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Renee Davis,1 Alex Taylor,1 Regan Nally,1 Kathleen F Benson,2 Paul Stamets,1 Gitte S Jensen2 1Fungi Perfecti, Olympia, WA 98507, USA; 2NIS Labs, Klamath Falls, OR 97601, USACorrespondence: Gitte S JensenNIS Labs, 1437 Esplanade, Klamath Falls, OR 97601, USATel +1 541 884-0112Fax +1403 441-5236Email gitte@nislabs.comPurpose: To compare three fractions of a medicinal mushroom blend (MMB), MyCommunity, on immune-activation, inflammation-regulation, and induction of biomarkers involved in regenerative functions.Methods: A seventeen-species MMB was sequentially extracted: first, saline solution at ambient temperature, followed by re-extraction of the solids in ethanol, and finally resuspension of the homogenized ethanol-insoluble solids in cell-culture media. Fractions were tested on peripheral blood mononuclear cells from three healthy donors. Immunostaining, flow-cytometry, and Luminex protein-arrays measured immune-cell activation and cytokine response. Dose-responses for induction of the CD69 early activation marker and individual cytokine and growth-factor responses for each donor were evaluated. The CD69 and the combined cytokine and growth-factor results were subjected to Non-metric Multidimensional Scaling (NMDS) and multivariate ordination to aid interpretation of the aggregate immune response and pairwise permutational MANOVA on a distance-matrix to evaluate statistical differences between treatments on pooled data from all donors.Results: Differential effects were induced by water-soluble, ethanol-soluble, and insoluble immunomodulatory compounds of the MMB. The aqueous and ethanol fractions upregulated expression of CD69 on all tested cell types. Monocyte-activation was correlated with the ethanol fraction, while NKT and non-NK non-T cell-activation was more closely correlated with the aqueous fraction. The solid fraction was the most potent inducer of Tumor Necrosis Factor-α, as well as the anti-viral cytokines interferon-γ, MCP-1 (CCL-2), MIP-1α (CCL-3), and MIP-1β (CCL-4), and induced G-CSF and b-FGF—growth-factors involved in regenerative functions—and the anti-inflammatory cytokine IL-1ra.Conclusion: The aqueous, ethanol, and insoluble compounds within MMB induced differential immune-activating, anti-inflammatory, and regenerative effects. This in vitro data suggests that, upon consumption, MMB may induce a concerted series of immunomodulatory events based on the differential solubility and bioavailability of the active constituents. These differential responses support both immune-activation and resolution of the host defense-induced inflammatory reactions, thus assisting a post-response return to homeostasis.Keywords: CD69, cytokines, growth factors, anti-viral peptides, medicinal mushrooms, mycelium, immune support, redundancy analysis, rda, multivariate ordination

The Atlantic meridional overturning circulation (AMOC) is a system of ocean currents that has an essential role in Earth’s climate, redistributing heat and influencing the carbon cycle1, 2. The AMOC has been shown to be weakening in recent years1; this decline may reflect decadal-scale variability in convection in the Labrador Sea, but short observational datasets preclude a longer-term perspective on the modern state and variability of Labrador Sea convection and the AMOC1, 3,4,5. Here we provide several lines of palaeo-oceanographic evidence that Labrador Sea deep convection and the AMOC have been anomalously weak over the past 150 years or so (since the end of the Little Ice Age, LIA, approximately ad 1850) compared with the preceding 1,500 years. Our palaeoclimate reconstructions indicate that the transition occurred either as a predominantly abrupt shift towards the end of the LIA, or as a more gradual, continued decline over the past 150 years; this ambiguity probably arises from non-AMOC influences on the various proxies or from the different sensitivities of these proxies to individual components of the AMOC. We suggest that enhanced freshwater fluxes from the Arctic and Nordic seas towards the end of the LIA—sourced from melting glaciers and thickened sea ice that developed earlier in the LIA—weakened Labrador Sea convection and the AMOC. The lack of a subsequent recovery may have resulted from hysteresis or from twentieth-century melting of the Greenland Ice Sheet6. Our results suggest that recent decadal variability in Labrador Sea convection and the AMOC has occurred during an atypical, weak background state. Future work should aim to constrain the roles of internal climate variability and early anthropogenic forcing in the AMOC weakening described here.

Research framework: In 1881 the French Third Republic allocated yearly pensions to nearly 25,000 elderly citizens as reparations for political oppression suffered thirty years earlier during the previous regime. To receive a pension, each former political prisoner ( proscrit ), their widows or children, wrote letters describing their punishment and the wider multi-generational impact of that oppression.Objectives: This article uncovers understandings shared by Republican administrators and a particular group of their staunch working-class supporters - artisans, rural laborers, and small-town shopkeepers - of the definitions of old age, expectations for life trajectories, and how gender affected both expectations and experiences.Methodology: Historical, qualitative analysis of archival documents at the French National Archives and departments of the Ain, Allier, Drôme, Hérault, Rhône, Saône-et-Loire, Vaucluse and Yonne, France.Results: Analysis demonstrates pension applicants drew upon common understandings of gender and age-based roles to strengthen their claims to pensions both as erstwhile heroes of the newly democratic regime and as members of an indigent, elderly poor worthy of government aid.Conclusions: Former proscrits , their families and Republican administrators shared assumptions about the definition of the onset of old age as linked to gender; about expectations that elderly men would work indefinitely in old age until physically unable to do so but that the specter of elderly working women was shameful and a blot on Republican values; and about an understanding that pensions allowed a dignified old-age for both male and female applicants by undoing dangerous shifts in gender roles perceived as triggered by the political oppression decades earlier.Contribution: The article contributes to scholarship on changing European understandings of the gendered dimensions of old age in the late 19th century, just before decades of social welfare legislation., Cadre de la recherche : En 1881, la Troisième République française allouait des pensions viagères à presque 25 000 vieux citoyens, comme réparation de l’oppression politique qu’ils avaient subie trente ans auparavant sous le régime précédent. Afin de recevoir une pension, chaque ancien proscrit, sa veuve ou ses enfants, devait décrire sa peine et les répercussions multigénérationnelles de ce châtiment dans une pétition.Objectifs : Cet article décrit le consensus de l’administration républicaine et d’une partie de ses fidèles partisans (artisans, paysans ouvriers et commerçants des petites villes) sur la définition de la vieillesse, sur ce qu’on espérait du bon déroulement des dernières années de la vie, et sur la façon dont le genre affectait à la fois l’anticipation et l’expérience de la vieillesse.Méthodologie : L’analyse historique et qualitative des fonds aux Archives nationales de France et aux Archives départementales de l’Ain, de l’Allier, de la Drôme, de l’Hérault, du Rhône, de la Saône-et-Loire, du Vaucluse, et de l’Yonne. Résultats : L’analyse montre que les demandeurs de pension orientaient leur pétition sur une idée précise des rôles de genre et d’âge pour renforcer leur droit à une pension basée sur leur double statut de héros républicain et vieillard indigent digne de l’aide gouvernementale.Conclusions : L’analyse montre que les demandeurs de pension s’appuyaient sur une vision commune de la vieillesse, dont le point de départ était lié au sexe de l’individu. Cette conception de la vieillesse comprenait l’attente que les vieillards devaient travailler sans relâche, jusqu’à épuisement physique total, alors que l’idée de vieilles femmes au travail était gênante et entachait les valeurs républicaines. Les demandeurs de pension estimaient que les pensions procureraient une vieillesse digne aux proscrits autant qu’à leur veuve, en annulant l’instabilité des rôles de genre enclenchée par l’oppression politique trente ans auparavant.Contribution : Cet article contribue à l’avancement des recherches sur la perception de la vieillesse et des rôles de genre à la fin de la vie en France à l’orée de législations sociales sur le continent européen.