bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRMT1 promotes neuroblastoma cell survival through ATF5
Authors: Hua Zhong-Yan , Hansen Jeanne N. , He Miao , Dai Shang-Kun , Choi Yoonjung , Fulton Melody D. , Lloyd Sarah M. , Szemes Marianna , Sen Ji , Ding Han-Fei , Angelastro James M. , Fei Xiang , Li Hui-Ping , Wu Chao-Ran , Yang Sheng-Yong , Malik Karim , Bao Xiaomin , George Zheng Y. , Liu Chang-Mei , Schor Nina F. , Li Zhi-Jie , Li Xing-Guo 
Published: May 2020

AbstractAberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of cancers, making PRMTs potential therapeutic targets. But it remains not well understood how PRMTs impact specific oncogenic pathways. We previously identified PRMTs as important regulators of cell growth in neuroblastoma, a deadly childhood tumor of the sympathetic nervous system. Here, we demonstrate a critical role for PRMT1 in neuroblastoma cell survival. PRMT1 depletion decreased the ability of murine neuroblastoma sphere cells to grow and form spheres, and suppressed proliferation and induced apoptosis of human neuroblastoma cells. Mechanistic studies reveal the prosurvival factor, activating transcription factor 5 (ATF5) as a downstream effector of PRMT1-mediated survival signaling. Furthermore, a diamidine class of PRMT1 inhibitors exhibited anti-neuroblastoma efficacy both in vitro and in vivo. Importantly, overexpression of ATF5 rescued cell apoptosis triggered by PRMT1 inhibition genetically or pharmacologically. Taken together, our findings shed new insights into PRMT1 signaling pathway, and provide evidence for PRMT1 as an actionable therapeutic target in neuroblastoma.
SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis
Authors: Du Xing , Li Qiqi , Yang Liu , Liu Lu , Cao Qiuyu , Li Qifa 
Published: May 2020

AbstractThe TGF-β and Wnt signaling pathways are interrelated in many cell types and tissues, and control cell functions in coordination. Here, we report that SMAD4, a downstream effector of the TGF-β signaling pathway, induces FZD4, a receptor of the Wnt signaling pathway, establishing a novel route of communication between these two pathways in granulosa cells (GCs). We found that SMAD4 is a strong inducer of FZD4, not only initiating FZD4 transcription but also activating FZD4-dependent Wnt signaling and GC apoptosis. Furthermore, we identified the direct and indirect mechanisms by which SMAD4 promotes expression of FZD4 in GCs. First, SMAD4 functions as a transcription factor to directly bind to the FZD4 promoter region to increase its transcriptional activity. Second, SMAD4 promotes production of SDNOR, a novel lncRNA that acts as a sponge for miR-29c, providing another mean to block miR-29c from degenerating FZD4 mRNA. Overall, our findings not only reveal a new channel of crosstalk between the TGF-β and Wnt signaling pathways, SMAD4–FZD4 axis, but also provide new insights into the regulatory network of GC apoptosis and follicular atresia. These RNA molecules, such as miR-29c and lnc-SDNOR, represent potential targets for treatment of reproductive diseases and improvement of female fertility.
Oxygen, life forms, and the evolution of sexes in multicellular eukaryotes
Authors: Hörandl Elvira , Hadacek Franz 
Published: May 2020

AbstractThe evolutionary advantage of different sexual systems in multicellular eukaryotes is still not well understood, because the differentiation into male and female individuals halves offspring production compared with asexuality. Here we propose that various physiological adaptations to oxidative stress could have forged sessility versus motility, and consequently the evolution of sexual systems in multicellular animals, plants, and fungi. Photosynthesis causes substantial amounts of oxidative stress in photoautotrophic plants and, likewise, oxidative chemistry of polymer breakdown, cellulose and lignin, for saprotrophic fungi. In both cases, its extent precludes motility, an additional source of oxidative stress. Sessile life form and the lack of neuronal systems, however, limit options for mate recognition and adult sexual selection, resulting in inefficient mate-searching systems. Hence, sessility requires that all individuals can produce offspring, which is achieved by hermaphroditism in plants and/or by multiple mating types in fungi. In animals, motility requires neuronal systems, and muscle activity, both of which are highly sensitive to oxidative damage. As a consequence, motility has evolved in animals as heterotrophic organisms that (1) are not photosynthetically active, and (2) are not primary decomposers. Adaptations to motility provide prerequisites for an active mating behavior and efficient mate-searching systems. These benefits compensate for the “cost of males”, and may explain the early evolution of sex chromosomes in metazoans. We conclude that different sexual systems evolved under the indirect physiological constraints of lifestyles.
Unexpected large eruptions from buoyant magma bodies within viscoelastic crust
Authors: Sigmundsson Freysteinn , Pinel Virginie , Grapenthin Ronni , Hooper Andrew , Halldórsson Sæmundur A. , Einarsson Páll , Ófeigsson Benedikt G. , Heimisson Elías R. , Jónsdóttir Kristín , Gudmundsson Magnús T. , Vogfjörd Kristín , Parks Michelle , Li Siqi , Drouin Vincent , Geirsson Halldór , Dumont Stéphanie , Fridriksdottir Hildur M. , Gudmundsson Gunnar B. , Wright Tim J. , Yamasaki Tadashi 
Published: May 2020

AbstractLarge volume effusive eruptions with relatively minor observed precursory signals are at odds with widely used models to interpret volcano deformation. Here we propose a new modelling framework that resolves this discrepancy by accounting for magma buoyancy, viscoelastic crustal properties, and sustained magma channels. At low magma accumulation rates, the stability of deep magma bodies is governed by the magma-host rock density contrast and the magma body thickness. During eruptions, inelastic processes including magma mush erosion and thermal effects, can form a sustained channel that supports magma flow, driven by the pressure difference between the magma body and surface vents. At failure onset, it may be difficult to forecast the final eruption volume; pressure in a magma body may drop well below the lithostatic load, create under-pressure and initiate a caldera collapse, despite only modest precursors.
DNA polymerase ε relies on a unique domain for efficient replisome assembly and strand synthesis
Authors: Meng Xiangzhou , Wei Lei , Devbhandari Sujan , Zhang Tuo , Xiang Jenny , Remus Dirk , Zhao Xiaolan 
Published: May 2020

AbstractDNA polymerase epsilon (Pol ε) is required for genome duplication and tumor suppression. It supports both replisome assembly and leading strand synthesis; however, the underlying mechanisms remain to be elucidated. Here we report that a conserved domain within the Pol ε catalytic core influences both of these replication steps in budding yeast. Modeling cancer-associated mutations in this domain reveals its unexpected effect on incorporating Pol ε into the four-member pre-loading complex during replisome assembly. In addition, genetic and biochemical data suggest that the examined domain supports Pol ε catalytic activity and symmetric movement of replication forks. Contrary to previously characterized Pol ε cancer variants, the examined mutants cause genome hyper-rearrangement rather than hyper-mutation. Our work thus suggests a role of the Pol ε catalytic core in replisome formation, a reliance of Pol ε strand synthesis on a unique domain, and a potential tumor-suppressive effect of Pol ε in curbing genome re-arrangements.
Non-perturbative terahertz high-harmonic generation in the three-dimensional Dirac semimetal Cd3As2
Authors: Kovalev Sergey , Dantas Renato M. A. , Germanskiy Semyon , Deinert Jan-Christoph , Green Bertram , Ilyakov Igor , Awari Nilesh , Chen Min , Bawatna Mohammed , Ling Jiwei , Xiu Faxian , van Loosdrecht Paul H. M. , Surówka Piotr , Oka Takashi , Wang Zhe 
Published: May 2020

AbstractHarmonic generation is a general characteristic of driven nonlinear systems, and serves as an efficient tool for investigating the fundamental principles that govern the ultrafast nonlinear dynamics. Here, we report on terahertz-field driven high-harmonic generation in the three-dimensional Dirac semimetal Cd3As2 at room temperature. Excited by linearly-polarized multi-cycle terahertz pulses, the third-, fifth-, and seventh-order harmonic generation is very efficient and detected via time-resolved spectroscopic techniques. The observed harmonic radiation is further studied as a function of pump-pulse fluence. Their fluence dependence is found to deviate evidently from the expected power-law dependence in the perturbative regime. The observed highly non-perturbative behavior is reproduced based on our analysis of the intraband kinetics of the terahertz-field driven nonequilibrium state using the Boltzmann transport theory. Our results indicate that the driven nonlinear kinetics of the Dirac electrons plays the central role for the observed highly nonlinear response.
Modular nonlinear hybrid plasmonic circuit
Authors: Tuniz Alessandro , Bickerton Oliver , Diaz Fernando J. , Käsebier Thomas , Kley Ernst-Bernhard , Kroker Stefanie , Palomba Stefano , de Sterke C. Martijn 
Published: May 2020

AbstractPhotonic integrated circuits (PICs) are revolutionizing nanotechnology, with far-reaching applications in telecommunications, molecular sensing, and quantum information. PIC designs rely on mature nanofabrication processes and readily available and optimised photonic components (gratings, splitters, couplers). Hybrid plasmonic elements can enhance PIC functionality (e.g., wavelength-scale polarization rotation, nanoscale optical volumes, and enhanced nonlinearities), but most PIC-compatible designs use single plasmonic elements, with more complex circuits typically requiring ab initio designs. Here we demonstrate a modular approach to post-processes off-the-shelf silicon-on-insulator (SOI) waveguides into hybrid plasmonic integrated circuits. These consist of a plasmonic rotator and a nanofocusser, which generate the second harmonic frequency of the incoming light. We characterize each component’s performance on the SOI waveguide, experimentally demonstrating intensity enhancements of more than 200 in an inferred mode area of 100 nm2, at a pump wavelength of 1320 nm. This modular approach to plasmonic circuitry makes the applications of this technology more practical.
Investigating the dynamics of microbial consortia in spatially structured environments
Authors: Gupta Sonali , Ross Tyler D. , Gomez Marcella M. , Grant Job L. , Romero Philip A. , Venturelli Ophelia S. 
Published: May 2020

ABSTRACTThe spatial organization of microbial communities arises from a complex interplay of biotic and abiotic interactions, and is a major determinant of ecosystem functions. Here we design a microfluidic platform to investigate how the spatial arrangement of microbes impacts gene expression and growth. We elucidate key biochemical parameters that dictate the mapping between spatial positioning and gene expression patterns. We show that distance can establish a low-pass filter to periodic inputs and can enhance the fidelity of information processing. Positive and negative feedback can play disparate roles in the synchronization and robustness of a genetic oscillator distributed between two strains to spatial separation. Quantification of growth and metabolite release in an amino-acid auxotroph community demonstrates that the interaction network and stability of the community are highly sensitive to temporal perturbations and spatial arrangements. In sum, our microfluidic platform can quantify spatiotemporal parameters influencing diffusion-mediated interactions in microbial consortia.
Representation of probabilistic outcomes during risky decision-making
Authors: Castegnetti Giuseppe , Tzovara Athina , Khemka Saurabh , Melinščak Filip , Barnes Gareth R. , Dolan Raymond J. , Bach Dominik R. 
Published: May 2020

AbstractGoal-directed behaviour requires prospectively retrieving and evaluating multiple possible action outcomes. While a plethora of studies suggested sequential retrieval for deterministic choice outcomes, it remains unclear whether this is also the case when integrating multiple probabilistic outcomes of the same action. We address this question by capitalising on magnetoencephalography (MEG) in humans who made choices in a risky foraging task. We train classifiers to distinguish MEG field patterns during presentation of two probabilistic outcomes (reward, loss), and then apply these to decode such patterns during deliberation. First, decoded outcome representations have a temporal structure, suggesting alternating retrieval of the outcomes. Moreover, the probability that one or the other outcome is being represented depends on loss magnitude, but not on loss probability, and it predicts the chosen action. In summary, we demonstrate decodable outcome representations during probabilistic decision-making, which are sequentially structured, depend on task features, and predict subsequent action.
Immune-profiling of ZIKV-infected patients identifies a distinct function of plasmacytoid dendritic cells for immune cross-regulation
Authors: Sun Xiaoming , Hua Stephane , Gao Ce , Blackmer Jane E. , Ouyang Zhengyu , Ard Kevin , Ciaranello Andrea , Yawetz Sigal , Sax Paul E. , Rosenberg Eric S. , Lichterfeld Mathias , Yu Xu G. 
Published: May 2020

AbstractZika virus (ZIKV) is a mosquito-borne pathogen with increasing public health significance. To characterize immune responses to ZIKV, here we examine transcriptional signatures of CD4 T, CD8 T, B, and NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with ZIKV infection. While gene expression patterns from most cell subsets display signs of impaired antiviral immune activity, pDCs from infected host have distinct transcriptional response associated with activation of innate immune recognition and type I interferon signaling pathways, but downregulation of key host factors known to support ZIKV replication steps; meanwhile, pDCs exhibit a unique expression pattern of gene modules that are correlated with alternative cell populations, suggesting collaborative interactions between pDCs and other immune cells, particularly B cells. Together, these results point towards a discrete but integrative function of pDCs in the human immune responses to ZIKV infection.
HIV-associated gut dysbiosis is independent of sexual practice and correlates with noncommunicable diseases
Authors: Vujkovic-Cvijin I. , Sortino O. , Verheij E. , Sklar J. , Wit F. W. , Kootstra N. A. , Sellers B. , Brenchley J. M. , Ananworanich J. , Loeff M. Schim van der , Belkaid Y. , Reiss P. , Sereti I. 
Published: May 2020

AbstractLoss of gut mucosal integrity and an aberrant gut microbiota are proposed mechanisms contributing to chronic inflammation and increased morbidity and mortality during antiretroviral-treated HIV disease. Sexual practice has recently been uncovered as a major source of microbiota variation, potentially confounding prior observations of gut microbiota alterations among persons with HIV (PWH). To overcome this and other confounding factors, we examine a well-powered subset of AGEhIV Cohort participants comprising antiretroviral-treated PWH and seronegative controls matched for age, body-mass index, sex, and sexual practice. We report significant gut microbiota differences in PWH regardless of sex and sexual practice including Gammaproteobacteria enrichment, Lachnospiraceae and Ruminococcaceae depletion, and decreased alpha diversity. Men who have sex with men (MSM) exhibit a distinct microbiota signature characterized by Prevotella enrichment and increased alpha diversity, which is linked with receptive anal intercourse in both males and females. Finally, the HIV-associated microbiota signature correlates with inflammatory markers including suPAR, nadir CD4 count, and prevalence of age-associated noncommunicable comorbidities.
Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease
Authors: Tiklová Katarína , Nolbrant Sara , Fiorenzano Alessandro , Björklund Åsa K. , Sharma Yogita , Heuer Andreas , Gillberg Linda , Hoban Deirdre B. , Cardoso Tiago , Adler Andrew F. , Birtele Marcella , Lundén-Miguel Hilda , Volakakis Nikolaos , Kirkeby Agnete , Perlmann Thomas , Parmar Malin 
Published: May 2020

AbstractCell replacement is a long-standing and realistic goal for the treatment of Parkinsonʼs disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.
Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver
Authors: Miao Lei , Lin Jiaqi , Huang Yuxuan , Li Linxian , Delcassian Derfogail , Ge Yifan , Shi Yunhua , Anderson Daniel G. 
Published: May 2020

AbstractLipid-like nanoparticles (LNPs) have potential as non-viral delivery systems for mRNA therapies. However, repeated administrations of LNPs may lead to accumulation of delivery materials and associated toxicity. To address this challenge, we have developed biodegradable lipids which improve LNPs clearance and reduce toxicity. We modify the backbone structure of Dlin-MC3-DMA by introducing alkyne and ester groups into the lipid tails. We evaluate the performance of these lipids when co-formulated with other amine containing lipid-like materials. We demonstrate that these formulations synergistically facilitate robust mRNA delivery with improved tolerability after single and repeated administrations. We further identify albumin-associated macropinocytosis and endocytosis as an ApoE-independent LNP cellular uptake pathway in the liver. Separately, the inclusion of alkyne lipids significantly increases membrane fusion to enhance mRNA release, leading to synergistic improvement of mRNA delivery. We believe that the rational design of LNPs with multiple amine-lipids increases the material space for mRNA delivery.
A redox-based electrogenetic CRISPR system to connect with and control biological information networks
Authors: Bhokisham Narendranath , VanArsdale Eric , Stephens Kristina T. , Hauk Pricila , Payne Gregory F. , Bentley William E. 
Published: May 2020

AbstractElectronic information can be transmitted to cells directly from microelectronics via electrode-activated redox mediators. These transmissions are decoded by redox-responsive promoters which enable user-specified control over biological function. Here, we build on this redox communication modality by establishing an electronic eCRISPR conduit of information exchange. This system acts as a biological signal processor, amplifying signal reception and filtering biological noise. We electronically amplify bacterial quorum sensing (QS) signaling by activating LasI, the autoinducer-1 synthase. Similarly, we filter out unintended noise by inhibiting the native SoxRS-mediated oxidative stress response regulon. We then construct an eCRISPR based redox conduit in both E. coli and Salmonella enterica. Finally, we display eCRISPR based information processing that allows transmission of spatiotemporal redox commands which are then decoded by gelatin-encapsulated E. coli. We anticipate that redox communication channels will enable biohybrid microelectronic devices that could transform our abilities to electronically interpret and control biological function.
Conserved protein Pir2ARS2 mediates gene repression through cryptic introns in lncRNAs
Authors: Thillainadesan Gobi , Xiao Hua , Holla Sahana , Dhakshnamoorthy Jothy , Jenkins Lisa M. Miller , Wheeler David , Grewal Shiv I. S. 
Published: May 2020

AbstractLong non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here, we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2ARS2 protein in association with splicing factors, which recruit RNA processing and chromatin-modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs.
Split Intein-Mediated Protein Ligation for detecting protein-protein interactions and their inhibition
Authors: Yao Zhong , Aboualizadeh Farzaneh , Kroll Jason , Akula Indira , Snider Jamie , Lyakisheva Anna , Tang Priscilla , Kotlyar Max , Jurisica Igor , Boxem Mike , Stagljar Igor 
Published: May 2020

AbstractHere, to overcome many limitations accompanying current available methods to detect protein-protein interactions (PPIs), we develop a live cell method called Split Intein-Mediated Protein Ligation (SIMPL). In this approach, bait and prey proteins are respectively fused to an intein N-terminal fragment (IN) and C-terminal fragment (IC) derived from a re-engineered split intein GP41-1. The bait/prey binding reconstitutes the intein, which splices the bait and prey peptides into a single intact protein that can be detected by regular protein detection methods such as Western blot analysis and ELISA, serving as readouts of PPIs. The method is robust and can be applied not only in mammalian cell lines but in animal models such as C. elegans. SIMPL demonstrates high sensitivity and specificity, and enables exploration of PPIs in different cellular compartments and tracking of kinetic interactions. Additionally, we establish a SIMPL ELISA platform that enables high-throughput screening of PPIs and their inhibitors.