Atrial fibrillation and electrophysiology in transgenic mice with cardiac-restricted overexpression of FKBP12

Cardiomyocyte-restricted overexpression of FK506-binding protein 12 transgenic (αMyHC-FKBP12) mice develop spontaneous atrial fibrillation (AF). The aim of the present study is to explore the mechanisms underlying the occurrence of AF in αMyHC-FKBP12 mice. Spontaneous AF was documented by telemetry in vivo and Langendorff-perfused hearts of αMyHC-FKBP12 and littermate control mice in vitro. Atrial conduction velocity was evaluated by optical mapping. The patch-clamp technique was applied to determine the potentially altered electrophysiology in atrial myocytes. Channel protein expression levels were evaluated by Western blot analyses. Spontaneous AF was recorded in four of seven αMyHC-FKBP12 mice but in none of eight nontransgenic (NTG) controls. Atrial conduction velocity was significantly reduced in αMyHC-FKBP12 hearts compared with NTG hearts. Interestingly, the mean action potential duration at 50% but not 90% was significantly prolonged in αMyHC-FKBP12 atrial myocytes compared with their NTG counterparts. Consistent with decreased conduction velocity, average peak Na+ current ( INa) density was dramatically reduced and the INa inactivation curve was shifted by approximately +7 mV in αMyHC-FKBP12 atrial myocytes, whereas the activation and recovery curves were unaltered. The Nav1.5 expression level was significantly reduced in αMyHC-FKBP12 atria. Furthermore, we found increases in atrial Cav1.2 protein levels and peak L-type Ca2+ current density and increased levels of fibrosis in αMyHC-FKBP12 atria. In summary, cardiomyocyte-restricted overexpression of FKBP12 reduces the atrial Nav1.5 expression level and mean peak INa, which is associated with increased peak L-type Ca2+ current and interstitial fibrosis in atria. The combined electrophysiological and structural changes facilitated the development of local conduction block and altered action potential duration and spontaneous AF. NEW & NOTEWORTHY This study addresses a long-standing riddle regarding the role of FK506-binding protein 12 in cardiac physiology. The work provides further evidence that FK506-binding protein 12 is a critical component for regulating voltage-gated sodium current and in so doing has an important role in arrhythmogenic physiology, such as atrial fibrillation

Progenetix: 12 years of oncogenomic data curation

DNA copy number aberrations (CNAs) can be found in the majority of cancer genomes and are crucial for understanding the potential mechanisms underlying tumor initiation and progression. Since the first release in 2001, the Progenetix project (http://www.progenetix.org) has provided a reference resource dedicated to provide the most comprehensive collection of genome-wide CNA profiles. Reflecting the application of comparative genomic hybridization techniques to tens of thousands of cancer genomes, over the past 12 years our data curation efforts have resulted in a more than 60-fold increase in the number of cancer samples presented through Progenetix. In addition, new data exploration tools and visualization options have been added. In particular, the gene-specific CNA frequency analysis should facilitate the assignment of cancer genes to related cancer types. In addition, the new user file processing interface allows users to take advantage of the online tools, including various data representation options for proprietary data pre-publication. In this update article, we report recent improvements of the database in terms of content, user interface and online tool

Morphology of AGN Emission Line Regions in SDSS-IV MaNGA Survey

Extended narrow-line regions (NLRs) around active galactic nuclei (AGN) are shaped by the distribution of gas in the host galaxy and by the geometry of the circumnuclear obscuration, and thus they can be used to test the AGN unification model. In this work, we quantify the morphologies of the narrow-line regions in 308 nearby AGNs ($z=0-0.14$, \lbol $\sim 10^{42.4-44.1}$ \erg{}) from the MaNGA survey. Based on the narrow-line region maps, we find that a large fraction (81\%) of these AGN have bi-conical NLR morphology. The distribution of their measured opening angles suggests that the intrinsic opening angles of the ionization cones has a mean value of 85--98$^\circ$ with a finite spread of 39-44$^\circ$ (1-$\sigma$). Our inferred opening angle distribution implies a number ratio of type I to type II AGN of 1:1.6--2.3, consistent with other measurements of the type I / type II ratio at low AGN luminosities. Combining these measurements with the WISE photometry data, we find that redder mid-IR color (lower effective temperature of dust) corresponds to stronger and narrower photo-ionized bicones. This relation is in agreement with the unification model that suggests that the bi-conical narrow-line regions are shaped by a toroidal dusty structure within a few pc from the AGN. Furthermore, we find a significant alignment between the minor axis of host galaxy disks and AGN ionization cones. Together, these findings suggest that obscuration on both circumnuclear ($\sim$pc) and galactic ($\sim$ kpc) scales are important in shaping and orienting the AGN narrow-line regions.Comment: 14 pages, 7 figures, and 1 table, accepted for publication in MNRA

arrayMap 2014: an updated cancer genome resource

Somatic copy number aberrations (CNA) represent a mutation type encountered in the majority of cancer genomes. Here, we present the 2014 edition of arrayMap (http://www.arraymap.org), a publicly accessible collection of pre-processed oncogenomic array data sets and CNA profiles, representing a vast range of human malignancies. Since the initial release, we have enhanced this resource both in content and especially with regard to data mining support. The 2014 release of arrayMap contains more than 64 000 genomic array data sets, representing about 250 tumor diagnoses. Data sets included in arrayMap have been assembled from public repositories as well as additional resources, and integrated by applying custom processing pipelines. Online tools have been upgraded for a more flexible array data visualization, including options for processing user provided, non-public data sets. Data integration has been improved by mapping to multiple editions of the human reference genome, with the majority of the data now being available for the UCSC hg18 as well as GRCh37 versions. The large amount of tumor CNA data in arrayMap can be freely downloaded by users to promote data mining projects, and to explore special events such as chromothripsis-like genome pattern

Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes.

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases

Imaging Extended Emission-Line Regions of Obscured AGN with the Subaru Hyper Suprime-Cam Survey

Narrow-line regions excited by active galactic nuclei (AGN) are important for studying AGN photoionization and feedback. Their strong [O III] lines can be detected with broadband images, allowing morphological studies of these systems with large-area imaging surveys. We develop a new technique to reconstruct the [O III] images using the Subaru Hyper Suprime-Cam (HSC) Survey aided with spectra from the Sloan Digital Sky Survey (SDSS). The technique involves a careful subtraction of the galactic continuum to isolate emission from the [O III]$\lambda$5007 and [O III]$\lambda$4959 lines. Compared to traditional targeted observations, this technique is more efficient at covering larger samples with less dedicated observational resources. We apply this technique to an SDSS spectroscopically selected sample of 300 obscured AGN at redshifts 0.1 - 0.7, uncovering extended emission-line region candidates with sizes up to tens of kpc. With the largest sample of uniformly derived narrow-line region sizes, we revisit the narrow-line region size-luminosity relation. The area and radii of the [O III] emission-line regions are strongly correlated with the AGN luminosity inferred from the mid-infrared (15 $\mu$m rest-frame) with a power-law slope of $0.62^{+0.05}_{-0.06} \pm 0.10$ (statistical and systemic errors), consistent with previous spectroscopic findings. We discuss the implications for the physics of AGN emission-line region and future applications of this technique, which should be useful for current and next-generation imaging surveys to study AGN photoionization and feedback with large statistical samples.Comment: 20 pages, 13 figures, MNRAS submitte

Vaccination against Foot-and-mouth disease : do initial conditions affect its benefit?

When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease

Single vortex-antivortex pair in an exciton polariton condensate

In a homogeneous two-dimensional system at non-zero temperature, although there can be no ordering of infinite range, a superfluid phase is predicted for a Bose liquid. The stabilization of phase in this superfluid regime is achieved by the formation of bound vortex-antivortex pairs. It is believed that several different systems share this common behaviour, when the parameter describing their ordered state has two degrees of freedom, and the theory has been tested for some of them. However, there has been no direct experimental observation of the phase stabilization mechanism by a bound pair. Here we present an experimental technique that can identify a single vortex-antivortex pair in a two-dimensional exciton polariton condensate. The pair is generated by the inhomogeneous pumping spot profile, and is revealed in the time-integrated phase maps acquired using Michelson interferometry, which show that the condensate phase is only locally disturbed. Numerical modelling based on open dissipative Gross-Pitaevskii equation suggests that the pair evolution is quite different in this non-equilibrium system compared to atomic condensates. Our results demonstrate that the exciton polariton condensate is a unique system for studying two-dimensional superfluidity in a previously inaccessible regime

Supersymmetric QCD: Exact Results and Strong Coupling

We revisit two longstanding puzzles in supersymmetric gauge theories. The first concerns the question of the holomorphy of the coupling, and related to this the possible definition of an exact (NSVZ) beta function. The second concerns instantons in pure gluodynamics, which appear to give sensible, exact results for certain correlation functions, which nonetheless differ from those obtained using systematic weak coupling expansions. For the first question, we extend an earlier proposal of Arkani-Hamed and Murayama, showing that if their regulated action is written suitably, the holomorphy of the couplings is manifest, and it is easy to determine the renormalization scheme for which the NSVZ formula holds. This scheme, however, is seen to be one of an infinite class of schemes, each leading to an exact beta function; the NSVZ scheme, while simple, is not selected by any compelling physical consideration. For the second question, we explain why the instanton computation in the pure supersymmetric gauge theory is not reliable, even at short distances. The semiclassical expansion about the instanton is purely formal; if infrared divergences appear, they spoil arguments based on holomorphy. We demonstrate that infrared divergences do not occur in the perturbation expansion about the instanton, but explain that there is no reason to think this captures all contributions from the sector with unit topological charge. That one expects additional contributions is illustrated by dilute gas corrections. These are infrared divergent, and so difficult to define, but if non-zero give order one, holomorphic, corrections to the leading result. Exploiting an earlier analysis of Davies et al, we demonstrate that in the theory compactified on a circle of radius beta, due to infrared effects, finite contributions indeed arise which are not visible in the formal limit that beta goes to infinity.Comment: 28 pages, two references added, one typo correcte