bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of stress-induced translational control by Porphyromonas gingivalis in host cells
Authors: Knowles Alex A , Campbell Susan G , Cross Neil A , Stafford Prachi 
Published: January 2022

ABSTRACTPeriodontitis, a chronic inflammatory gum disease, is caused in part by the periodontopathogen Porphyromonas gingivalis. Infection triggers activation of host inflammatory responses which induce stresses such as oxidative stress. Under such conditions, cells can activate the Integrated Stress Response (ISR), a signalling cascade which functions to determine cellular fate, by either downregulating protein synthesis and initiating a stress-response gene expression program, or if stress cannot be overcome, initiating programmed cell death. Recent studies have implicated the ISR signalling in both host antimicrobial defences and within the pathomechanism of certain microbes.In this study, we investigated how P. gingivalis infection alters translation attenuation during oxidative stress-induced activation of the ISR pathway in oral epithelial cells. P. gingivalis infection alone did not result in ISR activation. In contrast, infection coupled with stress led to differential stress granule formation and composition, along with dysregulation of the microtubule network. Infection also heightened stress-induced translational repression, a response which could not be rescued by ISRIB, a potent ISR inhibitor. Heightened translational repression during stress was observed with both P. gingivalis conditioned media and outer membrane vesicles, implicating the role of a secretory factor, probably proteases known as gingipains, in this exacerbated translational repression. The effects of gingipain inhibitors and gingipains-deficient P. gingivalis mutants further confirmed these pathogen-specific proteases as the effector.Gingipains are known to degrade the mammalian target of rapamycin (mTOR) and these studies implicate the gingipain-mTOR axis as the effector of host translational dysregulation during stress.
Circuit-seq: Circular reconstruction of cut in vitro transposed plasmids using Nanopore sequencing
Authors: Emiliani Francesco E. , Hsu Ian , McKenna Aaron 
Published: January 2022

AbstractRecombinant DNA is a fundamental tool in biotechnology and medicine. Validation of the resulting plasmid sequence is a critical and time-consuming step, which has been dominated for the last 35 years by Sanger sequencing. As plasmid sequences grow more complex with new DNA synthesis and cloning techniques, we need new approaches that address the corresponding validation challenges at scale. Here we prototype a high-throughput plasmid sequencing approach using DNA transposition and Oxford Nanopore sequencing. Our method, Circuit-seq, creates robust, full-length, and accurate plasmid assemblies without prior knowledge of the underlying sequence for approximately $1.50 per plasmid. We demonstrate the power of Circuit-seq across a wide range of plasmid sizes and complexities, generating accurate and contiguous plasmid maps. We then leverage our long read-data to characterize epigenetic marks and estimate plasmid contamination levels. Circuit-seq scales to large numbers of samples at a lower cost than commercial Sanger sequencing, accelerating a key step in synthetic biology, with low startup costs make it practical for individual laboratories.
Genome-wide analysis ofSchistosoma mansonireveals population structure and praziquantel drug selection pressure within Ugandan hot-spot communities
Authors: Vianney Tushabe John , Berger Duncan J. , Doyle Stephen R. , Sankaranarayanan Geetha , Serubanja Joel , Nakawungu Prossy Kabuubi , Besigye Fred , Sanya Richard E. , Holroyd Nancy , Allan Fiona , Webb Emily L. , Elliott Alison M. , Berriman Matt , Cotton James A. 
Published: January 2022

AbstractPopulations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment.Author summarySchistosomiasis is caused by parasitic helminths of the genusSchistosoma.Schistosoma mansoniis the primary cause of intestinal schistosomiasis, a devastating and widespread parasitic infection that causes morbidity, death and socio-economic impact on endemic communities across the world and especially sub-Saharan Africa. Using whole-genome sequencing, we were able to elucidate the parasite population within Lake Victoria island fishing communities in Uganda which are among the major hotspots for schistosomiasis. We further assessed genetic markers that might be linked to recent observations concerning reduced susceptibility to praziquantel, the major drug used in the treatment of this disease. Whole-genome data on the population genetics ofS. mansoniin an African setting will provide a strong basis for future functional genomics or transcriptomic studies that will be key to identifying drug targets, improving existing drugs or developing new therapeutic interventions.
Machine Learning for the Identification of Viral Attachment Machinery from Respiratory Virus Sequences
Authors: Demidkin Stepan , Shwarts Maïa , Chakravarty Arijit , Joseph-McCarthy Diane 
Published: January 2022

AbstractAt the outset of an emergent viral respiratory pandemic, sequence data is among the first molecular information available. As viral attachment machinery is a key target for therapeutic and prophylactic interventions, rapid identification of viral “spike” proteins from sequence can significantly accelerate the development of medical countermeasures. For five families of respiratory viruses, covering the vast majority of airborne and droplet-transmitted diseases, host cell entry is mediated by the binding of viral surface glycoproteins that interact with a host cell receptor. In this report it is shown that sequence data for an unknown virus belonging to one of the five families above provides sufficient information to identify the protein(s) responsible for viral attachment and to permit an assignment of viral family. Random forest models that take as input a set of respiratory viral sequences can classify the protein as “spike” vs. non-spike based on predicted secondary structure elements alone (with 97.8 % correctly classified) or in combination with N-glycosylation related features (with 98.1 % correctly classified). In addition, a Random Forest model developed using the same dataset and only secondary structural elements was able to predict the respiratory virus family of each protein sequence correctly 89.0 % of the time. Models were validated through 10-fold cross-validation as well as bootstrapping. Surprisingly, we showed that secondary structural element and N-glycosylation features were sufficient for model generation. The ability to rapidly identify viral attachment machinery directly from sequence data holds the potential to accelerate the design of medical countermeasures for future pandemics.
Inhibitory IL-10-producing CD4+ T cells develop in a T-bet-dependent manner and facilitate cytomegalovirus persistence via coexpression of arginase-1
Authors: Clement Mathew , Ladell Kristin , Miners Kelly L. , Marsden Morgan , Chapman Lucy , Figueras Anna Cardus , Scott Jake , Andrews Robert , Clare Simon , Kriukova Valeriia V. , Lupyr Ksenia R. , Britanova Olga V. , Withers David R. , Jones Simon A. , Chudakov Dmitriy M. , Price David A. , Humphreys Ian R. 
Published: January 2022

ABSTRACTInhibitory CD4+ T cells have been linked with suboptimal immune responses against cancer and pathogen chronicity, but the mechanisms that underpin the development of such regulatory networks in vivo have remained obscure. To address this knowledge gap, we performed a comprehensive functional, phenotypic, and transcriptomic analysis of IL-10-producing CD4+ T cells induced by chronic infection with murine cytomegalovirus (MCMV). We identified these cells as clonally expanded and highly differentiated TH1-like cells that developed at sites of viral persistence in a T-bet-dependent manner and coexpressed arginase-1 (Arg1), which promotes the catalytic breakdown of L-arginine. Mice lacking Arg1-expressing CD4+ T cells exhibited more robust antiviral immunity and were better able to control MCMV. Conditional deletion of T-bet in the CD4+ lineage suppressed the development of these inhibitory cells and also enabled better immune control of MCMV. Collectively, these data elucidated the ontogeny of IL-10-producing CD4+ T cells and revealed a previously unappreciated mechanism of immune regulation, whereby viral persistence was facilitated by the coexpression of Arg1.
Bistable nerve conduction
Authors: Zhang Zhaoyang , Qu Zhilin 
Published: January 2022

AbstractThe essence of the nerve system is to transmit information from and to different parts of the body in response to environmental changes. Here we show that a bistable conduction behavior can occur in the nerve system, which exhibits stimulus-dependent fast and slow conduction waves. The bistable behavior is caused by a positive feedback loop of the wavefront upstroke speed, mediated by the sodium channel inactivation properties, which is further potentiated by the calcium current. This provides a mechanism for the slow and fast conduction in the same nerve system observed experimentally. We show that the bistable conduction behavior is robust with respect to the experimentally determined activation thresholds of the known sodium and calcium channel families. The theoretical insights provide a generic mechanism for stimulus-dependent fast and slow conduction in the nerve system, which is applicable to conduction in other electrically excitable tissue, such as cardiac muscles.
Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine
Authors: Wu Yangtao , Wang Shaojuan , Zhang Yali , Yuan Lunzhi , Zheng Qingbing , Wei Min , Shi Yang , Wang Zikang , Ma Jian , Wang Kai , Nie Meifeng , Xiao Jin , Huang Zehong , Chen Peiwen , Guo Huilin , Lan Miaolin , Xu Jingjing , Hou Wangheng , Hong Yunda , Chen Dabing , Sun Hui , Xiong Hualong , Zhou Ming , Liu Che , Guo Wenjie , Guo Huiyu , Gao Jiahua , Li Zhixiong , Zhang Haitao , Wang Xinrui , Li Shaowei , Cheng Tong , Zhao Qinjian , Chen Yixin , Wu Ting , Zhang Tianying , Zhang Jun , Cao Hua , Zhu Huachen , Yuan Quan , Guan Yi , Xia Ningshao 
Published: January 2022

AbstractThe widespread SARS-CoV-2 in humans results in the continuous emergence of new variants. Recently emerged Omicron variant with multiple spike mutations sharply increases the risk of breakthrough infection or reinfection, highlighting the urgent need for new vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x), which showed high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine comprised of STFK and STFK1628x elicited high titers of broad-spectrum antibodies to neutralize all 14 circulating SARS-CoV-2 variants, including Omicron; and fully protected vaccinees from intranasal SARS-CoV-2 challenges of either the ancestral strain or immune-evasive Beta variant. Strikingly, the vaccination of hamsters with the bivalent vaccine completely blocked the within-cage virus transmission to unvaccinated sentinels, for either the ancestral SARS-CoV-2 or Beta variant. Thus, our study provides new insights and antigen candidates for developing next-generation COVID-19 vaccines.
Inhibitory CCK+ basket synapse defects in mouse models of dystroglycanopathy
Authors: Jahncke Jennifer N. , Miller Daniel S. , Krush Milana , Schnell Eric , Wright Kevin M. 
Published: January 2022

ABSTRACTDystroglycan (Dag1) is a transmembrane glycoprotein that links the extracellular matrix to the actin cytoskeleton. Mutations inDag1or the genes required for its glycosylation result in dystroglycanopathy, a type of congenital muscular dystrophy characterized by a wide range of phenotypes including muscle weakness, brain defects, and cognitive impairment. We investigated interneuron (IN) development, synaptic function, and associated seizure susceptibility in multiple mouse models that reflect the wide phenotypic range of dystroglycanopathy neuropathology. Mice that model severe dystroglycanopathy due to forebrain deletion ofDag1orPomt2, which is required for Dystroglycan glycosylation, show significant impairment of CCK+/CB1R+IN development. CCK+/CB1R+IN axons failed to properly target the somatodendritic compartment of pyramidal neurons in the hippocampus, resulting in synaptic defects and increased seizure susceptibility. Mice lacking the intracellular domain of Dystroglycan have milder defects in CCK+/CB1R+IN axon targeting, but exhibit dramatic changes in inhibitory synaptic function, indicating a critical postsynaptic role of this domain. In contrast, CCK+/CB1R+IN synaptic function and seizure susceptibility was normal in mice that model mild dystroglycanopathy due to partially reduced Dystroglycan glycosylation. Collectively, these data show that inhibitory synaptic defects and elevated seizure susceptibility are hallmarks of severe dystroglycanopathy, and show that Dystroglycan plays an important role in organizing functional inhibitory synapse assembly.
Nutrient and salt depletion synergistically boosts glucose metabolism in individual bacteria
Authors: Glover Georgina , Voliotis Margaritis , Łapińska Urszula , Invergo Brandon M. , Soanes Darren , O’Neill Paul , Moore Karen , Nikolic Nela , Petrov Peter G. , Milner David S. , Roy Sumita , Heesom Kate , Richards Thomas A. , Tsaneva-Atanasova Krasimira , Pagliara Stefano 
Published: January 2022

ABSTRACTThe interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.
Environmental cell for in situ X-ray synchrotron micro-CT imaging with simultaneous acoustic measurements
Authors: Drobchik Arkady N. , Nikitin Viktor V. , Fokin Mikhail I. , Dugarov Geser A. , Shevchenko Pavel D. , Deriy Alex L. , Manakov Andrey Yu. , Kuper Konstantin E. , Duchkov Anton A. 
Published: January 2022

Synchrotron radiation provides the necessary spatial and temporal resolution for non-invasive operando studies of dynamic processes under complex environmental conditions. Here a new environmental cell for simultaneous in situ dynamic X-ray imaging and measuring acoustic properties of geological samples is presented. The primary purpose of this cell is to study gas-hydrate formation in porous geo-materials and its influence on their acoustic properties. The cell is designed for cylindrical samples of 9 mm in diameter, confining and pore pressures up to 12 MPa, and temperatures from −20°C to room temperature. The cell is portable and can be easily assembled and operated at different X-ray sources. This cell enables a wide range of experiments studying physical/chemical processes in the Earth subsurface that change the mechanical properties of rocks (geochemical reactions, phase transitions, etc.).
Systematic fuzzy Navier–Stokes equations for aerospace vehicles
Authors: Chen ZY , Meng Yahui , Wang Ruei-Yuan , Chen Timothy 
Published: January 2022

Purpose
To prove the effectiveness of the proposed design method, this study aims to propose the Fisher equation and temperature cooling fins that control high-speed aerospace vehicles.

Design/methodology/approach
A new approach whereby the control of aerospace vehicles can be achieved by fuzzy controller and appropriate Navier–Stokes equations in this article. The design of the controller based on models of Navier–Stokes equations simplified complex mathematical simulations and approximations.

Findings
If the fuzzy controller cannot stabilize the system, the Navier–Stokes fuzzy function is injected into the system as a controller tool, and the system is asymptotically stabilized by adjusting the fuzzy parameters.

Originality/value
The simulation results show that if the tuning frequency is high enough, the fuzzy controller and fuzzy observer can create chaotic movements by adjusting the dither amplitude appropriately. The demonstration of the Fisher equation and the temperature-cooled fin control problem for high-speed aerospace vehicles has displayed the benefits of combining fuzzy control with the Navier–Stokes equation.
Branding through visitors: how cultural differences affect brand co-creation in independent hotels in Iran
Authors: Ranjbaran Alireza , Shabankareh Mohammadjavad , Nazarian Alireza , Seyyedamiri Nader 
Published: January 2022

Purpose
In most countries, independent hotels are a major contributor to both national economy and the hospitality sector, but to the best of the authors’ knowledge, there is a lack of any study on brand co-creation (BCC) in independent hotels. This study aims to examine the interrelationship of moral judgement (MJ), self–brand connection, customer–brand engagement (CBE), electronic word-of-mouth (eWOM) and how BCC occurs in independent hotels and contrasts visitors’ perspectives between two different Global Leadership and Organizational Behavior Effectiveness clusters in independent hotels. Furthermore, this study also examines the moderating impact of privacy concern (PC) on the relationship between eWOM and brand co-creation.

Design/methodology/approach
Data were collected from two groups of tourists, Iranian (290) and European (224), who visited and stayed in independent hotels in some major cities in Iran. The structural equation modelling using AMOS 22 was adopted to test the hypotheses.

Findings
The study’s findings revealed that there are significant differences between two culturally different travellers in terms of selected variables, suggesting that MJ is a main antecedent of CBE, which leads to eWOM among Iranian travellers, which consequently leads to BCC. Moreover, the study’s data indicates that European travellers show a high level of PCs while staying in independent hotels in Iran, which prevents them from sharing and getting engaged in the social media, which could delay the BCC process especially in international level.

Originality/value
This study contributes to literature by providing new insights on the differences in the concept of brand co-creation between two culturally different groups in the context of independent hotels, which require special attention of independent hotel managers.
Empirical research on the competitiveness of rural tourism destinations: a practical plan for rural tourism industry post-COVID-19
Authors: Chin Chee Hua 
Published: January 2022

PurposeFollowing COVID-19, the emphasis on tourism development has shifted to rural tourism and eco-destinations for preventive practice of the three Cs – confined spaces, close contact and crowded spaces. Given the potential growth of rural tourism destinations, to the best of the authors’ knowledge, this study is conceivably the first to provide empirical evidence for rural tourism development post-COVID-19, and this study aims to examine the relationship between the potential development of rural tourism destination competitiveness alongside the inherited, created and supporting resources as perceived by domestic tourists.Design/methodology/approachThis study sampled 172 respondents who were all domestic tourists in Malaysia. A partial least square (PLS)-structural equation modeling approach was used to evaluate the developed model, with PLS estimation and hypothesis testing performed using WarpPLS software.FindingsInterestingly, the findings indicate that rural tourism destinations in Sarawak derive competitive advantage from factors that are closely associated with urban destinations (i.e. created and supporting resources), whereas rural-related factors (i.e. inherited resources) are not perceived as a contributor to their competitive advantage.Practical implicationsThe findings will assist tourism planners in constructing a deployable rural tourism destination competency index to develop policies and programmes that address specific tourism or rural development objectives in Malaysia and beyond.Originality/valueThe value of present study lies in its examination of the tourists’ perspectives on the factors that provides addition to rural competitive advantage, with an emphasis on a relatively new and contentious post-COVID-19 topic, namely, rural tourism destinations.