The present disclosure is directed to the use of inhibitors of glutamate metabolism to treat cancers that have mutations in ARID1A. Thus, in accordance with the present disclosure, there is provided a method of treating a subject determined to have an ARIDIA-mutated cancer, pre-cancer or benign tumor comprising administering to said subject at least one inhibitor of glutamate metabolism.

Described are conformation-specific antibodies or antigen-binding fragments that specifically bind to the trans conformation of phosphorylated-Threonine254-Proline (pThr254-Pro) of the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Also described are related pharmaceutical compositions, polynucleotides, peptides, vectors, host cells, methods of production, methods of treatment, diagnostic methods, and kits.

An assay is disclosed based on the successful transmission of DLB, and to a much lesser extent PD, to cultured HEK cells expressing the A53T and E46K point mutation. DLB prion activity was achieved by treatment of brain homogenates with detergent extraction and limited proteolysis followed by polyoxometalate precipitation of the prions. The results show the MSA strain of α-synuclein prions differs from those causing PD and DLB. Manipulating dominant negative inhibition of α-synuclein prions has created a new approach to identifying novel prions and deciphering the features of their multiplication.

Alpha-Synuclein mutants and uses thereofare disclosed herein. The mutants of the present invention are non-self-aggregating forms of Alpha-Synuclein which make them a suitable candidate for use as substrates in aggregation assay for evaluating the presence of misfolded α-Syn protein. Also disclosed are kits and method for detection of synucleinopathies in individuals, using the mutants of the present invention.

Blood and bodily fluid reader systems, including circulating biomarkers involving multiple mitochondrial releasates for providing real-time, at-the-scene objective indicia of individuals sustaining mild TBI.

The present invention provides a method of diagnosing endometriosis and/or infertility in a subject, comprising: a) obtaining a sample from the subject; b) detecting a level of expression of a SIRT1 gene and/or protein in the sample; c) detecting a level of expression of a BCL6 gene and/or protein in the sample; d) comparing the level of expression detected in (b) with the level of expression of a SIRT1 gene and/or protein in a sample obtained from a control subject or a population of control subjects; e) comparing the level of expression detected in (c) with the level of expression of a BCL6 gene and/or protein in a sample obtained from a control subject or a population of control subjects; and f) diagnosing the subject as having infertility when the subject has a level of expression of the SIRT1 gene and/or protein greater than the level of expression of the SIRT1 gene and/or protein of the control subject or population of control subjects and also has a level of expression of the BCL6 gene and/or protein that is greater than the level of expression of the BCL6 gene and/or protein of the control subject or population of control subjects.

The present disclosure provides methods for isolating tumor-derived microparticles from a subject for analysis, specifically by isolating Tenascin-C positive microparticles from a sample from the subject to obtain tumor-derived microparticles. Methods for determining the expression status of biomarkers in the tumor-derived microparticles and methods for determining additional characteristics of the tumor-derived microparticles are also provided.

A 11-(4-chlorophenyl)-4-(2,3-dihydro-1H-indole-1-carbonyl)-3,11-dimethyl-5,10,dioxatricyclo[7.4.0.0,2,6,]trideca-1,3,6,8-tetraen-13-one compound and related derivatives, as well as the use thereof in a preparation of a medicament for treatment and/or prevention of diseases or disorders associated with a circadian rhythm. The compound is a CRY1-binding small molecule and also a destabilizer of CRY1, and is therefore useful, as pharmaceutical agent, especially in the treatment and/or prevention of disorders associated with the circadian rhythm, including CRY1-mediated diseases such as cancer.

Provided are biomarkers for predicting the efficacy of MDM2 inhibitor or Bcl-2/Bcl-xL dual inhibitors or Bcl-2 inhibitor or Bcl-xL inhibitor in treating cancer patients. Also provided are compositions, e.g., kits, for evaluating gene levels of the biomarkers and methods of using such gene levels to predict a cancer patient's response to the MDM2 inhibitors or Bcl-2/Bcl-xL dual inhibitors or Bcl-2 inhibitor or Bcl-xL inhibitor. Such information can be used in determining prognosis and treatment options for cancer patients.

A method of treating a cancer in a mammalian subject with a tumor signature characterized by any one or more of (i) a level of sirtuin (SIRT3) protein that is below a first predetermined threshold level, (ii) a level of manganese superoxide dismutase acetylated at the lysine 68 residue (AcK68) that exceeds a second predetermined threshold level, and (iii) expression levels of hypoxia-inducible factor 2.sub.α (HIF2.sub.α) that exceed a third predetermined threshold level indicative of lineage plasticity for stemness, the method comprising administering to the mammalian subject a therapeutically effective amount of a pentaaza macrocyclic ring complex corresponding to the Formula (I) below, optionally with administration of a further anti-cancer therapeutic agent.

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