2,868 research outputs found

    Silencing disease genes in the laboratory and the clinic

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    Synthetic nucleic acids are commonly used laboratory tools for modulating gene expression and have the potential to be widely used in the clinic. Progress towards nucleic acid drugs, however, has been slow and many challenges remain to be overcome before their full impact on patient care can be understood. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression. We first describe these two approaches and contrast their relative strengths and weaknesses for laboratory applications. We then review the choices faced during development of clinical candidates and the current state of clinical trials. Attitudes towards clinical development of nucleic acid silencing strategies have repeatedly swung from optimism to depression during the past 20 years. Our goal is to provide the information needed to design robust studies with oligonucleotides, making use of the strengths of each oligonucleotide technology

    Effect of chemical modifications on modulation of gene expression by duplex antigene RNAs that are complementary to non-coding transcripts at gene promoters

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    Antigene RNAs (agRNAs) are small RNA duplexes that target non-coding transcripts rather than mRNA and specifically suppress or activate gene expression in a sequence-dependent manner. For many applications in vivo, it is likely that agRNAs will require chemical modification. We have synthesized agRNAs that contain different classes of chemical modification and have tested their ability to modulate expression of the human progesterone receptor gene. We find that both silencing and activating agRNAs can retain activity after modification. Both guide and passenger strands can be modified and functional agRNAs can contain 2?F-RNA, 2?OMe-RNA, and locked nucleic acid substitutions, or combinations of multiple modifications. The mechanism of agRNA activity appears to be maintained after chemical modification: both native and modified agRNAs modulate recruitment of RNA polymerase II, have the same effect on promoter-derived antisense transcripts, and must be double-stranded. These data demonstrate that agRNA activity is compatible with a wide range of chemical modifications and may facilitate in vivo applications. <br/

    Applying the heat to research techniques for species conservation

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    The definitive version may be found at www.wiley.comClive R. Mcmahon, Corey J. A. Bradshaw and Graeme C. Hay

    Supplemental Material - A Joint Model for Disability, Self-Rated Health, and Mortality Among Medicare Beneficiaries—Differences by Chronic Disease and Race/Ethnicity

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    Supplemental Material for A Joint Model for Disability, Self-Rated Health, and Mortality Among Medicare Beneficiaries—Differences by Chronic Disease and Race/Ethnicity by Ana R. Quiñones, Gail McAvay, Brent Vander Wyk, Ling Han, Corey Nagel, and Heather G. Allore in Journal of Aging and Health.</p

    Potential role for telavancin in bacteremic infections due to gram-positive pathogens: Focus on staphylococcus aureus

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    Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections and the most frequent invasive infection due to methicillin-resistant S. aureus (MRSA). Treatment is challenging, particularly for MRSA, because of limited treatment options. Telavancin is a bactericidal lipoglycopeptide antibiotic that is active against a range of clinically relevant gram-positive pathogens including MRSA. In experimental animal models of sepsis telavancin was shown to be more effective than vancomycin. In clinically evaluable patients enrolled in a pilot study of uncomplicated SAB, cure rates were 88% for telavancin and 89% for standard therapy. Among patients with infection due to only gram-positive pathogens enrolled in the 2 phase 3 studies of telavancin for treatment of hospital-acquired pneumonia, cure rates for those with bacteremic S. aureus pneumonia were 41% (9/22, telavancin) and 40% (10/25, vancomycin) with identical mortality rates. These data support further evaluation of telavancin in larger, prospective studies of SAB

    CO 675 Group Counseling

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    Corey, G. (2000). Theory and Practice of Group Counseling (5th.edition). Pacific Grove, CA: Brooks/Cole Publishing Co. The text includes a rather thorough bibliography. Corey, G., Corey, M., & Haynes, R. (2000). Evolution of a Group (workbook and videotape), Pacific Grove, CA: Brooks/Cole.https://place.asburyseminary.edu/syllabi/3085/thumbnail.jp

    CO 675 Group Counseling Theories and Techniques

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    • Corey, G. (2000). Theory and Practice of Group Counseling (5th.edition). Pacific Grove, CA: Brooks/Cole Publishing Co. The text includes a rather thorough bibliography. • Corey, G., Corey, M., & Haynes, R. (2000). Evolution of a Group (workbook and videotape), Pacific Grove, CA: Brooks/Cole.https://place.asburyseminary.edu/syllabi/2664/thumbnail.jp

    CCDC 1910427: Experimental Crystal Structure Determination

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    Related Article: Otega A. Ejegbavwo, Corey R. Martin, Oyindamola A. Olorunfemi, Gabrielle A. Leith, Richard T. Ly, Allison M. Rice, Ekaterina A. Dolgopolova, Mark D. Smith, Stavros G. Karakalos, Nancy Birkner, Brian A. Powell, Shubham Pandey, Robert J. Koch, Scott T. Misture, Hans-Conrad zur Loye, Simon R. Phillpot, Kyle S. Brinkman, Natalia B. Shustova|2019|J.Am.Chem.Soc.|141|11628|doi:10.1021/jacs.9b0473

    CCDC 1910423: Experimental Crystal Structure Determination

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    Related Article: Otega A. Ejegbavwo, Corey R. Martin, Oyindamola A. Olorunfemi, Gabrielle A. Leith, Richard T. Ly, Allison M. Rice, Ekaterina A. Dolgopolova, Mark D. Smith, Stavros G. Karakalos, Nancy Birkner, Brian A. Powell, Shubham Pandey, Robert J. Koch, Scott T. Misture, Hans-Conrad zur Loye, Simon R. Phillpot, Kyle S. Brinkman, Natalia B. Shustova|2019|J.Am.Chem.Soc.|141|11628|doi:10.1021/jacs.9b0473

    CO 675 Group Counseling

    No full text
    Corey, G. (2008). Theory and Practice of Group Counseling (7th edition). Pacific Grove, CA: Brooks/Cole Publishing Co. The text includes a rather thorough bibliography. ISBN: 9780534641740 Corey, G., Corey, M., & Haynes, R. (2000). Evolution of a Group (workbook and videotape), Pacific Grove, CA: Brooks/Cole. ISBN: 0534363245https://place.asburyseminary.edu/syllabi/1253/thumbnail.jp
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