Mutations in the LIS1 gene cause lissencephaly, a human neuronal migration disorder. LIS1 binds dynein and the dynein-associated proteins Nde1 (formerly known as NudE), Ndel1 (formerly known as NUDEL), and CLIP-170, as well as the catalytic alpha dimers of brain cytosolic platelet activating factor acetylhydrolase (PAF-AH). The mechanism coupling the two diverse regulatory pathways remains unknown. We report the structure of LIS1 in complex with the alpha2/alpha2 PAF-AH homodimer. One LIS1 homodimer binds symmetrically to one alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta propellers. The same surface of LIS1 contains sites of mutations causing lissencephaly and overlaps with a putative dynein binding surface. Ndel1 competes with the alpha2/alpha2 homodimer for LIS1, but the interaction is complex and requires both the N- and C-terminal domains of LIS1. Our data suggest that the LIS1 molecule undergoes major conformational rearrangement when switching from a complex with the acetylhydrolase to the one with Ndel1.
Magnetic resonance (MR) imaging can provide critical diagnostic and anatomic information while avoiding the use of ionizing radiation, but it has a unique set of safety risks associated with its reliance on large static and changing magnetic fields, high-powered radiofrequency coil systems, and exogenous contrast agents. It is crucial for radiologists to understand these risks and how to mitigate them to protect themselves, their colleagues, and their patients from avoidable harm and to comply with safety regulations at MR imaging sites. Basic knowledge of MR imaging physics and hardware is necessary for radiologists to understand the origin of safety regulations and to avoid common misconceptions that could compromise safety. Each of the components of the MR imaging unit can be a factor in injuries to patients and personnel. Safety risks include translational force and torque, projectile injury, excessive specific absorption rate, burns, peripheral neurostimulation, interactions with active implants and devices, and acoustic injury. Standards for MR imaging device safety terminology were first issued in 2005 and are required by the U.S. Food and Drug Administration, with devices labeled as "MR safe," "MR unsafe," or "MR conditional." MR imaging contrast agent safety is also discussed. Additional technical and safety policies relate to pediatric, unconscious, incapacitated, or pregnant patients and pregnant imaging personnel. Division of the MR imaging environment into four distinct, clearly labeled zones--with progressive restriction of entry and increased supervision for higher zones--is a mandatory and key aspect in avoidance of MR imaging-related accidents. All MR imaging facilities should have a documented plan to handle emergencies within zone IV, including cardiac arrest or code, magnet quench, and fires. Policies from the authors' own practice are provided for additional reference. Online supplemental material is available for this article.
We describe the design and operation of an open-access, very-low-field, magnetic resonance imaging (MRI) system for in-vivo hyperpolarized 3 He imaging of the human lungs. This system permits the study of lung function in both horizontal and upright postures, a capability with important implications in pulmonary physiology and clinical medicine, including asthma and obesity. The imager uses a bi-planar B 0 coil design that produces an optimized 65 G (6.5 mT) magnetic field for 3 He MRI at 210 kHz. Three sets of bi-planar coils produce the x, y, and z magnetic field gradients while providing a 79-cm inter-coil gap for the imaging subject. We use solenoidal Q-spoiled RF coils for operation at low frequencies, and are able to exploit insignificant sample loading to allow for pretuning/matching schemes and for accurate pre-calibration of flip angles. We obtain sufficient SNR to acquire 2D 3 He images with up to 2.8 mm resolution, and present initial 2D and 3D 3 He images of human lungs in both supine and upright orientations. 1 H MRI can also be performed for diagnostic and calibration reasons.
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