bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activating PIK3CA mutation promotes adipogenesis of adipose-derived stem cells in macrodactyly via up-regulation of E2F1
Authors: Sun Bin , Jiang Yongkang , Cui Hengqing , Fang Xia , Han Gang , Dai Xinyi , Zhou Shengbo , Mao Hailei , Wang Bin 
Published: July 2020

AbstractMacrodactyly is a congenital malformation characterized by enlargement of bone and soft tissues in limbs, typically with excessive accumulation of adipose tissues. Although gain-of-function mutation of PIK3CA has been identified in macrodactyly, the mechanism of PIK3CA mutation in adipose accumulation is poorly understood. In this study, we found that adipocytes from macrodactyly were more hypertrophic than those observed in polydactyly. PIK3CA (H1047R) activating mutation and enhanced activity of PI3K/AKT pathway were detected in macrodactylous adipose-derived stem cells (Mac-ADSCs). Compared to polydactyly-derived ADSCs (Pol-ADSCs), Mac-ADSCs had higher potential in adipogenic differentiation. Knockdown of PIK3CA or inhibition by BYL-719, a potent inhibitor of PIK3CA, impaired adipogenesis of Mac-ADSCs in vitro. In vivo study, either transient treatment of ADSCs or intragastrical gavage with BYL-719 inhibited the adipose formation in patient-derived xenograft (PDX). Furthermore, RNA-seq revealed that E2F1 was up-regulated in Mac-ADSCs and its knockdown blocked the PIK3CA-promoted adipogenesis. Our findings demonstrated that PIK3CA activating mutation promoted adipogenesis of ADSCs in macrodactyly, and that this effect was exerted by the up-regulation of E2F1. This study revealed a possible mechanism for adipose accumulation in macrodactyly and suggested BYL-719 as a potential therapeutic agent for macrodactyly treatment.
Hybrid Fourier-domain mode-locked laser for ultra-wideband linearly chirped microwave waveform generation
Authors: Tang Jian , Zhu Beibei , Zhang Weifeng , Li Ming , Pan Shilong , Yao Jianping 
Published: July 2020

AbstractWe show the generation of a tunable linearly chirped microwave waveform (LCMW) with an ultra-large time-bandwidth product (TBWP) based on a hybrid Fourier-domain mode-locked (FDML) laser. The key device in the hybrid FDML laser is a silicon photonic integrated micro-disk resonator (MDR) which functions as an optical bandpass filter, to have strong wavelength selectivity and fast frequency tunability. By incorporating the integrated MDR in the fiber-based ring cavity to perform frequency-domain mode locking, an FDML laser is realized and a broadband frequency-chirped optical pulse is generated. By beating the frequency-chirped optical pulse with an optical carrier from a laser diode (LD) at a photodetector (PD), an LCMW is generated. The bandwidth of the LCMW is over 50 GHz and the temporal duration is over 30 µs, with an ultra-large TBWP of 1.5 × 106. Thanks to the strong tunability of the MDR in the FDML laser, the generated LCMW is fully tunable in terms of bandwidth, temporal duration, chirp rate, and center frequency.
Targeting QKI-7 in vivo restores endothelial cell function in diabetes
Authors: Yang Chunbo , Eleftheriadou Magdalini , Kelaini Sophia , Morrison Thomas , González Marta Vilà , Caines Rachel , Edwards Nicola , Yacoub Andrew , Edgar Kevin , Moez Arya , Ivetic Aleksandar , Zampetaki Anna , Zeng Lingfang , Wilkinson Fiona L. , Lois Noemi , Stitt Alan W. , Grieve David J. , Margariti Andriana 
Published: July 2020

AbstractVascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) in iPS cell-derived ECs when exposed to hyperglycemia, and in human iPS-ECs from diabetic patients. QKI-7 is also highly expressed in human coronary arterial ECs from diabetic donors, and on blood vessels from diabetic critical limb ischemia patients undergoing a lower-limb amputation. QKI-7 expression is tightly controlled by RNA splicing factors CUG-BP and hnRNPM through direct binding. QKI-7 upregulation is correlated with disrupted cell barrier, compromised angiogenesis and enhanced monocyte adhesion. RNA immunoprecipitation (RIP) and mRNA-decay assays reveal that QKI-7 binds and promotes mRNA degradation of downstream targets CD144, Neuroligin 1 (NLGN1), and TNF-α-stimulated gene/protein 6 (TSG-6). When hindlimb ischemia is induced in diabetic mice and QKI-7 is knocked-down in vivo in ECs, reperfusion and blood flow recovery are markedly promoted. Manipulation of QKI-7 represents a promising strategy for the treatment of diabetic vascular complications.
Emerging heterogeneous compartments by viruses in single bacterial cells
Authors: Trinh Jimmy T. , Shao Qiuyan , Guan Jingwen , Zeng Lanying 
Published: July 2020

AbstractSpatial organization of biological processes allows for variability in molecular outcomes and coordinated development. Here, we investigate how organization underpins phage lambda development and decision-making by characterizing viral components and processes in subcellular space. We use live-cell and in situ fluorescence imaging at the single-molecule level to examine lambda DNA replication, transcription, virion assembly, and resource recruitment in single-cell infections, uniting key processes of the infection cycle into a coherent model of phage development encompassing space and time. We find that different viral DNAs establish separate subcellular compartments within cells, which sustains heterogeneous viral development in single cells. These individual phage compartments are physically separated by the E. coli nucleoid. Our results provide mechanistic details describing how separate viruses develop heterogeneously to resemble single-cell phenotypes.
Escape from nonsense-mediated decay associates with anti-tumor immunogenicity
Authors: Litchfield Kevin , Reading James L. , Lim Emilia L. , Xu Hang , Liu Po , Al-Bakir Maise , Wong Yien Ning Sophia , Rowan Andrew , Funt Samuel A. , Merghoub Taha , Perkins David , Lauss Martin , Svane Inge Marie , Jönsson Göran , Herrero Javier , Larkin James , Quezada Sergio A. , Hellmann Matthew D. , Turajlic Samra , Swanton Charles 
Published: July 2020

AbstractFrameshift insertion/deletions (fs-indels) are an infrequent but highly immunogenic mutation subtype. Although fs-indels are degraded through the nonsense-mediated decay (NMD) pathway, we hypothesise that some fs-indels escape degradation and elicit anti-tumor immune responses. Using allele-specific expression analysis, expressed fs-indels are enriched in genomic positions predicted to escape NMD, and associated with higher protein expression, consistent with degradation escape (NMD-escape). Across four independent melanoma cohorts, NMD-escape mutations are significantly associated with clinical-benefit to checkpoint inhibitor (CPI) therapy (Pmeta = 0.0039). NMD-escape mutations are additionally found to associate with clinical-benefit in the low-TMB setting. Furthermore, in an adoptive cell therapy treated melanoma cohort, NMD-escape mutation count is the most significant biomarker associated with clinical-benefit. Analysis of functional T cell reactivity screens from personalized vaccine studies shows direct evidence of fs-indel derived neoantigens eliciting immune response, particularly those with highly elongated neo open reading frames. NMD-escape fs-indels represent an attractive target for biomarker optimisation and immunotherapy design.
Collective cell mechanics of epithelial shells with organoid-like morphologies
Authors: Rozman Jan , Krajnc Matej , Ziherl Primož 
Published: July 2020

AbstractThe study of organoids, artificially grown cell aggregates with the functionality and small-scale anatomy of real organs, is one of the most active areas of research in biology and biophysics, yet the basic physical origins of their different morphologies remain poorly understood. Here, we propose a mechanistic theory of epithelial shells which resemble small-organoid morphologies. Using a 3D surface tension-based vertex model, we reproduce the characteristic shapes from branched and budded to invaginated structures. We find that the formation of branched morphologies relies strongly on junctional activity, enabling temporary aggregations of topological defects in cell packing. To elucidate our numerical results, we develop an effective elasticity theory, which allows one to estimate the apico-basal polarity from the tissue-scale modulation of cell height. Our work provides a generic interpretation of the observed epithelial shell morphologies, highlighting the role of physical factors such as differential surface tension, cell rearrangements, and tissue growth.
Structural signatures in EPR3 define a unique class of plant carbohydrate receptors
Authors: Wong Jaslyn E. M. M. , Gysel Kira , Birkefeldt Thea G. , Vinther Maria , Muszyński Artur , Azadi Parastoo , Laursen Nick S. , Sullivan John T. , Ronson Clive W. , Stougaard Jens , Andersen Kasper R. 
Published: July 2020

AbstractReceptor-mediated perception of surface-exposed carbohydrates like lipo- and exo-polysaccharides (EPS) is important for non-self recognition and responses to microbial associated molecular patterns in mammals and plants. In legumes, EPS are monitored and can either block or promote symbiosis with rhizobia depending on their molecular composition. To establish a deeper understanding of receptors involved in EPS recognition, we determined the structure of the Lotus japonicus (Lotus) exopolysaccharide receptor 3 (EPR3) ectodomain. EPR3 forms a compact structure built of three putative carbohydrate-binding modules (M1, M2 and LysM3). M1 and M2 have unique βαββ and βαβ folds that have not previously been observed in carbohydrate binding proteins, while LysM3 has a canonical βααβ fold. We demonstrate that this configuration is a structural signature for a ubiquitous class of receptors in the plant kingdom. We show that EPR3 is promiscuous, suggesting that plants can monitor complex microbial communities though this class of receptors.
Cosmogenic exposure dating reveals limited long-term variability in erosion of a rocky coastline
Authors: Swirad Zuzanna M. , Rosser Nick J. , Brain Matthew J. , Rood Dylan H. , Hurst Martin D. , Wilcken Klaus M. , Barlow John 
Published: July 2020

AbstractPredicted sea-level rise and increased storminess are anticipated to lead to increases in coastal erosion. However, assessing if and how rocky coasts will respond to changes in marine conditions is difficult due to current limitations of monitoring and modelling. Here, we measured cosmogenic 10Be concentrations across a sandstone shore platform in North Yorkshire, UK, to model the changes in coastal erosion within the last 7 kyr and for the first time quantify the relative long-term erosive contribution of landward cliff retreat, and down-wearing and stripping of rock from the shore platform. The results suggest that the cliff has been retreating at a steady rate of 4.5 ± 0.63 cm yr−1, whilst maintaining a similar profile form. Our results imply a lack of a direct relationship between relative sea level over centennial to millennial timescales and the erosion response of the coast, highlighting a need to more fully characterise the spatial variability in, and controls on, rocky coast erosion under changing conditions.
Role of optimization algorithms based fuzzy controller in achieving induction motor performance enhancement
Authors: Hannan M. A. , Ali Jamal Abd. , Hossain Lipu M. S. , Mohamed A. , Ker Pin Jern , Indra Mahlia T. M. , Mansor M. , Hussain Aini , Muttaqi Kashem M. , Dong Z. Y. 
Published: July 2020

AbstractThree-phase induction motors (TIMs) are widely used for machines in industrial operations. As an accurate and robust controller, fuzzy logic controller (FLC) is crucial in designing TIMs control systems. The performance of FLC highly depends on the membership function (MF) variables, which are evaluated by heuristic approaches, leading to a high processing time. To address these issues, optimisation algorithms for TIMs have received increasing interest among researchers and industrialists. Here, we present an advanced and efficient quantum-inspired lightning search algorithm (QLSA) to avoid exhaustive conventional heuristic procedures when obtaining MFs. The accuracy of the QLSA based FLC (QLSAF) speed control is superior to other controllers in terms of transient response, damping capability and minimisation of statistical errors under diverse speeds and loads. The performance of the proposed QLSAF speed controller is validated through experiments. Test results under different conditions show consistent speed responses and stator currents with the simulation results.
Structural order in plasmonic superlattices
Authors: Schulz Florian , Pavelka Ondřej , Lehmkühler Felix , Westermeier Fabian , Okamura Yu , Mueller Niclas S. , Reich Stephanie , Lange Holger 
Published: July 2020

AbstractThe assembly of plasmonic nanoparticles into ordered 2D- and 3D-superlattices could pave the way towards new tailored materials for plasmonic sensing, photocatalysis and manipulation of light on the nanoscale. The properties of such materials strongly depend on their geometry, and accordingly straightforward protocols to obtain precise plasmonic superlattices are highly desirable. Here, we synthesize large areas of crystalline mono-, bi- and multilayers of gold nanoparticles >20 nm with a small number of defects. The superlattices can be described as hexagonal crystals with standard deviations of the lattice parameter below 1%. The periodic arrangement within the superlattices leads to new well-defined collective plasmon-polariton modes. The general level of achieved superlattice quality will be of benefit for a broad range of applications, ranging from fundamental studies of light–matter interaction to optical metamaterials and substrates for surface-enhanced spectroscopies.
Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages
Authors: Hirata Takumi , Arai Yasumichi , Yuasa Shinsuke , Abe Yukiko , Takayama Michiyo , Sasaki Takashi , Kunitomi Akira , Inagaki Hiroki , Endo Motoyoshi , Morinaga Jun , Yoshimura Kimio , Adachi Tetsuo , Oike Yuichi , Takebayashi Toru , Okano Hideyuki , Hirose Nobuyoshi 
Published: July 2020

AbstractSupercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105–109 years), 288 centenarians (100–104 years), and 531 very old people (85–99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.
Polypeptide formation in clusters of β-alanine amino acids by single ion impact
Authors: Rousseau Patrick , Piekarski Dariusz G. , Capron Michael , Domaracka Alicja , Adoui Lamri , Martín Fernando , Alcamí Manuel , Díaz-Tendero Sergio , Huber Bernd A. 
Published: July 2020

AbstractThe formation of peptide bonds by energetic processing of amino acids is an important step towards the formation of biologically relevant molecules. As amino acids are present in space, scenarios have been developed to identify the roots of life on Earth, either by processes occurring in outer space or on Earth itself. We study the formation of peptide bonds in single collisions of low-energy He2+ ions (α-particles) with loosely bound clusters of β-alanine molecules at impact energies typical for solar wind. Experimental fragmentation mass spectra produced by collisions are compared with results of molecular dynamics simulations and an exhaustive exploration of potential energy surfaces. We show that peptide bonds are efficiently formed by water molecule emission, leading to the formation of up to tetrapeptide. The present results show that a plausible route to polypeptides formation in space is the collision of energetic ions with small clusters of amino acids.
Identification of relevant genetic alterations in cancer using topological data analysis
Authors: Rabadán Raúl , Mohamedi Yamina , Rubin Udi , Chu Tim , Alghalith Adam N. , Elliott Oliver , Arnés Luis , Cal Santiago , Obaya Álvaro J. , Levine Arnold J. , Cámara Pablo G. 
Published: July 2020

AbstractLarge-scale cancer genomic studies enable the systematic identification of mutations that lead to the genesis and progression of tumors, uncovering the underlying molecular mechanisms and potential therapies. While some such mutations are recurrently found in many tumors, many others exist solely within a few samples, precluding detection by conventional recurrence-based statistical approaches. Integrated analysis of somatic mutations and RNA expression data across 12 tumor types reveals that mutations of cancer genes are usually accompanied by substantial changes in expression. We use topological data analysis to leverage this observation and uncover 38 elusive candidate cancer-associated genes, including inactivating mutations of the metalloproteinase ADAMTS12 in lung adenocarcinoma. We show thatADAMTS12−/−mice have a five-fold increase in the susceptibility to develop lung tumors, confirming the role ofADAMTS12as a tumor suppressor gene. Our results demonstrate that data integration through topological techniques can increase our ability to identify previously unreported cancer-related alterations.
STAT3 serine phosphorylation is required for TLR4 metabolic reprogramming and IL-1β expression
Authors: Balic Jesse J. , Albargy Hassan , Luu Kevin , Kirby Francis J. , Jayasekara W. Samantha N. , Mansell Finbar , Garama Daniel J. , De Nardo Dominic , Baschuk Nikola , Louis Cynthia , Humphries Fiachra , Fitzgerald Katherine , Latz Eicke , Gough Daniel J. , Mansell Ashley 
Published: July 2020

AbstractDetection of microbial components such as lipopolysaccharide (LPS) by Toll-like receptor 4 (TLR4) on macrophages induces a robust pro-inflammatory response that is dependent on metabolic reprogramming. These innate metabolic changes have been compared to aerobic glycolysis in tumour cells. However, the mechanisms by which TLR4 activation leads to mitochondrial and glycolytic reprogramming are unknown. Here we show that TLR4 activation induces a signalling cascade recruiting TRAF6 and TBK-1, while TBK-1 phosphorylates STAT3 on S727. Using a genetically engineered mouse model incapable of undergoing STAT3 Ser727 phosphorylation, we show ex vivo and in vivo that STAT3 Ser727 phosphorylation is critical for LPS-induced glycolytic reprogramming, production of the central immune response metabolite succinate and inflammatory cytokine production in a model of LPS-induced inflammation. Our study identifies non-canonical STAT3 activation as the crucial signalling intermediary for TLR4-induced glycolysis, macrophage metabolic reprogramming and inflammation.
Interactome of miRNAs and transcriptome of human umbilical cord endothelial cells exposed to short-term simulated microgravity
Authors: Kasiviswanathan Dharanibalan , Chinnasamy Perumal Rajadurai , Bhuvaneswari Srinivasan , Kumar Pavitra , Sundaresan Lakshmikirupa , Philip Manuel , Puthenpurackal Krishnankutty Sajesh , Chatterjee Suvro 
Published: July 2020

AbstractAdaptation of humans in low gravity conditions is a matter of utmost importance when efforts are on to a gigantic leap in human space expeditions for tourism and formation of space colonies. In this connection, cardiovascular adaptation in low gravity is a critical component of human space exploration. Deep high-throughput sequencing approach allowed us to analyze the miRNA and mRNA expression profiles in human umbilical cord vein endothelial cells (HUVEC), cultured under gravity (G), and stimulated microgravity (MG) achieved with a clinostat. The present study identified totally 1870 miRNAs differentially expressed in HUVEC under MG condition when compared to the cells subjected to unitary G conditions. The functional association of identified miRNAs targeting specific mRNAs revealed that miRNAs, hsa-mir-496, hsa-mir-151a, hsa-miR-296-3p, hsa-mir-148a, hsa-miR-365b-5p, hsa-miR-3687, hsa-mir-454, hsa-miR-155-5p, and hsa-miR-145-5p differentially regulated the genes involved in cell adhesion, angiogenesis, cell cycle, JAK-STAT signaling, MAPK signaling, nitric oxide signaling, VEGF signaling, and wound healing pathways. Further, the q-PCR based experimental studies of upregulated and downregulated miRNA and mRNAs demonstrate that the above reported miRNAs influence the cell proliferation and vascular functions of the HUVEC in MG conditions effectively. Consensus on the interactome results indicates restricted fluctuations in the transcriptome of the HUVEC exposed to short-term MG that could lead to higher levels of endothelial functions like angiogenesis and vascular patterning.
Projections of global-scale extreme sea levels and resulting episodic coastal flooding over the 21st Century
Authors: Kirezci Ebru , Young Ian R. , Ranasinghe Roshanka , Muis Sanne , Nicholls Robert J. , Lincke Daniel , Hinkel Jochen 
Published: July 2020

AbstractGlobal models of tide, storm surge, and wave setup are used to obtain projections of episodic coastal flooding over the coming century. The models are extensively validated against tide gauge data and the impact of uncertainties and assumptions on projections estimated in detail. Global “hotspots” where there is projected to be a significant change in episodic flooding by the end of the century are identified and found to be mostly concentrated in north western Europe and Asia. Results show that for the case of, no coastal protection or adaptation, and a mean RCP8.5 scenario, there will be an increase of 48% of the world’s land area, 52% of the global population and 46% of global assets at risk of flooding by 2100. A total of 68% of the global coastal area flooded will be caused by tide and storm events with 32% due to projected regional sea level rise.
Loss of Caveolin-1 and caveolae leads to increased cardiac cell stiffness and functional decline of the adult zebrafish heart
Authors: Grivas Dimitrios , González-Rajal Álvaro , Guerrero Rodríguez Carlos , Garcia Ricardo , de la Pompa José Luis 
Published: July 2020

AbstractCaveolin-1 is the main structural protein of caveolae, small membrane invaginations involved in signal transduction and mechanoprotection. Here, we generatedcav1-KOzebrafish lacking Cav1 and caveolae, and investigated the impact of this loss on adult heart function and response to cryoinjury. We found that cardiac function was impaired in adultcav1-KOfish, which showed a significantly decreased ejection fraction and heart rate. Using atomic force microscopy, we detected an increase in the stiffness of epicardial cells and cells of the cortical zone lacking Cav1/caveolae. This loss of cardiac elasticity might explain the decreased cardiac contraction and function. Surprisingly,cav1-KOmutants were able to regenerate their heart after a cryoinjury but showed a transient decrease in cardiomyocyte proliferation.