BUSCADOR RECOLECTA

Table S1. Content of individual phenolic compounds present in Brunfelsia grandiflora. Results represent the mean ± standard deviation (n = 4). N.D.: not detected; d.w.: dry weight. Table S2. Parte of 2.9. Molecular assay by Real-Time PCR. Forward and reverse sequences for genes related to cell death, the inflammasome complex and antioxidant biomarkers. Figure S1. Effect of B. grandiflora extract on SH-SY5Y cell viability. There are no statistical differences between the groups analyzed. Figure S2. Part of Figure 4 and 5. Effect of B. grandiflora extract on molecular expression of cell death and oxidative stress biomarkers in SH-SY5Y cells. There are no statistical differences between the groups analyzed., Peer reviewed

Contents: Point S1. Theoretical Details and Theoretical Conformational Search Results (S3): Table S1.1. Parameters of minimum energy structures of MC-1W to -5W within an energy window of 5.0 kJ mol-1 at the ωB97XD/Jun-cc-pVTZ level of theory.-- Table S1.2. Parameters of minimum energy structures of MC-1W to -5W within an energy window of 5.0 KJ mol-1 at the B3LYP-D3(BJ)/def2-TZVP level of theory.-- Table S1.3. Parameters of all minimum energy structures of MC-1W to -5W calculated at the ωB97XD/Jun-cc-pVTZ level of theory.-- Table S1.4. Parameters of all minimum energy structures of MC-1W to -5W calculated at the B3LYP-D3BJ/def2-TZVP level of theory.-- Figure S1.1. Geometries of the three MC monomeric conformers.-- Point S2. Experimental Details (S30).-- Point S3. Spectroscopic Analyses (S30): Table S3.1.1. Spectroscopic parameters for the 13C isotopologues of MC1-1W I.-- Table S3.1.2. Spectroscopic parameters for the 18O isotopologues of MC1-1W I and MC2-1W II.-- Table S3.1.3. Substitution (rs) and theoretical structural parameters for the hydrates.-- Table S3.2.1. Spectroscopic parameters for the 18O isotopologues of MC1-2W I Figure S3.2.1. The three lowest energy structures of the dihydrate at the ωB97XD/Jun-cc-pVTZ level of theory, together with the predicted dipole moment components (in Debye).-- Table S3.3.1. Spectroscopic parameters for the 18O isotopologues of MC1-3W II.-- Figure S3.5.1. Theoretical, effective, and substitution O···O lengths of MC1-1W I to MC1-5W I.-- Table S3.5.1 O···O distances of the donor-acceptor interacting pairs in the MC-nW clusters.-- Tables S3.6.1-3.6.10. Lists of experimental rotational transition frequencies of the observed MC-nW clusters.-- Point S4. Tunnelling Barriers (S61).-- Point S5. Conformer Interconversion and Large Amplitude Motions of MC-4W (S61): Figure S5.1. Four conformations of the tetrahydrate at the ωB97XD/Jun-cc-pVTZ level of theory.-- Figure S5.2. Atom numbering of MC1-4W for the atoms involved the dihedral energy scans.-- Figure S5.3. Potential energy scans of the water wagging motions in MC1-4W.-- Point S6. QTAIM and NCI Plots (S63): Figure S6.1. Results from NCI analyses of the example minimum energy structures associated with the droplet aggregation pathway.-- Figure S6.2. Results from QTAIM analyses of the minimum energy structures of the experimentally assigned hydrates.-- Point S7. Intermolecular Interactions Analyses (S65): Table S7.1. Natural bond orbital analyses of MC water clusters.-- Figure S7.1. Water unit labels.-- References (S66)., Peer reviewed

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC’s main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2’s Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies., Peer reviewed

8 figures, 4 tables.-- Under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/, Trassatti’s method.-- Supplementary tables.-- Supplementary figures.-- Trassatti’s method: In Trassatti’s method, the charge (q) in the voltammetry test is assumed to depend on the scan rate (υ) as follows: q=q_∞+a_1 υ^(-1/2) (S1) 1/q=1/q_T +a_2 υ^(1/2) (S2) where a_1 and a_2 are constants, q_∞ is the charge not limited by ion diffusion (υ→∞), and q_T is the total cell charge (υ→0). If the measurements are carried out under the same conditions, they can be applied in terms of capacitance as follows: C_((υ))=a_1 υ^(-1/2)+ C_EDL (S3) 1/C_((υ)) =a_2 υ^(1/2)+ 1/C_T (S4) where C_EDL is the capacitance arising from the electric double-layer (not limited by ion diffusion) and C_T is assumed to be the total capacitance, such as: C_T=C_PsC+C_EDL (S5) where C_PsC is the capacitance arising from Faradaic contributions. Figure S5C) and S5D) show, as an example, the intercept values of the linear regression for sample N8THC900-2 for equations S3 and S4, respectively., O. Pinto-Burgos thanks ANID - Subdirección de Capital Humano/Doctorado, #2019/21190633. V. Fierro, A. Celzard, and J. Castro-Gutiérrez acknowledge the financial support of the European Regional Development Fund (ERDF) through the TALiSMAN and TALiSMAN2 projects. P.S. Poon and J. Matos thank ANID-FONDEF project 19I10003 and ANID-FONDECYT project 1220228. J. Matos also thanks ANID-ANILLO project ATE220014., Peer reviewed

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC’s main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2’s Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies., Peer reviewed

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC’s main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2’s Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies., Peer reviewed

Phenotyping data of legumes-cereals intercrops under field conditions at Córdob-Spain during two consecutive seasons 2021-2022 and 2022-2023., PROYECTO P20_00986 PAIDI2020 Junta Andalucía., Peer reviewed

6 files, This dataset consists of the estimated decadal changes in the oceanic content of anthropogenic CO2 (∆Cant) between 1994, 2004 and 2014 as described in detail in Müller et al. (2023, in press, AGU Advances). These estimates have been derived from the GLODAPv2.2021 product (Lauvset et al., 2021) using the eMLR(C*) method developed by Clement & Gruber (2018). The datasets contain in addition to the standard estimate also 10 sensitivity cases, which are intended to assess the robustness of the standard estimates to different changes in the estimation procedure. All estimates are provided on a horizontal grid with 1° x 1° resolution. Two primary files are provided: one containing the full three-dimensional distribution of ∆Cant and one containing the vertically integrated values, i.e., the column inventories, 821003 - Climate-Carbon Interactions in the Coming Century (EC); 821001 - Southern Ocean Carbon and Heat Impact on Climate (EC), Peer reviewed

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC’s main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2’s Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies., Peer reviewed

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC’s main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2’s Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies., Peer reviewed