Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling.

Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling

Nanodelivery of a functional membrane receptor to manipulate cellular phenotype.

Modification of membrane receptor makeup is one of the most efficient ways to control input-output signals but is usually achieved by expressing DNA or RNA-encoded proteins or by using other genome-editing methods, which can be technically challenging and produce unwanted side effects. Here we develop and validate a nanodelivery approach to transfer in vitro synthesized, functional membrane receptors into the plasma membrane of living cells. Using β2-adrenergic receptor (β2AR), a prototypical G-protein coupled receptor, as an example, we demonstrated efficient incorporation of a full-length β2AR into a variety of mammalian cells, which imparts pharmacologic control over cellular signaling and affects cellular phenotype in an ex-vivo wound-healing model. Our approach for nanodelivery of functional membrane receptors expands the current toolkit for DNA and RNA-free manipulation of cellular function. We expect this approach to be readily applicable to the synthesis and nanodelivery of other types of GPCRs and membrane receptors, opening new doors for therapeutic development at the intersection between synthetic biology and nanomedicine

Development of 68Ga-labeled Hepatitis E virus nanoparticles for targeted drug delivery and diagnostics with PET

Peer reviewe

A Noninvasive, Orally Stable, Mucosa-Penetrating Polyvalent Vaccine Platform Based on Hepatitis E Virus Nanoparticle

Hepatitis E virus nanoparticle (HEVNP) is an orally stable, mucosa-penetrating delivery platform for noninvasive, targeted delivery of therapeutic and diagnostic agents. HEVNP does not carry HEV genomic RNA and is incapable of replication. The key characteristics that make HEVNP an ideal and unique vehicle for diagnostic and therapeutic delivery include surface plasticity, resistance to the harsh environment of the gastrointestinal (GI) tract, significant payload capacity, platform sustainability, and safety. Furthermore, HEVNP is easily produced using currently available expression/purification technologies; can be easily formulated as a liquid, powder, or solid; and can be distributed (and stored) without the need for a temperature-controlled supply chain

Continuous extremal optimization for Lennard-Jones Clusters

In this paper, we explore a general-purpose heuristic algorithm for finding high-quality solutions to continuous optimization problems. The method, called continuous extremal optimization(CEO), can be considered as an extension of extremal optimization(EO) and is consisted of two components, one is with responsibility for global searching and the other is with responsibility for local searching. With only one adjustable parameter, the CEO's performance proves competitive with more elaborate stochastic optimization procedures. We demonstrate it on a well known continuous optimization problem: the Lennerd-Jones clusters optimization problem.Comment: 5 pages and 3 figure

Responses of sub-ice platelet layer thickening rate and frazil-ice concentration to variations in ice-shelf water supercooling in McMurdo Sound, Antarctica

Persistent outflow of supercooled ice-shelf water (ISW) from beneath McMurdo Ice Shelf creates a rapidly growing sub-ice platelet layer (SIPL) with a unique crystallographic structure under the sea ice in McMurdo Sound, Antarctica. A vertically modified frazil-ice-laden ISW plume model that encapsulates the combined non-linear effects of the vertical distributions of supercooling and frazil concentration on frazil-ice growth is applied to McMurdo Sound and is shown to reproduce the observed ISW supercooling and SIPL distributions. Using this model, the dependence of the SIPL thickening rate and depth-averaged frazil-ice concentration on ISW supercooling in McMurdo Sound is investigated and found to be predominantly controlled by the vertical distribution of frazil concentration. The complex dependence on frazil concentration highlights the need to improve frazil-ice observations within the sea-ice–ocean boundary layer in McMurdo Sound.</p

Synthesis and ex vivo biodistribution of two 68Ga-labeled tetrazine tracers : comparison of pharmacokinetics

Peer reviewe