Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

Clinical experience with denosumab discontinuation.

Unlabelled: In patients receiving long-term treatment with denosumab, denosumab discontinuation via sequential treatment with zoledronate, resulted in a minor decrease in bone mass density (BMD) of 0-2.5% within the first year and stabile BMD in the second year, thus showing that repeated treatments with zoledronate limit the loss of BMD, when discontinuing denosumab.

Purpose: Discontinuing denosumab (DMAb) rapidly decreases bone mineral density (BMD) and increases the risk of multiple vertebral fractures.

Transition metal transporting P-type ATPases: terminal metal-binding domains serve as sensors for autoinhibitory tails.

Copper is an essential micronutrient and yet is highly toxic to cells at elevated concentrations. P-ATPase proteins are critical for this regulation, providing active extrusion across cellular membranes. One unique molecular adaptation of P-ATPases compared to other P-type ATPases is the presence of metal-binding domains (MBDs) at the cytosolic termini, which however are poorly characterized with an elusive mechanistic role.

Development of an immunoassay for quantification of soluble human CD40L (CD154) in plasma and serum samples.

When the membrane protein CD40 ligand (CD40L) on activated T cells binds the receptor CD40 on B-cells, it provides a co-stimulatory signal for B cell activation. Dysregulation of the CD40L:CD40 axis is associated with inflammatory and autoimmune diseases. The presence of soluble CD40L (sCD40L) in plasma is implicated in several diseases, from cardiovascular and autoimmune diseases to different types of cancer, and sCD40L has been suggested as a valuable marker of disease.