Loss of Caveolin-1 Accelerates Neurodegeneration and Aging

The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1), a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease.We analyzed brains from young (Yg, 3-6 months), middle age (Md, 12 months), aged (Ag, >18 months), and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression.Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease

Crystallographic data collection using a 0.22% bandwidth multilayer

To bridge the gap between traditional multilayer and crystal optics a high-resolution multilayer monochromator with a bandwidth of 0.22% has been designed and installed on a bending-magnet beamline (F3) at the Cornell High Energy Synchrotron Source (CHESS) to provide an unfocused monochromatic X-ray beam for protein crystallography experiments. Crystallographic data of excellent quality from a medium-sized protein, Concanavalin A, were collected and processed using standard Crystallographic programs. The data were successfully used for a structure solution and refinement. The flux from the multilayer monochromator is enhanced, relative to that from a flat Si(111) monochromator, by a factor of 5; consequently, data collection is faster and/or smaller samples may be used. At the same time, the bandwidth is narrow enough to avoid streaked spots. This experiment suggests that multilayer optics may play a valuable role in satisfying the demands of the structural biology community for rapid X-ray data collection, particularly at under-utilized bending-magnet beamlines. © 2005 International Union of Crystallography Printed in Great Britain - all rights reserved.link_to_subscribed_fulltex

Multilayer X-ray optics at CHESS

Almost half of the X-ray beamlines at the Cornell High Energy Synchrotron Source (CHESS) are based on multilayer optics. 'Traditional' multilayers with an energy resolution of ΔE/E≃ 2% are routinely used to deliver X-ray flux enhanced by a factor of 102 in comparison with standard Si(111) optics. Sagittal-focusing multilayers with fixed radius provide an additional factor of 10 gain in flux density. High-resolution multilayer optics with ΔE/E≃ 0.2% are now routinely used by MacCHESS crystallographers. New wide-bandpass multilayers with ΔE/E = 5% and 10% have been designed and tested for potential applications in macromolecular crystallography. Small d-spacing multilayers with d≤ 20 Å have been successfully used to extend the energy range of multilayer optics. Analysis of the main characteristics of the Mo/B4C and W/B4C small d-spacing multilayer optics shows enhancement in their performance at higher energies. Chemical vapour deposited SiC, with a bulk thermal conductivity of a factor of two higher than that of silicon, has been successfully introduced as a substrate material for multilayer optics. Characteristics of different types of multilayer optics at CHESS beamlines and their applications in a variety of scattering, diffraction and imaging techniques are discussed. © 2006 International Union of Crystallography. Printed in Great Britain - All rights reserved.link_to_subscribed_fulltex

Few-femtosecond timing at fourth-generation X-ray light sources

The combined qualities of ultra high intensity and ultra short pulse duration, available at 4th generation X ray light sources provide tremendous opportunities for investigation of ultrafast dynamics in complex systems. Such studies require femtosecond synchronization between pump and probe laser pulses. However, the necessary level of stability of the accelerator is currently impossible to achieve. Fortunately, this issue can be managed if the relative timing jitter between light sources is accurately monitored, allowing subsequent data sorting. We present a new, robust, non invasive approach that provides 4.6 fs rms temporal resolution. This is, to our knowledge, the best resolution ever achieved between an FEL and an external laser. Our method employs coherent terahertz radiation generated at the end of the X ray undulator by the same electron bunch that emits the X ray pulse. Therefore, this method can be universally applied at any advanced light source working with ultra short electron bunches and undulator