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Human type 1 conventional dendritic cells contribute to skin transplant rejection
No full textThe skin is the most immunogenic tissue in transplantation and the most difficult tissue in which to induce immune modulation. Batf3-dependent type 1 conventional dendritic cells (cDC1s) are important in initiating rejection in murine skin transplantation. In humans, the CD141+ cDC1 subset is the functional counterpart of the murine Batf3-dependent cDC1s. However, their contribution to the rejection of human skin allografts remains unknown. Using samples from human face and upper extremity transplant recipients, we demonstrated that CD141+ cDC1s are increased and more activated in human skin grafts than native skin tissue from the same individual. Moreover, circulating and tissue CD141+ cDC1s were elevated at rejection time points. Local modulation of graft CD141+ cDC1s decreased HLA-DR expression and increased regulatory T cells, which correlated with a decreased presence of skin allogeneic T cells in a humanized transplantation model. Thus, CD141+ cDC1s play an important role in rejecting human skin allografts, and their local modulation is a promising therapeutic approach
Societal implications of bioinspired technologies: introduction to the special issue
No full textThis Special Issue seeks to introduce a broad range of bioinspired technologies and provides an overview of the challenges regarding sustainability, ethical responsibility and societal acceptance. It adopts both a narrow and broad understanding of bioinspired technology. In a narrower sense, it refers to technologies that mimic natural forms, structures, or functional principles, typically developed within the field of biomimetics. More broadly, bioinspired technologies are defined as those designed with human or non-human nature in mind and adapted to meet the needs of both. The Special Issue addresses five key questions: First, it asks how the broad spectrum of bioinspired technologies can be categorized and classified. Second, it explores the extent to which bioinspired technologies contribute to a sustainable future and in particular to the development of sustainable technologies and what criteria can be used to ensure the sustainability of bioinspired technologies. Third, it presents methods for investigating and fostering societal acceptance of new bioinspired technologies. Fourth, central technical and societal areas are considered in which bioinspiration can contribute to a sustainable future. Lastly, it explores the ontological and ethical challenges associated with bioinspired technologies in so far as they undermine the previous distinction between ‘nature’ and ‘technology’
Strukturelle Veränderungen der Geschäftsfelder in der Videospielindustrie: eine empirische Analyse multinationaler Unternehmen
No full textEffects of marijuana and tobacco on male fertility and their relationship to genetic variation of mitochondrial cytochrome C oxidase genes
No full textAlthough tobacco smoking declined among men at reproductive age, the use of cannabis increased. The aim of our study was to determine the impact of tobacco and cannabis on sperm quality, sperm DNA integrity tested by Chromomycin A3 (CMA3) and acridine orange (AO) and their association to genetic variants in the Cytochrome C Oxidase 1, 2 and 3 genes (MT-CO1, MT-CO2, and MT-CO3). Semen samples were collected and divided into 37 non-smokers (NS), 39 tobacco smokers (TS), and 37 cannabis smokers (CS). MT-CO1, MT-CO2 and MT-CO3 genes were amplified by PCR and sequenced by Sanger. The results showed reductions in normal sperm morphology and non-progressive motility in TS and CS compared to NS (p < 0.001). However, immotile sperm, AO+, and CMA3 + scores were higher in the CS compared to TS and NS (p < 0.001). Twenty-three nucleotide substitutions (SNPs) detected in the MT-CO1 gene, 15 SNPs detected in the MT-CO2 gene, and 30 SNPs detected in the MT-CO3 gene. None of these SNPs was different between the three groups. Tobacco and cannabis smoking altered the motility and morphology of the spermatozoa and sperm DNA integrity but was not associated with genetic variants in the MT-CO1, MT-CO2 and MT-CO3 genes
Activated [alpha beta] T- and reduced mucosa-associated invariant T cells in LGI1- and CASPR2-encephalitis
No full textAnti-leucine-rich glioma inactivated-1 (LGI1) and anti-contactin-associated-protein-2 (CASPR2) autoimmune encephalitis (AIE) are common and characterized by pathogenic antibodies targeting neuronal autoantigens. However, the drivers of the antibody-secreting cells and involvement of T cells remain unresolved. We performed single-cell RNA sequencing of fresh CSF and parallel blood samples of 15 patients with LGI1-AIE (n = 9) and CASPR2-AIE (n = 6) compared with control patients [multiple sclerosis (n = 15) and idiopathic intracranial hypertension (n = 18)]. We validated our observations in independent cohorts using flow cytometry of CSF and blood. We confirmed autoantibody specificity using recombinant human monoclonal antibodies.In comparison to idiopathic intracranial hypertension and multiple sclerosis controls, we observed clonal CSF-specific antibody-secreting cell expansion in LGI1/CASPR2-AIE despite mostly normal CSF findings. Antibody-secreting cells were dominantly plasmablasts and transcribed IgG4 and IgG1/2 heavy chains. Expanded clones showed signs of affinity maturation and bound the respective neuronal autoantigen. Within CD4 and CD8 T-cell clusters, CD4 and CD8 central memory T cells were activated, clonally restricted and expanded. T-cell clones were often shared between CSF and blood. We also observed a shift of natural killer cells and loss of mucosa-associated invariant T (MAIT) cells in the CSF of LGI1-AIE and the blood of LGI1- and CASPR2-AIE compared with idiopathic intracranial hypertension and multiple sclerosis controls. MAIT-like T cells were detected in autopsied brains of LGI1- and CASPR2-AIE patients, and mice lacking MAIT cells displayed an increased antibody seroconversion and higher titres following active LGI1/CASPR2 immunization.Our data: (i) confirm the intrathecal antigen-specific plasma cell expansion in LGI1- and CASPR2-AIE in a large cohort of untreated AIE patients; (ii) suggest that activated and expanded central memory CD4 and CD8 T cells in the CSF participate in disease pathogenesis; and (iii) implicate invariant T-cell receptor-expressing lymphocytes in the brain, CSF and blood in disease pathogenesis
The application of a digital therapeutic reveals superior outcome compared to standard care in patients with anterior knee pain—a randomized controlled trial
No full textTwo-verb clusters in mennonite low german: the impact of auxiliary verb and clause type
No full textAlthough verb clusters in Continental West Germanic varieties are a well-researched topic, their derivation and the possible functions of their variants are still not yet fully understood. Both issues are discussed in the present paper, which is based on the translations of 46 English, Spanish, or Portuguese stimulus sentences by 321 North and South American speakers of Mennonite Low German. In order to analyze the variation in clause-final two-verb clusters, we focus on three structural factors, namely (i) the auxiliary verb, (ii) the structural link between the auxiliary verb and the main verb, and (iii) the type of the subordinate clause in which the cluster occurs. Regarding the first and the second factor, we will employ the cartographic approach in order to explain the impact of different auxiliary verbs. Regarding the third factor, it is somewhat surprising that the potential effect of the subordinate clause on the distribution of different cluster variants has received little attention in the research literature. Clause type will be shown to have such an effect and, therefore, we will assume that the speakers of MLG use different variants deliberately to indicate different degrees of clausal integration
Comparison of visual acuity outcomes of enhanced monofocal versus standard monofocal intraocular lenses from a randomized, multicenter, active-controlled trial
No full textPurposeTo compare visual performance of the Vivinex Impress enhanced monofocal intraocular lens (IOL) (HOYA Surgical Optics) with the Acrysof IQ monofocal IOL (Alcon Laboratories, Inc).MethodsIn this multicenter, active-controlled trial, participants were randomized 2:1 to bilateral implantation with the enhanced monofocal (test) or standard monofocal (control) IOL and examined through 12 months postoperatively for visual acuities, refractive outcomes, defocus curves, and pupil diameters.ResultsNinety-eight test and 46 control participants completed testing for the first implanted eye. The test arm demonstrated a statistically significant benefit in monocular distance-corrected intermediate visual acuity (DCIVA) (photopic: 1.2 lines, P ConclusionsCompared to a standard monofocal IOL, the Vivinex Impress enhanced monofocal IOL offers an extended range of vision, with significant improvements in intermediate vision and a DCIVA benefit unaffected by pupil size and axial length. This IOL is safe and effective for patients seeking improved intermediate vision following cataract surgery
