BUSCADOR RECOLECTA

Increased mitotic activity is associated with the genesis and aggressiveness of many cancers. To assess the clinical value of mitotic activity as prognostic biomarker, we performed a pan-cancer study on the mitotic network activity index (MNAI) constructed based on 54-gene mitotic apparatus network. Our pan-cancer assessment on TCGA (33 tumor types, 10,061 patients) and validation on other publicly available cohorts (23 tumor types, 9,209 patients) confirmed the significant association of MNAI with overall survival, progression-free survival, and other prognostic endpoints in multiple cancer types, including lower-grade gliomas (LGG), breast invasive carcinoma (BRCA), as well as many others. We also showed significant association between MNAI and genetic instability, which provides a biological explanation of its prognostic impact at pan-cancer landscape. Our association analysis revealed that patients with high MNAI benefitted more from anti-PD-1 and Anti-CTLA-4 treatment. In addition, we demonstrated that multimodal integration of MNAI and the AI-empowered Cellular Morphometric Subtypes (CMS) significantly improved the predictive power of prognosis compared to using MNAI and CMS alone. Our results suggest that MNAI can be used as a potential prognostic biomarker for different tumor types toward different clinical endpoints, and multimodal integration of MNAI and CMS exceeds individual biomarker for precision prognosis., Peer reviewed

Additional file 1: Table S1. Summary statistics of the Baikal 1600 m long-read sequencing and metagenomic assembly. Fig. S1. A Principal component analysis (PCA) between deep Lake Baikal metagenomes based on a Bray-Curtis similarity k-mer profile frequencies of sequencing reads. Red and blue dots represent summer and winter Illumina metagenomes, respectively, while the green dot is the sample retrieved in this study and sequenced with PacBio Sequel II. B Phylum-level composition based on 16S rRNA gene fragments (Illumina and PacBio CCS5 reads) of the different metagenomes. The single metagenome highlighted in green corresponds to the PacBio sequencing, whilst the rest of datasets belong to previous Illumina sequencing. The phylum Proteobacteria was divided into its class-level classification. Only those groups with abundance values larger than 1% in any of the metagenomes are shown. C Classification of the 1600 m PacBio CCS5 16S rRNA reads at a higher taxonomic resolution. Only sequences larger than 1000 nucleotides were considered. Sequences ascribed to the Ca. Patescibacteria phylum are highlighted in green. Table S2. Genomic parameters of LAGs recovered in this study. Table S3. Genomic parameters of LAGs recovered in this study with ANI > 99.5% to MAGs retrieved from Lake Baikal 1250 and 1350 m deep. Fig. S2. Alignment of two LAGs that are complete in a single contig and the respective MAG from the Illumina assembly. Table S4. Genomic parameters of the resulting bins from the Baikal 1600 m CCS sequences. The four Baikalibacteria bins are highlighted in yellow. Fig. S3. A Maximum likelihood phylogenetic tree of the Baikalibacteria 16S rRNA genes. Sequences outside the deep branch coming from Figure 1 were used as an outgroup for the tree. The reads from the four read bins are colored in the figure. B Diversity of 16S rRNA sequences of Baikalibacteria bins. Linear representation of selected CCS5 reads (indicated with a red circle in the left panel) containing a 16S rRNA gene. A pairwise blastn comparison among reads was performed to detect orthologous genes. Fig. S4. A Average nucleotide identity based on metagenomic reads (ANIr) of LAGs and the four Baikalibacteria Bins. B ANIr of ten randomly selected sequences of each Baikalibacteria bin. Fig. S5. Metagenomic recruitment of the largest fragment of Baikalibacteria RBin09 on Lake Thun 180 m deep. Fig. S6. Maximum likelihood phylogenetic tree of the a phytoene elongase (LyeJ), b carotenoid 3,4-desaturase (CrtD), and c bisanhydrobacterioruberin hydratase (CruF) proteins., Peer reviewed

(A) cbk1-5E-E164S cbk1-aid cdc15-2 (YMF3905), (B) cbk1-5E-E251S cbk1-aid cdc15-2 (YMF3910), (C) cbk1-5E-E409S cbk1-aid cdc15-2 (YMF3995), (D) cbk1-5E-E615T cbk1-aid cdc15-2 (YMF3906), and (E) cbk1-5E-E711S cbk1-aid cdc15-2 (YMF3907) cells were grown in YPD and arrested in late anaphase by shifting the temperature to 37 °C before the addition of rapamycin to half of the culture for 20 min. To allow progression through the cell cycle, cells were released in the absence (i) or presence (ii) of rapamycin. Samples were taken at the indicated times to determine cell-cycle progression by flow cytometry. (F) 3D Cbk1 structure (PDB 4LQS [48]) in which different protein domains are highlighted. Residue T574 in the activation loop, together with residues D475 and S409 in the kinase domain are denoted. (G) cbk1-T574A cbk1-aid cdc15-2 cells (YMF4191) were grown as above. FACS graphs can be found in the supplementary FACS file (S1 File)., pbio.3002263.s005.pdf, Peer reviewed

- Document S1. Figures S1–S7. - Table S1. List of differentially expressed genes in WT vs. mutant samples at 12 dpa with statistical data and TPM for each sample, related to Figure 6C. - Table S2. List of differentially expressed genes in WT vs. mutant samples at 14 dpa with statistical data and TPM for each sample, related to Figure 6C. - Table S3. Overlapping genes from the intersection of 12 dpa and 14 dpa lists of differentially expressed genes with statistical data and TPM for each sample, related to Figure 6C. - Table S4. Functional annotation results from common DEGs at 12 and 14 dpa that were upregulated in the WT blastema, related to Figure 6D. - Table S5. Functional annotation results from common DEGs at 12 and 14 dpa that were upregulated in the mutant blastema, related to Figure 6E. - Document S2. Article plus supplemental information., Peer reviewed

DNA extraction protocol (Cobas® DNA Sample Preparation Kit) Table S1. Panel of 29 genes analyzed with next generation sequencing, and distinction between nephropathic and phenocopy genes Table S2. Total variants, silent and non-silent mutations in FSGS patients Table S3. List of variants based on the UnifiedGenotyper and ACMG score Tabla S4. Frequency of variants annotated found in our study ..., Peer reviewed

Additional file 1: Supplementary Table 1. Detailed sequencing data obtained in this study., Horizon 2020 Framework Programme Ministerio de Ciencia e Innovación Generalitat Valenciana Consejo Superior de Investigaciones Cientificas (CSIC), Peer reviewed

Aquaculture is the fastest-growing food production sector and nowadays provides more food than extractive fishing. Studies focused on the understanding of how teleost growth is regulated are essential to improve fish production. Cysteamine (CSH) is a novel feed additive that can improve growth through the modulation of the GH/IGF axis; however, the underlying mechanisms and the interaction between tissues are not well understood. This study aimed to investigate the effects of CSH inclusion in diets at 1.65 g/kg of feed for 9 weeks and 1.65 g/kg or 3.3 g/kg for 9 weeks more, on growth performance and the GH/IGF-1 axis in plasma, liver, stomach, and white muscle in gilthead sea bream (Sparus aurata) fingerlings (1.8 ± 0.03 g) and juveniles (14.46 ± 0.68 g). Additionally, the effects of CSH stimulation in primary cultured muscle cells for 4 days on cell viability and GH/IGF axis relative gene expression were evaluated. Results showed that CSH-1.65 improved growth performance by 16% and 26.7% after 9 and 18 weeks, respectively, while CSH-3.3 improved 32.3% after 18 weeks compared to control diet (0 g/kg). However, no significant differences were found between both experimental doses. CSH reduced the plasma levels of GH after 18 weeks and increased the IGF-1 ones after 9 and 18 weeks. Gene expression analysis revealed a significant upregulation of the ghr-1, different igf-1 splice variants, igf-2 and the downregulation of the igf-1ra and b, depending on the tissue and dose. Myocytes stimulated with 200 µM of CSH showed higher cell viability and mRNA levels of ghr1, igf-1b, igf-2 and igf-1rb compared to control (0 µM) in a similar way to white muscle. Overall, CSH improves growth and modulates the GH/IGF-1 axis in vivo and in vitro toward an anabolic status through different synergic ways, revealing CSH as a feasible candidate to be included in fish feed., Peer reviewed

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Figure S1: Absorption spectra and standard curve of CIP at different concentrations in inorganic α-MEM solution at 25 ◦C.; Figure S2. (a,d) Optical micrographs, (b,e) 3D rendering and (c,f) variation of surface topography in 3D of (a–c) drug-free and (d–f) CIP-loaded HHC systems; Figure S3: Zwitterionic chelate complex of ciprofloxacin with Mg2+ and Ca2+ cations (M) released by PEO coating and Mg alloy; Figure S4: (a) Evolution of OCP for HHC and HH+CIP during 1 and 24 h of immersion. (b,c) Nyquist and Bode diagrams for HHC and HHC+CIP specimens after 1 h and 24 h of immersion in inorganic α-MEM solution at 37 ◦C; Table S1. Fitted electrical parameters of EIS spectra of HHC and HHC+CIP specimens after 1 h and 24 h of immersion in inorganic α-MEM solution at 37 ◦C. Chi-square range: 0.001446-0.003891, Peer reviewed

[Introduction]: Drought-associated tree mortality has been increasing worldwide since the last decades, impacting structure and functioning of forest ecosystems, with implications for energy, carbon and water fluxes. However, the understanding of the individual vulnerability to drought-induced mortality is still limited., [Methods]: We aimed to identify the factors that triggered the mortality of the widely distributed Pinus sylvestris L. in an extensive forest area in central Spain. We compared radial growth patterns in pairs of alive and recently dead individuals that co-occur in close proximity and present similar age and size, thereby isolating the effects of size and environment from the mortality process. Temporal dynamics of growth, growth synchrony, and growth sensitivity to water availability (precipitation minus potential evapotranspiration) were compared between alive and recently dead trees., [Results and discussion]: Over the last 50 years, although we did not detect significant differences in growth between alive and dead trees, an increase in the growth synchrony and sensitivity to water availability (i.e. slope of the climatic water balance in the growth model) was observed in all trees as drought intensity increased. 20 years before mortality, dead individuals showed lower growth synchrony and growth sensitivity to water availability than alive ones, without significant differences in growth. Recorded reduction in growth synchrony and growth sensitivity to water availability in dead trees suggests a decoupling between tree growth and climate, which could increase the risk of hydraulic failure and/or carbon starvation under increasingly arid conditions. Thus, the use of reduced growth sensitivity to water availability as potential early-warning signal of tree mortality, together with reduced growth synchrony, should be further explored, particularly in pine species in seasonally dry areas., Peer reviewed