Resultados de investigación

Table S1. Regional models driven by the ERA-Interim reanalysis from the European Centre for Medium-Range Weather Forecasts, for the 1989-2008 period. Table S2. EURO-CORDEX Regional models driven by the CMIP5 GCMs. Also shown the approximate spatial resolution from each GCM taken from https://portal.enes.org/data/enes-model-data/cmip5/resolution. Figure S1. Daily precipitation Intensity (left) and frequency (right) distributions taken from the hindcast EURO-CORDEX RCMs and ERA-Interim reanalysis (1989-2008) for the Iberian Peninsula. Also shown the Iberian Gridded Dataset distribution for the same domain and period. All RCM data was previously interpolated into the IGD 0.1o regular resolution. As for Era-Interim, two PDFs are shown, one for the original resolution of the low-resolution and other interpolated into the IGD resolution. The dash point and the value written refers to the 95th percentile of the observations for NGD on the original resolution (blue) and interpolated into the ERA-Interim resolution (red). The time periods are (a) Year, (b) DJF, (c) MAM, (d) JJA and (e) SON. Figure S2. Yearly and seasonal distribution added values (DAV) of the Iberian Peninsula, between the RCMs and the ERA-Interim reanalysis for the 1989-2008 period, taken from the Hindcast EURO-CORDEX simulations, with the NGD regular dataset as reference for (a) daily precipitation intensity, considering the whole PDF shown in the left panels of Figure S1, (b) daily precipitation frequency considering the whole PDF shown in the right panels of Figure S1, (c) daily precipitation intensity extremes, only considering the values above the observational 95th percentile shown in Figure S1 left side and (d) daily precipitation frequency extremes, only considering the values above the observational 95th percentile shown in the right side of Figure S1. All model data were previously interpolated to 0.1oregular resolution from the observations. Figure S3. Daily precipitation Intensity (left) and frequency (right) for the historical driving CMIP5 GCMs and EURO-CORDEX RCMs for the Iberian Peninsula, considering the 1971-2005 period, where all results were previously interpolated into the observational grid. The dash point and the value written refers to the 95th percentile of the bservations. (a) Year, (b) DJF, (c) MAM, (d) JJA and (e) SON. Figure S4. Daily precipitation Intensity (left) and frequency (right) for the historical driving CMIP5 GCMs and NGD observations interpolated into each GCM resolution for the Iberian Peninsula, considering the 1971-2005 period. Also shown the PDF from the NGD observations at the original resolution. (a) Year, (b) DJF, (c) MAM, (d) JJA and (e) SON. Figure S5. Yearly and seasonal distribution added values (DAV) of the Iberian Peninsula, between the RCMs and the CMIP5 GCMs for the 1989-2008 period, taken from the Historical EURO-CORDEX simulations, with the NGD regular dataset as reference for (a) daily precipitation intensity, considering the whole PDF shown in the left panels of Figure S3, (b) daily precipitation frequency considering the whole PDF shown in the right panels of Figure S3, (c) daily precipitation intensity extremes, only considering the values above the observational 95th percentile shown in Figure S3 left side and (d) daily precipitation frequency extremes, only considering the values above the observational 95th percentile shown in the right side of Figure S1. All model data were previously interpolated to 0.1o regular resolution from the observations. The thick blue lines separate the RCMs driven by different GCM., Peer reviewed

Table S1. Regional models forced by the ERA-Interim reanalysis from the European Centre for Medium-Range Weather Forecasts, for the 1989-2008 period. Table S2. EURO-CORDEX Regional models driven by the CMIP5 GCMs. Also shown the approximate spatial resolution from each GCM taken from https://portal.enes.org/data/enes-model-data/cmip5/resolution. Figure S1. Maximum (left) and minimum (right) daily temperature distributions taken from the hindcast EURO-CORDEX RCMs and ERA-Interim reanalysis (1989-2008) for the Iberian Peninsula. Also shown the Iberian Gridded Dataset distribution for the same domain and period. All RCM data was previously interpolated into the IGD 0.1o regular resolution. As for Era-Interim, two PDFs are shown, one for the original resolution of the low-resolution and other interpolated into the IGD resolution. The dash point and the value written refers to either the 90th percentile for max temperature or the 10th percentile for min temperature of the observations for NGD on the original resolution (blue) and interpolated into the ERA-Interim resolution (red). The time periods are (a) Year, (b) DJF, (c) MAM, (d) JJA and (e) SON. Figure S2. Yearly and seasonal distribution added values (DAV) of the Iberian Peninsula, between the RCMs and the ERA-Interim reanalysis for the 1989-2008 period, taken from the Hindcast EURO-CORDEX simulations, with the IGD regular dataset as a reference for (a) maximum daily temperature, considering the whole PDF, (b) minimum daily temperature considering the whole PDF. (c) maximum daily temperature extremes, only considering the values above the observational 90th percentile from maximum temperatures and (d) minimum temperature extremes only considering the values below the observational 10th percentile from minimum temperatures. All model data were previously interpolated to 0.1o regular resolution from the observations. Figure S3. Maximum (left) and minimum (right) daily temperature distribution for the historical EURO-CORDEX RCMs driven by the CMIP5 GCMs, for the Iberian Peninsula, considering the 1971-2005 period, where all results were previously interpolated into the observational grid. The dash point and the value written refers to the 90th percentile of the observations for the maximum temperature and to the 10th percentile of the observations for the minimum temperature. (a) Year, (b) DJF, (c) MAM, (d) JJA and (e) SON. Figure S4. Maximum (left) and minimum (right) daily temperature distributions for the historical driving CMIP5 GCMs and IGD observations interpolated into each GCM resolution for the Iberian Peninsula, considering the 1971-2005 period. Also shown the PDF from the IGD observations at the original resolution. (a) Year, (b) DJF, (c) MAM, (d) JJA and (e) SON. Figure S5. Yearly and seasonal distribution added values (DAV) of the Iberian Peninsula, between the RCMs and the CMIP5 GCMs for the 1989-2008 period, taken from the Historical EURO-CORDEX simulations, with the IGD regular dataset as a reference for (a) maximum daily temperature, considering the whole PDF shown in the left panels of Figure S3, (b) minimum daily temperature considering the whole PDF shown in the right panels of Figure S3, (c) maximum daily temperature extremes, only considering the values above the observational 90th percentile from maximum temperatures and (d) minimum daily temperature extremes, only considering the values below the bservational 10th percentile from minimum temperatures. All model data were previously interpolated to 0.1o regular resolution from the observations. The thick blue lines separate the RCMs driven by different GCM., Peer reviewed

18 pages. -- Appendix S1. Multiple paternity in clutches of wild sea turtles. Only those references reporting the number of clutches with multiple paternity were retained in Figure 1. -- Appendix S2. Full-sibling family assignments determined by COLONY2 software across 217 individual hawksbill turtles. -- Appendix S3. Full-sibling parentage assignments were inferred using COLONY2 software across 217 individual hawksbill turtles collected from six nests at Treasure Island (Set A and Set C, n = 93 and n = 94, respectively, three nests each) and from a single nest at Bounty Island (Set B, n = 30), Fiji, in the South Pacific., Peer reviewed

SUPPLEMENTAL TABLE 1. Data table show the list of genes from Apoptosis and Survival Tier 1 commercial plate for genes expression in samples taken from control NRVM in I/R, and in NRVM transfected with mimics of miR-29a or miR-251_1*. A mix of 4 cultures was added to each pool. Results are expressed in log fold change. SUPPLEMENTAL TABLE 2. Primers designed for genes RT- PCR purchased from Merck-Sigma-Aldrich (USA). SUPPLEMENTAL FIGURE 1. Cartoons outlining the experimental protocols of ischemia and reperfusion (I/R) conducted in vivo in animal models and in vitro in isolated cardiac myocytes. SUPPLEMENTAL FIGURE 2. miRNAs relative expression assessed in infarcted heart’s risk zones of I/R and I/R+Ucn-2 animal model at 1 week. SUPPLEMENTAL FIGURE 3. Control experiments for the expression of miR-29a and miR-451_1*. SUPPLEMENTAL FIGURE 4. miRNAs relative expression assessed in risk zones of infarcted hearts., Peer reviewed

Figure S1: Characterization of MZ and MM CRISPR/Cas9 generated iPSCs and iPSC derived hepatic cells, related to Figure 1. Figure S2: MZ and ZZ iHeps Demonstrate Metabolic and Mitochondrial Dysregulation, related to Figure 3 and Figure 4. Figure S3: Transcriptional Heterogeneity and Branch-Specific Activation of the UPR In MZ and ZZ iHeps related to Figure 3 and Figure 5. Table S1: Results for differential expression testing, GSEA Hallmark pathways, and GO terms related to mitochondria, ER and ER stress for PiZZ6 ZZ, MZ and MM iHep pairwise comparisons, related to Figure 2. "Table S4: Results of differential expression testing, GSEA analysis by original identity and Enrichr-generated enrichments from the top 50 differentially expressed genes for each Louvain cluster and cluster 0 vs 1 comparisons from scRNA seq for PiZZ1 ZZ, MZ, MM and PiZZ6 ZZ, related to Figure 5." Table S5: Results of Enrichr-generated enrichments from the top 50 differentially expressed genes for each Louvain cluster from scRNA seq for PiZZ100 ZZ and MM, related to Figure 5., Peer reviewed

Supplementary Table 1. Cardiac function assessed through echocardiography of patients included in the study. Supplementary Table 2. Adjusted means of metabolic phenotypes of fatty liver disease with visceral adipose tissue and visceral adipose tissue/subcutaneous adipose tissue ratio. Supplementary Table 3. Associations between metabolic phenotypes of fatty liver disease and high indexed epicardial adipose tissue (>68.1 mL). Supplementary Table 4. Associations between metabolic phenotypes of fatty liver disease and moderate to severe coronary artery calcification (Agatston CAC score>100)., [Background] To better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes., [Methods] Cross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography., [Results] Compared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively)., [Conclusion] MAFLD–T2D and MAFLD–OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting., Peer reviewed

Supplemental Table 1. Fatty acid composition in spleen cells of wild-type C57BL/6J mice at the end of 20-week dietary regimens. Supplemental Figure 1. An example of the gating strategy used to identify CD4+ (CD45+CD3+CD4+CD8–) and CD8+ (CD45+CD3+CD4–CD8+) T cells in spleen or bone marrow of wild-type C57BL/6J mice fed with the LFD and HFDs at the end of 20-week dietary regimens. SSC-A side scatter area, FSC-A forward scatter area, CD cluster of differentiation. Supplemental Figure 2. An example of the gating strategy used to identify CD3+ T cells and CD4+ and CD8+ T cell subsets in spleen cell suspensions of lean wild-type C57BL/6J mice after fatty acid treatment for 18 h. A similar gating strategy was used for bone marrow cell suspensions. SSC-A side scatter area, FSC-A forward scatter area, CD cluster of differentiation, 7-AAD 7-amino-actinomycin D. Supplemental Figure 3. CD3+ and CD4+ T cells in spleen cell suspensions of lean wild-type C57BL/6J mice treated with palmitic acid or oleic acid at indicated concentrations. The percentage relative to the negative control (cells without any treatment) of CD3+ and CD4+ T cells after the treatment of spleen cell suspensions with low-endotoxin fatty acid-free BSA control, BSA-palmitic acid complex (25-300 M) (A, D) or BSA-oleic acid complex (25-300 M) (B, E) for 18 h. The comparative of palmitic and oleic acids at 300 M is also shown (C, F). The data are presented as the mean (bars) and individual points ± SD values (n = 6), and those marked with different letters are significantly different (p<0.05). Differences between groups were assessed by one-way ANOVA with Tukey’s post hoc test or, in the case of variance heterogeneity, by Kruskal-Wallis with Bonferroni correction. CD cluster of differentiation, PA palmitic acid, OA oleic acid. Supplemental Figure 4. CD8+ T cells in spleen and CD3+ T cells in bone marrow (BM) cell suspensions of lean wild-type C57BL/6J mice treated with palmitic acid or oleic acid at indicated concentrations. The percentage relative to the negative control (cells without any treatment) of CD8+ T cells (spleen) and CD3+ T cells (BM) after the treatment of each cell suspension with low-endotoxin fatty acid-free BSA control, BSA-palmitic acid complex (25-300 M) (A, D) or BSA-oleic acid complex (25-300 M) (B, E) for 18 h. The comparative of palmitic and oleic acids at 300 M is also shown (C, F). The data are presented as the mean (bars) and individual points ± SD values (n = 6), and those marked with different letters are significantly different (p<0.05). Differences between groups were assessed by one-way ANOVA with Tukey’s post hoc test or, in the case of variance heterogeneity, by Kruskal-Wallis with Bonferroni correction. CD cluster of differentiation, PA palmitic acid, OA oleic acid. Supplemental Figure 5. CD4+ and CD8+ T cells in bone marrow (BM) cell suspensions of lean wild-type C57BL/6J mice treated with palmitic acid or oleic acid at indicated concentrations. The percentage relative to the negative control (cells without any treatment) of CD4+ and CD8+ T cells after the treatment of BM cell suspensions with low-endotoxin fatty acid-free BSA control, BSA-palmitic acid complex (300 M) (A, D) or BSA-oleic acid complex (300 M) (B, E) for 18 h. The comparative of palmitic and oleic acids at 300 M is also shown (C, F). The data are presented as the mean (bars) and individual points ± SD values (n = 6), and those marked with different letters are significantly different (p<0.05). Differences between groups were assessed by one-way ANOVA with Tukey’s post hoc test or, in the case of variance heterogeneity, by Kruskal-Wallis with Bonferroni correction. CD cluster of differentiation, PA palmitic acid, OA oleic acid., Peer reviewed

Supplementary Movie S1. FRAPexperiment in which the quick recovery of mEGFP-JMJD3 puncta after photobleaching is observed. Supplementary Movie S2. FRAP experiment in which the aggregation of mEGFP-JMJD3 is appreciated by means of a reduced mobility after photobleaching. Supplementary Data file 1. Table depicting the parameters that assess the quality of the Chst8 4C-seq experiments for each sample as previously described. Briefly, the % of reads containing VP sequence should be above 90, the % of fragments that map in cis above 50, and the % of reads that map in unique sites within 1Mb around VP above 60. Supplementary Data file 2 and 3. Tables containing the quality measurements for each sample of the Ldlrad4 4C-seq (2) and Aopep 4C-seq (3) experiments, according to the parameters previously described. Briefly, the % of reads containing VP sequence should be above 90, the % of fragments that map in cis above 50, and the % of reads that map in unique sites within 1Mb around VP above 60., Peer reviewed

A, Predictive models for hospital discharge during the first week in mild patients. B, Predictive models for worsening of clinical status during the first week in patients who were admitted mildly ill. AUC, area under the curve., Peer reviewed

S2 Fig. Migration and activation marker expressing in monocytes subset in mild and several/critical patients (S/C)., Peer reviewed