Methods of determining subcellular localization of nucleic acids, including RNA and DNA are described. In particular, the invention relates to a method combining proximity-specific labeling with crosslinking of nucleic acids to proteins and sequencing to identify nucleic acids within or near a particular subcellular compartment in vivo.

Optogenetic systems and methods for probing a specimen using spatio-temporally modulated illumination light are disclosed. A method may include generating illumination light, the illumination light including a plurality of illumination protocols temporally sampled and interleaved with one another at a time-division-multiplexed (TDM) sampling rate, each illumination protocol being for illuminating a respective region of interest (ROI) of a plurality of ROIs of the specimen. The illumination light may include either activation or excitation light, or both. The method may also include applying a spatio-temporal modulation to the illumination light and directing the resulting modulated illumination light onto the specimen. The modulation may include repeatedly imparting, at a pattern switching rate matched and synchronized with the TDM sampling rate, a sequence of a plurality of spatial modulation patterns to the plurality of temporally sampled and interleaved illumination protocols, each spatial modulation pattern mapping to a respective one of the ROIs.

In vitro methods and kits for modulating and studying mechanical movement of hepatic bile canaliculi lumen through activation or inhibition of the Rho-kinase molecular regulation pathway. In vitro methods and kits for modulating lumen opening and clearing using matrix metalloproteinases, as well as diagnostic methods based upon the same.

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to improved TfR-binding moieties capable of crossing the blood brain barrier (BBB) and capable of carrying and releasing cargo specifically targeted to the parenchymal tissue of the brain. The present invention relates to a transcytosis selection method to obtain VNARs against mammalian blood brain barrier (BBB) receptors using phage display libraries as well as against receptors found in other directional cell barrier systems like the gastrointestinal tract and other organs. The VNARs may be used alone or as components in compositions or as conjugates that target the particular receptor transport systems for delivery of therapeutics or diagnostics to the brain (in the case of BBB receptors) or other tissues.

Described herein are methods, compositions, kits and synthetic peptide shuttle agents relating to the transduction of proteinaceous and/or non-proteinaceous cargoes. The method generally comprises contacting target eukaryotic cells with a non-proteinaceous cargo and a concentration of a synthetic peptide shuttle agent sufficient to increase the transduction efficiency of the non-proteinaceous cargo, as compared to in the absence of said synthetic peptide shuttle agent. In embodiments, the non-proteinaceous cargo may be a drug, such as a small molecule drug, for treating a disease. In other embodiments, novel synthetic peptide shuttle agents having transduction activity for proteinaceous and/or non-proteinaceous cargoes are described, as well as the use of propidium iodide or other membrane-impermeable fluorescent DNA intercalating agent as a surrogate cargo for selecting versatile synthetic peptide shuttle agents having transduction activity for both proteinaceous and non-proteinaceous cargoes.

The present invention provides a system for the study of tau protein aggregation in neuronal cells in vitro which can be used to screen agents for therapeutic effectiveness against aggregates of tau protein or fragments thereof.

The present invention relates to a method for screening drug candidates for treating a disease using the interaction between calcium and phosphatidylinositol phosphate. Particularly in the present invention, it was confirmed that the concentration of calcium was increased in the obesity induced insulin resistance animal model and the increased calcium concentration inhibited the migration of Akt protein containing PH domain and the signal transduction, while the protein containing C2 domain was able to migrate to the cell membrane by binding to calcium/PIP complex even under the condition of high calcium concentration. Therefore, the investigation of the interaction between calcium and PIP can be a useful method for screening of drug candidates for treating metabolic disease, cancer or hypertension.

Provided herein are methods of identifying an agent that activates a protease-activated receptor 2 (PAR2)intracellularly. Also provided are isolated mutant PAR2 polypeptides, isolated polynucleotides encoding the mutant PAR2 polypeptides, vectors comprising the isolated polynucleotides, and host cells comprising the vectors.

Methods and compositions for accurate identification of Parkinson's disease are disclosed. More particularly, the disclosure is directed to the determination of Parkinson's disease in ante-mortem tissue samples.

The present disclosure relates generally to methods of inhibiting a tripartite VAP-A, ORP3 and Rab7 (VOR) protein complex in multicellular organisms, to methods of identifying agents which inhibit such complex and to the medical use of those agents. Inhibition of the VOR complex causes interference with at least one mechanism of intercellular communication, wherein the intercellular communication is mediated by receptor-ligand interaction and/or EVs, and viral infection involving the transport of endocytosed biomaterials to the nucleus of recipient cells.