Müller glia activation in response to inherited retinal degeneration is highly varied and disease-specific

Despite different aetiologies, most inherited retinal disorders culminate in photoreceptor loss, which induces concomitant changes in the neural retina, one of the most striking being reactive gliosis by Müller cells. It is typically assumed that photoreceptor loss leads to an upregulation of glial fibrilliary acidic protein (Gfap) and other intermediate filament proteins, together with other gliosis-related changes, including loss of integrity of the outer limiting membrane (OLM) and deposition of proteoglycans. However, this is based on a mix of both injury-induced and genetic causes of photoreceptor loss. There are very few longitudinal studies of gliosis in the retina and none comparing these changes across models over time. Here, we present a comprehensive spatiotemporal assessment of features of gliosis in the degenerating murine retina that involves Müller glia. Specifically, we assessed Gfap, vimentin and chondroitin sulphate proteoglycan (CSPG) levels and outer limiting membrane (OLM) integrity over time in four murine models of inherited photoreceptor degeneration that encompass a range of disease severities (Crb1rd8/rd8, Prph2+/Δ307, Rho-/-, Pde6brd1/rd1). These features underwent very different changes, depending upon the disease-causing mutation, and that these changes are not correlated with disease severity. Intermediate filament expression did indeed increase with disease progression in Crb1rd8/rd8 and Prph2+/Δ307, but decreased in the Prph2+/Δ307 and Pde6brd1/rd1 models. CSPG deposition usually, but not always, followed the trends in intermediate filament expression. The OLM adherens junctions underwent significant remodelling in all models, but with differences in the composition of the resulting junctions; in Rho-/- mice, the adherens junctions maintained the typical rod-Müller glia interactions, while in the Pde6brd1/rd1 model they formed predominantly between Müller cells in late stage of degeneration. Together, these results show that gliosis and its associated processes are variable and disease-dependent

Instanton-soliton loops in 5D super-Yang-Mills

C.P. is a Royal Society Research Fellow and is partly supported by U.S. DOE Grants DOESC0010008, DOE-ARRA-SC0003883 and DOE-DE-SC000789

From non-semisimple Hopf algebras to correlation functions for logarithmic CFT

We use factorizable finite tensor categories, and specifically the representation categories of factorizable ribbon Hopf algebras H, as a laboratory for exploring bulk correlation functions in local logarithmic conformal field theories. For any ribbon Hopf algebra automorphism omega of H we present a candidate for the space of bulk fields and endow it with a natural structure of a commutative symmetric Frobenius algebra. We derive an expression for the corresponding bulk partition functions as bilinear combinations of irreducible characters; as a crucial ingredient this involves the Cartan matrix of the category. We also show how for any candidate bulk state space of the type we consider, correlation functions of bulk fields for closed oriented world sheets of any genus can be constructed that are invariant under the natural action of the relevant mapping class group.Comment: 41 pages, several figures. version 2: typos corrected, bibliography updated, introduction extended, a few minor clarifications adde

An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D

Background: The phenotypic effects of sequence variations in protein-coding regions come about primarily via their effects on the resulting structures, for example by disrupting active sites or affecting structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms of their structural manifestation. Although many mutations occur within domains whose structure has been solved, many more occur within genes whose protein products have not been structurally characterized.Results: Here we present 3DSim (3D Structural Implication of Mutations), a database and web application facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein structures even where the structure of the protein of interest is unknown. The server displays information on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with domains predicted to belong to structural families in the CATH database. Mappings between domain sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 three-dimensional structures corresponding to CATH structural domains are currently included in 3DSim; these domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the distribution of mutations in structural space.Conclusion: The server is publicly available at http://3DSim.bioinfo.cnio.es/. In addition, the database containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the functionality is available through programmatic web service access

On Hierarchy and Equivalence of Relativistic Equations for Massive Fields

A non-canonical correspondence of the complete sets of solutions to the Dirac and Klein-Gordon free equations in Minkowski space-time is established. This allows for a novel viewpoint on the relationship of relativistic equations for different spins and on the origin of spinor transformations. In particular, starting from a solution to the Dirac equation, one obtains a chain of other solutions to both Dirac and Klein-Gordon equations. A comparison with the massless case is performed, and examples of non-trivial singular solutions are presented. A generalization to Riemannian space-time and inclusion of interactions are briefly discussed.Comment: 7 pages, twocolumn. Problem of construction the hierarchy of solutions in the massive case reformulate

Symbols of One-Loop Integrals From Mixed Tate Motives

We use a result on mixed Tate motives due to Goncharov (arXiv:alg-geom/9601021) to show that the symbol of an arbitrary one-loop 2m-gon integral in 2m dimensions may be read off directly from its Feynman parameterization. The algorithm proceeds via recursion in m seeded by the well-known box integrals in four dimensions. As a simple application of this method we write down the symbol of a three-mass hexagon integral in six dimensions.Comment: 13 pages, v2: minor typos correcte

Correlation Functions in 2-Dimensional Integrable Quantum Field Theories

In this talk I discuss the form factor approach used to compute correlation functions of integrable models in two dimensions. The Sinh-Gordon model is our basic example. Using Watson's and the recursive equations satisfied by matrix elements of local operators, I present the computation of the form factors of the elementary field $\phi(x)$ and the stress-energy tensor $T_{\mu\nu}(x)$ of the theory.Comment: 19pp, LATEX version, (talk at Como Conference on ``Integrable Quantum Field Theories''

Health of Philippine Emigrants Study (HoPES): study design and rationale.

BackgroundImmigrants to the United States are usually healthier than their U.S.-born counterparts, yet the health of immigrants declines with duration of stay in the U.S. This pattern is often seen for numerous health problems such as obesity, and is usually attributed to acculturation (the adoption of "American" behaviors and norms). However, an alternative explanation is secular trends, given that rates of obesity have been rising globally. Few studies of immigrants are designed to distinguish the effects of acculturation versus secular trends, in part because most studies of immigrants are cross-sectional, lack baseline data prior to migration, and do not have a comparison group of non-migrants in the country of origin. This paper describes the Health of Philippine Emigrants Study (HoPES), a study designed to address many of these limitations.MethodsHoPES is a dual-cohort, longitudinal, transnational study. The first cohort consisted of Filipinos migrating to the United States (n = 832). The second cohort consisted of non-migrant Filipinos who planned to remain in the Philippines (n = 805). Baseline data were collected from both cohorts in 2017 in the Philippines, with follow-up data collection planned over 3 years in either the U.S. for the migrant cohort or the Philippines for the non-migrant cohort. At baseline, interviewers administered semi-structured questionnaires that assessed demographic characteristics, diet, physical activity, stress, and immigration experiences. Interviewers also measured weight, height, waist and hip circumferences, blood pressure, and collected dried blood spot samples.DiscussionMigrants enrolled in the study appear to be representative of recent Filipino migrants to the U.S. Additionally, migrant and non-migrant study participants are comparable on several characteristics that we attempted to balance at baseline, including age, gender, and education. HoPES is a unique study that approximates a natural experiment from which to study the effects of immigration on obesity and other health problems. A number of innovative methodological strategies were pursued to expand the boundaries of current immigrant health research. Key to accomplishing this research was investment in building collaborative relationships with stakeholders across the U.S. and the Philippines with shared interest in the health of migrants

Form factors at strong coupling via a Y-system

We compute form factors in planar N=4 Super Yang-Mills at strong coupling. Namely we consider the overlap between an operator insertion and 2n gluons. Through the gauge/string duality these are given by minimal surfaces in AdS space. The surfaces end on an infinite periodic sequence of null segments at the boundary of AdS. We consider surfaces that can be embedded in AdS_3. We derive set of functional equations for the cross ratios as functions of the spectral parameter. These equations are of the form of a Y-system. The integral form of the Y-system has Thermodynamics Bethe Ansatz form. The area is given by the free energy of the TBA system or critical value of Yang-Yang functional. We consider a restricted set of operators which have small conformal dimension