A drug-repositioning screen using splicing-sensitive fluorescent reporters identifies novel modulators of VEGF-A splicing with anti-angiogenic properties.

Alternative splicing of the vascular endothelial growth factor A (VEGF-A) terminal exon generates two protein families with differing functions. Pro-angiogenic VEGF-Aa isoforms are produced via selection of the proximal 3' splice site of the terminal exon. Use of an alternative distal splice site generates the anti-angiogenic VEGF-Ab proteins.

Differential Expression of VEGF-A Isoforms Is Critical for Development of Pulmonary Fibrosis.

Rationale: Fibrosis after lung injury is related to poor outcome, and idiopathic pulmonary fibrosis (IPF) can be regarded as an exemplar. Vascular endothelial growth factor (VEGF)-A has been implicated in this context, but there are conflicting reports as to whether it is a contributory or protective factor. Differential splicing of the VEGF-A gene produces multiple functional isoforms including VEGF-Aa and VEGF-Ab, a member of the inhibitory family.

Serine-arginine protein kinase 1 (SRPK1), a determinant of angiogenesis, is upregulated in prostate cancer and correlates with disease stage and invasion.

Vascular endothelial growth factor (VEGF) undergoes alternative splicing to produce both proangiogenic and antiangiogenic isoforms. Preferential splicing of proangiogenic VEGF is determined by serine-arginine protein kinase 1 (SRPK1), which is upregulated in a number of cancers. In the present study, we aimed to investigate SRPK1 expression in prostate cancer (PCa) and its association with cancer progression.

Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration.

Diabetic peripheral neuropathy affects up to half of diabetic patients. This neuronal damage leads to sensory disturbances, including allodynia and hyperalgesia. Many growth factors have been suggested as useful treatments for prevention of neurodegeneration, including the vascular endothelial growth factor (VEGF) family.

Cathepsin C inhibitors: property optimization and identification of a clinical candidate.

A lead generation and optimization program delivered the highly selective and potent CatC inhibitor 10 as an in vivo tool compound and potential development candidate. Structural studies were undertaken to generate SAR understanding.

Federated queries for comparative effectiveness research: performance analysis.

This paper presents a study of the performance of federated queries implemented in a system that simulates the architecture proposed for the Scalable Architecture for Federated Translational Inquiries Network (SAFTINet). Performance tests were conducted using both physical hardware and virtual machines within the test laboratory of the Center for High Performance Computing at the University of Utah. Tests were performed on SAFTINet networks ranging from 4 to 32 nodes with databases containing synthetic data for several million patients.

SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases.

SRPK1 (serine-arginine protein kinase 1) is a protein kinase that specifically phosphorylates proteins containing serine-arginine-rich domains. Its substrates include a family of SR proteins that are key regulators of mRNA AS (alternative splicing). VEGF (vascular endothelial growth factor), a principal angiogenesis factor contains an alternative 3' splice site in the terminal exon that defines a family of isoforms with a different amino acid sequence at the C-terminal end, resulting in anti-angiogenic activity in the context of VEGF165-driven neovascularization.

Plasmapheresis in the management of choroidal vasculitis associated with C-anca positive renal vasculitis.

Purpose: The purpose of this study was to report the use of plasmapheresis in the management of choroidal vasculitis associated with Wegener granulomatosis.

Method: Case report.

Patient: A 50-year-old woman with acute renal failure as a result of glomerulonephritis of the Wegener granulomatosis type presented with sudden visual loss.

Overexpression of VEGF165b in podocytes reduces glomerular permeability.

The observation that therapeutic agents targeting vascular endothelial growth factor-A (VEGF-A) associate with renal toxicity suggests that VEGF plays a role in the maintenance of the glomerular filtration barrier. Alternative mRNA splicing produces the VEGF(xxx)b family, which consists of antiangiogenic peptides that reduce permeability and inhibit tumor growth; the contribution of these peptides to normal glomerular function is unknown. Here, we established and characterized heterozygous and homozygous transgenic mice that overexpress VEGF(165)b specifically in podocytes.

Elemental mapping and quantitative analysis of Cu, Zn, and Fe in rat brain sections by laser ablation ICP-MS.

This report details the application of laser ablation quadrupole ICP-MS for the (multi)elemental mapping of 100-microm-thick sections of rat brain. The laser spot size used was 60 microm, and the laser scan speed was 120 microm s(-1). The analysis was relatively rapid, allowing mapping of a whole brain thin section (approximately 1 cm2) in about 2 h.

Distribution and speciation of metals in annual rings of black willow.

Information on the spatial distribution and speciation of metals in nonhyperaccumulator plants is lacking. This study used synchrotron X-ray fluorescence (SXRF) compositional imaging to investigate the spatial distribution of Ni, Mn, Cu, Zn, and Fe in annual rings of black willow (Salix nigra L.) collected from a metal-contaminated area, and used X-ray absorption spectroscopy (XAS) to investigate Ni and Mn speciation in regions of the annual rings with elevated Ni concentrations.

Human podocytes express angiopoietin 1, a potential regulator of glomerular vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is abundantly expressed by podocytes, but its role in glomeruli is unknown. Angiopoietins are endothelial cell growth factors that function in concert with VEGF but have not previously been observed in human glomeruli. Angiopoietin 1 (Ang1) acts via the endothelial receptor Tie2 to promote maturation and stabilization of blood vessels, resisting angiogenesis and opposing some actions of VEGF.