bluuebunny/crossref_metadata_2025_split huggingface dataset:
A frequent ancestral NFKB1 variant predicts risk of infection or allergy
Authors: Chong A. Y. , Brenner N. , Jimenez-Kaufmann A. , Cortes A. , Hill M. , Littlejohns T. J. , Gilchrist J. J. , Fairfax B. P. , Knight J. C. , Hodel F. , Fellay J. , McVean G. , Moreno-Estrada A. , Waterboer T. , Hill A. V. S. , Mentzer A. J. 
Published: November 2022

AbstractInfectious agents contribute significantly to the global burden of diseases, through both acute infection and their chronic sequelae. We leveraged the UK Biobank to identify genetic loci that influence humoral immune response to multiple infections. From 45 genome-wide association studies in 9,611 participants from UK Biobank, we identifiedNFKB1as a locus associated with quantitative antibody responses to multiple pathogens including those from the herpes, retro- and polyoma-virus families. An insertion-deletion variant thought to affectNFKB1expression (rs28362491), was mapped as the likely causal variant. This variant has persisted throughout hominid evolution and could play a key role in regulation of the immune response. Using 121 infection and inflammation related traits in 487,297 UK Biobank participants, we show that the deletion allele was associated with an increased risk of infection from diverse pathogens but had a protective effect against allergic disease. We propose that altered expression ofNFKB1, as a result of the deletion, modulates haematopoietic pathways, and likely impacts cell survival, antibody production, and inflammation. Taken together, we show that disruptions to the tightly regulated immune processes may tip the balance between exacerbated immune responses and allergy, or increased risk of infection and impaired resolution of inflammation.
Effects of cardiac function alterations on the risk of postoperative thrombotic complications in patients receiving endovascular aortic repair
Authors: Sun Xiaoning , Li Siting , He Yuan , Liu Yuxi , Ma Tianxiang , Zeng Rong , Liu Zhili , Chen Yu , Zheng Yuehong , Liu Xiao 
Published: November 2022

AbstractChronic heart disease (CHD) is a common comorbidity of patients receiving endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA). The ventricular systolic function determines the hemodynamic environments in aorta, and thus regulating the formation of postoperative thrombus. However, the explicit relationship between ventricular systolic function and EVAR complication of thrombotic events is unknown. Here, we proposed a three-dimensional numerical model coupled with the lumped-elements heart model, which is capable of simulating thrombus formation in diverse systolic functions. The computational results demonstrate that thrombus tended to form on the interior side of the aorta arch and iliac branches, which is consistent with the four patients’ post-operative imaging follow-up. In addition, we found that the thrombus formation has negative correlations with the maximum ventricular contractile force (r=−0.2814±0.1012) and positive correlations with the minimum ventricular contractile force (r=0.238±0.074), whereas the effect of heart rate (r=−0.0148±0.1211) on thrombus formation is not significant. In conclusion, changes in ventricular systolic function may alter the risk of thrombotic events after EVAR repair, which could provide insight into the selection of adjuvant therapy strategies for AAA patients with CHD.
Induced responses contribute to rapid plant adaptation to herbivory
Authors: Malacrinò Antonino , Böttner Laura , Nouere Sara , Huber Meret , Schäfer Martin , Xu Shuqing 
Published: November 2022

AbstractHerbivory-induced responses in plants are typical examples of phenotypic plasticity, and their evolution is thought to be driven by herbivory. However, direct evidence of the role of induced responses in plant adaptive evolution to herbivores is scarce. Here, we experimentally evolved populations of an aquatic plant (Spirodela polyrhiza, giant duckweed) and its native herbivore (Lymnaea stagnalis, freshwater snail) testing whether herbivory drives rapid adaptive evolution in plant populations using a combination of bioassays, pool-sequencing, metabolite analyses, and amplicon metagenomics. We found that snail herbivory drove rapid phenotypic changes, increased herbivory resistance, and altered genotype frequencies in the plant populations. Additional bioassays suggested that evolutionary changes of induced responses contributed to the rapid increase of plant resistance to herbivory. This study provides direct evidence that herbivory-induced responses in plants can be subjected to selection and have an adaptive role by increasing resistance to herbivores.
Production of Rabies virus-specific monoclonal antibodies and evaluation of their neutralizing potential
Authors: Soliman Rafik , Hashem Zeinb , El-Hariri Mahmoud , Abo Elyazeed Heidy , Aboul-Ella Hassan 
Published: November 2022

AbstractRabies is a severe viral infection that causes acute encephalomyelitis, with a case fatality rate of nearly 100% following the onset of neurological clinical signs. Rabies irreversible clinical signs development can be effectively avoided with post-exposure prophylaxis (PEP), which includes vaccines and anti-rabies immunoglobulins (RIGs); however, there is no treatment for symptomatic rabies. The major PEP protocol faces serious access and implementation obstacles in association with a resource-limited setting, which could be successfully overcome by substituting RIGs for monoclonal antibodies (mAbs). Lower production costs, consistent supply availability, long-term storage/stability, and an improved safety profile are all advantages of mAbs. The current work focuses on the key characteristics of currently developed mAbs against rabies and highlights their potential as a novel therapeutic approach. Using immunizing Freund’s adjuvanted emulsions of inactivated purified Vero cell rabies vaccine (PVRV, VERORAB) produced byAventis Pasteurto immunize the BALB/c mice. The immunized BALB/c mice were tested for the production of anti-rabies virus-specific antibodies using Enzyme-linked immunosorbent assay (ELISA). High-responder mice were selected for the fusion process. Hybridomas recovered from the fusion process were selected and separated from the unfused cells and unfavorable fused cells by using the selective HAT medium. Twelve days post fusion the produced hybrids were screened for production of Rabies virus-specific antibodies using ELISA. Four murine hybridomas secreting rabies virus-specific monoclonal antibodies (mAbs) have been properly developed. These 4 stable hybrids were successfully cloned into 4 stable clones, namely, 1E4, 1E9, 2F3, 4E1. The rabies virus specific monoclonal antibodies produced by the 4 selected hybridomas were of IgM isotype. Using Western Blot technique, the specificity of the produced hybrids was confirmed. The neutralizing potential of the prepared mAbs was evaluated and the efficacy of mAbs cocktail prepared from the 4 hybridomas to protect mice in post exposure therapy was determined. The mAbs cocktail given to mice at 24 hours post infection was able to offer 100% protection to mice challenged with 1000 LD50 of rabies virus strain whereas all control mice developed the disease.
Inhibiting a promiscuous GPCR: iterative discovery of bitter taste receptor ligands
Authors: Fierro Fabrizio , Peri Lior , Hübner Harald , Tabor-Schkade Alina , Waterloo Lukas , Löber Stefan , Pfeiffer Tara , Weikert Dorothee , Dingjan Tamir , Margulis Eitan , Gmeiner Peter , Niv Masha Y 
Published: November 2022

AbstractThe human GPCR family comprises circa 800 members, activated by hundreds of thousands of compounds. Bitter taste receptors, TAS2Rs, constitute a large and distinct subfamily, expressed orally and extra-orally and involved in physiological and pathological conditions. TAS2R14 is the most promiscuous member, with over 150 agonists and 3 antagonists known prior to this study. Due to the scarcity of inhibitors and to the importance of chemical probes for exploring TAS2R14 functions, we aimed to discover new ligands for this receptor, with emphasis on antagonists. To cope with the lack of experimental structure of the receptor, we used a mixed experimental/computational methodology which iteratively improved the performance of the predicted structure. The increasing number of active compounds, obtained here through experimental screening of FDA-approved drug library, and of chemically synthesized flufenamic acid derivatives, enabled the refinement of the binding pocket, which in turn improved the structure-based virtual screening reliability. This mixed approach led to the identification of 10 new antagonists and 200 new agonists of TAS2R14, illustrating the untapped potential of rigorous medicinal chemistry for TAS2Rs. The iterative framework suggested residues involved in the activation process, is suitable for expanding bitter and bitter-masking chemical space, and is applicable to other promiscuous GPCRs lacking experimental structures.Graphical abstract
The first host-associated anaerobic isolate ofPsychrilyobacterprovides insights into its potential roles in the abalone gut
Authors: Liu Meijia , Wei Guangshan , Lai Qiliang , Huang Zhaobin , Li Min , Shao Zongze 
Published: November 2022

AbstractGut bacteria are essential to their hosts, but few studies have focused on marine animals.Psychrilyobacteris frequently related to various marine animals, but the relationship with host remains unknown due to lack of host-associated isolate or genomic information. Here, we combined of high-throughput sequencing, isolating and genomic analyses to uncover its potential role in host abalone. The high-throughput sequencing and literature compiling results indicated thatPsychrilyobacteris widely distributed in marine and terrestrial ecosystems with both host-associated and free-living lifestyles. It showed a strong preference for the guts of marine invertebrates, especially abalone, which generally persisted with high relative abundances. By mimicking the gut inner environment for enrichment, the first host-related pure culture ofPsychrilyobacterwas isolated from the abalone intestine. Phylogenetic, physiological and biochemical characterizations suggested that it represents a novel species namedPsychrilyobacter haliotisB1. Carbohydrate utilization experiments and genomic evidence indicated that B1 is good at fermenting diverse host-food-related monosaccharides and disaccharides but not polysaccharides, implying its critical roles in downstream fermentation instead of upstream food degradation in the gut. Furthermore, this strain showed potential to colonize the gut and benefit the host via different strategies, such as short-chain fatty acids (SCFAs) generation by fermenting carbohydrates and amino acids, and the production of diverse vitamins and antibiotics to support the host growth and antipathogenicity. To our knowledge, strain B1 represents the first host-related pure culture ofPsychrilyobacter, acting as a potential probiotic gut anaerobe dominating in diverse marine invertebrates.ImportancePsychrilyobacteris a globally distributing bacterial genus and with an inhabiting preference for guts of marine invertebrates. Due to the difficulty of cultivation and the limited genomic information, its role in host remains largely unknown. We isolated the first host-associatedPsychrilyobacterspecies from abalone gut and uncovered its functional potentials to the host through different mechanisms. Our findings provide some insights into the understanding of host-microbe interactions on a core taxon with the marine invertebrates, and the isolate has an application prospect as a probiotic in protection of marine animals.
Copiotrophs dominate rhizosphere microbiomes and growth rate potential is a major factor explaining the rhizosphere effect
Authors: López José L. , Pappas Nikolaos , Poppeliers Sanne WM , Sanchez-Gil Juan J. , Fourie-Fouche Arista , de Jonge Ronnie , Dutilh Bas E. 
Published: November 2022

AbstractThe structure and function of the root microbial community is shaped by plant root activity, enriching specific microbial taxa and functions from the surrounding soil as the plant root grows. Knowledge of bacterial rhizosphere competence traits are important for predictive microbiome modeling and the development of viable bioinoculants for sustainable agriculture solutions. In this work we compared growth rate potential, a complex trait that recently became predictable from bacterial genome sequences, to functional traits encoded by proteins. We analyzed 84 paired rhizosphere- and soil-derived 16S rRNA metabarcoding datasets from 18 different plants and soil types, performed differential abundance analyses and estimated growth rates for each bacterial genus. This analysis revealed that bacteria with a high growth rate potential consistently dominated the rhizosphere. Next, we analyzed the genome sequences of 3270 bacterial isolates and 6707 MAGs from 1121 plant- and soil-associated metagenomes, confirming this trend in different bacterial phyla. We next investigated which functional traits were enriched in the rhizosphere, expanding the catalog of rhizosphere-associated traits with hundreds of new functions. When we compared the importance of different functional categories to the predicted growth rate potential using a machine learning model, we found that growth rate potential was the main feature for differentiating rhizosphere and soil bacteria, revealing the broad importance of this factor for explaining the rhizosphere effect. Together, we contribute new understanding of the bacterial traits needed for rhizosphere competence. As this trait may be inferred from (meta-) genome data, our work has implications for understanding bacterial community assembly in the rhizosphere, where many uncultivated bacteria reside.
pLM-BLAST – distant homology detection based on direct comparison of sequence representations from protein language models
Authors: Kaminski Kamil , Ludwiczak Jan , Pawlicki Kamil , Alva Vikram , Dunin-Horkawicz Stanislaw 
Published: November 2022

AbstractMotivationThe detection of homology through sequence comparison is a typical first step in the study of protein function and evolution. In this work, we explore the applicability of protein language models to this task.ResultsWe introduce pLM-BLAST, a tool inspired by BLAST, that detects distant homology by comparing single-sequence representations (embeddings) derived from a protein language model, ProtT5. Our benchmarks reveal that pLM-BLAST maintains a level of accuracy on par with HHsearch for both highly similar sequences (with over 50% identity) and markedly divergent sequences (with less than 30% identity), while being significantly faster. Additionally, pLM-BLAST stands out among other embedding-based tools due to its ability to compute local alignments. We show that these local alignments, produced by pLM-BLAST, often connect highly divergent proteins, thereby highlighting its potential to uncover previously undiscovered homologous relationships and improve protein annotation.Availability and ImplementationpLM-BLAST is accessible via the MPI Bioinformatics Toolkit as a web server for searching precomputed databases (https://toolkit.tuebingen.mpg.de/tools/plmblast). It is also available as a standalone tool for building custom databases and performing batch searches (https://github.com/labstructbioinf/pLM-BLAST).
A non-invasive, fast on/off “Odourgenetic” Method to Manipulate Physiology
Authors: Wu Yanqiong , Su Shanchun , Xu Xueqin , Hao Xincai , Lu Wei , Li Xiaohui , Wang Linhan , Tian Wei , Gao Yan , Cao Gang , Ke Changbin 
Published: November 2022

SummaryManipulating molecular processes governing physiological functions has significant potential for clinical therapeutics and is an important approach to elucidate the cellular basis of physiological functions. Here, we designed a Odourgenetic system co-expressedDrosophilaodorant receptor system (DORs) consisting of OR35a and OR83b, which were exclusively activated by their odor ligand, 2-pentanone. Applying 2-pentanone to DOR-expressing cells or tissues induced calcium influx and membrane depolarization. By inhalation of 2-pentanone, we successfully applied DORs to manipulate behaviour, control insulin secretion and regulate blood glucose and manipulate muscle contraction and associated limb movement. Because 2-pentanone rapidly enters the blood upon inhalation and leaves the body by exhalation, this odorant can be used with DORs to manipulate cellular function, and the manipulation can be terminated at any time. Such feature approach significantly improves the safety and controllability of DORs used in the clinic. Thus, the present study developed a non-invasive, controllable, fast on/off method to manipulate cellular activity and behaviour on a time scale of minutes.
Doublet microtubule inner junction protein FAP20 recruits tubulin to the microtubule lattice
Authors: Bangera Mamata , Dungdung Archita , Prabhu Sujana , Sirajuddin Minhajuddin 
Published: November 2022

AbstractMotility of organisms involves beating of cilia and flagella that are composed of doublet microtubules. The doublets are made of A- and B-tubules that fuse together at two junctions. Among these, the outer junction is made of tripartite tubulin connections, while the inner junction contains distinct non-tubulin elements. The latter includes Flagellar-associated protein 20 (FAP20) and Parkin co-regulated gene protein (PACRG) that together link the A- and B- tubules at the inner junction. While the structures of doublet microtubules reveal molecular details, their assembly is poorly understood and examining proteins at the junctions can provide important clues. In this study, we purified recombinant FAP20 and characterized its effects on microtubule dynamics by TIRF microscopy. Usingin vitroreconstitution and cryo-electron microscopy, we conclusively show that FAP20 recruits free tubulin to the existing microtubule, where it mediates flexible lateral interactions between the microtubule lattice and tubulin dimers. Our structure of microtubule:FAP20:tubulin complex partially resembles the inner junction architecture, further providing insights into assembly steps involved in closure of B- tubule in a doublet microtubule.
What affects users to click social media ads and purchase intention? The roles of advertising value, emotional appeal and credibility
Authors: Chen Wen-Kuo , Ling Chia-Ju , Chen Chien-Wen 
Published: November 2022

PurposeThis study is based on a web-based advertising value model, adding emotional appeal, advertising credibility, advertising clicks, product evaluation and incentive to examine the impact on consumers' product evaluation and purchase intention.Design/methodology/approachIn total, 313 valid online questionnaires were collected from those who had browsed the social media advertisement.FindingsThe results show that advertising credibility and emotional appeal have a higher impact on advertising attitude than informativeness and irritation in the original web-based advertising value model.Research limitations/implicationsThe findings strengthen the literature on the antecedents of advertising attitude in social media context, confirming advertising clicks as a predictor of product evaluation, and determining that advertising attitude, product evaluation and incentive play key roles as predictors of consumer purchase intention.Practical implicationsThe findings are particularly relevant to advertising marketing managers. In the context of social media advertising, the advertising credibility of consumers is the key to increasing consumers' willingness to purchase. Advertisers must establish a good advertising reputation to consumers in the social media context.Originality/valueThis study combines the web-based advertising value model, advertising clicks, product evaluation and incentive to investigate the factors that influence customers' purchase decisions in the context of social media.
The influence of national culture on employee voice in small and medium enterprises: a cross-cultural perspective
Authors: McKearney Aidan , Prouska Rea , Tungtakanpoung Monrudee , Opute John 
Published: November 2022

PurposeThe purpose of this paper is to examine how employee voice in small and medium enterprises (SMEs) is shaped by national culture. Specifically, the paper explores the relationship between national culture and organisational norms and signals. Furthermore, it explores the impact of such norms on employee voice behaviours. The paper chooses to address these issues in the SME context, in three countries with divergent cultural dimensions.Design/methodology/approachThe authors use Kwon and Farndale’s (2020) typology as our “a priori” framework to explore the influence of national cultural values and cultural tightness on SME organisation norms, signals and employee voice behaviours. Our study uses qualitative data gathered through in-depth interviews with SME employees in England, Nigeria and Thailand.FindingsThe results from our interviews are presented thematically. The data illustrates how the cultural dimensions identified by Kwon and Farndale (2020) can have an influence on organisational voice norms. The dimensions are power distance, uncertainty avoidance, in-group collectivism, performance orientation, assertiveness and cultural tightness.Originality/valueHistorically, the impact of national culture as a macro factor on voice has been largely ignored by academic research. Studies in non-western contexts are especially rare. This paper derives its originality by offering unique insights into the culture–voice relationship from both western and non-western perspectives. This provides an international, cross-cultural, comparative dimension to our study. This research includes findings from under-researched settings in Nigeria and Thailand.
Intention to deceive: undergraduates' perception of fraudulent excuse-making
Authors: Che Ku Kassim Che Ku Hisam , Mohd Sallem Nur Raihana 
Published: November 2022

PurposeIssues on fraudulent excuses have become a common phenomenon at higher educational institutions. Although these misbehaviours can unfavourably impact the quality of graduates, nonetheless, these issues have been largely ignored as the focus of academic debates is placed more on other academic dishonest behaviours such as cheating in exams and plagiarisms. Therefore, the aim of this paper is to examine undergraduates' perception of fraudulent excuse-making and to offer a fruitful academic discussion on this deceitful behaviour that has been a somewhat undesirable culture in tertiary educational settings.Design/methodology/approachAn online self-administered questionnaire survey was conducted to 346 undergraduates at a Malaysian public university.FindingsThe results suggest that, while the number is low, fraudulent excuses are indeed being mobilised by undergraduate students in their attempt to avoid academic responsibility. The influence of demographic profiles on fraudulent excuse-making is also evident.Originality/valueA scarcity of studies on fraudulent excuses has contributed to a lack of understanding of the pertinent reasons and causes leading to the engagement of these misbehaviours. The paper hopes to shed some light that can be beneficial to the relevant managerial authorities within the university in any policy changes in an attempt to curb this problematic behaviour from continuously affecting the inner quality of graduates.