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Abstract Traits of the spore‐bearing generation have historically provided the basis for systematic concepts across the phylogenetic spectrum and depth of mosses. Whether taxa characterized by a simple sporophytic architecture are closely related or emerged from independent reduction is often ambiguous. Phylogenomic inferences in the Funariaceae, which hold the model taxonPhyscomitrium patens, revealed that several such shifts in sporophyte complexity occurred, and mostly within theEntosthodon‐Physcomitriumcomplex. Here, we report the rediscovery of the monospecific, Himalayan endemic generaBrachymeniopsisandClavitheca, after nearly 100 years and 40 years since their respective descriptions. The genera are characterized by, among other traits, their short sporophytes lacking the sporangial peristome teeth controlling spore dispersal. Phylogenomic inferences reveal thatBrachymeniopsis gymnostomaarose within the clade ofEntosthodons.str., a genus with typically long‐exserted capsules. We therefore propose to transferB. gymnostomato the genusEntosthodon, asE. gymnostomuscomb. nov.Furthermore,Clavitheca poeltii, the sole species of the genus, is morphologically highly similar toE. gymnostomus, and should also be transferred toEntosthodon, but is retained as a distinct taxon,E. poeltiicomb. nov., until additional populations allow for testing the robustness of the observed divergence in costa and seta length between the Nepalese and Chinese populations.more » « less
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Dual-hit strategy for therapeutic targeting of pancreatic cancer in patient-derived xenograft tumorsAbstract Purpose: Paracrine activation of pro-fibrotic hedgehog (HH) signaling in pancreatic ductal adenocarcinoma (PDAC) results in stromal amplification that compromises tumor drug delivery, efficacy, and patient survival. Interdiction of HH-mediated tumor-stroma crosstalk with smoothened (SMO) inhibitors (SHHi) ‘primes’ PDAC patient-derived xenograft (PDX) tumors for increased drug delivery by transiently increasing vascular patency/permeability, and thereby macromolecule delivery. However, patient tumor isolates vary in their responsiveness, and responders show co-induction of epithelial-mesenchymal transition (EMT). We aimed to identify the signal derangements responsible for EMT induction and reverse them, and devise approaches to stratify SHHi-responsive tumors non-invasively based on clinically-quantifiable parameters. Experimental design: Animals underwent diffusion-weighted magnetic resonance (DW-MR) imaging for measurement of intra-tumor diffusivity. In parallel, tissue-level deposition of nanoparticle probes was quantified as a marker of vascular permeability/perfusion. Transcriptomic and bioinformatic analysis was employed to investigate SHHi-induced gene reprogramming and identify key ‘nodes’ responsible for EMT induction. Results: multiple patient tumor isolates responded to short-term SHH inhibitor exposure with increased vascular patency and permeability, with proportionate increases in tumor diffusivity. Non-responding PDXs did not. SHHi-treated tumors showed elevated FGF drive and distinctly higher nuclear localization of fibroblast growth factor receptor (FGFR1) in EMT-polarized tumor cells. Pan-FGFR inhibitor NVP-BGJ398 (Infigratinib) reversed the SHHi-induced EMT marker expression and nuclear FGFR1 accumulation without compromising the enhanced permeability effect. Conclusion: This dual-hit strategy of SMO and FGFR inhibition provides a clinically-translatable approach to compromise the profound impermeability of PDAC tumors. Furthermore, clinical deployment of DW-MR imaging could fulfill the essential clinical-translational requirement for patient stratification.more » « less
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Abstract The quality of solar images plays an important role in the analysis of small events in solar physics. Therefore, the improvement of image resolution based on super-resolution (SR) reconstruction technology has aroused the interest of many researchers. In this paper, an improved conditional denoising diffusion probability model (ICDDPM) based on the Markov chain is proposed for the SR reconstruction of solar images. This method reconstructs high-resolution (HR) images from low-resolution images by learning a reverse process that adds noise to HR images. To verify the effectiveness of the method, images from the Goode Solar Telescope at the Big Bear Solar Observatory and the Helioseismic and Magnetic Imager (HMI) on the Solar Dynamics Observatory are used to train a network, and the spatial resolution of reconstructed images is 4 times that of the original HMI images. The experimental results show that the performance based on ICDDPM is better than the previous work in subject judgment and object evaluation indexes. The reconstructed images of this method have higher subjective vision quality and better consistency with the HMI images. And the structural similarity and rms index results are also higher than the compared method, demonstrating the success of the resolution improvement using ICDDPM.more » « less
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Frogs are ideal organisms for studying sex chromosome evolution because of their diversity in sex chromosome differentiation and sex-determination systems. We review 222 anuran frogs, spanning ~220 Myr of divergence, with characterized sex chromosomes, and discuss their evolution, phylogenetic distribution and transitions between homomorphic and heteromorphic states, as well as between sex-determination systems. Most (~75%) anurans have homomorphic sex chromosomes, with XY systems being three times more common than ZW systems. Most remaining anurans (~25%) have heteromorphic sex chromosomes, with XY and ZW systems almost equally represented. There are Y-autosome fusions in 11 species, and no W-/Z-/X-autosome fusions are known. The phylogeny represents at least 19 transitions between sex-determination systems and at least 16 cases of independent evolution of heteromorphic sex chromosomes from homomorphy, the likely ancestral state. Five lineages mostly have heteromorphic sex chromosomes, which might have evolved due to demographic and sexual selection attributes of those lineages. Males do not recombine over most of their genome, regardless of which is the heterogametic sex. Nevertheless, telomere-restricted recombination between ZW chromosomes has evolved at least once. More comparative genomic studies are needed to understand the evolutionary trajectories of sex chromosomes among frog lineages, especially in the ZW systems.more » « less
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Abstract Reproduction is a fundamental aspect of life that affects all levels of biology, from genomes and development to population dynamics and diversification. The first Tree of Sex database synthesized a vast diversity of reproductive strategies and their intriguing distribution throughout eukaryotes. A decade on, we are reviving this initiative and greatly expanding its scope to provide the most comprehensive integration of knowledge on eukaryotic reproduction to date. In this perspective, we first identify important gaps in our current knowledge of reproductive strategies across eukaryotes. We then highlight a selection of questions that will benefit most from this new Tree of Sex project, including those related to the evolution of sex, modes of sex determination, sex chromosomes, and the consequences of various reproductive strategies. Finally, we outline our vision for the new Tree of Sex database and the consortium that will create it (treeofsex.org). The new database will cover all Eukaryota and include a wide selection of biological traits. It will also incorporate genomic data types that were scarce or non-existent at the time of the first Tree of Sex initiative. The new database will be publicly accessible, stable, and self-sustaining, thus greatly improving the accessibility of reproductive knowledge to researchers across disciplines for years to come. Lastly, the consortium will persist after the database is created to serve as a collaborative framework for research, prioritizing ethical standards in the collection, use, and sharing of reproductive data. The new Tree of Sex consortium is open, and we encourage all who are interested in this topic to join us.more » « less
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