Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress.

The transmembrane protein neuropilin-1 (NRP1) promotes vascular endothelial growth factor (VEGF) and extracellular matrix signaling in endothelial cells (ECs). Although it is established that NRP1 is essential for angiogenesis, little is known about its role in EC homeostasis. Here, we report that NRP1 promotes mitochondrial function in ECs by preventing iron accumulation and iron-induced oxidative stress through a VEGF-independent mechanism in non-angiogenic ECs. Furthermore, NRP1-deficient ECs have reduced growth and show the hallmarks of cellular senescence. We show that a subcellular pool of NRP1 localizes in mitochondria and interacts with the mitochondrial transporter ATP-binding cassette B8 (ABCB8). NRP1 loss reduces ABCB8 levels, resulting in iron accumulation, iron-induced mitochondrial superoxide production, and iron-dependent EC senescence. Treatment of NRP1-deficient ECs with the mitochondria-targeted antioxidant compound mitoTEMPO or with the iron chelator deferoxamine restores mitochondrial activity, inhibits superoxide production, and protects from cellular senescence. This finding identifies an unexpected role of NRP1 in EC homeostasis

High current densities in copper microcoils : influence of substrate on failure mode

Copper planar microcoils were processed by U.V. lithography on SiO2/Si and Kapton®. The coils were packaged on different supports in order to create varying thermal exchange conditions. The electric current was increased step by step until the electric connection breaks, the microcoils remaining free on a thermal point of view. The copper temperature was estimated from its resistivity. It allowed to show that the thermal exchange mode of the wire-bonded microcoils is conductive. The current density was calculated taking into account the deterioration of the coils by oxidation. Its maximum value is linearly decreasing with the thermal exchange ability of the support. The failure modes of the microcoils are related to track melting and oxidation, the current density remaining one order too weak to induce electromigration

Neuropilin-1 interacts with VE-cadherin and TGFBR2 to stabilize adherens junctions and prevent activation of endothelium under flow.

Linear and disturbed flow differentially regulate gene expression, with disturbed flow priming endothelial cells (ECs) for a proinflammatory, atheroprone expression profile and phenotype. Here, we investigated the role of the transmembrane protein neuropilin-1 (NRP1) in ECs exposed to flow using cultured ECs, mice with an endothelium-specific knockout of NRP1, and a mouse model of atherosclerosis. We demonstrated that NRP1 was a constituent of adherens junctions that interacted with VE-cadherin and promoted its association with p120 catenin, stabilizing adherens junctions and inducing cytoskeletal remodeling in alignment with the direction of flow. We also showed that NRP1 interacted with transforming growth factor-β (TGF-β) receptor II (TGFBR2) and reduced the plasma membrane localization of TGFBR2 and TGF-β signaling. NRP1 knockdown increased the abundance of proinflammatory cytokines and adhesion molecules, resulting in increased leukocyte rolling and atherosclerotic plaque size. These findings describe a role for NRP1 in promoting endothelial function and reveal a mechanism by which NRP1 reduction in ECs may contribute to vascular disease by modulating adherens junction signaling and promoting TGF-β signaling and inflammation

Progress in OCT-based Through Silicon Via (TSV) metrology

International audienceWe report on progress in Time-Domain OCT (optical coherence tomography) applied to TSV (vertical interconnect accesses in silicon, enabling stacking of devices). Transitioning from the common scalar approach to an electromagnetic one, and combining it with a damped least squares approach, we enhance the accuracy of TSV height measurements

Pro-invasive effect of proto-oncogene PBF is modulated by an interaction with cortactin

Abstract CONTEXT: Metastatic disease is responsible for the majority of endocrine cancer deaths. New therapeutic targets are urgently needed to improve patient survival rates. OBJECTIVE: The proto-oncogene PTTG1-binding factor (PBF/PTTG1IP) is overexpressed in multiple endocrine cancers and circumstantially associated with tumor aggressiveness. This study aimed to understand the role of PBF in tumor cell invasion and identify possible routes to inhibit its action. Design, Setting, Patients, and Interventions: Thyroid, breast, and colorectal cells were transfected with PBF and cultured for in vitro analysis. PBF and cortactin (CTTN) expression was determined in differentiated thyroid cancer and The Cancer Genome Atlas RNA-seq data. PRIMARY OUTCOME MEASURE: Pro-invasive effects of PBF were evaluated by 2D Boyden chamber, 3D organotypic, and proximity ligation assays. RESULTS: Our study identified that PBF and CTTN physically interact and co-localize, and that this occurs at the cell periphery, particularly at the leading edge of migrating cancer cells. Critically, PBF induces potent cellular invasion and migration in thyroid and breast cancer cells, which is entirely abrogated in the absence of CTTN. Importantly, we found that CTTN is over-expressed in differentiated thyroid cancer, particularly in patients with regional lymph node metastasis, which significantly correlates with elevated PBF expression. Mutation of PBF (Y174A) or pharmacological intervention modulates the PBF: CTTN interaction and attenuates the invasive properties of cancer cells. CONCLUSION: Our results demonstrate a unique role for PBF in regulating CTTN function to promote endocrine cell invasion and migration, as well as identify a new targetable interaction to block tumor cell movement

Effect of undercut on the resonant behaviour of silicon nitride cantilevers

We present a systematic investigation of the dynamic properties of silicon nitride cantilevers in air. The thermal noise spectra of cantilevers have been measured using a home-made optical deflection setup. Torsional and flexural resonances up to the seventh mode are observed. The dependence of resonance frequencies on the dimensions and mode number is studied in detail. It is found that undercut increases the effective length of the cantilever by a value ?L, which depends on the undercut distance and the resonance mode shape, but not on the cantilever length. Finite element modelling confirms these experimental findings. A simple model is suggested for the shape of the undercut region, which agrees well with experimental findings. Using this model, the undercut cantilever can be approximated by a stepped beam, where the clamp distance depends on the underetch duration and the mode shape.Kavli Institute of NanoscienceApplied Science