bluuebunny/crossref_metadata_2025 huggingface dataset:
Melanoma subpopulations that rapidly escape MAPK pathway inhibition incur DNA damage and rely on stress signalling
Authors: Yang Chen , Tian Chengzhe , Hoffman Timothy E. , Jacobsen Nicole K. , Spencer Sabrina L.
Published: March 2021

Despite the increasing number of effective anti-cancer therapies, successful treatment is limited by the development of drug resistance. While the contribution of genetic factors to drug resistance is undeniable, little is known about how drug-sensitive cells first evade drug action to proliferate in drug. Here we track the responses of thousands of single melanoma cells to BRAF inhibitors and show that a subset of cells escapes drug via non-genetic mechanisms within the first three days of treatment. Cells that escape drug rely on ATF4 stress signalling to cycle periodically in drug, experience DNA replication defects leading to DNA damage, and yet out-proliferate other cells over extended treatment. Together, our work reveals just how rapidly melanoma cells can adapt to drug treatment, generating a mutagenesis-prone subpopulation that expands over time.
Robust nucleation control via crisscross polymerization of highly coordinated DNA slats
Authors: Minev Dionis , Wintersinger Christopher M. , Ershova Anastasia , Shih William M.
Published: March 2021

Natural biomolecular assemblies such as actin filaments or microtubules can exhibit all-or-nothing polymerization in a kinetically controlled fashion. The kinetic barrier to spontaneous nucleation arises in part from positive cooperativity deriving from joint-neighbor capture, where stable capture of incoming monomers requires straddling multiple subunits on a filament end. For programmable DNA self-assembly, it is likewise desirable to suppress spontaneous nucleation to enable powerful capabilities such as all-or-nothing assembly of nanostructures larger than a single DNA origami, ultrasensitive detection, and more robust algorithmic assembly. However, existing DNA assemblies use monomers with low coordination numbers that present an effective kinetic barrier only for slow, near-reversible growth conditions. Here we introduce crisscross polymerization of elongated slat monomers that engage beyond nearest neighbors which sustains the kinetic barrier under conditions that promote fast, irreversible growth. By implementing crisscross slats as single-stranded DNA, we attain strictly seed-initiated nucleation of crisscross ribbons with distinct widths and twists.
Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment
Authors: Zhang Min , Luo Jin-Li , Sun Qianqian , Harber James , Dawson Alan G. , Nakas Apostolos , Busacca Sara , Sharkey Annabel J. , Waller David , Sheaff Michael T. , Richards Cathy , Wells-Jordan Peter , Gaba Aarti , Poile Charlotte , Baitei Essa Y. , Bzura Aleksandra , Dzialo Joanna , Jama Maymun , Le Quesne John , Bajaj Amrita , Martinson Luke , Shaw Jacqui A. , Pritchard Catrin , Kamata Tamihiro , Kuse Nathaniel , Brannan Lee , De Philip Zhang Pan , Yang Hongji , Griffiths Gareth , Wilson Gareth , Swanton Charles , Dudbridge Frank , Hollox Edward J. , Fennell Dean A.
Published: March 2021

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/−3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/−22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.
Spatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis
Authors: Mantri Madhav , Scuderi Gaetano J. , Abedini-Nassab Roozbeh , Wang Michael F. Z. , McKellar David , Shi Hao , Grodner Benjamin , Butcher Jonathan T. , De Vlaminck Iwijn
Published: March 2021

Single-cell RNA sequencing is a powerful tool to study developmental biology but does not preserve spatial information about tissue morphology and cellular interactions. Here, we combine single-cell and spatial transcriptomics with algorithms for data integration to study the development of the chicken heart from the early to late four-chambered heart stage. We create a census of the diverse cellular lineages in developing hearts, their spatial organization, and their interactions during development. Spatial mapping of differentiation transitions in cardiac lineages defines transcriptional differences between epithelial and mesenchymal cells within the epicardial lineage. Using spatially resolved expression analysis, we identify anatomically restricted expression programs, including expression of genes implicated in congenital heart disease. Last, we discover a persistent enrichment of the small, secreted peptide, thymosin beta-4, throughout coronary vascular development. Overall, our study identifies an intricate interplay between cellular differentiation and morphogenesis.
A comprehensive influenza reporter virus panel for high-throughput deep profiling of neutralizing antibodies
Authors: Creanga Adrian , Gillespie Rebecca A. , Fisher Brian E. , Andrews Sarah F. , Lederhofer Julia , Yap Christina , Hatch Liam , Stephens Tyler , Tsybovsky Yaroslav , Crank Michelle C. , Ledgerwood Julie E. , McDermott Adrian B. , Mascola John R. , Graham Barney S. , Kanekiyo Masaru
Published: March 2021

Broadly neutralizing antibodies (bnAbs) have been developed as potential countermeasures for seasonal and pandemic influenza. Deep characterization of these bnAbs and polyclonal sera provides pivotal understanding for influenza immunity and informs effective vaccine design. However, conventional virus neutralization assays require high-containment laboratories and are difficult to standardize and roboticize. Here, we build a panel of engineered influenza viruses carrying a reporter gene to replace an essential viral gene, and develop an assay using the panel for in-depth profiling of neutralizing antibodies. Replication of these viruses is restricted to cells expressing the missing viral gene, allowing it to be manipulated in a biosafety level 2 environment. We generate the neutralization profile of 24 bnAbs using a 55-virus panel encompassing the near-complete diversity of human H1N1 and H3N2, as well as pandemic subtype viruses. Our system offers in-depth profiling of influenza immunity, including the antibodies against the hemagglutinin stem, a major target of universal influenza vaccines.
Dynamics of fMRI patterns reflect sub-second activation sequences and reveal replay in human visual cortex
Authors: Wittkuhn Lennart , Schuck Nicolas W.
Published: March 2021

Neural computations are often fast and anatomically localized. Yet, investigating such computations in humans is challenging because non-invasive methods have either high temporal or spatial resolution, but not both. Of particular relevance, fast neural replay is known to occur throughout the brain in a coordinated fashion about which little is known. We develop a multivariate analysis method for functional magnetic resonance imaging that makes it possible to study sequentially activated neural patterns separated by less than 100 ms with precise spatial resolution. Human participants viewed five images individually and sequentially with speeds up to 32 ms between items. Probabilistic pattern classifiers were trained on activation patterns in visual and ventrotemporal cortex during individual image trials. Applied to sequence trials, probabilistic classifier time courses allow the detection of neural representations and their order. Order detection remains possible at speeds up to 32 ms between items (plus 100 ms per item). The frequency spectrum of the sequentiality metric distinguishes between sub- versus supra-second sequences. Importantly, applied to resting-state data our method reveals fast replay of task-related stimuli in visual cortex. This indicates that non-hippocampal replay occurs even after tasks without memory requirements and shows that our method can be used to detect such spontaneously occurring replay.
ENSO modulates wildfire activity in China
Authors: Fang Keyan , Yao Qichao , Guo Zhengtang , Zheng Ben , Du Jianhua , Qi Fangzhong , Yan Ping , Li Jie , Ou Tinghai , Liu Jane , He Maosheng , Trouet Valerie
Published: March 2021

China is a key region for understanding fire activity and the drivers of its variability under strict fire suppression policies. Here, we present a detailed fire occurrence dataset for China, the Wildfire Atlas of China (WFAC; 2005–2018), based on continuous monitoring from multiple satellites and calibrated against field observations. We find that wildfires across China mostly occur in the winter season from January to April and those fire occurrences generally show a decreasing trend after reaching a peak in 2007. Most wildfires (84%) occur in subtropical China, with two distinct clusters in its southwestern and southeastern parts. In southeastern China, wildfires are mainly promoted by low precipitation and high diurnal temperature ranges, the combination of which dries out plant tissue and fuel. In southwestern China, wildfires are mainly promoted by warm conditions that enhance evaporation from litter and dormant plant tissues. We further find a fire occurrence dipole between southwestern and southeastern China that is modulated by the El Niño-Southern Oscillation (ENSO).
Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model
Authors: Driouich Jean-Sélim , Cochin Maxime , Lingas Guillaume , Moureau Grégory , Touret Franck , Petit Paul-Rémi , Piorkowski Géraldine , Barthélémy Karine , Laprie Caroline , Coutard Bruno , Guedj Jérémie , de Lamballerie Xavier , Solas Caroline , Nougairède Antoine
Published: March 2021

Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.
Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites
Authors: Feng Gaoqian , Wines Bruce D. , Kurtovic Liriye , Chan Jo-Anne , Boeuf Philippe , Mollard Vanessa , Cozijnsen Anton , Drew Damien R. , Center Rob J. , Marshall Daniel L. , Chishimba Sandra , McFadden Geoffrey I. , Dent Arlene E. , Chelimo Kiprotich , Boyle Michelle J. , Kazura James W. , Hogarth P. Mark , Beeson James G.
Published: March 2021

A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.
Simultaneous spatiotemporal super-resolution and multi-parametric fluorescence microscopy
Authors: Sankaran Jagadish , Balasubramanian Harikrushnan , Tang Wai Hoh , Ng Xue Wen , Röllin Adrian , Wohland Thorsten
Published: March 2021

Super-resolution microscopy and single molecule fluorescence spectroscopy require mutually exclusive experimental strategies optimizing either temporal or spatial resolution. To achieve both, we implement a GPU-supported, camera-based measurement strategy that highly resolves spatial structures (~100 nm), temporal dynamics (~2 ms), and molecular brightness from the exact same data set. Simultaneous super-resolution of spatial and temporal details leads to an improved precision in estimating the diffusion coefficient of the actin binding polypeptide Lifeact and corrects structural artefacts. Multi-parametric analysis of epidermal growth factor receptor (EGFR) and Lifeact suggests that the domain partitioning of EGFR is primarily determined by EGFR-membrane interactions, possibly sub-resolution clustering and inter-EGFR interactions but is largely independent of EGFR-actin interactions. These results demonstrate that pixel-wise cross-correlation of parameters obtained from different techniques on the same data set enables robust physicochemical parameter estimation and provides biological knowledge that cannot be obtained from sequential measurements.
Understanding contact electrification at liquid–solid interfaces from surface electronic structure
Authors: Sun Mingzi , Lu Qiuyang , Wang Zhong Lin , Huang Bolong
Published: March 2021

The charge transfer phenomenon of contact electrification even exists in the liquid–solid interface by a tiny droplet on the solid surface. In this work, we have investigated the contact electrification mechanism at the liquid–solid interface from the electronic structures at the atomic level. The electronic structures display stronger modulations by the outmost shell charge transfer via surface electrostatic charge perturbation than the inter-bonding-orbital charge transfer at the liquid–solid interface, supporting more factors being involved in charge transfer via contact electrification. Meanwhile, we introduce the electrochemical cell model to quantify the charge transfer based on the pinning factor to linearly correlate the charge transfer and the electronic structures. The pinning factor exhibits a more direct visualization of the charge transfer at the liquid–solid interface. This work supplies critical guidance for describing, quantifying, and modulating the contact electrification induced charge transfer systems in triboelectric nanogenerators in future works.
Structural and functional insights into esterase-mediated macrolide resistance
Authors: Zieliński Michał , Park Jaeok , Sleno Barry , Berghuis Albert M.
Published: March 2021

Macrolides 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

The 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

The 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

Memory 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

We 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

Many 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

Abstracts

Alzheimer’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

An 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

The 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

Advances 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

Individuals 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

High-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

Tripartite 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

Given 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

This 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.
Combining initial chest CT with clinical variables in differentiating coronavirus disease 2019 (COVID-19) pneumonia from influenza pneumonia
Authors: Zhao Shuang , Huang Zixing , Zeng Hanjiang , Chen Zhixia , Luo Fengming , Zhang Chongwei , Song Bin
Published: March 2021

Coronavirus disease 2019 (COVID-19) has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 has a similar pattern of infection, clinical symptoms, and chest imaging findings to influenza pneumonia. In this retrospective study, we analysed clinical and chest CT data of 24 patients with COVID-19 and 79 patients with influenza pneumonia. Univariate analysis demonstrated that the temperature, systolic pressure, cough and sputum production could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the clinical features are 0.783 and 0.747, and the AUC value is 0.819. Univariate analysis demonstrates that nine CT features, central–peripheral distribution, superior–inferior distribution, anterior–posterior distribution, patches of GGO, GGO nodule, vascular enlargement in GGO, air bronchogram, bronchiectasis within focus, interlobular septal thickening, could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the CT features are 0.750 and 0.962, and the AUC value is 0.927. Finally, a multivariate logistic regression model combined the variables from the clinical variables and CT features models was made. The combined model contained six features: systolic blood pressure, sputum production, vascular enlargement in the GGO, GGO nodule, central–peripheral distribution and bronchiectasis within focus. The diagnostic sensitivity and specificity for the combined features are 0.87 and 0.96, and the AUC value is 0.961. In conclusion, some CT features or clinical variables can differentiate COVID-19 from influenza pneumonia. Moreover, CT features combined with clinical variables had higher diagnostic performance.
Terahertz refractive index-based morphological dilation for breast carcinoma delineation
Authors: Cassar Quentin , Caravera Samuel , MacGrogan Gaëtan , Bücher Thomas , Hillger Philipp , Pfeiffer Ullrich , Zimmer Thomas , Guillet Jean-Paul , Mounaix Patrick
Published: March 2021

This paper reports investigations led on the combination of the refractive index and morphological dilation to enhance performances towards breast tumour margin delineation during conserving surgeries. The refractive index map of invasive ductal and lobular carcinomas were constructed from an inverse electromagnetic problem. Morphological dilation combined with refractive index thresholding was conducted to classify the tissue regions as malignant or benign. A histology routine was conducted to evaluate the performances of various dilation geometries associated with different thresholds. It was found that the combination of a wide structuring element and high refractive index was improving the correctness of tissue classification in comparison to other configurations or without dilation. The method reports a sensitivity of around 80% and a specificity of 82% for the best case. These results indicate that combining the fundamental optical properties of tissues denoted by their refractive index with morphological dilation may open routes to define supporting procedures during breast-conserving surgeries.
Exploring the use of web searches for risk communication during COVID-19 in Germany
Authors: Kristensen Kaja , Lorenz Eva , May Jürgen , Strauss Ricardo
Published: March 2021

Risk communication during pandemics is an element of utmost importance. Understanding the level of public attention—a prerequisite for effective communication—implicates expensive and time-consuming surveys. We hypothesise that the relative search volume from Google Trends could be used as an indicator of public attention of a disease and its prevention measures. The search terms ‘RKI’ (Robert Koch Institute, national public health authority in Germany), ‘corona’ and ‘protective mask’ in German language were shortlisted. Cross-correlations between these terms and the reported cases from 15 February to 27 April were conducted for each German federal state. The findings were contrasted against a timeline of official communications concerning COVID-19. The highest correlations of the term ‘RKI’ with reported COVID-19 cases were found between lags of − 2 and − 12 days, meaning web searches were already performed from 2 to 12 days before case numbers increased. A similar pattern was seen for the term ‘corona’. Cross-correlations indicated that most searches on ‘protective mask’ were performed from 6 to 12 days after the peak of cases. The results for the term ‘protective mask’ indicate a degree of confusion in the population. This is supported by conflicting recommendations to wear face masks during the first wave. The relative search volumes could be a useful tool to provide timely and location-specific information on public attention for risk communication.
Elucidation of Japanese pepper (Zanthoxylum piperitum De Candolle) domestication using RAD-Seq
Authors: Premarathne Maddumage Dona Ginushika Priyadarsh , Fukutome Nami , Yamasaki Kazuaki , Hayakawa Fumiyo , Nagano Atsushi J. , Mizuno Hisataka , Ibaragi Nobuo , Nagano Yukio
Published: March 2021

Japanese pepper, Zanthoxylum piperitum, is native to Japan and has four well-known lineages (Asakura, Takahara, Budou, and Arima), which are named after their production area or morphology. Restriction-site associated DNA sequencing (RAD-Seq) was used to analyse 93 accessions from various areas, including these four lineages. Single nucleotide variant analysis was used to classify the plants into eight groups: the Asakura and Arima lineages each had two groups, the Takahara and Budou lineages each had one group, and two additional groups were present. In one Asakura group and two Arima groups, the plants were present in agricultural fields and mountains, thus representing the early stage of domestication of the Japanese pepper. The second Asakura lineage group was closely related to plants present in various areas, and this represents the second stage of domestication of this plant because, after early domestication, genetically related lineages with desirable traits spread to the periphery. These results demonstrate that domestication of Japanese pepper is ongoing. In addition, this study shows that spineless plants are polyphyletic, despite the spineless lineage being considered a subspecies of Japanese pepper.
A chain mediation model on COVID-19 symptoms and mental health outcomes in Americans, Asians and Europeans
Authors: Wang Cuiyan , Chudzicka-Czupała Agata , Tee Michael L. , Núñez María Inmaculada López , Tripp Connor , Fardin Mohammad A. , Habib Hina A. , Tran Bach X. , Adamus Katarzyna , Anlacan Joseph , García Marta E. Aparicio , Grabowski Damian , Hussain Shahzad , Hoang Men T. , Hetnał Mateusz , Le Xuan T. , Ma Wenfang , Pham Hai Q. , Reyes Patrick Wincy C. , Shirazi Mahmoud , Tan Yilin , Tee Cherica A. , Xu Linkang , Xu Ziqi , Vu Giang T. , Zhou Danqing , Chan Natalie A. , Kuruchittham Vipat , McIntyre Roger S. , Ho Cyrus S. H. , Ho Roger , Sears Samuel F.
Published: March 2021

The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. This study aimed to test the model triggered by physical symptoms resembling COVID-19 infection, in which the need for health information and perceived impact of the pandemic mediated the path sequentially, leading to adverse mental health outcomes. A cross-sectional research design with chain mediation model involving 4612 participants from participating 8 countries selected via a respondent-driven sampling strategy was used. Participants completed online questionnaires on physical symptoms, the need for health information, the Impact of Event Scale-Revised (IES-R) questionnaire and Depression, Anxiety and Stress Scale (DASS-21). The results showed that Poland and the Philippines were the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest mean scores in these areas. Chain mediation model showed the need for health information, and the perceived impact of the pandemic were sequential mediators between physical symptoms resembling COVID-19 infection (predictor) and consequent mental health status (outcome). Excessive and contradictory health information might increase the perceived impact of the pandemic. Rapid COVID-19 testing should be implemented to minimize the psychological burden associated with physical symptoms, whilst public mental health interventions could target adverse mental outcomes associated with the pandemic.