PSD-95 Is Associated with the Postsynaptic Density and Not with the Presynaptic Membrane at Forebrain Synapses

PSD-95, a prominent protein component of the postsynaptic density (PSD) fraction from rat forebrain, has been localized by light microscopy to dendrites of hippocampal neurons (Cho et al., 1992) and to the presynaptic plexus of cerebellar basket cells (Kistner et al., 1993). Here we extend these studies to show that an affinity-purified antibody to PSD-95 labels the dendrites of most neurons in the forebrain and of a subset of neurons in the cerebellum. To confirm that PSD-95 is associated with the PSD at forebrain synapses and to clarify whether it is also associated with the presynaptic membrane, we employed immunogold electron microscopy of forebrain synaptosomes. Gold-labeled antibodies to PSD-95 labeled postsynaptic densities in both intact and lysed forebrain synaptosomes but did not label presynaptic terminals or the presynaptic membrane. The asymmetric distribution of PSD-95 at synapses contrasts with that of its homologs, disks-large and ZO-1, which are arranged symmetrically at septate and tight junctions, respectively

Wave shapes in alternating DSC

ADSC with its periodical temperature programs combines the features of DSC measured at high heating rate (high sensitivity) with those at low heating rate (high temperature resolution). In addition, the "reversing” cp effects can be separated from the "non-reversing” latent heat effects. Various periodical temperature programs can be applied. This paper compares the different possible temperature programs and their algorithms for the cp determination for metal, metal oxide and polymer of various properties. Simulated and measured results for various wave shapes and samples are presented. The relevant sample properties and their influence on the measurements are identified and guiding rules for the proper choice of the various experimental parameters are given. Measurements with different samples, performed with the new METTLER TOLEDO STARe-System, are shown and compared with the simulation results. The simulations and the measurements clearly show that the alternating techniques can yield new information about sample properties, but are susceptible to the proper choice of the various experimental parameter

FACTS Special Issue on Migration and Health

Migration is a global phenomenon involving hundreds of millions of people, with major social and economic impacts on migrants in their countries of origin and destination and on their communities. In the U.S., California is by far the most affected state by these population movements. The University of California Global Health Institute (UCGHI), Center of Expertise on Migration and Health (COEMH) is devoted to systematically studying the health consequences of global population movements and developing more effective strategies to address them. A key objective of the Center is to enhance educational opportunities related to migration and health. To do this, the Center implements graduate education, conducts research on immigrant and refugee communities, establishes distance education opportunities, and develops transnational collaborations. These activities provide a rich, real-world environment for training the next generation of leaders who will respond to emerging health issues related to migration. The Center’s annual Research Training Workshop is one such activity, resulting in rich discussions, cross-disciplinary interactions, and invaluable learning opportunities. This special issue on migration and health stems from the Research Training Workshop held on June 21-23, 2011, which was organized by COEMH. The workshop brought nineteen graduate students and postdoctoral fellows together in a multi-disciplinary setting to present their research and receive constructive feedback from University of California faculty members. Each paper presented in this special issue represents a unique issue related to migration and health.L'immigration est un phénomène mondial qui concerne des centaines de millions de personnes, et qui a des conséquences socio-économiques majeures sur les migrants dans leur pays d'origine et dans leur pays de destination, et également sur leurs communautés. Aux Etats-Unis, la Californie est de loin l'état le plus touché par ces mouvements de population. Le COEMH (Center of Expertise on Migration and Health) de l’UCGHI (University of California Global Health Institute), est spécialisé dans l'étude systématique des conséquences des mouvements de population sur la santé et dans l'élaboration de stratégies efficaces pour y remédier. L'un des objectifs clés du Centre est d'accroître les opportunités d'apprentissage liées à l'immigration et à la santé. Pour cela, le Centre met un œuvre un enseignement supérieur, conduit des recherches sur les communautés d'immigrants et de réfugiés, crée des opportunités d'enseignement à distance, et développe des collaborations transnationales. Ces activités constituent un environnement concret permettant de former la prochaine génération de dirigeants qui devra faire face aux problèmes de santé émergents liés à l'immigration. Le Research Training Workshop est l'une des initiatives annuelles du Centre. Il consiste en des débats approfondis, des interactions pluridisciplinaires et des opportunités d'apprentissage utiles. Ce numéro spécial consacré à l'immigration et à la santé découle du Research Training Workshop organisé par le COEMH du 21 au 23 juin 2011. Cet atelier a réuni dix-neuf étudiants diplômés et post-doctorants dans un contexte pluridisciplinaire qui ont présenté leurs travaux de recherche et reçu des commentaires constructifs de la part des membres de la faculté de l'Université de Californie. Chaque article de ce numéro spécial traite d'un sujet spécifique lié à l'immigration et à la santé.La migración es un fenómeno de escala mundial que involucra a cientos de millones de personas  y tiene un impacto social y económico tanto en los inmigrantes, como ensus países de origen y  destino, y en las comunidades en las que viven. En los Estados Unidos, el estado más afectado por estos movimientos de población es  California. El Centro de Expertos en Migración y Salud (COEMH por sus siglas en inglés) del Instituto de Salud Global de la Universidad de California (UCGHI por sus siglas en inglés) se dedica a realizar estudios sistemáticos sobre las consecuencias que estos  movimientos de población mundial tienen sobre la salud,  a fin de crear estrategias efectivas para abordarlos. Un objetivo clave del Centro es mejorar las oportunidades educativas relacionadas con la inmigración y la salud.  Para ello, el Centro imparte enseñanza universitaria, realiza estudios sobre las comunidades de inmigrantes y refugiados, crea oportunidades de educación a distancia y desarrolla colaboraciones transnacionales. Estas actividades proporcionan un ambiente rico en experiencias reales  para formar a la próxima generación de líderes que darán respuesta a los problemas de salud emergentes relacionados con la migración. Una de estas oportunidades que el Centro ofrece anualmente es el Taller de Formación e Investigación  que propicia profusos debates, e interacciones interdisciplinarias, además de valiosas oportunidades de aprendizaje. Este número especial sobre inmigración y salud nació a partir del Taller de Formación e Investigación celebrado del 21 al 23 de junio de 2011, organizado por COEMH. El taller reunió a 19 estudiantes de postgrado y becarios posdoctorales en un entorno multidisciplinario dónde pudieron presentar sus investigaciones y escuchar opiniones constructivas por parte del cuerpo de docentes de la Universidad de California. Cada trabajo presentado en este número especial representa un aspecto único relacionado con la migración y la salud

The Influence of the Degree of Heterogeneity on the Elastic Properties of Random Sphere Packings

The macroscopic mechanical properties of colloidal particle gels strongly depend on the local arrangement of the powder particles. Experiments have shown that more heterogeneous microstructures exhibit up to one order of magnitude higher elastic properties than their more homogeneous counterparts at equal volume fraction. In this paper, packings of spherical particles are used as model structures to computationally investigate the elastic properties of coagulated particle gels as a function of their degree of heterogeneity. The discrete element model comprises a linear elastic contact law, particle bonding and damping. The simulation parameters were calibrated using a homogeneous and a heterogeneous microstructure originating from earlier Brownian dynamics simulations. A systematic study of the elastic properties as a function of the degree of heterogeneity was performed using two sets of microstructures obtained from Brownian dynamics simulation and from the void expansion method. Both sets cover a broad and to a large extent overlapping range of degrees of heterogeneity. The simulations have shown that the elastic properties as a function of the degree of heterogeneity are independent of the structure generation algorithm and that the relation between the shear modulus and the degree of heterogeneity can be well described by a power law. This suggests the presence of a critical degree of heterogeneity and, therefore, a phase transition between a phase with finite and one with zero elastic properties.Comment: 8 pages, 6 figures; Granular Matter (published online: 11. February 2012

C-Terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors

NMDA receptors interact via the extended intracellular C-terminal domain of the NR2 subunits with constituents of the postsynaptic density for purposes of retention, clustering, and functional regulation at central excitatory synapses. To examine the role of the C-terminal domain of NR2A in the synaptic localization and function of NR2A-containing NMDA receptors in hippocampal Schaffer collateral–CA1 pyramidal cell synapses, we analyzed mice which express NR2A only in its C-terminally truncated form. In CA1 cell somata, the levels, activation, and deactivation kinetics of extrasynaptic NMDA receptor channels were comparable in wild-type and mutant NR2A^(ΔC/ΔC) mice. At CA1 cell synapses, however, the truncated receptors were less concentrated than their full-length counterparts, as indicated by immunodetection in cultured neurons, synaptosomes, and postsynaptic densities. In the mutant, the NMDA component of evoked EPSCs was reduced in a developmentally progressing manner and was even more reduced in miniature EPSCs (mEPSCs) elicited by spontaneous glutamate release. Moreover, pharmacologically isolated NMDA currents evoked by synaptic stimulation had longer latencies and displayed slower rise and decay times, even in the presence of an NR2B-specific antagonist. These data strongly suggest that the C-terminal domain of NR2A subunits is important for the precise synaptic arrangement of NMDA receptors

The minimum orbital period in thermal-timescale mass transfer

We show that the usual picture of supersoft X-ray binary evolution as driven by conservative thermal-timescale mass transfer cannot explain the short orbital periods of RX J0537.7-7034 (3.5 hr) and 1E 0035.4-7230 (4.1 hr). Non-conservative evolution may produce such periods, but requires very significant mass loss, and is highly constrained.Comment: 6 pages, 5 figures; to appear in MNRA

Keck Spectroscopy of Faint 3<z<8 Lyman Break Galaxies:- Evidence for a Declining Fraction of Emission Line Sources In the Redshift Range 6<z<8

Using deep Keck spectroscopy of Lyman break galaxies selected from infrared imaging data taken with WFC3/IR onboard the Hubble Space Telescope, we present new evidence for a reversal in the redshift-dependent fraction of star forming galaxies with detectable Lyman alpha emission in the redshift range 6.3 < z < 8.8. Our earlier surveys with the DEIMOS spectrograph demonstrated a significant increase with redshift in the fraction of line emitting galaxies over the interval 4 < z < 6, particularly for intrinsically faint systems which dominate the luminosity density. Using the longer wavelength sensitivities of LRIS and NIRSPEC, we have targeted 19 Lyman break galaxies selected using recent WFC3/IR data whose photometric redshifts are in the range 6.3 < z < 8.8 and which span a wide range of intrinsic luminosities. Our spectroscopic exposures typically reach a 5-sigma sensitivity of < 50 A for the rest-frame equivalent width (EW) of Lyman alpha emission. Despite the high fraction of emitters seen only a few hundred million years later, we find only 2 convincing and 1 possible line emitter in our more distant sample. Combining with published data on a further 7 sources obtained using FORS2 on the ESO VLT, and assuming continuity in the trends found at lower redshift, we discuss the significance of this apparent reversal in the redshift-dependent Lyman alpha fraction in the context of our range in continuum luminosity. Assuming all the targeted sources are at their photometric redshift and our assumptions about the Lyman alpha EW distribution are correct, we would expect to find so few emitters in less than 1% of the realizations drawn from our lower redshift samples. Our new results provide further support for the suggestion that, at the redshifts now being probed spectroscopically, we are entering the era where the intergalactic medium is partially neutral.Comment: 8 pages, 5 figures, Accepted to ApJ 10/1/1

Trends in Cancer-Center Spending on Advertising in the United States, 2005 to 2014

In the United States, cancer centers commonly advertise clinical services directly to the public. Potential benefits of such advertising include informing patients about available treatments and reducing the stigma of cancer.1, 2 Potential risks include misleading vulnerable patients and creating false hopes, increasing demand for unnecessary tests and treatments, adversely affecting existing clinician-patient relationships, and increasing healthcare costs.3, 4 Understanding trends in the advertising spending of cancer centers and the characteristics of the centers that spend the most can inform the debate about the impact of these advertisements. Our hypothesis was that advertising spending has increased and that spending is concentrated among for-profit cancer centers

The importance of structural softening for the evolution and architecture of passive margins

Lithospheric extension can generate passive margins that bound oceans worldwide. Detailed geological and geophysical studies in present and fossil passive margins have highlighted the complexity of their architecture and their multi-stage deformation history. Previous modeling studies have shown the significant impact of coarse mechanical layering of the lithosphere (2 to 4 layer crust and mantle) on passive margin formation. We built upon these studies and design high-resolution (~100-300 m) thermo-mechanical numerical models that incorporate finer mechanical layering (kilometer scale) mimicking tectonically inherited heterogeneities. During lithospheric extension a variety of extensional structures arises naturally due to (1) structural softening caused by necking of mechanically strong layers and (2) the establishment of a network of weak layers across the deforming multi-layered lithosphere. We argue that structural softening in a multi-layered lithosphere is the main cause for the observed multi-stage evolution and architecture of magma-poor passive margins