In one embodiment, the invention provides a method of treating a subject suffering from a Mycobacterium infection by administering to the subject a therapeutically-effective amount of a degradative autophagy agonist or a secretory autophagy antagonist. In another embodiment, the invention provides a method of treating a subject suffering from one or more diseases selected from the group consisting of a Mycobacterium infection, an inflammatory disorder, an immune disorder, a cancer and a neurodegenerative disorder by administering to the subject a therapeutically-effective amount of a TBK-1 antagonist (e.g. BX795 or amlexanox). Related pharmaceutical compositions, diagnostic and screening assays and kits are also provided.

The present invention relates to the discovery that the T1R receptors assemble to form functional taste receptors. Particularly, it has been discovered that co-expression of T1R1 and T1R3 results in a taste receptor that responds to umami taste stimuli, including monosodium glutamate. Also, it has been discovered that co-expression of the T1R2 and T1R3 receptors results in a taste receptor that responds to sweet taste stimuli including naturally occurring and artificial sweeteners. Also the present invention relates to the use of hetero-oligomeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli.

The present disclosure relates to kits, compositions and methods for detecting fungal species, viruses and/or protein variants in a sample, e.g., a biological sample. For example, but not by way of limitation, the present disclosure provides living yeast biosensors that have been genetically engineered to detect fungal species, viruses and/or protein variants in a sample, e.g., a biological sample.

A human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of human CC chemokine receptor 4 (CCR4) but does not react with a human blood platelet; a human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of CCR4 and has a cytotoxic activity against a CCR4-expressing cell; and a medicament, a therapeutic agent or a diagnostic agent comprising at least one of the antibodies and the antibody fragments thereof as an active ingredient.

The present invention relates to the discovery that the T1R receptors assemble to form functional taste receptors. Particularly, it has been discovered that co-expression of T1R1 and T1R3 results in a taste receptor that responds to umami taste stimuli, including monosodium glutamate. Also, it has been discovered that co-expression of the T1 R2 and T1R3 receptors results in a taste receptor that responds to sweet taste stimuli including naturally occurring and artificial sweeteners.

Also the present invention relates to the use of hetero-oligomeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli.

Further, the invention relates to the constitutive of cell lines that stably or transiently co-express a combination of T1R1 and T1R3; or T1R2 and T1R3; under constitutive or inducible conditions. The use of these cells lines in cell-based assays to identify umami and sweet taste modulatory compounds is also provided, particularly high throughput screening assays that detect receptor activity by use of fluorometric imaging.

Finally, the invention relates to the discovery that some compounds, e.g., lactisole, inhibit both the activities of human T1R2/T1R3 and T1R1/T1R3 receptors, and accordingly the sweet and umami taste, suggesting that these receptors may be the only sweet and umami receptors.

The present invention relates to the discovery that the T1R receptors assemble to form functional taste receptors. Particularly, it has been discovered that co-expression of T1R1 and T1R3 results in a taste receptor that responds to umami taste stimuli, including monosodium glutamate. Also, it has been discovered that co-expression of the T1R2 and T1R3 receptors results in a taste receptor that responds to sweet taste stimuli including naturally occurring and artificial sweeteners. Also the present invention relates to the use of hetero-oligomeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli.

The present disclosure generally relates to the expression of T1R1+3 taste receptors in eukaryotic cells, such as U2OS cells. The disclosure also relates to the expression of a chimeric T1R3 taste receptor subunit to enable the T1R1 taste receptor subunit to achieve a higher level of sensitivity to umami compounds. Also disclosed are methods of expressing T1R1+3 taste receptors in such cells, and methods of screening for substances that modulate T1R1+3 receptor sensing, and which, therefore, may be useful as modulators of umami taste.

Aspects of the disclosure relate to compositions and methods for the diagnosis and/or treatment of C9orf72 negative sporadic amyotrophic lateral sclerosis (C9 sALS). In some embodiments, the disclosure relates to identifying a subject as having C9orf72 negative (C9) sALS by detecting expression or activity of repeat-associated non-ATG (RAN) translation proteins (e.g., RAN proteins). In some embodiments, the methods and compositions of the disclosure identify certain gene or genes which comprise mutation(s) leading to the expression of the detected RAN proteins, and which were previously unknown to be associated with sALS. In some embodiments, said gene(s) can be used to identify or diagnose subjects having, suspected of having, or at risk of developing sALS which is unrelated to expansion mutations within the C9orf72 and/or SCA36 genetic loci (e.g., C9 sALS). In some embodiments, the disclosure relates to methods of treating C9 sALS by administering to a subject in need thereof an agent that reduces expression or activity of RAN proteins.

Disclosed herein is a G protein-coupled receptor (GPCR) assay platform comprised of two complementary systems that equate dynamic intermolecular interactions between a receptor and transducer with more complex stimulus-response cascades in living cells. In the disclosed in vitro ADSoRB method, the forced dissociation of transducers like G protein heterotrimers from receptors alters receptor conformations and ligand interactions to simulate pathway activation in a cell. In the disclosed TRUPATH method, measuring the extent of engineered G protein heterotrimer complex dissociation provides single transducer resolution in a cell.

Methods and applications to label, detect and engineer native or recombinant CB1 and CB2 receptors for cannabinoid chemicals are provided. Also disclosed are uses to detect the dynamics and real time pharmacokinetics of cannabinoid receptors, and purification of cannabinoid receptors in vivo (humans, animals etc.) and in vitro (in the cells).