Relationship between ankle brachial index and arterial remodeling in pseudoxanthoma elasticum

ObjectivesPseudoxanthoma elasticum (PXE) is an inherited metabolic disease characterized by elastic fiber fragmentation and calcification in the cutaneous, ophthalmologic, and vascular tissues. Cardiovascular manifestations such as peripheral arterial disease (PAD) are frequent in PXE. Because of the changes in the elastic properties and medial calcification of the arterial wall in PXE, the impact of the arterial remodeling on the ankle brachial index (ABI), a well-established diagnostic method for the detection and follow-up of PAD, remains to be determined in this disease. Methods This was a cross-sectional, comparative, open study, which took place at the PXE Consultation Center, University Hospital of Angers. The subjects were 53 patients (mean age, 49 ± 14 years; 35 females) with PXE clinically proven on the basis of established criteria (skin changes, angioid streaks, and skin biopsy). The ABI at rest, symptoms of intermittent claudication (IC), carotid intima-media thickness (IMT), carotid-femoral pulse wave velocity (c-f PWV), compliance (CC), and β stiffness index were measured in a single-center cohort. Results Forty-five percent of the PXE patients had an ABI ≤0.90, but only one patient had an ABI >1.40. IC was found in 23% of the patients with an ABI ≤0.90. There were no significant differences between the patients with a low and normal ABI in terms of IMT (P = .566) or β stiffness index (P = .194), but differences were significant for c-f PWV (P = .010) and CC (P = .011). Adjusted multivariate linear regression for the Framingham-Laurier score showed that patients with a low ABI had less compliant carotid arteries (B = 0.318, P = .039). Conclusions PAD detected by a low ABI is very frequent in PXE, although with limited prevalence of symptomatic claudication. Unexpectedly, ABI was low in such calcifying PAD and associated with lower CC, independently of atherosclerosis risk factors. These findings demonstrate that PXE represents a unique monogenic model of PAD in which the specific arterial wall remodeling could change the diagnostic value of the ABI to detect PAD

ABCC6 is a basolateral plasma membrane protein

RATIONALE:: ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein. OBJECTIVE:: In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment. METHODS AND RESULTS:: We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum. CONCLUSIONS:: Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation. © 2013 American Heart Association, Inc

Alteration of Extracellular Nucleotide Metabolism in Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum (PXE) is a rare genetic condition primarily caused by hepatic ABCC6 transporter dysfunction. Most clinical manifestations of PXE are due to premature calcification of elastic fibers. However, the vascular impact of PXE is pleiotropic and remains ill defined. ABCC6 expression has recently been associated with cellular nucleotide export. We studied the impact of ABCC6 deficiency on blood levels of adenosine triphosphate and related metabolites and on soluble nucleotidase activities in PXE patients and Abcc6 mice. In addition, we investigated the expression of genes encoding ectocellular purinergic signaling proteins in mouse liver and aorta. Plasma adenosine triphosphate and pyrophosphate levels were significantly reduced in PXE patients and in Abcc6 mice, whereas adenosine concentration was not modified. Moreover, 5\u27-nucleotidase/CD73 activity was increased in the serum of PXE patients and Abcc6 mice. Consistent with alterations of purinergic signaling, the expression of genes involved in purine and phosphate transport/metabolism was dramatically modified in Abcc6 mouse aorta, with much less impact on the liver. ABCC6 deficiency causes impaired vascular homeostasis and tissue perfusion. Our findings suggest that these alterations are linked to changes in extracellular nucleotide metabolism that are remote from the liver. This opens new perspectives for the understanding of PXE pathophysiology

The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification

Vascular calcification is a complex and dynamic process occurring in various physiological conditions such as aging and exercise or in acquired metabolic disorders like diabetes or chronic renal insufficiency. Arterial calcifications are also observed in several genetic diseases revealing the important role of unbalanced or defective anti- or pro-calcifying factors. Pseudoxanthoma elasticum (PXE) is an inherited disease (OMIM 264800) characterized by elastic fiber fragmentation and calcification in various soft conjunctive tissues including the skin, eyes, and arterial media. The PXE disease results from mutations in the ABCC6 gene, encoding an ATP-binding cassette transporter primarily expressed in the liver, kidneys suggesting that it is a prototypic metabolic soft-tissue calcifying disease of genetic origin. The clinical expression of the PXE arterial disease is characterized by an increased risk for coronary (myocardial infarction), cerebral (aneurysm and stroke), and lower limb peripheral artery disease. However, the structural and functional changes in the arterial wall induced by PXE are still unexplained. The use of a recombinant mouse model inactivated for the Abcc6 gene is an important tool for the understanding of the PXE pathophysiology although the vascular impact in this model remains limited to date. Overlapping of the PXE phenotype with other inherited calcifying diseases could bring important informations to our comprehension of the PXE disease

DEMOCRATIC TRANSITION AND REFLECTION ON INDONESIA'S EFFORTS TO ENCOURAGE DEMOCRATIZATION IN MYANMAR

This paper aims to analyze the motives and forms of Indonesia’s effort towards Myanmar in promoting democratization. To achieve these objectives, described the historical aspects of Indonesia-Myanmar relations, democratic transition in both countries, and other forms of Indonesian support for Myanmar in encouraging democratization. Qualitative methods is used in this study to collect and analyze data from interviews and literature studies. Based on this research, found that Indonesia's support for Myanmar in encouraging democratization was influenced by the historical aspects of bilateral relations between Indonesia and Myanmar, the success of Indonesia's transition to democracy, and the similarities of socio-cultural characteristics in both countries. Indonesia's foreign policy towards Myanmar in supporting democratization is done bilaterally, regionally within ASEAN, and multilaterally within UN forums. The principle of active and independent foreign policy and ASEAN norms become the guidance for Indonesia in supporting democratization of Myanmar

Multitemporal Very High Resolution from Space: Outcome of the 2016 IEEE GRSS Data Fusion Contest

In this paper, the scientific outcomes of the 2016 Data Fusion Contest organized by the Image Analysis and Data Fusion Technical Committee of the IEEE Geoscience and Remote Sensing Society are discussed. The 2016 Contest was an open topic competition based on a multitemporal and multimodal dataset, which included a temporal pair of very high resolution panchromatic and multispectral Deimos-2 images and a video captured by the Iris camera on-board the International Space Station. The problems addressed and the techniques proposed by the participants to the Contest spanned across a rather broad range of topics, and mixed ideas and methodologies from the remote sensing, video processing, and computer vision. In particular, the winning team developed a deep learning method to jointly address spatial scene labeling and temporal activity modeling using the available image and video data. The second place team proposed a random field model to simultaneously perform coregistration of multitemporal data, semantic segmentation, and change detection. The methodological key ideas of both these approaches and the main results of the corresponding experimental validation are discussed in this paper

Pseudomonas protegens sp. nov., widespread plant-protecting bacteria producing the biocontrol compounds 2,4-diacetylphloroglucinol and pyoluteorin

Fluorescent Pseudomonas strains producing the antimicrobial secondary metabolite 2,4-diacetylphloroglucinol (Phl) play a prominent role in the biocontrol of plant diseases. A subset of Phl-producing fluorescent Pseudomonas strains, which can additionally synthesize the antimicrobial compound pyoluteorin (Plt), appears to cluster separately from other fluorescent Pseudomonas spp. based on 16S rRNA gene analysis and shares at most 98.4% 16S rRNA gene sequence identity with any other Pseudomonas species. In this study, a polyphasic approach based on molecular and phenotypic methods was used to clarify the taxonomy of representative Phl+ Plt+ strains isolated from tobacco, cotton or wheat on different continents. Phl+ Plt+ strains clustered separately from their nearest phylogenetic neighbors (i.e. species from the ‘P. syringae’, ‘P. fluorescens’ and ‘P. chlororaphis’ species complexes) based on rpoB, rpoD or gyrB phylogenies. DNA-DNA hybridization experiments clarified that Phl+ Plt+ strains formed a tight genomospecies that was distinct from P. syringae, P. fluorescens, or P. chlororaphis type strains. Within Phl+ strains, the Phl+ Plt+ strains were differentiated from other biocontrol fluorescent Pseudomonas strains that produced Phl but not Plt, based on phenotypic and molecular data. Discriminative phenotypic characters were also identified by numerical taxonomic analysis and siderotyping. Altogether, this polyphasic approach supported the conclusion that Phl+ Plt+ fluorescent Pseudomonas strains belonged to a novel species for which the name Pseudomonas protegens is proposed, with CHA0T (=CFBP 6595T, =DSM 19095T) as the type strain

Two-dimensional simulations of internal gravity waves in a 5 M⊙M_{\odot} Zero-Age-Main-Sequence model

Main-sequence intermediate-mass stars present a radiative envelope that supports internal gravity waves (IGWs). Excited at the boundary with the convective core, IGWs propagate towards the stellar surface and are suspected to impact physical processes such as rotation and chemical mixing. Using the fully compressible time-implicit code MUSIC, we study IGWs in two-dimensional simulations of a zero-age-main-sequence 5 solar mass star model up to 91\% of the stellar radius with different luminosity and radiative diffusivity enhancements. Our results show that low frequency waves excited by core convection are strongly impacted by radiative effects as they propagate. This impact depends on the radial profile of radiative diffusivity which increases by almost 5 orders of magnitude between the centre of the star and the top of the simulation domain. In the upper layers of the simulation domain, we observe an increase of the temperature. Our study suggests that this is due to heat added in these layers by IGWs damped by radiative diffusion. We show that non-linear effects linked to large amplitude IGWs may be relevant just above the convective core. Both these effects are intensified by the artificial enhancement of the luminosity and radiative diffusivity, with enhancement factors up to $10^4$ times the realistic values. Our results also highlight that direct comparison between numerical simulations with enhanced luminosity and observations must be made with caution. Finally, our work suggests that thermal effects linked to the damping of IGWs could have a non-negligible impact on stellar structure.Comment: 15 pages, 10 figures, accepted for publication in MNRA

List of New Names of Plant Pathogenic Bacteria (2008-2010)

In 2010 the International Society of Plant Pathology Committee on the Taxonomy of Plant Pathogenic Bacteria published the Comprehensive List of Names of Plant Pathogenic Bacteria, 1980-2007 to provide an authoritative register of names of plant pathogens. In this manuscript we update the list of names by cataloguing names published from 2008 to 2010. We provide those names that have been validly and effectively published in this time frame, the proposed names that we judged to be invalid and names published earlier that did not make the previous lists. We also discuss problems that arise in the naming of strains that fall into the status Candidatus and nomenclatural problems in the genus Xanthomonas