bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts
Authors: Suryawanshi Hemant , Yang Hua , Lubetzky Michelle , Morozov Pavel , Lagman Mila , Thareja Gaurav , Alonso Alicia , Li Carol , Snopkowski Catherine , Belkadi Aziz , Mueller Franco B. , Lee John R. , Dadhania Darshana M. , Salvatore Steven P. , Seshan Surya V. , Sharma Vijay K. , Suhre Karsten , Suthanthiran Manikkam , Tuschl Thomas , Muthukumar Thangamani 
Published: September 2020

AbstractWe tested the hypothesis that single-cell RNA-sequencing (scRNA-seq) analysis of human kidney allograft biopsies will reveal distinct cell types and states and yield insights to decipher the complex heterogeneity of alloimmune injury. We selected 3 biopsies of kidney cortex from 3 individuals for scRNA-seq and processed them fresh using an identical protocol on the 10x Chromium platform; (i) HK: native kidney biopsy from a living donor, (ii) AK1: allograft kidney with transplant glomerulopathy, tubulointerstitial fibrosis, and worsening graft function, and (iii) AK2: allograft kidney after successful treatment of active antibody-mediated rejection. We did not study T-cell-mediated rejections. We generated 7217 high-quality single cell transcriptomes. Taking advantage of the recipient-donor sex mismatches revealed by X and Y chromosome autosomal gene expression, we determined that in AK1 with fibrosis, 42 months after transplantation, more than half of the kidney allograft fibroblasts were recipient-derived and therefore likely migratory and graft infiltrative, whereas in AK2 without fibrosis, 84 months after transplantation, most fibroblasts were donor-organ-derived. Furthermore, AK1 was enriched for tubular progenitor cells overexpressing profibrotic extracellular matrix genes. AK2, eight months after successful treatment of rejection, contained endothelial cells that expressed T-cell chemoattractant cytokines. In addition to these key findings, our analysis revealed unique cell types and states in the kidney. Altogether, single-cell transcriptomics yielded novel mechanistic insights, which could pave the way for individualizing the care of transplant recipients.
Genome assembly and transcriptome analysis provide insights into the anti-schistosome mechanism ofMicrotus fortis
Authors: Li Hong , Wang Zhen , Chai Shumei , Bai Xiong , Ding Guohui , Li Junyi , Xiao Qingyu , Miao Benpeng , Lin Weili , Feng Jie , Gao Cheng , Li Yuanyuan , Li Bin , Hu Wei , Lin Jiaojiao , Fu Zhiqiang , Xie Jianyuan , Li Yixue 
Published: September 2020

ABSTRACTMicrotus fortis(M. fortis) so far is the only mammal host that exhibits intrinsic resistance againstSchistosoma japonicuminfection. However, the underlying molecular mechanisms of this intrinsic resistance are not yet known. Here we performed the firstde novogenome assembly ofM. fortis, comprehensive gene annotation and evolution analysis. Furthermore, we compared the recovery rate of schistosome, pathological change and liver transcriptome between non-permissive hostM. fortisand susceptible host mouse at different time points after Schistosome infection. We reveal that Immune response ofM. fortisand mouse is different in time and type.M. fortisactivates immune and inflammatory responses on the 10thdays post infection, involving in multiple pathways, such as leukocyte extravasation, antibody activation (especially IgG3), Fc-gamma receptor mediated phagocytosis, and interferon signaling cascade. The strong immune responses ofM. fortisin early stages of infection play important roles in preventing the development of schistosome. On the contrary, intense immune response occurred in mouse in late stages of infection (28~42 days post infection), and cannot eliminate schistosome. Infected mouse suffers severe pathological injury and continuous decrease of important functions such as cell cycle and lipid metabolism. Our findings offer new insights to the intrinsic resistance mechanism ofM. fortisagainst schistosome infection. The genome sequence also provides bases for future studies of other important traits inM. fortis.
Cell-to-cell spread inhibiting antibodies constitute a correlate of protection against Herpes Simplex Virus Type 1 reactivations
Authors: Wolf Susanne , Alt Mira , Dittrich Robin , Dirks Miriam , Schipper Leonie , Aufderhorst Ulrich Wilhelm , Rainer Kordula , Dittmer Ulf , Witzke Oliver , Giebel Bernd , Trilling Mirko , Heilingloh Christiane Silke , Lotfi Ramin , Roggendorf Michael , Krawczyk Adalbert 
Published: September 2020

AbstractHerpes simplex viruses (HSV) cause ubiquitous human infections. For vaccine development, knowledge concerning correlates of protection against HSV is essential. Therefore, we investigated if humans principally can produce highly protective cell-to-cell spread inhibiting antibodies upon natural infection and whether such antibody responses correlate with protection from HSV reactivation. We established a high-throughput HSV-1 GFP reporter virus-based assay and screened 2496 human plasma samples for HSV-1 cell-to-cell spread inhibiting antibodies. We conducted a survey among the blood donors to analyze the correlation between the presence of cell-to-cell spread inhibiting antibodies in plasma and the frequency of HSV reactivations. In total, 128 of 2496 blood donors (5.1 %) exhibited high levels of HSV-1 cell-to-cell spread inhibiting antibodies in the plasma. Such individuals showed a significantly lower frequency of HSV reactivations compared to subjects without sufficient levels of HSV-1 cell-to-cell spread inhibiting antibodies. This study provides two important findings: (I) a fraction of humans produce HSV cell-to-cell spread inhibiting antibodies upon natural infection and (II) such antibodies correlate with protection against recurrent HSV. Moreover, these elite neutralizers can provide promising material for hyperimmunoglobulin, the isolation of superior antiviral antibodies and information for the design of a vaccine against HSV.ImportanceHerpes simplex virus 1 infections can cause painful mucosal lesions at the oral or genital tract and severe, life threatening disease in immunosuppressed patients or neonates. There is no approved vaccine available, and the emergence of drug resistances especially in long time treated patients makes the treatment increasingly difficult. We tested 2496 people for HSV-1 cell-to-cell spread inhibiting antibodies. Five percent exhibited functional titers such antibodies and showed significantly lower risk of reactivations, uncovering cell-to-cell spread inhibiting antibodies as a correlate of protection against Herpes simplex virus reactivations. Isolation of the cell-to-cell spread inhibiting antibodies from B-cells of these donors may contribute to develop novel antibody-based interventions for prophylactic and therapeutic use and provide starting material for vaccine development.
Effects of kin recognition on root traits of wheat germplasm over 100 years of breeding
Authors: Kiær Lars Pødenphant , Weiner Jacob , Rasmussen Camilla Ruø 
Published: September 2020

SummaryPlant root and shoot growth has been shown to depend on the relatedness of co-cultivated genotypes, implying the existence of ‘kin recognition’ mechanisms mediated by root exudates. If confirmed, this has important implications for crop breeding.We present the first large-sale investigation of kin recognition in a crop germplasm collection comprising 30 North-European cultivars and landraces of spring wheat, spanning 100 years of breeding history. In a full diallelin vitrobioassay, we compared root growth of seedlings when growing in pure substrate, or in substrate previously occupied by a donor seedling from the same (KIN) or another (NONKIN) genotype.Seedlings growing in KIN or NONKIN substrate generally had longer but not more roots than seedlings growing in pure substrate. Responses were generally larger in longer roots, suggesting that root elongation was promoted throughout the growth period. Responses to KIN and NONKIN substrates were found to range from positive to negative, with root length responses to kin being increasingly positive with year of release. Seedlings growing in KIN substrate generally had shorter but not fewer roots than seedlings growing in NONKIN substrate. This kin recognition ranged from positive to negative across the specific donor-receiver combinations and did not change systematically with year of release of either genotype. Root traits in both KIN and NONKIN substrate were affected by both donor and receiver genotype, and these effects were generally larger than the effect of specific combinations. Genotypes showing higher levels of kin recognition also tended to invoke larger responses in other genotypes. Kin recognition was reduced in most cases by the addition of sodiumorthovanadate, a chemical inhibitor, supporting the hypothesis that kin responses were mediated by changes in the chemical constitution of the substrate.The identified patterns of kin recognition across the germplasm collection were complex, suggesting a multigenic background and shared breeding history of the genotypes. We conclude that kin response represents a potential target for crop breeding which can improve root foraging and competitive interactions.
Sex, males, and hermaphrodites in the scale insectIcerya purchasi
Authors: Mongue Andrew J. , Michaelides Sozos , Coombe Oliver , Tena Alejandro , Kim Dong-Soon , Normark Benjamin B. , Gardner Andy , Hoddle Mark S. , Ross Laura 
Published: September 2020

AbstractAndrodioecy (the coexistence of males and hermaphrodites) is a rare mating system for which the evolutionary dynamics are poorly understood. Here we study the only presumed case of androdioecy in insects, found in the cottony cushion scale,Icerya purchasi. In this species, female-like hermaphrodites have been shown to produce sperm and self-fertilize. However, rare males are sometimes observed too. In a large population-genetic analysis, we show for the first time that although self-fertilization appears to be the primary mode of reproduction, rare outbreeding events between males and hermaphrodites do occur, and we thereby confirm androdioecy as the mating system ofI. purchasi. Thus, this insect appears to have the colonization advantages of a selfing organism while also benefitting from periodic reintroduction of genetic variation through outbreeding with males.
QSIPrep: An integrative platform for preprocessing and reconstructing diffusion MRI
Authors: Cieslak Matthew , Cook Philip A. , He Xiaosong , Yeh Fang-Cheng , Dhollander Thijs , Adebimpe Azeez , Aguirre Geoffrey K. , Bassett Danielle S. , Betzel Richard F. , Bourque Josiane , Cabral Laura M. , Davatzikos Christos , Detre John , Earl Eric , Elliott Mark A. , Fadnavis Shreyas , Fair Damien A. , Foran Will , Fotiadis Panagiotis , Garyfallidis Eleftherios , Giesbrecht Barry , Gur Ruben C. , Gur Raquel E. , Kelz Max , Keshavan Anisha , Larsen Bart S. , Luna Beatriz , Mackey Allyson P. , Milham Michael , Oathes Desmond J. , Perrone Anders , Pines Adam R. , Roalf David R. , Richie-Halford Adam , Rokem Ariel , Sydnor Valerie J. , Tapera Tinashe M. , Tooley Ursula A. , Vettel Jean M. , Yeatman Jason D. , Grafton Scott T. , Satterthwaite Theodore D. 
Published: September 2020

ABSTRACTDiffusion-weighted magnetic resonance imaging (dMRI) has become the primary method for non-invasively studying the organization of white matter in the human brain. While many dMRI acquisition sequences have been developed, they all sample q-space in order to characterize water diffusion. Numerous software platforms have been developed for processing dMRI data, but most work on only a subset of sampling schemes or implement only parts of the processing workflow. Reproducible research and comparisons across dMRI methods are hindered by incompatible software, diverse file formats, and inconsistent naming conventions. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing upon a diverse set of software suites to capitalize upon their complementary strengths, QSIPrep automatically applies best practices for dMRI preprocessing, including denoising, distortion correction, head motion correction, coregistration, and spatial normalization. Throughout, QSIPrep provides both visual and quantitative measures of data quality as well as “glass-box” methods reporting. Taken together, these features facilitate easy implementation of best practices for processing of diffusion images while simultaneously ensuring reproducibility.
Melanopsin retinal ganglion cell-driven contribution to visual and cognitive brain responses in LHON
Authors: Evangelisti Stefania , Morgia Chiara La , Testa Claudia , Manners David N , Brizi Leonardo , Bianchini Claudio , Carbonelli Michele , Barboni Piero , Sadun Alfredo A. , Tonon Caterina , Carelli Valerio , Vandewalle Gilles , Lodi Raffaele 
Published: September 2020

AbstractMelanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive photoreceptors contributing to visual and non-image-forming functions of the eye. Isolating mRGC roles in humans is challenging, therefore mRGCs functions remains to be fully characterized.We explored mRGCs contribution to light-driven visual and cognitive brain responses in Leber’s Hereditary Optic Neuropathy (LHON), given mRGC relative sparing in LHON. Twelve patients and twelve matched healthy controls (HC) participated in an fMRI protocol including visual and visual-cognitive paradigms under blue (480nm) and red light (620nm).Higher occipital activation was found in response to sustained bluevs.red stimulation in LHONvs.HC. Similarly, brain responses to the executive task were larger under bluevs.red light in LHON over lateral prefrontal cortex.These findings are in line with LHON mRGCs relative sparing and support mRGCs contribution to non-visual and visual functions in humans, with potential implication for visual rehabilitation in optic neuropathy patients.
Pharmacological and genetic manipulations of Ca2+signaling have contrasting effects on auxin-regulated trafficking
Authors: Wang Ren , Himschoot Ellie , Grenzi Matteo , Chen Jian , Krebs Melanie , Schumacher Karin , Nowack Moritz K. , Van Damme Daniël , De Smet Ive , Beeckman Tom , Costa Alex , Friml Jiří , Vanneste Steffen 
Published: September 2020

ABSTRACTA large part of a plants’ developmental plasticity relies on the activities of the phytohormone auxin and the regulation of its own distribution. This process involves a cohort of transcriptional and non-transcriptional effects of auxin on polar auxin transport, regulating the abundancy, biochemical activity and polar localization of the molecular components, predominantly PIN auxin exporters. While the transcriptional auxin signaling cascade has been well characterized, the mechanism and role of non-transcriptional auxin signaling remains largely elusive. Here, we addressed the potential involvement of auxin-induced Ca2+signaling in auxin’s inhibitory effect on PIN endocytic trafficking. On the one hand, exogenous manipulations of Ca2+availability and signaling effectively antagonized auxin effects suggesting that auxin-induced Ca2+signaling is required for inhibition of internalization. On the other hand, we addressed the auxin-mediated inhibition of PIN internalization in the auxin signaling (tir1afb2,3) or Ca2+channel (cngc14) mutants. These mutants were strongly defective in auxin-triggered Ca2+signaling, but not in auxin-inhibited internalization. These data imply that, while Ca2+signaling may be required for normal PIN trafficking, auxin-mediated increase in Ca2+signaling is not a direct part of a downstream mechanism that mediates auxin effects on Brefeldin A-visualized PIN intercellular aggregation. These contrasting results obtained by comparing the mutant analysis versus the exogenous manipulations of Ca2+availability and signaling illustrate the critical importance of genetics to unravel the role of Ca2+in a process of interest.
A trans-omics comparison reveals common gene expression strategies in four model organisms and exposes similarities and differences between them
Authors: Forés-Martos Jaume , Forte Anabel , García-Martínez José , Pérez-Ortín José E. 
Published: September 2020

AbstractThe ultimate goal of gene regulation should focus on the protein level. However, as mRNA is an obligate intermediary, and because the amounts of mRNAs and proteins are controlled by their synthesis and degradation rates, the cellular amount of a given protein can be attained following different strategies. By studying omics datasets for six expression variables (mRNA and protein amounts, plus their synthesis and decay rates), we previously demonstrated the existence of common expression strategies (CES) for functionally-related genes in the yeastSaccharomyces cerevisiae. Here we extend that study to two other eukaryotes: the distantly related yeastSchizosaccharomyces pombeand cultured human HeLa cells. We also use genomic datasets from the model prokaryoteEscherichia colias an external reference. We show that CES are also present in all the studied organisms and the differences in them between organisms can be used to establish their phylogenetic relationships. The phenogram based on 6VP has the expected topology for the phylogeny of these four organisms, but shows interesting branch length differences to DNA sequence-based trees.The analysis of the correlations among the six variables supports that most gene expression control occurs in actively growing organisms at the transcription rate level, and that translation plays a minor role in it. We propose that all living cells use CES for the genes acting on the same physiological pathways, especially for those belonging to stable macromolecular complexes, but CES have been modeled by evolution to adapt to the specific life circumstances of each organism. The obtained phenograms may reflect both evolutionary constraints in expression strategies, and lifestyle convergences.
Determination of the molecular reach of the protein tyrosine phosphatase SHP-1
Authors: Clemens Lara , Kutuzov Mikhail , Bayer Kristina Viktoria , Goyette Jesse , Allard Jun , Dushek Omer 
Published: September 2020

AbstractImmune receptor signalling proceeds by the binding (or tethering) of enzymes to their cytoplasmic tails before they catalyse reactions on substrates within reach. This is the case for the enzyme SHP-1 that, upon tethering to the inhibitory receptor PD-1, dephosphorylates membrane substrates to suppress T cell activation. Precisely how tethering regulates SHP-1 activity is incompletely understood. Here, we use surface plasmon resonance to measure binding, catalysis, and molecular reach for PD-1 tethered SHP-1 reactions. We find that the reach of PD-1—SHP-1 complexes is dominated by the 13.0 nm reach of SHP-1 itself. This is longer than an estimate from the structure of the allosterically active conformation (5.3 nm), suggesting that SHP-1 explores multiple active conformations. Using modelling, we show that when uniformly distributed, PD-1—SHP-1 complexes can only reach 15% of substrates but this increases to 90% when they are co-clustered. When within reach, we show that membrane recruitment increases the activity of SHP-1 by a 1000-fold increase in local concentration. The work highlights how molecular reach regulates the activity of membrane-recruited SHP-1 with insights applicable to other membrane-tethered reactions.Significance statementImmune receptors transduce signals by recruiting (or tethering) cytoplasmic enzymes to their tails at the membrane. When tethered, these enzymes catalyse reactions on other substrates to propagate signalling. Precisely how membrane tethering regulates enzyme activity is incompletely understood. Unlike other tethered reactions, where the enzyme tethers to the substrate, the substrate in this case is a different receptor tail. Therefore, the ability of the receptor-tethered enzyme to reach a substrate can be critical in controlling reaction rates. In this work, we determine the molecular reach for the enzyme SHP-1 and the receptor PD-1 to which it can tether, and show how molecular reach controls receptor signalling.
BayesSpace enables the robust characterization of spatial gene expression architecture in tissue sections at increased resolution
Authors: Zhao Edward , Stone Matthew R. , Ren Xing , Pulliam Thomas , Nghiem Paul , Bielas Jason H. , Gottardo Raphael 
Published: September 2020

AbstractRecently developed spatial gene expression technologies such as the Spatial Transcriptomics and Visium platforms allow for comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing methods for analyzing spatial gene expression data often do not efficiently leverage the spatial information and fail to address the limited resolution of the technology. Here, we introduce BayesSpace, a fully Bayesian statistical method for clustering analysis and resolution enhancement of spatial transcriptomics data that seamlessly integrates into current transcriptomics analysis workflows. We show that BayesSpace improves the identification of transcriptionally distinct tissues from spatial transcriptomics samples of the brain, of melanoma, and of squamous cell carcinoma. In particular, BayesSpace’s improved resolution allows the identification of tissue structure that is not detectable at the original resolution and thus not recovered by other methods. Using anin silicodataset constructed from scRNA-seq, we demonstrate that BayesSpace can spatially resolve expression patterns to near single-cell resolution without the need for external single-cell sequencing data. In all, our results illustrate the utility BayesSpace has in facilitating the discovery of biological insights from a variety of spatial transcriptomics datasets.
Laser nanobubbles induce immunogenic cell death in breast cancer
Authors: Nguyen Hieu T.M. , Katta Nitesh , Widman Jessica A. , Takematsu Eri , Feng Xu , Torres Susana H. , Betancourt Tania , Baker Aaron B. , Suggs Laura J. , Milner Thomas E. , Tunnell James W. 
Published: September 2020

ABSTRACTRecent advances in immunotherapy have highlighted a need for therapeutics that initiate immunogenic cell death in tumors to stimulate the body’s immune response to cancer. This study examines whether laser-generated bubbles surrounding nanoparticles (“nanobubbles”) induce an immunogenic response for cancer treatment. A single nanosecond laser pulse at 1064 nm generates micron-sized bubbles surrounding gold nanorods in the cytoplasm of breast cancer cells. Cell death occurred in cells treated with nanorods and irradiated but not in cells with irradiation treatment alone. Cells treated with nanorods and irradiation had increased damage-associated molecular patterns (DAMPs), including increased expression of chaperone proteins human high mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and heat shock protein 70 (HSP70). This enhanced expression of DAMPs led to the activation of dendritic cells. Overall, this treatment approach is a rapid and highly specific method to eradicate tumor cells with simultaneous immunogenic cell death signaling, showing potential as a combination strategy for immunotherapy.