bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractSingle-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

AbstractWhether 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

AbstractQuantification 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

AbstractPancreatic 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

AbstractAu 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

AbstractThe 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

AbstractPlant-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

AbstractIncorporating 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

AbstractRecent 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

AbstractFolding 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

AbstractDe 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

AbstractThis 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.
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

AbstractUnderstanding 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

AbstractRecent 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

AbstractSleep 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.