Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Theoretical Methods for Wave Propagation across Jointed Rock Masses

Different methods are presently available for the analysis of wave propagation across jointed rock masses with the consideration of multiple wave reflections between joints. These methods can be divided into two categories. One is based on the displacement discontinuity model for representing rock joints, where the displacements across a joint are discontinuous and the tractions are continuous, and the other is the equivalent medium method. For the first category, there are three methods, i.e., method of characteristics (MC), scattering matrix method (SMM) and virtual wave source method (VWS). MC solves the equation of motion by using the theory of characteristic curves. SMM is based on the definition of the scattering matrix in which the reflection and transmission coefficients of a set of joints are stored. VWS method replaces the joints in the rock mass with a virtual concept. For the second category, equivalent medium model treats the problem in the frame of continuum mechanics and simplifies it from an explicit wave propagation equation. The objective of this paper is to review and compare these theoretical methods. The comparison shows that the four solutions agree very well with each other. Some additional considerations about the advantages and disadvantages of these methods are also given in the pape

The identification of family subtype based on the assessment of subclinical levels of psychosis in relatives

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a complex psychiatric disorder characterized by high phenotypic heterogeneity. Previous studies have distinguished between familial and sporadic forms of schizophrenia and have suggested clinical differentiation between patients and relatives from sporadic and multiplex families. We will introduce a more refined method to distinguish between family subtypes based on psychosis dimension profiles in the relatives of schizophrenia patients.</p> <p>Methods</p> <p>Positive, negative, disorganization, mania, and depression scores were assessed in 1,392 relatives. Mixed Model Latent Class Analysis was used to identify family subtypes. A family subtype is a relatively homogeneous group of families with similar symptom profiles in the relatives in these families. Next, we investigated in 616 schizophrenia patients whether family subtype was associated with symptom profiles, IQ, cannabis dependence/abuse, or age of onset of psychosis.</p> <p>Results</p> <p>Based on the data of relatives, we identified two different family types: “healthy” and “at risk for psychiatric disorder”. Patients from at risk families obtained higher positive scores compared to patients from healthy families (Wald(1) = 6.6293, p = 0.010). No significant differences were found in any of the remaining variables.</p> <p>Conclusions</p> <p>Our findings confirm the existence of high-risk families and although we did not establish an etiological basis for the distinction between family types, genetic studies might reveal whether family subtype is associated with genetic heterogeneity.</p

Wave Propagation in Discontinuous Media by the Scattering Matrix Method

Propagation of elastic waves in discontinuous media is studied in this paper by the scattering matrix method (SMM). An electromagnetic transmission line analogy is also used to set up the mathematical model. The SMM operates in the frequency domain and allows for all wave polarizations (P, SV and SH). Rock masses are examples of discontinuous media in which the discontinuities (fractures or joints) influence wave propagation. Both elastic and viscoelastic joints are considered and the latter are described by Kelvin-Voigt, Maxwell and Burgers models. Rock joints with Coulomb slip behavior are also analyzed, by applying the averaging principle of Caughy (J Appl Mech 27:640-643, 1960). The evaluation of the effects of periodic discontinuities in a homogeneous medium is presented by introducing the concept of Bloch waves. The dispersion curves of these waves are useful to explain the existence of frequency bands of strong attenuation, also in the case of lossless (perfectly elastic) structures. Simple expressions of transmission and reflection coefficients are obtained. Finally, the SMM results are compared with those computed via the distinct element method (DEM). The comparisons are performed on a medium with joints with Coulomb slip behavior and the agreement is satisfactory, although the SMM must be applied in conjunction with the equivalent linearization technique. Even if the DEM is much more general, the SMM in these simple cases is extremely faster and provides a higher physical insigh