bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis
Authors: Sletten Arthur C. , Davidson Jessica W. , Yagabasan Busra , Moores Samantha , Schwaiger-Haber Michaela , Fujiwara Hideji , Gale Sarah , Jiang Xuntian , Sidhu Rohini , Gelman Susan J. , Zhao Shuang , Patti Gary J. , Ory Daniel S. , Schaffer Jean E. 
Published: September 2021

AbstractDyslipidemia and resulting lipotoxicity are pathologic signatures of metabolic syndrome and type 2 diabetes. Excess lipid causes cell dysfunction and induces cell death through pleiotropic mechanisms that link to oxidative stress. However, pathways that regulate the response to metabolic stress are not well understood. Herein, we show that disruption of the box H/ACA SNORA73 small nucleolar RNAs encoded within the small nucleolar RNA hosting gene 3 (Snhg3) causes resistance to lipid-induced cell death and general oxidative stress in cultured cells. This protection from metabolic stress is associated with broad reprogramming of oxidative metabolism that is dependent on the mammalian target of rapamycin signaling axis. Furthermore, we show that knockdown of SNORA73 in vivo protects against hepatic steatosis and lipid-induced oxidative stress and inflammation. Our findings demonstrate a role for SNORA73 in the regulation of metabolism and lipotoxicity.
Carbon clusters formed from shocked benzene
Authors: Dattelbaum D. M. , Watkins E. B. , Firestone M. A. , Huber R. C. , Gustavsen R. L. , Ringstrand B. S. , Coe J. D. , Podlesak D. , Gleason A. E. , Lee H. J. , Galtier E. , Sandberg R. L. 
Published: September 2021

AbstractBenzene (C6H6), while stable under ambient conditions, can become chemically reactive at high pressures and temperatures, such as under shock loading conditions. Here, we report in situ x-ray diffraction and small angle x-ray scattering measurements of liquid benzene shocked to 55 GPa, capturing the morphology and crystalline structure of the shock-driven reaction products at nanosecond timescales. The shock-driven chemical reactions in benzene observed using coherent XFEL x-rays were a complex mixture of products composed of carbon and hydrocarbon allotropes. In contrast to the conventional description of diamond, methane and hydrogen formation, our present results indicate that benzene’s shock-driven reaction products consist of layered sheet-like hydrocarbon structures and nanosized carbon clusters with mixed sp2-sp3 hybridized bonding. Implications of these findings range from guiding shock synthesis of novel compounds to the fundamentals of carbon transport in planetary physics.
Structure of the human marker of self 5-transmembrane receptor CD47
Authors: Fenalti Gustavo , Villanueva Nicolas , Griffith Mark , Pagarigan Barbra , Lakkaraju Sirish Kaushik , Huang Richard Y.-C. , Ladygina Nadia , Sharma Alok , Mikolon David , Abbasian Mahan , Johnson Jeffrey , Hadjivassiliou Haralambos , Zhu Dan , Chamberlain Philip P. , Cho Ho , Hariharan Kandasamy 
Published: September 2021

AbstractCD47 is the only 5-transmembrane (5-TM) spanning receptor of the immune system. Its extracellular domain (ECD) is a cell surface marker of self that binds SIRPα and inhibits macrophage phagocytosis, and cancer immuno-therapy approaches in clinical trials are focused on blocking CD47/SIRPα interaction. We present the crystal structure of full length CD47 bound to the function-blocking antibody B6H12. CD47 ECD is tethered to the TM domain via a six-residue peptide linker (114RVVSWF119) that forms an extended loop (SWF loop), with the fundamental role of inserting the side chains of W118 and F119 into the core of CD47 extracellular loop region (ECLR). Using hydrogen-deuterium exchange and molecular dynamics simulations we show that CD47’s ECLR architecture, comprised of two extracellular loops and the SWF loop, creates a molecular environment stabilizing the ECD for presentation on the cell surface. These findings provide insights into CD47 immune recognition, signaling and therapeutic intervention.
DEEP picker is a deep neural network for accurate deconvolution of complex two-dimensional NMR spectra
Authors: Li Da-Wei , Hansen Alexandar L. , Yuan Chunhua , Bruschweiler-Li Lei , Brüschweiler Rafael 
Published: September 2021

AbstractThe analysis of nuclear magnetic resonance (NMR) spectra for the comprehensive and unambiguous identification and characterization of peaks is a difficult, but critically important step in all NMR analyses of complex biological molecular systems. Here, we introduce DEEP Picker, a deep neural network (DNN)-based approach for peak picking and spectral deconvolution which semi-automates the analysis of two-dimensional NMR spectra. DEEP Picker includes 8 hidden convolutional layers and was trained on a large number of synthetic spectra of known composition with variable degrees of crowdedness. We show that our method is able to correctly identify overlapping peaks, including ones that are challenging for expert spectroscopists and existing computational methods alike. We demonstrate the utility of DEEP Picker on NMR spectra of folded and intrinsically disordered proteins as well as a complex metabolomics mixture, and show how it provides access to valuable NMR information. DEEP Picker should facilitate the semi-automation and standardization of protocols for better consistency and sharing of results within the scientific community.
Ultra-thin self-healing vitrimer coatings for durable hydrophobicity
Authors: Ma Jingcheng , Porath Laura E. , Haque Md Farhadul , Sett Soumyadip , Rabbi Kazi Fazle , Nam SungWoo , Miljkovic Nenad , Evans Christopher M. 
Published: September 2021

AbstractDurable hydrophobic materials have attracted considerable interest in the last century. Currently, the most popular strategy to achieve hydrophobic coating durability is through the combination of a perfluoro-compound with a mechanically robust matrix to form a composite for coating protection. The matrix structure is typically large (thicker than 10 μm), difficult to scale to arbitrary materials, and incompatible with applications requiring nanoscale thickness such as heat transfer, water harvesting, and desalination. Here, we demonstrate durable hydrophobicity and superhydrophobicity with nanoscale-thick, perfluorinated compound-free polydimethylsiloxane vitrimers that are self-healing due to the exchange of network strands. The polydimethylsiloxane vitrimer thin film maintains excellent hydrophobicity and optical transparency after scratching, cutting, and indenting. We show that the polydimethylsiloxane vitrimer thin film can be deposited through scalable dip-coating on a variety of substrates. In contrast to previous work achieving thick durable hydrophobic coatings by passively stacking protective structures, this work presents a pathway to achieving ultra-thin (thinner than 100 nm) durable hydrophobic films.
Programmable receptors enable bacterial biosensors to detect pathological biomarkers in clinical samples
Authors: Chang Hung-Ju , Zúñiga Ana , Conejero Ismael , Voyvodic Peter L. , Gracy Jerome , Fajardo-Ruiz Elena , Cohen-Gonsaud Martin , Cambray Guillaume , Pageaux Georges-Philippe , Meszaros Magdalena , Meunier Lucy , Bonnet Jerome 
Published: September 2021

AbstractBacterial biosensors, or bactosensors, are promising agents for medical and environmental diagnostics. However, the lack of scalable frameworks to systematically program ligand detection limits their applications. Here we show how novel, clinically relevant sensing modalities can be introduced into bactosensors in a modular fashion. To do so, we have leveraged a synthetic receptor platform, termed EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) which supports the modular assembly of sensing modules onto a high-performance, generic signaling scaffold controlling gene expression in E. coli. We apply EMeRALD to detect bile salts, a biomarker of liver dysfunction, by repurposing sensing modules from enteropathogenic Vibrio species. We improve the sensitivity and lower the limit-of-detection of the sensing module by directed evolution. We then engineer a colorimetric bactosensor detecting pathological bile salt levels in serum from patients having undergone liver transplant, providing an output detectable by the naked-eye. The EMeRALD technology enables functional exploration of natural sensing modules and rapid engineering of synthetic receptors for diagnostics, environmental monitoring, and control of therapeutic microbes.
Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation
Authors: Turco Eleonora , Savova Adriana , Gere Flora , Ferrari Luca , Romanov Julia , Schuschnig Martina , Martens Sascha 
Published: September 2021

AbstractThe autophagic degradation of misfolded and ubiquitinated proteins is important for cellular homeostasis. In this process, which is governed by cargo receptors, ubiquitinated proteins are condensed into larger structures and subsequently become targets for the autophagy machinery. Here we employ in vitro reconstitution and cell biology to define the roles of the human cargo receptors p62/SQSTM1, NBR1 and TAX1BP1 in the selective autophagy of ubiquitinated substrates. We show that p62 is the major driver of ubiquitin condensate formation. NBR1 promotes condensate formation by equipping the p62-NBR1 heterooligomeric complex with a high-affinity UBA domain. Additionally, NBR1 recruits TAX1BP1 to the ubiquitin condensates formed by p62. While all three receptors interact with FIP200, TAX1BP1 is the main driver of FIP200 recruitment and thus the autophagic degradation of p62–ubiquitin condensates. In summary, our study defines the roles of all three receptors in the selective autophagy of ubiquitin condensates.
Artificial sodium-selective ionic device based on crown-ether crystals with subnanometer pores
Authors: Ye Tingyan , Hou Gaolei , Li Wen , Wang Chaofeng , Yi Kangyan , Liu Nannan , Liu Jian , Huang Shaoming , Gao Jun 
Published: September 2021

AbstractBiological sodium channels ferry sodium ions across the lipid membrane while rejecting potassium ions and other metal ions. Realizing such ion selectivity in an artificial solid-state ionic device will enable new separation technologies but remains highly challenging. In this work, we report an artificial sodium-selective ionic device, built on synthesized porous crown-ether crystals which consist of densely packed 0.26-nm-wide pores. The Na+ selectivity of the artificial sodium-selective ionic device reached 15 against K + , which is comparable to the biological counterpart, 523 against Ca2 + , which is nearly two orders of magnitude higher than the biological one, and 1128 against Mg2 + . The selectivity may arise from the size effect and molecular recognition effect. This work may contribute to the understanding of the structure-performance relationship of ion selective nanopores.
Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
Authors: Jain Yachna , Chandradoss Keerthivasan Raanin , A. V. Anjoom , Bhattacharya Jui , Lal Mohan , Bagadia Meenakshi , Singh Harpreet , Sandhu Kuljeet Singh 
Published: September 2021

AbstractThe rodents of hystricomorpha and sciuromorpha suborders exhibit remarkably lower incidence of cancer. The underlying genetic basis remains obscure. We report a convergent evolutionary split of human 3p21.31, a locus hosting a large number of tumour-suppressor genes (TSGs) and frequently deleted in several tumour types, in hystrico- and sciuromorphs. Analysis of 34 vertebrate genomes revealed that the synteny of 3p21.31 cluster is functionally and evolutionarily constrained in most placental mammals, but exhibit large genomic interruptions independently in hystricomorphs and sciuromorphs, owing to relaxation of underlying constraints. Hystrico- and sciuromorphs, therefore, escape from pro-tumorigenic co-deletion of several TSGs in cis. The split 3p21.31 sub-clusters gained proximity to proto-oncogene clusters from elsewhere, which might further nullify pro-tumorigenic impact of copy number variations due to co-deletion or co-amplification of genes with opposing effects. The split of 3p21.31 locus coincided with the accelerated rate of its gene expression and the body mass evolution of ancestral hystrico- and sciuromorphs. The genes near breakpoints were associated with the traits specific to hystrico- and sciuromorphs, implying adaptive significance. We conclude that the convergently evolved chromosomal interruptions of evolutionarily constrained 3p21.31 cluster might have impacted evolution of cancer resistance, body mass variation and ecological adaptations in hystrico- and sciuromorphs.
Social perception of young adults prolongs the lifespan of aged Drosophila
Authors: Cho Li-Chun , Yu Chih-Chieh , Kao Chih-Fei 
Published: September 2021

AbstractLifespan is modulated at distinct levels by multiple factors, including genetic backgrounds, the environment, behavior traits, metabolic status, and more interestingly, sensory perceptions. However, the effects of social perception between individuals living in the same space remain less clear. Here, we used the Drosophila model to study the influences of social perception on the lifespan of aged fruit flies. We found the lifespan of aged Drosophila is markedly prolonged after being co-housed with young adults of the same gender. Moreover, the changes of lifespan were affected by several experimental contexts: (1) the ratios of aged and young adults co-housed, (2) the chronological ages of two populations, and (3) the integrity of sensory modalities. Together, we hypothesize the chemical/physical stimuli derived from the interacting young adults are capable of interfering with the physiology and behavior of aged flies, ultimately leading to the alteration of lifespan.
Precision cooking for printed foods via multiwavelength lasers
Authors: Blutinger Jonathan David , Tsai Alissa , Storvick Erika , Seymour Gabriel , Liu Elise , Samarelli Noà , Karthik Shravan , Meijers Yorán , Lipson Hod 
Published: September 2021

AbstractAdditive manufacturing of food is a method of creating three-dimensional edible products layer-by-layer. While food printers have been in use since 2007, commercial cooking appliances to simultaneously cook and print food layers do not yet exist. A key challenge has been the spatially controlled delivery of cooking energy. Here, we explore precision laser cooking which offers precise temporal and spatial control over heat delivery and the ability to cook, broil, cut and otherwise transform food products via customized software-driven patterns, including through packaging. Using chicken as a model food, we combine the cooking capabilities of a blue laser (λ = 445 nm), a near-infrared (NIR) laser (λ = 980 nm), and a mid-infrared (MIR) laser (λ = 10.6 μm) to broil printed chicken and find that IR light browns more efficiently than blue light, NIR light can brown and cook foods through packaging, laser-cooked foods experience about 50% less cooking loss than foods broiled in an oven, and calculate the cooking resolution of a laser to be ~1 mm. Infusing software into the cooking process will enable more creative food design, allow individuals to more precisely customize their meals, disintermediate food supply chains, streamline at-home food production, and generate horizontal markets for this burgeoning industry.
RecA finds homologous DNA by reduced dimensionality search
Authors: Wiktor Jakub , Gynnå Arvid H. , Leroy Prune , Larsson Jimmy , Coceano Giovanna , Testa Ilaria , Elf Johan 
Published: September 2021

AbstractHomologous recombination is essential for the accurate repair of double-stranded DNA breaks (DSBs)1. Initially, the RecBCD complex2 resects the ends of the DSB into 3′ single-stranded DNA on which a RecA filament assembles3. Next, the filament locates the homologous repair template on the sister chromosome4. Here we directly visualize the repair of DSBs in single cells, using high-throughput microfluidics and fluorescence microscopy. We find that, in Escherichia coli, repair of DSBs between segregated sister loci is completed in 15 ± 5 min (mean ± s.d.) with minimal fitness loss. We further show that the search takes less than 9 ± 3 min (mean ± s.d) and is mediated by a thin, highly dynamic RecA filament that stretches throughout the cell. We propose that the architecture of the RecA filament effectively reduces search dimensionality. This model predicts a search time that is consistent with our measurement and is corroborated by the observation that the search time does not depend on the length of the cell or the amount of DNA. Given the abundance of RecA homologues5, we believe this model to be widely conserved across living organisms.
Non-respiratory particles emitted by guinea pigs in airborne disease transmission experiments
Authors: Asadi Sima , Tupas Manilyn J. , Barre Ramya S. , Wexler Anthony S. , Bouvier Nicole M. , Ristenpart William D. 
Published: September 2021

AbstractAnimal models are often used to assess the airborne transmissibility of various pathogens, which are typically assumed to be carried by expiratory droplets emitted directly from the respiratory tract of the infected animal. We recently established that influenza virus is also transmissible via “aerosolized fomites,” micron-scale dust particulates released from virus-contaminated surfaces (Asadi et al. in Nat Commun 11(1):4062, 2020). Here we expand on this observation, by counting and characterizing the particles emitted from guinea pig cages using an Aerodynamic Particle Sizer (APS) and an Interferometric Mie Imaging (IMI) system. Of over 9000 airborne particles emitted from guinea pig cages and directly imaged with IMI, none had an interference pattern indicative of a liquid droplet. Separate measurements of the particle count using the APS indicate that particle concentrations spike upwards immediately following animal motion, then decay exponentially with a time constant commensurate with the air exchange rate in the cage. Taken together, the results presented here raise the possibility that a non-negligible fraction of airborne influenza transmission events between guinea pigs occurs via aerosolized fomites rather than respiratory droplets, though the relative frequencies of these two routes have yet to be definitively determined.
A plant host, Nicotiana benthamiana, enables the production and study of fungal lignin-degrading enzymes
Authors: Khlystov Nikita A. , Yoshikuni Yasuo , Deutsch Samuel , Sattely Elizabeth S. 
Published: September 2021

AbstractLignin has significant potential as an abundant and renewable source for commodity chemicals yet remains vastly underutilized. Efforts towards engineering a biochemical route to the valorization of lignin are currently limited by the lack of a suitable heterologous host for the production of lignin-degrading enzymes. Here, we show that expression of fungal genes in Nicotiana benthamiana enables production of members from seven major classes of enzymes associated with lignin degradation (23 of 35 tested) in soluble form for direct use in lignin activity assays. We combinatorially characterized a subset of these enzymes in the context of model lignin dimer oxidation, revealing that fine-tuned coupling of peroxide-generators to peroxidases results in more extensive C-C bond cleavage compared to direct addition of peroxide. Comparison of peroxidase isoform activity revealed that the extent of C-C bond cleavage depends on peroxidase identity, suggesting that peroxidases are individually specialized in the context of lignin oxidation. We anticipate the use of N. benthamiana as a platform to rapidly produce a diverse array of fungal lignin-degrading enzymes will facilitate a better understanding of their concerted role in nature and unlock their potential for lignin valorization, including within the plant host itself.
Rates of contributory de novo mutation in high and low-risk autism families
Authors: Yoon Seungtai , Munoz Adriana , Yamrom Boris , Lee Yoon-ha , Andrews Peter , Marks Steven , Wang Zihua , Reeves Catherine , Winterkorn Lara , Krieger Abba M. , Buja Andreas , Pradhan Kith , Ronemus Michael , Baldwin Kristin K. , Levy Dan , Wigler Michael , Iossifov Ivan 
Published: September 2021

AbstractAutism arises in high and low-risk families. De novo mutation contributes to autism incidence in low-risk families as there is a higher incidence in the affected of the simplex families than in their unaffected siblings. But the extent of contribution in low-risk families cannot be determined solely from simplex families as they are a mixture of low and high-risk. The rate of de novo mutation in nearly pure populations of high-risk families, the multiplex families, has not previously been rigorously determined. Moreover, rates of de novo mutation have been underestimated from studies based on low resolution microarrays and whole exome sequencing. Here we report on findings from whole genome sequence (WGS) of both simplex families from the Simons Simplex Collection (SSC) and multiplex families from the Autism Genetic Resource Exchange (AGRE). After removing the multiplex samples with excessive cell-line genetic drift, we find that the contribution of de novo mutation in multiplex is significantly smaller than the contribution in simplex. We use WGS to provide high resolution CNV profiles and to analyze more than coding regions, and revise upward the rate in simplex autism due to an excess of de novo events targeting introns. Based on this study, we now estimate that de novo events contribute to 52–67% of cases of autism arising from low risk families, and 30–39% of cases of all autism.
QSPcc reduces bottlenecks in computational model simulations
Authors: Tomasoni Danilo , Paris Alessio , Giampiccolo Stefano , Reali Federico , Simoni Giulia , Marchetti Luca , Kaddi Chanchala , Neves-Zaph Susana , Priami Corrado , Azer Karim , Lombardo Rosario 
Published: September 2021

AbstractMathematical models have grown in size and complexity becoming often computationally intractable. In sensitivity analysis and optimization phases, critical for tuning, validation and qualification, these models may be run thousands of times. Scientific programming languages popular for prototyping, such as MATLAB and R, can be a bottleneck in terms of performance. Here we show a compiler-based approach, designed to be universal at handling engineering and life sciences modeling styles, that automatically translates models into fast C code. At first QSPcc is demonstrated to be crucial in enabling the research on otherwise intractable Quantitative Systems Pharmacology models, such as in rare Lysosomal Storage Disorders. To demonstrate the full value in seamlessly accelerating, or enabling, the R&D efforts in natural sciences, we then benchmark QSPcc against 8 solutions on 24 real-world projects from different scientific fields. With speed-ups of 22000x peak, and 1605x arithmetic mean, our results show consistent superior performances.