bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling pathways and intervention therapies in sepsis
Authors: Zhang Yun-yu , Ning Bo-tao 
Published: November 2021

AbstractSepsis is defined as life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection. Over decades, advanced understanding of host–microorganism interaction has gradually unmasked the genuine nature of sepsis, guiding toward new definition and novel therapeutic approaches. Diverse clinical manifestations and outcomes among infectious patients have suggested the heterogeneity of immunopathology, while systemic inflammatory responses and deteriorating organ function observed in critically ill patients imply the extensively hyperactivated cascades by the host defense system. From focusing on microorganism pathogenicity, research interests have turned toward the molecular basis of host responses. Though progress has been made regarding recognition and management of clinical sepsis, incidence and mortality rate remain high. Furthermore, clinical trials of therapeutics have failed to obtain promising results. As far as we know, there was no systematic review addressing sepsis-related molecular signaling pathways and intervention therapy in literature. Increasing studies have succeeded to confirm novel functions of involved signaling pathways and comment on efficacy of intervention therapies amid sepsis. However, few of these studies attempt to elucidate the underlining mechanism in progression of sepsis, while other failed to integrate preliminary findings and describe in a broader view. This review focuses on the important signaling pathways, potential molecular mechanism, and pathway-associated therapy in sepsis. Host-derived molecules interacting with activated cells possess pivotal role for sepsis pathogenesis by dynamic regulation of signaling pathways. Cross-talk and functions of these molecules are also discussed in detail. Lastly, potential novel therapeutic strategies precisely targeting on signaling pathways and molecules are mentioned.
Translation stalling proline motifs are enriched in slow-growing, thermophilic, and multicellular bacteria
Authors: Brewer Tess E , Wagner Andreas 
Published: November 2021

Abstract
Rapid bacterial growth depends on the speed at which ribosomes can translate mRNA into proteins. mRNAs that encode successive stretches of proline can cause ribosomes to stall, substantially reducing translation speed. Such stalling is especially detrimental for species that must grow and divide rapidly. Here, we focus on di-prolyl motifs (XXPPX) and ask whether their prevalence varies with growth rate. To find out we conducted a broad survey of such motifs in &gt;3000 bacterial genomes across 35 phyla. Indeed, fast-growing species encode fewer motifs than slow-growing species, especially in highly expressed proteins. We also found many di-prolyl motifs within thermophiles, where prolines can help maintain proteome stability. Moreover, bacteria with complex, multicellular lifecycles also encode many di-prolyl motifs. This is especially evident in the slow-growing phylum Myxococcota. Bacteria in this phylum encode many serine-threonine kinases, and many di-prolyl motifs at potential phosphorylation sites within these kinases. Serine-threonine kinases are involved in cell signaling and help regulate developmental processes linked to multicellularity in the Myxococcota. Altogether, our observations suggest that weakened selection on translational rate, whether due to slow or thermophilic growth, may allow di-prolyl motifs to take on new roles in biological processes that are unrelated to translational rate.
Oxytocin-pathway polygenic scores for severe mental disorders and metabolic phenotypes in the UK Biobank
Authors: Winterton Adriano , Bettella Francesco , de Lange Ann-Marie G. , Haram Marit , Steen Nils Eiel , Westlye Lars T. , Andreassen Ole A. , Quintana Daniel S. 
Published: November 2021

AbstractOxytocin is a neuromodulator and hormone that is typically associated with social cognition and behavior. In light of its purported effects on social cognition and behavior, research has investigated its potential as a treatment for psychiatric illnesses characterized by social dysfunction, such as schizophrenia and bipolar disorder. While the results of these trials have been mixed, more recent evidence suggests that the oxytocin system is also linked with cardiometabolic conditions for which individuals with severe mental disorders are at a higher risk for developing. To investigate whether the oxytocin system has a pleiotropic effect on the etiology of severe mental illness and cardiometabolic conditions, we explored oxytocin’s role in the shared genetic liability of schizophrenia, bipolar disorder, type-2 diabetes, and several phenotypes linked with cardiovascular disease and type 2 diabetes risk using a polygenic pathway-specific approach. Analysis of a large sample with about 480,000 individuals (UK Biobank) revealed statistically significant associations across the range of phenotypes analyzed. By comparing these effects to those of polygenic scores calculated from 100 random gene sets, we also demonstrated the specificity of many of these significant results. Altogether, our results suggest that the shared effect of oxytocin-system dysfunction could help partially explain the co-occurrence of social and cardiometabolic dysfunction in severe mental illnesses.
Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture
Authors: Álvarez Eva G. , Demeulemeester Jonas , Otero Paula , Jolly Clemency , García-Souto Daniel , Pequeño-Valtierra Ana , Zamora Jorge , Tojo Marta , Temes Javier , Baez-Ortega Adrian , Rodriguez-Martin Bernardo , Oitaben Ana , Bruzos Alicia L. , Martínez-Fernández Mónica , Haase Kerstin , Zumalave Sonia , Abal Rosanna , Rodríguez-Castro Jorge , Rodriguez-Casanova Aitor , Diaz-Lagares Angel , Li Yilong , Raine Keiran M. , Butler Adam P. , Otero Iago , Ono Atsushi , Aikata Hiroshi , Chayama Kazuaki , Ueno Masaki , Hayami Shinya , Yamaue Hiroki , Maejima Kazuhiro , Blanco Miguel G. , Forns Xavier , Rivas Carmen , Ruiz-Bañobre Juan , Pérez-del-Pulgar Sofía , Torres-Ruiz Raúl , Rodriguez-Perales Sandra , Garaigorta Urtzi , Campbell Peter J. , Nakagawa Hidewaki , Van Loo Peter , Tubio Jose M. C. 
Published: November 2021

AbstractMost cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration.
Hydrothermal plumes as hotspots for deep-ocean heterotrophic microbial biomass production
Authors: Cathalot Cécile , Roussel Erwan G. , Perhirin Antoine , Creff Vanessa , Donval Jean-Pierre , Guyader Vivien , Roullet Guillaume , Gula Jonathan , Tamburini Christian , Garel Marc , Godfroy Anne , Sarradin Pierre-Marie 
Published: November 2021

AbstractCarbon budgets of hydrothermal plumes result from the balance between carbon sinks through plume chemoautotrophic processes and carbon release via microbial respiration. However, the lack of comprehensive analysis of the metabolic processes and biomass production rates hinders an accurate estimate of their contribution to the deep ocean carbon cycle. Here, we use a biogeochemical model to estimate the autotrophic and heterotrophic production rates of microbial communities in hydrothermal plumes and validate it with in situ data. We show how substrate limitation might prevent net chemolithoautotrophic production in hydrothermal plumes. Elevated prokaryotic heterotrophic production rates (up to 0.9 gCm−2y−1) compared to the surrounding seawater could lead to 0.05 GtCy−1 of C-biomass produced through chemoorganotrophy within hydrothermal plumes, similar to the Particulate Organic Carbon (POC) export fluxes reported in the deep ocean. We conclude that hydrothermal plumes must be accounted for as significant deep sources of POC in ocean carbon budgets.
Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
Authors: Zhang Qianqian , Cheng Sijin , Wang Yongzhi , Wang Mengdi , Lu Yufeng , Wen Zengqi , Ge Yuxin , Ma Qiang , Chen Youqiao , Zhang Yaowu , Cao Ren , Li Min , Liu Weihao , Wang Bo , Wu Qian , Jia Wenqing , Wang Xiaoqun 
Published: November 2021

AbstractSpinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.
Photoluminescence mechanism of carbon dots: triggering high-color-purity red fluorescence emission through edge amino protonation
Authors: Zhang Qing , Wang Ruoyu , Feng Bowen , Zhong Xiaoxia , Ostrikov Kostya 
Published: November 2021

AbstractDue to complex structure and surface functionalities, photoluminescence mechanisms of Carbon Dots are unknown, and it is challenging to synthesize Carbon Dots to achieve the desired optical properties. Herein, Carbon Dots simultaneously exhibiting high-color-purity (FWHM~24 nm) long wavelength one-photon fluorescence emission at 620 nm and NIR induced two-photon fluorescence emission at 630 and 680 nm are prepared by edge amino protonation treatment. Systematic analysis reveals that the protonation of 2,3-diaminophenazine changes the molecular state of Carbon Dots, decreases the photon transition band gap, and triggers red fluorescence emission with the dramatically narrowed peak width. As the oxidation products of reactant o-phenylendiamine, the emergence of 2,3-diaminophenazine as a photoluminescence determiner suggests that fluorophore products of precursor conversion are viable determinants of the desired luminescence properties of Carbon Dots. This work shows a new way for predicting and controlling photoluminescence properties of Carbon Dots, and may guide the development of tunable Carbon Dots for a broad range of applications.
Thermal dynamics and electronic temperature waves in layered correlated materials
Authors: Mazza Giacomo , Gandolfi Marco , Capone Massimo , Banfi Francesco , Giannetti Claudio 
Published: November 2021

AbstractUnderstanding the mechanism of heat transfer in nanoscale devices remains one of the greatest intellectual challenges in the field of thermal dynamics, by far the most relevant under an applicative standpoint. When thermal dynamics is confined to the nanoscale, the characteristic timescales become ultrafast, engendering the failure of the common description of energy propagation and paving the way to unconventional phenomena such as wave-like temperature propagation. Here, we explore layered strongly correlated materials as a platform to identify and control unconventional electronic heat transfer phenomena. We demonstrate that these systems can be tailored to sustain a wide spectrum of electronic heat transport regimes, ranging from ballistic, to hydrodynamic all the way to diffusive. Within the hydrodynamic regime, wave-like temperature oscillations are predicted up to room temperature. The interaction strength can be exploited as a knob to control the dynamics of temperature waves as well as the onset of different thermal transport regimes.
A full gap above the Fermi level: the charge density wave of monolayer VS2
Authors: van Efferen Camiel , Berges Jan , Hall Joshua , van Loon Erik , Kraus Stefan , Schobert Arne , Wekking Tobias , Huttmann Felix , Plaar Eline , Rothenbach Nico , Ollefs Katharina , Arruda Lucas Machado , Brookes Nick , Schönhoff Gunnar , Kummer Kurt , Wende Heiko , Wehling Tim , Michely Thomas 
Published: November 2021

AbstractIn the standard model of charge density wave (CDW) transitions, the displacement along a single phonon mode lowers the total electronic energy by creating a gap at the Fermi level, making the CDW a metal–insulator transition. Here, using scanning tunneling microscopy and spectroscopy and ab initio calculations, we show that VS2 realizes a CDW which stands out of this standard model. There is a full CDW gap residing in the unoccupied states of monolayer VS2. At the Fermi level, the CDW induces a topological metal-metal (Lifshitz) transition. Non-linear coupling of transverse and longitudinal phonons is essential for the formation of the CDW and the full gap above the Fermi level. Additionally, x-ray magnetic circular dichroism reveals the absence of net magnetization in this phase, pointing to coexisting charge and spin density waves in the ground state.
Ultra-rapid and highly efficient enrichment of organic pollutants via magnetic mesoporous nanosponge for ultrasensitive nanosensors
Authors: Zhang Lingling , Guo Yu , Hao Rui , Shi Yafei , You Hongjun , Nan Hu , Dai Yanzhu , Liu Danjun , Lei Dangyuan , Fang Jixiang 
Published: November 2021

AbstractCurrently, owing to the single-molecule-level sensitivity and highly informative spectroscopic characteristics, surface-enhanced Raman scattering (SERS) is regarded as the most direct and effective detection technique. However, SERS still faces several challenges in its practical applications, such as the complex matrix interferences, and low sensitivity to the molecules of intrinsic small cross-sections or weak affinity to the surface of metals. Here, we show an enrichment-typed sensing strategy with both excellent selectivity and ultrahigh detection sensitivity based on a powerful porous composite material, called mesoporous nanosponge. The nanosponge consists of porous β-cyclodextrin polymers immobilized with magnetic NPs, demonstrating remarkable capability of effective and fast removal of organic micropollutants, e.g., ~90% removal efficiency within ~1 min, and an enrichment factor up to ~103. By means of this current enrichment strategy, the limit of detection for typical organic pollutants can be significantly improved by 2~3 orders of magnitude. Consequently, the current enrichment strategy is proved to be applicable in a variety of fields for portable and fast detection, such as Raman and fluorescent sensing.
High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer
Authors: Rogic Anita , Pant Ila , Grumolato Luca , Fernandez-Rodriguez Ruben , Edwards Andrew , Das Suvendu , Sun Aaron , Yao Shen , Qiao Rui , Jaffer Shabnam , Sachidanandam Ravi , Akturk Guray , Karlic Rosa , Skobe Mihaela , Aaronson Stuart A. 
Published: November 2021

AbstractInflammatory Breast Cancer (IBC) is a highly aggressive malignancy with distinct clinical and histopathological features whose molecular basis is unresolved. Here we describe a human IBC cell line, A3250, that recapitulates key IBC features in a mouse xenograft model, including skin erythema, diffuse tumor growth, dermal lymphatic invasion, and extensive metastases. A3250 cells express very high levels of the CCL2 chemokine and induce tumors enriched in macrophages. CCL2 knockdown leads to a striking reduction in macrophage densities, tumor proliferation, skin erythema, and metastasis. These results establish IBC-derived CCL2 as a key factor driving macrophage expansion, and indirectly tumor growth, with transcriptomic analysis demonstrating the activation of multiple inflammatory pathways. Finally, primary human IBCs exhibit macrophage infiltration and an enriched macrophage RNA signature. Thus, this human IBC model provides insight into the distinctive biology of IBC, and highlights potential therapeutic approaches to this deadly disease.
Interaction of two MADS-box genes leads to growth phenotype divergence of all-flesh type of tomatoes
Authors: Huang Baowen , Hu Guojian , Wang Keke , Frasse Pierre , Maza Elie , Djari Anis , Deng Wei , Pirrello Julien , Burlat Vincent , Pons Clara , Granell Antonio , Li Zhengguo , van der Rest Benoît , Bouzayen Mondher 
Published: November 2021

AbstractAll-flesh tomato cultivars are devoid of locular gel and exhibit enhanced firmness and improved postharvest storage. Here, we show that SlMBP3 is a master regulator of locular tissue in tomato fruit and that a deletion at the gene locus underpins the All-flesh trait. Intriguingly, All-flesh varieties lack the deleterious phenotypes reported previously for SlMBP3 under-expressing lines and which preclude any potential commercial use. We resolve the causal factor for this phenotypic divergence through the discovery of a natural mutation at the SlAGL11 locus, a close homolog of SlMBP3. Misexpressing SlMBP3 impairs locular gel formation through massive transcriptomic reprogramming at initial phases of fruit development. SlMBP3 influences locule gel formation by controlling cell cycle and cell expansion genes, indicating that important components of fruit softening are determined at early pre-ripening stages. Our findings define potential breeding targets for improved texture in tomato and possibly other fleshy fruits.
N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization
Authors: Freibert Sven-A. , Boniecki Michal T. , Stümpfig Claudia , Schulz Vinzent , Krapoth Nils , Winge Dennis R. , Mühlenhoff Ulrich , Stehling Oliver , Cygler Miroslaw , Lill Roland 
Published: November 2021

AbstractSynthesis of iron-sulfur (Fe/S) clusters in living cells requires scaffold proteins for both facile synthesis and subsequent transfer of clusters to target apoproteins. The human mitochondrial ISCU2 scaffold protein is part of the core ISC (iron-sulfur cluster assembly) complex that synthesizes a bridging [2Fe-2S] cluster on dimeric ISCU2. Initial iron and sulfur loading onto monomeric ISCU2 have been elucidated biochemically, yet subsequent [2Fe-2S] cluster formation and dimerization of ISCU2 is mechanistically ill-defined. Our structural, biochemical and cell biological experiments now identify a crucial function of the universally conserved N-terminal Tyr35 of ISCU2 for these late reactions. Mixing two, per se non-functional ISCU2 mutant proteins with oppositely charged Asp35 and Lys35 residues, both bound to different cysteine desulfurase complexes NFS1-ISD11-ACP, restores wild-type ISCU2 maturation demonstrating that ionic forces can replace native Tyr-Tyr interactions during dimerization-induced [2Fe-2S] cluster formation. Our studies define the essential mechanistic role of Tyr35 in the reaction cycle of de novo mitochondrial [2Fe-2S] cluster synthesis.
A benchmark study of simulation methods for single-cell RNA sequencing data
Authors: Cao Yue , Yang Pengyi , Yang Jean Yee Hwa 
Published: November 2021

AbstractSingle-cell RNA-seq (scRNA-seq) data simulation is critical for evaluating computational methods for analysing scRNA-seq data especially when ground truth is experimentally unattainable. The reliability of evaluation depends on the ability of simulation methods to capture properties of experimental data. However, while many scRNA-seq data simulation methods have been proposed, a systematic evaluation of these methods is lacking. We develop a comprehensive evaluation framework, SimBench, including a kernel density estimation measure to benchmark 12 simulation methods through 35 scRNA-seq experimental datasets. We evaluate the simulation methods on a panel of data properties, ability to maintain biological signals, scalability and applicability. Our benchmark uncovers performance differences among the methods and highlights the varying difficulties in simulating data characteristics. Furthermore, we identify several limitations including maintaining heterogeneity of distribution. These results, together with the framework and datasets made publicly available as R packages, will guide simulation methods selection and their future development.
A transposon expression burst accompanies the activation of Y-chromosome fertility genes during Drosophila spermatogenesis
Authors: Lawlor Matthew A. , Cao Weihuan , Ellison Christopher E. 
Published: November 2021

AbstractTransposable elements (TEs) must replicate in germline cells to pass novel insertions to offspring. In Drosophila melanogaster ovaries, TEs can exploit specific developmental windows of opportunity to evade host silencing and increase their copy numbers. However, TE activity and host silencing in the distinct cell types of Drosophila testis are not well understood. Here, we reanalyze publicly available single-cell RNA-seq datasets to quantify TE expression in the distinct cell types of the Drosophila testis. We develop a method for identification of TE and host gene expression modules and find that a distinct population of early spermatocytes expresses a large number of TEs at much higher levels than other germline and somatic components of the testes. This burst of TE expression coincides with the activation of Y chromosome fertility factors and spermatocyte-specific transcriptional regulators, as well as downregulation of many components of the piRNA pathway. The TEs expressed by this cell population are specifically enriched on the Y chromosome and depleted on the X chromosome, relative to other active TEs. These data suggest that some TEs may achieve high insertional activity in males by exploiting a window of opportunity for mobilization created by the activation of spermatocyte-specific and Y chromosome-specific transcriptional programs.