bluuebunny/crossref_metadata_2025_split huggingface dataset:
New broad-spectrum anti-Flavivirus human antibodies with Zika virus-neutralizing potential
Authors: de Oliveira França Renato Kaylan Alves , Silva Jacyelle Medeiros , Rodrigues Lucas Silva , Maranhão Andrea Queiroz , Brigido Marcelo Macedo 
Published: April 2022

AbstractFlavivirus infections show recurrent outbreaks and can be responsible for disease complications such as Hemorrhagic Dengue Fever and Congenital Zika Virus Syndrome. Effective therapeutic interventions are still a challenge. Antibodies can provide significant protection, although antibody response may fail due to ADE (Antibody-Dependent Enhancement) reactions or immune escape mutations. To generate effective neutralizing antibodies, the choice of the target antigen is a crucial part of the process. Human anti-Flavivirus antibodies were selected from a combinatorial library displayed on a phage surface. The antibodies were selected against a mimetic peptide based on the fusion loop region in Domain II of the protein E, which is highly conserved among different Flavivirus. Four rounds of selection were performed using the synthetic peptide in two strategies: the first was using acidic elution of bound phages, and the second was applying a competing procedure. After panning, the selected VH and VL domains were determined by combining NGS and bioinformatic approaches. Three different human monoclonal antibodies were expressed as scFvs and further characterized. All showed binding capacity to Zika (ZIKV), Yellow Fever (YFV), and Dengue (DENV) viruses. Two of these antibodies, AZ1p and AZ6m, could neutralize the ZIKV infection in a PRNT assay. These new antibodies have the potential to be used in therapeutic intervention against different Flavivirus illnesses and, due to the conservation of the fusion loop region, they may be resistant to scape mutations.Author summaryThe central idea of this work is to present a possible unique therapeutic approach to combat different diseases that cause health problems annually, such as Dengue and yellow fever infections and Zika congenital syndromes. The viruses that cause these diseases, of the Flavivirus genus, typically have disease amplification reactions and evasion mechanisms of the immune response that hinder the success of specific therapies and vaccines and require new forms of effective and safe treatments. We have developed new neutralizing human antibodies so that they bind to a highly conserved region of Flavivirus, called the fusion loop, and in such a way as to avoid adverse effects associated with anti-Flavivirus antibodies. We showed that the antibodies have high cross-reactivity against different Flaviviruses and we exemplified their neutralizing capacity for Zika virus infection in an ex vivo assay. New monoclonal antibodies such as those presented here may contribute to the control of important tropical diseases in a safer and more efficient way.
Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity
Authors: Huang Shijia , Jia Aolin , Song Wen , Hessler Giuliana , Meng Yonggang , Sun Yue , Xu Lina , Laessle Henriette , Jirschitzka Jan , Ma Shoucai , Xiao Yu , Yu Dongli , Hou Jiao , Liu Ruiqi , Sun Huanhuan , Liu Xiaohui , Han Zhifu , Chang Junbiao , Parker Jane E. , Chai Jijie 
Published: April 2022

AbstractPlant nucleotide-binding leucine-rich-repeat receptors (NLRs) with an N-terminal toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded NADase activity for immune signaling. TIR-NLR (TNL) signaling requires conserved helper NLRs NRG1 and ADR1 and the lipase-like protein EDS1 that functions as a heterodimer with each of its paralogs PAD4 and SAG101. We show that TIR-containing proteins catalyze production of 2’-(5’’-phosphoribosyl)-5’-adenosine mono-/di-phosphate (pRib-AMP/ADP)in vitroandin planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP/ADP. pRib-ADP binding triggers a conformational change in the PAD4 C-terminal domain to allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP/ADP as a missing link in TIR signaling via EDS1-PAD4 and as likely second messengers for plant immunity.
Explaining flexible continuous speech comprehension from individual motor rhythms
Authors: Lubinus Christina , Keitel Anne , Obleser Jonas , Poeppel David , Rimmele Johanna M. 
Published: April 2022

AbstractWhen speech is too fast, the tracking of the acoustic signal along the auditory pathway deteriorates, leading to suboptimal speech segmentation and decoding of speech information. Thus, speech comprehension is limited by the temporal constraints of the auditory system. Here we ask whether individual differences in auditory-motor coupling strength in part shape these temporal constraints. In two behavioral experiments, we characterize individual differences in the comprehension of naturalistic speech as function of the individual synchronization between the auditory and motor systems and the preferred frequencies of the systems. Obviously, speech comprehension declined at higher speech rates. Importantly, however, both higher auditory-motor synchronization and higher spontaneous speech motor production rates were predictive of better speech-comprehension performance. Furthermore, performance increased with higher working memory capacity (Digit Span) and higher linguistic, model-based sentence predictability – particularly so at higher speech rates and for individuals with high auditory-motor synchronization. These findings support the notion of an individual preferred auditory– motor regime that allows for optimal speech processing. The data provide evidence for a model that assigns a central role to motor-system-dependent individual flexibility in continuous speech comprehension.
Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation
Authors: Quandt Jasmin , Muik Alexander , Salisch Nadine , Lui Bonny Gaby , Lutz Sebastian , Krüger Kimberly , Wallisch Ann-Kathrin , Adams-Quack Petra , Bacher Maren , Finlayson Andrew , Ozhelvaci Orkun , Vogler Isabel , Grikscheit Katharina , Hoehl Sebastian , Goetsch Udo , Ciesek Sandra , Türeci Özlem , Sahin Ugur 
Published: April 2022

AbstractOmicron is the evolutionarily most distinct SARS-CoV-2 variant (VOC) to date and displays multiple amino acid alterations located in neutralizing antibody sites of the spike (S) protein. We report here that Omicron breakthrough infection in BNT162b2 vaccinated individuals results in strong neutralizing activity not only against Omicron, but also broadly against previous SARS-CoV-2 VOCs and against SARS-CoV-1. We found that Omicron breakthrough infection mediates a robust B cell recall response, and primarily expands preformed memory B cells that recognize epitopes shared broadly by different variants, rather than inducing new B cells against strictly Omicron-specific epitopes. Our data suggest that, despite imprinting of the immune response by previous vaccination, the preformed B cell memory pool has sufficient plasticity for being refocused and quantitatively remodeled by exposure to heterologous S protein, thus allowing effective neutralization of variants that evade a previously established neutralizing antibody response.One Sentence SummaryBreakthrough infection in individuals double- and triple-vaccinated with BNT162b2 drives cross-variant neutralization and memory B cell formation.
Evidence that Nek1 does not phosphorylate Rad54-S572 during recovery from IR
Authors: Ghosh Ishita , Khalil Md Imtiaz , De Benedetti Arrigo 
Published: April 2022

ABSTRACTA main focus of the work in our lab is on the activity of Tousled Like Kinase 1 (TLK1) in the area of DNA Damage and Repair. As one of its key interactor, TLK1 phosphorylates NIMA related kinase 1 (Nek1), and Nek1 was reported by Spies et al. to phosphorylate and regulate the activity of the key HRR protein Rad541, which suggested an intriguing signal transduction pathway: TLK1>Nek1>Rad54. In an effort to confirm such relations, we now report that we have not been able to reproduce key findings from that study. Specifically, we found that Nek1 does not phosphorylate RAD54-S572 as was reported. We generated Nek1-KO mouse NT1 cells2 and Nek1-Knock-down in Hek293 (same cells as in Spies et al.), and the pRAD54-S572 signal does not change with our custom Ab, with or w/o IR. When we used an Ab from the Lobrich lab, it detected an immunoreactive band of wrong size for RAD54, which also did not change after IR even in synchronized G2 cells, contrary to their report. We also note that their P-assignment was based on guessing a weak consensus Nek1 sequence, and that site-directed mutagenesis of RAD54-S572 failed to yield biological effects in their in in vitro studies1. To conclusively establish that S572 is not a site of phosphorylation of Nek1, we carried out a IVK with purified Nek1 and RAD54 followed by MS analysis of the phosphatides, which revealed several but not S572. We also could not reproduce their copurification of Nek1-RAD54 by coIP, calling into question this interaction. Neither we could reproduce their results demonstrating the importance of Nek1 for HRR using the same SceI-mediated DR-GFP conversion assays.
Actin turnover required for adhesion-independent bleb migration
Authors: Copos Calina , Strychalski Wanda 
Published: April 2022

AbstractCell migration is critical for many vital processes, such as wound healing, as well as harmful processes, like cancer metastasis. Experiments have highlighted the diversity in migration strategies employed by cells in physiologically relevant environments. In 3D fibrous matrices and confinement between two surfaces, some cells migrate using round membrane protrusions, called blebs. In bleb-based migration, the role of substrate adhesion is thought to be minimal, and it remains unclear if a cell can migrate without any adhesion complexes. We present a 2D computational fluid-structure model of a cell using cycles of bleb expansion and retraction in a channel with several geometries. The cell model consists of a plasma membrane, an underlying actin cortex, and viscous cytoplasm. Cellular structures are immersed in viscous fluid which permeates them, and the fluid equations are solved using the method of regularized Stokeslets. Simulations show that the cell cannot effectively migrate when the actin cortex is modeled as a purely elastic material. We find that cells do migrate in rigid channels if actin turnover is included with a viscoelastic description for the cortex. Our study highlights the non-trivial relationship between cell rheology and its external environment during migration with cytoplasmic streaming.
Topographically distinct adaptive landscapes for teeth, skeletons, and size explain the adaptive radiation of Carnivora (Mammalia)
Authors: Slater Graham J. 
Published: April 2022

AbstractModels of adaptive radiation were originally developed to explain the early, rapid appearance of distinct modes of life within diversifying clades. Phylogenetic tests of this hypothesis have yielded limited support for temporally declining rates of phenotypic evolution across diverse clades, but the concept of an adaptive landscape that links form to fitness, while also crucial to these models, has received more limited attention. Using methods that assess the temporal accumulation of morphological variation and estimate the topography of the underlying adaptive landscape, I found evidence of an early partitioning of mandibulo-dental morphological variation in Carnivora (Mammalia) that occurs on an adaptive landscape with multiple peaks, consistent with classic ideas about adaptive radiation. Although strong support for this mode of adaptive radiation is present in traits related to diet, its signal is not present in body mass data or for traits related to locomotor behavior and substrate use. These findings suggest that adaptive radiations may occur along some axes of ecomorphological variation without leaving a signal in others and that their dynamics are more complex than simple univariate tests might suggest.
Frequency of change determines effectiveness of microbial response strategies in sulfidic stream microbiomes
Authors: Li Shengjie , Mosier Damon , Dong Xiaoli , Kouris Angela , Ji Guodong , Strous Marc , Diao Muhe 
Published: April 2022

AbstractNature challenges microbes with change at different frequencies and demands an effective response for survival. Here, we used controlled laboratory experiments to investigate the ecological success of different response strategies, such as post-translational modification, transcriptional regulation, and specialized versus adaptable metabolisms. For this, we inoculated replicated chemostats with an enrichment culture obtained from sulfidic stream microbiomes 16 weeks prior. The chemostats were submitted to alternatingly oxic and anoxic conditions at three frequencies, with periods of 1 day, 4 days and 16 days. The microbial response was recorded with 16S rRNA gene amplicon sequencing, shotgun metagenomics, transcriptomics and proteomics. Metagenomics resolved 26 nearly complete genomes of bacterial populations, mainly affiliated with Proteobacteria and Bacteroidetes. Almost all these populations maintained a steady growth rate under both redox conditions at all three frequencies of change. Apparently, oscillating oxic/anoxic conditions selected for generalistic species, rather than species specializing in only a single condition. Rapid (1-day) dynamics yielded more stochasticity, both in community dynamics and gene expression, indicating that bet-hedging might be an effective coping strategy for relatively rapid environmental change. Codon-usage bias, previously associated with copiotrophic and oligotrophic lifestyles, was found to be a powerful predictor of ecological success at different frequencies, with copiotrophs and oligotrophs more successful at a rapid and a slow pace of change, respectively, independent of growth rate.
Spatial-CITE-seq: spatially resolved high-plex protein and whole transcriptome co-mapping
Authors: Liu Yang , DiStasio Marcello , Su Graham , Asashima Hiromitsu , Enninful Archibald , Qin Xiaoyu , Deng Yanxiang , Bordignon Pino , Cassano Marco , Tomayko Mary , Xu Mina , Halene Stephanie , Craft Joseph E. , Hafler David , Fan Rong 
Published: April 2022

AbstractWe present spatial-CITE-seq for high-plex protein and whole transcriptome co-mapping, which was firstly demonstrated for profiling 189 proteins and transcriptome in multiple mouse tissue types. It was then applied to human tissues to measure 273 proteins and transcriptome that revealed spatially distinct germinal center reaction in tonsil and early immune activation in skin at the COVID-19 mRNA vaccine injection site. Spatial-CITE-seq may find a range of applications in biomedical research.
A 3’ UTR-derived small RNA connecting nitrogen and carbon metabolism in enteric bacteria
Authors: Walling Lauren R. , Kouse Andrew B. , Shabalina Svetlana A. , Zhang Hongen , Storz Gisela 
Published: April 2022

ABSTRACTIncreasing numbers of small, regulatory RNAs (sRNAs) corresponding to 3’ untranslated regions (UTR) are being discovered in bacteria. One such sRNA, denoted GlnZ, corresponds to the 3’ UTR of the Escherichia coli glnA mRNA encoding glutamine synthetase. Several forms of GlnZ, processed from the glnA mRNA, are detected in cells growing with limiting ammonium. GlnZ levels are regulated transcriptionally by the NtrC transcription factor and post-transcriptionally by RNase III. Consistent with the expression, E. coli cells lacking glnZ show delayed outgrowth from nitrogen starvation compared to wild type cells. Transcriptome-wide RNA-RNA interactome datasets indicated that GlnZ binds to multiple target RNAs. Immunoblot and assays of fusions confirmed GlnZ-mediated repression of glnP and sucA, encoding proteins that contribute to glutamine transport and the citric acid cycle, respectively. Although the overall sequences of GlnZ from E. coli K-12, Enterohemorrhagic E. coli and Salmonella enterica have significant differences due to various sequence insertions, all forms of the sRNA were able to regulate the two targets characterized. Together our data show that GlnZ promotes survival of E. coli under low nitrogen conditions by modulating genes that affect carbon and nitrogen flux.
Evolutionary relations between mycorrhizal symbiosis and plant–plant communication in trees
Authors: Yamawo Akira , Tomika Hagiwara , Yoshida Satomi , Misuzu Ohno , Nakajima Riku , Mori Yusuke , Hayashi Tamayo , Yamagishi Hiroki , Shiojiri Kaori 
Published: April 2022

AbstractEcological factors that drive the evolution of plant–plant communication via volatile organic compounds (VOCs) have not been elucidated. Here, we examined the relationship between type of mycorrhizal symbiosis (arbuscular mycorrhiza, AM; ectomycorrhizal mycorrhiza, ECM) and plant-plant communication within tree species. We hypothesized that ECM promotes plant-plant communication among conspecific individuals in trees, because it promotes their cooccurrence through positive plant-soil feedback. We tested communication using saplings of nine tree species with either AM or ECM, either exposed for 10 days to volatiles from an injured conspecific or not exposed. We evaluated the number of insect-damaged leaves and the area of leaf damage after 1 and 2 months in the field. Most exposed ECM-associated trees had less leaf damage than controls. However, AM-associated trees did not differ in leaf damage between treatments. We combined our results with those of previous studies and analysed the evolutionary relation between mycorrhizal type and the presence or absence of plant–plant communication within tree species. ECM symbiosis is associated with the evolution of plant–plant communication within species. These results suggest that the evolution of types of mycorrhizal symbiosis associates with the evolution of plant-plant communications within tree species.
Warranty or education?: An analysis of marketing strategy choices for remanufactured products
Authors: Wang Manman , Ang Sheng , Yang Feng , Song Jian 
Published: April 2022

PurposeImplementing effective marketing strategies can reduce consumers' perceived risks and promote the development of the remanufacturing market. The paper aims to explore the impact of two marketing strategies on the remanufacturing decisions of an original equipment manufacturer (OEM) and investigates the design of the optimal warranty service (WS) and consumer education (CE) strategies. Moreover, the authors also examine the optimal marketing strategy choices using the three criteria of OEM: profitability, consumer surplus and environmental impact (EI).Design/methodology/approachThe authors develop a stylized model by game theory, which characterizes how an OEM that produces and sells both new and remanufactured products (RPs) should design the optimal remanufacturing marketing activity, and how to choose between different remanufacturing marketing strategies. Moreover, consumer's utility theory is used to describe consumers' perception of different remanufacturing marketing strategies to derive product demand.FindingsThe results reveal that increasing the warranty and education levels will not always improve the firm's profitability; the result depends heavily on the size of the functionality-oriented consumer (FOC) segment. Remanufacturing marketing strategies might harm the OEM, consumers and environment under certain conditions. Moreover, the optimal marketing strategy selections are jointly influenced by the FOC segment and the new production cost. There exist triple-win regions in which the OEM should not hesitate to perform WS and CE.Originality/valueFew studies focus on the design and choice of remanufacturing marketing strategies, especially considering the role of consumer perceived behavior. This research contributes the behavioral remanufacturing marketing management and provides managerial implications for the implementation of OEM remanufacturing marketing strategy.
A systematic international entrepreneurship review and future research agenda
Authors: Nave Edgar , Ferreira João J. 
Published: April 2022

PurposeInternational entrepreneurship (IE) has received a considerable amount of attention in the recent decades as a result of globalization enabling access to new international markets and business opportunities. Despite the growing increase in academic publications, IE still faces certain inconsistencies, with doubts remaining as regards its boundaries and the thematic groups making up the field. The purpose of this article is to systematically analyse the IE, mapping the intellectual territory and the evolution of the field.Design/methodology/approachIndexed to Web of Science( WoS) database until 2021, from 52 journals, 130 articles were selected, applying content analyses techniques to identify the main research lines.FindingsThe results reveal that IE presents four conceptual themes/clusters: (1) international business networks and opportunities; (2) institutional environments; (3) the characteristics and motivations of entrepreneurs; and (4) internationalisation drivers and processes. Extant analysis show that IE has progressed immensely, concentrating a good diversity of subtopics and research trends. An integrative framework bringing together 27 years of publications and 67 future research lines, detailed by cluster, were also presented in this study to improve understanding and guide future studies.Originality/valueThis review makes a broad contribution to the IE literature, assisting in consolidating the academic field, expanding and complementing the results of previous theoretical–conceptual studies. We reflect and individually discuss the state of the art of the four streams that characterize IE to identify key themes, points of convergence and advance new subfields.
How opening windows and other measures decrease virus concentration in a moving car
Authors: Shu Shuai , Mitchell Thomas Elliot , Wiggins Megan Rhian Rosemary , You Sizeng , Thomas Hywel , Li Chenfeng 
Published: April 2022

PurposeDue to the ongoing Covid-19 pandemic, ventilation in a small cabin where social distancing cannot be guaranteed is extremely important. This study aims to find out the best configuration of open and closed windows in a moving car at varying speeds to improve the ventilation efficiency. The effectiveness of other mitigation measures including face masks, taxi screens and air conditioning (AC) systems are also evaluated.Design/methodology/approachEach window is given three opening levels: fully open, half open and fully closed. For a car with four windows, this yields 81 different configurations. The location of virus source is also considered, either emitting from the driver or from the rear seat passenger. Then three different travelling speeds, 5 m/s, 10 m/s and 15 m/s, are examined for the window opening/closing configurations that provide the best ventilation effect. A study into the effectiveness of face masks is realised by adjusting virus injection amounts; and the simulation of taxi screens and AC system simply requires a small modification to the car model.FindingsThe numerical studies identify the top window opening/closing configurations that provide the most efficient ventilation at different moving speeds, along with a comprehensive ranking list. The results show that fully opening all windows is not always the best choice. Simulations evaluating other mitigation measures confirm good effect of face masks and poor performance of taxi screens and AC systems.Originality/valueThis work is the first large-scale numerical simulation and parametric study about different window opening/closing configurations of a moving car. The results provide useful guides for travellers in shared cars to mitigate Covid-19 transmission risks. The findings are helpful to both individuals' health and society's recovery in the Covid-19 era and they also provide useful information to protect people from other respiratory infectious diseases such as influenza.