bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness ofPseudomonas aeruginosatype VI secretion system relies on toxin potency and type IV pili-dependent interaction
Authors: Rudzite Marta , Endres Robert G. , Filloux Alain 
Published: December 2022

AbstractThe type VI secretion system (T6SS) is an antibacterial weapon that is used by numerous Gram-negative bacteria to gain competitive advantage by injecting toxins into adjacent prey cells. Predicting the outcome of a T6SS-dependent competition is not only reliant on presence-absence of the system but instead involves a multiplicity of factors.Pseudomonas aeruginosapossesses 3 distinct T6SSs and a set of more than 20 toxic effectors with diverse functions including disruption of cell wall integrity, degradation of nucleic acids or metabolic impairment. We generated a comprehensive collection of mutants with various degrees of T6SS activity and/or sensitivity to each individual T6SS toxin. By imaging whole mixed bacterial macrocolonies, we then investigated how theseP. aeruginosastrains gain a competitive edge in multiple attacker/prey combinations. We observed that the potency of single T6SS toxin varies significantly from one another as measured by monitoring the community structure, with some toxins acting better in synergy or requiring a higher payload. Remarkably the degree of intermixing between preys and attackers is also key to the competition outcome and is driven by the frequency of contact as well as the ability of the prey to move away from the attacker using type IV pili-dependent twitching motility. Finally, we implemented a computational model to better understand how changes in T6SS firing behaviours or cell-cell contacts lead to population level competitive advantages, thus providing conceptual insight applicable to all types of contact-based competition.
Regulation of pSYSA defense plasmid copy number inSynechocystisthrough RNase E and a highly transcribed asRNA
Authors: Kaltenbrunner Alena , Reimann Viktoria , Hoffmann Ute A. , Aoyagi Tomohiro , Sakata Minori , Nimura-Matsune Kaori , Watanabe Satoru , Steglich Claudia , Wilde Annegret , Hess Wolfgang R. 
Published: December 2022

ABSTRACTSynthetic biology approaches toward the development of cyanobacterial producer strains require the availability of appropriate sets of plasmid vectors. A factor for the industrial usefulness of such strains is their robustness against pathogens, such as bacteriophages infecting cyanobacteria. Therefore, it is of great interest to understand the native plasmid replication systems and the CRISPR-Cas based defense mechanisms already present in cyanobacteria. In the model cyanobacteriumSynechocystissp. PCC 6803, four large and three smaller plasmids exist. The ∼100 kb plasmid pSYSA is specialized in defense functions by encoding all three CRISPR-Cas systems and several toxin-antitoxin systems. The expression of genes located on pSYSA depends on the plasmid copy number in the cell. The pSYSA copy number is positively correlated with the expression level of the endoribonuclease E. As molecular basis for this correlation we identified the RNase E-mediated cleavage within the pSYSA-encodedssr7036transcript. Together with a cis-located abundant antisense RNA (asRNA1), this mechanism resembles the control of ColE1-type plasmid replication by two overlapping RNAs, RNA I and II. In the ColE1 mechanism, two non-coding RNAs interact, supported by the small protein Rop, which is encoded separately. In contrast, in pSYSA the similar-sized protein Ssr7036 is encoded within one of the interacting RNAs and it is this mRNA that likely primes pSYSA replication. Essential for plasmid replication is furthermore the downstream encoded protein Slr7037 featuring primase and helicase domains. Deletion ofslr7037led to the integration of pSYSA into the chromosome or the other large plasmid pSYSX. Moreover, the presence ofslr7037was required for successful replication of a pSYSA-derived vector in another model cyanobacterium,Synechococcus elongatusPCC 7942. Therefore, we annotated the protein encoded byslr7037as Cyanobacterial Rep protein A1 (CyRepA1). Our findings open new perspectives on the development of shuttle vectors for genetic engineering of cyanobacteria and of modulating the activity of the entire CRISPR-Cas apparatus inSynechocystissp. PCC 6803.
A putative design for electromagnetic activation of split proteins for molecular and cellular manipulation
Authors: Grady Connor J. , Schossau Jory , Ashbaugh Ryan C. , Pelled Galit , Gilad Assaf A. 
Published: December 2022

AbstractThe ability to manipulate cellular function using an external stimulus is a powerful strategy for studying complex biological phenomena. One approach to modulate the function of the cellular environment is split proteins. In this method, a biologically active protein or an enzyme is fragmented so that it reassembles only upon a specific stimulus. While there are many tools available to induce these systems, nature has provided other mechanisms that can be utilized to expand the split protein toolbox. Here we show a novel method for reconstituting split proteins using magnetic stimulation. We have found that the Electromagnetic Perceptive Gene (EPG) changes conformation due to magnetic fields stimulation. By fusing split fragments of a certain protein to both termini of the EPG, the fragments can be reassembled into a functional protein under magnetic stimulation due to conformational change. We show this effect with three separate split proteins; NanoLuc, APEX2, and Herpes Simplex Virus Type-1 Thymidine Kinase. Our results show for the first time, that reconstitution of split proteins can be achieved only with magnetic fields. We anticipate that this study will be a starting point for future magnetically inducible split protein designs for cellular perturbation and manipulation. With this technology, we can help to expand the toolbox of the split protein platform and allow better elucidation of complex biological systems.
Leveraging the Genetic Correlation between Traits Improves the Detection of Epistasis in Genome-wide Association Studies
Authors: Stamp Julian , DenAdel Alan , Weinreich Daniel , Crawford Lorin 
Published: December 2022

AbstractEpistasis, commonly defined as the interaction between genetic loci, is known to play an important role in the phenotypic variation of complex traits. As a result, many statistical methods have been developed to identify genetic variants that are involved in epistasis, and nearly all of these approaches carry out this task by focusing on analyzing one trait at a time. Previous studies have shown that jointly modeling multiple phenotypes can often dramatically increase statistical power for association mapping. In this study, we present the “multivariate MArginal ePIstasis Test” (mvMAPIT) — a multi-outcome generalization of a recently proposed epistatic detection method which seeks to detectmarginal epistasisor the combined pairwise interaction effects between a given variant and all other variants. By searching for marginal epistatic effects, one can identify genetic variants that are involved in epistasis without the need to identify the exact partners with which the variants interact — thus, potentially alleviating much of the statistical and computational burden associated with conventional explicit search-based methods. Our proposed mvMAPIT builds upon this strategy by taking advantage of correlation structure between traits to improve the identification of variants involved in epistasis. We formulate mvMAPIT as a multivariate linear mixed model and develop a multi-trait variance component estimation algorithm for efficient parameter inference andP-value computation. Together with reasonable model approximations, our proposed approach is scalable to moderately sized GWA studies. With simulations, we illustrate the benefits of mvMAPIT over univariate (or single-trait) epistatic mapping strategies. We also apply mvMAPIT framework to protein sequence data from two broadly neutralizing anti-influenza antibodies and approximately 2,000 heterogenous stock of mice from the Wellcome Trust Centre for Human Genetics. The mvMAPIT R package can be downloaded athttps://github.com/lcrawlab/mvMAPIT.
Ultra-long-range interactions between active regulatory elements
Authors: Friman Elias T. , Flyamer Ilya M. , Boyle Shelagh , Bickmore Wendy A. 
Published: December 2022

AbstractContacts between enhancers and promoters are thought to relate to their ability to activate transcription. Investigating mechanisms that drive such chromatin interactions is therefore important for understanding gene regulation. Here, we have determined contact frequencies between millions of pairs of cis-regulatory elements from chromosome conformation capture datasets and analysed a collection of hundreds of DNA-binding factors for binding at regions of enriched contacts. This analysis revealed enriched contacts at sites bound by many factors associated with active transcription. We show that active regulatory elements, independent of cohesin and polycomb, interact with each other across distances of 10s of megabases in vertebrate and invertebrate genomes and that interactions correlate and change with activity. However, these ultra-long-range interactions are not dependent on RNA polymerase II transcription or several transcription cofactors. We propose that long-range interactions between cis-regulatory elements are driven by three distinct mechanisms – cohesin-mediated loop extrusion, polycomb contacts, and association between active regions.
Differential sensing by theC. albicansGpr1 receptor results in morphogenesis, β-glucan masking and survival in macrophages
Authors: Van Genechten Wouter , Wijnants Stefanie , Vreys Jolien , Van Dijck Patrick 
Published: December 2022

AbstractThe human fungal pathogen,Candida albicans, is very proficient at several classical virulence factors such as morphogenesis, adhesion, biofilm formation and immune evasion through β-glucan masking. The protein kinase A (PKA) pathway is involved in both morphogenesis and β-glucan masking. Several signals converge onto the PKA pathway, but it contains only a single upstream G-protein coupled receptor, Gpr1. We identified specific residues within the N-terminal tail of Gpr1 that are required for methionine-induced morphogenesis through Tpk2. Furthermore, we observe that Gpr1-Gpa2 has an active role in exposing glucans. Even though Gpr1 is required for survival whenC. albicansis challenged with macrophages, specifically disrupting morphogenesis did not attenuate this survival. Additionally, constitutive β-glucan masking did not improveC. albicanssurvival rates in the macrophage assay. Taken together, this indicates that Gpr1 may regulate additional mechanisms, possibly through glutamine 461, which are crucial in a macrophage context.Significance StatementCandida albicansis a human fungal pathogen mostly present as a commensal in the gastrointestinal tract. It can rapidly adapt to its everchanging environment through continuous monitoring of extracellular signals. These extracellular signals include methionine and lactate which induce respectively morphogenesis and β-glucan masking through the G-protein coupled receptor, Gpr1. Through a mutagenic approach we different amino acids of the receptor sense methionine and/or lactate but we show that Gpr1 may have an additional ligand that affect its survival in macrophages.
Chromosome-level, nanopore-only genome and allele-specific DNA methylation of Pallas’s cat,Otocolobus manul
Authors: Flack Nicole , Drown Melissa , Walls Carrie , Pratte Jay , McLain Adam , Faulk Christopher 
Published: December 2022

ABSTRACTPallas’s cat, or the manul cat (Otocolobus manul), is a small felid native to the grasslands and steppes of central Asia. Population strongholds in Mongolia and China face growing challenges from climate change, habitat fragmentation, poaching, and other sources. These threats, combined withO. manul’s zoo collection popularity and value in evolutionary biology, necessitate improvement of species genomic resources. We used standalone nanopore sequencing to assemble a 2.5 Gb, 61-contig nuclear assembly and 17,097 bp mitogenome forO. manul. The primary nuclear assembly had 56x sequencing coverage, a contig N50 of 118 Mb, and a 94.7% BUSCO completeness score forCarnivora-specific genes. High genome collinearity withinFelidaepermitted alignment-based scaffolding onto the fishing cat (Prionailurus viverrinus) reference genome. Manul contigs spanned all 19 felid chromosomes with an inferred total gap length of less than 400 kilobases. Modified basecalling and variant phasing produced an alternate pseudohaplotype assembly and allele-specific DNA methylation calls; sixty-one differentially methylated regions were identified between haplotypes. Nearest features included classical imprinted genes, non-coding RNAs, and putative novel imprinted loci. The assembled mitogenome successfully resolved existing discordance betweenFelinaenuclear and mtDNA phylogenies. All assembly drafts were generated from 158 Gb of sequence using seven minION flow cells.
Virulence Differences of Monkeypox Virus Clades 1, 2a and 2b.1 in a Small Animal Model
Authors: Americo Jeffrey L. , Earl Patricia L. , Moss Bernard 
Published: December 2022

ABSTRACTHuman monkeypox, a disease with similarities to smallpox, is endemic in Africa where it has persisted as a zoonosis with limited human-to-human spread. Unexpectedly, the disease expanded globally in 2022 driven by human-to-human transmission outside of Africa. It is not yet known whether the latter is due solely to behavioral and environmental factors or whether the monkeypox virus is adapting to a new host. Genome sequencing has revealed differences between the current outbreak strains, classified as clade 2b, and the prior clade 2a and clade 1 viruses but whether these differences contribute to virulence or transmission has not been determined. We demonstrate that the wild-derived inbred CAST/EiJ mouse provides an exceptional animal model for investigating clade differences in monkeypox virus virulence and show that the order is clade 1 > clade 2a > clade 2b.1. The greatly reduced replication of the clade 2b.1 major outbreak strain in mice and absence of lethality at 100-times the lethal dose of a closely related clade 2a virus, despite similar multiplication in cell culture, suggest that clade 2b is evolving diminished virulence or adapting to other species.SIGNIFICANCEThree clades of monkeypox virus are recognized: clade 1 is present in the Congo Basin, causes 10% human mortality and is transmitted by rodents with little human-to-human spread; clade 2a exists in West Africa, has a low mortality and is also a zoonosis; clade 2b is currently spreading globally by human transmission. The genetic basis for differences in virulence and transmission have not been determined. A major roadblock is the need for a small animal model that can be studied under the stringent safety conditions required. Here we demonstrate that the three clades exhibit highly significant differences in CAST/EiJ mice in the order clade 1 > clade 2a > clade 2b, similar to the severity of clinical disease.
Lean construction and resilience while coping with the COVID-19 pandemic: an analysis of construction companies in Brazil
Authors: Simeão Isaías , Ferreira Karine Araujo 
Published: December 2022

Purpose
Despite the benefits provided by the implementation of the lean philosophy, the most recent research discusses whether the high degrees of efficiency obtained with the implementation this philosophy could contribute positively or negatively in current pandemic scenario. This study aims to analyze how resilient construction industry companies in Brazil were in the face of the COVID-19 pandemic, comparing the performance of construction companies with different implementation levels of lean construction.

Design/methodology/approach
Three case studies were carried out in construction companies in Brazil with different application levels of the lean philosophy.

Findings
Among the results obtained, greater resilience to face COVID-19 was verified in those with a higher implementation level of the lean philosophy. Additionally, it was found that the larger the size of the companies surveyed, the greater the level of implementation of the lean philosophy.

Research limitations/implications
Due to the state of pandemic, and the work carried out in the home office, contact with companies was restricted. In addition, few companies actually adopt the lean philosophy in the construction sector in Brazil. Most of companies use only a few lean construction tools in specific sectors. For the few others who actually implement the philosophy, the acceptance to participate in the research was low.

Originality/value
The lean construction is something very new and innovative for the construction sector in Brazil, and there is little evidence of its use. Few companies adopt the philosophy in the country, and many of them also did not experience such an impactful moment in their entire existence. Thus, the analysis of the relationship between lean construction and resilience in the civil construction sector in Brazil is something innovative.
A bibliometric analysis of IJQRM journal (2002–2022)
Authors: Singh Navjit , Gupta Akriti , Kapur Bharti 
Published: December 2022

PurposeThe purpose of this study is to explore the trends in publications made to International Journal of Quality and Reliability Management (IJQRM) for time period ranging from 2002–2022. In this study authors performed bibliometric analysis on the publications extracted from Scopus database using citations, authors, keywords and bibliographic coupling methods. The analysis helped authors highlighting the achievements of the journal towards the development of field of “quality” and “reliability” management and explore future avenues to be researched upon in the domain.Design/methodology/approachIn this paper outputs derived through VoS viewer and bibliographic data of Scopus were used to examine various tabular and pictorial aspects of the authors, sources, documents, countries and keywords analysis.FindingsThe analysis results revealed that International Journal of Quality and Reliability Management (IJQRM) has got incredible 33,344 citations since 2002 with average citation count per document at 22.69. Sohal A.S. from Monash University, Australia has topped the list of most influential authors in terms of citations per document (107.20 citations/doc) published with IJQRM. However, Antony J. with massive 39 publications in total with 2074 citations is the most prominent contributor for the journal. The author has gained 6% of the total journal citations. The contributions from India, United Kingdom (UK), United States of America (USA), Iran, Australia, Portugal, Brazil, Spain, Sweden, Malaysia and Saudi Arabia are more noteworthy.Research limitations/implicationsThe study has implications for future researchers and journal editorial team to explore possibilities in tapping various uncovered and upcoming research areas related to the scope of journal. The findings of the study may prompt research initiatives linked to diverse fields in sync with changes happening across globe such as: Artificial Intelligence, Robotics, Data Science etc.Originality/valueThe study is an attempt to investigate the long standing heritage offered by IJQRM to the world of quality and reliability management. The authors tried to unearth some hidden facts about the IJQRM and attempted to showcase the past and explore future directions to the researchers and editorial team.
Collegiate social class and connectedness: class in a transitional period of life
Authors: Grabsch Dustin K. , Jennings-Rentz Alexander , Kunovich Robert M. , Hinduja Sakshi , Chinnam Dedeepya 
Published: December 2022

PurposeThis research study set out to answer the following question: How does social class relate to social connectedness in college?Design/methodology/approachThe authors operationalized a nonexperimental, cross-sectional and analytical study design to analyze 271 survey responses.FindingsThis study illustrates that discretionary income has the most dramatic practical significance on the social connectedness of undergraduate students at the research site. As the body of knowledge regarding effective measures of social class for collegians increases, institutions should consider more innovative measures like discretionary spending, perceived social class and others during this unique transitional period of life.Originality/valueA widened perspective of social class in college could aid in supporting the university and college goals of student success and social well-being.
The global foreign direct investment network: evolution and influencing factors
Authors: Li Bing , Shi Zhihui , Guo Wei 
Published: December 2022

PurposeAs foreign direct investment (FDI) plays an important role in economic globalization. This paper examines the structural features of the global FDI network based on FDI flows data and changes in the position of countries within the network.Design/methodology/approachIn order to study the structural characteristics of the global FDI network and the status and changes of countries in the global FDI network, the authors build the investment network and apply the QAP (Quadratic Assignment Procedure) analysis to examine the evolutionary characteristics of the network and its influencing factors.FindingsThe global FDI network becomes more interconnected and has a clear “core-periphery” structure. The network connections and volumes have increased dramatically and most countries spread their assets across multiple countries, while only a handful of countries have concentrated investments. The topological structure of the global FDI network has changed noticeably, although this process has been slow and stable and countries in the core position have remained largely intact. The authors find that trade relations between countries, geographic distance and differences in economic size, income levels and institutional environments all have a significant impact on the global FDI network.Research limitations/implicationsAlthough we find some valuable results, some aspects need further investigation. For example, how a country uses the investment network to boost its economy and how the different industries in the investment network change over time. It is important to get the industry-level details to understand the impact of the global investment network from a government's perspective.Practical implicationsFDI affects the distribution of international capital and contributes to the development of the global economy. Therefore, it is important to study the characteristics of the global FDI network and its development patterns. With more understanding about the network as well as its evolutionary pattern, the government can possibly carry out some policies to promote direct investments as well as economic development.Social implicationsAll countries should actively engage in international direct investments and strengthen their economic ties. At the same time, they can put more emphasis on inward or outward FDI based on their own level of economic development to better establish the circulation channel for domestic and international capital.Originality/valueThis paper examines foreign direct investments through the lens of a global network. In contrast to traditional bilateral studies, this paper focuses on the network structure and evolution, reflecting the dynamics of the entire direct investment system as well as the changing positions of participating countries.