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A lack of communities' readiness for change is reported as a major barrier toward an effective implementation of health promoting interventions in community settings. Adding an alternative readiness assessment approach to existing research practice, this study aimed to investigate how a selected community could be evaluated in-depth regarding its readiness for change based on multiple key informant perspectives, with the intention of using this knowledge for the preparation of improved local physical activity (PA) interventions for men above 50 years of age. We conducted semi-structured face-to-face key informant interviews with stakeholders and relevant persons from a local German community (N = 15). The interview guide was based on a comprehensive summary of community readiness dimensions. After verbatim transcription, we conducted thematic analysis to synthesize the complex results regarding community readiness related to PA. The data supported that the community disposed of a variety of resources regarding PA and showed signs of readiness for change. However, a certain degree of saturation regarding PA programs existed. The need for health enhancing PA interventions for men was only partly recognized. The local authority considered PA to be particularly important in the context of mobility and traffic safety. Including multiple stakeholders contributed to a balanced and in-depth assessment of community readiness and was helpful for determining starting points for tailored PA interventions due to the detection of complex relationships and structures. The study delivers preliminary evidence that a qualitative multi-perspective community readiness assessment adds value to quantified single-perspective readiness assessment research practice.Health promotion increasingly employs participatory approaches, but the question arises whether the likely higher costs of participation also translate into greater benefits. This article takes a first step toward a full health economic evaluation by comprehensively reporting the costs of a specific participatory approach, Cooperative Planning, in a German research consortium to promote physical activity. We conducted a costing analysis of Cooperative Planning at 22 sites across six settings. Project teams used a custom template to record resource use. We calculated average costs per meeting, site and setting using the opportunity costs approach, and obtained feedback from participating researchers. A total of 144 planning meetings with an average of nine participants were conducted. Costs per meeting varied significantly across settings. Differences were mostly attributable to varying meeting duration, preparation time and numbers of participants. Across settings, human resources accounted for roughly 95% of the costs. Implementing researchers reported challenges regarding the logic and methods of the health economic analysis. A participatory approach to physical activity promotion may cause substantially varying costs in different settings despite similar cost structures. However, their value for money could turn out comparably favorable if (and only if) the expected benefits is indeed forthcoming. Despite some challenges implementing the costing exercise into the logistics of ongoing participatory projects, this analysis may pave the way toward a full health economic evaluation, and the template may be useful to future participatory health promotion projects.Due to the beneficial impact of regular physical activity (PA) on non-communicable diseases, the number of countries integrating exercise referral schemes (ERSs) into their healthcare systems is growing. Owing to the limitations of existing PA promotion concepts in Germany's healthcare system, efforts are currently being made towards developing a nationwide referral pathway. A research group at the Friedrich-Alexander-University Erlangen-Nürnberg is coordinating these efforts within a project funded by the Federal Ministry of Health. The aim is to develop, implement and evaluate a regional-level ERS that has the potential to be scaled up across Germany in the event of its demonstrated effectiveness. The project is based on an adapted Cooperative Planning approach requiring interaction between the academic sector and different actors of the healthcare sector. The present commentary reflects on challenges faced in the early stages of the co-production process. Besides the development of an adequate co-production methodology, it critically discusses stakeholder participation, knowledge gaps and actors' willingness to take responsibility. In addition, although patients are represented by dedicated organizations, their perspective cannot be adequately captured using a co-production approach. Despite the joint development of an ERS, there remain important questions regarding the appropriateness of the co-production approach in a healthcare setting.The Hippo transcriptional coactivators YAP and TAZ exert critical roles in morphogenesis, organ size determination and tumorigenesis in many tissues. Although Hippo kinase cascade activity was recently reported in the anterior pituitary gland in mice, the role of the Hippo effectors in regulating gonadotropin production remains unknown. The objective of this study was therefore to characterize the roles of YAP and TAZ in gonadotropin synthesis and secretion. Using a conditional gene targeting approach (cKO), we found that gonadotrope-specific inactivation of Yap and Taz resulted in increased circulating levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in adult male mice, along with increased testosterone levels and testis weight. Female cKO mice had increased circulating LH (but not FSH) levels, which were associated with a hyperfertility phenotype characterized by higher ovulation rates and larger litter sizes. Unexpectedly, the loss of YAP/TAZ did not appear to affect the expression of gonadotropin subunit genes, yet both basal and GnRH-induced LH secretion were increased in cultured pituitary cells from cKO mice. Likewise, pharmacologic inhibition of YAP binding to the TEAD family of transcription factors increased both basal and GnRH-induced LH secretion in LβT2 gonadotrope-like cells in vitro without affecting Lhb expression. Conversely, mRNA levels of ChgA and SgII, which encode key secretory granule cargo proteins, were decreased following pharmacologic inhibition of YAP/TAZ, suggesting a mechanism whereby YAP/TAZ regulate the LH secretion machinery in gonadotrope cells. Together, these findings represent the first evidence that Hippo signaling may play a role in regulating pituitary LH secretion.The mitochondrial genome sequences of Denierella emmerichi, Epicauta curvispina, and Meloe poggii were determined. Their mitochondrial genomes were found to contain 37 genes (13 protein-coding genes [PCGs], 22 tRNA genes, and 2 rRNAs), of which 4 PCGs, 8 tRNA genes, and 2 rRNAs are encoded by the N-strand, and the remaining genes are encoded by the J-strand. The mitochondrial genomes of D. emmerichi, E. curvispina, and M. poggii are 15,702 bp, 15,813 bp, and 15,626 bp in length, respectively, and their guanine-cytosine contents are 28%, 33%, and 36%, respectively. The 13 PCGs of D. emmerichi, E. curvispina, and M. poggii use ATN as the standard start codon and TAA, TAG, and T as the stop codons. The Bayesian inference and maximum likelihood phylogenetic analysis results based on the 13 PCGs and 13 PCGs + 2rRNAs datasets of the mitochondrial genomes of the Meloidae support Epicauta (Coleoptera Meloidae) ([D. emmerichi, E. curvispina, E. ruficeps, E. [https://www.selleckchem.com/products/glumetinib.html Glumetinib manufacturer] aptera] + [E. chinensis, E. impressicornis, E. gorhami, E. tibialis]). We believe that this research enriches the literature on the mitochondrial genomics of Meloidae and serves as a foundation for the further study of the phylogenetic relationships and characterization of Meloidae and Coleoptera.We present Monte Carlo Physarum Machine (MCPM) a computational model suitable for reconstructing continuous transport networks from sparse 2D and 3D data. MCPM is a probabilistic generalization of Jones's (2010) agent-based model for simulating the growth of Physarum polycephalum (slime mold). We compare MCPM to Jones's work on theoretical grounds, and describe a task-specific variant designed for reconstructing the large-scale distribution of gas and dark matter in the Universe known as the cosmic web. To analyze the new model, we first explore MCPM's self-patterning behavior, showing a wide range of continuous network-like morphologies-called polyphorms-that the model produces from geometrically intuitive parameters. Applying MCPM to both simulated and observational cosmological data sets, we then evaluate its ability to produce consistent 3D density maps of the cosmic web. Finally, we examine other possible tasks where MCPM could be useful, along with several examples of fitting to domain-specific data as proofs of concept.Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T-cells. Long-term remissions are rare in CTCL, and the pathophysiology of long-lasting disease control is unknown. Mogamulizumab is a defucosylated anti-human CCR4 antibody that depletes CCR4-expressing CTCL tumor cells and peripheral blood memory regulatory T cells. Prolonged remissions and immune side effects have been observed in mogamulizumab-treated CTCL patients. We report that mogamulizumab induced skin rashes in 32% of 44 CTCL patients. These rashes were associated with long-term CTCL remission, even in the absence of specific CTCL treatment. CTCL patients with mogamulizumab-induced rash had significantly higher overall survival (hazard ratio, 0.16 (0.04-0.73, p=0.01)). Histopathology and immunohistochemistry of the rashes revealed granulomatous and lichenoid patterns with CD163 macrophagic and CD8 T-cell infiltrates. Depletion of skin CTCL cells was confirmed by high-throughput sequencing analysis of TCRβ genes and in blood by flow cytometry. New reactive T-cell clones were recruited in skin. Gene expression analysis showed overexpression of CXCL9 and CXCL11, two chemokines involved in CXCR3-expressing T-cell homing to skin. Single-cell RNA sequencing analysis in skin of CTCL patients confirmed that CXCL9 and CXCL11 were primarily macrophage-derived and that skin T-cells expressed CXCR3. Finally, patients with rashes had a significantly higher proportion of exhausted reactive blood T-cells expressing TIGIT and PD1 at baseline compared to patients without rash, which decreased under mogamulizumab treatment, consistent with an activation of the antitumor immunity. Together, these data suggest that mogamulizumab may induce long-term immune control in CTCL patients by activation of the macrophagic and T-cell immune responses.Aneuploidy is frequently observed in oocytes and early embryos, begging the question of how genome integrity is monitored and preserved during this critical period. SMC3 is a subunit of the cohesin complex that supports genome integrity, but its role in maintaining the genome in this window of mammalian development is unknown. We discovered that although depletion of Smc3 following meiotic S phase in mouse oocytes allowed accurate meiotic chromosome segregation, adult females were infertile. We provide evidence that DNA lesions accumulated following S phase in SMC3-deficient zygotes, followed by mitosis with lagging chromosomes, elongated spindles, micronuclei, and arrest at the 2-cell stage. Remarkably, although centromeric cohesion was defective, the dosage of SMC3 was sufficient to enable embryogenesis in juvenile mutant females. Our findings suggest that despite previous reports of aneuploidy in early embryos, chromosome missegregation in zygotes halts embryogenesis at the 2-cell stage. Smc3 is a maternal gene with essential functions in repair of spontaneous damage associated with DNA replication and subsequent chromosome segregation in zygotes, making cohesin a key protector of the zygotic genome.