Identification and Characterization of the Wild Mouse Gut Microbiome as the Optimal Standard for Laboratory Mice

This technology includes identification of the wild mouse microbiome as a method to increase resistance to lethal viral infection. We establish that the gut microbiome of barrier-raised C57BL/6 mice is dysbiotic compared to that of their outbred, wild-living progenitors, Mus musculus domesticus. We find that the multigenerational offspring of pregnant germfree C57BL/6 mice reconstituted with the gut microbiome of wild mice exhibit a less inflammatory response and increased survival following influenza A virus infection.

Transgenic Mice with Conditionally Activated Islet Beta Cell M3 Muscarinic Acetylcholine Receptor for Improving Glucose Tolerance in High-fat Diet Obese Insulin-resistant Mice

This technology includes transgenic mice in which designer rat M3 muscarinic receptor mutants were expressed only in islet 13-cells (directed by rat insulin promoter II), were unable to bind acetylcholine (the endogenous ligand) but could be selectively activated by an otherwise pharmacologically inert compound (clozapine-N-oxide (CNO)). The R-q receptor contained a Y148C point mutation, which enabled CNO to selectively activate G proteins of the Gq/11 family. The R-5 receptor contained an A238G mutation, which enabled CNO to selectively activate G proteins of the G5 family.

MiR-193b and MiR-365-1 are Not Required for the Development and Function of Brown Fat in the Mouse

This technology includes the discovery that two specific microRNAs are not required for the development and function of brown fat in mice. Effects of inactivating microRNAs in cell culture in vitro have not always been reproduced in vivo. The paper tests the effect of inactivating two microRNAs, miR-193b and miR-365-1 on the differentiation, function and development of brown adipose tissue. In contrast to positive results previously observed in vitro, the mouse in vivo studies failed to demonstrate significant effects.

New Heterocyclic Scaffold-Based Inhibitors of the Polo-Box Domain of Polo-like Kinase 1 for the Treatment of Cancer

Polo-like kinase 1 (Plk1), a member of the Polo-like kinase family, plays a critical role in regulating mitosis and cell cycle progression. Aberrant expression of Plk1 has been observed in a variety of human cancers, and it is known to be associated with tumorigenesis as well as poor prognosis in cancer patients. Unlike normal cells, some cancer cells are dependent on augmented Plk1 levels to remain viable and are killed when Plk1 function is attenuated.

Thyclotide Peptide Conjugates With Cell Permeability And Inhibitory Activity

Thyclotides are oligomeric molecules with chiral tetrahydrofuran (THF) diamine units consisting of either R,R or
S,S stereochemistry. Thyclotide sequences with R,R stereochemistry bind to complementary DNA and RNA
sequences with strong affinity and sequence specificity, while thyclotides with S,S stereochemistry have a helical
handedness that does not allow binding to DNA or RNA. Thyclotides are cell permeable and can be used to
suppress microRNA activity in cells. Peptides are oligomeric molecules consisting of amino acids found in

A3 Adenosine Receptor Positive Allosteric Modulators

Selective A3AR agonists are sought as potential agents for treating inflammatory diseases,
chronic pain, cancer and non-alcoholic steatohepatitis (NASH). NIDDK investigators have invented 
new chemical composition as positive allosteric modulators (PAMs) of the A3AR. These chemical 
compounds contain sterically constrained, bridged modifications and cycloalkyl rings of various 
sizes, as well as modifications of the 4-arylamino group. The compounds have added 

Heterocyclic P2Y14 Antagonists for the Treatment of Various Conditions

The technology discloses composition of compounds that are highly selective P2Y14 receptor antagonists,
with moderate affinity with insignificant antagonism of other P2Y receptors. These compounds might provide a
treatment for patients for various disease conditions, including lung inflammation, kidney inflammation,
asthma, diabetes, obesity, and neuropathic pain of diverse states. In vivo data using mouse lines with the
receptor knocked out in specific tissues showed that P2Y14 receptor antagonists act on adipocytes to improve

Vitamin C renal leak as a clinical diagnostic tool in the detection, monitoring, and management of acute and chronic diseases

This technology includes a clinical diagnostic tool for measuring vitamin C elimination by human kidneys that can be used for detecting, monitoring, and managing acute and chronic diseases. Findings revealed significant associations between vitamin C renal leak status and clinical variables affecting renal function and blood glucose. The technology uses vitamin C depletion-repletion kinetics and pharmacokinetic models to establish a physiological vitamin C renal threshold.

P2Y14 Receptor Antagonists for the Treatment of Inflammatory Diseases, Including Pulmonary and Renal Conditions and Chronic Pain

This technology includes the development of selective P2Y14R antagonists for the treatment of asthma, sterile inflammation of the kidney, diabetes, and neurodegeneration. The P2Y14 receptor (P2Y14R) is a target for the treatment of inflammatory diseases, including pulmonary and renal conditions. Selective P2Y14R antagonists have demonstrated efficacy in animal models of asthma, pain, diabetes, and acute kidney injury. However, the prototypical antagonist is not optimal for in vivo administration, as it displays a low oral bioavailability.

Selective A3 Adenosine Receptor Agonists for the Treatment of Chronic Neuropathic Pain and Other Conditions

This technology includes the creation and use of A3 adenosine receptor (A3AR)-selective agonists for treating chemotherapy-induced peripheral neuropathy, chronic neuropathic pain, rheumatoid arthritis, psoriasis, and other conditions. A3 receptors for adenosine are found in most cells and endogenous activation of the A3 receptors can result in apoptosis, thereby relieving the inflammation or targeting a tumor. A3AR agonists have been a promising strategy for the treatment of various diseases.

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