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Total 63 results found since Jan 2013.
Radiation killing is regulated by LGP2 Medical Sciences
An siRNA screen targeting 89 IFN stimulated genes in 14 different cancer cell lines pointed to the RIG-I (retinoic acid inducible gene I)–like receptor Laboratory of Genetics and Physiology 2 (LGP2) as playing a key role in conferring tumor cell survival following cytotoxic stress induced by ionizing radiation (IR). Studies...
Source: Proceedings of the National Academy of Sciences - January 28, 2014 Category: Science Authors: Widau, R. C., Parekh, A. D., Ranck, M. C., Golden, D. W., Kumar, K. A., Sood, R. F., Pitroda, S. P., Liao, Z., Huang, X., Darga, T. E., Xu, D., Huang, L., Andrade, J., Roizman, B., Weichselbaum, R. R., Khodarev, N. N. Tags: PNAS Plus Source Type: research
Inheritance of Trans Chromosomal Methylation Plant Biology
Hybridization in plants leads to transinteractions between the parental genomes and epigenomes that can result in changes to both 24 nt siRNA and cytosine methylation (mC) levels in the hybrid. In Arabidopsis the principle processes altering the hybrid methylome are Trans Chromosomal Methylation (TCM) and Trans Chromosomal deMethylation (TCdM) in...
Source: Proceedings of the National Academy of Sciences - February 4, 2014 Category: Science Authors: Greaves, I. K., Groszmann, M., Wang, A., Peacock, W. J., Dennis, E. S. Tags: Biological Sciences Source Type: research
Speeding evolution Engineering
As medicines become increasingly complex, their delivery becomes more challenging. To function, medicines must effectively navigate the body and reach their site of action. When the impediments to their delivery become too great, drug delivery vehicles are used. Small interfering RNA (siRNA) is a complex class of medicine. These duplex...
Source: Proceedings of the National Academy of Sciences - March 18, 2014 Category: Science Authors: Putnam, D. Tags: Commentaries Source Type: research
RPL39, MLF2 alter tumor initiation and metastasis Cell Biology
We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and...
Source: Proceedings of the National Academy of Sciences - June 17, 2014 Category: Science Authors: Dave, B., Granados-Principal, S., Zhu, R., Benz, S., Rabizadeh, S., Soon-Shiong, P., Yu, K.-D., Shao, Z., Li, X., Gilcrease, M., Lai, Z., Chen, Y., Huang, T. H.- M., Shen, H., Liu, X., Ferrari, M., Zhan, M., Wong, S. T. C., Kumaraswami, M., Mittal, V., Ch Tags: Biological Sciences Source Type: research
Correlating animal and human data with CALAA-01 Medical Sciences
Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01 is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA interference (RNAi)–based, experimental therapeutic to be administered to cancer patients. Here, we report the results from the initial phase...
Source: Proceedings of the National Academy of Sciences - August 5, 2014 Category: Science Authors: Zuckerman, J. E., Gritli, I., Tolcher, A., Heidel, J. D., Lim, D., Morgan, R., Chmielowski, B., Ribas, A., Davis, M. E., Yen, Y. Tags: Biological Sciences Source Type: research
Satellite siRNA promotes Drosophila X recognition Genetics
Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt...
Source: Proceedings of the National Academy of Sciences - November 18, 2014 Category: Science Authors: Menon, D. U., Coarfa, C., Xiao, W., Gunaratne, P. H., Meller, V. H. Tags: Biological Sciences Source Type: research
Protein kinase IKK{beta} activates IRF5 Biochemistry
The siRNA knockdown of IFN Regulatory Factor 5 (IRF5) in the human plasmacytoid dendritic cell line Gen2.2 prevented IFNβ production induced by compound CL097, a ligand for Toll-like receptor 7 (TLR7). CL097 also stimulated the phosphorylation of IRF5 at Ser462 and stimulated the nuclear translocation of wild-type IRF5, but not...
Source: Proceedings of the National Academy of Sciences - December 9, 2014 Category: Science Authors: Lopez-Pelaez, M., Lamont, D. J., Peggie, M., Shpiro, N., Gray, N. S., Cohen, P. Tags: Biological Sciences Source Type: research
Lack of pairing triggers multigenerational RNAe Genetics
Single-copy transgenes in Caenorhabditis elegans can be subjected to a potent, irreversible silencing process termed small RNA-induced epigenetic silencing (RNAe). RNAe is promoted by the Piwi Argonaute protein PRG-1 and associated Piwi-interacting RNAs (piRNAs), as well as by proteins that promote and respond to secondary small interfering RNA (siRNA) production....
Source: Proceedings of the National Academy of Sciences - May 19, 2015 Category: Science Authors: Leopold, L. E., Heestand, B. N., Seong, S., Shtessel, L., Ahmed, S. Tags: PNAS Plus Source Type: research
Production of functional siRNAs by human Dicer Microbiology
Although RNA interference (RNAi) functions as a potent antiviral innate-immune response in plants and invertebrates, mammalian somatic cells appear incapable of mounting an RNAi response and few, if any, small interfering RNAs (siRNAs) can be detected. To examine why siRNA production is inefficient, we have generated double-knockout human cells lacking...
Source: Proceedings of the National Academy of Sciences - December 15, 2015 Category: Science Authors: Kennedy, E. M., Whisnant, A. W., Kornepati, A. V. R., Marshall, J. B., Bogerd, H. P., Cullen, B. R. Tags: PNAS Plus Source Type: research
NIR nanoparticles for imaging and siRNA delivery Medical Sciences
Anaplastic thyroid cancer (ATC), one of the most aggressive solid tumors, is characterized by rapid tumor growth and severe metastasis to other organs. Owing to the lack of effective treatment options, ATC has a mortality rate of ∼100% and median survival of less than 5 months. RNAi nanotechnology represents a...
Source: Proceedings of the National Academy of Sciences - July 11, 2016 Category: Science Authors: Liu, Y., Gunda, V., Zhu, X., Xu, X., Wu, J., Askhatova, D., Farokhzad, O. C., Parangi, S., Shi, J. Tags: Physical Sciences Source Type: research
Drosophila antiviral response Microbiology
Since its discovery, RNA interference has been identified as involved in many different cellular processes, and as a natural antiviral response in plants, nematodes, and insects. In insects, the small interfering RNA (siRNA) pathway is the major antiviral response. In recent years, the Piwi-interacting RNA (piRNA) pathway also has been...
Source: Proceedings of the National Academy of Sciences - July 18, 2016 Category: Science Authors: Petit, M., Mongelli, V., Frangeul, L., Blanc, H., Jiggins, F., Saleh, M.-C. Tags: PNAS Plus Source Type: research
Selective NP delivery to cancer over normal cells Engineering
Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, we report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. Selective polyplex nanoparticles (NPs) were identified by high-throughput...
Source: Proceedings of the National Academy of Sciences - September 26, 2016 Category: Science Authors: Yan, Y., Liu, L., Xiong, H., Miller, J. B., Zhou, K., Kos, P., Huffman, K. E., Elkassih, S., Norman, J. W., Carstens, R., Kim, J., Minna, J. D., Siegwart, D. J. Tags: PNAS Plus Source Type: research
FoxO6 is essential in cortical development Neuroscience
The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6+/− and FoxO6−/− mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach,...
Source: Proceedings of the National Academy of Sciences - November 7, 2016 Category: Science Authors: Paap, R. H., Oosterbroek, S., Wagemans, C. M. R. J., von Oerthel, L., Schellevis, R. D., Vastenhouw-van der Linden, A. J. A., Groot Koerkamp, M. J. A., Hoekman, M. F. M., Smidt, M. P. Tags: PNAS Plus Source Type: research
FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development Neuroscience
The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6+/− and FoxO6−/− mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach,...
Source: Proceedings of the National Academy of Sciences - November 7, 2016 Category: Science Authors: Ricardo H. Paap, Saskia Oosterbroek, Cindy M. R. J. Wagemans, Lars von Oerthel, Raymond D. Schellevis, Annemarie J. A. Vastenhouw-van der Linden, Marian J. A. Groot Koerkamp, Marco F. M. Hoekman, Marten P. Smidt Tags: PNAS Plus Source Type: research
Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA production Biochemistry
The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ∼22–24-nt miRNAs from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high fidelity is unknown. Here we report...
Source: Proceedings of the National Academy of Sciences - December 5, 2016 Category: Science Authors: Suresh K. Kandasamy, Ryuya Fukunaga Tags: Biological Sciences Source Type: research
