Structural diversity of neuronal calcium sensor proteins and insights for activation of retinal guanylyl cyclase by GCAP1.

Neuronal calcium sensor (NCS) proteins, a sub-branch of the calmodulin superfamily, are expressed in the brain and retina where they transduce calcium signals and are genetically linked to degenerative diseases. The amino acid sequences of NCS proteins are highly conserved but their physiological functions are quite different. Retinal recoverin controls Ca(2) (+)-dependent inactivation of light-excited rhodopsin during phototransduction, guanylyl cyclase activating proteins 1 and 2 (GCAP1 and GCAP2) promote Ca(2) (+)-dependent activation of retinal guanylyl cyclases, and neuronal frequenin (NCS-1) modulates synaptic activity and neuronal secretion. Here we review the molecular structures of myristoylated forms of NCS-1, recoverin, and GCAP1 that all look very different, suggesting that the attached myristoyl group helps to refold these highly homologous proteins into different three-dimensional folds. Ca(2) (+)-binding to both recoverin and NCS-1 cause large protein conformational changes that ejects the covalently attached myristoyl group into the solvent exterior and promotes membrane targeting (Ca(2) (+)-myristoyl switch). The GCAP proteins undergo much smaller Ca(2) (+)-induced conformational changes and do not possess a Ca(2) (+)-myristoyl switch. Recent structures of GCAP1 in both its activator and Ca(2) (+)-bound inhibitory states will be discussed to understand structural determinants that control their Ca(2) (+)-dependent activation of retinal guanylyl cyclases

Optical measurements of aerosol size distributions in Great Smoky Mountains National Park: particle hygroscopicity and its impact on visibility

National Park Service.Includes bibliographical references (pages 70-73).Aerosol size distributions were measured during the 1995 Southeastern Aerosol and Visibility Study (SEAVS) in Great Smoky Mountains National Park using a PMS ASASP-X optical aerosol spectrometer. Ambient aerosol was conditioned in a relative humidity (RH) controlled inlet before sampling. 130 dry (RH ~ 15%) and 112 humidified aerosol size distributions, plus 24 distributions at ambient RH, were recorded during daylight hours for aerosol in the size range 0.1 < Dp <2.5 µ. Particle light scattering from the ASASP-X was inverted to particle sizes using Mie theory and applying a refractive index of either 1.530-0i or 1.501-0i for dry conditions, depending on the ambient aerosol chemical composition. A dry aerosol volume concentration time line from this work, when compared with a similar time line of aerosol mass concentration from IMPROVE samplers, indicates the ASASP-X provided a reliable representation of temporal trends in the ambient aerosol loading. The median dry aerosol geometric mass mean diameter measured during SEAVS was 0.28 µm, with a range from 0.24 to 0.38 µm, and median geometric standard deviation of 1.64. Sequential dry and humidified aerosol size distributions were corrected for refractive index dependence on RH and used to derive ambient aerosol hygroscopicity as a function of RH. This work demonstrates that experimentally derived water absorption is equivalent to or less than predicted by theory, assuming ambient aerosol water uptake is dictated by ionic compounds that have a chemical composition consistent with the particle fine mass measured during SEAVS. In this work, special consideration is given to the uncertainty in derived aerosol water contents and the degree to which this uncertainty propagates to estimates of light scattering. An ultimate goal of this project is to augment visibility and radiative transfer models through a better understanding of how RH affects the ambient aerosol size distribution in the southeastern U.S.Funding agency: National Park Service # 1443-CA0001-92-0006 96.5

QMDS: A File System Metadata Management Service Supporting a Graph Data Model-Based Query Language

Proposes QMDS: a file system metadata management service that integrates all file system metadata and uses a graph model with attributes on nodes and edges

Psychosocial treatments of behavior symptoms in dementia: a systematic review of reports meeting quality standards.

OBJECTIVE: To provide a systematic review of selected experimental studies of psychosocial treatments of behavioral disturbances in dementia. Psychosocial treatments are defined here as strategies derived from one of three psychologically oriented paradigms (learning theory, unmet needs and altered stress thresholds). METHOD: English language reports published or in press by December 2006 were identified by means of database searches, checks of previous reviews and contact with recognized experts. Papers were appraised with respect to study design, participants' characteristics and reporting details. Because people with dementia often respond positively to personal contact, studies were included only if control conditions entailed similar levels of social attention or if one treatment was compared with another. RESULTS: Only 25 of 118 relevant studies met every specification. Treatment proved more effective than an attention control condition in reducing behavioral symptoms in only 11 of the 25 studies. Effect sizes were mostly small or moderate. Treatments with moderate or large effect sizes included aromatherapy, ability-focused carer education, bed baths, preferred music and muscle relaxation training. CONCLUSIONS: Some psychosocial interventions appear to have specific therapeutic properties, over and above those due to the benefits of participating in a clinical trial. Their effects were mostly small to moderate with a short duration of action. This limited action means that treatments will work best in specific, time-limited situations. In the few studies that addressed within-group differences, there were marked variations in response. Some participants benefited greatly from a treatment, while others did not. Interventions proved more effective when tailored to individuals' preferences

DI-MMAP: A High Performance Memory-Map Runtime for Data-Intensive Applications

Abstract not provide

Structural and functional conservation of key domains in InsP3 and ryanodine receptors.

Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6 Å) and without (3.0 Å) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore