Empirical models for estimating air temperature using MODIS Land Surface Temperature (and Spatiotemporal Variables) in the Hurd Peninsula of Livingston Island, Antarctica, between 2000 and 2016

In this article, we present empirical models for estimating daily mean air temperature (Ta) in the Hurd Peninsula of Livingston Island (Antarctica) using Moderate Resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST) data and spatiotemporal variables. The models were obtained and validated using the daily mean Ta from three Spanish in situ meteorological stations (AEMET stations), Juan Carlos I (JCI), Johnsons Glacier (JG), and Hurd Glacier (HG), and three stations in our team’s monitoring sites, Incinerador (INC), Reina Sofía (SOF), and Collado Ramos (CR), as well as daytime and nighttime Terra-MODIS LST and Aqua-MODIS LST data between 2000 and 2016. Two types of multiple linear regression (MLR) models were obtained: models for each individual station (for JCI, INC, SOF, and CR—not for JG and HG due to a lack of data) and global models using all stations. In the study period, the JCI and INC stations were relocated, so we analyzed the data from both locations separately (JCI1 and JCI2; INC1 and INC2). In general, the best individual Ta models were obtained using daytime Terra LST data, the best results for CR being followed by JCI2, SOF, and INC2 (R2 = 0.5–0.7 and RSE = 2 °C). Model cross validation (CV) yielded results similar to those of the models (for the daytime Terra LST data: R2CV = 0.4–0.6, RMSECV = 2.5–2.7 °C, and bias = −0.1 to 0.1 °C). The best global Ta model was also obtained using daytime Terra LST data (R2 = 0.6 and RSE = 2 °C; in its validation: R2CV = 0.5, RMSECV = 3, and bias = −0.03), along with the significant (p < 0.05) variables: linear time (t) and two time harmonics (sine-cosine), distance to the coast (d), slope (s), curvature (c), and hour of LST observation (H). Ta and LST data were carefully corrected and filtered, respectively, prior to its analysis and comparison. The analysis of the Ta time series revealed different cooling/warming trends in the locations, indicating a complex climatic variability at a spatial scale in the Hurd Peninsula. The variation of Ta in each station was obtained by the Locally Weighted Regression (LOESS) method. LST data that was not “good quality” usually underestimated Ta and were filtered, which drastically reduced the LST data (<5% of the studied days). Despite the shortage of “good” MODIS LST data in these cold environments, all months were represented in the final dataset, demonstrating that the MODIS LST data, through the models obtained in this article, are useful for estimating long-term trends in Ta and generating mean Ta maps at a global level (1 km2 spatial resolution) in the Hurd Peninsula of Livingston Island

Splicing Factor SLU7 Prevents Oxidative Stress-Mediated Hepatocyte Nuclear Factor 4α Degradation, Preserving Hepatic Differentiation and Protecting From Liver Damage

Background and Aims: Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors like SLU7. How these factors interact and become dysregulated and the impact of their impairment in driving liver disease are not fully understood. Approach and Results: Expression of SLU7 and that of the adult and oncofetal isoforms of HNF4α, driven by its promoter 1 (P1) and P2, respectively, was studied in diseased human and mouse livers. Hepatic function and damage response were analyzed in wild-type and Slu7-haploinsufficient/heterozygous (Slu7) mice undergoing chronic (CCl) and acute (acetaminophen) injury. SLU7 expression was restored in CCl-injured mice using SLU7-expressing adeno-associated viruses (AAV-SLU7). The hepatocellular SLU7 interactome was characterized by mass spectrometry. Reduced SLU7 expression in human and mouse diseased livers correlated with a switch in HNF4α P1 to P2 usage. This response was reproduced in Slu7 mice, which displayed increased sensitivity to chronic and acute liver injury, enhanced oxidative stress, and marked impairment of hepatic functions. AAV-SLU7 infection prevented liver injury and hepatocellular dedifferentiation. Mechanistically we demonstrate a unique role for SLU7 in the preservation of HNF4α1 protein stability through its capacity to protect the liver against oxidative stress. SLU7 is herein identified as a key component of the stress granule proteome, an essential part of the cell’s antioxidant machinery. Conclusions: Our results place SLU7 at the highest level of hepatocellular identity control, identifying SLU7 as a link between stress-protective mechanisms and liver differentiation. These findings emphasize the importance of the preservation of hepatic functions in the protection from liver injury.Supported by MINECO/AEI/FEDER (UE SAF2016-75972-R, PID2019-104265RB-I00/AEI/10.13039/501100011033, and PID2019-104878RB-100/AEI/10.13039/501100011033), CIBERehd, Fundación La Caixa (HEPACARE), an AECC postdoctoral fellowship (POSTD18014AREC, to M.A.), a Ministerio de Educación FPU fellowship (FPU18/01461, to M.G.R.), a Ministerio de Educación FPI fellowship (BES-2017-079883, to M.R.); a Ramón y Cajal Program contract (RYC2018-024475-1, to M.G.F.B.), the Fundación Eugenio Rodríguez Pascual, the Fundación Mario Losantos, the Fundación M. Torres, and a generous donation from Mr. Eduardo Avila

Splicing factor SLU7 prevents oxidative stress-mediated hepatocyte nuclear factor 4α degradation, preserving hepatic differentiation and protecting from liver damage

Background and Aims: Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors like SLU7. How these factors interact and become dysregulated and the impact of their impairment in driving liver disease are not fully understood. Approach and Results: Expression of SLU7 and that of the adult and oncofetal isoforms of HNF4α, driven by its promoter 1 (P1) and P2, respectively, was studied in diseased human and mouse livers. Hepatic function and damage response were analyzed in wild-type and Slu7-haploinsufficient/heterozygous (Slu7+/−) mice undergoing chronic (CCl4) and acute (acetaminophen) injury. SLU7 expression was restored in CCl4-injured mice using SLU7-expressing adeno-associated viruses (AAV-SLU7). The hepatocellular SLU7 interactome was characterized by mass spectrometry. Reduced SLU7 expression in human and mouse diseased livers correlated with a switch in HNF4α P1 to P2 usage. This response was reproduced in Slu7+/− mice, which displayed increased sensitivity to chronic and acute liver injury, enhanced oxidative stress, and marked impairment of hepatic functions. AAV-SLU7 infection prevented liver injury and hepatocellular dedifferentiation. Mechanistically we demonstrate a unique role for SLU7 in the preservation of HNF4α1 protein stability through its capacity to protect the liver against oxidative stress. SLU7 is herein identified as a key component of the stress granule proteome, an essential part of the cell’s antioxidant machinery. Conclusions: Our results place SLU7 at the highest level of hepatocellular identity control, identifying SLU7 as a link between stress-protective mechanisms and liver differentiation. These findings emphasize the importance of the preservation of hepatic functions in the protection from liver injury.Supported by MINECO/AEI/FEDER (UE SAF2016‐75972‐R, PID2019‐104265RB‐I00/AEI/10.13039/501100011033, and PID2019‐104878RB‐100/AEI/10.13039/501100011033), CIBERehd, Fundación La Caixa (HEPACARE), an AECC postdoctoral fellowship (POSTD18014AREC, to M.A.), a Ministerio de Educación FPU fellowship (FPU18/01461, to M.G.R.), a Ministerio de Educación FPI fellowship (BES‐2017‐079883, to M.R.); a Ramón y Cajal Program contract (RYC2018‐024475‐1, to M.G.F.B.), the Fundación Eugenio Rodríguez Pascual, the Fundación Mario Losantos, the Fundación M. Torres, and a generous donation from Mr. Eduardo Avila

Oral Methylthioadenosine Administration Attenuates Fibrosis and Chronic Liver Disease Progression in Mdr2−/− Mice

BACKGROUND: Inflammation and fibrogenesis are directly related to chronic liver disease progression, including hepatocellular carcinoma (HCC) development. Currently there are few therapeutic options available to inhibit liver fibrosis. We have evaluated the hepatoprotective and anti-fibrotic potential of orally-administered 5'-methylthioadenosine (MTA) in Mdr2(-/-) mice, a clinically relevant model of sclerosing cholangitis and spontaneous biliary fibrosis, followed at later stages by HCC development. METHODOLOGY: MTA was administered daily by gavage to wild type and Mdr2(-/-) mice for three weeks. MTA anti-inflammatory and anti-fibrotic effects and potential mechanisms of action were examined in the liver of Mdr2(-/-) mice with ongoing fibrogenesis and in cultured liver fibrogenic cells (myofibroblasts). PRINCIPAL FINDINGS: MTA treatment reduced hepatomegaly and liver injury. α-Smooth muscle actin immunoreactivity and collagen deposition were also significantly decreased. Inflammatory infiltrate, the expression of the cytokines IL6 and Mcp-1, pro-fibrogenic factors like TGFβ2 and tenascin-C, as well as pro-fibrogenic intracellular signalling pathways were reduced by MTA in vivo. MTA inhibited the activation and proliferation of isolated myofibroblasts and down-regulated cyclin D1 gene expression at the transcriptional level. The expression of JunD, a key transcription factor in liver fibrogenesis, was also reduced by MTA in activated myofibroblasts. CONCLUSIONS/SIGNIFICANCE: Oral MTA administration was well tolerated and proved its efficacy in reducing liver inflammation and fibrosis. MTA may have multiple molecular and cellular targets. These include the inhibition of inflammatory and pro-fibrogenic cytokines, as well as the attenuation of myofibroblast activation and proliferation. Downregulation of JunD and cyclin D1 expression in myofibroblasts may be important regarding the mechanism of action of MTA. This compound could be a good candidate to be tested for the treatment of (biliary) liver fibrosis

CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in Spanish rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis, which is the main cause of increased cardiovascular (CV) morbidity and mortality in RA patients. CARD8 is a constituent of inflammasome, which regulates interleukin 1-beta production, and has been associated with a worse disease course in early RA. One thousand six hundred twenty-one patients fulfilling the 1987 ACR classification criteria for RA and 1300 matched controls, were genotyped for the CARD8 rs2043211 (30T > A, p.C10X) single-nucleotide polymorphism (SNP) using predesigned TaqMan SNP genotyping assay. The genotyping success rate in our study was greater than 94%. We assessed CARD8 rs2043211 gene polymorphism results in 1530 Spanish RA patients in whom information on CV disease and CV risk factors was available at the time of the study. Also, a subgroup of patients with no history of CV events (n = 276) was assessed for the potential influence of the rs2043211 variant in the development of subclinical atherosclerosis, by measurement of carotid intima-media thickness (IMT) and presence of carotid plaques. No statistically significant differences in allele or genotype frequencies for the rs2043211 CARD8 gene variant between patients with RA and controls were seen. Similarly, CARD8 rs2043211 (30T > A, p.C10X) SNP did not influence the development of CV events or the risk of CV events throughout the time. Likewise, no significant association between this gene variant and carotid IMT or the presence of plaques was found. In summary, our results do not support a role of the CARD8 rs2043211 gene variant in susceptibility to RA or in the development of CV disease in patients with RA

CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in spanish rheumatoid arthritis patients

This is a copy of an article published in the DNA Cell Biology (01-01-2013) copyright Mary Ann Liebert, Inc. DNA Cell Biology is avalaible online at: http://online.liebertpub.comRheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis, which is the main cause of increased cardiovascular (CV) morbidity and mortality in RA patients. CARD8 is a constituent of inflammasome, which regulates interleukin 1-beta production, and has been associated with a worse disease course in early RA. One thousand six hundred twenty-one patients fulfilling the 1987 ACR classification criteria for RA and 1300 matched controls, were genotyped for the CARD8 rs2043211 (30T > A, p.C10X) single-nucleotide polymorphism (SNP) using predesigned TaqMan SNP genotyping assay. The genotyping success rate in our study was greater than 94%. We assessed CARD8 rs2043211 gene polymorphism results in 1530 Spanish RA patients in whom information on CV disease and CV risk factors was available at the time of the study. Also, a subgroup of patients with no history of CV events (n = 276) was assessed for the potential influence of the rs2043211 variant in the development of subclinical atherosclerosis, by measurement of carotid intima-media thickness (IMT) and presence of carotid plaques. No statistically significant differences in allele or genotype frequencies for the rs2043211 CARD8 gene variant between patients with RA and controls were seen. Similarly, CARD8 rs2043211 (30T > A, p.C10X) SNP did not influence the development of CV events or the risk of CV events throughout the time. Likewise, no significant association between this gene variant and carotid IMT or the presence of plaques was found. In summary, our results do not support a role of the CARD8 rs2043211 gene variant in susceptibility to RA or in the development of CV disease in patients with RAThis work was supported by grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spain), and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I +D+ i 2008–2011 (FEDER). M.G.B. is a beneficiary of a grant from Fundación Española de Reumatología (FER)

Variability of the air temperature and its comparison with MODIS Land Surface Temperature in the Hurd Peninsula of the Livingston Island, Antarctica, between 2000 and 2016

Ponencia presentada en: XVIII Congreso de la Asociación Española de Teledetección celebrado en Valladolid del 24 al 27 septiembre 2019.[ES]En los ambientes polares, tan vulnerables al cambio climático, el estudio de la temperatura es imprescindible. Por ello, y en el marco del proyecto PERMASNOW, en este trabajo hemos estudiado en detalle la variación de la temperatura del aire (Ta) en la península Hurd de la isla Livingston (Antártida) y hemos tratado de estimarla a partir de los datos de temperatura de la superficie terrestre (LST, por sus siglas en inglés) del sensor MODIS entre los años 2000 y 2016. Utilizamos datos de Ta media diaria obtenidos en seis puntos, tres estaciones meteorológicas de AEMET y tres estaciones del proyecto PERMASNOW: Juan Carlos I (JCI), Glaciar Johnson (GJ), Glaciar Hurd (GH), Incinerador (INC), Reina Sofía (RS) y Collado Ramos (CR), respectivamente. Los datos MODIS LST son los diurnos y nocturnos de los satélites Terra y Aqua. La tendencia en Ta se ha analizado mediante la regresión localmente ponderada (LOESS, por sus siglas en inglés) y la relación Ta -LST con regresiones lineales múltiples. Concluimos que Ta en el área de estudio varía: se observa en la estación JCI, más cercana a la costa, una tendencia al enfriamiento con valores entre –2,3 y –3,0°C década–1. En cambio, las estaciones más alejadas de la costa y de mayor altitud muestran una tendencia al calentamiento (entre +0,2 y +0,8°C década-1). Los mejores modelos de estimación de Ta a partir de LST y variables temporales se obtienen con los datos diurnos de Terra (R2 = 0,5-0,7; RSE = 2°C), exceptuando GJ, donde la variable LST no es significativa. Con la validación cruzada (CV) se aprecian también, excepto en GJ, mejores resultados con los datos diurnos de Terra (R2 CV = 0,5-0,6; RMSECV = 2,5-2,6°C). Finalmente, concluimos que los datos MODIS LST son útiles para estimar tendencias de Ta a largo plazo en el área de estudio.[EN]In polar zones, where satellite data are very useful due to the limited in situ data, it is therefore essential to study the air temperature behaviour. In the framework of the PERMASNOW project we estimated the air temperature (Ta) in the Hurd Peninsula of Livingston Island (Antarctica) from the land surface temperature (LST) data of the MODIS between 2000 and 2016. We worked with Ta data obtained at six stations (3 AEMET meteorological stations and 3 PERMASNOW project stations: Juan Carlos I (JCI), Johnson Glacier (JG), Hurd Glacier (HG), Incinerator (INC), Reina Sofia (RS) and Collado Ramos (CR), respectively. In addition, we analyzed daytime and nighttime LST data from the Terra and Aqua satellites. Locally weighted regression (LOESS) and multiple linear regressions were used for statistical analysis. We conclude that the Ta in the study area varies: a cooling trend with values between –2.3 and –3.0°C decade-1 is observed in JCI, which is closer to the coast. On the other hand, the stations farther from the coast and at higher altitudes show a warming trend (between +0.2 and +0.8°C decade-1). The best Ta models are obtained with Terra daytime data (R2 = 0.5-0.7 and RSE = 2°C), except JG, where the LST variable is not significant. With cross validation (CV), better results are also seen, except in JG, with the daytime Terra data (R2 CV = 0.5-0.6, RMSECV = 2.5-2.6°C). In summary, MODIS LST data are useful for estimating long-term Ta trends in the study area.Esta investigación fue posible gracias a la financiación de la Agencia Estatal de Investigación a través del proyecto PERMASNOW [CTM2014-52021-R], la ayuda de la Universidad de Oviedo al Grupo de Investigación RSApps en 2018 [PAPI-18-GR-2016-0005] y las ayudas obtenidas por A.C.-P. (“Severo Ochoa” del Gobierno del Principado de Asturias [BP17-151] y “Ayuda Predoctoral” de la Universidad de Oviedo)

Analysis of the Interferon Gamma (rs2430561, +874T/A) Functional Gene Variant in Relation to the Presence of Cardiovascular Events in Rheumatoid Arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. METHODS: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA. RESULTS: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not. CONCLUSION: Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients

Lack of Association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and Carotid Intima-Media Thickness, Carotid Plaques, and Cardiovascular Disease in Patients with Rheumatoid Arthritis

Introduction. Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT) and presence/absence of carotid plaques) and CV disease in RA. Material and Methods. 2140 Spanish RA patients were genotyped for the 5 polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 620 of these patients by carotid ultrasonography technology. Results. No statistically significant differences were found when each polymorphism was assessed according to cIMT values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV disease after adjusting for potential confounders. Conclusion. Our results do not confirm association between ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807, PIK3CG rs17398575, and EDNRA rs1878406 and subclinical atherosclerosis and CV disease in RA.European Union FEDER Funds and “Fondo de Investigación Sanitaria” (Grants PI06/0024, PS09/00748, and PI12/00060) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009/0013 and RD12/0009/0004 (RIER) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain) and in part by grants from the European IMI BTCure Program.Peer reviewe

Decreasing the Expression of GABAA[alfa]5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome

Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABAmediated inhibition. Because of the well-known modulatory role of GABAA ?5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABAA ?5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABAA ?5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice.We show that reducing the expression of GABAA ?5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved longterm potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABAA ?5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS.This work was supported by the Jérôme Lejeune Foundation, Fundación Tatiana Pérez de Guzmán el Bueno and the Spanish Ministry of Economy and Competitiveness (PSI2016-76194-R/ AEI/FEDER/UE