BUSCADOR RECOLECTA

Supplementary Figure S5: Immune signatures and IMMETCOLS in 75 samples of 75 mCRC. A) heatmap of transcriptomics immune signatures in 75 mCRC stratified according to IMMETCOLS. GEP is the average expression of the genes of the GEP signature. Immunophenoscore is the aggregate of the MHC (Antigen Processing), EC (Effector cells), CP (Checkpoints and Immunomodulators) and SC (Suppressor cells) scores. B) Average immunophenogram in each IMMETCOLS cluster in the 75 mCRC. Inner circle plots each of the four Immunophenoscore components with higher values representing a more immunogenic phenotype. The outer cycle plots the expression of markers used to compute each of the immunophenoscore components., Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of immune check point inhibitors. In this study, we developed an immune-metabolic signature suitable for personalized ICI therapies. A classifier using an immune-metabolic signature (IMMETCOLS) was developed on a training set of 77 metastatic colorectal cancer (mCRC) samples and validated on 4,200 tumors from the TCGA database belonging to 11 types. Here, we reveal that the IMMETCOLS signature classifies tumors into three distinct immune-metabolic clusters. Cluster 1 displays markers of enhanced glycolisis, hexosamine byosinthesis and epithelial-to-mesenchymal transition. On multivariate analysis, cluster 1 tumors were enriched in pro-immune signature but not in immunophenoscore and were associated with the poorest median survival. Its predicted tumor metabolic features suggest an acidic-lactate-rich tumor microenvironment (TME) geared to an immunosuppressive setting, enriched in fibroblasts. Cluster 2 displays features of gluconeogenesis ability, which is needed for glucose-independent survival and preferential use of alternative carbon sources, including glutamine and lipid uptake/β-oxidation. Its metabolic features suggest a hypoxic and hypoglycemic TME, associated with poor tumor-associated antigen presentation. Finally, cluster 3 is highly glycolytic but also has a solid mitochondrial function, with concomitant upregulation of glutamine and essential amino acid transporters and the pentose phosphate pathway leading to glucose exhaustion in the TME and immunosuppression. Together, these findings suggest that the IMMETCOLS signature provides a classifier of tumors from diverse origins, yielding three clusters with distinct immune-metabolic profiles, representing a new predictive tool for patient selection for specific immune-metabolic therapeutic approaches., Peer reviewed

Raw microscopy data for Fig2A and G in .lif format in a single zip file., Resources available on the publisher's site: https://doi.org/10.25452/figshare.plus.19064324.v1, Marie Skłodowska-Curie grant agreement No. 754510 Ministry of Science, Innovation and Universities PGC2018-095616-B-I00 Ministry of Science, Innovation and Universities PGC2018-099562-B-I00 NIH Intramural Funding, National Cancer Institute, Peer reviewed

Raw microscopy data for Fig6A, F, G, S1 and S2 (.lif or .jpg format) in a single zip file., Resources available on the publisher's site: https://doi.org/10.25452/figshare.plus.18310361.v1, Deutsche Forschungsgemeinschaft DFG PH144/4-1 and PH144/6-1, Peer reviewed

Source microscopy data for Fig8A, B, C, D and S1 (.lif and .jpg file) in a single zip file., Resources available on the publisher's site: https://doi.org/10.25452/figshare.plus.18312410.v1, Deutsche Forschungsgemeinschaft DFG PH144/4-1 and PH144/6-1, Peer reviewed

Additional file 12 Figure S7. Scheme of the effect of Myosin over F-actin. (1), Myosin movement in parallel f-Actin. (2) F-actin sliding. (3) Tension building in the filaments. (4) Release from cortex after threshold tension is reached. After release, tension (illustrated in red) is redistributed to other F-actin in the network., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Appendix A: videos showing the spatial and temporal evolution of CO2: Videos displaying the spatial and temporal evolution of CO2 levels within the classroom for continuous ventilation conditions: First campaign day: file '20201210_CO2evolution_H=150cm.avi': https://nube.liftec.unizar-csic.es/index.php/s/rqdn9PG9T1dS1OB. Second campaign day: file '20201211_CO2evolution_H=150cm.avi': https://nube.liftec.unizar-csic.es/index.php/s/NsZV3bfypk9O49. Appendix B: CO2 evolution with time for different sensors within the classroom: This appendix provides additional information regarding the differences found between the 17 sensors located in the classroom. B1. Differences in height: In order to facilitate the readability of graphs, the 9 sensors used to ascertain differences in height (H1 to H9, see right side of Figure 2) have been grouped into 3 series representing the average of the 3 sensors at each measuring day. B2. Differences among zones: As for the 11 sensors used to assess differences among room zones (see left side of Figure 2), in this case only the three analyzers with clearer deviations (that is, P1, P2 and T9) will be plotted along with the plane average.-- Under a Creative Commons license cc-by-nc-nd 4.0., This work was conducted in the framework of the ‘Study of measures for prevention of airborne transmission of COVID-19 in schools and public transport in the city of Zaragoza’, in collaboration with the City Council of Zaragoza. The research group is a member of Aireamos, a group created in Spain to promote ventilation and CO2 monitoring as key measures to prevent airborne transmission of COVID-19. The authors would like to warmly thank the teaching staff and the students of CEIP Santo Domingo for their full availability and implication throughout the test campaign., The campaign described in this work consisted in 4 complete school days (10th, 11th, 15th and December 18, 2020). Ambient conditions during the first 3 days were typical of Continental-Mediterranean climate winters (Zaragoza has a Köppen-Geiger climate classification of BSk). Temperature records at the starting of these school days ranged between 6 and 8 °C, steadily increasing until reaching 10–15 °C at the end. By contrast, the fourth day (18th December) was foggy, with considerably lower and more stable temperatures (4–6 °C throughout all the school day). Wind velocities were typically below 10 km/h for all the cases, about half of the historic average in Zaragoza for December (Hernández, 1990). Therefore, velocities were sufficiently low and similar throughout the test period to discard any significant influence of wind on the differences found among the various strategies explored. 17 sensors were located in the classroom., Appendix A: videos showing the spatial and temporal evolution of CO2: First campaign day. Second campaign day. Appendix B: CO2 evolution with time for different sensors within the classroom: B1. Differences in height: Figure B1. Temporal evolution of CO2 recorded at the different heights for the first measuring day. Figure B2. Temporal evolution of CO2 recorded at the different heights for the third measuring day. Figure B3. Temporal evolution of CO2 recorded at the different heights for the fourth measuring day. B2. Differences among zones: Figure B4. Temporal evolution of CO2 for the first measuring day. Analysis in terms of differences among zones. Figure B5. Temporal evolution of CO2 for the second measuring day. Analysis in terms of differences among zones. Figure B6. Temporal evolution of CO2 for the third measuring day. Analysis in terms of differences among zones. Figure B7. Temporal evolution of CO2 for the fourth measuring day. Analysis in terms of differences among zones., Peer reviewed

Here you can found the two SPSS database to replicate the analyses for the validation of the ABC Connectedness to Nature Scale, validated in a paper published at the Environmental Education Research (doi: 10.1080/13504622.2022.2111407)., Peer reviewed

All images show projections of confocal sections, except D, I, L, O, and Q, which show single confocal sections. (A, B) The overexpression of GFP-kkv in the trachea leads to the presence of intracellular chitin vesicles at early stages (pink arrowheads) (A, A’). At later stages, intracellular chitin vesicles are not present, and chitin is deposited extracellularly in the lumen (blue arrowheads and inset) (B, B’). (C, C’) In exp reb mutants, the overexpression of GFP-kkv in the trachea produces intracellular chitin punctae until late stages (pink arrowheads). (D) The overexpression of GFP-kkv in salivary glands produces intracellular chitin vesicles (pink arrowheads). (E) Schematic representation of Exp protein. (F, G) In exp reb mutants, the expression of a wild-type form of exp/reb rescues the lack of extracellular chitin deposition (F, white arrow and inset), while expΔMH2/rebΔMH2 do not (G, white arrow points to absence of CBP). (H, I) The co-overexpression of GFP-kkv and expΔMH2 in control embryo does not produce morphogenetic defects in trachea (H) or extracellular chitin deposition in salivary glands (white arrow) (I); however, intracellular chitin punctae are present (pink arrowheads in H, I, and inset in H). (J) The coexpression of GFP-kkv and expΔMH2 in exp reb mutants produces intracellular chitin particles (pink arrowheads) but does not rescue the lack of extracellular chitin deposition. (K, L) RebΔMH2 localises apically in trachea (K) and in salivary glands (L). (M) MH2-reb is not able to rescue the absence of extracellular chitin deposition in exp reb mutants. (N, O) The simultaneous expression of MH2-reb and GFP-kkv does not produce morphogenetic defects or ectopic chitin deposition in trachea (N) and in salivary glands (white arrow in O), but intracellular chitin vesicles are present (pink arrowhead in O). (P, Q) MH2-Exp protein does not localize apically in trachea (P) or in salivary gland (Q). Scale bars A-C, F-H, J, M, N: 25 μm; D, I, K, L, O-Q: 10 μm., Peer reviewed

The excerpted portion of the immunoblot shown in the figures is highlighted by a black box., Peer reviewed

All images correspond to projections of confocal sections. (A-D) At early stages, overexpressed GFP-Kkv accumulates apically (white arrow in B) and in intracellular punctae (blue arrow in B), as endogenous Kkv (white and blue arrows in A), but also in the whole cell. At later stages, GFP-Kkv shows a pattern in stripes that corresponds to the taenidial folds (inset in D), in a comparable pattern to the endogenous Kkv (inset in C). Endogenous Kkv at late stages localises mainly apical and almost no intracellular punctae are detected (C). GFP-Kkv also localises mainly apical, but in addition, Kkv intracellular punctae are also detected (blue arrow in D). (E-H) In trachea, the simultaneous overexpression of reb and GFP-kkv anticipates chitin deposition (compare E and F). At later stages, this results in different morphogenetic defects like short and straight tubes and defects in branch fusion (compare H and G). (I) In salivary glands, the coexpression of reb and GFP-kkv promotes accumulation of chitin in the lumen. Scale bars: 10 μm., Peer reviewed