bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma
Authors: Giuliani Virginia , Miller Meredith A. , Liu Chiu-Yi , Hartono Stella R. , Class Caleb A. , Bristow Christopher A. , Suzuki Erika , Sanz Lionel A. , Gao Guang , Gay Jason P. , Feng Ningping , Rose Johnathon L. , Tomihara Hideo , Daniele Joseph R. , Peoples Michael D. , Bardenhagen Jennifer P. , Geck Do Mary K. , Chang Qing E. , Vangamudi Bhavatarini , Vellano Christopher , Ying Haoqiang , Deem Angela K. , Do Kim-Anh , Genovese Giannicola , Marszalek Joseph R. , Kovacs Jeffrey J. , Kim Michael , Fleming Jason B. , Guccione Ernesto , Viale Andrea , Maitra Anirban , Emilia Di Francesco M. , Yap Timothy A. , Jones Philip , Draetta Giulio , Carugo Alessandro , Chedin Frederic , Heffernan Timothy P. 
Published: July 2021

AbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.
Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis
Authors: Menon Siddharth , Salhotra Ankit , Shailendra Siny , Tevlin Ruth , Ransom Ryan C. , Januszyk Michael , Chan Charles K. F. , Behr Björn , Wan Derrick C. , Longaker Michael T. , Quarto Natalina 
Published: July 2021

AbstractCranial sutures are major growth centers for the calvarial vault, and their premature fusion leads to a pathologic condition called craniosynostosis. This study investigates whether skeletal stem/progenitor cells are resident in the cranial sutures. Prospective isolation by FACS identifies this population with a significant difference in spatio-temporal representation between fusing versus patent sutures. Transcriptomic analysis highlights a distinct signature in cells derived from the physiological closing PF suture, and scRNA sequencing identifies transcriptional heterogeneity among sutures. Wnt-signaling activation increases skeletal stem/progenitor cells in sutures, whereas its inhibition decreases. CrossingAxin2LacZ/+mouse, endowing enhanced Wnt activation, to aTwist1+/−mouse model of coronal craniosynostosis enriches skeletal stem/progenitor cells in sutures restoring patency. Co-transplantation of these cells with Wnt3a prevents resynostosis following suturectomy inTwist1+/−mice. Our study reveals that decrease and/or imbalance of skeletal stem/progenitor cells representation within sutures may underlie craniosynostosis. These findings have translational implications toward therapeutic approaches for craniosynostosis.
Quasi-equilibrium phase coexistence in single component supercritical fluids
Authors: Lee Seungtaek , Lee Juho , Kim Yeonguk , Jeong Seokyong , Kim Dong Eon , Yun Gunsu 
Published: July 2021

AbstractIn their supercritical state simple fluids are generally thought to assume a homogeneous phase throughout all combinations of pressures and temperatures, although various response functions or transport properties may exhibit anomalous behavior, characterizing a state point as either more gas-like or liquid-like, respectively. While a large body of results has been compiled in the last two decades regarding the details of the supercritical phase in thermodynamic equilibrium, far less studies have been dedicated to out-of-equilibrium situations that nevertheless occur along with the handling of substances such as carbon dioxide or Argon. Here we consider successive compression-expansion cycles of equal amounts of Argon injected into a high-pressure chamber, traversing the critical pressure at two times the critical temperature. Due to expansion cooling, the fluid temporarily becomes sub-critical, and light scattering experiments show the formation of sub-micron-sized droplets and nanometer-scale clusters, both of which are distinct from spontaneous density fluctuations of the supercritical background and persist for a surprisingly long time. A kinetic rate model of the exchange of liquid droplets with the smaller clusters can explain this behavior. Our results indicate non-equilibrium aspects of supercritical fluids that may prove important for their processing in industrial applications.
Mobility patterns are associated with experienced income segregation in large US cities
Authors: Moro Esteban , Calacci Dan , Dong Xiaowen , Pentland Alex 
Published: July 2021

AbstractTraditional understanding of urban income segregation is largely based on static coarse-grained residential patterns. However, these do not capture the income segregation experience implied by the rich social interactions that happen in places that may relate to individual choices, opportunities, and mobility behavior. Using a large-scale high-resolution mobility data set of 4.5 million mobile phone users and 1.1 million places in 11 large American cities, we show that income segregation experienced in places and by individuals can differ greatly even within close spatial proximity. To further understand these fine-grained income segregation patterns, we introduce a Schelling extension of a well-known mobility model, and show that experienced income segregation is associated with an individual’s tendency to explore new places (place exploration) as well as places with visitors from different income groups (social exploration). Interestingly, while the latter is more strongly associated with demographic characteristics, the former is more strongly associated with mobility behavioral variables. Our results suggest that mobility behavior plays an important role in experienced income segregation of individuals. To measure this form of income segregation, urban researchers should take into account mobility behavior and not only residential patterns.
Badland landscape response to individual geomorphic events
Authors: Yang Ci-Jian , Turowski Jens M. , Hovius Niels , Lin Jiun-Chuan , Chang Kuo-Jen 
Published: July 2021

AbstractLandscapes form by the erosion and deposition of sediment, driven by tectonic and climatic forcing. The principal geomorphic processes of badland – landsliding, debris flow and runoff erosion – are similar to those in full scale mountain topography, but operate faster. Here, we show that in the badlands of SW Taiwan, individual rainfall events cause quantifiable landscape change, distinct for the type of rainfall. Typhoon rain reduced hillslope gradients, while lower-intensity precipitation either steepened or flattened the landscape, depending on its initial topography. The steep topography observed in our first survey is inconsistent with the effects of any of the rainfall events. We suggest that it is due to the 2016 Mw 6.4 Meinong earthquake. The observed pattern in the badlands was mirrored in the response of the Taiwan mountain topography to typhoon Morakot in 2009, confirming that badlands offer special opportunities to quantify natural landscape dynamics on observational time scales.
A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial
Authors: Folegatti Pedro M. , Harrison Kate , Preciado-Llanes Lorena , Lopez Fernando Ramos , Bittaye Mustapha , Kim Young Chan , Flaxman Amy , Bellamy Duncan , Makinson Rebecca , Sheridan Jonathan , Azar Sasha R. , Campos Rafael Kroon , Tilley Mark , Tran Nguyen , Jenkin Daniel , Poulton Ian , Lawrie Alison , Roberts Rachel , Berrie Eleanor , Rossi Shannan L. , Hill Adrian , Ewer Katie J. , Reyes-Sandoval Arturo 
Published: July 2021

AbstractChikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.
Exites in Cambrian arthropods and homology of arthropod limb branches
Authors: Liu Yu , Edgecombe Gregory D. , Schmidt Michel , Bond Andrew D. , Melzer Roland R. , Zhai Dayou , Mai Huijuan , Zhang Maoyin , Hou Xianguang 
Published: July 2021

AbstractThe last common ancestor of all living arthropods had biramous postantennal appendages, with an endopodite and exopodite branching off the limb base. Morphological evidence for homology of these rami between crustaceans and chelicerates has, however, been challenged by data from clonal composition and from knockout of leg patterning genes. Cambrian arthropod fossils have been cited as providing support for competing hypotheses about biramy but have shed little light on additional lateral outgrowths, known as exites. Here we draw on microtomographic imaging of the Cambrian great-appendage arthropodLeanchoiliato reveal a previously undetected exite at the base of most appendages, composed of overlapping lamellae. A morphologically similar, and we infer homologous, exite is documented in the same position in members of the trilobite-allied Artiopoda. This early Cambrian exite morphology supplements an emerging picture from gene expression that exites may have a deeper origin in arthropod phylogeny than has been appreciated.
Engineering polar vortex from topologically trivial domain architecture
Authors: Tan Congbing , Dong Yongqi , Sun Yuanwei , Liu Chang , Chen Pan , Zhong Xiangli , Zhu Ruixue , Liu Mingwei , Zhang Jingmin , Wang Jinbin , Liu Kaihui , Bai Xuedong , Yu Dapeng , Ouyang Xiaoping , Wang Jie , Gao Peng , Luo Zhenlin , Li Jiangyu 
Published: July 2021

AbstractTopologically nontrivial polar structures are not only attractive for high-density data storage, but also for ultralow power microelectronics thanks to their exotic negative capacitance. The vast majority of polar structures emerging naturally in ferroelectrics, however, are topologically trivial, and there are enormous interests in artificially engineered polar structures possessing nontrivial topology. Here we demonstrate reconstruction of topologically trivial strip-like domain architecture into arrays of polar vortex in (PbTiO3)10/(SrTiO3)10 superlattice, accomplished by fabricating a cross-sectional lamella from the superlattice film. Using a combination of techniques for polarization mapping, atomic imaging, and three-dimensional structure visualization supported by phase field simulations, we reveal that the reconstruction relieves biaxial epitaxial strain in thin film into a uniaxial one in lamella, changing the subtle electrostatic and elastostatic energetics and providing the driving force for the polar vortex formation. The work establishes a realistic strategy for engineering polar topologies in otherwise ordinary ferroelectric superlattices.
Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
Authors: Wang Weiwei , Gao Yan , Tang Yanting , Zhou Xiaoting , Lai Yuezheng , Zhou Shan , Zhang Yuying , Yang Xiuna , Liu Fengjiang , Guddat Luke W. , Wang Quan , Rao Zihe , Gong Hongri 
Published: July 2021

AbstractCytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase.
Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes
Authors: Thomson-Luque Richard , Votborg-Novél Lasse , Ndovie Wanangwa , Andrade Carolina M. , Niangaly Moussa , Attipa Charalampos , Lima Nathalia F. , Coulibaly Drissa , Doumtabe Didier , Guindo Bouréima , Tangara Bourama , Maiga Fayçal , Kone Abdoulaye Kassoum , Traore Karim , Kayentao Kassoum , Ongoiba Aissata , Doumbo Safiatou , Thera Mahamadou A. , Traoré Boubacar , Seydel Karl , Osório Nuno S. , Portugal Silvia 
Published: July 2021

AbstractFollowing Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.
Modelling a multiplex brain network by local transfer entropy
Authors: Parente Fabrizio , Colosimo Alfredo 
Published: July 2021

AbstractThis paper deals with the information transfer mechanisms underlying causal relations between brain regions under resting condition. fMRI images of a large set of healthy individuals from the 1000 Functional Connectomes Beijing Zang dataset have been considered and the causal information transfer among brain regions studied using Transfer Entropy concepts. Thus, we explored the influence of a set of states in two given regions at time t (At Bt.) over the state of one of them at a following time step (Bt+1) and could observe a series of time-dependent events corresponding to four kinds of interactions, or causal rules, pointing to (de)activation and turn off mechanisms and sharing some features with positive and negative functional connectivity. The functional architecture emerging from such rules was modelled by a directional multilayer network based upon four interaction matrices and a set of indexes describing the effects of the network structure in several dynamical processes. The statistical significance of the models produced by our approach was checked within the used database of homogeneous subjects and predicts a successful extension, in due course, to detect differences among clinical conditions and cognitive states.
Sublinear domination and core–periphery networks
Authors: Papachristou Marios 
Published: July 2021

AbstractIn this paper we devise a generative random network model with core–periphery properties whose core nodes act as sublinear dominators, that is, if the network has n nodes, the core has size o(n) and dominates the entire network. We show that instances generated by this model exhibit power law degree distributions, and incorporates small-world phenomena. We also fit our model in a variety of real-world networks.
Antagonist effects of grain boundaries between the trapping process and the fast diffusion path in nickel bicrystals
Authors: Li J. , Hallil A. , Metsue A. , Oudriss A. , Bouhattate J. , Feaugas X. 
Published: July 2021

AbstractHydrogen-grain-boundaries interactions and their role in intergranular fracture are well accepted as one of the key features in understanding hydrogen embrittlement in a large variety of common engineer situations. These interactions implicate some fundamental processes classified as segregation, trapping and diffusion of the solute which can be studied as a function of grain boundary configuration. In the present study, we carried out an extensive analysis of four grain-boundaries based on the complementary of atomistic calculations and experimental data. We demonstrate that elastic deformation has an important contribution on the segregation energy which cannot be simply reduced to a volume change and need to consider the deviatoric part of strain. Additionally, some significant configurations of the segregation energy depend on the long-range elastic distortion and allows to rationalize the elastic contribution in three terms. By investigating the different energy barriers involved to reach all the segregation sites, the antagonist impact of grain boundaries on hydrogen diffusion and trapping process was elucidated. The segregation energy and migration energy are two fundamental parameters in order to classify the grain-boundaries as a trapping location or short circuit for diffusion.
Brain-dead and coma patients exhibit different serum metabolic profiles: preliminary investigation of a novel diagnostic approach in neurocritical care
Authors: Dawiskiba Tomasz , Wojtowicz Wojciech , Qasem Badr , Łukaszewski Marceli , Mielko Karolina Anna , Dawiskiba Agnieszka , Banasik Mirosław , Skóra Jan Paweł , Janczak Dariusz , Młynarz Piotr 
Published: July 2021

AbstractThere is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic profiles were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic profiling allowed us to quantify 43 resonance signals, of which 34 were identified. Multivariate statistical modeling revealed a highly significant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The findings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.
A neural pathomics framework for classifying colorectal cancer histopathology images based on wavelet multi-scale texture analysis
Authors: Trivizakis Eleftherios , Ioannidis Georgios S. , Souglakos Ioannis , Karantanas Apostolos H. , Tzardi Maria , Marias Kostas 
Published: July 2021

AbstractColorectal cancer (CRC) constitutes the third most commonly diagnosed cancer in males and the second in females. Precise histopathological classification of CRC tissue pathology is the cornerstone not only for diagnosis but also for patients’ management decision making. An automated system able to accurately classify different CRC tissue regions may increase diagnostic precision and alleviate clinical workload. However, tissue classification is a challenging task due to the variability in morphological and textural characteristics present in histopathology images. In this study, an artificial neural network was trained to classify between eight classes of CRC tissue image patches derived from a public dataset with 5000 CRC histopathology image tiles. A total of 532 multi-level pathomics features examined at different scales were extracted by visual descriptors such as local binary patterns, wavelet transforms and Gabor filters. An exhaustive evaluation involving a variety of wavelet families and parameters was performed in order to shed light on the impact of scale on pathomics based CRC tissue differentiation. Our model achieved a performance accuracy of 95.3% with tenfold cross validation demonstrating superior performance compared to 87.4% reported in recent studies. Furthermore, we experimentally showed that the first and the second levels of the wavelet approximations can be used without compromising classification performance.
High-resolution model of Arabidopsis Photosystem II reveals the structural consequences of digitonin-extraction
Authors: Graça André T. , Hall Michael , Persson Karina , Schröder Wolfgang P. 
Published: July 2021

AbstractIn higher plants, the photosynthetic process is performed and regulated by Photosystem II (PSII). Arabidopsis thaliana was the first higher plant with a fully sequenced genome, conferring it the status of a model organism; nonetheless, a high-resolution structure of its Photosystem II is missing. We present the first Cryo-EM high-resolution structure of Arabidopsis PSII supercomplex with average resolution of 2.79 Å, an important model for future PSII studies. The digitonin extracted PSII complexes demonstrate the importance of: the LHG2630-lipid-headgroup in the trimerization of the light-harvesting complex II; the stabilization of the PsbJ subunit and the CP43-loop E by DGD520-lipid; the choice of detergent for the integrity of membrane protein complexes. Furthermore, our data shows at the anticipated Mn4CaO5-site a single metal ion density as a reminiscent early stage of Photosystem II photoactivation.