Proc natl acad sci u s a

Abstract : A yugioh dragons component of scientific communication is sufficient information for other researchers in the field to reproduce published findings. For computational and data-enabled research, this has often been interpreted to mean making available the raw data from which results were generated, the computer code that generated the findings, and any additional information needed such as workflows and input parameters. Many journals are revising author guidelines to include data and code availability.

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Proc natl acad sci u s a

A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. The method results in quantitative transfer of ribosomal proteins from gels containing urea. For sodium dodecyl sulfate gels, the original band pattern was obtained with no loss of resolution, but the transfer was not quantitative. The method allows detection of proteins by autoradiography and is simpler than conventional procedures. The immobilized proteins were detectable by immunological procedures. All additional binding capacity on the nitrocellulose was blocked with excess protein; then a specific antibody was bound and, finally, a second antibody directed against the first antibody. The second antibody was either radioactively labeled or conjugated to fluorescein or to peroxidase. The specific protein was then detected by either autoradiography, under UV light, or by the peroxidase reaction product, respectively. In the latter case, as little as pg of protein was clearly detectable. It is anticipated that the procedure will be applicable to analysis of a wide variety of proteins with specific reactions or ligands. Abstract A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. Substances Antigens Ribosomal Proteins Cellulose.

Proceedings of the National Academy of Sciences.

National Academy of Sciences. Proceedings of the National Academy of Sciences Proc. Scopus source ID. Biodiversity Heritage Library. BHL bibliography ID. English Wikipedia.

Lipid nanoparticles LNPs are a clinically mature technology for the delivery of genetic medicines but have limited therapeutic applications due to liver accumulation. Recently, our laboratory developed selective organ targeting SORT nanoparticles that expand the therapeutic applications of genetic medicines by enabling delivery of messenger RNA mRNA and gene editing systems to non-liver tissues. To understand how SORT nanoparticles surpass the delivery barrier of liver hepatocyte accumulation, we studied the mechanistic factors which define their organ-targeting properties. Additionally, we provide evidence for an endogenous targeting mechanism whereby organ targeting occurs via 1 desorption of poly ethylene glycol lipids from the LNP surface, 2 binding of distinct proteins to the nanoparticle surface because of recognition of exposed SORT molecules, and 3 subsequent interactions between surface-bound proteins and cognate receptors highly expressed in specific tissues. These findings establish a crucial link between the molecular composition of SORT nanoparticles and their unique and precise organ-targeting properties and suggest that the recruitment of specific proteins to a nanoparticle's surface can enable drug delivery beyond the liver. Keywords: endogenous targeting; gene editing; lipid nanoparticles; mRNA delivery. Abstract Lipid nanoparticles LNPs are a clinically mature technology for the delivery of genetic medicines but have limited therapeutic applications due to liver accumulation. Publication types Research Support, N.

Proc natl acad sci u s a

Glucagon-like peptide-1 receptor GLP-1R agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. The molecule is highly potent and selective against other class B G protein-coupled receptors GPCRs with a pharmacokinetic profile favorable for oral administration. A high-resolution structure of LY in complex with active-state GLP-1R revealed a unique binding pocket in the upper helical bundle where the compound is bound by the extracellular domain ECD , extracellular loop 2, and transmembrane helices 1, 2, 3, and 7. This mechanism creates a distinct receptor conformation that may explain the partial agonism and biased signaling of the compound. Further, interaction between LY and the primate-specific Trp33 of the ECD informs species selective activity for the molecule. In efficacy studies, oral administration of LY resulted in glucose lowering in humanized GLP-1R transgenic mice and insulinotropic and hypophagic effects in nonhuman primates, demonstrating an effect size in both models comparable to injectable exenatide. Together, this work determined the molecular basis for the activity of an oral agent being developed for the treatment of type 2 diabetes mellitus, offering insights into the activation of class B GPCRs by nonpeptide ligands. Keywords: LY; OWL; cryoelectron microscopy; glucagon-like peptide-1 receptor; type 2 diabetes mellitus.

Molarity of h2so4

Russian Wikipedia. In other projects. The controversial Younger Dryas impact hypothesis , which evolved directly from pseudoscience and now forms the basis for the pseudoarchaeology of Graham Hancock 's Ancient Apocalypse , was first published in PNAS using a nonstandard review system, according to a comprehensive refutation by Holliday et al Tools What links here. XCV, no. This page was last edited on 22 March , at BFI journal list. Namespaces Item Discussion. The Atlanta Journal-Constitution. Milwaukee Journal Sentinel.

Natural genes and proteins often contain tandemly repeated sequence motifs that dramatically increase physiological specificity and activity. Given the selective value of such repeats, it is likely that several different mechanisms have been responsible for their generation.

Retrieved September 28, August 29, ERA journal list. National Academy of Sciences U. August 16, Category : Publications. Haworth Press. PMID: O2k and HRR. BEC editorial.