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Engineered chimeric antigen receptors (CARs) that are expressed in cytotoxic T cells and natural killer (NK) cells have been used to specifically target tumor cells. However, CAR-T and CAR-NK cells are still subject to down regulation by their inhibitory receptors after injection into patients.

Heparan sulfate proteoglycan (HSPG) is a group of lipid-anchored proteoglycans, engaged in a variety of key biological functions on cell surface. HSPG-mediated endocytosis of neurotoxic protein aggregates has been linked to aging related neurodegenerative diseases. Labeling HSPG is a promising technique to trace cell profile in cell research, monitor its trafficking in live cells and in tissues. Researchers at the NIDDK have discovered a method in which a positively charged fluorescent protein binds specifically to HSPG on cell surface.

The technology describes the composition of small molecule compounds that are antagonists of the P2Y14 receptor. Also provided are methods of using the compounds, including a method of treating a disorder, such as inflammation, diabetes, insulin resistance, hyperglycemia, a lipid disorder, obesity, a condition associated with metabolic syndrome, and asthma, and a method of antagonizing P2Y14 receptor activity in a cell.

The rapid worldwide spread and impact of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a need for accurate, reliable, and readily accessible testing on a massive scale.

The technology discloses composition of compounds that fully antagonize the human P2Y14 receptor, with moderate affinity with insignificant antagonism of other P2Y receptors. Therefore, they are highly selective P2Y14 receptor antagonists. Even though there is no P2Y14 receptor modulators in clinical use currently, selective P2Y14 receptor antagonists are sought as potential therapeutic treatments for asthma, cystic fibrosis, inflammation and possibly diabetes and neurodegeneration.

The coronavirus disease 2019 (COVID-19) is caused by a novel RNA enveloped coronavirus, SARS-CoV-2 when the virus enters human airway cells via an ACE2-mediated entry process. This entry pathway is facilitated by the cell surface heparan sulfate proteoglycan (HSPG), which enhances viral attachment to the cell surface. Researchers at NIDDK and NCATS have discovered a collection of FDA-approved drugs that can interfere with the entry of SARS-CoV-2. These drugs can be grouped into three classes based on the distinct steps in the viral entry pathway that they target.

During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.

Immunoglobulins play a key role in the immune system. CDC has developed and tested hybridoma cell lines (monoclonal antibody (mAb) clones) for human IgG and other immunoglobulins. The mAbs generated from those hybridomas could be used as a reagent (second Ab) of anti-human immunoglobins in a diagnostic assay for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19 (coronavirus disease 2019) and other assays that detect antigen specific antibodies from human sera.

Rotaviruses cause severe gastroenteritis in humans and animals globally. Currently, there are eight known serogroups (A-H) of rotaviruses. Group C rotavirus (GpC RV) causes sporadic cases and outbreaks of acute diarrhea in children and adults worldwide. GpC RV is also associated with diarrhea in swine. Currently, no simple and reliable diagnostic test exists for GpC RV, so disease prevalence remains unknown.

Scientists at NCATS have developed a novel Cellular Thermal Shift Assay (CETSA), named “Real-time CETSA” in which temperature-induced aggregation of proteins can be monitored in cells in real time across a range of compound concentrations and simultaneously across a temperature gradient in a high-throughput manner. Real-time CETSA streamlines the thermal shift assay and allows investigators to capture full aggregation profiles for every sample.