bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D printing of inherently nanoporous polymers via polymerization-induced phase separation
Authors: Dong Zheqin , Cui Haijun , Zhang Haodong , Wang Fei , Zhan Xiang , Mayer Frederik , Nestler Britta , Wegener Martin , Levkin Pavel A. 
Published: January 2021

Abstract3D printing offers enormous flexibility in fabrication of polymer objects with complex geometries. However, it is not suitable for fabricating large polymer structures with geometrical features at the sub-micrometer scale. Porous structure at the sub-micrometer scale can render macroscopic objects with unique properties, including similarities with biological interfaces, permeability and extremely large surface area, imperative inter alia for adsorption, separation, sensing or biomedical applications. Here, we introduce a method combining advantages of 3D printing via digital light processing and polymerization-induced phase separation, which enables formation of 3D polymer structures of digitally defined macroscopic geometry with controllable inherent porosity at the sub-micrometer scale. We demonstrate the possibility to create 3D polymer structures of highly complex geometries and spatially controlled pore sizes from 10 nm to 1000 µm. Produced hierarchical polymers combining nanoporosity with micrometer-sized pores demonstrate improved adsorption performance due to better pore accessibility and favored cell adhesion and growth for 3D cell culture due to surface porosity. This method extends the scope of applications of 3D printing to hierarchical inherently porous 3D objects combining structural features ranging from 10 nm up to cm, making them available for a wide variety of applications.
Disulfide disruption reverses mucus dysfunction in allergic airway disease
Authors: Morgan Leslie E. , Jaramillo Ana M. , Shenoy Siddharth K. , Raclawska Dorota , Emezienna Nkechinyere A. , Richardson Vanessa L. , Hara Naoko , Harder Anna Q. , NeeDell James C. , Hennessy Corinne E. , El-Batal Hassan M. , Magin Chelsea M. , Grove Villalon Diane E. , Duncan Gregg , Hanes Justin S. , Suk Jung Soo , Thornton David J. , Holguin Fernando , Janssen William J. , Thelin William R. , Evans Christopher M. 
Published: January 2021

AbstractAirway mucus is essential for lung defense, but excessive mucus in asthma obstructs airflow, leading to severe and potentially fatal outcomes. Current asthma treatments have minimal effects on mucus, and the lack of therapeutic options stems from a poor understanding of mucus function and dysfunction at a molecular level and in vivo. Biophysical properties of mucus are controlled by mucin glycoproteins that polymerize covalently via disulfide bonds. Once secreted, mucin glycopolymers can aggregate, form plugs, and block airflow. Here we show that reducing mucin disulfide bonds disrupts mucus in human asthmatics and reverses pathological effects of mucus hypersecretion in a mouse allergic asthma model. In mice, inhaled mucolytic treatment loosens mucus mesh, enhances mucociliary clearance, and abolishes airway hyperreactivity (AHR) to the bronchoprovocative agent methacholine. AHR reversal is directly related to reduced mucus plugging. These findings establish grounds for developing treatments to inhibit effects of mucus hypersecretion in asthma.
Stream-specific feedback inputs to the primate primary visual cortex
Authors: Federer Frederick , Ta’afua Seminare , Merlin Sam , Hassanpour Mahlega S. , Angelucci Alessandra 
Published: January 2021

AbstractThe sensory neocortex consists of hierarchically-organized areas reciprocally connected via feedforward and feedback circuits. Feedforward connections shape the receptive field properties of neurons in higher areas within parallel streams specialized in processing specific stimulus attributes. Feedback connections have been implicated in top-down modulations, such as attention, prediction and sensory context. However, their computational role remains unknown, partly because we lack knowledge about rules of feedback connectivity to constrain models of feedback function. For example, it is unknown whether feedback connections maintain stream-specific segregation, or integrate information across parallel streams. Using viral-mediated labeling of feedback connections arising from specific cytochrome-oxidase stripes of macaque visual area V2, here we show that feedback to the primary visual cortex (V1) is organized into parallel streams resembling the reciprocal feedforward pathways. This suggests that functionally-specialized V2 feedback channels modulate V1 responses to specific stimulus attributes, an organizational principle potentially extending to feedback pathways in other sensory systems.
RETRACTED ARTICLE:The Arabidopsis NOT4A E3 ligase promotes PGR3 expression and regulates chloroplast translation
Authors: Bailey Mark , Ivanauskaite Aiste , Grimmer Julia , Akintewe Oluwatunmise , Payne Adrienne C. , Osborne Rory , Labandera Anne-Marie , Etherington Ross D. , Rantala Marjaana , Baginsky Sacha , Mulo Paula , Gibbs Daniel J. 
Published: January 2021

AbstractChloroplast function requires the coordinated action of nuclear- and chloroplast-derived proteins, including several hundred nuclear-encoded pentatricopeptide repeat (PPR) proteins that regulate plastid mRNA metabolism. Despite their large number and importance, regulatory mechanisms controlling PPR expression are poorly understood. Here we show that the Arabidopsis NOT4A ubiquitin-ligase positively regulates the expression of PROTON GRADIENT REGULATION 3 (PGR3), a PPR protein required for translating several thylakoid-localised photosynthetic components and ribosome subunits within chloroplasts. Loss of NOT4A function leads to a strong depletion of cytochrome b6f and NAD(P)H dehydrogenase (NDH) complexes, as well as plastid 30 S ribosomes, which reduces mRNA translation and photosynthetic capacity, causing pale-yellow and slow-growth phenotypes. Quantitative transcriptome and proteome analysis of thenot4amutant reveal it lacksPGR3expression, and that its molecular defects resemble those of apgr3mutant. Furthermore, we show that normal plastid function is restored tonot4athrough transgenicPGR3expression. Our work identifies NOT4A as crucial for ensuring robust photosynthetic function during development and stress-response, through promoting PGR3 production and chloroplast translation.
Data-independent acquisition method for ubiquitinome analysis reveals regulation of circadian biology
Authors: Hansen Fynn M. , Tanzer Maria C. , Brüning Franziska , Bludau Isabell , Stafford Che , Schulman Brenda A. , Robles Maria S. , Karayel Ozge , Mann Matthias 
Published: January 2021

AbstractProtein ubiquitination is involved in virtually all cellular processes. Enrichment strategies employing antibodies targeting ubiquitin-derived diGly remnants combined with mass spectrometry (MS) have enabled investigations of ubiquitin signaling at a large scale. However, so far the power of data independent acquisition (DIA) with regards to sensitivity in single run analysis and data completeness have not yet been explored. Here, we develop a sensitive workflow combining diGly antibody-based enrichment and optimized Orbitrap-based DIA with comprehensive spectral libraries together containing more than 90,000 diGly peptides. This approach identifies 35,000 diGly peptides in single measurements of proteasome inhibitor-treated cells – double the number and quantitative accuracy of data dependent acquisition. Applied to TNF signaling, the workflow comprehensively captures known sites while adding many novel ones. An in-depth, systems-wide investigation of ubiquitination across the circadian cycle uncovers hundreds of cycling ubiquitination sites and dozens of cycling ubiquitin clusters within individual membrane protein receptors and transporters, highlighting new connections between metabolism and circadian regulation.
Reaction kinetics and interplay of two different surface states on hematite photoanodes for water oxidation
Authors: Li Jingguo , Wan Wenchao , Triana Carlos A. , Chen Hang , Zhao Yonggui , Mavrokefalos Christos K. , Patzke Greta R. 
Published: January 2021

AbstractUnderstanding the function of surface states on photoanodes is crucial for unraveling the underlying reaction mechanisms of water oxidation. For hematite photoanodes, only one type of surface states with higher oxidative energy (S1) has been proposed and verified as reaction intermediate, while the other surface state located at lower potentials (S2) was assigned to inactive or recombination sites. Through employing rate law analyses and systematical (photo)electrochemical characterizations, here we show that S2 is an active reaction intermediate for water oxidation as well. Furthermore, we demonstrate that the reaction kinetics and dynamic interactions of both S1 and S2 depend significantly on operational parameters, such as illumination intensity, nature of the electrolyte, and applied potential. These insights into the individual reaction kinetics and the interplay of both surface states are decisive for designing efficient photoanodes.
In situ NMR reveals real-time nanocrystal growth evolution via monomer-attachment or particle-coalescence
Authors: Mashiach Reut , Weissman Haim , Avram Liat , Houben Lothar , Brontvein Olga , Lavie Anna , Arunachalam Vaishali , Leskes Michal , Rybtchinski Boris , Bar-Shir Amnon 
Published: January 2021

AbstractUnderstanding inorganic nanocrystal (NC) growth dynamic pathways under their native fabrication environment remains a central goal of science, as it is crucial for rationalizing novel nanoformulations with desired architectures and functionalities. We here present an in-situ method for quantifying, in real time, NCs’ size evolution at sub-nm resolution, their concentration, and reactants consumption rate for studying NC growth mechanisms. Analyzing sequential high-resolution liquid-state 19F-NMR spectra obtained in-situ and validating by ex-situ cryoTEM, we explore the growth evolution of fluoride-based NCs (CaF2 and SrF2) in water, without disturbing the synthesis conditions. We find that the same nanomaterial (CaF2) can grow by either a particle-coalescence or classical-growth mechanism, as regulated by the capping ligand, resulting in different crystallographic properties and functional features of the fabricated NC. The ability to reveal, in real time, mechanistic pathways at which NCs grow open unique opportunities for tunning the properties of functional materials.
Transcription shapes genome-wide histone acetylation patterns
Authors: Martin Benjamin J. E. , Brind’Amour Julie , Kuzmin Anastasia , Jensen Kristoffer N. , Liu Zhen Cheng , Lorincz Matthew , Howe LeAnn J. 
Published: January 2021

AbstractHistone acetylation is a ubiquitous hallmark of transcription, but whether the link between histone acetylation and transcription is causal or consequential has not been addressed. Using immunoblot and chromatin immunoprecipitation-sequencing in S. cerevisiae, here we show that the majority of histone acetylation is dependent on transcription. This dependency is partially explained by the requirement of RNA polymerase II (RNAPII) for the interaction of H4 histone acetyltransferases (HATs) with gene bodies. Our data also confirms the targeting of HATs by transcription activators, but interestingly, promoter-bound HATs are unable to acetylate histones in the absence of transcription. Indeed, HAT occupancy alone poorly predicts histone acetylation genome-wide, suggesting that HAT activity is regulated post-recruitment. Consistent with this, we show that histone acetylation increases at nucleosomes predicted to stall RNAPII, supporting the hypothesis that this modification is dependent on nucleosome disruption during transcription. Collectively, these data show that histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.
Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity
Authors: Garcia-Cortadella R. , Schwesig G. , Jeschke C. , Illa X. , Gray Anna L. , Savage S. , Stamatidou E. , Schiessl I. , Masvidal-Codina E. , Kostarelos K. , Guimerà-Brunet A. , Sirota A. , Garrido J. A. 
Published: January 2021

AbstractGraphene active sensors have demonstrated promising capabilities for the detection of electrophysiological signals in the brain. Their functional properties, together with their flexibility as well as their expected stability and biocompatibility have raised them as a promising building block for large-scale sensing neural interfaces. However, in order to provide reliable tools for neuroscience and biomedical engineering applications, the maturity of this technology must be thoroughly studied. Here, we evaluate the performance of 64-channel graphene sensor arrays in terms of homogeneity, sensitivity and stability using a wireless, quasi-commercial headstage and demonstrate the biocompatibility of epicortical graphene chronic implants. Furthermore, to illustrate the potential of the technology to detect cortical signals from infra-slow to high-gamma frequency bands, we perform proof-of-concept long-term wireless recording in a freely behaving rodent. Our work demonstrates the maturity of the graphene-based technology, which represents a promising candidate for chronic, wide frequency band neural sensing interfaces.
Self-assembled organic nanomedicine enables ultrastable photo-to-heat converting theranostics in the second near-infrared biowindow
Authors: Xiang Huijing , Zhao Lingzhi , Yu Luodan , Chen Hongzhong , Wei Chenyang , Chen Yu , Zhao Yanli 
Published: January 2021

AbstractDevelopment of organic theranostic agents that are active in the second near-infrared (NIR-II, 1000–1700 nm) biowindow is of vital significance for treating deep-seated tumors. However, studies on organic NIR-II absorbing agents for photo-to-heat energy-converting theranostics are still rare simply because of tedious synthetic routes to construct extended π systems in the NIR-II region. Herein, we design a convenient strategy to engineer highly stable organic NIR-II absorbing theranostic nanoparticles (Nano-BFF) for effective phototheranostic applications via co-assembling first NIR (NIR-I, 650–1000 nm) absorbing boron difluoride formazanate (BFF) dye with a biocompatible polymer, endowing the Nano-BFF with remarkable theranostic performance in the NIR-II region. In vitro and in vivo investigations validate that Nano-BFF can serve as an efficient theranostic agent to achieve photoacoustic imaging guided deep-tissue photonic hyperthermia in the NIR-II biowindow, achieving dramatic inhibition toward orthotopic hepatocellular carcinoma. This work thus provides an insight into the exploration of versatile organic NIR-II absorbing nanoparticles toward future practical applications.
Topographic maps representing haptic numerosity reveals distinct sensory representations in supramodal networks
Authors: Hofstetter Shir , Cai Yuxuan , Harvey Ben M. , Dumoulin Serge O. 
Published: January 2021

AbstractDedicated maps for cognitive quantities such as timing, size and numerosity support the view that topography is a general principle of brain organization. To date, however, all of these maps were driven by the visual system. Here, we ask whether there are supramodal topographic maps representing cognitive dimensions irrespective of the stimulated sensory modality. We measured haptically and visually driven numerosity-selective neural responses using model-based analyses and ultra-high field (7T) fMRI. We found topographically organized neural populations tuned to haptic numerosity. The responses to visual or haptic numerosity shared a similar cortical network. However, the maps of the two modalities only partially overlap. Thus, although both visual and haptic numerosities are processed in a similar supramodal functional network, the underlying neural populations may be related, but distinct. Therefore, we hypothesize that overlap between modality-specific maps facilitates cross-modal interactions and supramodal representation of cognitive quantities.
Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)
Authors: van Kampen Jeroen J. A. , van de Vijver David A. M. C. , Fraaij Pieter L. A. , Haagmans Bart L. , Lamers Mart M. , Okba Nisreen , van den Akker Johannes P. C. , Endeman Henrik , Gommers Diederik A. M. P. J. , Cornelissen Jan J. , Hoek Rogier A. S. , van der Eerden Menno M. , Hesselink Dennis A. , Metselaar Herold J. , Verbon Annelies , de Steenwinkel Jurriaan E. M. , Aron Georgina I. , van Gorp Eric C. M. , van Boheemen Sander , Voermans Jolanda C. , Boucher Charles A. B. , Molenkamp Richard , Koopmans Marion P. G. , Geurtsvankessel Corine , van der Eijk Annemiek A. 
Published: January 2021

AbstractKey questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5–11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4–17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.
Characterization of a new Leishmania major strain for use in a controlled human infection model
Authors: Ashwin Helen , Sadlova Jovana , Vojtkova Barbora , Becvar Tomas , Lypaczewski Patrick , Schwartz Eli , Greensted Elizabeth , Van Bocxlaer Katrien , Pasin Marion , Lipinski Kai S. , Parkash Vivak , Matlashewski Greg , Layton Alison M. , Lacey Charles J. , Jaffe Charles L. , Volf Petr , Kaye Paul M. 
Published: January 2021

AbstractLeishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical strain ofLeishmania major. Two fresh strains ofL. majorfrom Israel were initially compared by genome sequencing, in vivo infectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.
Human-driven greenhouse gas and aerosol emissions cause distinct regional impacts on extreme fire weather
Authors: Touma Danielle , Stevenson Samantha , Lehner Flavio , Coats Sloan 
Published: January 2021

AbstractAttribution studies have identified a robust anthropogenic fingerprint in increased 21st century wildfire risk. However, the risks associated with individual aspects of anthropogenic aerosol and greenhouse gases (GHG) emissions, biomass burning and land use/land cover change remain unknown. Here, we use new climate model large ensembles isolating these influences to show that GHG-driven increases in extreme fire weather conditions have been balanced by aerosol-driven cooling throughout the 20th century. This compensation is projected to disappear due to future reductions in aerosol emissions, causing unprecedented increases in extreme fire weather risk in the 21st century as GHGs continue to rise. Changes to temperature and relative humidity drive the largest shifts in extreme fire weather conditions; this is particularly apparent over the Amazon, where GHGs cause a seven-fold increase by 2080. Our results allow increased understanding of the interacting roles of anthropogenic stressors in altering the regional expression of future wildfire risk.
Mechanisms for <100> interstitial dislocation loops to diffuse in BCC iron
Authors: Gao N. , Yao Z. W. , Lu G. H. , Deng H. Q. , Gao F. 
Published: January 2021

AbstractThe mobility of dislocation loops in materials is a principle factor in understanding the mechanical strength, and the evolution of microstructures due to deformation and radiation. In body-centered cubic (BCC) iron, the common belief is that <100> interstitial dislocation loops are immobile once formed. However, using self-adaptive accelerated molecular dynamics (SSAMD), a new diffusion mechanism has been discovered for <100> interstitial dislocation loops. The key aspect of the mechanism is the changing of the habit planes between the {100} plane and the {110} plane, which provides a path for the <100> loops to diffuse one-dimensionally. The migration behavior modeled with SSAMD is further confirmed by in-situ transmission electron microscopy (TEM) measurements, and represents a significant step for understanding the formation of <100> loop walls and the mechanical behavior of BCC Fe under irradiation.
Statistically defined visual chunks engage object-based attention
Authors: Lengyel Gábor , Nagy Márton , Fiser József 
Published: January 2021

AbstractAlthough objects are the fundamental units of our representation interpreting the environment around us, it is still not clear how we handle and organize the incoming sensory information to form object representations. By utilizing previously well-documented advantages of within-object over across-object information processing, here we test whether learning involuntarily consistent visual statistical properties of stimuli that are free of any traditional segmentation cues might be sufficient to create object-like behavioral effects. Using a visual statistical learning paradigm and measuring efficiency of 3-AFC search and object-based attention, we find that statistically defined and implicitly learned visual chunks bias observers’ behavior in subsequent search tasks the same way as objects defined by visual boundaries do. These results suggest that learning consistent statistical contingencies based on the sensory input contributes to the emergence of object representations.
LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding
Authors: Shin Chun-Shik , Meng Shuxia , Garbis Spiros D. , Moradian Annie , Taylor Robert W. , Sweredoski Michael J. , Lomenick Brett , Chan David C. 
Published: January 2021

AbstractMost mitochondrial precursor polypeptides are imported from the cytosol into the mitochondrion, where they must efficiently undergo folding. Mitochondrial precursors are imported as unfolded polypeptides. For proteins of the mitochondrial matrix and inner membrane, two separate chaperone systems, HSP60 and mitochondrial HSP70 (mtHSP70), facilitate protein folding. We show that LONP1, an AAA+ protease of the mitochondrial matrix, works with the mtHSP70 chaperone system to promote mitochondrial protein folding. Inhibition of LONP1 results in aggregation of a protein subset similar to that caused by knockdown of DNAJA3, a co-chaperone of mtHSP70. LONP1 is required for DNAJA3 and mtHSP70 solubility, and its ATPase, but not its protease activity, is required for this function. In vitro, LONP1 shows an intrinsic chaperone-like activity and collaborates with mtHSP70 to stabilize a folding intermediate of OXA1L. Our results identify LONP1 as a critical factor in the mtHSP70 folding pathway and demonstrate its proposed chaperone activity.