Mechanisms of Action Underlying Conductance-Modifying Positive Allosteric Modulators of the NMDA Receptor.

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate a slow, Ca-permeable component of excitatory neurotransmission. Modulation of NMDAR function has the potential for disease modification as NMDAR dysfunction has been implicated in neurodevelopment, neuropsychiatric, neurologic, and neurodegenerative disorders. We recently described the thieno[2,3-day]pyrimidin-4-one (EU1622) class of positive allosteric modulators, including several potent and efficacious analogs.

A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.

The clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy.

Indoor Air Quality Assessments in 10 Long-Term Care Facilities during the COVID-19 Pandemic, California, 2021-2023.

Objectives: This study aimed to assess indoor air quality (IAQ) in long-term care facilities (LTCFs) in California during the COVID-19 pandemic and evaluate their implementation of IAQ best practices described by public health authorities to control respiratory pathogen transmission via inhalation.

Design: This observational study conducted IAQ assessments in a convenience sample of LTCFs to gather qualitative data on the implementation of IAQ best practices. The design included 5 pilot visits to develop a standardized method of data collection and then systematic data collection at 10 facilities.

Molecular mechanism of ligand gating and opening of NMDA receptor.

Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor (NMDAR) is unique among all ligand-gated channels, requiring two ligands-glutamate and glycine-for activation. These receptors function as heterotetrameric ion channels, with the channel opening dependent on the simultaneous binding of glycine and glutamate to the extracellular ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, respectively.

A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants.

The receptor tyrosine kinase FGFR3 is frequently mutated in bladder cancer and is a validated therapeutic target. Although pan-FGFR tyrosine kinase inhibitors (TKI) have shown clinical efficacy, toxicity and acquired resistance limit the benefit of these agents. While antibody-based therapeutics can offer superior selectivity than TKIs, conventional ligand-blocking antibodies are usually ineffective inhibitors of constitutively active receptor tyrosine kinases.