The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation

<p>Abstract</p> <p>Background</p> <p>Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.</p> <p>Methods</p> <p>To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls.</p> <p>Results</p> <p>Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected.</p> <p>Conclusion</p> <p>These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.</p

The ecology, subsistence and diet of ~45,000-year-old Homo sapiens at Ilsenhöhle in Ranis, Germany

Recent excavations at Ranis (Germany) identified an early dispersal of Homo sapiens into the higher latitudes of Europe by 45,000 years ago. Here we integrate results from zooarchaeology, palaeoproteomics, sediment DNA and stable isotopes to characterize the ecology, subsistence and diet of these early H. sapiens. We assessed all bone remains (n = 1,754) from the 2016-2022 excavations through morphology (n = 1,218) or palaeoproteomics (zooarchaeology by mass spectrometry (n = 536) and species by proteome investigation (n = 212)). Dominant taxa include reindeer, cave bear, woolly rhinoceros and horse, indicating cold climatic conditions. Numerous carnivore modifications, alongside sparse cut-marked and burnt bones, illustrate a predominant use of the site by hibernating cave bears and denning hyaenas, coupled with a fluctuating human presence. Faunal diversity and high carnivore input were further supported by ancient mammalian DNA recovered from 26 sediment samples. Bulk collagen carbon and nitrogen stable isotope data from 52 animal and 10 human remains confirm a cold steppe/tundra setting and indicate a homogenous human diet based on large terrestrial mammals. This lower-density archaeological signature matches other Lincombian-Ranisian-Jerzmanowician sites and is best explained by expedient visits of short duration by small, mobile groups of pioneer H. sapiens. [Abstract copyright: © 2024. The Author(s).

Stable isotopes show Homo sapiens dispersed into cold steppes ~45,000 years ago at Ilsenhöhle in Ranis, Germany

The spread of Homo sapiens into new habitats across Eurasia ~45,000 years ago and the concurrent disappearance of Neanderthals represents a critical evolutionary turnover in our species' history. 'Transitional' technocomplexes, such as the Lincombian-Ranisian-Jerzmanowician (LRJ), characterize the European record during this period but their makers and evolutionary significance have long remained unclear. New evidence from Ilsenhöhle in Ranis, Germany, now provides a secure connection of the LRJ to H. sapiens remains dated to ~45,000 years ago, making it one of the earliest forays of our species to central Europe. Using many stable isotope records of climate produced from 16 serially sampled equid teeth spanning ~12,500 years of LRJ and Upper Palaeolithic human occupation at Ranis, we review the ability of early humans to adapt to different climate and habitat conditions. Results show that cold climates prevailed across LRJ occupations, with a temperature decrease culminating in a pronounced cold excursion at ~45,000-43,000 cal BP. Directly dated H. sapiens remains confirm that humans used the site even during this very cold phase. Together with recent evidence from the Initial Upper Palaeolithic, this demonstrates that humans operated in severe cold conditions during many distinct early dispersals into Europe and suggests pronounced adaptability. [Abstract copyright: © 2024. The Author(s).

Homo sapiens reached the higher latitudes of Europe by 45,000 years ago

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe1. Local hybridization between the two groups occurred2, but not on all occasions3. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups4. One such technocomplex for which the makers are unknown is the Lincombian–Ranisian–Jerzmanowician (LRJ), which has been described in northwestern and central Europe5,6,7,8. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-0

Th IL-4 and GM-CSF. Differentiation into mature DCs (mDCs) was achieved by addition of an inflammatory cytokine cocktail for 24 hours. To study the impact of various hormones on the maturation process, maturation was performed in the presence or absence of Dex, TGF-β1, ActA or InA. Subsequently, the cells were analyzed for surface expression of CD40, CD83, CD86 and HLA-DR by flow cytometry. Representative histograms (left panel) are depicted for each hormonal treatment (grey shaded areas); analysis of corresponding iDCs (grey line) and mDCs (black line) are shown in each histogram for control. In addition, statistical analysis of the mean fluorescence intensity (MFI) as a quantitative measure for surface expression levels is depicted as bar diagrams (right panel). n = 14.<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-4

Th IL-4 and GM-CSF. Differentiation into mature DCs (mDCs) was achieved by addition of an inflammatory cytokine cocktail for 24 hours. To study the impact of various hormones on the maturation process, maturation was performed in the presence or absence of Dex, TGF-β1, ActA or InA. Subsequently, the cells were analyzed for surface expression of CD40, CD83, CD86 and HLA-DR by flow cytometry. Representative histograms (left panel) are depicted for each hormonal treatment (grey shaded areas); analysis of corresponding iDCs (grey line) and mDCs (black line) are shown in each histogram for control. In addition, statistical analysis of the mean fluorescence intensity (MFI) as a quantitative measure for surface expression levels is depicted as bar diagrams (right panel). n = 14.<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-3

Der different culture conditions with T lymphocytes at the indicated ratios. T-cell proliferation induced by iDCs, mDCs or DCs matured in the presence of Dex, TGF-β1, ActA or InA was measured on the basis of the measured optical density as described in the methods section. Mean +/- SEM; n = 8. At a DC:T ratio of 1:10, the reduction of the T-cell stimulatory capacity of the DCs was significantly reduced by all four hormones. Each bar represents n = 8 independent experiments.<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-2

Ce of the four hormones was analyzed by cytokine bead array for the production of IL-8, IL-10, MCP-1 and RANTES. Mean +/- SEM, n = 7- 8; ** p < 0,01 (hormonal treatment vs. mDC).<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p

A multistakeholder development process to prioritize and translate COVID-19 health recommendations for patients, caregivers and the public. A case study of the COVID-19 recommendation map

To develop a digital communication tool to improve the implementation of up-to-date COVID-19 recommendations. Specifically, to improve patient, caregiver and public understanding of healthcare recommendations on prevention, diagnoses and treatment. Multi-stakeholder engagement design. In conjunction with the COVID-19 Recommendations and Gateway to Contextualization RecMap, we co-developed a stakeholder prioritization, drafting and editing process to enhance guideline communication and understanding. This paper presents the multi-stakeholder development process with three distinct plain language recommendation formats: formal recommendation, good practice statement, and additional guidance. Our case study of COVID-19 plain language recommendations PLRs addresses both public health interventions (e.g., vaccination, face masks) and clinical interventions (e.g., home pulse oximetry). This paper presents a novel approach to engaging stakeholders in improving the communication and understanding of published guidelines during the COVID-19 pandemic