Engineered polypeptides useful in synthesizing acyl amino acids are provided. Also provided are methods of making acyl amino acids using engineered polypeptides.

A composition for reducing a level of senescence of a cell or subject, a method of reducing a level of senescence in a cell or subject by using the composition, and a method of preventing and treating symptoms or diseases related to or caused by senescence of a cell or subject.

Methods of treating subjects with cancer and screening for MDM2 inhibitors that may be effective cancer therapeutics are provided herein. The cancers that may be treated using MDM2 inhibitors using the methods described herein include those that are or may become resistant to treatment with tyrosine kinase inhibitors. Methods of treating subjects with cancers that have, or develop in response to treatment with tyrosine kinase inhibitors, elevated levels of MDM2, Mcl-1 or PP5 or decreased levels of Huwe1 or CAS using MDM2 inhibitors are provided herein. The MDM2 inhibitors may be effective at treating these cancers alone or in combination with a tyrosine kinase inhibitor regardless of p53 status (mutant or wild-type) of the cancer.

The present disclosure relates to methods of screening salmonids for increased resistance to viral infection, such as infectious pancreatic necrosis virus (IP-NV) infection. The present disclosure also relates to fish which have been genetic modified to have increased resistance to viral/IPNV infection. The present disclosure further relates to the use of these fish, which have been identified. or genetically modified to have increased genetic resistance. in aquaculture breeding programs and/or production. The present disclosure further relates to the use of small molecules which target NAE1 and their use in therapy or prevention of viral/IPNV infection.

The present invention relates to new BARD1 isoforms specific to lung cancer and colorectal cancer, a method for detecting thereof and a method for treating and/or preventing lung cancer and colorectal cancer.

A method of inducing Parkin expression; inhibiting oxidative stress; and inhibiting cell death of cells by administering deferasirox, hydrocortisone, ketorolac, dexamethasone, and prednisone, a pharmaceutically acceptable salt, stereoisomer, derivative, or solvate thereof to the cell, optionally in a subject, as well as a method of preventing or treating neurodegenerative disease in the subject.

The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Their intriguing mode of assembly has long been proposed to feature a non-ribosomal peptide synthetase, a presumed intramolecular Diels-Alderase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of their cyclodipeptide-based structural core. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report a comparative analysis of four natural product metabolic systems of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)/()-notoamide, paraherquamide and malbrancheamide, in which we propose an enzyme for each step in the biosynthetic pathway based on deep annotation and on-going biochemical studies.

The invention provides isolated nucleic acids molecules, designated UBA3, UAE, or UBA6, or other E1 enzyme variant nucleic acid molecules, which encode novel E1 enzyme variant proteins. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing UBA3, UAE, or UBA6, or other E1 enzyme variant nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a UBA3, UAE, or UBA6, or other E1 enzyme variant gene has been introduced or disrupted. The invention still further provides isolated UBA3, UAE, or UBA6, or other E1 enzyme variant proteins, fusion proteins, antigenic peptides and anti-UBA3, UAE, or UBA6, or other E1 enzyme variant antibodies. The invention provides methods to identify agents that inhibit UBA3, UAE, or UBA6, or other E1 enzyme variant expression or activity. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

The present invention relates to new BARD1 isoforms specific to lung cancer and colorectal cancer, a method for detecting thereof and a method for treating and/or preventing lung cancer and colorectal cancer.

This present technology relates to the use of inflammation-enabling polypeptides (or their coding sequences) to screen for agents useful for the prevention, treatment and/or alleviations of symptoms associated with an inflammatory disorder, to identify individuals susceptible of developing an exacerbated inflammatory response as well as to determine if a therapeutic regimen is capable of preventing, treating or alleviating the symptoms associated to an inflammatory disorder in an individual. The present technology also provides methods for preventing, treating and/or alleviating the symptoms associated to an inflammatory condition based on the inhibition of expression or activity of the inflammation-enabling targets.