BUSCADOR RECOLECTA

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See the supplementary material for further details on the electronic structure and quantum dynamical methods, electronic diabatic Hamiltonians, and characterization of the normal modes used in the simulations., Peer reviewed

Microglial cells are recognized as very dynamic brain cells, screening the environment and sensitive to signals from all other cell types in health and disease. Apolipoprotein D (ApoD), a lipid-binding protein of the Lipocalin family, is required for nervous system optimal function and proper development and maintenance of key neural structures. ApoD has a cell and state-dependent expression in the healthy nervous system, and increases its expression upon aging, damage or neurodegeneration. An extensive overlap exists between processes where ApoD is involved and those where microglia have an active role. However, no study has analyzed the role of ApoD in microglial responses. In this work, we test the hypothesis that ApoD, as an extracellular signal, participates in the intercellular crosstalk sensed by microglia and impacts their responses upon physiological aging or damaging conditions. We find that a significant proportion of ApoD-dependent aging transcriptome are microglia-specific genes, and show that lack of ApoD in vivo dysregulates microglial density in mouse hippocampus in an age-dependent manner. Murine BV2 and primary microglia do not express ApoD, but it can be internalized and targeted to lysosomes, where unlike other cell types it is transiently present. Cytokine secretion profiles and myelin phagocytosis reveal that ApoD has both long-term pre-conditioning effects on microglia as well as acute effects on these microglial immune functions, without significant modification of cell survival. ApoD-triggered cytokine signatures are stimuli (paraquat vs. Aβ oligomers) and sex-dependent. Acute exposure to ApoD induces microglia to switch from their resting state to a secretory and less phagocytic phenotype, while long-term absence of ApoD leads to attenuated cytokine induction and increased myelin uptake, supporting a role for ApoD as priming or immune training factor. This knowledge should help to advance our understanding of the complex responses of microglia during aging and neurodegeneration, where signals received along our lifespan are combined with damage-triggered acute signals, conditioning both beneficial roles and limitations of microglial functions., Peer reviewed

[Introduction]: The Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease., [Methods]: We analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells., [Results]: Exposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines., [Conclusion]: We have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage., Peer reviewed

S1 Fig. Workflow for the manual and automatic text-mining searches. A starting list of 6034 mammal viruses was used to obtain, which were then reviewed using both manual and PubmedKB-based automated strategies. The resulting virus-receptor pairs were combined with known databases and manually curated (see text for full description). M, manual strategy; PKB, PubmedKB strategy., S2 Fig. Roles of known receptors according to viral family. Only families with at least 10 known virus-host interactions are represented. Families of enveloped and non-enveloped viruses are shown, and within each group, families are sorted by the fraction of known receptors that are sufficient for viral entry (main plus alternative receptors)., S3 Fig. Research effort versus the known number of host proteins used as receptors for different viral families. Data points correspond to individual viruses. Those corresponding to the indicated family are shown in color (blue for non-enveloped viruses; yellow for enveloped viruses), and grey points correspond to all other viruses. The colored and grey dashed lines show the GLM prediction obtained specifically for the family and all viruses, respectively. Only families with at least 5 viral species in the dataset were considered., S1 Table. Database of virus receptors generated in this study. The following information is provided: the viral species, number of PubMed records and Genbank sequences available for each virus, viral family, presence of an envelope, number of host species, receptor symbol, receptor nature, functional role of the receptor, corresponding gene symbol, original publication PMID, year of discovery, and whether the virus-receptor interaction was reported in previous reviews and databases., S2 Table. Scores obtained from the GBM. The gene symbol, assigned score (probability of being a receptor), and whether the corresponding protein is a known receptor are indicated., S3 Table. Relevant features identified by the GBM. Gain represents the relative contribution of each variable to the model prediction. Cover indicates the relative number of observations that are related to a given variable., Peer reviewed

S1 Fig. Time of exposure. We tested the effect of the exposure time to CPC. To do so, IAV/WSN/33 was incubated with CPC at 0.1% for 2 minutes, 1 minute, or 30 seconds. Next, the virus was diluted and used to infect MDCK cells as previously described. After 48 hours of infection, the viral load was assessed by TCID50. We used a 2-minute treatment with SDS at 0.05% as a positive control and PBS solution as a negative control. No differences in the viral load were observed between the 2 minutes, 1 minute, or 30 seconds exposure., Peer reviewed

Figure S1: Differences in the composition of each donor attributed to protocol variations; Table S1: Abundance matrix displaying viral counts across samples. Table S2: Relative abundance of the viral families identified for each sample in the study, used for Figure 3., Peer reviewed

The incorporation of novel, functional, and sustainable foods in human diets is increasing because of their beneficial effects and environmental-friendly nature. Chia (Salvia hispanica L.) has proved to be a suitable source of bioactive peptides via enzymatic hydrolysis. These peptides could be responsible for modulating several physiological processes if able to reach the target organ. The bioavailable peptides contained in a hydrolysate obtained with Alcalase, as functional foods, were identified using a transwell system with Caco-2 cell culture as the absorption model. Furthermore, 20 unique peptides with a molecular weight lower than 1000 Da and the higher statistical significance of the peptide-precursor spectrum match (−10 log P) were assessed by in silico tools to suggest which peptides could be those exerting the demonstrated bioactivity. From the characterized peptides, considering the molecular features and the results obtained, the peptides AGDAHWTY, VDAHPIKAM, PNYHPNPR, and ALPPGAVHW are anticipated to be contributing to the antioxidant and/or ACE inhibitor activity of the chia protein hydrolysates., Peer reviewed

1 file, The Greenland-Portugal A25 OVIDE line is carried out biennially since 2002. The section is composed of 98 stations where hydrographic, biogeochemical and current measurements are carried out down to the bottom. OVIDE is a contribution to the international programs Go-Ship, IOCCP, and CLIVAR. This data set contains the final (adjusted) CTDO2 data, Peer reviewed

Supplementary Table S1. Maternal age, maternal weight status, mode of delivery, gestational age, birth weight, gender, and human milk sampling time of entire study group and subgroups., Peer reviewed