BUSCADOR RECOLECTA

Usage Policies The wwPDB policy states that data files contained in the PDB archive are available under the CC0 1.0 Universal (CC0 1.0) Public Domain Dedicatio, Spanish Ministry of Science, Innovation, and Universities, Spanish Ministry of Economy and Competitiveness, 9guk.pdb, Peer reviewed

DatamainfiguresNew.xlsx. Datasupplementaryfigures.xlsx, The coordination of food intake, energy storage, and expenditure involves complex interactions between hypothalamic neurons and peripheral tissues including pancreatic islets, adipocytes, muscle, and liver. Previous research shows that deficiency of the transcription factor Alx3 alters pancreatic islet-dependent glucose homeostasis. In this study we carried out a comprehensive assessment of metabolic alterations in Alx3 deficiency. We report that Alx3-deficient mice exhibit decreased food intake without changes in body weight, along with reduced energy expenditure and altered respiratory exchange ratio. Magnetic resonance imaging reveals increased adiposity and decreased muscle mass, which was associated with markers of motor and sympathetic denervation. By contrast, Alx3-deficient mice on a high-fat diet show attenuated weight gain and improved insulin sensitivity, compared to control mice. Gene expression analysis demonstrates altered lipogenic and lipolytic gene profiles. In wild type mice Alx3 is expressed in hypothalamic arcuate nucleus neurons, but not in major peripheral metabolic organs. Functional diffusion-weighted magnetic resonance imaging reveals selective hypothalamic responses to fasting in the arcuate nucleus of Alx3-deficient mice. Additionally, altered expression of proopiomelanocortin and melanocortin-3 receptor mRNA in the hypothalamus suggests impaired regulation of feeding behavior. This study highlights the crucial role for Alx3 in governing food intake, energy homeostasis, and metabolic nutrient partitioning, thereby influencing body mass composition., Peer reviewed

This study investigates the transesterification of isoflavones puerarin and β-D-fructofuranosyl-(2→6)-puerarin to enhance their lipophilicity for specific pharmacological applications. The process achieved high yields (80-100%) in the isoflavones conversion when commercial lipases from Candida antarctica (CALB) and Thermomyces lanuginosus (TL IM) were used. The acylation patterns between CALB and TL IM varied depending on the substrate; both enzymes yielded principally monoacylated products from puerarin and β-D-fructofuranosyl-(2→6)-puerarin. However, TL IM also produced di- and triacylated derivatives of β-D-fructofuranosyl-(2→6)-puerarin in substantial amounts. Structural characterization by NMR identified puerarin-6ʹʹ-O-laurate and β-D-fructofuranosyl-(2→6)-puerarin-6ʹʹʹ-O-laurate as the primary products in CALB and TL IM reactions. These acyl derivatives presented improved lipophilicity (Log P from −1.0 − 0.16 to 3.26 − 3.58) and antioxidant activity (67.2-97.3 to 102.5-131.4 µM TE/mmol). Therefore, these compounds have potential pharmacological applications., Thanks for the financial support of CONACYT (Mexico) through the Ph.D. scholarship 268290 for ACV. This work was supported in Mexico by the CONACYT project CONACYT-SENER 250014. In Spain, this work was supported by the Spanish Ministry of Science and Innovation (Grant PID2019-105838RB-C31 and PDC2022-133134-C21)., Peer reviewed

Usage Policies The wwPDB policy states that data files contained in the PDB archive are available under the CC0 1.0 Universal (CC0 1.0) Public Domain Dedicatio, Spanish Ministry of Science, Innovation, and Universities, Spanish Ministry of Economy and Competitiveness, 9gug.pdb, Peer reviewed

Usage Policies The wwPDB policy states that data files contained in the PDB archive are available under the CC0 1.0 Universal (CC0 1.0) Public Domain Dedicatio, Spanish Ministry of Science, Innovation, and Universities, Spanish Ministry of Economy and Competitiveness, 9guh.pdb, Peer reviewed

Usage Policies The wwPDB policy states that data files contained in the PDB archive are available under the CC0 1.0 Universal (CC0 1.0) Public Domain Dedicatio, Spanish Ministry of Science, Innovation, and Universities, Spanish Ministry of Economy and Competitiveness, 9gqu.pdb, Peer reviewed

Heterotrimeric Gα:Gβγ G proteins function as molecular switches downstream of G protein-coupled receptors (GPCRs). They alternate between a heterotrimeric GDP-bound OFF-state and a GTP-bound ON-state in which GαGTP is separated from the Gβγ dimer. Consequently, pharmacological tools to securely prevent the OFF-ON transition are of utmost importance to investigate their molecular switch function, specific contribution to GPCR signal transduction, and potential as drug targets. FR900359 (FR) and YM-254890 (YM), two natural cyclic peptides and highly specific inhibitors of Gq/11 heterotrimers, are exactly such tools. To date, their efficient and long-lasting inhibition of Gq/11 signaling has been attributed solely to a wedge-like binding to Gα, thereby preventing separation of the GTPase and α-helical domains and thus GDP release. Here, we use X-ray crystallography, biochemical and signaling assays, and BRET-based biosensors to show that FR and YM also function as stabilizers of the Gα:Gβγ subunit interface. Our high-resolution structures reveal a network of residues in Gα and two highly conserved amino acids in Gβ that are targeted by FR and YM to glue the Gβγ complex to the inactive GαGDP subunit. Unlike all previously developed nucleotide-state specific inhibitors that sequester Gα in its OFF-state but compete with Gβγ, FR and YM actively promote the inhibitory occlusion of GαGDP by Gβγ. In doing so, they securely lock the entire heterotrimer, not just Gα, in its inactive state. Our results identify FR and YM as molecular glues for Gα and Gβγ that combine simultaneous binding to both subunits with inhibition of G protein signaling., We thank the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project numbers 290827466/FOR2372 (Grants CR464/7-1 to M.C., KO 902/17-2 to G.M.K., 216619161 to G.S., 418513893 to X.D., 290847012 to E.K., and 494832089/GRK2873 to E.K. and L.J.), and the Swiss NSF—Project numbers 192780 (to X.D.) and 183563 (to G.S., under the Sinergia program) for funding. M.J.R. received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant agreement No. 701647. We thank the SLS beamline scientists for their support during crystallography data collection., Peer reviewed

Peer reviewed

Project: Integrated Assessment of Atlantic Marine Ecosystems in Space and Time (iAtlantic)., Dendrophyllia_Bycatch * Latitude: 43.398822 * Longitude: -8.700804 * Date/Time: 2019-09-11T00:00:00 * Elevation: -150.0 m * Location: Atlantic Ocean * Method/Device: Accidental bycatch sampling., El dataset se puede consultar y descargar en el siguiente enlace https://doi.org/10.1594/PANGAEA.963072, A 9-month aquarium experiment with the cold-water Dendrophyllia cornigera was conducted to investigate the single and combined effects of warming, acidification and deoxygenation on its ecophysiological response. The experiment took place at the Aquarium finisterrae (A Coruña, Spain) between 2022-05-06 and 2023-02-24. Treatment values for each parameter (current in situ vs. climate change) were: 12 °C and 15 °C (temperature); ~7.99 and 7.69 (pH); ~8.63 mg/L and 6.45 mg/L (dissolved oxygen concentration). A total of eight treatments (with 3 replicates each, 5 L aquaria) were set up. Concentrations of dissolved nitrates, nitrite, silicate and phosphate were analysed from each experimental aquaria after one, six and nine months. Inorganic nutrient concentrations in seawater were determined using a SFA (Segmented Flow Autoanalyzer) (Aminot & Kérouel, 2007) with a SEAL Analytical QuAAtro analyzer using established colorimetric methods (Hydes et al. 2010 & Becker et al. 2020). RMNs (Reference Material for nutrients in seawater) with different concentration ranges were used for quality control and accuracy of our analysis. Low nutrient seawater (surface seawater filtered and aged) is also used to control low nutrient concentrations., Horizon 2020 (H2020), grant/award no. 818123: Integrated Assessment of Atlantic Marine Ecosystems in Space and Time, Peer reviewed

Project: Integrated Assessment of Atlantic Marine Ecosystems in Space and Time (iAtlantic)., Dendrophyllia_Bycatch * Latitude: 43.398822 * Longitude: -8.700804 * Date/Time: 2019-09-11T00:00:00 * Elevation: -150.0 m * Location: Atlantic Ocean * Method/Device: Accidental bycatch sampling, El dataset se puede consultar y descargar en el siguiente enlace https://doi.org/10.1594/PANGAEA.966668, A 9-month aquarium experiment with the cold-water Dendrophyllia cornigera was conducted to investigate the single and combined effects of warming, acidification and deoxygenation on its ecophysiological response. The experiment took place at the Aquarium finisterrae (A Coruña, Spain) between 2022-05-06 and 2023-02-24. Treatment values for each parameter (current in situ vs. climate change) were: 12 °C and 15 °C (temperature); ~7.99 and 7.69 (pH); ~8.63 mg/L and 6.45 mg/L (dissolved oxygen concentration). A total of eight treatments (with 3 replicates each, 5 L aquaria) were set up. Measurements for pH and total alkalinity (TA) were performed on seawater samples from all the experimental aquaria every 1 – 2 months. Samples for pH were directly collected on cylindrical 10 cm cuvettes and analysed on daily basis. After being thermostated at 25ºC, samples were measured using a manual spectrophotometrical procedure with a Sigma Aldrich impure indicator (Clayton and Byrne, 1993). TA was measured following the double end point potentiometric technique by Pérez and Fraga (1987a) and Pérez et al. (2000). Measurements of Certified Reference Material (Dickson's lab, SIO) were performed in order to control the accuracy of the TA measurements. The uncertainty of TA and pH is about 3 μmol/kg and 0.005 pH units, respectively. In situ additional CO2 system variables were calculated using the R package seacarb (Gattuso et al. 2023) using in situ temperature, salinity, measured pH and TA, the dissociation constants of carbonic acid in seawater (K1 and K2) by Lueker et al. (2000), the equilibrium constant of hydrogen fluoride by Perez and Fraga (1987b), the concentration of total boron by Uppström (1974) formulation, and the stability constant of hydrogen sulphate by Dickson (1990). Mean values for the concentration of silicate and phosphate on the aquaria experiments were used in the CO2 calculations, respectively, mean (and standard) deviations as 2.1 (0.4) and 0.31 (0.03) μmol/kg., Horizon 2020 (H2020), grant/award no. 818123: Integrated Assessment of Atlantic Marine Ecosystems in Space and Time, Peer reviewed