bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid prototyping and design of cybergenetic single-cell controllers
Authors: Kumar Sant , Rullan Marc , Khammash Mustafa 
Published: October 2021

AbstractThe design and implementation of synthetic circuits that operate robustly in the cellular context is fundamental for the advancement of synthetic biology. However, their practical implementation presents challenges due to low predictability of synthetic circuit design and time-intensive troubleshooting. Here, we present the Cyberloop, a testing framework to accelerate the design process and implementation of biomolecular controllers. Cellular fluorescence measurements are sent in real-time to a computer simulating candidate stochastic controllers, which in turn compute the control inputs and feed them back to the controlled cells via light stimulation. Applying this framework to yeast cells engineered with optogenetic tools, we examine and characterize different biomolecular controllers, test the impact of non-ideal circuit behaviors such as dilution on their operation, and qualitatively demonstrate improvements in controller function with certain network modifications. From this analysis, we derive conditions for desirable biomolecular controller performance, thereby avoiding pitfalls during its biological implementation.
Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases
Authors: Yang Yuanhao , Musco Hannah , Simpson-Yap Steve , Zhu Zhihong , Wang Ying , Lin Xin , Zhang Jiawei , Taylor Bruce , Gratten Jacob , Zhou Yuan 
Published: October 2021

AbstractAn epidemiological association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is well established, but whether this reflects a shared genetic aetiology, and whether consistent genetic relationships exist between MS and the two predominant IBD subtypes, ulcerative colitis (UC) and Crohn’s disease (CD), remains unclear. Here, we use large-scale genome-wide association study summary data to investigate the shared genetic architecture between MS and IBD overall and UC and CD independently. We find a significantly greater genetic correlation between MS and UC than between MS and CD, and identify three SNPs shared between MS and IBD (rs13428812), UC (rs116555563) and CD (rs13428812, rs9977672) in cross-trait meta-analyses. We find suggestive evidence for a causal effect of MS on UC and IBD using Mendelian randomization, but no or weak and inconsistent evidence for a causal effect of IBD or UC on MS. We observe largely consistent patterns of tissue-specific heritability enrichment for MS and IBDs in lung, spleen, whole blood and small intestine, and identify cell-type-specific enrichment for MS and IBDs in CD4+T cells in lung and CD8+cytotoxic T cells in lung and spleen. Our study sheds light on the biological basis of comorbidity between MS and IBD.
A longitudinal sampling study of transcriptomic and epigenetic profiles in patients with thrombocytopenia syndrome
Authors: Wang Yafen , Han Shaoqing , Ran Ruoxi , Li Anling , Liu Huanyu , Liu Mingjun , Duan Yongwei , Zhang Xiong , Zhao Zhigang , Song Shihui , Weng Xiaocheng , Liu Song-Mei , Zhou Xiang 
Published: October 2021

AbstractSevere fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease caused by a new type of SFTS virus (SFTSV). Here, a longitudinal sampling study is conducted to explore the differences in transcript levels after SFTSV infection, and to characterize the transcriptomic and epigenetic profiles of hospitalized patients. The results reveal significant changes in the mRNA expression of certain genes from onset to recovery. Moreover, m6A-seq reveals that certain genes related with immune regulation may be regulated by m6A. Besides the routine tests such as platelet counts, serum ALT and AST levels testing, distinct changes in myocardial enzymes, coagulation function, and inflammation are well correlated with the clinical data and sequencing data, suggesting that clinical practitioners should monitor the above indicators to track disease progression and guide personalized treatment. In this study, the transcript changes and RNA modification may lend a fresh perspective to our understanding of the SFTSV and play a significant role in the discovery of drugs for effective treatment of this disease.
Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome
Authors: Porcu Eleonora , Sadler Marie C. , Lepik Kaido , Auwerx Chiara , Wood Andrew R. , Weihs Antoine , Sleiman Maroun S. Bou , Ribeiro Diogo M. , Bandinelli Stefania , Tanaka Toshiko , Nauck Matthias , Völker Uwe , Delaneau Olivier , Metspalu Andres , Teumer Alexander , Frayling Timothy , Santoni Federico A. , Reymond Alexandre , Kutalik Zoltán 
Published: October 2021

AbstractComparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease under scrutiny. We propose a method to decompose the observational correlation between gene expression and phenotypes driven by confounders, forward- and reverse causal effects. The bi-directional causal effects between gene expression and complex traits are obtained by Mendelian Randomization integrating summary-level data from GWAS and whole-blood eQTLs. Applying this approach to complex traits reveals that forward effects have negligible contribution. For example, BMI- and triglycerides-gene expression correlation coefficients robustly correlate with trait-to-expression causal effects (rBMI = 0.11, PBMI = 2.0 × 10−51 and rTG = 0.13, PTG = 1.1 × 10−68), but not detectably with expression-to-trait effects. Our results demonstrate that studies comparing the transcriptome of diseased and healthy subjects are more prone to reveal disease-induced gene expression changes rather than disease causing ones.
Optomechanical synchronization across multi-octave frequency spans
Authors: Rodrigues Caique C. , Kersul Cauê M. , Primo André G. , Lipson Michal , Alegre Thiago P. Mayer , Wiederhecker Gustavo S. 
Published: October 2021

AbstractExperimental exploration of synchronization in scalable oscillator microsystems has unfolded a deeper understanding of networks, collective phenomena, and signal processing. Cavity optomechanical devices have played an important role in this scenario, with the perspective of bridging optical and radio frequencies through nonlinear classical and quantum synchronization concepts. In its simplest form, synchronization occurs when an oscillator is entrained by a signal with frequency nearby the oscillator’s tone, and becomes increasingly challenging as their frequency detuning increases. Here, we experimentally demonstrate entrainment of a silicon-nitride optomechanical oscillator driven up to the fourth harmonic of its 32 MHz fundamental frequency. Exploring this effect, we also experimentally demonstrate a purely optomechanical RF frequency divider, where we performed frequency division up to a 4:1 ratio, i.e., from 128 MHz to 32 MHz. Further developments could harness these effects towards frequency synthesizers, phase-sensitive amplification and nonlinear sensing.
Evolutionarily informed machine learning enhances the power of predictive gene-to-phenotype relationships
Authors: Cheng Chia-Yi , Li Ying , Varala Kranthi , Bubert Jessica , Huang Ji , Kim Grace J. , Halim Justin , Arp Jennifer , Shih Hung-Jui S. , Levinson Grace , Park Seo Hyun , Cho Ha Young , Moose Stephen P. , Coruzzi Gloria M. 
Published: October 2021

AbstractInferring phenotypic outcomes from genomic features is both a promise and challenge for systems biology. Using gene expression data to predict phenotypic outcomes, and functionally validating the genes with predictive powers are two challenges we address in this study. We applied an evolutionarily informed machine learning approach to predict phenotypes based on transcriptome responses shared both within and across species. Specifically, we exploited the phenotypic diversity in nitrogen use efficiency and evolutionarily conserved transcriptome responses to nitrogen treatments across Arabidopsis accessions and maize varieties. We demonstrate that using evolutionarily conserved nitrogen responsive genes is a biologically principled approach to reduce the feature dimensionality in machine learning that ultimately improved the predictive power of our gene-to-trait models. Further, we functionally validated seven candidate transcription factors with predictive power for NUE outcomes in Arabidopsis and one in maize. Moreover, application of our evolutionarily informed pipeline to other species including rice and mice models underscores its potential to uncover genes affecting any physiological or clinical traits of interest across biology, agriculture, or medicine.
Out-of-equilibrium processes in crystallization of organic-inorganic perovskites during spin coating
Authors: Pratap Shambhavi , Babbe Finn , Barchi Nicola S. , Yuan Zhenghao , Luong Tina , Haber Zach , Song Tze-Bin , Slack Jonathan L. , Stan Camelia V. , Tamura Nobumichi , Sutter-Fella Carolin M. , Müller-Buschbaum Peter 
Published: October 2021

AbstractComplex phenomena are prevalent during the formation of materials, which affect their processing-structure-function relationships. Thin films of methylammonium lead iodide (CH3NH3PbI3, MAPI) are processed by spin coating, antisolvent drop, and annealing of colloidal precursors. The structure and properties of transient and stable phases formed during the process are reported, and the mechanistic insights of the underlying transitions are revealed by combining in situ data from grazing-incidence wide-angle X-ray scattering and photoluminescence spectroscopy. Here, we report the detailed insights on the embryonic stages of organic-inorganic perovskite formation. The physicochemical evolution during the conversion proceeds in four steps: i) An instant nucleation of polydisperse MAPI nanocrystals on antisolvent drop, ii) the instantaneous partial conversion of metastable nanocrystals into orthorhombic solvent-complex by cluster coalescence, iii) the thermal decomposition (dissolution) of the stable solvent-complex into plumboiodide fragments upon evaporation of solvent from the complex and iv) the formation (recrystallization) of cubic MAPI crystals in thin film.
Extensive regulation of enzyme activity by phosphorylation in Escherichia coli
Authors: Schastnaya Evgeniya , Raguz Nakic Zrinka , Gruber Christoph H. , Doubleday Peter Francis , Krishnan Aarti , Johns Nathan I. , Park Jimin , Wang Harris H. , Sauer Uwe 
Published: October 2021

AbstractProtein serine/threonine/tyrosine (S/T/Y) phosphorylation is an essential and frequent post-translational modification in eukaryotes, but historically has been considered less prevalent in bacteria because fewer proteins were found to be phosphorylated and most proteins were modified to a lower degree. Recent proteomics studies greatly expanded the phosphoproteome of Escherichia coli to more than 2000 phosphorylation sites (phosphosites), yet mechanisms of action were proposed for only six phosphosites and fitness effects were described for 38 phosphosites upon perturbation. By systematically characterizing functional relevance of S/T/Y phosphorylation in E. coli metabolism, we found 44 of the 52 mutated phosphosites to be functional based on growth phenotypes and intracellular metabolome profiles. By effectively doubling the number of known functional phosphosites, we provide evidence that protein phosphorylation is a major regulation process in bacterial metabolism. Combining in vitro and in vivo experiments, we demonstrate how single phosphosites modulate enzymatic activity and regulate metabolic fluxes in glycolysis, methylglyoxal bypass, acetate metabolism and the split between pentose phosphate and Entner-Doudoroff pathways through mechanisms that include shielding the substrate binding site, limiting structural dynamics, and disrupting interactions relevant for activity in vivo.
Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism
Authors: Massart Julie , Sjögren Rasmus J. O. , Egan Brendan , Garde Christian , Lindgren Magnus , Gu Weifeng , Ferreira Duarte M. S. , Katayama Mutsumi , Ruas Jorge L. , Barrès Romain , O’Gorman Donal J. , Zierath Juleen R. , Krook Anna 
Published: October 2021

AbstractSkeletal muscle is a highly adaptable tissue and remodels in response to exercise training. Using short RNA sequencing, we determine the miRNA profile of skeletal muscle from healthy male volunteers before and after a 14-day aerobic exercise training regime. Among the exercise training-responsive miRNAs identified, miR-19b-3p was selected for further validation. Overexpression of miR-19b-3p in human skeletal muscle cells increases insulin signaling, glucose uptake, and maximal oxygen consumption, recapitulating the adaptive response to aerobic exercise training. Overexpression of miR-19b-3p in mouse flexor digitorum brevis muscle enhances contraction-induced glucose uptake, indicating that miR-19b-3p exerts control on exercise training-induced adaptations in skeletal muscle. Potential targets of miR-19b-3p that are reduced after aerobic exercise training include KIF13A, MAPK6, RNF11, and VPS37A. Amongst these, RNF11 silencing potentiates glucose uptake in human skeletal muscle cells. Collectively, we identify miR-19b-3p as an aerobic exercise training-induced miRNA that regulates skeletal muscle glucose metabolism.
Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis
Authors: Kuzumi Ai , Yoshizaki Ayumi , Matsuda Kazuki M. , Kotani Hirohito , Norimatsu Yuta , Fukayama Maiko , Ebata Satoshi , Fukasawa Takemichi , Yoshizaki-Ogawa Asako , Asano Yoshihide , Morikawa Kyojiro , Kazoe Yutaka , Mawatari Kazuma , Kitamori Takehiko , Sato Shinichi 
Published: October 2021

AbstractSystemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.
Relationship of insect biomass and richness with land use along a climate gradient
Authors: Uhler Johannes , Redlich Sarah , Zhang Jie , Hothorn Torsten , Tobisch Cynthia , Ewald Jörg , Thorn Simon , Seibold Sebastian , Mitesser Oliver , Morinière Jérôme , Bozicevic Vedran , Benjamin Caryl S. , Englmeier Jana , Fricke Ute , Ganuza Cristina , Haensel Maria , Riebl Rebekka , Rojas-Botero Sandra , Rummler Thomas , Uphus Lars , Schmidt Stefan , Steffan-Dewenter Ingolf , Müller Jörg 
Published: October 2021

AbstractRecently reported insect declines have raised both political and social concern. Although the declines have been attributed to land use and climate change, supporting evidence suffers from low taxonomic resolution, short time series, a focus on local scales, and the collinearity of the identified drivers. In this study, we conducted a systematic assessment of insect populations in southern Germany, which showed that differences in insect biomass and richness are highly context dependent. We found the largest difference in biomass between semi-natural and urban environments (−42%), whereas differences in total richness (−29%) and the richness of threatened species (−56%) were largest from semi-natural to agricultural environments. These results point to urbanization and agriculture as major drivers of decline. We also found that richness and biomass increase monotonously with increasing temperature, independent of habitat. The contrasting patterns of insect biomass and richness question the use of these indicators as mutual surrogates. Our study provides support for the implementation of more comprehensive measures aimed at habitat restoration in order to halt insect declines.
Metal-catalyst-free gas-phase synthesis of long-chain hydrocarbons
Authors: Martínez Lidia , Merino Pablo , Santoro Gonzalo , Martínez José I. , Katsanoulis Stergios , Ault Jesse , Mayoral Álvaro , Vázquez Luis , Accolla Mario , Dazzi Alexandre , Mathurin Jeremie , Borondics Ferenc , Blázquez-Blázquez Enrique , Shauloff Nitzan , Lebrón-Aguilar Rosa , Quintanilla-López Jesús E. , Jelinek Raz , Cernicharo José , Stone Howard A. , de la Peña O’Shea Victor A. , de Andres Pedro L. , Haller George , Ellis Gary J. , Martín-Gago José A. 
Published: October 2021

AbstractDevelopment of sustainable processes for hydrocarbons synthesis is a fundamental challenge in chemistry since these are of unquestionable importance for the production of many essential synthetic chemicals, materials and carbon-based fuels. Current industrial processes rely on non-abundant metal catalysts, temperatures of hundreds of Celsius and pressures of tens of bars. We propose an alternative gas phase process under mild reaction conditions using only atomic carbon, molecular hydrogen and an inert carrier gas. We demonstrate that the presence of CH2 and H radicals leads to efficient C-C chain growth, producing micron-length fibres of unbranched alkanes with an average length distribution between C23-C33. Ab-initio calculations uncover a thermodynamically favourable methylene coupling process on the surface of carbonaceous nanoparticles, which is kinematically facilitated by a trap-and-release mechanism of the reactants and nanoparticles that is confirmed by a steady incompressible flow simulation. This work could lead to future alternative sustainable synthetic routes to critical alkane-based chemicals or fuels.
Quantification of the Li-ion diffusion over an interface coating in all-solid-state batteries via NMR measurements
Authors: Liu Ming , Wang Chao , Zhao Chenglong , van der Maas Eveline , Lin Kui , Arszelewska Violetta A. , Li Baohua , Ganapathy Swapna , Wagemaker Marnix 
Published: October 2021

AbstractA key challenge for solid-state-batteries development is to design electrode-electrolyte interfaces that combine (electro)chemical and mechanical stability with facile Li-ion transport. However, while the solid-electrolyte/electrode interfacial area should be maximized to facilitate the transport of high electrical currents on the one hand, on the other hand, this area should be minimized to reduce the parasitic interfacial reactions and promote the overall cell stability. To improve these aspects simultaneously, we report the use of an interfacial inorganic coating and the study of its impact on the local Li-ion transport over the grain boundaries. Via exchange-NMR measurements, we quantify the equilibrium between the various phases present at the interface between an S-based positive electrode and an inorganic solid-electrolyte. We also demonstrate the beneficial effect of the LiI coating on the all-solid-state cell performances, which leads to efficient sulfur activation and prevention of solid-electrolyte decomposition. Finally, we report 200 cycles with a stable capacity of around 600 mAh g−1 at 0.264 mA cm−2 for a full lab-scale cell comprising of LiI-coated Li2S-based cathode, Li-In alloy anode and Li6PS5Cl solid electrolyte.
Enhanced North Pacific subtropical gyre circulation during the late Holocene
Authors: Zhang Yancheng , Zheng Xufeng , Kong Deming , Yan Hong , Liu Zhonghui 
Published: October 2021

AbstractThe North Pacific Subtropical Gyre circulation redistributes heat from the Western Pacific Warm Pool towards the mid- to high-latitude North Pacific. However, the driving mechanisms of this circulation and how it changed over the Holocene remain poorly understood. Here, we present alkenone-based sea surface temperature reconstructions along the Kuroshio, California and Alaska currents that cover the past ~7,000 years. These and other paleorecords collectively demonstrate a coherent intensification of the boundary currents, and thereby the basin-scale subtropical gyre circulation, since ~3,000–4,000 years ago. Such enhanced circulation during the late Holocene appears to have resulted from a long-term southward migration of the Intertropical Convergence Zone, associated with Holocene ocean cooling. Our results imply that the North Pacific Subtropical Gyre circulation could be weakened under future global warming.
Indian Ocean Dipole leads to Atlantic Niño
Authors: Zhang Lei , Han Weiqing 
Published: October 2021

AbstractAtlantic Niño is the Atlantic equivalent of El Niño-Southern Oscillation (ENSO), and it has prominent impacts on regional and global climate. Existing studies suggest that the Atlantic Niño may arise from local atmosphere-ocean interaction and is sometimes triggered by the Atlantic Meridional Mode (AMM), with overall weak ENSO contribution. By analyzing observational datasets and performing numerical model experiments, here we show that the Atlantic Niño can be induced by the Indian Ocean Dipole (IOD). We find that the enhanced rainfall in the western tropical Indian Ocean during positive IOD weakens the easterly trade winds over the tropical Atlantic, causing warm anomalies in the central and eastern equatorial Atlantic basin and therefore triggering the Atlantic Niño. Our finding suggests that the cross-basin impact from the tropical Indian Ocean plays a more important role in affecting interannual climate variability than previously thought.
Coupling complementary strategy to flexible graph neural network for quick discovery of coformer in diverse co-crystal materials
Authors: Jiang Yuanyuan , Yang Zongwei , Guo Jiali , Li Hongzhen , Liu Yijing , Guo Yanzhi , Li Menglong , Pu Xuemei 
Published: October 2021

AbstractCocrystal engineering have been widely applied in pharmaceutical, chemistry and material fields. However, how to effectively choose coformer has been a challenging task on experiments. Here we develop a graph neural network (GNN) based deep learning framework to quickly predict formation of the cocrystal. In order to capture main driving force to crystallization from 6819 positive and 1052 negative samples reported by experiments, a feasible GNN framework is explored to integrate important prior knowledge into end-to-end learning on the molecular graph. The model is strongly validated against seven competitive models and three challenging independent test sets involving pharmaceutical cocrystals, π–π cocrystals and energetic cocrystals, exhibiting superior performance with accuracy higher than 96%, confirming its robustness and generalization. Furthermore, one new energetic cocrystal predicted is successfully synthesized, showcasing high potential of the model in practice. All the data and source codes are available at https://github.com/Saoge123/ccgnet for aiding cocrystal community.