Provided herein are isolated polynucleotide encoding modified click beetle luciferase polypeptides that have enhanced luminescence and longer wavelength near-infrared signals. The disclosure also relates to near-infrared bioluminescence systems that include said modified click beetle luciferase polypeptides and novel luciferin derivatives, as well as methods of using said modified click beetle luciferase polypeptides and bioluminescence systems.

The disclosure relates to methods of preventing or treating age-related diseases or conditions in a subject. The method comprises targeting the kynurenine pathway.

A method for assessing an effect of hypoxia on a tissue includes providing a sample of the tissue in a hermetically sealed container, determining a first amount of a reaction substrate(e.g., protocatechuic acid) to be introduced into the sealed container and determining a second amount of a reaction enzyme (e.g., protocatechuate dioxygenase) to be introduced into the sealed container. The method further includes introducing the reaction substrate and the reaction enzyme into the sealed container. At least one of the first amount of the reaction substrate and the second amount of the reaction enzyme is selected to induce at least one of a predetermined amount of hypoxia less than anoxia and a predetermined rate of hypoxia in the tissue during a reaction between the reaction substrate and the reaction enzyme. Values of properties of the tissue can be measured before and after the reaction to assess effects of hypoxia.

An apparatus includes a housing and an actuator. The housing, which defines a reagent volume that can receive a reagent container, can be removably coupled to a reaction chamber. A delivery portion of the housing defines a delivery path between the reagent volume and the reaction chamber when the housing is coupled to the reaction chamber. The delivery path includes a protrusion such that the delivery path has a discontinuous inner surface. The actuator can be moved to convey a reagent from the reagent container into the reaction chamber via the delivery path.

The present invention relates to methods for predicting the survival time of patients suffering from a micro satellite unstable cancer. In particular, the present invention relates to a method for predicting the survival time of a patient suffering from a micro satellite unstable cancer comprising i) determining the expression level of at least one gene encoding for an immune checkpoint protein in a tumor tissue sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) concluding that the patient will have a long survival time when the level determined at step i) is lower than the predetermined reference value or concluding that the patient will have a short survival time when the level determined at step i) is higher than the predetermined reference value.

Provided herein is a large immuno-sorbent surface area assay (ALISSA) for the rapid and sensitive detection of botulinum neurotoxins (BoNTs) and anthrax toxin. This assay is designed to capture a low number of toxin molecules and to measure their intrinsic protease activity via conversion of a fluorogenic or luminescent substrate. Also provided herein are novel peptides that can be specifically cleaved by BoNT and novel peptides that are resistant to cleavage by BoNT. The combination of these cleavable and control peptides can be used for implementation of an exemplary ALISSA used to specifically detect BoNT enzymatic activity. Furthermore, the ALISSA as described herein may also be used in a column based format for use in a high-throughput system for testing large quantities of samples.

The disclosure relates to a recombinant membrane span protein complex, comprising (1) a fusion protein, comprising a membrane span protein fused to a kinase domain, preferably a constitutive kinase and (2) a reporter construct comprising a polypeptide, interacting with the membrane span protein, fused to a reporter phosphorylation domain. The disclosure relates further to the uses of such membrane span protein complex for the detection of compounds that interact with the membrane span protein and for the screening and/or detection of inhibitors of the compound-membrane span protein interactions. In a preferred embodiment, the membrane span protein is a G protein coupled receptor (GPCR) and the method is used for the screening and/or detection of inhibitors of the ligand-receptor binding.

Described are substituted imidazo[1,2-a]pyrazine compounds, which are coelenterazine analogues, kits comprising the analogues, and methods of using the compounds for the detection of luminescence in luciferase-based assays. Also described are methods from making the compounds, such as a method using aminopyrazine acetophosphonates as synthesis intermediates.

The disclosure relates to compounds that are, e.g., PAP Associated Domain Containing 5 (PAPD5) inhibitors and methods of use thereof.

Disclosed are methods and compositions which may be used in human cytochrome P450 (CYP450) enzyme phenotyping. The methods and compositions typically utilize a mélange of substrates for different CYP450 enzymes which may be administered orally to a patient. Subsequently, the metabolites of the substrates may be detected in the patient's saliva as well as any non-metabolized substrates to calculate a metabolic ratio for any given CYP450 enzyme in order to generate a phenytopic CYP450 enzyme profile for the patient.