摘要:
The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.
摘要:
The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.
摘要:
The present invention provides a low-cost cell-free assay, the α-test, that provides point-of-care CD4 enumeration using a single platform assay thereby eliminating the need for high-end instrumentation, calibrated pipetting, and specialized technical training. The number of CD4 T cells in blood is driven by the concentration of the protein α1proteinase inhibitor (α1PI, α1antitrypsin, serpin A1). The invention features, in part, methods for determining the number of CD4+ T cells in a sample comprising determining the concentration of alpha 1 proteinase inhibitor (α1PI) in a sample; wherein the number of CD4+ T-cells is related to the concentration of α1PI.
摘要:
Provided herein are, inter alia, methods for identifying a candidate compound for treating the toxic effects of compounds or molecules that bind to albumin in a subject. The methods include identifying test compounds that inhibit the binding between FcRn and albumin.
摘要:
The present application relates to immunogenic compositions comprising staphylococcal PNAG which is less than 40% N-acetylated and is conjugated to a carrier protein by a linker bonded to an amine group on PNAG to form a PNAG conjugate. Methods of using and processes to make an immunogenic composition are also described.
摘要:
Method of treating or preventing the inflammatory response of colitis in a subject comprising administering to the subject an effective amount of a substance that modulates IL-13 activity (FIG. 3). The invention also provides a method of treating or preventing the inflammatory response of colitis in a subject comprising administering to the subject an effective amount of a substance that modulates NK-T cell activity. The invention also provides for the screening of substances that treat or prevent the inflammatory response of colitis.
摘要:
The present invention generally relates to polymers and macromolecules, in particular, to block polymers useful in particles such as nanoparticles. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. In some cases, the nanoparticle may contain a drug. The moiety, in some embodiments, may have a molecular weight greater than about 1000 Da; for example, the moiety may include a polypeptide or a polynucleotide, such as an aptamer. The moiety may also be a targeting moiety, an imaging moiety, a chelating moiety, a charged moiety, or a therapeutic moiety. Another aspect of the invention is directed to systems and methods of producing such polymeric conjugates. In some embodiments, a solution containing a polymer is contacted with a liquid, such as an immiscible liquid, to form nanoparticles containing the polymeric conjugate. Other aspects of the invention are directed to methods using such libraries, methods of using or administering such polymeric conjugates, methods of promoting the use of such polymeric conjugates, kits involving such polymeric conjugates, or the like.
摘要:
A method for treating inflammatory joint diseases by inhibiting cadherin-11 mediated cellular function using a cadherin-11 modulating agent is provided. Also provided are screening assays for identifying pharmaceutical lead compounds capable of modulating cellular functions of cadherin-11 such as cell proliferation, apoptosis, factor secretion, and binding of cadherin-11 to cadherin-11 counter-receptor inhibiting binding of cadherin-11 to its counter-receptor either in the context of a cell or in soluble form.
摘要:
Aspirin (ASA) triggers a switch in the biosynthesis of lipid mediators, inhibiting prostanoid production and initiating 15-epi-lipoxin generation, through the acetylation of cyclooxygenase II.
摘要:
The present invention represents a new approach to data analysis for multivariate classification, particularly as used in medical diagnostics. The invention is in part an intuitive decision making tool for rapid classification of “objects” (e.g., cell, tissue or tumor samples) from evaluation of many simultaneous “variables” (e.g., quantitative gene expression profiles). The data analysis methods of the invention provide the end user with a simplified and robust output for diagnostic classification of objects based on identifying and evaluating multiple variables of predetermined diagnostic relevance. The raw data generated by analysis of the variables is transformed by application or appropriate algorithms to scaleless rank differentials between the variables. The rank orders of variables are used to classify tissues based on readily observable user interfaces, such as a graphical (e.g., visual) user interface or an auditory user interface.