Methods for selecting a microbe for co-formulation with a carrier are provided. In some examples, the methods include identifying a microbe that comprises one or more dipicolinic acid (DPA) synthase genes, a microbe that expresses one or more DPA synthase proteins, and/or a microbe that produces DPA; and selecting the microbe for co-formulation with a carrier. The methods optionally include co-formulating the selected microbe with the carrier. In some examples, the methods include detecting one or more DPA synthase genes or one or more DpaA and/or DpaB proteins in a microbe. In other examples, the methods include detecting DPA in a microbe or medium containing a microbe, for example, utilizing a fluorescence assay. Microbial compositions including one or more microbes that comprise one or more DPA synthase genes, express one or more DPA synthase proteins and/or produce DPA are also provided.

Methods for determining the likelihood that a subject suffering from a solid tumor cancer will benefit from treatment with an illudin are disclosed herein. Further, there are also methods for treatment based on such determination. In several embodiments, markers prostaglandin reductase 1 (PTGR1), Protein Tyrosine Phosphatase Non-Receptor Type 14 (PTPN14), Aspartate Beta-Hydroxylase (ASPH) together with one or more genes or alone may be used to enhance or guide treatment with an illudin. In certain embodiments, the protein or gene may be expressed or methylated.

The invention provides therapeutic compositions that contain an inhibitor of dihydroorotate dehydrogenase (DHODH) and promote sustained elevation of dihydroorotate (DHO) levels in a patient. The compositions are useful for treating disorders associated with unregulated DHODH activity, such as acute myeloid leukemia. The invention also provides methods of determining therapeutically effective doses of compositions that contain a DHODH inhibitor. The invention further provides methods of synthesis of 2-(2′-halo-1-1′-biphenyl-4-yl)-quinoline carboxylic acids, which are useful as DHODH inhibitors.

The invention provides methods for adjusting a drug dosing regimen, including a drug dosage and schedule of administration, in individuals who have previously received at least one dose of the drug. Adjustments to the dosage and/or schedule are made based on measured levels of the drug or metabolite of the drug and a biomarker of engagement of the drug with its target. The methods are useful for administration of therapeutic agents, such as brequinar, that alter metabolic pathways.

This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid -oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid -oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.

Methods are provided for assembly of a target polynucleotide sequence comprising at least a first double stranded polynucleotide (DSP) and at least second DSP, and optionally further DSPs. The method comprises an assembly reaction comprising steps including providing a first single stranded polynucleotide (SSP) comprising the polynucleotide sequence of one strand of the first DSP, and a second SSP comprising the polynucleotide sequence of one strand of the second DSP and converting the SSPs to double stranded form via a primer and polymerase-mediated extension reaction. The DSPs comprise polynucleotide sequences that are complementary to other polynucleotide sequences within the assembly reaction such that the ordering and directionality of each of the first and second, and further DSPs is determined by unique overhang pairing. Nucleic acid libraries and methods of making such libraries are also provided.

The invention relates to 5-fluoro-2-deoxyuridine-5-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373), or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer, in particular by intravenous infusion for a continuous period of up to 10 hours. The invention also relates to methods of treating cancer by administration of NUC-3373 to particular sub-groups of cancer patient. The invention further relates to methods for selecting a patient for treatment with NUC-3373.

Devices and methods for sensing analytes in a solution sample are provided. The device includes a substrate, a conversion component configured to convert the analyte in the sample solution into a metabolite, and an aptamer sensor configured to measure a presence of the metabolite, the aptamer sensor located on the substrate.

The invention relates to a method for determining the activity of a component of the electron transport chain or any associated protein thereof and for determining the effect of a compound on the activity of a component of the electron transport chain or any associated protein thereof. The invention also relates to a kit comprising a redox probe, at least one electron donor compound of a component of the electron transport chain or a protein associated thereof and optionally comprising a sample comprising mitochondrial membranes and to the use of said kit in the methods of the invention.

The present disclosure relates to methods for detecting brain tumors and assessing the recurrence of such tumors by administering a pharmaceutical composition comprising 5-aminolevulinic acid (5-ALA) and detecting the conversion of 5-ALA to protoporphyrin IX (PPIX) associated with brain-derived microparticles.