Integration Of Elements Research Articles

Exploring the diversity of anti-defense systems across prokaryotes, phages, and mobile genetic elements.

The co-evolution of prokaryotes, phages, and mobile genetic elements (MGEs) over the past billions of years has driven the emergence and diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences, and are typically small, creating a challenge to detect anti-defense homologs across the prokaryotic genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired genome or MGE. Here, we developed "AntiDefenseFinder" - a free open-source tool and web service that detects 156 anti-defense systems (of one or more proteins) in any genomic sequence. Using this dataset, we identified 47,981 anti-defense systems distributed across prokaryotes, phage, and MGEs. We found that some genes co-localize in "anti-defense islands", including E. coli T4 and Lambda phages, although many are standalone. Out of the 112 systems detected in bacteria, 100 systems localize only or preferentially in prophages, plasmids, phage satellites, integrons, and integrative and conjugative elements. However, over 80% of anti-Pycsar protein 1 (Apyc1) resides in non-mobile regions of bacteria. Evolutionary and functional analyses revealed that Apyc1 likely originated in bacteria to regulate cNMP signaling, but was co-opted multiple times by phages to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions, and a deeper understanding of host-pathogen arms race.

Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae

AimsTo investigate the molecular events associated with acquiring macrolide resistance genes [mefE/mel (Mega) or ermB] in Streptococcus pneumoniae (Spn) during nasopharyngeal colonization. Methods and resultsGenomic analysis of 128 macrolide-resistant Spn isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn916-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn916-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (>23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose. ConclusionsPneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.

Petroglyphs as a paleobiogeographic guide for Arabian ostrich ecology and reintroduction

The Arabian ostrich (Struthio camelus syriacus) was an integral element in the wildlife of the Middle East until its extinction in the mid-20th century. Here we discuss the historic and archaeological record that provides baseline information on the past distribution of ostriches in the Negev Desert (Israel). Specifically, we focus on survey data of ancient petroglyph depictions of ostriches and examine their spatial distribution. Through the application of models of optimal habitat reconstruction using data on the houbara bustard as a proxy species for the ostrich, correlated with the spatial distribution of the ostrich petroglyphs and ecological data on the region, we identified the optimal areas that the Syrian ostrich could have inhabited in the past. Finally, we applied our model to examine reintroduction programs of a closely related ostrich subspecies, S. c. camelus, that have been carried out in the Negev to date.

The Accuracy of Supervised Learning Algorithm on Machine Learning Implementation: a Literature Review

Machine Learning has become an integral element in technological development, having a significant impact on various sectors of life. This study explores the contribution of Machine Learning in big data processing, automated decision making, and predictive system development. The advantages of Machine Learning, especially in supervised learning, are emphasized by discussing algorithms such as regression, Support Vector Machines (SVM), and Neural Networks. Literature research includes five journals related to supervised learning applications, highlighting findings such as the effectiveness of the Random Forest algorithm in diagnosing pregnancy, the contribution of the SVM model in predicting student study periods, and the level of accuracy with the hybrid LSH and k-NN methods for weather prediction. The practical implementation of fruit detection using cameras shows real application in facilitating price checks and fruit recognition. In conclusion, the literature review confirms the potential and relevance of Machine Learning techniques, especially supervised learning, in providing solutions to various challenges in various sectors. It is recommended that further research explore different industrial sectors or specific case studies to gain a more comprehensive and relevant perspective on current trends in the development of Machine Learning techniques

The serotonergic psychedelic N,N-dipropyltryptamine alters information-processing dynamics in in vitro cortical neural circuits

Abstract Most of the recent work in psychedelic neuroscience has been done using non-invasive neuroimaging, with data recorded from the brains of adult volunteers under the influence of a variety of drugs. While this data provides holistic insights into the effects of psychedelics on whole-brain dynamics, the effects of psychedelics on the meso-scale dynamics of neuronal circuits remains much less explored. Here, we report the effects of the serotonergic psychedelic N,N-diproptyltryptamine (DPT) on information-processing dynamics in a sample of in vitro organotypic cultures of cortical tissue from post-natal rats. Three hours of spontaneous activity were recorded: an hour of pre-drug control, and hour of exposure to 10 μM DPT solution, and a final hour of washout, once again under control conditions. We found that DPT reversibly alters information dynamics in multiple ways: first, the DPT condition was associated with higher entropy of spontaneous firing activity and reduced the amount of time information was stored in individual neurons. Second, DPT also reduced the reversibility of neural activity, increasing the entropy produced and suggesting a drive away from equilibrium. Third, DPT altered the structure of neuronal circuits, decreasing the overall information flow coming into each neuron, but increasing the number of weak connections, creating a dynamic that combines elements of integration and disintegration. Finally, DPT decreased the higher-order statistical synergy present in sets of three neurons. Collectively, these results paint a complex picture of how psychedelics regulate information processing in meso-scale neuronal networks in cortical tissue. Implications for existing hypotheses of psychedelic action, such as the Entropic Brain Hypothesis, are discussed.

Swearing Oaths and Affixing Seals: Acts of Citizenship and Belonging Among Jews in the Medieval Holy Roman Empire

This study investigates ‘acts of citizenship’ and forms of belonging among Jews within the medieval Holy Roman Empire. Positing that citizenship was not just a matter of official status, it looks at ‘acts of citizenship’, such as oath-taking and sealing practices, showing how these were integral elements in the relationship between an individual and the town in which they lived. I argue that both oath-taking and sealing practices, with their performative elements, are therefore valuable indicators of Jewish belonging in urban settings. Through this investigation, a deeper understanding of the multifaceted and ever-changing roles that Jews had and were able to obtain in the medieval Holy Roman Empire can be gained and, ultimately, also applied to other social groups.

Identification of novel Tet(X6)-Tet(X2) recombinant variant in Elizabethkingia meningoseptica from a bullfrog farm and downstream river in China.

The dissemination of strains producing tetracyclines monooxygenase Tet(X) from breeding farms to the natural environment poses a potential threat to public health. Antimicrobial susceptibility testing and WGS were performed to identify resistance phenotypes and genotypes. Cloning experiments, sequence alignment, and homology modeling were used to characterize the function and formation mechanisms of the recombinant variant. The mobilization potential of Tet(X) was assessed by collinearity analysis, conjugation experiments, and phylogenetic analysis. Three tet(X)-producing Elizabethkingia meningoseptica strains were isolated from bullfrog breeding ponds, the sewage outlet, and downstream river in Zhejiang Province, China. These strains carry a novel Tet(X) variant, differing from Tet(X6) by seven residues, and possess the ability to degrade tetracyclines. Interestingly, the novel Tet(X) is a recombinant variant formed by homologous recombination of Tet(X6) and the C-terminal of Tet(X2). Further analysis revealed that Tet(X6) formed several Tet(X) variants, including Tet(X5), through homologous recombination. The novel tet(X) gene is located on a circularizable integrative and conjugative element (ICEEmeChn3), with ISwz1 participating in the recombination of its multi-drug resistance region, potentially facilitating the mobilization and recombination of tet(X) in early hosts. These three strains were clonally transmitted and shared a close genetic relationship (SNP < 62) with a clinically-sourced strain isolated from the same province. To our knowledge, this is the first report of homologous recombination between Tet(X) variants with differing activities. These clonal strains provide evidence of the transmission of tet(X)-positive strains from aquaculture sewage to the natural environment, highlighting the need to strengthen the monitoring and management of this emerging farming model.

The lactococcal ICE-ome encodes a repertoire of exchangeable traits with potential industrial relevance

Dairy industries apply selected lactococcal strains and mixed cultures to produce diverse fermented products with distinctive flavor and texture properties. Innovation of the starter culture functionality in cheese applications embraces natural biodiversity of the Lactococcus species to identify novel strains with alternative flavor or texture forming capacities and/or increased processing robustness and phage resistance. Mobile genetic elements (MGE), like integrative conjugative elements (ICEs) play an important role in shaping the biodiversity of bacteria. Besides the genes involved in the conjugation of ICEs from donor to recipient strains, these elements also harbor cargo genes that encode a wide range of functions. The definition of such cargo genes can only be achieved by accurate identification of the ICE boundaries (delimiting). Here, we delimited 25 ICEs in lactococcal genome sequences with low contig numbers using insertion-sites flanking single-copy core-genome genes as markers for each of the distinct ICE-integrases we identified previously within the conserved ICE-core genes. For ICEs in strains for which genome information with large numbers of contigs is available, we exemplify that CRISPR-Cas9 driven ICE-curing, followed by resequencing, allows accurate delimitation and cargo definition of ICEs. Finally, we compare and contrast the cargo gene repertoire of the 26 delimited lactococcal ICEs, identifying high plasticity among the cargo of lactococccal ICEs and a range of encoded functions that is of apparent industrial interest, including restriction modification, abortive infection, and stress adaptation genes.

Pan-European survey on medication adherence management by healthcare professionals.

While medication adherence (MA) is a key prerequisite for achieving optimal clinical and economic outcomes, nonadherence is highly prevalent. Assessing how healthcare professionals (HCPs) in Europe manage MA, focusing on measurement, reporting and interventions, is the subject of this study. A cross-sectional study was conducted among 40 European countries and quantitative analysis was conducted via an online survey. The multi-language online survey was created using Webropol 3.0 survey and reporting tool. Descriptive statistics and chi-squared tests were applied. In total, 2875 HCPs (pharmacists: 39.9%; physicians: 36.7%; nurses: 16.4%) from 37 European countries participated. The most used methods for MA assessment were direct communication with patients (86.4%) and referring to personal patient records (56.7%) (P < 0.0001). Physicians (74.9%) and nurses (58.8%) were more aware of problems related to MA in contrast to pharmacists (48.6%) (P < 0.001). Almost all HCPs (92.6%) indicated that MA-enhancing interventions involved mainly direct communication with nonadherent patients (93.3%) and their caregivers (55.7%). Medication review and related optimization of therapy were mainly performed in Western European countries (46.8%). Technological solutions were ranked as one of the less applied approaches (10-15%) (P < 0.001). HCPs in all European regions recognize MA management as an integral element of overall patient-centred care. More efforts are needed to ensure timely, adequate and relevant MA assessment, reporting and improvement and involvement of all HCPs, especially among pharmacists who were generally less aware of MA issues. Promotion and use of digital technological solutions should be the focus of current and future clinical practice to optimize MA management processes.

Local Genomic Surveillance of Invasive Streptococcus pyogenes in Eastern North Carolina (ENC) in 2022-2023.

The recent increase in Group A Streptococcus (GAS) incidences in several countries across Europe and some areas of the Unites States (U.S.) has raised concerns. To understand GAS diversity and prevalence, we conducted a local genomic surveillance in Eastern North Carolina (ENC) in 2022-2023 with 95 isolates and compared its results to those of the existing national genomic surveillance in the U.S. in 2015-2021 with 13,064 isolates. We observed their epidemiological changes before and during the COVID-19 pandemic and detected a unique sub-lineage in ENC among the most common invasive GAS strain, ST28/emm1. We further discovered a multiple-copy insertion sequence, ISLgar5, in ST399/emm77 and its single-copy variants in some other GAS strains. We discovered ISLgar5 was linked to a Tn5801-like tetM-carrying integrative and conjugative element, and its copy number was associated with an ermT-carrying pRW35-like plasmid. The dynamic insertions of ISLgar5 may play a vital role in genome fitness and adaptation, driving GAS evolution relevant to antimicrobial resistance and potentially GAS virulence.

Genomic insights into the 2022–2023Vibrio cholerae outbreak in Malawi

Malawi experienced its deadliest Vibrio cholerae (Vc) outbreak following devastating cyclones, with >58,000 cases and >1700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022–2023 Vc outbreak isolates. Our results demonstrate the predominance of ST69 clone, also known as the seventh cholera pandemic El Tor (7PET) lineage, expressing O1 Ogawa (~ 80%) serotype followed by Inaba (~ 16%) and sporadic non-O1/non-7PET serogroups (~ 4%). Phylogenetic reconstruction revealed that the Malawi outbreak strains correspond to a recent importation from Asia into Africa (sublineage AFR15). These isolates harboured known antimicrobial resistance and virulence elements, notably the ICEGEN/ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTXφ prophage with the ctxB7 genotype compared to historical Malawian Vc isolates. These data suggest that the devastating cyclones coupled with the recent importation of 7PET serogroup O1 strains, may explain the magnitude of the 2022–2023 cholera outbreak in Malawi.

Rehabilitation for spinal muscular atrophy patients in China: a national cross-sectional study

BackgroundThe management of Spinal Muscular Atrophy (SMA) requires a multidisciplinary treatment approach, wherein rehabilitation constitutes an integral element. In this study, we examined the effects of rehabilitation among Chinese SMA patients and assessed the real-world efficacy of rehabilitation interventions.MethodsWe conducted a cross-sectional online survey on SMA patients from June 9, 2023, to June 30, 2023, through the Meier Advocacy & Support Center using data from the Center’s database and electronic questionnaires. The rehabilitation situation of the participants over the past 14 months were investigated. Logistic binary regression was used to analyze the relationship between Pediatric Quality of Life Inventory(PedsQL™) scores and rehabilitation.ResultA total of 186 questionnaires were finally analyzed. Only 29 patients did not rehabilitated in the past 14 months. A significant correlation between age and type of rehabilitation, as well as between age and duration of rehabilitation. Patients receiving no rehabilitation or solely home-based rehabilitation exhibited a higher median age of 8.4 compared to those undergoing standard rehabilitation or a combination of standard and home-based rehabilitation, with a median age of 4.9 (z-score = -4.49, p-value < 0.001). In addition, long-term rehabilitation (OR = 0.314, 95%CI = 0.106–0.927, p = 0.04) were negatively correlated with lower PedsQL™ Neuromuscular Module scores, and PedsQL scores in the long-term rehabilitation group were higher than those in the short-term and no-rehabilitation groups (54.2 ± 15.1 vs. 45.9 ± 14.4 and 42.3 ± 14.3, p = 0.01), with the most significant difference observed in the physical function section (59.0 ± 15.8 vs. 46.8 ± 15.2 and 45.6 ± 15.9, p < 0.01). Mobility and exercise (OR = 0.26, 95%CI = 0.08–0.81, p = 0.02), as well as assistive technology (OR = 0.28, 95%CI = 0.10–0.82, p = 0.02), were independently associated with a lower score in a negative direction.ConclusionThe study found that long-term rehabilitation was linked to higher PedsQL scores in SMA patients, highlighting the need for standardized rehabilitation programs to enhance function and quality of life.

Beav: a bacterial genome and mobile element annotation pipeline.

Annotation of genome features, such as the presence of genes and their predicted function, or larger loci encoding secretion systems or biosynthetic gene clusters, is necessary for understanding the functions encoded by an organism. Genomes can also host diverse mobile genetic elements, such as integrative and conjugative elements and/or phages, that are often not annotated by existing pipelines. These elements can horizontally mobilize genes encoding for virulence, antimicrobial resistance, or other adaptive functions and alter the phenotype of an organism. We developed a software pipeline, called Beav, that combines new and existing tools for the comprehensive annotation of these and other major features. Existing pipelines often misannotate loci important for virulence or mutualism in plant-associated bacteria. Beav includes custom databases and optional workflows for the improved annotation of plant-associated bacteria. Beav is designed to be easy to install and run, making comprehensive genome annotation broadly available to the research community.

Numerical Computation of 2D Domain Integrals in Boundary Element Method by (α, β) Distance Transformation for Transient Heat Conduction Problems

When the time-dependent boundary element method, also termed the pseudo-initial condition method, is employed for solving transient heat conduction problems, the numerical evaluation of domain integrals is necessitated. Consequently, the accurate calculation of the domain integrals is of crucial importance for analyzing transient heat conduction. However, as the time step decreases progressively and approaches zero, the integrand of the domain integrals is close to singular, resulting in large errors when employing standard Gaussian quadrature directly. To solve the problem and further improve the calculation accuracy of the domain integrals, an (α, β) distance transformation is presented. Distance transformation is a simple and efficient method for eliminating near-singularity, typically applied to nearly singular integrals. Firstly, the (α, β) coordinate transformation is introduced. Then, a new distance transformation for the domain integrals is constructed by replacing the shortest distance with the time step. With the new method, the integrand of the domain integrals is substantially smoothed, and the singularity arising from small time steps in the domain integrals is effectively eliminated. Thus, more accurate results can be obtained by the (α, β) distance transformation. Different sizes of time steps, positions of source point, and shapes of integration elements are considered in numerical examples. Comparative studies of the numerical results for the domain integrals using various methods demonstrate that higher accuracy and efficiency are achieved by the proposed method.

Study on the effect of room temperature/low temperature environment on the electrical contact plug/pulling wear performance of different copper-based coated conductive connection terminals

This paper explores the wear and tribology performance of three types of terminals, each coated with a different metallic surface (gold, silver, tin), in an environment of fluctuating temperatures. As integral elements of electronic connectors, these terminals are essential for maintaining stable contact resistance, which is crucial to the safety of the entire electrical system. The study reveals that the friction coefficients of the coated terminals are lower at low temperatures compared to ambient temperature. Furthermore, the cooler conditions help maintain more consistent contact resistance. Specifically, the terminals with gold coating mainly experience adhesive and abrasive wear during initial low plug/pull tests, with adhesive wear becoming more dominant in later stages. In contrast, terminals with silver coating primarily suffer from abrasive wear, while those coated with tin tend to show predominantly adhesive wear during initial plug/pull cycles.

Evaluation in the Context of Early Language Education Activities

A subject around which a series of specialized debates revolve is evaluation, which is attributed the quality of being an integrative element of the educational process, alongside teaching and learning. In the context of current pedagogical thinking, evaluation is an action focused on the child's learning process, engaging their cognitive processes, as well as the regulation and self-regulation of knowledge. In other words, the process of evaluation goes beyond its traditional meaning – that of control, examination, and sanction – and tends towards a dynamic focused particularly on the child's mental processes, so that they can be aware of what they learn, how they learn, and especially why they learn. In this article, we have attempted to present some aspects related to didactic evaluation seen as a validation of the correctness of educational sequences, components of the didactic process, and a means of delimiting, fixing, and intervening in educational content and objectives. Educational activity in kindergarten is complex and requires varied, multiple forms of evaluation adapted to the particularities of preschoolers. The diversity of teaching situations, as well as the multitude of evaluation objectives, require the conception and application of different strategies to mediate the evaluative process

Private welfare for workers. Corporate welfare at Fiat in the era of Vittorio Valletta (1946-1966)1

ABSTRACT Fiat (Fabbrica Italiana Automobili Torino) was for a good part of the twentieth century Italy’s largest industrial company. Historians and sociologists have extensively investigated its productive expansion in the automotive industry, as well as the leading role it played in introducing and applying Taylorist and Fordist techniques of mass production to the Italian manufacturing sector. The analysis of the organization of the social policies that the company established for its employees from the 1920s onward has been, however, less considered. Yet, the complex of welfare, recreational and cultural services made available to workers was so pervasive that it seems interesting to reconstruct its history and assess the impact it had on the lives of employees. It can be argued that the corporate welfare made up by the Turin company during the years when Vittorio Valletta led it (1946–1966) was an integral element of the Fordist model of mass production, aimed not only to counterbalance the strain of assembly line work with social benefits, but also to replicate in daily life the regimentation that office and factory workers experienced in the hours they spent in the mills.

Omnichannel word-of-mouth genesis: the confluence of online-offline experiences, social influence and skepticism

PurposeThis research aims to examine the integral elements of omnichannel retailing, an evolving approach that blends online and offline shopping experiences. It focuses on how various factors – merchandise variety, monetary saving, personal interaction, complaint handling, social influence, perceived crowd and skepticism – affect relative advantage, consumer satisfaction and word-of-mouth (WOM) advocacy in an omnichannel context.Design/methodology/approachA comprehensive survey was conducted with 258 participants, and the data were analyzed using partial least squares structural equation modeling (PLS-SEM). This methodology provided insights into the complex relationships between different omnichannel retailing factors and their impact on customer satisfaction and WOM.FindingsThe study found that monetary saving influences both relative advantage and satisfaction. Personal interaction was observed to affect complaint handling and relative advantage. Importantly, relative advantage was found to impact both satisfaction and WOM. Additionally, the study highlighted the roles of social influence and satisfaction in enhancing WOM.Originality/valueThis research adds to the existing literature by providing a nuanced understanding of the dynamics of consumer engagement in omnichannel retailing. It bridges a gap in existing research by concurrently examining the impact of online and offline retail factors on consumer satisfaction and WOM in an omnichannel setting.

On Some Aspects of the Procedure of Enforcement Proceedings

In a rule-of-law state, the execution of a judicial act is an integral element of the constitutional right to judicial protection. Problems arising in the general procedure for enforcement proceedings are relevant in theory and legal practice. The purpose of the study is to conduct a comprehensive analysis of the general procedure for enforcement proceedings. The research methods are logical, comparative legal, critical, chronological and other methods were used. The results obtained are recommended for solving problems related to the execution of a judicial act, expanding theoretical ideas regarding the general procedure for enforcement proceedings, and developing recommendations for improving practice in this direction.

Prevalence and characterization of an integrative and conjugative element carrying tet(X) gene in Elizabethkingia meningoseptica

ObjectivesTo investigate the tet(X) gene, a determinant of tigecycline resistance, in the emerging pathogen Elizabethkingia meningoseptica and its association with an integrative and conjugative element (ICE). MethodsAll E. meningoseptica genomes from the National Center for Biotechnology Information (n = 87) were retrieved and annotated for resistome searches using the CARD database. A phylogenic analysis was performed based on the E. meningoseptica core genome. The ICE was identified through comparative genomics with other ICEs occurring in Elizabethkingia spp. ResultsPhylogenetic analysis revealed E. meningoseptica genomes from six countries distributed across different lineages, some of which persisted for years. The common resistome of these genomes included blaBlaB, blaCME, blaGOB, ranA/B, aadS, and catB (genes associated with resistance to β-lactams, aminoglycosides, and chloramphenicol). Some genomes also presented additional resistance genes (dfrA, ereD, blaVEB, aadS, and tet(X)). Interestingly, tet(X) and aadS were located in an ICE of 49 769 bp (ICEEmSQ101), which was fully obtained from the E. meningoseptica SQ101 genome. We also showed evidence that the other 27 genomes harboured this ICE. The distribution of ICEEmSQ101, carrying tet(X), was restricted to a single Chinese lineage. ConclusionsThe tet(X) gene is not prevalent in the species E. meningoseptica, as previously stated for the genus Elizabethkingia, since it is present only in a single Chinese lineage. We identified that several E. meningoseptica genomes harboured an ICE that mobilized the Elizabethkingia tet(X) gene and exhibited characteristics similar to the ICEs of other Flavobacteria, which would favour their transmission in this bacterial family.