ADAM2 Interactions with Mouse Eggs and Cell Lines Expressing α4/α9 (ITGA4/ITGA9) Integrins: Implications for Integrin-Based Adhesion and Fertilization

Integrins are heterodimeric cell adhesion molecules, with 18 α (ITGA) and eight β (ITGB) subunits forming 24 heterodimers classified into five families. Certain integrins, especially the α(4)/α(9) (ITGA4/ITGA9) family, interact with members of the ADAM (a disintegrin and metalloprotease) family. ADAM2 is among the better characterized and also of interest because of its role in sperm function. Having shown that ITGA9 on mouse eggs participates in mouse sperm-egg interactions, we sought to characterize ITGA4/ITGA9-ADAM2 interactions.An anti-β(1)/ITGB1 function-blocking antibody that reduces sperm-egg binding significantly inhibited ADAM2 binding to mouse eggs. Analysis of integrin subunit expression indicates that mouse eggs could express at least ten different integrins, five in the RGD-binding family, two in the laminin-binding family, two in the collagen-binding family, and ITGA9-ITGB1. Adhesion assays to characterize ADAM2 interactions with ITGA4/ITGA9 family members produced the surprising result that RPMI 8866 cell adhesion to ADAM2 was inhibited by an anti-ITGA9 antibody, noteworthy because ITGA9 has only been reported to dimerize with ITGB1, and RPMI 8866 cells lack detectable ITGB1. Antibody and siRNA studies demonstrate that ITGB7 is the β subunit contributing to RPMI 8866 adhesion to ADAM2.These data indicate that a novel integrin α-β combination, ITGA9-ITGB7 (α(9)β(7)), in RPMI 8866 cells functions as a binding partner for ADAM2. ITGA9 had previously only been reported to dimerize with ITGB1. Although ITGA9-ITGB7 is unlikely to be a widely expressed integrin and appears to be the result of "compensatory dimerization" occurring in the context of little/no ITGB1 expression, the data indicate that ITGA9-ITGB7 functions as an ADAM binding partner in certain cellular contexts, with implications for mammalian fertilization and integrin function

Effect of heating on the suppression of tearing modes in tokamaks

The suppression of (neoclassical) tearing modes is of great importance for the success of future fusion reactors like ITER. Electron cyclotron waves can suppress islands, both by driving noninductive current in the island region and by heating the island, causing a perturbation to the Ohmic plasma current. This Letter reports on experiments on the TEXTOR tokamak, investigating the effect of heating, which is usually neglected. The unique set of tools available on TEXTOR, notably the dynamic ergodic divertor to create islands with a fully known driving term, and the electron cyclotron emission imaging diagnostic to provide detailed 2D electron temperature information, enables a detailed study of the suppression process and a comparison with theory.open1159Nsciescopu

Magnetic Resonance Imaging in Peripheral Arterial Disease Reproducibility of the Assessment of Morphological and Functional Vascular Status

Objectives: The aim of the current study was to test the reproducibility of different quantitative magnetic resonance imaging (MRI) methods to assess the morphologic and functional peripheral vascular status and vascular adaptations over time in patients with peripheral arterial disease (PAD). Materials and methods: Ten patients with proven PAD (intermittent claudication) and arterial collateral formation within the upper leg and 10 healthy volunteers were included. All subjects underwent 2 identical MR examinations of the lower extremities on a clinical 1.5-T MR system, with a time interval of at least 3 days. The MR protocol consisted of 3D contrast-enhanced MR angiography to quantify the number of arteries and artery diameters of the upper leg, 2D cine MR phase contrast angiography flow measurements in the popliteal artery, dynamic contrast-enhanced (DCE) perfusion imaging to determine the influx constant and area under the curve, and dynamic blood oxygen level-dependent (BOLD) imaging in calf muscle to measure maximal relative T2* changes and time-to-peak. Data were analyzed by 2 independent MRI readers. Interscan and inter-reader reproducibility were determined as outcome measures and expressed as the coefficient of variation (CV). Results: Quantification of the number of arteries, artery diameter, and blood flow proved highly reproducible in patients (CV = 2.6%, 4.5%, and 15.8% at interscan level and 9.0%, 8.2%, and 7.0% at interreader level, respectively). Reproducibility of DCE and BOLD MRI was poor in patients with a CV up to 50.9%. Conclusions: Quantification of the morphologic vascular status by contrast-enhanced MR angiography, as well as phase contrast angiography MRI to assess macrovascular blood flow proved highly reproducible in both PAD patients and healthy volunteers and might therefore be helpful in studying the development of collateral arteries in PAD patients and in unraveling the mechanisms underlying this process. Functional assessment of the microvascular status using DCE and BOLD, MRI did not prove reproducible at 1.5 T and is therefore currently not suitable for (clinical) application in PAD