Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism

Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues—K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis.Ministerio de Ciencia, Innovación y Universidades PID2020-117116RB-I00, BFU2017-87721, RTI2018-101840-BI00, PID2021-126096NB-I00, RED2018-102379-TXunta de Galicia 2021-CP085, 2020-PG0157Fundación BBVA RTC2019-007125-1Proyectos Investigación en Salud DTS20/00138, DTS20/00138European Community 2019-WATCH- 81033

Demonstration of local adaptation in maize landraces by reciprocal transplantation.

Populations are locally adapted when they exhibit higher fitness than foreign populations in their native habitat. Maize landrace adaptations to highland and lowland conditions are of interest to researchers and breeders. To determine the prevalence and strength of local adaptation in maize landraces, we performed a reciprocal transplant experiment across an elevational gradient in Mexico. We grew 120 landraces, grouped into four populations (Mexican Highland, Mexican Lowland, South American Highland, South American Lowland), in Mexican highland and lowland common gardens and collected phenotypes relevant to fitness and known highland-adaptive traits such as anthocyanin pigmentation and macrohair density. 67k DArTseq markers were generated from field specimens to allow comparisons between phenotypic patterns and population genetic structure. We found phenotypic patterns consistent with local adaptation, though these patterns differ between the Mexican and South American populations. Quantitative trait differentiation (Q ST) was greater than neutral allele frequency differentiation (F ST) for many traits, signaling directional selection between pairs of populations. All populations exhibited higher fitness metric values when grown at their native elevation, and Mexican landraces had higher fitness than South American landraces when grown in these Mexican sites. As environmental distance between landraces' native collection sites and common garden sites increased, fitness values dropped, suggesting landraces are adapted to environmental conditions at their natal sites. Correlations between fitness and anthocyanin pigmentation and macrohair traits were stronger in the highland site than the lowland site, supporting their status as highland-adaptive. These results give substance to the long-held presumption of local adaptation of New World maize landraces to elevation and other environmental variables across North and South America

Do planalto ás terras baixas: novas achegas á ocupación da península do Barbanza dende a Prehistoria ata o Medievo

We review the survey works carried through in the district of Barbanza, now extended to the pa-rishes of Macenda and Bealo in search of livestock / pastoral settlements. In the course of these explorations a Copper Age site was discovered and, nearby, a previously unknown hillfort. An ac-count is given of the results of the digging in two sites; one related to husbandry tasks, that presents a structural and chronological palimpsest (Rio Barbanza); and another more, related to territorial control systems (Outeiro da Torre).Procédese á revisión dos traballos de prospección previa na serra do Barbanza e ampliados aos montes de Macenda e Bealo na procura de asentamentos gandeiros/pastorís, no curso deses traballos localizáronse ademáis un interesante xacemento de cronoloxía calcolítca e un castro inédito. Asemade, dáse conta dos resultados das intervencións en dous xacementos, un de carácter gandeiro que presenta un palimpsesto estrutural e cronolóxico (Río Barbanza), e outro relacionado con sistemas de control territorial (Outeiro da Torre)

Hepatocyte-specific O-GlcNAc transferase downregulation ameliorates nonalcoholic steatohepatitis by improving mitochondrial function

Objective O-GlcNAcylation is a post-translational modification that directly couples the processes of nutrient sensing, metabolism, and signal transduction, affecting protein function and localization, since the O-linked N-acetylglucosamine moiety comes directly from the metabolism of glucose, lipids, and amino acids. The addition and removal of O-GlcNAc of target proteins are mediated by two highly conserved enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), respectively. Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer, diabetes, and cardiovascular diseases. The contribution of deregulated O-GlcNAcylation to the progression and pathogenesis of NAFLD remains intriguing, and a better understanding of its roles in this pathophysiological context is required to uncover novel avenues for therapeutic intervention. By using a translational approach, our aim is to describe the role of OGT and O-GlcNAcylation in the pathogenesis of NAFLD. Methods We used primary mouse hepatocytes, human hepatic cell lines and in vivo mouse models of steatohepatitis to manipulate O-GlcNAc transferase (OGT). We also studied OGT and O-GlcNAcylation in liver samples from different cohorts of people with NAFLD. Results O-GlcNAcylation was upregulated in the liver of people and animal models with steatohepatitis. Downregulation of OGT in NAFLD-hepatocytes improved diet-induced liver injury in both in vivo and in vitro models. Proteomics studies revealed that mitochondrial proteins were hyper-O-GlcNAcylated in the liver of mice with steatohepatitis. Inhibition of OGT is able to restore mitochondrial oxidation and decrease hepatic lipid content in in vitro and in vivo models of NAFLD. Conclusions These results demonstrate that deregulated hyper-O-GlcNAcylation favors NAFLD progression by reducing mitochondrial oxidation and promoting hepatic lipid accumulation.ACKNOWLEDGEMENTS. This work was supported by grants from: FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación (MLM-C: PID2020-117116RB-I00; CD: BFU2017-87721; ML: RTI2018e101840-B-I00; RN: PID2021-126096NB-I00 and RED2018-102379-T); Xunta de Galicia (RN: 2021-CP085 and 2020-PG0157); Fundación BBVA (to RN); Subprograma Retos Colaboración RTC2019-007125-1 (to MLM-C); Proyectos Investigación en Salud DTS20/00138 (to MLM-C); Proyectos Investigación en Salud (MLMC: DTS20/00138); Fundación Atresmedia (to ML and RN), Fundación La Caixa (to ML and RN); la Caixa Foundation Program HR17-00601 (to MLM-C); Gilead Sciences International Research Scholars Program in Liver Disease (to MVR); and the European Foundation for the Study of Diabetes (to RN and GS). This research also received funding from the European Community’s H2020 Framework Programme (ERC Synergy Grant-2019-WATCH-810331, to RN, VP and MS). The Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn) and the Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Hepáticas y Digestivas (CIBERehd) are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain, which is supported by FEDER funds. We thank MINECO for the Severo Ochoa Excellence Accreditation bioGUNE (SEV-2016- 0644) to CIC

Zotracos surveys: basic hydrographic and chemical data

Este dataset está compuesto por 2 archivos, de los cuales el primero es el conjunto de datos con 371 análisis de muestras de agua de temperatura, salinidad, oxígeno, nutrientes, pH, alcalinidad, clorofila y materia orgánica, y el otro (Readme.txt) incluye una pequeña descripción de las variables calculadasLa zona costera de transición del noroeste de la Península Ibérica fue objeto de muestreo en tres cruceros realizados del 4 al 2 de diciembre de 2004, del 7 al 14 de febrero y del 23 al 30 de octubre de 2005 a bordo del buque oceanográfico "Cornide de Saavedra". Se muestreo a lo largo de un transecto latitudinal centrado a 41.92°N, cerca de la desembocadura del río Miño y otro frente a la Ría de Vigo. Un total de 5 a 7 estaciones fueron ocupadas durante cada crucero. La salinidad y la temperatura se registraron con una sonda de profundidad de conductividad-temperatura SBE 9/11 conectada al muestreador de roseta con doce botellas de PVC Niskin de 10 L con muelles internos de acero inoxidable. Las mediciones de la conductividad se convirtieron en valores prácticos de la escala de salinidad con la ecuación de la UNESCO (1986). La precisión de las mediciones de CTD para temperatura y salinidad fueron de 0,004 DEG-C y 0,005, respectivamente. Las muestras para los análisis de oxígeno disuelto, pH, alcalinidad total, sales de nutrientes, carbono orgánico disuelto y particulado y nitrógeno fueron recogidas semanalmente con la roseta de 12 botellas Niskin. Para la determinación de nutrientes, las muestras de agua se recogieron en botellas de polietileno de 50 ml y se mantuvieron frías (4ºC) hasta su análisis en el laboratorio utilizando procedimientos estándar de análisis de flujo segmentado. Las precisiones fueron 0,02 micromol/kg para nitrito, 0,1 micromol/kg para nitrato, 0,05 microM para amonio, 0,02 micromol/kg para fosfato y 0,05 micromol/kg para silicato. El oxígeno se determinó por titulación potenciométrica de Winkler utilizando un analizador Titrino 720 con una precisión de ±0,5 micromol/kg. Las muestras de alcalinidad total (TA) y pH (escala de concentración total de hidrógeno, 25°C) se recogieron en frascos de vidrio de 500 ml y se analizaron en pocas horas en el laboratorio base. El pH del agua de mar se midió espectrofotométricamente siguiendo a Clayton y Byrne (1993) aplicándose una adición de 0,0047 (DelValls & Dickson, 1998). La precisión fue 0,003 unidades de pH. El TA se determinó por titulación a pH 4,4 con HCl, según el método potenciométrico de Pérez y Fraga (1987) con una precisión de ±2 micromol/kg. La materia orgánica suspendida se recolectó bajo vacío en filtros precombustionados (450ºC, 4 horas) Whatman GF/F de 25 mm de diámetro y 0,7 micrómetros de tamaño nominal de poro (POC/PON, 0,5-1,5 L de agua de mar). Todos los filtros se secaron durante la noche y se congelaron (-20ºC) antes del análisis. Las mediciones de POC y PON se realizaron con un analizador Perkin Elmer 2400 CHN. Se utilizó un estándar de acetanilida diariamente. La precisión del método es de 0,3 micromol C/L y 0,1 micromol N/LCSIC y Plan Nacional de I+D del Gobierno de España1 data csv ‘29CS20041004_hy1.csv’ file and 1 readme.txt filePeer reviewe