BUSCADOR RECOLECTA

(A) Position of ovaries within a Drosophila female (left) and schematic of Drosophila ovaries showing an ovariole and its egg chambers (right). BC, border cells; Oo, oocyte; NCs, nurse cells; FCs, follicle cells; StFCs, stretch FCs; BM, basement membrane. (B) Diagram of an ovariole showing stages 8, 9, and 10 egg chambers (S8–S10). Anterior is left, posterior right. (C) Three-dimensional diagram of a S9 egg chamber showing the migration of the BCs between the NCs. (D–G’) Stills taken from live imaging of migrating BCs from egg chambers of the indicated genotypes. Discontinuous yellow lines demarcate the region between the anterior border of the egg chamber and the oocyte anterior membrane. (H–J) Quantification of BC migration speed during the whole migratory process (H) and during the early (I) and late (J) phases in egg chambers of the indicated genotypes. The statistical significance of differences was assessed with a t test, ** P value < 0.01. Horizontal and vertical lines indicate mean and SD, respectively. Scale bars in A’, B’, C’ and D’, 20 μm. The raw data underlying panels H–J are available in S1 Data., Peer reviewed

Solvents (chloroform and ethyl acetate) were obtained from Scharlau chemical company. The seawater (supplied by Rioka del Cantábrico, S.L.) was taken from the Matxitxako cape at the Urdaibai biosphere reserve in the Cantabrian Sea (Spain). The microalgae Chlorella Vulgaris was acquired to Biotiva (Germany) as a fine dehydrated powder and used without additional treatment. Almond hulls were from Marcona-type almonds harvested in Spain.-- A stainless-steel batch autoclave (300 mL) equipped with a speed-controlled mechanical stirrer (Parker Autoclave Engineers) was used for the hydrothermal experiments.-- Under a Creative Commons license BY-NC 4.0., The proximate analysis of algae and almond hulls were analyzed by thermogravimetric analysis (ISO-18134:2016, ISO-18122:2016 and ISO-18123:2016). The elemental composition of the feedstocks was determined using an elemental analyzer. The biochemical composition of almond hulls was determined by chemical titration according to Hu et al, whereas biochemical composition was provided by the supplier.-- Table S1: Properties and composition of seawater. Table S2: Characterization results of C. vulgaris and almond hulls. Table S3: Processing conditions and experimental results for the co-HTT of C. vulgaris and almond hulls. Table S4: Relative influence of feedstock composition and processing conditions and interactions based on ANOVA analyses and cause-effect Pareto principle. Table S5: Detailed GC-MS peak area for biocrude (area%). Table S6: Process Optimization: Theoretical values vs. Experimental values., Peer reviewed

Suppl. Figure 1. Percentage of FES patients in symptomatic remission throughout the study., Suppl. Figure 2. Percentage of FES patients in functional remission throughout the study., Suppl. Figure 3. Clustered boxplot displaying the mean depression scores per time point (measured using the Hamilton Depression Rating Scale) in the subgroup meeting criteria for a depressive episode at baseline (assessed through the SCID-I) versus the subgroup without a depressive episode at baseline., Suppl. Table 1. Baseline demographics and clinical characteristics of study completers and drop-outs., Suppl. Table 2. Number of patients in symptomatic and functional remission throughout the period of follow-up., Suppl. Table 3. Generalized linear mixed models: pairwise contrasts for symptomatic and functional remission., Suppl. Table 4. Linear mixed models: estimated marginal means for PANSS, GAF, SOFAS, CGI, GF-S, GF-R and HAM-D., Suppl. Table 5. Linear mixed models: estimates of fixed effect time on PANSS, GAF, SOFAS, CGI, GF-S, GF-R and HAM-D., Suppl. Table 6. Number of patients admitted to the hospital since the previous visit due to psychotic symptoms and due to psychiatric reasons in general., Suppl. Table 7. Substances used at least once in the past three months (WHO-ASSIST)., Suppl. Table 8. Number of patients reporting daily or almost daily substance use in the past three months, separated per time point and substance category (WHO-ASSIST)., Suppl. Table 9. Number of patients reporting daily or almost daily substance use in the past three months, separated for the group of symptomatic remitters and non-remitters at month 12., Suppl. Table 10. Baseline demographics and clinical characteristics of symptomatic remitters and non-remitters at month 12., Suppl. Table 11. Summary of sociodemographics and baseline clinical characteristics of FES participants, separated per country., Suppl. Table 12. Number of FES patients in symptomatic remission throughout the period of follow-up, separated per country., Suppl. Table 13. Number of FES patients in functional remission throughout the period of follow-up, separated per country., Suppl. Table 14. Number of FES patients admitted to the hospital for psychiatric reasons throughout the period of follow-up, separated per country., Suppl. Table 15. Number of FES patients admitted to the hospital for psychosis throughout the period of follow-up, separated per country., Suppl. Table 16. Number of FES patients using antipsychotic medication throughout the period of follow-up, separated per country., Suppl. Table 17. Overview of subjects not meeting eligibility criteria., Suppl. Table 18. Number of patients in symptomatic and functional remission throughout the period of follow-up when using alternative definitions., Suppl. Table 19. Generalized linear mixed models: pairwise contrasts for symptomatic and functional remission when using alternative definitions., Peer reviewed

(A–B’) Stills taken from live imaging of migrating BCs from egg chambers of the indicated genotypes. (C) Quantification of the migration defects in egg chambers of the specified genotypes. The statistical significance of differences was assessed with a t test, *** P value < 0.001. Horizontal and vertical lines indicate mean and SD, respectively. Scale bars in A’ and B’, 20 μm. The raw data underlying panel C are available in S1 Data., Peer reviewed

(A–D) S9 controls tjGal4, tj>LanB1RNAi, mirrGal4 and mirr>EHBP1mCh egg chambers stained with the F-actin marker Rhodamine-Phalloidin (F-actin, red) and the DNA marker Hoechst (blue). Arrows in A indicate the curvature of the membranes between an anterior (A) and an anterior central NC (Ca); between 2 central NCs -a Ca and a Cp (a posterior central NC); between a Cp and a posterior (P) NC and between a P NC and the oocyte membrane. (E, F) Quantification of the radius of curvature of A, Ca, Cp and P NCs in S9 egg chambers of the indicated genotypes. BC clusters are marked with a red circle. (G–I) Stills taken from live imaging of migrating BCs from egg chambers of the indicated genotypes. (J) Quantification of BC migration speed in egg chambers of the indicated genotypes. The statistical significance of differences was assessed with a t test. Horizontal and vertical lines indicate mean and SD, respectively. Scale bars in A–D and G–I’, 20 μm. The raw data underlying panels E, F, and J are available in S1 Data., Peer reviewed

(A–B’) Stills taken from live imaging of migrating BCs from egg chambers of the indicated genotypes. (C) Quantification of the migration defects in egg chambers of the specified genotypes. The statistical significance of differences was assessed with a t test, *** P value < 0.001. Horizontal and vertical lines indicate mean and SD, respectively. Scale bars in A’ and B’, 20 μm. The raw data underlying panel C and D are available in S1 Data., Peer reviewed

[Measurement details] In static measurements, the whole batch dispersion, having well-defined density and deflocculant ratio, was gently stirred with a spoon for approximately 1 min, and a fraction of it was transferred to a 50-mL vial. The measurement probe was inserted in the fluid, following instructions from the respective providers. In dynamic measurements, 3 batches of the clay dispersion (ρ = 1.55 g·cm-3, deflocculant ratio 0.44 wt.%) were added together into a 2 L rectangular hermetic container. Prior to measurements, the dispersion was gently mixed with a spoon. Both the viscometer probe and the stirring rotor, operating at 1,000 rpm, were simultaneously located at opposite sides of the container. In the casting experiments, two different products were used: i) the Euroarce sanitary slip (ρ = 1.96 g·cm-3); and ii) an aqueous dilution of that sanitary slip, resulting in a density of ρ = 1.81 g·cm-3. The slip was hand stirred with a spoon and transferred into a plaster mould through a filling hole. The plaster mould, used to conform bar specimens measuring 12 x 3 x 1.5 cm3, consists of two symmetrical components joined together with adhesive tape. For measurement purposes, the VRV probe was introduced in the filled mould through the filling hole.-- Under a Creative Commons license BY-NC-ND 4.0., [Materials and equipment] Industrias Químicas del Ebro (Zaragoza, Spain) supplied the deflocculant solution of sodium silicate (3.3 SiO2·Na2O, 43% dry mass, NASIL 3.35). Elemental analysis was acquired from Energy-dispersive X-ray spectroscopy (EDX) in a SEM-EDX Hitachi S-3400 N, equipped with a Si EDX analyser Röntec XFlash. Crystal structure was assessed by powder X-ray diffraction (XRD) in a Bruker AXS D8 Advance diffractometer. Electrolytic conductivity was measured using an Orion Star A112, with a 2-electrode probe, reference 011050MD, which had a nominal cell constant of 1.0 cm-1 and a measurement range from 1 μS·cm-1 to 20 mS·cm-1. The flow curve was determined in a Rotovisco Rheometer from Thermo Scientific. The rotatory viscometer was a Brookfield DV-E (Brookfield Engineering, Middleboro, Massachusetts, USA), using LV3 and LV4 spindles, and operating at 30 rpm.-- [Preparation of clay dispersions] Dispersions were prepared from the raw clay at two concentrations, resulting in different final densities, and various ratios of deflocculant sodium silicate.-- [Chemical composition and mineralogical characterization] Both elemental analysis by EDX and the XRD pattern confirmed that the raw clay consisted of a mixture of alumiosilicate minerals.-- [Flow curve] The general flow characteristics of a control Euroarce clay dispersion, performed with a rotational rheometer, revealed the characteristic non-Newtonian shear-thinning behavior, where viscosity (η) strongly decreased with stirring shear rate (𝛾̇) (Figure S2) (Amorós et al., 2002; Amorós et al., 2010). The flow curve (η vs. 𝛾̇) was well fitted to the Sisko equation (Sisko, 1958): 𝜂=𝜂∞+𝐾𝛾̇𝑛−1 (Equation S1) where η∞, K and n are parameters accounting for the viscosity of the Newtonian flow unit, the consistency factor and the power law index, respectively (Blissett and Rowson, 2013).-- [Electrolytic conductivity] To evaluate the applicability of the VRV in monitoring clay viscosity, dispersions with well-defined densities (either 1.55 or 1.39 g·cm-3) and quantities of sodium silicate (< 0.7 wt.%) were examined.-- [Thixotropy assessment and the effect of density] A further assessment of thixotropy with the VRV is shown in Figure S5. Viscometer curves η vs. t were measured on four samples of a clay dispersion batch, each subjected to different initial rest periods. After the rest time, the dispersion was put in contact with the vibrational probe, and η value was monitored for a time of 30 min.-- Experimental; Chemical composition and mineralogical characterization; Flow curve; Electrolytic conductivity; Deflocculation curve; Thixotropy assessment and the effect of density., Peer reviewed

(A–D, G–J’) S9 egg chambers of the designated genotypes stained with anti-pSqh (red) and the DNA marker Hoechst (blue) showing pSqh levels in the NCs (A–D) and the BCs (G–J’). (E, F, K, L) Quantification of pSqh levels in the NCs (E, F) and in the BCs (K, L) of egg chambers of the specified genotypes. G’–J’ Magnifications of the white boxes in G–J. The statistical significance of differences was assessed with a t test, * P value < 0.05, ** P value < 0.01, and *** P value < 0.001. Horizontal and vertical lines indicate mean and SD, respectively. Scale bar in A, 20 μm. The raw data underlying panels E, F, K, and L are available in S1 Data., Peer reviewed

A–D) Schematic drawings of early S9 (A), middle S9 (B), late S9 (C), and S10 egg chamber illustrating the BCs (yellow), NCs (gray), FCs (purple), BM (green), and the point of ablation in the NCs (blue bar). (A’–D’) Images of life control egg chambers of the indicated developmental stages expressing Resille-GFP before and after NC bonds are ablated. Blue bars indicate points of ablation. (E) Schematic representation of an egg chamber and the point of ablation in NCs. (F, G) Quantification of the initial velocity of vertex displacement of the indicated ablated bonds. The statistical significance of differences was assessed with a t test, * P value < 0.05 and ** P value < 0.01. Horizontal and vertical lines indicate mean and SD, respectively. Scale bar in A’–D’, 10 μm. The raw data underlying panels F and G are available in S1 Data., Peer reviewed

Experimental and computational details, characterization data, rate constants measured, Cartesian coordinates and energies of the stationary points located, and crystallographic data for (±)-6 and (SP)-12., Peer reviewed