bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active coacervate droplets as a model for membraneless organelles and protocells
Authors: Donau Carsten , Späth Fabian , Sosson Marilyne , Kriebisch Brigitte A. K. , Schnitter Fabian , Tena-Solsona Marta , Kang Hyun-Seo , Salibi Elia , Sattler Michael , Mutschler Hannes , Boekhoven Job 
Published: October 2020

AbstractMembraneless organelles like stress granules are active liquid-liquid phase-separated droplets that are involved in many intracellular processes. Their active and dynamic behavior is often regulated by ATP-dependent reactions. However, how exactly membraneless organelles control their dynamic composition remains poorly understood. Herein, we present a model for membraneless organelles based on RNA-containing active coacervate droplets regulated by a fuel-driven reaction cycle. These droplets emerge when fuel is present, but decay without. Moreover, we find these droplets can transiently up-concentrate functional RNA which remains in its active folded state inside the droplets. Finally, we show that in their pathway towards decay, these droplets break apart in multiple droplet fragments. Emergence, decay, rapid exchange of building blocks, and functionality are all hallmarks of membrane-less organelles, and we believe that our work could be powerful as a model to study such organelles.
Controlling the symmetry of inorganic ionic nanofilms with optical chirality
Authors: Kelly Christopher , MacLaren Donald A. , McKay Katie , McFarlane Anthony , Karimullah Affar S. , Gadegaard Nikolaj , Barron Laurence D. , Franke-Arnold Sonja , Crimin Frances , Götte Jörg B. , Barnett Stephen M. , Kadodwala Malcolm 
Published: October 2020

AbstractManipulating symmetry environments of metal ions to control functional properties is a fundamental concept of chemistry. For example, lattice strain enables control of symmetry in solids through a change in the nuclear positions surrounding a metal centre. Light–matter interactions can also induce strain but providing dynamic symmetry control is restricted to specific materials under intense laser illumination. Here, we show how effective chemical symmetry can be tuned by creating a symmetry-breaking rotational bulk polarisation in the electronic charge distribution surrounding a metal centre, which we term a meta-crystal field. The effect arises from an interface-mediated transfer of optical spin from a chiral light beam to produce an electronic torque that replicates the effect of strain created by high pressures. Since the phenomenon does not rely on a physical rearrangement of nuclear positions, material constraints are lifted, thus providing a generic and fully reversible method of manipulating effective symmetry in solids.
Near-real-time monitoring of global CO2 emissions reveals the effects of the COVID-19 pandemic
Authors: Liu Zhu , Ciais Philippe , Deng Zhu , Lei Ruixue , Davis Steven J. , Feng Sha , Zheng Bo , Cui Duo , Dou Xinyu , Zhu Biqing , Guo Rui , Ke Piyu , Sun Taochun , Lu Chenxi , He Pan , Wang Yuan , Yue Xu , Wang Yilong , Lei Yadong , Zhou Hao , Cai Zhaonan , Wu Yuhui , Guo Runtao , Han Tingxuan , Xue Jinjun , Boucher Olivier , Boucher Eulalie , Chevallier Frédéric , Tanaka Katsumasa , Wei Yiming , Zhong Haiwang , Kang Chongqing , Zhang Ning , Chen Bin , Xi Fengming , Liu Miaomiao , Bréon François-Marie , Lu Yonglong , Zhang Qiang , Guan Dabo , Gong Peng , Kammen Daniel M. , He Kebin , Schellnhuber Hans Joachim 
Published: October 2020

AbstractThe COVID-19 pandemic is impacting human activities, and in turn energy use and carbon dioxide (CO2) emissions. Here we present daily estimates of country-level CO2 emissions for different sectors based on near-real-time activity data. The key result is an abrupt 8.8% decrease in global CO2 emissions (−1551 Mt CO2) in the first half of 2020 compared to the same period in 2019. The magnitude of this decrease is larger than during previous economic downturns or World War II. The timing of emissions decreases corresponds to lockdown measures in each country. By July 1st, the pandemic’s effects on global emissions diminished as lockdown restrictions relaxed and some economic activities restarted, especially in China and several European countries, but substantial differences persist between countries, with continuing emission declines in the U.S. where coronavirus cases are still increasing substantially.
CRISPR screening of porcine sgRNA library identifies host factors associated with Japanese encephalitis virus replication
Authors: Zhao Changzhi , Liu Hailong , Xiao Tianhe , Wang Zichang , Nie Xiongwei , Li Xinyun , Qian Ping , Qin Liuxing , Han Xiaosong , Zhang Jinfu , Ruan Jinxue , Zhu Mengjin , Miao Yi-Liang , Zuo Bo , Yang Kui , Xie Shengsong , Zhao Shuhong 
Published: October 2020

AbstractJapanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, the host factors critical for its entry, replication, and assembly are poorly understood. Here, we design a porcine genome-scale CRISPR/Cas9 knockout (PigGeCKO) library containing 85,674 single guide RNAs targeting 17,743 protein-coding genes, 11,053 long ncRNAs, and 551 microRNAs. Subsequently, we use the PigGeCKO library to identify key host factors facilitating JEV infection in porcine cells. Several previously unreported genes required for JEV infection are highly enriched post-JEV selection. We conduct follow-up studies to verify the dependency of JEV on these genes, and identify functional contributions for six of the many candidate JEV-related host genes, includingEMC3andCALR. Additionally, we identify that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPGs sulfurylation, facilitate JEV entry into porcine cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this study identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to treat and prevent diseases caused by JEV.
Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients
Authors: Block Matthew S. , Dietz Allan B. , Gustafson Michael P. , Kalli Kimberly R. , Erskine Courtney L. , Youssef Bahaaeldin , Vijay Geraldine V. , Allred Jacob B. , Pavelko Kevin D. , Strausbauch Michael A. , Lin Yi , Grudem Megan E. , Jatoi Aminah , Klampe Carolyn M. , Wahner-Hendrickson Andrea E. , Weroha S. John , Glaser Gretchen E. , Kumar Amanika , Langstraat Carrie L. , Solseth Mary L. , Deeds Michael C. , Knutson Keith L. , Cannon Martin J. 
Published: October 2020

AbstractIn ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.
Pan-cancer analysis reveals TAp63-regulated oncogenic lncRNAs that promote cancer progression through AKT activation
Authors: Napoli Marco , Li Xiaobo , Ackerman Hayley D. , Deshpande Avani A. , Barannikov Ivan , Pisegna Marlese A. , Bedrosian Isabelle , Mitsch Jürgen , Quinlan Philip , Thompson Alastair , Rajapakshe Kimal , Coarfa Cristian , Gunaratne Preethi H. , Marchion Douglas C. , Magliocco Anthony M. , Tsai Kenneth Y. , Flores Elsa R. 
Published: October 2020

AbstractThe most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of the PI3K/AKT pathway, two events crucial for cancer progression. Mutations in TP53 lead to the inhibition of the tumour and metastasis suppressor TAp63, a p53 family member. By performing a mouse-human cross species analysis between the TAp63 metastatic mammary adenocarcinoma mouse model and models of human breast cancer progression, we identified two TAp63-regulated oncogenic lncRNAs, TROLL-2 and TROLL-3. Further, using a pan-cancer analysis of human cancers and multiple mouse models of tumour progression, we revealed that these two lncRNAs induce the activation of AKT to promote cancer progression by regulating the nuclear to cytoplasmic translocation of their effector, WDR26, via the shuttling protein NOLC1. Our data provide preclinical rationale for the implementation of these lncRNAs and WDR26 as therapeutic targets for the treatment of human tumours dependent upon mutant TP53 and/or the PI3K/AKT pathway.
Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning
Authors: McCullough Kenneth M. , Chatzinakos Chris , Hartmann Jakob , Missig Galen , Neve Rachael L. , Fenster Robert J. , Carlezon William A. , Daskalakis Nikolaos P. , Ressler Kerry J. 
Published: October 2020

AbstractFear and extinction learning are adaptive processes caused by molecular changes in specific neural circuits. Neurons expressing the corticotropin-releasing hormone gene (Crh) in central amygdala (CeA) are implicated in threat regulation, yet little is known of cell type-specific gene pathways mediating adaptive learning. We translationally profiled the transcriptome of CeA Crh-expressing cells (Crh neurons) after fear conditioning or extinction in mice using translating ribosome affinity purification (TRAP) and RNAseq. Differential gene expression and co-expression network analyses identified diverse networks activated or inhibited by fear vs extinction. Upstream regulator analysis demonstrated that extinction associates with reduced CREB expression, and viral vector-induced increased CREB expression in Crh neurons increased fear expression and inhibited extinction. These findings suggest that CREB, within CeA Crh neurons, may function as a molecular switch that regulates expression of fear and its extinction. Cell-type specific translational analyses may suggest targets useful for understanding and treating stress-related psychiatric illness.
Observation of a high degree of stopping for laser-accelerated intense proton beams in dense ionized matter
Authors: Ren Jieru , Deng Zhigang , Qi Wei , Chen Benzheng , Ma Bubo , Wang Xing , Yin Shuai , Feng Jianhua , Liu Wei , Xu Zhongfeng , Hoffmann Dieter H. H. , Wang Shaoyi , Fan Quanping , Cui Bo , He Shukai , Cao Zhurong , Zhao Zongqing , Cao Leifeng , Gu Yuqiu , Zhu Shaoping , Cheng Rui , Zhou Xianming , Xiao Guoqing , Zhao Hongwei , Zhang Yihang , Zhang Zhe , Li Yutong , Wu Dong , Zhou Weimin , Zhao Yongtao 
Published: October 2020

AbstractIntense particle beams generated from the interaction of ultrahigh intensity lasers with sample foils provide options in radiography, high-yield neutron sources, high-energy-density-matter generation, and ion fast ignition. An accurate understanding of beam transportation behavior in dense matter is crucial for all these applications. Here we report the experimental evidence on one order of magnitude enhancement of intense laser-accelerated proton beam stopping in dense ionized matter, in comparison with the current-widely used models describing individual ion stopping in matter. Supported by particle-in-cell (PIC) simulations, we attribute the enhancement to the strong decelerating electric field approaching 1 GV/m that can be created by the beam-driven return current. This collective effect plays the dominant role in the stopping of laser-accelerated intense proton beams in dense ionized matter. This finding is essential for the optimum design of ion driven fast ignition and inertial confinement fusion.
Vegetation forcing modulates global land monsoon and water resources in a CO2-enriched climate
Authors: Cui Jiangpeng , Piao Shilong , Huntingford Chris , Wang Xuhui , Lian Xu , Chevuturi Amulya , Turner Andrew G. , Kooperman Gabriel J. 
Published: October 2020

AbstractThe global monsoon is characterised by transitions between pronounced dry and wet seasons, affecting food security for two-thirds of the world’s population. Rising atmospheric CO2 influences the terrestrial hydrological cycle through climate-radiative and vegetation-physiological forcings. How these two forcings affect the seasonal intensity and characteristics of monsoonal precipitation and runoff is poorly understood. Here we use four Earth System Models to show that in a CO2-enriched climate, radiative forcing changes drive annual precipitation increases for most monsoon regions. Further, vegetation feedbacks substantially affect annual precipitation in North and South America and Australia monsoon regions. In the dry season, runoff increases over most monsoon regions, due to stomatal closure-driven evapotranspiration reductions and associated atmospheric circulation change. Our results imply that flood risks may amplify in the wet season. However, the lengthening of the monsoon rainfall season and reduced evapotranspiration will shorten the water resources scarcity period for most monsoon regions.
Physical limits to sensing material properties
Authors: Beroz Farzan , Zhou Di , Mao Xiaoming , Lubensky David K. 
Published: October 2020

AbstractAll materials respond heterogeneously at small scales, which limits what a sensor can learn. Although previous studies have characterized measurement noise arising from thermal fluctuations, the limits imposed by structural heterogeneity have remained unclear. In this paper, we find that the least fractional uncertainty with which a sensor can determine a material constant λ0 of an elastic medium is approximately $$\delta {\lambda }_{0}/{\lambda }_{0} \sim ({\Delta }_{\lambda }^{1/2}/{\lambda }_{0}){(d/a)}^{D/2}{(\xi /a)}^{D/2}$$
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, and D > 1, where a is the size of the sensor, d is its spatial resolution, ξ is the correlation length of fluctuations in λ0, Δλ is the local variability of λ0, and D is the dimension of the medium. Our results reveal how one can construct devices capable of sensing near these limits, e.g. for medical diagnostics. We use our theoretical framework to estimate the limits of mechanosensing in a biopolymer network, a sensory process involved in cellular behavior, medical diagnostics, and material fabrication.
Conformational equilibrium shift underlies altered K+ channel gating as revealed by NMR
Authors: Iwahashi Yuta , Toyama Yuki , Imai Shunsuke , Itoh Hiroaki , Osawa Masanori , Inoue Masayuki , Shimada Ichio 
Published: October 2020

AbstractThe potassium ion (K+) channel plays a fundamental role in controlling K+ permeation across the cell membrane and regulating cellular excitabilities. Mutations in the transmembrane pore reportedly affect the gating transitions of K+ channels, and are associated with the onset of neural disorders. However, due to the lack of structural and dynamic insights into the functions of K+ channels, the structural mechanism by which these mutations cause K+ channel dysfunctions remains elusive. Here, we used nuclear magnetic resonance spectroscopy to investigate the structural mechanism underlying the decreased K+-permeation caused by disease-related mutations, using the prokaryotic K+ channel KcsA. We demonstrated that the conformational equilibrium in the transmembrane region is shifted toward the non-conductive state with the closed intracellular K+-gate in the disease-related mutant. We also demonstrated that this equilibrium shift is attributable to the additional steric contacts in the open-conductive structure, which are evoked by the increased side-chain bulkiness of the residues lining the transmembrane helix. Our results suggest that the alteration in the conformational equilibrium of the intracellular K+-gate is one of the fundamental mechanisms underlying the dysfunctions of K+ channels caused by disease-related mutations.
Biomarkers for the toxicity of sublethal concentrations of triclosan to the early life stages of carps
Authors: Dar Owias Iqbal , Sharma Sunil , Singh Kirpal , Sharma Anket , Bhardwaj Renu , Kaur Arvinder 
Published: October 2020

AbstractAccumulation, contents of protein, non-enzymatic antioxidant glutathione (GSH and GSSG), lipid peroxidation product (melondialdehyde-MDA) and organic acids (fumarate, succinate, malate and citrate), and activities of neurological (acetylcholinesterase-AChE), detoxification (glutathione S-transferase-GST) and metabolic (lactate dehydrogenase-LDH, aspartate transaminase-AST and alanine transaminase-ALT) enzymes were recorded in the hatchlings of Cyprinus carpio, Ctenopharyngodon idella, Labeo rohita and Cirrhinus mrigala after 7 and 14 days exposure and 10 days post exposure (recovery period) to sublethal concentrations (0.005, 0.01, 0.02 and 0.05 mg/L) of triclosan, a highly toxic and persistent biocide used in personal care products. Accumulation was maximum between 7–14 days at 0.01 mg/L for C. carpio and L. rohita but at 0.005 mg/L for C. idella and C. mrigala. No triclosan was observed at 0.005 mg/L in C. carpio and C. mrigala after recovery. Significant decline in protein, glutathione and acetylcholinesterase but increase in glutathione S-transferase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, melondialdehyde and organic acids over control during exposure continued till the end of recovery period. Integrated biomarker response (IBR) analysis depicted higher star plot area for glutathione and glutathione S-transferase during initial 7 days of exposure, thereafter, during 7–14 days of exposure and the recovery period, higher star plot area was observed for acetylcholinesterase, aspartate transaminase, alanine transaminase and organic acids. Higher star plot area was observed for protein in all the species throughout the study. The study shows that L. rohita is most sensitive and glutathione, acetylcholinesterase, aspartate transaminase and alanine transaminase are the biomarkers for the toxicity of sublethal concentrations of TCS.
Transforming self-reported outcomes from a stroke register to the modified Rankin Scale: a cross-sectional, explorative study
Authors: Abzhandadze Tamar , Reinholdsson Malin , Palstam Annie , Eriksson Marie , Sunnerhagen Katharina S. 
Published: October 2020

AbstractThe aim was to create an algorithm to transform self-reported outcomes from a stroke register to the modified Rankin Scale (mRS). Two stroke registers were used: the Väststroke, a local register in Gothenburg, Sweden, and the Riksstroke, a Swedish national register. The reference variable, mRS (from Väststroke), was mapped with seven self-reported questions from Riksstroke. The transformation algorithm was created as a result of manual mapping performed by healthcare professionals. A supervised machine learning method—decision tree—was used to further evaluate the transformation algorithm. Of 1145 patients, 54% were male, the mean age was 71 y. The mRS grades 0, 1 and 2 could not be distinguished as a result of manual mapping or by using the decision tree analysis. Thus, these grades were merged. With manual mapping, 78% of the patients were correctly classified, and the level of agreement was almost perfect, weighted Kappa (Kw) was 0.81. With the decision tree, 80% of the patients were correctly classified, and substantial agreement was achieved, Kw = 0.67. The self-reported outcomes from a stroke register can be transformed to the mRS. A mRS algorithm based on manual mapping might be useful for researchers using self-reported questionnaire data.
Unravelling the health status of brachycephalic dogs in the UK using multivariable analysis
Authors: O’Neill D. G. , Pegram C. , Crocker P. , Brodbelt D. C. , Church D. B. , Packer R. M. A. 
Published: October 2020

AbstractBrachycephalic dog breeds are regularly asserted as being less healthy than non-brachycephalic breeds. Using primary-care veterinary clinical data, this study aimed to identify predispositions and protections in brachycephalic dogs and explore differing inferences between univariable and multivariable results. All disorders during 2016 were extracted from a random sample of 22,333 dogs within the VetCompass Programme from a sampling frame of 955,554 dogs under UK veterinary care in 2016. Univariable and multivariable binary logistic regression modelling explored brachycephaly as a risk factor for each of a series of common disorders. Brachycephalic dogs were younger, lighter and less likely to be neutered than mesocephalic, dolichocephalic and crossbred dogs. Brachycephalic differed to non-brachycephalic types in their odds for 10/30 (33.33%) common disorders. Of these, brachycephalic types were predisposed for eight disorders and were protected for two disorders. Univariable and multivariable analyses generated differing inference for 11/30 (30.67%) disorders. This study provides strong evidence that brachycephalic breeds are generally less healthy than their non-brachycephalic counterparts. Results from studies that report only univariable methods should be treated with extreme caution due to potential confounding effects that have not been accounted for during univariable study design or analysis.
Genome wide in-silico miRNA and target network prediction from stress responsive Horsegram (Macrotyloma uniflorum) accessions
Authors: Yasin Jeshima Khan , Mishra Bharat Kumar , Pillai M. Arumugam , Verma Nidhi , Wani Shabir H. , Elansary Hosam O. , El-Ansary Diaa O. , Pandey P. S. , Chinnusamy Viswanathan 
Published: October 2020

AbstractHorsegram (Macrotyloma uniflorum (Lam.) Verdc.) is a drought hardy food and fodder legume of Indo-African continents with diverse germplasm sources demonstrating alternating mechanisms depicting contrasting adaptations to different climatic zones. Tissue specific expression of genes contributes substantially to location specific adaptations. Regulatory networks of such adaptive genes are elucidated for downstream translational research. MicroRNAs are small endogenous regulatory RNAs which alters the gene expression profiles at a particular time and type of tissue. Identification of such small regulatory RNAs in low moisture stress hardy crops can help in cross species transfer and validation confirming stress tolerance ability. This study outlined prediction of conserved miRNAs from transcriptome shotgun assembled sequences and EST sequences of horsegram. We could validate eight out of 15 of the identified miRNAs to demonstrate their role in deficit moisture stress tolerance mechanism of horsegram variety Paiyur1 with their target networks. The putative mumiRs were related to other food legumes indicating the presence of gene regulatory networks. Differential miRNA expression among drought specific tissues indicted the probable energy conservation mechanism. Targets were identified for functional characterization and regulatory network was constructed to find out the probable pathways of post-transcriptional regulation. The functional network revealed mechanism of biotic and abiotic stress tolerance, energy conservation and photoperiod responsiveness.