Type 3 innate lymphoid cells: Guardians of epithelial barriers

In the past few years, an emerging group of innate lymphoid cells (ILCs) has been identified in mucosa I tissues. ILCs are found close to epithelial barriers, where they constitute a major source of the homeostatic cytokine interleukin 22. ILC cytokine profiles resemble those produced by helper T cells, yet they lack antigen specificity and provide a quicker immune response. Recent studies brought to light a previously unappreciated role of ILCs in protecting against enteric pathogens and promoting homeostasis in mucosal tissues. However, the role of ILCs in tissue damage in the absence of pathogenic infections remains unknown. This thesis aims to investigate the contribution of type 3 innate lymphoid cells (ILC3) in intestinal epithelial damage responses. Activation mechanisms and effector functions of ILC3 will be discussed in the context of intestinal damage

Yap1-Driven Intestinal Repair Is Controlled by Group 3 Innate Lymphoid Cells

Intestinal repair is driven by epithelial stem cells, but how these stem cells are instructed to initiate repair was unknown. Here, Romera-Hernández et al. report that epithelial proliferation after damage is independent of the stem cell-protective signal IL-22 but requires ILC3-dependent amplification of regenerative YAP1 signaling in stem cells.Tissue repair requires temporal control of progenitor cell proliferation and differentiation to replenish damaged cells. In response to acute insult, group 3 innate lymphoid cells (ILC3s) regulate intestinal stem cell maintenance and subsequent tissue repair. ILC3-derived IL-22 is important for stem cell protection, but the mechanisms of ILC3-driven tissue regeneration remain incompletely defined. Here we report that ILC3-driven epithelial proliferation and tissue regeneration are independent of IL-22. In contrast, ILC3s amplify the magnitude of Hippo-Yap1 signaling in intestinal crypt cells, ensuring adequate initiation of tissue repair and preventing excessive pathology. Mechanistically, ILC3-driven tissue repair is Stat3 indepe

La Cuevona de Avín (Avín, Asturias, North Spain): A new Late Pleistocene site in the lower valley of the River Güeña

The archaeological investigations carried out in the last twenty years in the Lower Valley of the River Güeña (Asturias, central part of northern Spain) have documented different prehistoric sites, particularly with Middle and Upper Palaeolithic occupations. This paper presents the first results of the archaeological excavation carried out in the cave of La Cuevona de Avín. From the systematic study of the biotic and abiotic remains, a total of three occupation phases (Phases 1 to 3) have been determined, dated in the Late Pleistocene. The lithic studies indicate the use of local raw materials (mainly quartzite), but also regional ones (different types of flint) in the whole sequence. Retouched implements are typologically representative only during the Upper Magdalenian (Phase II) and use-wear analysis indicates the manufacture and use of artefacts in situ during this phase. Archaeozoological studies reveal continuity in subsistence strategies throughout the sequence, noting specialization in red deer hunting during the Azilian (Phase I), and more diversified prey in the older phases of the sequence. © 2022 The Author(s

Higgs decay to dark matter in low energy SUSY: is it detectable at the LHC ?

Due to the limited statistics so far accumulated in the Higgs boson search at the LHC, the Higgs boson property has not yet been tightly constrained and it is still allowed for the Higgs boson to decay invisibly to dark matter with a sizable branching ratio. In this work, we examine the Higgs decay to neutralino dark matter in low energy SUSY by considering three different models: the minimal supersymmetric standard model (MSSM), the next-to-minimal supersymmetric standard models (NMSSM) and the nearly minimal supersymmetric standard model (nMSSM). Under current experimental constraints at 2-sigma level (including the muon g-2 and the dark matter relic density), we scan over the parameter space of each model. Then in the allowed parameter space we calculate the branching ratio of the SM-like Higgs decay to neutralino dark matter and examine its observability at the LHC by considering three production channels: the weak boson fusion VV->h, the associated production with a Z-boson pp->hZ+X or a pair of top quarks pp->htt_bar+X. We find that in the MSSM such a decay is far below the detectable level; while in both the NMSSM and nMSSM the decay branching ratio can be large enough to be observable at the LHC.Comment: Version in JHE

Functional differences between human NKp44- and NKp44+ RORC+ innate lymphoid cells

Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC+ innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC+ innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44+ IL-22 producing cells are present in tonsils while NKp44- IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44+ ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44+ ILC are the main ILC subset producing IL-22. NKp44- ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses

Priority use cases for antibody-detecting assays of recent malaria exposure as tools to achieve and sustain malaria elimination

Measurement of malaria specific antibody responses represents a practical and informative method for malaria control programs to assess recent exposure to infection. Technical advances in recombinant antigen production, serological screening platforms, and analytical methods have enabled the identification of several target antigens for laboratory based and point-of-contact tests. Questions remain as to how these serological assays can best be integrated into malaria surveillance activities to inform programmatic decision-making. This report synthesizes discussions from a convening at Institut Pasteur in Paris in June 2017 aimed at defining practical and informative use cases for serology applications and highlights five programmatic uses for serological assays including: documenting the absence of transmission; stratification of transmission; measuring the effect of interventions; informing a decentralized immediate response; and testing and treating P. vivax hypnozoite carriers

The Imaging Magnetograph eXperiment (IMaX) for the Sunrise balloon-borne solar observatory

The Imaging Magnetograph eXperiment (IMaX) is a spectropolarimeter built by four institutions in Spain that flew on board the Sunrise balloon-borne telesocope in June 2009 for almost six days over the Arctic Circle. As a polarimeter IMaX uses fast polarization modulation (based on the use of two liquid crystal retarders), real-time image accumulation, and dual beam polarimetry to reach polarization sensitivities of 0.1%. As a spectrograph, the instrument uses a LiNbO3 etalon in double pass and a narrow band pre-filter to achieve a spectral resolution of 85 mAA. IMaX uses the high Zeeman sensitive line of Fe I at 5250.2 AA and observes all four Stokes parameters at various points inside the spectral line. This allows vector magnetograms, Dopplergrams, and intensity frames to be produced that, after reconstruction, reach spatial resolutions in the 0.15-0.18 arcsec range over a 50x50 arcsec FOV. Time cadences vary between ten and 33 seconds, although the shortest one only includes longitudinal polarimetry. The spectral line is sampled in various ways depending on the applied observing mode, from just two points inside the line to 11 of them. All observing modes include one extra wavelength point in the nearby continuum. Gauss equivalent sensitivities are four Gauss for longitudinal fields and 80 Gauss for transverse fields per wavelength sample. The LOS velocities are estimated with statistical errors of the order of 5-40 m/s. The design, calibration and integration phases of the instrument, together with the implemented data reduction scheme are described in some detail.Comment: 17 figure

Unexplored olive cultivars from the Valencian Community (Spain): some chemical characteristics as a valorization strategy

[EN] The olive processing industry has till date been dominated by a small group of cultivars, leading to the possibility of some olive cultivars becoming extinct in the near future. In this study, we determined the composition of some chemical components in the olive oils from 31 minor olive cultivars of the Valencian Community. Our main aim was to identify suitable cultivars, which could produce differentiated olive oils, thus aiming towards their valorization. The average oil content of minor olive cultivars was found to be good, with some of them reporting approximately 60% (dry basis). On average, the total phenolic content was 229mg kg(-1), with cv. Mas Blanc reporting the highest content (570mg kg(-1)). Among the various tocopherols found in olives, -tocopherol was the main constituent, with a maximum concentration of 290.6mg kg(-1). Linoleic acid was the main polyunsaturated fatty acid and varied between 3.4% (cv. Del Pomet) and 16.9% (cv. Blanqueta Enguera). Special attention needs to be paid to the composition of sterols, since some olive oils exceeded the limits established for some sterols by the current European legislation. Some of the cultivars studied were highly productive, and originated differentiated olive oils with a rich composition of antioxidants and essential fatty acids. In some cases, these beneficial compounds were higher than those of commercial oils obtained from the most common cultivars worldwide. These results could contribute to the commercial exploitation of some of the studied cultivars.Salazar-García, DC.; Malheiro, R.; Pereira, JA.; López- Cortés, I. (2019). Unexplored olive cultivars from the Valencian Community (Spain): some chemical characteristics as a valorization strategy. European Food Research and Technology. 245(2):325-334. https://doi.org/10.1007/s00217-018-3164-7S3253342452Avidan B, Birger R, Abed-El-Hadi F, Salmon O, Hekster O, Friedman Y, Lavee S (2011) Adopting vigorous olive cultivars to high density hedgerow cultivation by soil applications of uniconazole, a gibberellin synthesis inhibitor. Span J Agric Res 9:821–830Barranco D, Rallo L (2000) Olive cultivars in Spain. HortTechnology 10:107–110Navero DB (2000) World catalogue of olive varieties. International Olive Oil Council, MadridBorges TH, Pereira JA, Cabrera-Vique C, Lara L, Oliveira AF, Seiquer I (2017) Characterization of Arbequina virgin olive oils produced in different regions of Brazil and Spain: physicochemical properties, oxidative stability and fatty acid profile. Food Chem 215:454–462Laroussi-Mezghani S, Le Dréau Y, Molinet J, Hammami M, Grati-Kamoun N, Artaud J (2016) Biodiversity of Tunisian virgin olive oils: varietal origin classification according to their minor compounds. Eur Food Res Technol 242:1087–1099Kosma I, Vavoura M, Kontakos S, Karabagias I, Kontominas M, Apostolos K, Badeka A (2016) Characterization and classification of extra virgin olive oil from five less well-known Greek olive cultivars. J Am Oil Chem Soc 93:837–848Reboredo-Rodríguez P, González-Barreiro C, Cancho-Grande B, Valli E, Bendini A, Toschi TG, Simal-Gandara J (2016) Characterization of virgin olive oils produced with autochthonous Galician varieties. Food Chem 212:162–171Kyçyk O, Aguillera MP, Gaforio JJ, Jiménez A, Beltrán G (2016) Sterol composition of virgin olive oil of forty-three olive cultivars from the World Collection Olive Germplasm Bank of Cordoba. J Sci Food Agric 96:4143–4150Ruiz-Domínguez ML, Raigón MD, Prohens J (2013) Diversity for olive oil composition in a collection of varieties from the region of Valencia (Spain). Food Res Int 54:1941–1949Mateos R, Dominguez MM, Espartero JL, Cert A (2003) Antioxidant effect of phenolic compounds, α-tocopherol, and other minor components in virgin olive oil. J Agric Food Chem 51:7170–7175Hermoso M, Uceda M, García A, Morales B, Frias ML, Fernández A (1991) Elaboración de Aceite de Calidad. Consejeria de Agricultura y Pesca, SevillaMalheiro R, Rodrigues N, Bissaro C, Leimann F, Casal S, Ramalhosa E, Pereira JA (2017) Improvement of sensorial and volatile profiles of olive oil by addition of olive leaves. Eur J Lipid Sci Technol 119:1700177Commission Delegated Regulation (EU) 2016/2095 amending Regulation (EEC) No 2568/91 on the characteristics of olive oil and olive-residue oil and on the relevant methods of analysis. Off J Eur Union L:326Slover HT, Thompson RH, Merola GV (1983) Tocopherol and sterol determination by capillary gas chromatography. J Am Oil Chem Soc 60:1524–1528Sousa A, Casal S, Malheiro R, Lamas H, Bento A, Pereira JA (2015) Aromatized olive oil: Influence of flavouring in quality, composition, stability, antioxidants, and antiradical potential. LWT Food Sci Technol 60:22–28Limón P, Malheiro R, Casal S, Acién-Fernández FG, Fernández-Sevilla JM, Rodrigues N, Cruz R, Bermejo R, Pereira JA (2015) Improvement of stability and carotenoids fraction of virgin olive oil by addition of microalgae Scenedesmus almeriensis extracts. Food Chem 175:203–211Motilva MJ, Tovar MJ, Romero MP, Alegre S, Girona J (2000) Influence of regulated deficit irrigation strategies applied to olive trees (Arbequina cultivar) on oil yield and oil composition during the fruit ripening period. J Sci Food Agric 80:2037–2043Palese AM, Nuzzo V, Favati F, Pietrafesa A, Celano G, Xiloyannis C (2010) Effects of water deficit on the vegetative response, yield and oil quality of olive trees (Olive europaea L., cv Coratina) grown under intensive cultivation. Sci Hortic 125:222–229Allalout A, Krichèn D, Methenni K, Taamalli A, Oueslati I, Daoud D, Zarrouk M (2009) Characterization of virgin olive oil from Super Intensive Spanish and Greek varieties grown in northern Tunisia. Sci Hortic 120:77–83Simopoulos AP, DiNicolantonio JJ (2016) The importance of a balanced ω-6 to ω-3 ratio in the prevention and management of obesity. Open Heart 3:e000385Marongui B, Özcan MM, Rosa A, Dessi MA, Piras A, AlJuhaimi F (2015) Monitoring of the fatty acid compositions of some olive oils. Riv Ital Sostanze Grasse 92:39–42Paiva-Martins F, Kiritsakis A (2017) Olive fruit and olive oil composition and their functionalcompounds. In: Kiritsakis A, Shahidi F (eds) Olives and olive oil as functional foods. Bioactivity, chemistry and processing. Wiley, Hoboken, pp 81–116Shahzad N, Khan W, Shadab MD, Ali A, Saluja SS, Sharma S, Al-Allaf FA, Abduljaleel Z, Ibrahim IAA (2017) Phytosterols as a natural anticancer agent: current status and future perspective. Biomed Pharmacol 88:786–794Covas MI, Ruiz-Gutiérrez V, de la Torre R, Kafatos A, Lamuela-Raventós RM, Osada J, Owen RW, Visioli F (2006) Minor components of olive oil: evidence to date of health benefits in humans. Nutr Rev 64:S20–S30Pirodi M, Albini A, Fabiani R, Giovannelli L, Luceri C, Natella F, Rosignoli P, Rossi T, Taticchi A, Servili M, Galli F (2017) Nutrigenomics of extra-virgin olive oil: a review. Biofactors 43:17–41Franco MN, Galeano-Díaz T, Sánchez J, De Miguel C, Martín-Vertedor D (2014) Total phenolic compounds and tocopherols profiles of seven olive oil varieties grown in the South-West of Spain. J Oleo Sci 63:115–125Aparicio R, Roda L, Albi MA, Gutiérrez F (1999) Effect of various compounds on virgin olive oil stability measured by Rancimat. J Agric Food Chem 47:4150–4155Bullota S, Celano M, Lepore SM, Montalcini T, Pujia A, Russo D (2014) Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases. J Transl Med 12:1–9Krychene D, Salvador MD, Fregapane G (2015) Stability of virgin olive oil phenolic compounds during long-term storage (18 months) at temperatures of 5–50 °C. J Agric Food Chem 63:6779–6786Aparicio-Ruiz R, García-González DL, Oliver-Pozo C, Tena N, Morales MT, Aparicio A (2016) Phenolic profile of virgin olive oils with and without sensory defects: oils with non-oxidative defects exhibit a considerable concentration of phenols. Eur J Lipid Sci Technol 118:299–307Yorulmaz A, Poyrazoğlu ES, Özcan MM, Tekin A (2012) Phenolic profiles of Turkish olives and olive oils. Eur J Lipid Sci Technol 14:1083–1093Arslan A, Özcan MM (2011) Phenolic profile and antioxidant activity of olive fruits of the Turkish variety “Sarıulak” from different locations. Grasas Aceites 64:453–461Dağdelen A, Tümen G, Özcan MM, Dündar E (2013) Phenolics profiles of olive fruits (Olea europaea L.) and oils from Ayvalık, Domat and Gemlik varieties at different ripening stages. Food Chem 136:41–45Malheiro R, Rodrigues N, Pereira JA (2015). In: Boskou D (ed) Olive and olive oil bioactive constituents. AOCS Press, UrbanaCriado MN, Morelló JR, Motilva MJ, Romero MP (2004) Effect of growing area on pigment and phenolic fractions of virgin olive oils of the Arbequina variety in Spain. J Am Oil Chem Soc 81:633–640Gómez-Rico A, Fregapane G, Salvador MD (2008) Effect of cultivar and ripening on minor components in Spanish olive fruits and their corresponding virgin olive oils. Food Res Int 41:433–440Parkinson L, Cicerale S (2016) The health benefiting mechanisms of virgin olive oil phenolic compounds. Molecules 21:1734Lerma-García MJ, Herrero-Martínez JM, Ramis-Ramos G, Simó-Alfonso EF (2008) Prediction of the genetic variety of Spanish extra virgin olive oils using fatty acid and phenolic compound profiles established by direct infusion mass spectrometry. Food Chem 108:1142–1148Luna G, Morales MT, Aparicio R (2006) Characterisation of 39 varietal virgin olive oils by their volatile compositions. Food Chem 98:243–252Arslan A, Özcan MM (2011) Influence of growing area and harvest date on the organic acid composition of olive fruits from Gemlik variety. Sci Hortic 130:633–64

Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells.

Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs initiate C-C motif chemokine receptor 7 (CCR7) expression and migrate into lymph nodes to direct T cell activation and differentiation. The mechanistic underpinnings of DC migration from the tissues to lymph nodes have been largely elucidated, contributing greatly to our understanding of DC functionality and intestinal immunity. In contrast, the molecular mechanisms allowing DCs to efficiently migrate through the complex extracellular matrix of the intestinal lamina propria prior to antigen encounter are still incompletely understood. Here we show that small intestinal murine CD11b <sup>+</sup> CD103 <sup>+</sup> DCs express Placenta-expressed transcript 1 (Plet1), a glycophoshatidylinositol (GPI)-anchored surface protein involved in migration of keratinocytes during wound healing. In the absence of Plet1, CD11b <sup>+</sup> CD103 <sup>+</sup> DCs display aberrant migratory behavior, and accumulate in the small intestine, independent of CCR7 responsiveness. RNA-sequencing indicated involvement of Plet1 in extracellular matrix-interactiveness, and subsequent in-vitro migration assays revealed that Plet1 augments the ability of DCs to migrate through extracellular matrix containing environments. In conclusion, our findings reveal that expression of Plet1 facilitates homeostatic interstitial migration of small intestinal DCs

Innate Immune Activation in Intestinal Homeostasis

Loss of intestinal immune regulation leading to aberrant immune responses to the commensal microbiota are believed to precipitate the chronic inflammation observed in the gastrointestinal tract of patients with inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Innate immune receptors that recognize conserved components derived from the microbiota are widely expressed by both epithelial cells and leucocytes of the gastrointestinal tract and play a key role in host protection from infectious pathogens; yet precisely how pathogenic and commensal microbes are distinguished is not understood. Furthermore, aberrant innate immune activation may also drive intestinal pathology, as patients with IBD exhibit extensive infiltration of innate immune cells to the inflamed intestine, and polymorphisms in many innate immunity genes influence susceptibility to IBD. Thus, a balanced interaction between the microbiota and innate immune activation is required to maintain a healthy mutualistic relationship between the microbiota and the host, which when disturbed can result in intestinal inflammation