Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism

Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies

Surface functionalization of titanium with silver nanoparticles

This study aims to investigate the most efficient ways for metallic samples functionalization with silver nanoparticles (AgNPs). Three different techniques of surface functionalization have been used for the coating of titanium metal, i.e. the sessile drop method (evaporation), dip-coating and electrophoretic deposition (EPD). AgNPs stabilized with polyvinylpyrrolidone had a spherical shape and the metallic core diameter, charge and polydispersity index were 70±20 nm, -15 mV and 0.192, respectively. SEM analysis revealed that AgNPs were homogeneously distributed over the entire surface and did not form the particle agglomerates only in case of EPD. Thus, EPD method and spherical AgNPs can be used for further investigation concerning the preparation of biocomposites with antibacterial and bioactive properties

Data from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth

&lt;div&gt;Abstract&lt;p&gt;The junctional adhesion molecule-C (JAM-C) was recently described as an adhesion molecule localized at interendothelial contacts and involved in leukocyte transendothelial migration. The protein JAM-C interacts with polarity complex molecules and regulates the activity of the small GTPase Cdc42. The angiogenesis process involves rearrangement of endothelial junctions and implicates modulation of cell polarity. We tested whether JAM-C plays a role in angiogenesis using tumor grafts and hypoxia-induced retinal neovascularization. Treatment with a monoclonal antibody directed against JAM-C reduces tumor growth and infiltration of macrophages into tumors. The antibody decreases angiogenesis in the model of hypoxia-induced retinal neovascularization &lt;i&gt;in vivo&lt;/i&gt; and vessel outgrowth from aortic rings &lt;i&gt;in vitro&lt;/i&gt;. Importantly, the antibody does not induce pathologic side effects &lt;i&gt;in vivo&lt;/i&gt;. These findings show for the first time a role for JAM-C in angiogenesis and define JAM-C as a valuable target for antitumor therapies.&lt;/p&gt;&lt;/div&gt;</jats:p

Supplementary Figure 2 from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth

Supplementary Figure 2 from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth</jats:p

Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth

The junctional adhesion molecule-C (JAM-C) was recently described as an adhesion molecule localized at interendothelial contacts and involved in leukocyte transendothelial migration. The protein JAM-C interacts with polarity complex molecules and regulates the activity of the small GTPase Cdc42. The angiogenesis process involves rearrangement of endothelial junctions and implicates modulation of cell polarity. We tested whether JAM-C plays a role in angiogenesis using tumor grafts and hypoxia-induced retinal neovascularization. Treatment with a monoclonal antibody directed against JAM-C reduces tumor growth and infiltration of macrophages into tumors. The antibody decreases angiogenesis in the model of hypoxia-induced retinal neovascularization in vivo and vessel outgrowth from aortic rings in vitro. Importantly, the antibody does not induce pathologic side effects in vivo. These findings show for the first time a role for JAM-C in angiogenesis and define JAM-C as a valuable target for antitumor therapies

Supplementary Figure Legends from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth

Supplementary Figure Legends from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth</jats:p

Supplementary Figure 1 from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth

Supplementary Figure 1 from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth</jats:p

Supplementary Figure Legends from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth

Supplementary Figure Legends from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth</jats:p

Supplementary Figure 2 from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth

Supplementary Figure 2 from Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth</jats:p