bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional insights into esterase-mediated macrolide resistance
Authors: Zieliński Michał , Park Jaeok , Sleno Barry , Berghuis Albert M. 
Published: March 2021

AbstractMacrolides are a class of antibiotics widely used in both medicine and agriculture. Unsurprisingly, as a consequence of their exensive usage a plethora of resistance mechanisms have been encountered in pathogenic bacteria. One of these resistance mechanisms entails the enzymatic cleavage of the macrolides’ macrolactone ring by erythromycin esterases (Eres). The most frequently identified Ere enzyme is EreA, which confers resistance to the majority of clinically used macrolides. Despite the role Eres play in macrolide resistance, research into this family enzymes has been sparse. Here, we report the first three-dimensional structures of an erythromycin esterase, EreC. EreC is an extremely close homologue of EreA, displaying more than 90% sequence identity. Two structures of this enzyme, in conjunction with in silico flexible docking studies and previously reported mutagenesis data allowed for the proposal of a detailed catalytic mechanism for the Ere family of enzymes, labeling them as metal-independent hydrolases. Also presented are substrate spectrum assays for different members of the Ere family. The results from these assays together with an examination of residue conservation for the macrolide binding site in Eres, suggests two distinct active site archetypes within the Ere enzyme family.
New material platform for superconducting transmon qubits with coherence times exceeding 0.3 milliseconds
Authors: Place Alexander P. M. , Rodgers Lila V. H. , Mundada Pranav , Smitham Basil M. , Fitzpatrick Mattias , Leng Zhaoqi , Premkumar Anjali , Bryon Jacob , Vrajitoarea Andrei , Sussman Sara , Cheng Guangming , Madhavan Trisha , Babla Harshvardhan K. , Le Xuan Hoang , Gang Youqi , Jäck Berthold , Gyenis András , Yao Nan , Cava Robert J. , de Leon Nathalie P. , Houck Andrew A. 
Published: March 2021

AbstractThe superconducting transmon qubit is a leading platform for quantum computing and quantum science. Building large, useful quantum systems based on transmon qubits will require significant improvements in qubit relaxation and coherence times, which are orders of magnitude shorter than limits imposed by bulk properties of the constituent materials. This indicates that relaxation likely originates from uncontrolled surfaces, interfaces, and contaminants. Previous efforts to improve qubit lifetimes have focused primarily on designs that minimize contributions from surfaces. However, significant improvements in the lifetime of two-dimensional transmon qubits have remained elusive for several years. Here, we fabricate two-dimensional transmon qubits that have both lifetimes and coherence times with dynamical decoupling exceeding 0.3 milliseconds by replacing niobium with tantalum in the device. We have observed increased lifetimes for seventeen devices, indicating that these material improvements are robust, paving the way for higher gate fidelities in multi-qubit processors.
A flexible ultrasensitive optoelectronic sensor array for neuromorphic vision systems
Authors: Zhu Qian-Bing , Li Bo , Yang Dan-Dan , Liu Chi , Feng Shun , Chen Mao-Lin , Sun Yun , Tian Ya-Nan , Su Xin , Wang Xiao-Mu , Qiu Song , Li Qing-Wen , Li Xiao-Ming , Zeng Hai-Bo , Cheng Hui-Ming , Sun Dong-Ming 
Published: March 2021

AbstractThe challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 107 A/W and a specific detectivity of 2 × 1016 Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 μW/cm2.
Adult-born neurons immature during learning are necessary for remote memory reconsolidation in rats
Authors: Lods Marie , Pacary Emilie , Mazier Wilfrid , Farrugia Fanny , Mortessagne Pierre , Masachs Nuria , Charrier Vanessa , Massa Federico , Cota Daniela , Ferreira Guillaume , Abrous Djoher Nora , Tronel Sophie 
Published: March 2021

AbstractMemory reconsolidation, the process by which memories are again stabilized after being reactivated, has strengthened the idea that memory stabilization is a highly plastic process. To date, the molecular and cellular bases of reconsolidation have been extensively investigated particularly within the hippocampus. However, the role of adult neurogenesis in memory reconsolidation is unclear. Here, we combined functional imaging, retroviral and chemogenetic approaches in rats to tag and manipulate different populations of rat adult-born neurons. We find that both mature and immature adult-born neurons are activated by remote memory retrieval. However, only specific silencing of the adult-born neurons immature during learning impairs remote memory retrieval-induced reconsolidation. Hence, our findings show that adult-born neurons immature during learning are required for the maintenance and update of remote memory reconsolidation.
Bayesian force fields from active learning for simulation of inter-dimensional transformation of stanene
Authors: Xie Yu , Vandermause Jonathan , Sun Lixin , Cepellotti Andrea , Kozinsky Boris 
Published: March 2021

AbstractWe present a way to dramatically accelerate Gaussian process models for interatomic force fields based on many-body kernels by mapping both forces and uncertainties onto functions of low-dimensional features. This allows for automated active learning of models combining near-quantum accuracy, built-in uncertainty, and constant cost of evaluation that is comparable to classical analytical models, capable of simulating millions of atoms. Using this approach, we perform large-scale molecular dynamics simulations of the stability of the stanene monolayer. We discover an unusual phase transformation mechanism of 2D stanene, where ripples lead to nucleation of bilayer defects, densification into a disordered multilayer structure, followed by formation of bulk liquid at high temperature or nucleation and growth of the 3D bcc crystal at low temperature. The presented method opens possibilities for rapid development of fast accurate uncertainty-aware models for simulating long-time large-scale dynamics of complex materials.
Robust anomalous metallic states and vestiges of self-duality in two-dimensional granular In-InOx composites
Authors: Zhang Xinyang , Hen Bar , Palevski Alexander , Kapitulnik Aharon 
Published: March 2021

AbstractMany experiments investigating magnetic-field tuned superconductor-insulator transition (H-SIT) often exhibit low-temperature resistance saturation, which is interpreted as an anomalous metallic phase emerging from a ‘failed superconductor’, thus challenging conventional theory. Here we study a random granular array of indium islands grown on a gateable layer of indium-oxide. By tuning the intergrain couplings, we reveal a wide range of magnetic fields where resistance saturation is observed, under conditions of careful electromagnetic filtering and within a wide range of linear response. Exposure to external broadband noise or microwave radiation is shown to strengthen the tendency of superconductivity, where at low field a global superconducting phase is restored. Increasing magnetic field unveils an ‘avoided H-SIT’ that exhibits granularity-induced logarithmic divergence of the resistance/conductance above/below that transition, pointing to possible vestiges of the original emergent duality observed in a true H-SIT. We conclude that anomalous metallic phase is intimately associated with inherent inhomogeneities, exhibiting robust behavior at attainable temperatures for strongly granular two-dimensional systems.
ADAS-viewer: web-based application for integrative analysis of multi-omics data in Alzheimer’s disease
Authors: Han Seonggyun , Shin Jaehang , Jung Hyeim , Ryu Jane , Minassie Habtamu , Nho Kwangsik , Koh Insong , Lee Younghee 
Published: March 2021

AbstractsAlzheimer’s disease (AD) is a neurodegenerative disorder and is represented by complicated biological mechanisms and complexity of brain tissue. Our understanding of the complicated molecular architecture that contributes to AD progression benefits from performing comprehensive and systemic investigations with multi-layered molecular and biological data from different brain regions. Since recently different independent studies generated various omics data in different brain regions of AD patients, multi-omics data integration can be a useful resource for better comprehensive understanding of AD. Here we present a web platform, ADAS-viewer, that provides researchers with the ability to comprehensively investigate and visualize multi-omics data from multiple brain regions of AD patients. ADAS-viewer offers means to identify functional changes in transcript and exon expression (i.e., alternative splicing) along with associated genetic or epigenetic regulatory effects. Specifically, it integrates genomic, transcriptomic, methylation, and miRNA data collected from seven different brain regions (cerebellum, temporal cortex, dorsolateral prefrontal cortex, frontal pole, inferior frontal gyrus, parahippocampal gyrus, and superior temporal gyrus) across three independent cohort datasets. ADAS-viewer is particularly useful as a web-based application for analyzing and visualizing multi-omics data across multiple brain regions at both transcript and exon level, allowing the identification of candidate biomarkers of Alzheimer’s disease.
Adjuvanted recombinant hemagglutinin H7 vaccine to highly pathogenic influenza A(H7N9) elicits high and sustained antibody responses in healthy adults
Authors: Oshansky Christine M. , King James , Lu Di , Zhou James , Pavetto Corrina , Horwith Gary , Biscardi Karen , Nguyen Bai , Treanor John J. , Chen Li-Mei , Jepson Brett ,   BPI17002 Study Coordination Team, Colfer Chad , Hylton Penny , Little James , O’Hara Michael , Tresnjak-Smith Silvija , Walker Robert , Yeh Bai , Bright Rick A. , Johnson Robert A. , Cioce Vittoria , Donis Ruben O. 
Published: March 2021

AbstractAn unprecedented number of human infections with avian influenza A(H7N9) in the fifth epidemic wave during the winter of 2016–2017 in China and their antigenic divergence from the viruses that emerged in 2013 prompted development of updated vaccines for pandemic preparedness. We report on the findings of a clinical study in healthy adults designed to evaluate the safety and immunogenicity of three dose levels of recombinant influenza vaccine derived from highly pathogenic A/Guangdong/17SF003/2016 (H7N9) virus adjuvanted with AS03 or MF59 oil-in water emulsions. Most of the six study groups meet the FDA CBER-specified vaccine licensure criterion of 70% seroprotection rate (SPR) for hemagglutination inhibition antibodies to the homologous virus. A substantial proportion of subjects show high cross-reactivity to antigenically distinct heterologous A(H7N9) viruses from the first epidemic wave of 2013. These results provide critical information to develop a pandemic response strategy and support regulatory requirements for vaccination under Emergency Use Authorization.
The formation of araneiforms by carbon dioxide venting and vigorous sublimation dynamics under martian atmospheric pressure
Authors: Mc Keown Lauren , McElwaine J. N. , Bourke M. C. , Sylvest M. E. , Patel M. R. 
Published: March 2021

AbstractThe local redistribution of granular material by sublimation of the southern seasonal $${\hbox {CO}}_2$$

CO
2

ice deposit is one of the most active surface shaping processes on Mars today. This unique geomorphic mechanism is hypothesised to be the cause of the dendritic, branching, spider-like araneiform terrain and associated fans and spots—features which are native to Mars and have no Earth analogues. However, there is a paucity of empirical data to test the validity of this hypothesis. Additionally, it is unclear whether some araneiform patterns began as radial and then grew outward, or whether troughs connected at mutual centres over time. Here we present the results of a suite of laboratory experiments undertaken to investigate if the interaction between a sublimating $${\hbox {CO}}_2$$

CO
2

ice overburden containing central vents and a porous, mobile regolith will mobilise grains from beneath the ice in the form of a plume to generate araneiform patterns. We quantify the branching and area of the dendritic features that form. We provide the first observations of plume activity via $${\hbox {CO}}_2$$

CO
2

sublimation and consequent erosion to form araneiform features. We show that $${\hbox {CO}}_2$$

CO
2

sublimation can be a highly efficient agent of sediment transport under present day Martian atmospheric pressure and that morphometry is governed by the Shields parameter.
In depth characterisation of the biomolecular coronas of polymer coated inorganic nanoparticles with differential centrifugal sedimentation
Authors: Perez-Potti André , Lopez Hender , Pelaz Beatriz , Abdelmonem Abuelmagd , Soliman Mahmoud G. , Schoen Ingmar , Kelly Philip M. , Dawson Kenneth A. , Parak Wolfgang J. , Krpetic Zeljka , Monopoli Marco P. 
Published: March 2021

AbstractAdvances in nanofabrication methods have enabled the tailoring of new strategies towards the controlled production of nanoparticles with attractive applications in healthcare. In many cases, their characterisation remains a big challenge, particularly for small-sized functional nanoparticles of 5 nm diameter or smaller, where current particle sizing techniques struggle to provide the required sensitivity and accuracy. There is a clear need for the development of new reliable characterisation approaches for the physico-chemical characterisation of nanoparticles with significant accuracy, particularly for the analysis of the particles in the presence of complex biological fluids. Herein, we show that the Differential Centrifugal Sedimentation can be utilised as a high-precision tool for the reliable characterisation of functional nanoparticles of different materials. We report a method to correlate the sedimentation shift with the polymer and biomolecule adsorption on the nanoparticle surface, validating the developed core–shell model. We also highlight its limit when measuring nanoparticles of smaller size and the need to use several complementary methods when characterising nanoparticle corona complexes.
Individuals with dyslexia use a different visual sampling strategy to read text
Authors: Franzen Léon , Stark Zoey , Johnson Aaron P. 
Published: March 2021

AbstractIndividuals with dyslexia present with reading-related deficits including inaccurate and/or less fluent word recognition and poor decoding abilities. Slow reading speed and worse text comprehension can occur as secondary consequences of these deficits. Reports of visual symptoms such as atypical eye movements during reading gave rise to a search for these deficits’ underlying mechanisms. This study sought to replicate established behavioral deficits in reading and cognitive processing speed while investigating their underlying mechanisms in more detail by developing a comprehensive profile of eye movements specific to reading in adult dyslexia. Using a validated standardized reading assessment, our findings confirm a reading speed deficit among adults with dyslexia. We observed different eye movements in readers with dyslexia across numerous eye movement metrics including the duration of a stop (i.e., fixation), the length of jumps (i.e., saccades), and the number of times a reader’s eyes expressed a jump atypical for reading. We conclude that individuals with dyslexia visually sample written information in a laborious and more effortful manner that is fundamentally different from those without dyslexia. Our findings suggest a mix of aberrant cognitive linguistic and oculomotor processes being present in adults with dyslexia.
Effects of high-intensity interval training in more or less active mice on biomechanical, biophysical and biochemical bone parameters
Authors: Polisel Emanuel E. C. , Beck Wladimir R. , Scariot Pedro P. M. , Pejon Taciane M. M. , Gobatto Claudio A. , Manchado-Gobatto Fúlvia B. 
Published: March 2021

AbstractHigh-intensity interval training (HIIT) is of scientific interest due its role in improving physical fitness, but the effects of HIIT on bone health need be carefully explored. Further, it is necessary to know whether HIIT effects on bone health are dependent on the physical activity levels. This may be experimentally tested since we have built a large cage (LC) that allows animals to move freely, promoting an increase of spontaneous physical activity (SPA) in comparison to a small cage (SC). Thus, we examined the effects of HIIT on biophysical, biomechanical and biochemical parameters of bone tissue of C57BL/6J mice living in cages of two different sizes: small (SC) or large (LC) cages with 1320 cm2 and 4800 cm2 floor space, respectively. Male mice were subdivided into two groups within each housing type: Control (C) and Trained (T). At the end of the interventions, all mice were euthanized to extract the femur bone for biophysical, biomechanical and biochemical analyses. Based a significant interaction from two-way ANOVA, trained mice kept in large cage (but not for trained mice housed in SC) exhibited a reduction of tenacity and displacement at failure in bone. This suggests that long-term HIIT program, in addition with a more active lifestyle correlates with exerts negative effects on the bone of healthy mice. A caution must also be raised about the excessive adoption of physical training, at least regarding bone tissue. On the other hand, increased calcium was found in femur of mice housed in LC. In line with this, LC-C mice were more active (i.e. SPA) than other groups. This implies that an active lifestyle without long-term high intensity physical training seems to play a role in promoting benefits to bone tissue. Our data provides new insights for treatment of osteo-health related disorders.
Characterisation of a tripartite α-pore forming toxin from Serratia marcescens
Authors: Churchill-Angus Alicia M. , Schofield Thomas H. B. , Marlow Thomas R. , Sedelnikova Svetlana E. , Wilson Jason S. , Rafferty John B. , Baker Patrick J. 
Published: March 2021

AbstractTripartite members of the ClyA family of α-PFTs have recently been identified in a number of pathogenic Gram-negative bacteria, including the human pathogen Serratia marcescens. Structures of a Gram-negative A component and a tripartite α-PFT complete pore are unknown and a mechanism for pore formation is still uncertain. Here we characterise the tripartite SmhABC toxin from S. marcescens and propose a mechanism of pore assembly. We present the structure of soluble SmhA, as well as the soluble and pore forms of SmhB. We show that the β-tongue soluble structure is well conserved in the family and propose two conserved latches between the head and tail domains that are broken on the soluble to pore conformational change. Using the structures of individual components, sequence analysis and docking predictions we illustrate how the A, B and C protomers would assemble on the membrane to produce a complete tripartite α-PFT pore.
Highly sensitive and multiplexed one-step RT-qPCR for profiling genes involved in the circadian rhythm using microparticles
Authors: Kim Mi Yeon , Jung Seungwon , Kim Junsun , Lee Heon Jeong , Jeong Seunghwa , Sim Sang Jun , Kim Sang Kyung 
Published: March 2021

AbstractGiven the growing interest in molecular diagnosis, highly extensive and selective detection of genetic targets from a very limited amount of samples is in high demand. We demonstrated the highly sensitive and multiplexed one-step RT-qPCR platform for RNA analysis using microparticles as individual reactors. Those particles are equipped with a controlled release system of thermo-responsive materials, and are able to capture RNA targets inside. The particle-based assay can successfully quantify multiple target RNAs from only 200 pg of total RNA. The assay can also quantify target RNAs from a single cell with the aid of a pre-concentration process. We carried out 8-plex one-step RT-qPCR using tens of microparticles, which allowed extensive mRNA profiling. The circadian cycles were shown by the multiplex one-step RT-qPCR in human cell and human hair follicles. Reliable 24-plex one-step RT-qPCR was developed using a single operation in a PCR chip without any loss of performance (i.e., selectivity and sensitivity), even from a single hair. Many other disease-related transcripts can be monitored using this versatile platform. It can also be used non–invasively for samples obtained in clinics.
High-intensity leg cycling alters the molecular response to resistance exercise in the arm muscles
Authors: Moberg Marcus , Apró William , Cervenka Igor , Ekblom Björn , van Hall Gerrit , Holmberg Hans-Christer , Ruas Jorge L. , Blomstrand Eva 
Published: March 2021

AbstractThis study examined acute molecular responses to concurrent exercise involving different muscles. Eight men participated in a randomized crossover-trial with two sessions, one where they performed interval cycling followed by upper body resistance exercise (ER-Arm), and one with upper body resistance exercise only (R-Arm). Biopsies were taken from the triceps prior to and immediately, 90- and 180-min following exercise. Immediately after resistance exercise, the elevation in S6K1 activity was smaller and the 4E-BP1:eIF4E interaction greater in ER-Arm, but this acute attenuation disappeared during recovery. The protein synthetic rate in triceps was greater following exercise than at rest, with no difference between trials. The level of PGC-1α1 mRNA increased to greater extent in ER-Arm than R-Arm after 90 min of recovery, as was PGC-1α4 mRNA after both 90 and 180 min. Levels of MuRF-1 mRNA was unchanged in R-Arm, but elevated during recovery in ER-Arm, whereas MAFbx mRNA levels increased slightly in both trials. RNA sequencing in a subgroup of subjects revealed 862 differently expressed genes with ER-Arm versus R-Arm during recovery. These findings suggest that leg cycling prior to arm resistance exercise causes systemic changes that potentiate induction of specific genes in the triceps, without compromising the anabolic response.