Posts Tagged ‘demonstrate’

Amazon river dolphins (Inia geoffrensis) modify biosonar output level and directivity during prey interception in the wild [RESEARCH ARTICLE]

Michael Ladegaard, Frants Havmand Jensen, Kristian Beedholm, Vera Maria Ferreira da Silva, and Peter Teglberg MadsenToothed whales have evolved to live in extremely different habitats and yet they all rely strongly on echolocation for finding and catc…

Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination

Zika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins2,3. Here, we demonstrate that a single low-dose intradermal immunization with lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope (prM-E) glycoproteins of a 2013 ZIKV outbreak strain elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNPs protected mice from ZIKV challenges at 2 weeks or 5 months post-vaccination, and a single dose of 50 μg was sufficient to protect non-human primates from a challenge at 5 weeks post-vaccination. These data demonstrate that nucleoside-modified mRNA-LNPs elicit rapid and durable protective immunity and thus represent a new and promising vaccine candidate for the global fight against ZIKV.

Language and cranial features linked, developed at same time?

From ScienceDaily: The formation of different languages and language groupings appears to have happened in the same broad period and geographical locations as the development of facial features in various human populations, according to linguistics professor, Gerhard Jäger, and paleoanthropologists, Professor Katerina Harvati and Dr. Hugo Reyes-Centeno. In their study, the researchers examined 265 skulls […]

Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography

Riboswitches are RNA structural elements generally located in the 3′untranslated region (3′UTR) of mRNA. In the genetic regulation, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform1,2,3. A complete understanding of the structural basis for this mechanism requires the ability to study structural changes over time4. Here we apply femtosecond X-ray free electron laser (XFEL) pulses5,6 to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction prior to diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction involving two apo, one ligand-bound intermediate, and the final bound states. These structures support a reaction mechanism model with at least four states and illustrate the structural basis for signal transmission. The two apo conformers differ significantly in the three-way junction and the P1 switch helix relative to the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With a >10-minute delay, the RNA molecules were fully converted to the bound state, in which the substantial conformational changes resulted in conversion of the space group. Such drastic changes in crystallo highlight the important opportunities that micro/nanocrystals may offer in these and similar time-resolved diffraction studies. These results all together demonstrate the potential of ‘mix-and-inject’ time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those involving large conformational changes.

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