Cultured Peribulbar Dermal Sheath Cells Can Induce Hair Follicle Development and Contribute to the Dermal Sheath and Dermal Papilla

Green fluorescent protein (GFP)-expressing wild-type, and nontransgenic mouse vibrissa follicle cells were cultured and implanted to mouse ears and footpads. Dermal papiller (DP)-derived cells and cells from the peribulbar dermal sheath “cup” (DSC) induced new hair follicles in both implanted ears and footpads, while nonbulbar dermal sheath cells did not. Confocal microscopy revealed that GFP-expressing DP and DSC cells induced hair growth associated with the formation of DP exclusively comprised of fluorescent cells. In mouse ears, but not footpads, fluorescent DP and DSC cells could also be identified in DP along with nonfluorescent cells. DSC cells were characterized in vivo and in vitro by low alkaline phosphatase activity in contrast to high alkaline phosphatase in DP cells. The results indicate transplanted DP and DSC cells were equally capable of DP formation and hair follicle induction. This suggests the DP and peribulbar DSC may be functionally similar. In addition to observing papillae exclusively composed of GFP-expressing cells, DP and DSC cells may also have combined with resident cells to form papillae composed of implanted GFP-expressing cells and host-derived non-GFP-expressing cells. Alkaline phosphatase expression may be utilized as a simple marker to identify hair follicle mesenchyme derived cells with hair follicle inductive abilities

Concomitant Sjögren’s disease as a biomarker for treatment effectiveness in rheumatoid arthritis:results from the Swiss clinical quality management cohort

Objective: To investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren’s disease (SjD). Methods: In this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders.Results: We identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07-1.6]; OMA HR 1.12 [0.91-1.37]; JAKi HR 0.97 [0.62-1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46-0.84]) and JAKi (HR 0.52 [0.28-0.96]).Conclusion: RA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi. <br/

Pantropical modelling of canopy functional traits using Sentinel-2 remote sensing data

Funding Information: This work is a product of the Global Ecosystems Monitoring (GEM) network (gem.tropicalforests.ox.ac.uk). J.A.G. was funded by the Natural Environment Research Council (NERC; NE/T011084/1 and NE/S011811/1) and the Netherlands Organisation for Scientific Research (NWO) under the Rubicon programme with project number 019.162LW.010. The traits field campaign was funded by a grant to Y.M. from the European Research Council (Advanced Grant GEM-TRAIT: 321131) under the European Union‘s Seventh Framework Programme (FP7/2007-2013), with additional support from NERC Grant NE/D014174/1 and NE/J022616/1 for traits work in Peru, NERC Grant ECOFOR (NE/K016385/1) for traits work in Santarem, NERC Grant BALI (NE/K016369/1) for plot and traits work in Malaysia and ERC Advanced Grant T-FORCES (291585) to Phillips for traits work in Australia. Plot setup in Ghana and Gabon were funded by a NERC Grant NE/I014705/1 and by the Royal Society-Leverhulme Africa Capacity Building Programme. The Malaysia campaign was also funded by NERC GrantNE/K016253/1. Plot inventories in Peru were supported by funding from the US National Science Foundation Long-Term Research in Environmental Biology program (LTREB; DEB 1754647) and the Gordon and Betty Moore Foundation Andes-Amazon Program. Plots inventories in Nova Xavantina (Brazil) were supported by the National Council for Scientific and Technological Development (CNPq), Long Term Ecological Research Program (PELD), Proc. 441244/2016-5, and the Foundation of Research Support of Mato Grosso (FAPEMAT), Project ReFlor, Proc. 589267/2016. During data collection, I.O. was supported by a Marie Curie Fellowship (FP7-PEOPLE-2012-IEF-327990). GEM trait data in Gabon was collected under authorisation to Y.M. and supported by the Gabon National Parks Agency. D.B. was funded by the Fondation Wiener-Anspach. W.D.K. acknowledges support from the Faculty Research Cluster ‘Global Ecology’ of the University of Amsterdam. M.S. was funded by a grant from the Ministry of Education, Youth and Sports of the Czech Republic (INTER-TRANSFER LTT19018). Y.M. is supported by the Jackson Foundation. We thank the two anonymous reviewers and Associate Editor G. Henebry for their insightful comments that helped improved this manuscript.Peer reviewedPostprin

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Die Bronzehand von Prêles (Kt. Bern/CH) – die älteste anthropomorphe Bronzeplastik Europas?

Die Bronzehand von Prêles wurde im Herbst 2017 von Metallsondengängern entdeckt. Mittels der Radiokarbonmethode konnte die metallene Hand in die Mittelbronzezeit ins 15. bzw. 14. Jahrhundert v. Chr. datiert werden. Bislang liegen keinerlei Vergleichsfunde vor: Die Bronzehand von Prêles ist damit womöglich die älteste anthropomorphe Bronzeplastik Europas. Eine Nachgrabung 2018 erbrachte den Nachweis, dass die bronzene Hand aus dem Grab eines erwachsenen Mannes stammt, der am Ort einer älteren, noch undatierten Steinkonstruktion beigesetzt wurde. Die Funktion der Bronzehand bleibt vorerst unbekannt. Möglich scheint eine Verwendung in Verbindung mit Repräsentation, in rituellem oder kultischem Kontext ebenso wie als symbolische Prothese

Reduced Expression of Interleukin-2 Decreases the Frequency of Alopecia Areata Onset in C3H/HeJ Mice

Alopecia areata (AA) is an autoimmune hair loss disease, that can be transferred between C3H/HeJ mice by skin grafting. We explored whether AA susceptibility is influenced by the availability of interleukin (IL)-2, a cytokine with leukocyte activating and regulatory properties. Mice heterozygous for a targeted deletion of IL-2 from the histocompatible C3.129P2(B6)-Il2tm1Hor substrain, that produce reduced levels of IL-2, were examined for AA development after grafting skin from AA-affected C3H/HeJ mice. After grafting, nine of 19 (47%) heterozygous IL-2+/-versus 16 of 18 (88%) IL-2+/+ wild-type littermates developed AA. Although dense follicular leukocyte infiltrates were apparent in AA affected wild-type mice, AA-developing IL-2+/- littermates had a reduced leukocyte infiltration, and AA-resistant IL-2+/- mice had no inflammation. Lymph node cell analysis revealed a reduction in leukocyte activation markers in AA-developing IL-2+/- mice. IL-2+/- mice presented with low level expression of cytokines (IL-4, IL-10, interferon-γ, transforming growth factor-β), upregulation of tumor necrosis factor receptors, and increased leukocyte apoptosis susceptibility independent of AA expression. In the skin, CD4+ cells and monocytes were reduced; activation markers were not upregulated and very few CD44v3+ or CD44v10+ leukocytes were recovered. Taken together, our data suggest that AA resistance of IL-2+/- mice is because of the failure of activated leukocyte recruitment, thus pointing toward an involvement of IL-2 in AA pathogenesis

Additional file 1 of Concomitant Sjögren’s disease as a biomarker for treatment effectiveness in rheumatoid arthritis - results from the Swiss clinical quality management cohort

Supplementary Material

A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion

Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed. Similar mixtures were manufactured with a lab-scale extruder, for face to face comparison. The properties of MinEx extrudates widely translated to those manufactured with a lab-scale extruder. Plasticizers, Polyethyleneglycol 4000 (PEG4000) and Poloxamer 188, were homogenously distributed but decreased the storage stability of the extrudates. Stearic acid was found condensed in ultrathin nanoplatelets which did not impact the storage stability of the system. Depending on their distribution and physicochemical properties, plasticizers can modulate storage stability and dissolution performance of extrudates. MinEx is a valuable prototyping-screening method and enables rational selection of plasticizers in a time and material sparing manner. In eight out of eight cases the properties of the extrudates translated to products manufactured in lab-scale extrusion trials

Elektronische Dateien zu: Die Ufersiedlungen von Sutz-Lattrigen 3830 bis 3560 v. Chr. und ihre Kontaktnetze.

Tabellen mit den Basisdaten der Auswertungen der Ufersiedlungen von Sutz-Lattrigen zu den Publikationen: Regine Stapfer mit Beiträgen von John Francuz, Matthias Bolliger, Gisela Thierrin-Michael und Albert Hafner, Die Ufersiedlungen von Sutz-Lattrigen 3830 bis 3560 v. Chr. und ihre Kontaktnetze. Band 1: Siedlungsgeschichte, Dendrochronologie und Gefässkeramik. Bern 2023. Regine Stapfer, Jonas Kissling, Delphine Schiess, Jehanne Affolter, Stéphane Dévaud, Jürgen Fischer, Lea Emmenegger, Sabine Deschler-Erb, Antoinette Rast-Eicher, Christoph Brombacher, Manar Kerdy, Marguerita Schäfer, Jörg Schibler, John Francuz, Matthias Bolliger, Gisela Thierrin-Michael und Albert Hafner, Die Ufersiedlungen von Sutz-Lattrigen 3830 bis 3560 v. Chr. und ihre Kontaktnetze. Band 2: Funde aus Stein, organischem Material und Kupfer; Katalog und Tafeln. Bern 2023

Die Ufersiedlungen von Sutz-Lattrigen 3830 bis 3560 v. Chr. und ihre Kontaktnetze. Band 2: Funde aus Stein, organischem Material und Kupfer; Katalog und Tafeln

In der zweibändigen Publikation zu den Ufersiedlungen von Sutz-Lattrigen 3830–3560 v. Chr. werden die Ergebnisse der von 1991 bis 2003 durchgeführten umfassenden Tauchgrabungen vorgelegt. Anhand der dendrochronologischen Analyse können vier Siedlungen und ihre Entwicklung rekonstruiert werden. Die Funde aus Keramik, Stein, Knochen und organischem Material werden typochronolgisch ausgewertet und durch umfassende Untersuchungen von Herstellungstechnik und Rohmaterialherkunft ergänzt. Die Funde und die Wirtschaftsweise der Siedlungen am Bielersee-Südufer zeigen im Vergleich mit anderen ähnlich datierten Fundstellen unterschiedliche Kontaktnetzte und Mobilität der Siedlungsgemeinschaft in näher und weiter entfernte Gebiete