SUMOylation regulates LKB1 localization and its oncogenic activity in liver cancer

BACKGROUND: Even though liver kinase B1 (LKB1) is usually described as a tumor suppressor in a wide variety of tissues, it has been shown that LKB1 aberrant expression is associated with bad prognosis in Hepatocellular Carcinoma (HCC). METHODS: Herein we have overexpressed LKB1 in human hepatoma cells and by using histidine pull-down assay we have investigated the role of the hypoxia-related post-translational modification of Small Ubiquitin-related Modifier (SUMO)ylation in the regulation of LKB1 oncogenic role. Molecular modelling between LKB1 and its interactors, involved in regulation of LKB1 nucleocytoplasmic shuttling and LKB1 activity, was performed. Finally, high affinity SUMO binding entities-based technology were used to validate our findings in a pre-clinical mouse model and in clinical HCC. FINDINGS: We found that in human hepatoma cells under hypoxic stress, LKB1 overexpression increases cell viability and aggressiveness in association with changes in LKB1 cellular localization. Moreover, by using site-directed mutagenesis, we have shown that LKB1 is SUMOylated by SUMO-2 at Lys178 hampering LKB1 nucleocytoplasmic shuttling and fueling hepatoma cell growth. Molecular modelling of SUMO modified LKB1 further confirmed steric impedance between SUMOylated LKB1 and the STe20-Related ADaptor cofactor (STRADα), involved in LKB1 export from the nucleus. Finally, we provide evidence that endogenous LKB1 is modified by SUMO in pre-clinical mouse models of HCC and clinical HCC, where LKB1 SUMOylation is higher in fast growing tumors. INTERPRETATION: Overall, SUMO-2 modification of LKB1 at Lys178 mediates LKB1 cellular localization and its oncogenic role in liver cancer. FUND: This work was supported by grants from NIH (US Department of Health and Human services)-R01AR001576-11A1 (J.M.M and M.L.M-C.), Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M.-C), MINECO: SAF2017-87301-R and SAF2014-52097-R integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M., respectively), BFU2015-71017/BMC MINECO/FEDER, EU (to A.D.Q. and I.D.M.), BIOEF (Basque Foundation for Innovation and Health Research): EITB Maratoia BIO15/CA/014; Instituto de Salud Carlos III:PIE14/00031, integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovacion 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M), Asociación Española contra el Cáncer (T.C.D, P·F-T and M.L.M-C), Daniel Alagille award from EASL (to T.C.D), Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M and M.A), La Caixa Foundation Program (to M.L.M), Programma di Ricerca Regione-Università 2007-2009 and 2011-2012, Regione Emilia-Romagna (to E.V.), Ramón Areces Foundation and the Andalusian Government (BIO-198) (A.D.Q. and I.D.M.), ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.), MINECO:SAF2015-64352-R (P.A.), Institut National du Cancer, FRANCE, INCa grant PLBIO16-251 (M.S.R.), MINECO - BFU2016-76872-R to (E.B.). Work produced with the support of a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (M.V-R). Finally, Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). Funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

Tropical Atlantic variability modes (1979–2002). Part I: Time-evolving SST modes related to West African rainfall

This work presents a description of the 1979–2002 tropical Atlantic (TA) SST variability modes coupled to the anomalous West African (WA) rainfall during the monsoon season. The time-evolving SST patterns, with an impact on WA rainfall variability, are analyzed using a new methodology based on maximum covariance analysis. The enhanced Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) dataset, which includes measures over the ocean, gives a complete picture of the interannual WA rainfall patterns for the Sahel dry period. The leading TA SST pattern, related to the Atlantic El Niño, is coupled to anomalous precipitation over the coast of the Gulf of Guinea, which corresponds to the second WA rainfall principal component. The thermodynamics and dynamics involved in the generation, development, and damping of this mode are studied and compared with previous works. The SST mode starts at the Angola/Benguela region and is caused by alongshore wind anomalies. It then propagates westward via Rossby waves and damps because of latent heat flux anomalies and Kelvin wave eastward propagation from an off-equatorial forcing. The second SST mode includes the Mediterranean and the Atlantic Ocean, showing how the Mediterranean SST anomalies are those that are directly associated with the Sahelian rainfall. The global signature of the TA SST patterns is analyzed, adding new insights about the Pacific– Atlantic link in relation to WA rainfall during this period. Also, this global picture suggests that the Mediterranean SST anomalies are a fingerprint of large-scale forcing. This work updates the results given by other authors, whose studies are based on different datasets dating back to the 1950s, including both the wet and the dry Sahel periods

Climate services for irrigation management

Ponencia presentada en: 10º Simpósio de Meteorologia e Geofísica da APMG, celebrado del 20 al 22 de marzo de 2017 en Lisboa, PortugalAEMET is contributing with the provision of climate services related with seasonal forecasts to the MOSES (Managing crOp water Saving with Enterprise Services) EU H2020 project. The main objective of MOSES project is to put in place and demonstrate at the real scale of application an information platform devoted to planning of irrigation water resources, to support water procurement and management agencies (e.g. reclamation consortia, irrigation districts, etc.). Its main goals are saving water, improving services to farmers and reducing monetary and energy costs. MOSES is a multi-disciplinary project involving 16 partners and the AEMET main contribution consists of producing weather and climate forecasts up to seasonal timescale for two demonstration areas over Spain and another one over Morocco selected for their agricultural value

MOOCEP: A method for Building Massive Online Courses for Elderly People: Using a MOOCEP creation

Today, the population of elderly people has increased significantly in relation to the total world population. In recent years, this segment of population has shown a greater adherence and interest in technological advances, among them the Internet and its services; this, with the aim of develop different activities such as entertainment, obtain current information, learning different topics, among others. However, applications and websites do not take into account the specific requirements of elderly people. Hence, it is necessary to have methodologies, processes and tools that take into account appropriate forms of interaction specific to this vulnerable sector of the population. This article is an extension to the one presented at the INCISCOS 2017 conference, which proposed a methodology for the creation of massive online courses, called MOOCEP. In this work, it has been considered convenient to test the devices created with the use of MOOCEP, by presenting these resources to elderly people, in order to make a comparison of the before and after knowledge of the various topics presented in the learning platform

Impact of the SARS-CoV-2 Pandemic on the Prevalence and Incidence of Gastrointestinal Viruses in Children up to Five Years Old: a Retrospective Cohort Study

The aim is determining the impact of non-pharmaceutical measures (NPIs) against SARS-CoV-2 in the incidence and prevalence of gastrointestinal viruses (GV) in children. Demographic, analytical, and clinical data of children from which samples were received at the Hospital Universitario La Paz (Madrid, Spain) and that had a gastrointestinal infection with a positive sample through multiplex-PCR for GV were collected. The time periods included were prepandemic (P1): March 14, 2019 to March 14, 2020 and pandemic (P2): March 15, 2020 to March 15, 2021. The global prevalence, relative incidence (RI, per 1,000 admissions) and absolute incidence (AI, per 100,000 population) of GV were compared for both time periods. The prevalence of GV versus SARS-CoV-2 was determined for P2. Seven-hundred and 50 out of 2,547 children analyzed in P1 and 106 out of 1,368 in P2 were positive by PCR for GV (46.3% decrease in P2). Prevalence and RI of GV declined in P2, except for the RI of rotavirus. Adenovirus showed the largest decreased of prevalence and RI (100%), followed by sapovirus. Astrovirus reduction was less pronounced (3.1% versus 0.4%). Norovirus was the most frequent virus in both time periods and its prevalence and RI also decreased in P2 (15.2% versus 4.7% and 3.40 versus 1.74, respectively). Rotavirus had the smallest decrease in prevalence (2.6% versus 2.5%), and its RI increased during P2 from 0.7 to 0.93. After removing the rotavirus vaccine strains from the analysis, the prevalence and RI decreased during P2 (2.1% to 0.7% and 0.5 to 0.3, respectively). The AI decreased during P2 in all GV, and the prevalence of SARS-CoV-2 and GV was inversely proportional over time. Prevalence and incidence of GV have decreased during the pandemic, probably due to the implementation of NPIs against this virus and the reduction of health care attention to infections other than COVID-19. The differences in the decrease of prevalence and incidence for each virus may be explained by differences in the transmission and the resistance in the environment. Prevalence and RI of rotavirus might be biased since the PCR used detects both the infecting and the vaccine strains. IMPORTANCE Our original article contains an analysis of the impact of the measures applied against SARS-CoV-2 on the prevalence and incidence of GV in children. The small number of studies published to date that analyze the impact of these measures individually on each of the GV makes our study of great interest at this tim

Hippocampal neurogenesis and Arc expression are enhanced in high-fat fed prepubertal female pigs by a diet including omega-3 fatty acids and Bifidobacterium breve CECT8242

Obesity during childhood has become a pandemic disease, mainly caused by a diet rich in sugars and fatty acids. Among other negative effects, these diets can induce cognitive impairment and reduce neuroplasticity. It is well known that omega-3 and probiotics have a beneficial impact on health and cognition, and we have hypothesized that a diet enriched with Bifidobacterium breve and omega-3 could potentiate neuroplasticity in prepubertal pigs on a high-fat diet.info:eu-repo/semantics/publishedVersio

High-Temperature Short-Time and Holder Pasteurization of Donor Milk: Impact on Milk Composition

Holder pasteurization (HoP; 62.5 °C, 30 min) is commonly used to ensure the microbiological safety of donor human milk (DHM) but diminishes its nutritional properties. A high-temperature short-time (HTST) system was designed as an alternative for human milk banks. The objective of this study was to evaluate the effect of this HTST system on different nutrients and the bile salt stimulated lipase (BSSL) activity of DHM. DHM was processed in the HTST system and by standard HoP. Macronutrients were measured with a mid-infrared analyzer. Lactose, glucose, myo-inositol, vitamins and lipids were assayed using chromatographic techniques. BSSL activity was determined using a kit. The duration of HTST treatment had a greater influence on the nutrient composition of DHM than did the tested temperature. The lactose concentration and the percentage of phospholipids and PUFAs were higher in HTST-treated than in raw DHM, while the fat concentration and the percentage of monoacylglycerides and SFAs were lower. Other nutrients did not change after HTST processing. The retained BSSL activity was higher after short HTST treatment than that following HoP. Overall, HTST treatment resulted in better preservation of the nutritional quality of DHM than HoP because relevant thermosensitive components (phospholipids, PUFAs, and BSSL) were less affected.This research was funded by grants from the Spanish Research Projects in Health funded by ISCIII-the state plan for scientific and technical research and innovation and European Regional Development Fund (ERDF) (ref. PI12/02128 and PI15/00995) and by ALG2016-75476-R project from the Ministerio de Economía, Industria y Competitividad (Spain). Moreover, this work has received a grant from the Hero Institute for Infant Nutrition (Alcantarilla, Murcia, España; 2012). Additionally, this study was supported by RETICS “Maternal and Child Health and Development Network” (SAMID Network), funded by the PN I+D+i 2008-2011 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion and the ERDF (ref. RD12/0026)

El subjuntivo como concordancia modal : nueva propuesta gramatical y bases teóricas para su aplicación didáctica

Partimos de la idea de que el modo subjuntivo en español es un epifenómeno y exploramos aquí una de sus manifestaciones. Estudiamos la teoría de que la flexión verbal subjuntiva en oraciones subordinadas sustantivas en español se trata en realidad de un modal tácito. Nuestra propuesta sitúa este modal en la oración matriz, siendo el subjuntivo una morfología concordante. Así mismo, revisamos el tratamiento del subjuntivo en una gramática de enseñanza de español como lengua extranjera (ELE) para señalar qué aspectos de nuestra propuesta pueden complementar estas explicaciones de acuerdo con el postulado de una Gramática Universal.La nostra premissa és que el mode subjuntiu en espanyol és un epifenomen i explorem aquí una de les seves manifestacions. Estudiem la teoria de que la flexió verbal subjuntiva en oracions subordinades substantives en espanyol es tracta en realitat d'un modal tàcit. La nostra proposta situa aquest modal a l'oració matrium, essent el subjuntiu una morfologia concordant. Així mateix, revisem el tractament del subjuntiu en una grmàtica d'ensenyament de l'espanyol com a llengua estrangera (ELE) per assenyalar quins aspectes de la nostra proposta poden complementar aquestes explicacions d'acord amb el postulat d'una Gramàtica Universal

A hydrophobic release agent containing SiO2-CH3 submicron-sized particles for waterproofing mortar structures

Hydrophobic release agents were developed from SiO2-CH3 submicron-sized particles containing hydrophilic and hydrophobic functional groups dispersed into a vegetable oil as support. The SiO2-CH3 submicron-sized particles were synthesized by changing the molar ratio between the precursors Tetraethyl orthosilicate (TEOS) and Methyltriethoxysilane (MTES) from 0.66 to 5 (MTEOS-0.66 to MTEOS-5), being the relative amount of SiO2-CH3 quantified by FTIR technique. Mortar specimens having hydrophobic properties were manufactured using 3 wt% of the above SiO2-CH3 submicron-sized particles. Additionally, the concentration effect was studied by using MTEOS-0.66 within 3–10 wt%. The hydrophobic properties of the mortar specimens were checked by measuring the contact angle within water droplets and surface. The particle size increased with the MTES/TEOS molar ratio and according to the hydrophobic properties, the proper release agent must be synthesized by using MTEOS-2.5 dispersed into the vegetable oil and having a concentration of 3 wt%. This hydrophobic release agent led mortar surfaces with contact angles higher than 145°. Waterproofing and mechanical studies on concrete specimens allowed to conclude that this demoulding agent does not have a high penetration depth but improved the concrete waterproofing properties, without depletion in the compressive strength