| 81. |
- Mercier, N, et al.
(författare)
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Semicarbazide-Sensitive Amine Oxidase Increases in Calcific Aortic Valve Stenosis and Contributes to Valvular Interstitial Cell Calcification
- 2020
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Ingår i: Oxidative medicine and cellular longevity. - : Hindawi Limited. - 1942-0994 .- 1942-0900. ; 2020, s. 5197376-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Calcific aortic valve stenosis (CAVS) is a common disease associated with aging. Oxidative stress participates in the valve calcification process in CAVS. Semicarbazide-sensitive amine oxidase (SSAO), also referred to as vascular adhesion protein 1 (VAP-1), transforms primary amines into aldehydes, generating hydrogen peroxide and ammonia. SSAO is expressed in calcified aortic valves, but its role in valve calcification has remained largely unexplored. The aims of this study were to characterize the expression and the activity of SSAO during aortic valve calcification and to establish the effects of SSAO inhibition on human valvular interstitial cell (VIC) calcification. Methods. Human aortic valves from n=80 patients were used for mRNA extraction and expression analysis, Western blot, SSAO activity determination, immunohistochemistry, and the isolation of primary VIC cultures. Results. SSAO mRNA, protein, and activity were increased with increasing calcification within human aortic valves and localized in the vicinity of the calcified zones. The valvular SSAO upregulation was consistent after stratification of the subjects according to cardiovascular and CAVS risk factors associated with increased oxidative stress: body mass index, diabetes, and smoking. SSAO mRNA levels were significantly associated with poly(ADP-ribose) polymerase 1 (PARP1) in calcified tissue. Calcification of VIC was inhibited in the presence of the specific SSAO inhibitor LJP1586. Conclusion. The association of SSAO expression and activity with valvular calcification and oxidative stress as well as the decreased VIC calcification by SSAO inhibition points to SSAO as a possible marker and therapeutic target to be further explored in CAVS.
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| 82. |
- Monelli, Erika, et al.
(författare)
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Angiocrine polyamine production regulates adiposity
- 2022
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Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 4:3, s. 327-
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Tidskriftsartikel (refereegranskat)abstract
- Reciprocal interactions between endothelial cells (ECs) and adipocytes are fundamental to maintain white adipose tissue (WAT) homeostasis, as illustrated by the activation of angiogenesis upon WAT expansion, a process that is impaired in obesity. However, the molecular mechanisms underlying the crosstalk between ECs and adipocytes remain poorly understood. Here, we show that local production of polyamines in ECs stimulates adipocyte lipolysis and regulates WAT homeostasis in mice. We promote enhanced cell-autonomous angiogenesis by deleting Pten in the murine endothelium. Endothelial Pten loss leads to a WAT-selective phenotype, characterized by reduced body weight and adiposity in pathophysiological conditions. This phenotype stems from enhanced fatty acid beta-oxidation in ECs concomitant with a paracrine lipolytic action on adipocytes, accounting for reduced adiposity. Combined analysis of murine models, isolated ECs and human specimens reveals that WAT lipolysis is mediated by mTORC1-dependent production of polyamines by ECs. Our results indicate that angiocrine metabolic signals are important for WAT homeostasis and organismal metabolism. Endothelial cells in white adipose tissue are shown to produce polyamines, which regulate adipocyte lipolysis, thus demonstrating how local angiocrine signals contribute to healthy adipose tissue homeostasis.
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| 83. |
- Müller, Niels A., et al.
(författare)
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A single gene underlies the dynamic evolution of poplar sex determination.
- 2020
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Ingår i: Nature Plants. - : Springer Nature. - 2055-0278 .- 2055-026X. ; 6:6, s. 630-637
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Tidskriftsartikel (refereegranskat)abstract
- Although hundreds of plant lineages have independently evolved dioecy (that is, separation of the sexes), the underlying genetic basis remains largely elusive. Here we show that diverse poplar species carry partial duplicates of the ARABIDOPSIS RESPONSE REGULATOR 17 (ARR17) orthologue in the male-specific region of the Y chromosome. These duplicates give rise to small RNAs apparently causing male-specific DNA methylation and silencing of the ARR17 gene. CRISPR–Cas9-induced mutations demonstrate that ARR17 functions as a sex switch, triggering female development when on and male development when off. Despite repeated turnover events, including a transition from the XY system to a ZW system, the sex-specific regulation of ARR17 is conserved across the poplar genus and probably beyond. Our data reveal how a single-gene-based mechanism of dioecy can enable highly dynamic sex-linked regions and contribute to maintaining recombination and integrity of sex chromosomes.
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| 84. |
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| 85. |
- Perez-Torrado, F. J., et al.
(författare)
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La erupción submarina de La Restinga en la islade El Hierro, Canarias : Octubre 2011-Marzo 2012
- 2012
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Ingår i: Estudios Geológicos. - : Editorial CSIC. - 0367-0449 .- 1988-3250. ; 68:1, s. 5-27
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Tidskriftsartikel (refereegranskat)abstract
- The first signs of renewed volcanic activity at El Hierro began in July 2011 with the occurrence of abundant, low-magnitude earthquakes. The increasing seismicity culminated on October 10, 2011, with the onset of a submarine eruption about 2 km offshore from La Restinga, the southernmost village on El Hierro. The analysis of seismic and deformation records prior to, and throughout, the eruption allowed the reconstruction of its main phases: 1) ascent of magma and migration of hypocentres from beneath the northern coast (El Golfo) towards the south rift zone, close to La Restinga, probably marking the hydraulic fracturing and the opening of the eruptive conduit; and 2) onset and development of a volcanic eruption indicated by sustained and prolonged harmonic tremor whose intensity varied with time. The features monitored during the eruption include location, depth and morphological evolution of the eruptive source and emission of floating volcanic bombs. These bombs initially showed white, vesiculated cores (originated by partial melting of underlying pre-volcanic sediments upon which the island of El Hierro was constructed) and black basanite rims, and later exclusively hollow basanitic lava balloons. The eruptive products have been matched with a fissural submarine eruption without ever having attained surtseyan explosiveness. The eruption has been active for about five months and ended in March 2012, thus becoming the second longest reported historical eruption in the Canary Islands after the Timanfaya eruption in Lanzarote (1730-1736). This eruption provided the first opportunity in 40 years to manage a volcanic crisis in the Canary Islands and to assess the interpretations and decisions taken, thereby gaining experience for improved management of future volcanic activity. Seismicity and deformation during the eruption were recorded and analysed by the Instituto Geografico Nacional (IGN). Unfortunately, a lack of systematic sampling of erupted pyroclasts and lavas, as well as the sporadic monitoring of the depth and growth of the submarine vent by deployment of a research vessel, hampered a comprehensive assessment of hazards posed during volcanic activity. Thus, available scientific data and advice were not as high quality as they could have been, thereby limiting the authorities in making the proper decisions at crucial points during the crisis. The response in 2011-12 to the El Hierro eruption has demonstrated that adequate infrastructure and technical means exist in the Canary Islands for the early detection of potential eruptive hazards. However, it also has taught us that having detailed emergency management plans may be of limited value without an accompanying continuous, well-integrated scientific monitoring effort (open to national and international collaboration) during all stages of an eruption.
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| 86. |
- Perez-Torrado, F.J., et al.
(författare)
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The submarine erupton of La Restinga (El Hierro, Canary Islands): : October 2011 - March 2012
- 2012
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Ingår i: Estudios Geológicos. - : Editorial CSIC. - 1988-3250 .- 0367-0449. ; 68:1
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Tidskriftsartikel (refereegranskat)abstract
- Los primeros indicios de una posible erupción volcánica en El Hierro se percibieron a partir de julio de 2011 en forma de sismos de baja intensidad pero anormalmente numerosos. La intensificación de la sismicidad culminó con el inicio de la erupción submarina el 10 de octubre de 2011 a unos 2 km al sur de La Restinga. La sismicidad y deformación del terreno que precedieron y acompañaron a esta erupción han permitido reconstruir las principales fases de actividad volcánica: 1) generación y ascenso del magma con migración de los hipocentros sísmicos desde el norte, en el Golfo, hasta el rift sur, en La Restinga, marcando la apertura hidráulica del conducto magmático; y 2) inicio y continuidad de la erupción volcánica evidenciada por un tremor armónico continuo de intensidad variable en el tiempo. Las características observadas a lo largo de la erupción, principalmente localización, profundidad y evolución morfológica del foco emisor, así como emisión de materiales volcánicos flotantes, inicialmente con un núcleo blanco poroso (procedentes de la fusión parcial de sedimentos de la capa superior de la corteza oceánica anteriores a la construcción del edificio insular de El Hierro) envuelto por una corteza basanítica y después huecas (lava balloons), se han correspondido con una erupción submarina fisural profunda sin que nunca hayan intervenido mecanismos más explosivos tipo surtseyano. La erupción se mantuvo activa durante unos cinco meses, dándose por finalizada en marzo del 2012, convirtiéndose de este modo en la segunda erupción histórica más longeva de Canarias después de la de Timanfaya (1730-36) en Lanzarote. Esta erupción ha supuesto la primera oportunidad en 40 años de gestionar una crisis volcánica en Canarias y de analizar las observaciones e interpretaciones y las decisiones adoptadas, con objeto de mejorar la gestión de futuras crisis volcánicas. El Instituto Geográfico Nacional (IGN) se encargó de adquirir y analizar la información sísmica y de deformación durante todo el proceso. Sin embargo, no se dispuso inicialmente de un barco oceanográfico que realizara estudios sistemáticos de la profundidad y progresión de la erupción, así como de toma de muestras de los materiales emitidos (piroclastos y lavas), elementos claves para la determinación de la peligrosidad eruptiva. Estas deficiencias en el seguimiento científico del proceso eruptivo dificultaron en algunos momentos la toma de decisiones de protección civil. El análisis de la crisis ha puesto de manifiesto que, aunque se disponga de una infraestructura técnica adecuada para la detección temprana de crisis eruptivas en el archipiélago, de poco valen las medidas administrativas planificadas sin un seguimiento científico continuo e integrador del proceso eruptivo, abierto a la colaboración científica nacional e internacional.
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| 87. |
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| 88. |
- Timofeeva, Maria N, et al.
(författare)
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Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer.
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10(-7)), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10(-7)); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10(-7) and OR = 1.09, P = 7.4 × 10(-8)); rs1129406 (12q13) in ATF1 (OR = 1.11, P = 8.3 × 10(-9)), all reaching exome-wide significance levels. Gene based tests identified associations between CRC and PCDHGA genes (P < 2.90 × 10(-6)). We found an excess of rare, damaging variants in base-excision (P = 2.4 × 10(-4)) and DNA mismatch repair genes (P = 6.1 × 10(-4)) consistent with a recessive mode of inheritance. This study comprehensively explores the contribution of coding sequence variation to CRC risk, identifying associations with coding variation in 4 genes and PCDHG gene cluster and several candidate recessive alleles. However, these findings suggest that recurrent, low-frequency coding variants account for a minority of the unexplained heritability of CRC.
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| 89. |
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| 90. |
- Wiesmaier, S., et al.
(författare)
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Bimodality of lavas in the teide-pico viejo succession in tenerife-the role of crustal melting in the origin of recent phonolites
- 2012
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Ingår i: Journal of Petrology. - : Oxford University Press (OUP). - 0022-3530 .- 1460-2415. ; 53:12, s. 2465-2495
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Tidskriftsartikel (refereegranskat)abstract
- In Tenerife, lavas of the recent Teide-Pico Viejo central complex show a marked bimodality in composition from initially mafic lavas (200-30 ka) to highly differentiated phonolites (30-0 ka). After this abrupt change, the bimodality of the lavas continued to manifest itself between the now felsic Teide-Pico Viejo central complex and the adjacent, but exclusively mafic, rift zones. Whole-rock trace element fingerprinting distinguishes three compositional groups (mafic, transitional, felsic). Groundmass Sr-Nd-Pb-O and feldspar δ. 18O data demonstrate open-system behaviour for the petrogenesis of the Teide-Pico Viejo felsic lavas by high. 87Sr/. 86Sr ratios of up to 0·7049, uniform. 206Pb/. 204Pb (19·75-19·78), variable. 207Pb/. 204Pb (15·53-15·62) and heterogeneous δ. 18O values (5·43-6·80‰). However, ocean sediment contamination can be excluded because of the low. 206Pb/. 204Pb ratios of North Atlantic sediments. Isotope mixing hyperbolae reproduce the entire Teide-Pico Viejo succession and require an assimilant of predominantly felsic composition. Unsystematic and heterogeneous variation of δ. 18O in fresh and unaltered feldspars across the Teide-Pico Viejo succession indicates magmatic addition of diverse δ. 18O assimilants, altered near surface at high and low temperatures. The best fit for these requirements is provided by nepheline syenite that occurs as fresh or altered lithic blocks in voluminous pre-Teide ignimbrite deposits and is similarly heterogeneous in oxygen isotope composition. Nepheline syenite blocks are considered to represent deep remnants of associated earlier eruptions and were thus available for assimilation at depth. Rare earth element modelling indicates that nepheline syenite needs to be melted in bulk to form a suitable end-member composition. Using this assimilant, energy-constrained assimilation fractional crystallization (EC-AFC) modelling reproduces the bulk of the succession, which leads us to suggest that Teide-Pico Viejo petrogenesis is governed by assimilation and fractional crystallization. Both mixing hyperbolae and EC-AFC models indicate that assimilation is more pronounced for the more felsic lavas. The maximum assimilation is evident in the most strongly differentiated (and the most radiogenic in Sr) lava and computes to >97·8% of the assimilant. This most evolved eruption probably represents nepheline syenite bulk melts that formed spatially decoupled from juvenile material. This study therefore recognizes a wider variability of magmatic differentiation processes at Teide-Pico Viejo than previously thought.
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