bluuebunny/crossref_metadata_2025 huggingface dataset:
A histone H3K4me1-specific binding protein is required for siRNA accumulation and DNA methylation at a subset of loci targeted by RNA-directed DNA methylation
Authors: Niu Qingfeng , Song Zhe , Tang Kai , Chen Lixian , Wang Lisi , Ban Ting , Guo Zhongxin , Kim Chanhong , Zhang Heng , Duan Cheng-Guo , Zhang Huiming , Zhu Jian-Kang , Du Jiamu , Lang Zhaobo
Published: June 2021

In plants, RNA-directed DNA methylation (RdDM) is a well-known de novo DNA methylation pathway that involves two plant-specific RNA polymerases, Pol IV and Pol V. In this study, we discovered and characterized an RdDM factor, RDM15. Through DNA methylome and genome-wide siRNA analyses, we show that RDM15 is required for RdDM-dependent DNA methylation and siRNA accumulation at a subset of RdDM target loci. We show that RDM15 contributes to Pol V-dependent downstream siRNA accumulation and interacts with NRPE3B, a subunit specific to Pol V. We also show that the C-terminal tudor domain of RDM15 specifically recognizes the histone 3 lysine 4 monomethylation (H3K4me1) mark. Structure analysis of RDM15 in complex with the H3K4me1 peptide showed that the RDM15 tudor domain specifically recognizes the monomethyllysine through an aromatic cage and a specific hydrogen bonding network; this chemical feature-based recognition mechanism differs from all previously reported monomethyllysine recognition mechanisms. RDM15 and H3K4me1 have similar genome-wide distribution patterns at RDM15-dependent RdDM target loci, establishing a link between H3K4me1 and RDM15-mediated RdDM in vivo. In summary, we have identified and characterized a histone H3K4me1-specific binding protein as an RdDM component, and structural analysis of RDM15 revealed a chemical feature-based lower methyllysine recognition mechanism.
Manifestations of metastable criticality in the long-range structure of model water glasses
Authors: Gartner Thomas E. , Torquato Salvatore , Car Roberto , Debenedetti Pablo G.
Published: June 2021

Much attention has been devoted to water’s metastable phase behavior, including polyamorphism (multiple amorphous solid phases), and the hypothesized liquid-liquid transition and associated critical point. However, the possible relationship between these phenomena remains incompletely understood. Using molecular dynamics simulations of the realistic TIP4P/2005 model, we found a striking signature of the liquid-liquid critical point in the structure of water glasses, manifested as a pronounced increase in long-range density fluctuations at pressures proximate to the critical pressure. By contrast, these signatures were absent in glasses of two model systems that lack a critical point. We also characterized the departure from equilibrium upon vitrification via the non-equilibrium index; water-like systems exhibited a strong pressure dependence in this metric, whereas simple liquids did not. These results reflect a surprising relationship between the metastable equilibrium phenomenon of liquid-liquid criticality and the non-equilibrium structure of glassy water, with implications for our understanding of water phase behavior and glass physics. Our calculations suggest a possible experimental route to probing the existence of the liquid-liquid transition in water and other fluids.
Synthetic extracellular matrices with tailored adhesiveness and degradability support lumen formation during angiogenic sprouting
Authors: Liu Jifeng , Long Hongyan , Zeuschner Dagmar , Räder Andreas F. B. , Polacheck William J. , Kessler Horst , Sorokin Lydia , Trappmann Britta
Published: June 2021

A major deficit in tissue engineering strategies is the lack of materials that promote angiogenesis, wherein endothelial cells from the host vasculature invade the implanted matrix to form new blood vessels. To determine the material properties that regulate angiogenesis, we have developed a microfluidic in vitro model in which chemokine-guided endothelial cell sprouting into a tunable hydrogel is followed by the formation of perfusable lumens. We show that long, perfusable tubes only develop if hydrogel adhesiveness and degradability are fine-tuned to support the initial collective invasion of endothelial cells and, at the same time, allow for matrix remodeling to permit the opening of lumens. These studies provide a better understanding of how cell-matrix interactions regulate angiogenesis and, therefore, constitute an important step towards optimal design criteria for tissue-engineered materials that require vascularization.
The lysosomal Ragulator complex plays an essential role in leukocyte trafficking by activating myosin II
Authors: Nakatani Takeshi , Tsujimoto Kohei , Park JeongHoon , Jo Tatsunori , Kimura Tetsuya , Hayama Yoshitomo , Konaka Hachiro , Morita Takayoshi , Kato Yasuhiro , Nishide Masayuki , Koyama Shyohei , Nada Shigeyuki , Okada Masato , Takamatsu Hyota , Kumanogoh Atsushi
Published: June 2021

Lysosomes are involved in nutrient sensing via the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 is tethered to lysosomes by the Ragulator complex, a heteropentamer in which Lamtor1 wraps around Lamtor2–5. Although the Ragulator complex is required for cell migration, the mechanisms by which it participates in cell motility remain unknown. Here, we show that lysosomes move to the uropod in motile cells, providing the platform where Lamtor1 interacts with the myosin phosphatase Rho-interacting protein (MPRIP) independently of mTORC1 and interferes with the interaction between MPRIP and MYPT1, a subunit of myosin light chain phosphatase (MLCP), thereby increasing myosin II–mediated actomyosin contraction. Additionally, formation of the complete Ragulator complex is required for leukocyte migration and pathophysiological immune responses. Together, our findings demonstrate that the lysosomal Ragulator complex plays an essential role in leukocyte migration by activating myosin II through interacting with MPRIP.
A deep learning approach to identify gene targets of a therapeutic for human splicing disorders
Authors: Gao Dadi , Morini Elisabetta , Salani Monica , Krauson Aram J. , Chekuri Anil , Sharma Neeraj , Ragavendran Ashok , Erdin Serkan , Logan Emily M. , Li Wencheng , Dakka Amal , Narasimhan Jana , Zhao Xin , Naryshkin Nikolai , Trotta Christopher R. , Effenberger Kerstin A. , Woll Matthew G. , Gabbeta Vijayalakshmi , Karp Gary , Yu Yong , Johnson Graham , Paquette William D. , Cutting Garry R. , Talkowski Michael E. , Slaugenhaupt Susan A.
Published: June 2021

Pre-mRNA splicing is a key controller of human gene expression. Disturbances in splicing due to mutation lead to dysregulated protein expression and contribute to a substantial fraction of human disease. Several classes of splicing modulator compounds (SMCs) have been recently identified and establish that pre-mRNA splicing represents a target for therapy. We describe herein the identification of BPN-15477, a SMC that restores correct splicing of ELP1 exon 20. Using transcriptome sequencing from treated fibroblast cells and a machine learning approach, we identify BPN-15477 responsive sequence signatures. We then leverage this model to discover 155 human disease genes harboring ClinVar mutations predicted to alter pre-mRNA splicing as targets for BPN-15477. Splicing assays confirm successful correction of splicing defects caused by mutations in CFTR, LIPA, MLH1 and MAPT. Subsequent validations in two disease-relevant cellular models demonstrate that BPN-15477 increases functional protein, confirming the clinical potential of our predictions.
Quantitative single-cell proteomics as a tool to characterize cellular hierarchies
Authors: Schoof Erwin M. , Furtwängler Benjamin , Üresin Nil , Rapin Nicolas , Savickas Simonas , Gentil Coline , Lechman Eric , Keller Ulrich auf dem , Dick John E. , Porse Bo T.
Published: June 2021

Large-scale single-cell analyses are of fundamental importance in order to capture biological heterogeneity within complex cell systems, but have largely been limited to RNA-based technologies. Here we present a comprehensive benchmarked experimental and computational workflow, which establishes global single-cell mass spectrometry-based proteomics as a tool for large-scale single-cell analyses. By exploiting a primary leukemia model system, we demonstrate both through pre-enrichment of cell populations and through a non-enriched unbiased approach that our workflow enables the exploration of cellular heterogeneity within this aberrant developmental hierarchy. Our approach is capable of consistently quantifying ~1000 proteins per cell across thousands of individual cells using limited instrument time. Furthermore, we develop a computational workflow (SCeptre) that effectively normalizes the data, integrates available FACS data and facilitates downstream analysis. The approach presented here lays a foundation for implementing global single-cell proteomics studies across the world.
Proline/arginine dipeptide repeat polymers derail protein folding in amyotrophic lateral sclerosis
Authors: Babu Maria , Favretto Filippo , de Opakua Alain Ibáñez , Rankovic Marija , Becker Stefan , Zweckstetter Markus
Published: June 2021

Amyotrophic lateral sclerosis and frontotemporal dementia are two neurodegenerative diseases with overlapping clinical features and the pathological hallmark of cytoplasmic deposits of misfolded proteins. The most frequent cause of familial forms of these diseases is a hexanucleotide repeat expansion in the non-coding region of theC9ORF72gene that is translated into dipeptide repeat polymers. Here we show that proline/arginine repeat polymers derail protein folding by sequestering molecular chaperones. We demonstrate that proline/arginine repeat polymers inhibit the folding catalyst activity of PPIA, an abundant molecular chaperone and prolyl isomerase in the brain that is altered in amyotrophic lateral sclerosis. NMR spectroscopy reveals that proline/arginine repeat polymers bind to the active site of PPIA. X-ray crystallography determines the atomic structure of a proline/arginine repeat polymer in complex with the prolyl isomerase and defines the molecular basis for the specificity of disease-associated proline/arginine polymer interactions. The combined data establish a toxic mechanism that is specific for proline/arginine dipeptide repeat polymers and leads to derailed protein homeostasis inC9orf72-associated neurodegenerative diseases.
Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission
Authors: Chang Xiao L. , Webb Gabriela M. , Wu Helen L. , Greene Justin M. , Abdulhaqq Shaheed , Bateman Katherine B. , Reed Jason S. , Pessoa Cleiton , Weber Whitney C. , Maier Nicholas , Chew Glen M. , Gilbride Roxanne M. , Gao Lina , Agnor Rebecca , Giobbi Travis , Torgerson Jeffrey , Siess Don , Burnett Nicole , Fischer Miranda , Shiel Oriene , Moats Cassandra , Patterson Bruce , Dhody Kush , Kelly Scott , Pourhassan Nader , Magnani Diogo M. , Smedley Jeremy , Bimber Benjamin N. , Haigwood Nancy L. , Hansen Scott G. , Brown Timothy R. , Ndhlovu Lishomwa C. , Sacha Jonah B.
Published: June 2021

In the absence of a prophylactic vaccine, the use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic, but its efficacy is hampered by incomplete patient adherence and ART-resistant variants. Here, we report that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of CCR5-tropic SHIVSF162P3. Injection of Leronlimab weekly at 10 mg/kg provides significant but partial protection, while biweekly 50 mg/kg provides complete protection from SHIV acquisition. Tissue biopsies from protected macaques post challenge show complete CCR5 receptor occupancy and an absence of viral nucleic acids. After Leronlimab washout, protected macaques remain aviremic, and adoptive transfer of hematologic cells into naïve macaques does not transmit viral infection. These data identify CCR5 blockade with Leronlimab as a promising approach to HIV prophylaxis and support initiation of clinical trials.
Multiplexed live-cell profiling with Raman probes
Authors: Chen Chen , Zhao Zhilun , Qian Naixin , Wei Shixuan , Hu Fanghao , Min Wei
Published: June 2021

Single-cell multiparameter measurement has been increasingly recognized as a key technology toward systematic understandings of complex molecular and cellular functions in biological systems. Despite extensive efforts in analytical techniques, it is still generally challenging for existing methods to decipher a large number of phenotypes in a single living cell. Herein we devise a multiplexed Raman probe panel with sharp and mutually resolvable Raman peaks to simultaneously quantify cell surface proteins, endocytosis activities, and metabolic dynamics of an individual live cell. When coupling it to whole-cell spontaneous Raman micro-spectroscopy, we demonstrate the utility of this technique in 14-plexed live-cell profiling and phenotyping under various drug perturbations. In particular, single-cell multiparameter measurement enables powerful clustering, correlation, and network analysis with biological insights. This profiling platform is compatible with live-cell cytometry, of low instrument complexity and capable of highly multiplexed measurement in a robust and straightforward manner, thereby contributing a valuable tool for both basic single-cell biology and translation applications such as high-content cell sorting and drug discovery.
Anatomical dissociation of intracerebral signals for reward and punishment prediction errors in humans
Authors: Gueguen Maëlle C. M. , Lopez-Persem Alizée , Billeke Pablo , Lachaux Jean-Philippe , Rheims Sylvain , Kahane Philippe , Minotti Lorella , David Olivier , Pessiglione Mathias , Bastin Julien
Published: June 2021

Whether maximizing rewards and minimizing punishments rely on distinct brain systems remains debated, given inconsistent results coming from human neuroimaging and animal electrophysiology studies. Bridging the gap across techniques, we recorded intracerebral activity from twenty participants while they performed an instrumental learning task. We found that both reward and punishment prediction errors (PE), estimated from computational modeling of choice behavior, correlate positively with broadband gamma activity (BGA) in several brain regions. In all cases, BGA scaled positively with the outcome (reward or punishment versus nothing) and negatively with the expectation (predictability of reward or punishment). However, reward PE were better signaled in some regions (such as the ventromedial prefrontal and lateral orbitofrontal cortex), and punishment PE in other regions (such as the anterior insula and dorsolateral prefrontal cortex). These regions might therefore belong to brain systems that differentially contribute to the repetition of rewarded choices and the avoidance of punished choices.
Critical angle reflection imaging for quantification of molecular interactions on glass surface
Authors: Ma Guangzhong , Liang Runli , Wan Zijian , Wang Shaopeng
Published: June 2021

Quantification of molecular interactions on a surface is typically achieved via label-free techniques such as surface plasmon resonance (SPR). The sensitivity of SPR originates from the characteristic that the SPR angle is sensitive to the surface refractive index change. Analogously, in another interfacial optical phenomenon, total internal reflection, the critical angle is also refractive index dependent. Therefore, surface refractive index change can also be quantified by measuring the reflectivity near the critical angle. Based on this concept, we develop a method called critical angle reflection (CAR) imaging to quantify molecular interactions on glass surface. CAR imaging can be performed on SPR imaging setups. Through a side-by-side comparison, we show that CAR is capable of most molecular interaction measurements that SPR performs, including proteins, nucleic acids and cell-based detections. In addition, we show that CAR can detect small molecule bindings and intracellular signals beyond SPR sensing range. CAR exhibits several distinct characteristics, including tunable sensitivity and dynamic range, deeper vertical sensing range, fluorescence compatibility, broader wavelength and polarization of light selection, and glass surface chemistry. We anticipate CAR can expand SPR′s capability in small molecule detection, whole cell-based detection, simultaneous fluorescence imaging, and broader conjugation chemistry.
Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade
Authors: Nielsen Sebastian R. , Strøbech Jan E. , Horton Edward R. , Jackstadt Rene , Laitala Anu , Bravo Marina C. , Maltese Giorgia , Jensen Adina R. D. , Reuten Raphael , Rafaeva Maria , Karim Saadia A. , Hwang Chang-Il , Arnes Luis , Tuveson David A. , Sansom Owen J. , Morton Jennifer P. , Erler Janine T.
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC.
Glucose-oxidase like catalytic mechanism of noble metal nanozymes
Authors: Chen Jinxing , Ma Qian , Li Minghua , Chao Daiyong , Huang Liang , Wu Weiwei , Fang Youxing , Dong Shaojun
Published: June 2021

Au nanoparticles (NPs) have been found to be excellent glucose oxidase mimics, while the catalytic processes have rarely been studied. Here, we reveal that the process of glucose oxidation catalyzed by Au NPs is as the same as that of natural glucose oxidase, namely, a two-step reaction including the dehydrogenation of glucose and the subsequent reduction of O2 to H2O2 by two electrons. Pt, Pd, Ru, Rh, and Ir NPs can also catalyze the dehydrogenation of glucose, except that O2 is preferably reduced to H2O. By the electron transfer feature of noble metal NPs, we overcame the limitation that H2O2 must be produced in the traditional two-step glucose assay and realize the rapid colorimetric detections of glucose. Inspired by the electron transport pathway in the catalytic process of natural enzymes, noble metal NPs have also been found to mimic various enzymatic electron transfer reactions including cytochrome c, coenzymes as well as nitrobenzene reductions.
A recombined Sr26 and Sr61 disease resistance gene stack in wheat encodes unrelated NLR genes
Authors: Zhang Jianping , Hewitt Timothy C. , Boshoff Willem H. P. , Dundas Ian , Upadhyaya Narayana , Li Jianbo , Patpour Mehran , Chandramohan Sutha , Pretorius Zacharias A. , Hovmøller Mogens , Schnippenkoetter Wendelin , Park Robert F. , Mago Rohit , Periyannan Sambasivam , Bhatt Dhara , Hoxha Sami , Chakraborty Soma , Luo Ming , Dodds Peter , Steuernagel Burkhard , Wulff Brande B. H. , Ayliffe Michael , McIntosh Robert A. , Zhang Peng , Lagudah Evans S.
Published: June 2021

The re-emergence of stem rust on wheat in Europe and Africa is reinforcing the ongoing need for durable resistance gene deployment. Here, we isolate from wheat, Sr26 and Sr61, with both genes independently introduced as alien chromosome introgressions from tall wheat grass (Thinopyrum ponticum). Mutational genomics and targeted exome capture identify Sr26 and Sr61 as separate single genes that encode unrelated (34.8%) nucleotide binding site leucine rich repeat proteins. Sr26 and Sr61 are each validated by transgenic complementation using endogenous and/or heterologous promoter sequences. Sr61 orthologs are absent from current Thinopyrum elongatum and wheat pan genome sequences, contrasting with Sr26 where homologues are present. Using gene-specific markers, we validate the presence of both genes on a single recombinant alien segment developed in wheat. The co-location of these genes on a small non-recombinogenic segment simplifies their deployment as a gene stack and potentially enhances their resistance durability.
A Bacillus thuringiensis Cry protein controls soybean cyst nematode in transgenic soybean plants
Authors: Kahn Theodore W. , Duck Nicholas B. , McCarville Michael T. , Schouten Laura Cooper , Schweri Kathryn , Zaitseva Jelena , Daum Julia
Published: June 2021

Plant-parasitic nematodes (PPNs) are economically important pests of agricultural crops, and soybean cyst nematode (SCN) in particular is responsible for a large amount of damage to soybean. The need for new solutions for controlling SCN is becoming increasingly urgent, due to the slow decline in effectiveness of the widely used native soybean resistance derived from genetic line PI 88788. Thus, developing transgenic traits for controlling SCN is of great interest. Here, we report a Bacillus thuringiensis delta-endotoxin, Cry14Ab, that controls SCN in transgenic soybean. Experiments in C. elegans suggest the mechanism by which the protein controls nematodes involves damaging the intestine, similar to the mechanism of Cry proteins used to control insects. Plants expressing Cry14Ab show a significant reduction in cyst numbers compared to control plants 30 days after infestation. Field trials also show a reduction in SCN egg counts compared with control plants, demonstrating that this protein has excellent potential to control PPNs in soybean.
Self-sustained green neuromorphic interfaces
Authors: Fu Tianda , Liu Xiaomeng , Fu Shuai , Woodard Trevor , Gao Hongyan , Lovley Derek R. , Yao Jun
Published: June 2021

Incorporating neuromorphic electronics in bioelectronic interfaces can provide intelligent responsiveness to environments. However, the signal mismatch between the environmental stimuli and driving amplitude in neuromorphic devices has limited the functional versatility and energy sustainability. Here we demonstrate multifunctional, self-sustained neuromorphic interfaces by achieving signal matching at the biological level. The advances rely on the unique properties of microbially produced protein nanowires, which enable both bio-amplitude (e.g., <100 mV) signal processing and energy harvesting from ambient humidity. Integrating protein nanowire-based sensors, energy devices and memristors of bio-amplitude functions yields flexible, self-powered neuromorphic interfaces that can intelligently interpret biologically relevant stimuli for smart responses. These features, coupled with the fact that protein nanowires are a green biomaterial of potential diverse functionalities, take the interfaces a step closer to biological integration.
HiC-DC+ enables systematic 3D interaction calls and differential analysis for Hi-C and HiChIP
Authors: Sahin Merve , Wong Wilfred , Zhan Yingqian , Van Deynze Kinsey , Koche Richard , Leslie Christina S.
Published: June 2021

Recent genome-wide chromosome conformation capture assays such as Hi-C and HiChIP have vastly expanded the resolution and throughput with which we can study 3D genomic architecture and function. Here, we present HiC-DC+, a software tool for Hi-C/HiChIP interaction calling and differential analysis using an efficient implementation of the HiC-DC statistical framework. HiC-DC+ integrates with popular preprocessing and visualization tools and includes topologically associating domain (TAD) and A/B compartment callers. We found that HiC-DC+ can more accurately identify enhancer-promoter interactions in H3K27ac HiChIP, as validated by CRISPRi-FlowFISH experiments, compared to existing methods. Differential HiC-DC+ analyses of published HiChIP and Hi-C data sets in settings of cellular differentiation and cohesin perturbation systematically and quantitatively recovers biological findings, including enhancer hubs, TAD aggregation, and the relationship between promoter-enhancer loop dynamics and gene expression changes. HiC-DC+ therefore provides a principled statistical analysis tool to empower genome-wide studies of 3D chromatin architecture and function.
Structural-profiling of low molecular weight RNAs by nanopore trapping/translocation using Mycobacterium smegmatis porin A
Authors: Wang Yuqin , Guan Xiaoyu , Zhang Shanyu , Liu Yao , Wang Sha , Fan Pingping , Du Xiaoyu , Yan Shuanghong , Zhang Panke , Chen Hong-Yuan , Li Wenfei , Zhang Daoqiang , Huang Shuo
Published: June 2021

Folding of RNA can produce elaborate tertiary structures, corresponding to their diverse roles in the regulation of biological activities. Direct observation of RNA structures at high resolution in their native form however remains a challenge. The large vestibule and the narrow constriction of a Mycobacterium smegmatis porin A (MspA) suggests a sensing mode called nanopore trapping/translocation, which clearly distinguishes between microRNA, small interfering RNA (siRNA), transfer RNA (tRNA) and 5 S ribosomal RNA (rRNA). To further profit from the acquired event characteristics, a custom machine learning algorithm is developed. Events from measurements with a mixture of RNA analytes can be automatically classified, reporting a general accuracy of ~93.4%. tRNAs, which possess a unique tertiary structure, report a highly distinguishable sensing feature, different from all other RNA types tested in this study. With this strategy, tRNAs from different sources are measured and a high structural conservation across different species is observed in single molecule.
Intracellular artificial supramolecules based on de novo designed Y15 peptides
Authors: Miki Takayuki , Nakai Taichi , Hashimoto Masahiro , Kajiwara Keigo , Tsutsumi Hiroshi , Mihara Hisakazu
Published: June 2021

De novo designed self-assembling peptides (SAPs) are promising building blocks of supramolecular biomaterials, which can fulfill a wide range of applications, such as scaffolds for tissue culture, three-dimensional cell culture, and vaccine adjuvants. Nevertheless, the use of SAPs in intracellular spaces has mostly been unexplored. Here, we report a self-assembling peptide, Y15 (YEYKYEYKYEYKYEY), which readily forms β-sheet structures to facilitate bottom-up synthesis of functional protein assemblies in living cells. Superfolder green fluorescent protein (sfGFP) fused to Y15 assembles into fibrils and is observed as fluorescent puncta in mammalian cells. Y15 self-assembly is validated by fluorescence anisotropy and pull-down assays. By using the Y15 platform, we demonstrate intracellular reconstitution of Nck assembly, a Src-homology 2 and 3 domain-containing adaptor protein. The artificial clusters of Nck induce N-WASP (neural Wiskott-Aldrich syndrome protein)-mediated actin polymerization, and the functional importance of Nck domain valency and density is evaluated.
Entropy generation analysis for MHD flow of water past an accelerated plate
Authors: Abdelhameed Tarek N.
Published: June 2021

This article examines the entropy generation in the magnetohydrodynamics (MHD) flow of Newtonian fluid (water) under the effect of applied magnetic in the absence of an induced magnetic field. More precisely, the flow of water is considered past an accelerated plate such that the fluid is receiving constant heating from the initial plate. The fluid disturbance away from the plate is negligible, therefore, the domain of flow is considered as semi-infinite. The flow and heat transfer problem is considered in terms of differential equations with physical conditions and then the corresponding equations for entropy generation and Bejan number are developed. The problem is solved for exact solutions using the Laplace transform and finite difference methods. Results are displayed in graphs and tables and discussed for embedded flow parameters. Results showed that the magnetic field has a strong influence on water flow, entropy generation, and Bejan number.
Author Correction: Mayetiola destructor (Diptera: Cecidomyiidae) host preference and survival on small grains with respect to leaf reflectance and phytohormone concentrations
Authors: Sadeghi Rohollah , Odubiyi Steven , Nikoukar Atoosa , Schroeder Kurtis L. , Rashed Arash
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Multi-community effects of organic and conventional farming practices in vineyards
Authors: Ostandie Noémie , Giffard Brice , Bonnard Olivier , Joubard Benjamin , Richart-Cervera Sylvie , Thiéry Denis , Rusch Adrien
Published: June 2021

Understanding the response of biodiversity to organic farming is crucial to design more sustainable agriculture. While it is known that organic farming benefits biodiversity on average, large variability in the effects of this farming system exists. Moreover, it is not clear how different practices modulate the performance of organic farming for biodiversity conservation. In this study, we investigated how the abundance and taxonomic richness of multiple species groups responds to certified organic farming and conventional farming in vineyards. Our analyses revealed that farming practices at the field scale are more important drivers of community abundance than landscape context. Organic farming enhanced the abundances of springtails (+ 31.6%) and spiders (+ 84%), had detrimental effects on pollinator abundance (− 11.6%) and soil microbial biomass (− 9.1%), and did not affect the abundance of ground beetles, mites or microarthropods. Farming practices like tillage regime, insecticide use and soil copper content drove most of the detected effects of farming system on biodiversity. Our study revealed varying effects of organic farming on biodiversity and clearly indicates the need to consider farming practices to understand the effects of farming systems on farmland biodiversity.
Fronto-striatal structures related with model-based control as an endophenotype for obsessive–compulsive disorder
Authors: Kasal Meltem I. , Besiroglu Lutfullah , Zorlu Nabi , Dikmeer Nur , Bilge Aslıhan , Durmaz Ercan , Polat Serap , Gelal Fazil , Rapp Michael , Heinz Andreas , Sebold Miriam
Published: June 2021

Recent theories suggest a shift from model-based goal-directed to model-free habitual decision-making in obsessive–compulsive disorder (OCD). However, it is yet unclear, whether this shift in the decision process is heritable. We investigated 32 patients with OCD, 27 unaffected siblings (SIBs) and 31 healthy controls (HCs) using the two-step task. We computed behavioral and reaction time analyses and fitted a computational model to assess the balance between model-based and model-free control. 80 subjects also underwent structural imaging. We observed a significant ordered effect for the shift towards model-free control in the direction OCD > SIB > HC in our computational parameter of interest. However less directed analyses revealed no shift towards model-free control in OCDs. Nonetheless, we found evidence for reduced model-based control in OCDs compared to HCs and SIBs via 2nd stage reaction time analyses. In this measure SIBs also showed higher levels of model-based control than HCs. Across all subjects these effects were associated with the surface area of the left medial/right dorsolateral prefrontal cortex. Moreover, correlations between bilateral putamen/right caudate volumes and these effects varied as a function of group: they were negative in SIBs and OCDs, but positive in HCs. Associations between fronto-striatal regions and model-based reaction time effects point to a potential endophenotype for OCD.
Reversed and increased functional connectivity in non-REM sleep suggests an altered rather than reduced state of consciousness relative to wake
Authors: Houldin Evan , Fang Zhuo , Ray Laura B. , Stojanoski Bobby , Owen Adrian M. , Fogel Stuart M.
Published: June 2021

Sleep resting state network (RSN) functional connectivity (FC) is poorly understood, particularly for rapid eye movement (REM), and in non-sleep deprived subjects. REM and non-REM (NREM) sleep involve competing drives; towards hypersynchronous cortical oscillations in NREM; and towards wake-like desynchronized oscillations in REM. This study employed simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to explore whether sleep RSN FC reflects these opposing drives. As hypothesized, this was confirmed for the majority of functional connections modulated by sleep. Further, changes were directional: e.g., positive wake correlations trended towards negative correlations in NREM and back towards positive correlations in REM. Moreover, the majority did not merely reduce magnitude, but actually either reversed and strengthened in the opposite direction, or increased in magnitude during NREM. This finding supports the notion that NREM is best expressed as having altered, rather than reduced FC. Further, as many of these functional connections comprised “higher-order” RSNs (which have been previously linked to cognition and consciousness), such as the default mode network, this finding is suggestive of possibly concomitant alterations to cognition and consciousness.
Effects of urban functional fragmentation on nitrogen dioxide (NO2) variation with anthropogenic-emission restriction in China
Authors: Meng Yuan , Wong Man Sing , Xing Hanfa , Zhu Rui , Qin Kai , Kwan Mei-Po , Lee Kwon Ho , Kwok Coco Yin Tung , Li Hon
Published: June 2021

Urban functional fragmentation plays an important role in assessing Nitrogen Dioxide (NO2) emissions and variations. While the mediated impact of anthropogenic-emission restriction has not been comprehensively discussed, the lockdown response to the novel coronavirus disease 2019 (COVID-19) provides an unprecedented opportunity to meet this goal. This study proposes a new idea to explore the effects of urban functional fragmentation on NO2 variation with anthropogenic-emission restriction in China. First, NO2 variations are quantified by an Autoregressive Integrated Moving Average with external variables-Dynamic Time Warping (SARIMAX-DTW)-based model. Then, urban functional fragmentation indices including industrial/public Edge Density (ED) and Landscape Shape Index (LSI), urban functional Aggregation Index (AI) and Number of Patches (NP) are developed. Finally, the mediated impacts of anthropogenic-emission restriction are assessed by evaluating the fragmentation-NO2 variation association before and during the lockdown during COVID-19. The findings reveal negative effects of industrial ED, public LSI, urban functional AI and NP and positive effects of public ED and industrial LSI on NO2 variation based on the restricted anthropogenic emissions. By comparing the association analysis before and during lockdown, the mediated impact of anthropogenic-emission restriction is revealed to partially increase the effect of industrial ED, industrial LSI, public LSI, urban functional AI and NP and decrease the effect of public ED on NO2 variation. This study provides scientific findings for redesigning the urban environment in related to the urban functional configuration to mitigating the air pollution, ultimately developing sustainable societies.
Comparative analysis of phenotypic plasticity sheds light on the evolution and molecular underpinnings of locust phase polyphenism
Authors: Foquet Bert , Castellanos Adrian A. , Song Hojun
Published: June 2021

Locusts exhibit one of nature’s most spectacular examples of complex phenotypic plasticity, in which changes in density cause solitary and cryptic individuals to transform into gregarious and conspicuous locusts forming large migrating swarms. We investigated how these coordinated alternative phenotypes might have evolved by studying the Central American locust and three closely related non-swarming grasshoppers in a comparative framework. By experimentally isolating and crowding during nymphal development, we induced density-dependent phenotypic plasticity and quantified the resulting behavioural, morphological, and molecular reaction norms. All four species exhibited clear plasticity, but the individual reaction norms varied among species and showed different magnitudes. Transcriptomic responses were species-specific, but density-responsive genes were functionally similar across species. There were modules of co-expressed genes that were highly correlated with plastic reaction norms, revealing a potential molecular basis of density-dependent phenotypic plasticity. These findings collectively highlight the importance of studying multiple reaction norms from a comparative perspective.
Association between nocturnal activity of the sympathetic nervous system and cognitive dysfunction in obstructive sleep apnoea
Authors: Alomri Ridwan M. , Kennedy Gerard A. , Wali Siraj Omar , Alhejaili Faris , Robinson Stephen R.
Published: June 2021

Obstructive sleep apnoea (OSA) is associated with repetitive breathing obstructions during sleep. These episodes of hypoxia and associated arousals from sleep induce physiological stress and nocturnal over-activation of the sympathetic nervous system (SNS). One consequence of OSA is impairment in a range of cognitive domains. Previous research into cognitive impairment in OSA have focussed on intermittent hypoxia and disrupted sleep, but not nocturnal over-activation of the SNS. Therefore, we investigated whether nocturnal over-activity of the SNS was associated with cognitive impairments in OSA. The extent of nocturnal SNS activation was estimated from heart rate variability (HRV), pulse wave amplitude (PWA) and stress response biomarkers (cortisol and glucose levels). OSA severity was significantly associated with PWA indices and the HRV low frequency/ high frequency ratio (p < 0.05). Morning blood glucose levels were significantly associated with the duration of a blood oxygen saturation (SaO2) < 90% (p < 0.01). PWA and HRV were significantly associated with the time taken to perform a task involving visuospatial functioning (p < 0.05), but not with impairments in sustained attention, reaction time or autobiographical memory. These results suggest that the visuospatial dysfunction observed in people with OSA is associated with increased nocturnal activity of the SNS.
Longitudinal national-level monitoring of on-farm broiler welfare identifies consistently poorly performing farms
Authors: Mullan Siobhan , Stuijfzand Bobby , Butterworth Andrew
Published: June 2021

A range of welfare outcome measures relating to on-farm welfare are monitored in UK slaughterhouses to check compliance with the European Broiler Directive. A national dataset from 438,155 batches of chickens between 2010 and 2014 and from 228,795 batches between 2016 and 2018 was analysed. The data contained information about 3.1 billion chickens. The highest mean proportion for a single condition was for ascites/oedema in 2016–2018 at 0.384%, affecting 3.9 million chickens/year sent to slaughter during that time, followed by abnormal colour/fevered at 0.324%, affecting 3.4 million chickens/year. Identifying farms most likely to have poor welfare is an important strategy for improving animal welfare overall, and for maximising the capacity for checking regulatory compliance when resources are limited. We found a greater proportion of broiler farms overall remained consistently in the best quartile (16.4%) rather than the worst quartile (6.6%). Farms that exceeded a Government ‘trigger’ threshold for poor welfare were significantly more likely to subsequently improve than ‘non-trigger’ farms, although they usually remained in the worst performing quartile of farms.
Architecting functionalized carbon microtube/carrollite nanocomposite demonstrating significant microwave characteristics
Authors: Peymanfar Reza , Selseleh-Zakerin Elnaz , Ahmadi Ali , Tavassoli Seyed Hassan
Published: June 2021

Biomass-derived materials have recently received considerable attention as lightweight, low-cost, and green microwave absorbers. On the other hand, sulfide nanostructures due to their narrow band gaps have demonstrated significant microwave characteristics. In this research, carbon microtubes were fabricated using a biowaste and then functionalized by a novel complementary solvothermal and sonochemistry method. The functionalized carbon microtubes (FCMT) were ornamented by CuCo2S4 nanoparticles as a novel spinel sulfide microwave absorber. The prepared structures illustrated narrow energy band gap and deposition of the sulfide structures augmented the polarizability, desirable for dielectric loss and microwave attenuation. Eventually, the architected structures were blended by polyacrylonitrile (PAN) to estimate their microwave absorbing and antibacterial characteristics. The antibacterial properties against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were scrupulously assessed. Noteworthy, the maximum reflection loss (RL) of the CuCo2S4/PAN with a thickness of 1.75 mm was 61.88 dB at 11.60 GHz, while the architected FCMT/PAN composite gained a broadband efficient bandwidth as wide as 7.91 GHz (RL > 10 dB) and 3.25 GHz (RL > 20 dB) with a thickness of 2.00 mm. More significantly, FCMT/CuCo2S4/PAN demonstrated an efficient bandwidth of 2.04 GHz (RL > 20 dB) with only 1.75 mm in thickness. Interestingly, FCMT/CuCo2S4/PAN and CuCo2S4/PAN composites demonstrated an electromagnetic interference shielding efficiency of more than 90 and 97% at the entire x and ku-band frequencies, respectively.
Electricity-producing Staphylococcus epidermidis counteracts Cutibacterium acnes
Authors: Marito Shinta , Keshari Sunita , Traisaeng Supitchaya , My Do Thi Tra , Balasubramaniam Arun , Adi Prakoso , Hsieh Ming-Fa , Herr Deron Raymond , Huang Chun-Ming
Published: June 2021

Staphylococcus epidermidis (S. epidermidis) ATCC 12228 was incubated with 2% polyethylene glycol (PEG)-8 Laurate to yield electricity which was measured by a voltage difference between electrodes. Production of electron was validated by a Ferrozine assay. The anti-Cutibacterium acnes (C. acnes) activity of electrogenic S. epidermidis was assessed in vitro and in vivo. The voltage change (~ 4.4 mV) reached a peak 60 min after pipetting S. epidermidis plus 2% PEG-8 Laurate onto anodes. The electricity produced by S. epidermidis caused significant growth attenuation and cell lysis of C. acnes. Intradermal injection of C. acnes and S. epidermidis plus PEG-8 Laurate into the mouse ear considerably suppressed the growth of C. acnes. This suppressive effect was noticeably reversed when cyclophilin A of S. epidermidis was inhibited, indicating the essential role of cyclophilin A in electricity production of S. epidermidis against C. acnes. In summary, we demonstrate for the first time that skin S. epidermidis, in the presence of PEG-8 Laurate, can mediate cyclophilin A to elicit an electrical current that has anti-C. acnes effects. Electricity generated by S. epidermidis may confer immediate innate immunity in acne lesions to rein in the overgrowth of C. acnes at the onset of acne vulgaris.
Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic
Authors: Xiao Xiao , Newman Chris , Buesching Christina D. , Macdonald David W. , Zhou Zhao-Min
Published: June 2021

Here we document 47,381 individuals from 38 species, including 31 protected species sold between May 2017 and November 2019 in Wuhan’s markets. We note that no pangolins (or bats) were traded, supporting reformed opinion that pangolins were not likely the spillover host at the source of the current coronavirus (COVID-19) pandemic. While we caution against the misattribution of COVID-19’s origins, the wild animals on sale in Wuhan suffered poor welfare and hygiene conditions and we detail a range of other zoonotic infections they can potentially vector. Nevertheless, in a precautionary response to COVID-19, China’s Ministries temporarily banned all wildlife trade on 26th Jan 2020 until the COVID-19 pandemic concludes, and permanently banned eating and trading terrestrial wild (non-livestock) animals for food on 24th Feb 2020. These interventions, intended to protect human health, redress previous trading and enforcement inconsistencies, and will have collateral benefits for global biodiversity conservation and animal welfare.
Feeling of guilt explains why people react differently to resource depletion warnings
Authors: Baumgartner Thomas , Lobmaier Janek S. , Ruffieux Nicole , Knoch Daria
Published: June 2021

Despite insistent warnings from climate scientists, the global environmental situation is further deteriorating. To date, only very few studies have investigated the impact of warnings on sustainable decision-making in controlled laboratory settings. Moreover, the few existing studies mainly looked at average warning reactions rather than taking individual differences into account. Here, we investigated individual differences in the reaction to resource depletion warnings and scrutinized the impact of emotions on behavioural changes by applying a resource dilemma task with warnings. Data-driven and model-free cluster analyses identified four different types of consumption behaviour. Importantly, guilt was positively related to sustainable decision-making after warnings. In contrast, a lack of guilt was associated with no behavioural change or even worse with more unsustainable behaviour after warnings. These findings contribute to the debate over effective climate change communication by demonstrating that issuing warnings about the climate crisis only leads to the intended behavioural changes if people experience guilt.
A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19
Authors: Santos-Beneit Fernando , Raškevičius Vytautas , Skeberdis Vytenis A. , Bordel Sergio
Published: June 2021

In this study we have developed a method based on Flux Balance Analysis to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19. A literature search was carried out in order to identify suitable inhibitors of these enzymes, which were confirmed by docking calculations. In total, 10 targets and 12 bioactive molecules have been predicted. Among the most promising molecules we identified Triacsin C, which inhibits ACSL3, and which has been shown to be very effective against different viruses, including positive-sense single-stranded RNA viruses. Similarly, we also identified the drug Celgosivir, which has been successfully tested in cells infected with different types of viruses such as Dengue, Zika, Hepatitis C and Influenza. Finally, other drugs targeting enzymes of lipid metabolism, carbohydrate metabolism or protein palmitoylation (such as Propylthiouracil, 2-Bromopalmitate, Lipofermata, Tunicamycin, Benzyl Isothiocyanate, Tipifarnib and Lonafarnib) are also proposed.
Author Correction: Retention of Mitochondria in Mature Human Red Blood Cells as the Result of Autophagy Impairment in Rett Syndrome
Authors: Sbardella Diego , Tundo Grazia Raffaella , Campagnolo Luisa , Valacchi Giuseppe , Orlandi Augusto , Curatolo Paolo , Borsellino Giovanna , D’Esposito Maurizio , Ciaccio Chiara , Di Cesare Silvia , Pierro Donato Di , Galasso Cinzia , Santarone Marta Elena , Hayek Joussef , Coletta Massimiliano , Marini Stefano
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.