The disclosure provides compositions and methods for the detection of renal disease and periodontal disease in mammals.

The present application discloses a method for treating a protein deficiency in the central nervous system of a subject in need thereof, comprising systemically administering to the subject a therapeutically effective dose of a fusion polypeptide comprising the first protein, wherein the fusion polypeptide comprises: (a) the first protein; (b) a second protein that provides extended circulation-lifetime in vivo and (c) blood brain barrier crossing facilitating peptide; wherein the fusion polypeptide crosses the blood brain barrier (BBB).

Disclosed herein are inventive polypeptides (e.g., comprising a thermal sensitive ion channel or variant thereof and a domain 5 of kininogen 1 or variant or fragment thereof) and nucleic acid molecules encoding inventive polypeptides. Also disclosed are methods for modulating a cell comprising administering certain compositions (e.g., pharmaceutical compositions of the nucleic acid molecule) and applying a static magnetic field or an electromagnetic field. Methods for treating diseases or disorders in an animal (e.g., a human) comprising administering certain compositions (e.g., pharmaceutical compositions of the nucleic acid molecule) and applying a static magnetic field or an electromagnetic field, are further disclosed.

The invention relates to a polypeptide, such as an Affimer polypeptide, comprising an amino acid sequence having at least 80% identity to amino acid residues 1 to 11, 13 to 15, 17 to 19, 21 to 25, 27 to 28, 35 to 37, 39, 41, 43 to 44, 46 to 47, 49 to 50, 52 to 53, 55 to 58, 63 to 64, 66, 68 to 82, 84 to 85, and 87 to 98 of SEQ ID NO: 1; characterised in that said polypeptide comprises one or more mutations relative to SEQ ID NO: 1 selected from the group consisting of: T51L, T51V, M65V, N32G, A59I, L38A, V20I, A40I, L38V, A12I, A12V, I16L, V20L, Q26E, E29M, T31K, N32D, N32H, T34V, T34R, T34D, T34P, A40V, Q42D, T45I, T45V, V48E, V48G, V48A, T51F, T51A, A59L, L67I, (V20I, L38A), (V20L, L38A), (V20I, L38V), (V20L, L38V), (E29K, K30E, E33K), (Y54D, T83D, Q86E), (A59L, G60N, D61G, N62K), (A59V, D61N, N62K), (G60N, D61G, N62K), (G60N, D61, N62G), D61, (A59L, G60N, D61, N62G), (A59V, G60N, D61G, N62K), (A59I, G60N, D61G, N62K), (A59I, G60N, D61, N62G), (A59V, G60N, D61, N62G), (A59V, D61), (G60P, D61, N62P), (G60P, D61P, N62K), (G60P, D61, N62G), (G60P, D61G, N62K), (D61N, N62K) and (T83D, Q86E). The invention also relates to various methods and nucleic acids.

It is disclosed herein that RPE degeneration in human cell culture and in mouse models is driven by a non-canonical inflammasome pathway that results in activation of caspase-4 (also known as caspase-11 in mouse) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-? (IFN-?) production and gasdermin D-dependent interleukin-18 (IL-18) secretion. Reduction of DICER1 or accumulation of Alu RNA triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Collectively, these data highlight an unexpected role for cGAS in responding to mobile element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial damage-induced NLRP3 activation, and expand the immune sensing repertoire of cGAS and caspase-4 to non-infectious human disease. Coupled with the unexpected result that caspase-4, gasdermin D, IFN-?, and cGAS are elevated in the RPE of human eyes with geographic atrophy, these findings also identify new targets for a major cause of blindness.

The invention relates to a polypeptide, such as an Affimer polypeptide, comprising an amino acid sequence having at least 80% identity to amino acid residues 1 to 11, 13 to 15, 17 to 19, 21 to 25, 27 to 28, 35 to 37, 39, 41, 43 to 44, 46 to 47, 49 to 50, 52 to 53, 55 to 58, 63 to 64, 66, 68 to 82, 84 to 85, and 87 to 98 of SEQ ID NO: 1; characterised in that said polypeptide comprises one or more mutations relative to SEQ ID NO: 1 selected from the group consisting of: T51L, T51V, M65V, N32G, A59I, L38A, V20I, A40I, L38V, A12I, A12V, I16L, V20L, Q26E, E29M, T31K, N32D, N32H, T34V, T34R, T34D, T34P, A40V, Q42D, T45I, T45V, V48E, V48G, V48A, T51F, T51A, A59L, L67I, (V20I, L38A), (V20L, L38A), (V20I, L38V), (V20L, L38V), (E29K, K30E, E33K), (Y54D, T83D, Q86E), (A59L, G60N, D61G, N62K), (A59V, D61N, N62K), (G60N, D61G, N62K), (G60N, ?D61, N62G), ?D61, (A59L, G60N, ?D61, N62G), (A59V, G60N, D61G, N62K), (A59I, G60N, D61G, N62K), (A59I, G60N, ?D61, N62G), (A59V, G60N, ?D61, N62G), (A59V, ?D61), (G60P, ?D61, N62P), (G60P, D61P, N62K), (G60P, ?D61, N62G), (G60P, D61G, N62K), (D61N, N62K) and (T83D, Q86E). The invention also relates to various methods and nucleic acids.

The present invention relates to a microorganism for drug delivery, which has been transformed with a gene construct including a therapeutically active peptide, is delivered safely into the intestines through oral administration, and expresses and secretes a cystatin in the gastrointestinal tract, and also relates to a pharmaceutical composition for prevention or treatment of gastrointestinal disease, which includes the same. The present invention demonstrates the safety and superiority of lactic acid bacteria as a system for delivering a protein-based drug, and thus it is expected the lactic acid bacteria will be widely used as an agent for treatment of gastrointestinal disease in the medical field.

The present invention provides a method of stratifying a patient suffering from CKD into one of stages 1-3 of CKD, comprising determining the level of the biomarkers FABP1, -GT, AST, creatinine and cystatin C in a sample obtained from the patient and comparing the level of FABP1 in the sample to a control value and the levels of -GT, AST, creatinine and cystatin C in the sample to a range of control values for each biomarker, wherein an increased level of FABP1 compared to the control value and levels of -GT, AST, creatinine and cystatin C within the range of control values for each biomarker indicate that the patient suffers from stage 1 CKD or wherein an increased level of FABP1 compared to the control value, levels of -GT and AST within the range of control values for each biomarker, and increased levels of creatinine and cystatin C compared to an upper threshold of the control range for these biomarkers indicate that the patient suffers from stage 2 or stage 3 CKD.

The present disclosure provides CAPN5 substrates and CAPN5 inhibitors, nucleic acids encoding CAPN5 substrates or CAPN5 inhibitors, methods to deliver CAPN5 substrate or CAPN5 inhibitor agents to the eye, and methods of identifying inhibitors of CAPN5.

The present disclosure provides CAPN5 substrates and CAPN5 inhibitors, nucleic acids encoding CAPN5 substrates or CAPN5 inhibitors, methods to deliver CAPN5 substrate or CAPN5 inhibitor agents to the eye, and methods of identifying inhibitors of CAPN5.