bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic genotype networks
Authors: Santos-Moreno Javier , Tasiudi Eve , Kusumawardhani Hadiastri , Stelling Joerg , Schaerli Yolanda 
Published: September 2022

AbstractGenotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. They facilitate evolutionary innovation by enabling the exploration of different neighborhoods in genotype space. Genotype networks, first suggested by theoretical models, have been empirically confirmed for proteins and RNAs. Comparative studies also support their existence for gene regulatory networks (GRNs), but direct experimental evidence is lacking. Here, we report the construction of three interconnected genotype networks of synthetic GRNs producing three distinct gene expression phenotypes inEscherichia coli. These genotype networks, composed of over twenty different synthetic GRNs, provide robustness in face of mutations while enabling transitions to innovative phenotypes. Through realistic mathematical modeling, we quantify robustness and evolvability for the complete genotype-phenotype map and link these features mechanistically to GRN motifs. Our work thereby exemplifies how GRN evolution along genotype networks might be driving evolutionary innovation.
IFITM3 blocks influenza virus entry by sorting lipids and stabilizing hemifusion
Authors: Klein Steffen , Golani Gonen , Lolicato Fabio , Lahr Carmen , Beyer Daniel , Herrmann Alexia , Wachsmuth-Melm Moritz , Reddmann Nina , Brecht Romy , Hosseinzadeh Mehdi , Kolovou Androniki , Makroczyova Jana , Peterl Sarah , Schorb Martin , Schwab Yannick , Brügger Britta , Nickel Walter , Schwarz Ulrich S. , Chlanda Petr 
Published: September 2022

ABSTRACTInterferon-induced transmembrane protein 3 (IFITM3) inhibits the entry of numerous viruses through undefined molecular mechanisms. IFITM3 localizes in the endosomal-lysosomal system and specifically impacts virus fusion with target cell membranes. We found that IFITM3 induces local lipid sorting, resulting in an increased concentration of lipids disfavoring viral fusion at the hemifusion site. This increases the energy barrier for fusion pore formation and the hemifusion dwell time, promoting viral degradation in lysosomes.In situcryo-electron tomography captured IFITM3-mediated arrest of influenza A virus membrane fusion. Observation of hemifusion diaphragms between viral particles and late endosomal membranes confirmed hemifusion stabilization as a molecular mechanism of IFITM3. The presence of the influenza fusion protein hemagglutinin in post-fusion conformation close to hemifusion sites further indicated that IFITM3 does not interfere with the viral fusion machinery. Collectively, these findings show that IFITM3 induces lipid sorting to stabilize hemifusion and prevent virus entry into target cells.
Outsourcing Memory Through Niche Construction
Authors: Lee Edward D. , Flack Jessica C. , Krakauer David C. 
Published: September 2022

Adaptation to changing environments is a universal feature of life and can involve the organism modifying itself in response to the environment as well as actively modifying the environment to control selection pressures. The latter case couples the organism to environment. Then, how quickly should the organism change in response to the environment? We formulate this question in terms of how memory duration scales with environmental rate of change when there are trade-offs in remembering vs. forgetting. We derive a universal scaling law for optimal memory duration, taking into account memory precision as well as two components of environmental volatility, bias and stability. We find sublinear scaling with any amount of environmental volatility. We use a memory complexity measure to explore the strategic conditions (game dynamics) favoring actively reducing environmental volatility—outsourcing memory through niche construction—over investing in neural tissue. We predict stabilizing niche construction will evolve when neural tissue is costly, the environment is variable, and it is beneficial to be able to encode a rich repertoire of environmental states.Significance StatementAll organisms must adapt to changing environments, but adaptation can modify the environment itself. We solve a version of this problem in terms of how long organisms remember. Shorter memory should be better for variable environments and longer for slow changing ones, but environmental variability depends on feedback. Surprisingly, we find the same mathematical law in both cases, revealing how much shorter memory should be relative to the environmental timescale. We consider how this depends on memory complexity and metabolic costs in populations, allowing us to predict a general set of conditions for when organism will outsource memory to the environment: when maintaining a brain is costly, the environment fluctuates quickly, and organisms inhabit a complex environment.
Variable effects on virulence of bacteriophage resistance mechanisms in extraintestinal pathogenicEscherichia coli
Authors: Gaborieau Baptiste , Delattre Raphaëlle , Adiba Sandrine , Clermont Olivier , Denamur Erick , Ricard Jean-Damien , Debarbieux Laurent 
Published: September 2022

AbstractBacteria exposed to killing agents such as antibiotics or viruses develop resistance. While phage therapy, the use of bacteriophages (phages) for treating bacterial infections, is proposed to answer the antibiotic resistance crisis, bacterial resistance to phages remains poorly characterized during phage treatment. We studied a large population of phage-resistant extra-intestinal pathogenicEscherichia coli536 clones emerging from bothin vitro(non-limited liquid medium) andin vivo(murine pneumonia) conditions. Genome sequencing revealed a mutational convergence of phage resistance mechanisms towards the modification of two cell-wall components, the K15 capsule and the LPS, whatever the condition, showing that their identification could be predicted from thein vitroconditions. The fitness cost of all phage resistant clones was broad in terms of growth rate and resistance to grazing by amoeba and could not discriminate K15 capsule to LPS mutants. By contrast, the virulence of the clones tested in mice showed that K15 capsule mutants were as virulent as the wildtype strain while LPS mutants were strongly attenuated. We also found that resistance to one phage led to the sensitization to other phages. In clinics, to control phage-resistant clones that remains virulent phage cocktail should include phages infecting both phage susceptible and future phage resistant clones.ImportanceEscherichia coliis a leading cause of life-threatening infections, including pneumonia acquired during ventilatory assistance for patients hospitalized in Intensive Care Unit, and a major multidrug resistant pathogen. A century-old concept, phage therapy (i.e. using specific anti-bacterial viruses), is being clinically re-evaluated supported with hundreds of successful compassionate phage treatments. However, along billions of years of coevolution bacteria have developed many ways to resist to phages. Phage resistance occurring during phage therapy remains often overlooked despite its critical role for a successful outcome. During this work we characterized phage resistant mutants in a virulent extra-intestinal pathogenicE colistrain and found that (1) phage resistance taking place during a phage treatmentin vivocould be predicted from anin vitroassay; (2) phage resistance has, often but not always, a major fitness cost in terms of virulence; and (3) could be countered by appropriate cocktails of phages.
Phagocytosis via complement receptor 3 enables microbes to evade killing by neutrophils
Authors: Smirnov Asya , Daily Kylene P. , Gray Mary C. , Ragland Stephanie A. , Werner Lacie M. , Johnson M. Brittany , Eby Joshua C. , Hewlett Erik L. , Taylor Ronald P. , Criss Alison K. 
Published: September 2022

ABSTRACTComplement receptor 3 (CR3; CD11b/CD18; αmβ2integrin) is a conserved phagocytic receptor. The active conformation of CR3 binds the iC3b fragment of complement C3 as well as many host and microbial ligands, leading to actin-dependent phagocytosis. There are conflicting reports about how CR3 engagement affects the fate of phagocytosed substrates. Using imaging flow cytometry, we confirmed that binding and internalization of iC3b-opsonized polystyrene beads by primary human neutrophils was CR3-dependent. iC3b-opsonized beads did not stimulate neutrophil reactive oxygen species (ROS), and most beads were found in primary granule-negative phagosomes. Similarly,Neisseria gonorrhoeae(Ngo) that does not express phase-variable Opa proteins suppresses neutrophil ROS and delays phagolysosome formation. Here, binding and internalization of Opa-deleted (Δopa) Ngo by adherent human neutrophils was inhibited using blocking antibodies against CR3 and by adding neutrophil inhibitory factor, which targets the CD11b I-domain. Neutrophils did not produce detectable amounts of C3 to opsonize Ngo. Conversely, overexpressing CD11b in HL-60 promyelocytes enhanced Δopa Ngo phagocytosis, which required CD11b I domain. Phagocytosis of Ngo was also inhibited in mouse neutrophils that were CD11b-deficient or treated with anti-CD11b. Phorbol ester treatment upregulated surface CR3 on neutrophils in suspension, enabling CR3-dependent phagocytosis of Δopa Ngo. Neutrophils exposed to Δopa Ngo had limited phosphorylation of Erk1/2, p38, and JNK. Neutrophil phagocytosis of unopsonizedMycobacterium smegmatis, which also resides in immature phagosomes, was CR3-dependent and did not elicit ROS. We suggest that CR3-mediated phagocytosis is a silent mode of entry into neutrophils, which is appropriated by diverse pathogens to subvert phagocytic killing.
Distinct features in fish Bouncer proteins determine sperm-egg compatibility
Authors: Gert Krista R.B. , Panser Karin , Surm Joachim , Steinmetz Benjamin S. , Schleiffer Alexander , Moran Yehu , Kondrashov Fyodor , Pauli Andrea 
Published: September 2022

AbstractAll sexually reproducing organisms depend on fertilization to survive as species. Despite the importance of fertilization, the mechanisms that drive sperm-egg compatibility are poorly understood. In fish, the egg protein Bouncer is necessary for fertilization and is species-specific between medaka and zebrafish. Here, we investigate whether Bouncer is generally species-specific in fish and identify features mediating its medaka/zebrafish specificity. In vitro fertilization experiments using zebrafish and medaka show that Bouncer is not a general specificity factor. Instead, its homologs exhibit wide compatibility with sperm, in line with the pervasive purifying selection that dominates Bouncer’s evolution. We further uncover specific features of Bouncer— distinct amino acid residues and N-glycosylation patterns—that differentially influence the function of medaka and zebrafish Bouncer homologs and contribute to medaka/zebrafish specificity. This work reveals important themes central to understanding Bouncer’s function in sperm binding and clarifying the molecular requirements for Bouncer’s sperm interaction partner.
Temperature causes species-specific responses to UV-induced DNA damage in amphibian larvae
Authors: Hird Coen , Franklin Craig E. , Cramp Rebecca L. 
Published: September 2022

ABSTRACTAnthropogenic ozone depletion has led to a 2-5% increase in ultraviolet B radiation (UVBR) levels reaching the earth’s surface. Exposure to UVBR causes harmful DNA damage in amphibians, but this is minimized by DNA repair enzymes such as thermally sensitive CPD-photolyase, with cool temperatures slowing repair rates. It is unknown whether amphibian species differ in the repair response to a given dose of UVBR across temperatures. We reared larvae of three species (Limnodynastes peronii, Limnodynastes tasmaniensis, and Platyplectrum ornatum) at 25°C and acutely exposed them to 80 μW cm−2 UVBR for 2 h at either 20°C or 30°C. UVBR-mediated DNA damage was measured as larvae repaired damage in photoreactive light at their exposure temperatures. Cool temperatures increased DNA damage in all two species and slowed DNA repair rate in P. ornatum. The magnitude of DNA damage incurred from UVBR was species-specific. P. ornatum had the lowest CPDs and DNA repair rates, and the depressive effects of low temperature on photorepair were greater in L. tasmaniensis. Considering the susceptibility of most aquatic organisms to UVBR, this research highlighted a need to consider the complexity of species-specific physiology when forecasting the influence of changing UVBR and temperature in aquatic ecosystems.
A dueling-competent signal-sensing module guides precise delivery of cargo proteins into target cells by engineered Pseudomonas aeruginosa
Authors: Wu Li-Li , Yan Shuangquan , Pei Tong-Tong , Tang Ming-Xuan , Li Hao , Liang Xiaoye , Sun Shuyang , Dong Tao 
Published: September 2022

AbstractTo recognize and manipulate a specific microbe of a crowded community is a highly challenging task in synthetic biology. Here, we introduce a highly-selective protein delivery platform, termed DUEC, which responds to direct contact of attacking cells by engineering the tit-for-tat/dueling response of H1-T6SS (type VI secretion system) in Pseudomonas aeruginosa. Using a Cre-recombinase-dependent reporter, we screened H1-T6SS secreted substrates and developed Tse6N as the most effective secretion tag for Cre delivery. DUEC cells can discriminately deliver the Tse6N-Cre cargo into the cytosol of T6SS+ but not T6SS−Vibrio cholerae cells in a mixed population. These data demonstrate that the DUEC cell is not only a prototypical physical-contact sensor and delivery platform but also may be coupled with recombination-based circuits with the potential for complex tasks in mixed microbial communities.
SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b
Authors: Aloise Chiara , Schipper Jelle G. , van Vliet Arno , Oymans Judith , Donselaar Tim , Hurdiss Daniel L. , de Groot Raoul J. , van Kuppeveld Frank J.M. 
Published: September 2022

ABSTRACTThe nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding - prevented PKR activation, inhibited β-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Similar observations were made for the N protein of human coronavirus 229E, suggesting that this may be a general trait conserved among members of other orthocoronavirus (sub)genera.SIGNIFICANCE STATEMENTSARS-CoV-2 nucleocapsid protein N is an antagonist of innate immunity but how it averts virus detection by intracellular sensors remains subject to debate. We provide evidence that SARS-CoV-2 N, by sequestering dsRNA through domain N2b, prevents PKR-mediated activation of the integrated stress response as well as detection by RIG-I-like receptors and ensuing type I interferon expression. This function, conserved in human coronavirus 229E, is not affected by mutations that prevent posttranslational modifications, previously implicated in immune evasion, or that target its binding to stress granule scaffold proteins. Our findings further our understanding of how SARS-CoV-2 evades innate immunity, how this may drive viral evolution and why increased N expression may have been a selective advantage to SARS-CoV-2 variants of concern.
Which structure of academic articles do referees pay more attention to?: perspective of peer review and full-text of academic articles
Authors: Qin Chenglei , Zhang Chengzhi 
Published: September 2022

PurposeThe purpose of this paper is to explore which structures of academic articles referees would pay more attention to, what specific content referees focus on, and whether the distribution of PRC is related to the citations.Design/methodology/approachFirstly, utilizing the feature words of section title and hierarchical attention network model (HAN) to identify the academic article structures. Secondly, analyzing the distribution of PRC in different structures according to the position information extracted by rules in PRC. Thirdly, analyzing the distribution of feature words of PRC extracted by the Chi-square test and TF-IDF in different structures. Finally, four correlation analysis methods are used to analyze whether the distribution of PRC in different structures is correlated to the citations.FindingsThe count of PRC distributed in Materials and Methods and Results section is significantly more than that in the structure of Introduction and Discussion, indicating that referees pay more attention to the Material and Methods and Results. The distribution of feature words of PRC in different structures is obviously different, which can reflect the content of referees' concern. There is no correlation between the distribution of PRC in different structures and the citations.Research limitations/implicationsDue to the differences in the way referees write peer review reports, the rules used to extract position information cannot cover all PRC.Originality/valueThe paper finds a pattern in the distribution of PRC in different academic article structures proving the long-term empirical understanding. It also provides insight into academic article writing: researchers should ensure the scientificity of methods and the reliability of results when writing academic article to obtain a high degree of recognition from referees.
Entrepreneurial intentions of university students in the Kingdom of Saudi Arabia
Authors: Alshagawi Mohammed , Ghaleb Mohanad Mohammed 
Published: September 2022

Purpose
The purpose of this paper is to examine the role of theory of planned behaviour (TPB) motivational factors, social valuation of entrepreneurship and entrepreneurial risk perception in predicting entrepreneurial intentions (EIs) of university students in the Kingdom of Saudi Arabia.

Design/methodology/approach
A quantitative approach was adopted, and a sample of 802 students from a large public university in Saudi Arabia is studied. Structural equation modelling is used to test the relationships among the conceptual model constructs.

Findings
This study found a negative and significant impact of entrepreneurial risk perception on student’s entrepreneurial attitude, perceived behavioural control (PBC) and intention. Social valuation of entrepreneurship was found to have a positive and significant impact on entrepreneurial attitude, PBC and subjective norms. This study provides partial support for the TPB. While the impact of entrepreneurial attitudes and PBC is significant, subjective norms has insignificant impact on EIs.

Research limitations/implications
Several recommendations are proposed from the results of this study for policymakers, universities and other educational institutes to encourage student’s entrepreneurship motivation and intention and reducing the negative effect of risk perceptions. Implications for future research are also presented.

Originality/value
This study integrated three main streams of research which are psychology of risk (entrepreneurial risk perception), the TPB and social context (social valuation of entrepreneurship) to examine the formation of students entrepreneurial motivations and intentions.
Examining the impact of COVID-19 pandemic on international migrants' repatriation intention using structural equation modeling
Authors: Kaur Amanpreet , Kumar Vikas , Kaur Prabhjot 
Published: September 2022

PurposeCOVID-19 pandemic has shattered the economic systems all around the world while creating numerous problems which were faced by all, especially international migrants. The present study offers a qualitative and quantitative perspective on the distress of international migrants and their repatriation intention during the pandemic period.Design/methodology/approachIn-depth semi-structured interviews of 30 respondents belonging to five host nations, Australia, the USA, the UK, New Zealand and Canada, revealed diverse issues. Based on qualitative study findings and past literature, 22 purposeful statements about six constructs – financial issues, social issues, mobility constraints, psychological problems, healthcare issues, and repatriation intentions – were developed. These statements were measured on a seven-point Likert scale and shared online with international migrants from India residing in the host nations. Data collected from 496 international migrants from October 2020 to July 2021 were used to analyze the influence of various determinants on the repatriation intentions by partial least square-structural equation modeling using SmartPLS software.FindingsThe analysis results revealed that the role of financial, social, mobility, psychological and healthcare issues was significant in strengthening the repatriation intentions of the migrants. There is a need to create job opportunities, retrain laid-off workers and formulate migrant inclusive policies.Originality/valueAlthough some studies have highlighted a few problems faced by international migrants, their impact on repatriation intentions has not been studied yet. The present study fills this gap and analyzes the repatriation intention of international migrants in light of different problems they faced during the pandemic.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-04-2022-0233.