Disclosed are products and methods for monitoring Klotho protein levels and for stabilizing Klotho protein in a mammalian blood sample, especially at room temperature or without freezing, for a period of time. Methods of detecting and quantifying Klotho protein levels, particularly endogenous and/or exogenous soluble alpha Klotho protein levels, methods of diagnosing Klotho protein deficiency, and methods of increasing Klotho protein levels or production, particularly endogenous and/or exogenous soluble alpha Klotho protein level(s), expression, or production, in a mammalian subject, and products useful in performing the same, including diagnostic kits and compositions for treating Klotho protein deficiency, are disclosed. Compositions are configured or formulated to augment natural soluble alpha Klotho protein production, attenuate Klotho protein damage or degradation, and/or supplement Klotho protein levels with exogenous, recombinant protein. Treatment methods and uses include administration of the compositions to human or non-human mammalian subjects.

The present invention is related to novel methods for categorizing and treating a population of subjects that are at risk for increased pulmonary exacerbation and disease progression.

The invention relates to compounds that interact with heparanase, uses in heparanase screening, uses in in vitro and in vivo imaging (e g , positron emission tomography (PET) and magnetic resonance imaging (MRI)), methods of synthesis, methods of modulating heparanase activity, and methods of treating disease and disorders associated with heparanase. The compounds of the invention are also useful in treating one or more diseases or disorders associated with the function of heparanase.

Methods of analyzing glycosylated biomolecules include the steps of producing a deglycosylation mixture of biomolecules deglycosylated by natural or synthetic enzymatic or chemical techniques; providing a reagent solution having a labeling reagent in a polar aprotic, non-nucleophilic organic solvent; and mixing the deglycosylation mixture with the reagent solution in an excess of labeling reagent to produce derivatized glycosylamines. The method steps can be carried out purposefully without depletion of protein matter. A quenching solution can be added to the reaction mixture so that the pH of the reaction mixture is shifted to above 10. The yield of derivatized glycosylamines can be in an amount of about 80 to about 100 mole percent of the reaction mixture with minimal overlabeling, less than 0.2 mole percent. The derivizated glycosylamines can be separated from the reaction mixture and detected by chromatographic detection, fluorescence detection, mass spectrometry (“MS”), or Ultra Violet (“UV”) detection and/or a combination thereof.

A fluorescent probe for sialidase activity detection, is a compound represented by the following general formula or a salt thereof.

##STR00001##

R.sub.1, if present, represents the same or different monovalent substituent present on a benzene ring. R.sub.2 and R.sub.3 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a halogen atom. R.sub.4 and R.sub.5 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a halogen atom. R.sub.6 represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a fluorinated alkyl group having 1 to 5 carbon atoms. R.sub.6′ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R.sub.6′ may form, together with R.sub.3 or R.sub.5 a five to seven-membered heterocyclyl or heteroaryl containing a nitrogen atom to which R.sub.6′ is bonded.

A method of selecting a treatment for a subject having cancer is disclosed. The method comprises: (a) determining a level of catalytic activity of at least one DNA repair enzyme in a biological sample of the subject; and (b) selecting an immune checkpoint regulator as a treatment for a subject having a statistically significant different level of catalytic activity of said DNA repair enzyme as compared to the catalytic activity of said DNA repair enzyme in a biological sample of a healthy subject.

Provided are in vitro and in vivo methods for determining whether a patient with Fabry disease will respond to treatment with a specific pharmacological chaperone.

The present invention relates to methods, kits, and compositions for: i) detecting the level of 3-bromotyrosine in a sample that has been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine, and/or ii) detecting the level of 4-O-glucuronide-3-bromotyrosine, and/or the combined level of both 4-O-glucuronide-3-bromotyrosine and 3-bromotyrosine, in a sample that has not been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine. In certain embodiments, such detected levels are used to: i) identify the presence, severity, or risk of an eosinophilic disorder (e.g., asthma or a TH2-high eosinophilic disorder); ii) identify therapy effective for treating asthma or an eosinophilic disorder; or iii) identify patients suitable for treatment with therapeutic agents targeted to asthma or an eosinophilic disorder.

The present invention provides compounds useful as inhibitors of TIR NADase activity, compositions thereof, and methods of using the same. The present invention is useful for inhibition of TIR-domain NADase activity and/or treating microbial infection and/or modulating microbial physiology.

Some embodiments provided herein relate to combined assays. In some embodiments, an assay for identifying influenza type A or influenza type B is combined with an assay for determining the sensitivity of an influenza neuraminidase to an antiviral drug.