The subject invention pertains to methods of treating colorectal cancer by administering an atypical PKC inhibitor. The inhibitors of aPKC useful in the methods of the instant invention include ACPD, ICA-1, DNDA and ζ-Stat. Also provided are methods of measuring the susceptibility of colon cancer cells of a subject to inhibitors of aPKCs.

Provided are methods of treating or preventing Ca.sup.2+/calmodulin-dependent kinase II (CaMKII)-mediated diseases, methods of alleviating cardiac injury, methods of stimulating the activity of ubiquitin-conjugating enzyme, methods of preventing degradation of ubiquitin-conjugating enzyme, methods of preventing cardiomyocyte death, methods of reducing DNA damage in a cell, methods for diagnosing CaMKII-mediated diseases, kits for diagnosing CaMKII-mediated diseases, biomarkers for diagnosing a CaMKII-mediated disease, and use of CaMKIIδ9 as a biomarker for diagnosing a CaMKII-mediated disease. Also provided herein are methods for identifying molecules, isolated polypeptides, isolated nucleic acids, and antagonists thereof.

The present invention relates to improvements in female health monitoring and treatment wherein menstrual blood samples are analyzed for biomarkers of interests to monitor the health status and treatment of a female patient.

Therapeutic treatments of a tumor expressing pT346 PDK1, including glioma expressing pT346 PDK1, are disclosed.

The present invention relates to a combined preparation comprising (i) a modulator of pyruvate kinase M2 (PKM2) activity, and (ii) an agent providing high mobility group box 1 (HMGB1) polypeptide or a derivative thereof. The present invention also relates to the aforesaid combined preparation for use as a medicament and for use in the treatment of inappropriate cellular proliferation, preferably in the treatment of cancer. Moreover, the present invention relates to a method for determining whether a subject suffering from inappropriate cellular proliferation is amenable to a treatment comprising administration of a modulator of PKM2 activity as the only PKM2 inhibitor and to treatment methods related thereto.

This disclosure provides methods, systems, and compositions of matter for studying solvent accessibility and three-dimensional structure of biological molecules. A plasma can be used to generate marker radicals, which can interact with a biological molecule and mark the solvent-accessible portions of the biological molecule.

The invention relates to a method for treating mitochondrial genetic diseases. The inventors have worked with primary fibroblasts from patients and control individuals and collected protein lysates for western blotting. Importantly, they observed that the genetic mitochondrial disorders, show a significant increase in phosphorylation of ribosomal protein S6 (pS6) compared to control fibroblasts, indicative of hyperactivated mTOR signaling. Patients with mitochondrial disorders and controls cells were treated for 48 hours with DMSO or BYL719. All lines from patients with mitochondrial diseases show reduced membrane potential, determined by TMRE staining intensity, and abnormal morphology, fragmentation and the presence of depolarized (low TMRE staining) mitochondria. Treatment with BYL719 attenuated these phenotypes in all MELAS fibroblasts while having no overt impact on the control cells. Similar experiments using flow cytometry confirmed membrane potential (TMRE) rescue by BYL719 treatment in MELAS fibroblasts.

A system for the electrochemical detection of triglyceride levels includes a test strip including an electrode and a counter electrode, the electrode and counter electrode located proximate to a sample reception area; and a coating on one of the electrode and counter electrode, the coating including a reagent coating for triglycerides.

The present invention relates to a high mobility group box 1 (HMGB1) polypeptide, wherein in said HMGB1 polypeptide at least one, preferably two, more preferably three, most preferably all four tyrosine residues at positions corresponding to amino acid positions Y109, Y144, Y155 and/or Y162 of human HMGB1 have been exchanged to an amino acid residue independently selected from glutamic acid, glutamine, aspartic acid, asparagine, homoglutamic acid (2-aminohexanedioic acid), and homoglutamine (2,6-diamino-6-oxohexanoic acid). The present invention further relates to a polynucleotide encoding a polypeptide according to the present invention, to a vector comprising said polynucleotide, and to a host cell comprising said polypeptide, said polynucleotide and/or said vector. Also, the present invention relates to methods, kits, and uses related thereto.

Ischemic conditions are a leading cause of death for both men and women. Ischemia, a condition characterized by reduced blood flow and oxygen to an organ. Re-establishment of blood flow, or reperfusion, and re-oxygenation of the affected area following an pot ischemic episode is critical to limit irreversible damage. However, reperfusion also associates potentially damaging consequences. For NI instance, increased vascular permeability is an important contributor to edema and tissue damage following ischemic events. Here the inventors shows that genetic inhibition of PI3K-C2β reduces cerebral infarction in two ischemia/reperfusion (UR) models and improves neurological outcome. The genetic inhibition stabilizes the blood-brain barrier (BBB) after ischemic stroke and reduces inflammation. Accordingly, the present invention relates to a method for the preservation of vascular endothelial cell barrier integrity in a patient in need thereof comprising administering to the subject a therapeutically effective amount of a PI3KC2β inhibitor.