2011; 93:1142-51. doi: 10.3945/ajcn.110.005926 68. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN. ... Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, Deconde R, Chen M, Rajapakse I, et al. ...doi:10.18632/aging.101168 pmid:28198702 pmcid:PMC5361673 fatcat:qcsv2ykkw5dmjp643lphknqloy
J. ... , Hilary, 13104, 28704 Rose, Jacqueline, 33920 Rose, James, 32976 Rose, Jennifer S., 16082, 16086, 18622 Rose, John Creighton, 15418 Rose, John, 14536, 30596 Rose, Jonathan, 24649 Rose, Julia Hannum, 15259 ...
N., 117 27977 Rose, John, 18838, 35168 Rosenberg, Samuel J Maat Rose, Julia Hannum, 25244 Rosenberg, Stanley D., 11149 Rose, Kevin, 8529 24246 Rose, Linda E., 31836 Rosenberg, Steven A., 9019 Rose, Linda ... ., Rolls, J. ...
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