bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-scale Simulations of MUT-16 Scaffold Protein Phase Separation and Client Recognition
Authors: Gaurav Kumar , Busetto Virginia , Páez-Moscoso Diego Javier , Changiarath Arya , Hanson Sonya M. , Falk Sebastian , Ketting René F. , Stelzl Lukas S. 
Published: April 2024

AbstractPhase separation of proteins plays a critical role in cellular organisation. How phase separated protein condensates underpin biological function and how condensates achieve specificity remain elusive. We investigated the phase separation of MUT-16, a scaffold protein inMutator foci, and its role in recruiting the client protein MUT-8, a key component in RNA silencing inC. elegans. We employed a multiscale approach that combined coarse-grained (residue-level CALVADOS2 and near-atomistic Martini3) and atomistic simulations. Simulations across different resolutions provide a consistent perspective on how MUT-16 condensates recruit MUT-8, enabling the fine-tuning of chemical details while balancing the computational cost. Both coarse-grained models (CALVADOS2 and Martini3) predicted the relative phase separation propensities of MUT-16’s disordered regions, which we confirmed throughin vitroexperiments. Simulations also identified key sequence features and residues driving phase separation while revealing differences in residue interaction propensities between CALVADOS2 and Martini3. Furthermore, Martini3 and 350 µs atomistic simulations on Folding@Home of MUT-8’s N-terminal prion-like domain with MUT-16 M8BR cluster highlighted the importance of cation-πinteractions between Tyr residues of MUT-8 and Arg residues of MUT-16 M8BR. Lys residues were observed to be more prone to interact in Martini3. Atomistic simulations revealed that the guanidinium group of Arg also engages in sp2-πinteractions and hydrogen bonds with the backbone of Tyr, making Arg-Tyr interactions stronger than Lys-Tyr, where these additional favourable contacts are absent. In agreement with our simulations,in vitroco-expression pulldown experiments demonstrated a progressive loss of MUT-8 recruitment following the mutation of Arg in MUT-16 M8BR to Lys or Ala, confirming the critical role of Arg in this interaction. These findings advance our understanding of MUT-16 phase separation and subsequent MUT-8 recruitment, key processes in assemblingMutator focithat drive RNA silencing inC. elegans.Statement of SignificanceIn cells proteins phase separate and form condensates. These protein condensates can play important role in bringing molecules together and facilitate biochemical processes. In this work, we used molecular dynamics simulations to understand how MUT-16 phase separates and forms the scaffold of the so-calledMutator focus.Mutator fociproduce small RNA which help to regulates genes. As the scaffold of theMutator focus, MUT-16 recruit multiple proteins which are important for the production of such small RNAs.
Latent-based Directed Evolution accelerated by Gradient Ascent for Protein Sequence Design
Authors: Ngo Nhat Khang , Tran Thanh V. T. , Duy Nguyen Viet Thanh , Hy Truong Son 
Published: April 2024

AbstractDirected evolution has been the most effective method for protein engineering that optimizes biological functionalities through a resource-intensive process of screening or selecting among a vast range of mutations. To mitigate this extensive procedure, recent advancements in machine learning-guided methodologies center around the establishment of a surrogate sequence-function model. In this paper, we propose Latent-based Directed Evolution (LDE), an evolutionary algorithm designed to prioritize the exploration of high-fitness mutants in the latent space. At its core, LDE is a regularized variational autoencoder (VAE), harnessing the capabilities of the state-of-the-art Protein Language Model (pLM), ESM-2, to construct a meaningful latent space of sequences. From this encoded representation, we present a novel approach for efficient traversal on the fitness landscape, employing a combination of gradient-based methods and directed evolution. Experimental evaluations conducted on eight protein sequence design tasks demonstrate the superior performance of our proposed LDE over previous baseline algorithms. Our implementation is publicly available athttps://github.com/HySonLab/LatentDE.
The MorbidGenes panel: a monthly updated list of diagnostically relevant rare disease genes derived from diverse sources
Authors: Jauss Robin-Tobias , Popp Bernt , Bachmann Joachim , Jamra Rami Abou , Platzer Konrad 
Published: April 2024

AbstractPurposeWith exome sequencing now standard, diagnostic labs are in need of a, in principle, to-the-day-accurate list of genes associated with rare diseases. Manual curation efforts are slow and often disease specific, while efforts relying on single sources are too inaccurate and may result in false-positive or false-negative genes.MethodsWe established the MorbidGenes panel based on a list of publicly available databases: OMIM, PanelApp, SysNDD, ClinVar, HGMD and GenCC. A simple logic allows inclusion of genes that are supported by at least one of these sources, providing a list of all genes with diagnostic relevance.ResultsThe panel is freely available athttps://morbidgenes.uni-leipzig.deand currently includes 4960 genes (as of March 2024) with minimally sufficient evidence on disease causality to classify them as diagnostically relevant.ConclusionThe MorbidGenes panel is an open and comprehensive overview of diagnostically relevant rare disease genes based on a diverse set of resources. The panel is updated monthly to keep up with the ever increasing number of rare disease genes.
Scn2adeletion disrupts oligodendroglia function: Implication for myelination, neural circuitry, and auditory hypersensitivity in ASD
Authors: Bae Han-Gyu , Wu Wan-Chen , Nip Kaila , Gould Elizabeth , Kim Jun Hee 
Published: April 2024

AbstractAutism spectrum disorder (ASD) is characterized by a complex etiology, with genetic determinants significantly influencing its manifestation. Among these, theScn2agene emerges as a pivotal player, crucially involved in both glial and neuronal functionality. This study elucidates the underexplored roles ofScn2ain oligodendrocytes, and its subsequent impact on myelination and auditory neural processes. The results reveal a nuanced interplay between oligodendrocytes and axons, whereScn2adeletion causes alterations in the intricate process of myelination. This disruption, in turn, instigates changes in axonal properties and neuronal activities at the single cell level. Furthermore, oligodendrocyte-specificScn2adeletion compromises the integrity of neural circuitry within auditory pathways, leading to auditory hypersensitivity—a common sensory abnormality observed in ASD. Through transcriptional profiling, we identified alterations in the expression of myelin-associated genes, highlighting the cellular consequences engendered byScn2adeletion. In summary, the findings provide unprecedented insights into the pathway fromScn2adeletion in oligodendrocytes to sensory abnormalities in ASD, underscoring the integral role ofScn2a-mediated myelination in auditory responses. This research thereby provides novel insights into the intricate tapestry of genetic and cellular interactions inherent in ASD.
Electrical stimulation of grape berries as new alternative for post-harvest infection management
Authors: Fernandes Mariana , Rodrigues Flávio , Cardoso Vanessa F. , Silva Filipe , Fernandes Margarida M. 
Published: April 2024

AbstractViticulture stands out as a primary agricultural sector in the EU. However, an intensive regime of chemical pesticides is used to meet production standards. Consequently, the EU has taken measures to encourage the promotion of sustainable agrochemical practices. It has recently been demonstrated that low voltage and electrical current can also successfully destroy different type of microorganisms such as bacteria and fungi. However, the application of electric current has not been much explored for preventing early stages of fresh fruit rotting. As a result, an innovative setup was developed to study the effect of an alternating current (50 mA) on grapes previously contaminated withE. coli. A visual analysis of the state of degradation of the grapes 12 days after the electrical treatment allowed us to conclude that the contaminated grapes subjected to electrical treatment (at day 1) did not show visual contamination, when compared to the contaminated grapes without electrical treatment, presenting a similar appearance to the grapes used as control. The quantitative assay also confirmed this result since on the NB agar plates it was possible to visualize a significant reduction in colonies, corresponding to 2 log10CFU/mL, indicating that approximately 99% of theE. colipreviously attached to the berry’ surface was eradicated. This environmentally sustainable solution aims to reduce dependence on pesticides. Still, other studies will focus on validating its effectiveness against target microorganisms and optimizing a conductive network for applying electrical stimuli to a bunch of grapes.
The link between space and time along the human cortical hierarchy
Authors: Centanino Valeria , Fortunato Gianfranco , Bueti Domenica 
Published: April 2024

AbstractIn humans, very few studies have directly tested the link between the neural coding of time and space. Here we combined ultra-high field functional magnetic resonance imaging with neuronal-based modeling to investigate how and where the processing and the representation of a visual stimulus duration is linked to that of its spatial location. Results show a transition in the neural response to duration: from monotonic and spatially-dependent in early visual cortex, to unimodal and spatially-invariant in frontal cortex. This transition begins in extrastriate areas V3AB, and it fully displays in the intraparietal sulcus (IPS), where both unimodal and monotonic responses are present and where neuronal populations are selective to either space, time or both. In IPS, space and time topographies show a specific relationship, although along the cortical hierarchy duration maps compared to spatial ones are smaller in size, less clustered and more variable across participants. These results help to identify the mechanisms through which humans perceive the duration of a visual object with a specific spatial location and precisely characterize the functional link between time and space processing, highlighting the importance of space-time interactions in shaping brain responses.
A spatio-temporaral atlas of the growing brain for fMRI studies
Authors: Murgasova Maria , Doria Valentina , Srinivasan Latha , Aljabar Paul , Edwards David , Rueckert Daniel 
Published: April 2024

AbstractSpatio-temporal atlases of the growing brain can help when building models of brain development, not only for anatomical structure, but also for the changing patterns of activation within the brain. In this paper, we build such an age-dependent atlas using registrations among a large number of anatomical datasets, acquired from neonatal subjects of different ages, and followed by kernel-based regression. fMRI activation data are then registered to this atlas to build a model of the development of brain networks, such as the default and motor networks, at this early age.
Closing the gap: Examining the impact of source habitat proximity on plant and soil microbial communities in post-mining spoil heap primary succession
Authors: Mészárošová Lenka , Kuťáková Eliška , Kohout Petr , Münzbergová Zuzana , Baldrian Petr 
Published: April 2024

AbstractRevegetation of barren substrates is often determined by the composition and distance of the nearest plant community, serving as a source of colonising propagules. Whether such dispersal effect can be observed during the development of soil microbial communities, is not clear. In this study, we aimed to elucidate which factors structure plant and soil bacterial and fungal communities during primary succession on a limestone quarry spoil heap, focusing on the effect of distance to the adjoining xerophilous grassland.We established a grid of 35 plots covering three successional stages – initial barren substrate, early successional community and late successional grassland ecosystem, the latter serving as the primary source of soil colonization. On these plots, we performed vegetation surveys of plant community composition and collected soil cores to analyse soil chemical properties and bacterial and fungal community composition.The composition of early successional plant community was significantly affected by the proximity of the source late successional community, however, the effect weakened when the distance exceeded 20 m. Early successional microbial communities were structured mainly by the local plant community composition and soil chemical properties, with minimal contribution of the source community proximity.These results show that on small spatial scales, species migration is an important determinant of plant community composition during primary succession while the establishment of soil microbial communities is not limited by dispersal and is primarily driven by local biotic and abiotic conditions.
Multicomponent depolymerization of actin filament pointed ends by cofilin and cyclase-associated protein depends upon filament age
Authors: Towsif Ekram M. , Miller Blake Andrew , Ulrichs Heidi , Shekhar Shashank 
Published: April 2024

AbstractIntracellular actin networks assemble through the addition of ATP-actin subunits at the growing barbed ends of actin filaments. This is followed by “aging” of the filament via ATP hydrolysis and subsequent phosphate release. Aged ADP-actin subunits thus “treadmill” through the filament before being released back into the cytoplasmic monomer pool as a result of depolymerization at filament pointed ends. The necessity for aging before filament disassembly is reinforced by preferential binding of cofilin to aged ADP-actin subunits over newly-assembled ADP-Piactin subunits in the filament. Consequently, investigations into how cofilin influences pointed-end depolymerization have, thus far, focused exclusively on aged ADP-actin filaments. Using microfluidics-assisted Total Internal Reflection Fluorescence (mf-TIRF) microscopy, we reveal that, similar to their effects on ADP filaments, cofilin and cyclase-associated protein (CAP) also promote pointed-end depolymerization of ADP-Pifilaments. Interestingly, the maximal rates of ADP-Pifilament depolymerization by CAP and cofilin together remain approximately 20–40 times lower than for ADP filaments. Further, we find that the promotion of ADP-Pipointed-end depolymerization is conserved for all three mammalian cofilin isoforms. Taken together, the mechanisms presented here open the possibility of newly-assembled actin filaments being directly disassembled from their pointed-ends, thus bypassing the slow step of Pirelease in the aging process.
Antimicrobial activity of the BAM complex-targeting peptides against multidrug-resistant gram-negative bacteria
Authors: Yoshihara Eisaku , Kakizoe Hidefumi , Umezawa Kazuo , Wakamatsu Kentaro , Asai Satomi 
Published: April 2024

ABSTRACTMultidrug-resistant (MDR) Gram-negative bacteria represent a notable public health threat, necessitating the urgent development of new antimicrobial agents. The β-barrel assembly machinery (BAM) complex, crucial for the biogenesis of outer membrane proteins in Gram-negative bacteria, emerges as a promising target for drug development. The BAM complex comprises five proteins (BamA–E), and its functionality might be disrupted by peptides targeting the BamA and BamB interface. We synthesized the peptide LTLR, located in the BamB interaction region with BamA inPseudomonas aeruginosa, and assessed its anti-P. aeruginosaactivity. This peptide demonstrated potential in enhancing antibiotic efficacy againstP. aeruginosa. Conversely, LRTL, a scrambled version of LTLR, lacked activity, underscoring the importance of specific target site binding for the peptide’s adjuvant effect. Subsequently, we tested the hypothesis that peptide dimerization enhances its effectiveness. A dimeric peptide, composed of two LTLR sequences, was tested and found to possess bactericidal activity againstP. aeruginosa, an outcome not observed with the monomeric form. Importantly, this dimeric peptide also showed bactericidal activity against MDRP. aeruginosastrains. In summary, our findings offer a foundation for developing novel antimicrobial agents against MDR Gram-negative bacteria.IMPORTANCEThis work demonstrates that (1) the β-barrel assembly machinery (BAM) complex-targeting peptides can exhibit antimicrobial activity and that (2) the dimeric forms of these peptides exhibit bactericidal activity against multidrug-resistant (MDR) strains ofP. aeruginosaandA. baumannii.
Correlations between organizational change and resilience
Authors: Sawalha Ihab Hanna 
Published: April 2024

PurposeThis study aims to: (1) investigate the relationship/connection between organizational change (OC) and organizational resilience (OR) and (2) provide a basis for understanding how organizational change can underpin or build organizational resilience.Design/methodology/approachAn extensive literature review has been made to discuss the goals of OC as well as the enablers of OR. A number of conceptual models have been introduced to demonstrate the correlation between OC and OR and the potential role of OC in supporting OR. Empirical findings were also introduced in order to support the theoretical basis of this research.FindingsThis study argues that OC can be practiced for the purpose of building or supporting OR. A variety of views have been introduced to demonstrate the correlation between OC and OR and the role of OC in supporting OR.Practical implicationsThe purpose and scope of OC should not only be confined to enabling organizations to respond to the dynamics of their business environments but also to enable organizations to withstand a wider range of internal disruptions, major incidents and external factors. This perspective provides a broader insight that is different from the traditional conceptualization of the goals and purpose of OC.Originality/valueTo the author’s knowledge, this is one of very few studies that discuss the correlation between OC and OR and the role of OC in building OR. This explains the need for more practical change initiatives that aim to elevate levels of OR.
The implications of economic freedom and gender ideologies on women's opportunity-to-necessity entrepreneurship
Authors: Hechavarría Diana M. , Guerrero Maribel , Terjesen Siri , Grady Azucena 
Published: April 2024

PurposeThis study explores the relationship between economic freedom and gender ideologies on the allocation of women’s opportunity-to-necessity entrepreneurship across countries. Opportunity entrepreneurship is typically understood as one’s best option for work, whereas necessity entrepreneurship describes the choice as driven by no better option for work. Specifically, we examine how economic freedom (i.e. each country’s policies that facilitate voluntary exchange) and gender ideologies (i.e. each country’s propensity for gendered separate spheres) affect the distribution of women’s opportunity-to-necessity entrepreneurship across countries.Design/methodology/approachWe construct our sample by matching data from the following country-level sources: the Global Entrepreneurship Monitor’s Adult Population Survey (APS), the Fraser Institute’s Economic Freedom Index (EFI), the European/World Value Survey’s Integrated Values Survey (IVS) gender equality index, and other covariates from the IVS, Varieties of Democracy (V-dem) World Bank (WB) databases. Our final sample consists of 729 observations from 109 countries between 2006 and 2018. Entrepreneurial activity motivations are measured by the ratio of the percentage of women’s opportunity-driven total nascent and early-stage entrepreneurship to the percentage of female necessity-driven total nascent and early-stage entrepreneurship at the country level. Due to a first-order autoregressive process and heteroskedastic cross-sectional dependence in our panel, we estimate a fixed-effect regression with robust standard errors clustered by country.FindingsAfter controlling for multiple macro-level factors, we find two interesting findings. First, economic freedom positively affects the ratio of women’s opportunity-to-necessity entrepreneurship. We find that the size of government, sound money, and business and credit regulations play the most important role in shaping the distribution of contextual motivations over time and between countries. However, this effect appears to benefit efficiency and innovation economies more than factor economies in our sub-sample analysis. Second, gender ideologies of political equality positively affect the ratio of women’s opportunity-to-necessity entrepreneurship, and this effect is most pronounced for efficiency economies.Originality/valueThis study offers one critical contribution to the entrepreneurship literature by demonstrating how economic freedom and gender ideologies shape the distribution of contextual motivation for women’s entrepreneurship cross-culturally. We answer calls to better understand the variation within women’s entrepreneurship instead of comparing women’s and men’s entrepreneurial activity. As a result, our study sheds light on how structural aspects of societies shape the allocation of women’s entrepreneurial motivations through their institutional arrangements.
Understanding mature students' intention to use mobile learning in higher education: integrating personality traits and UTAUT
Authors: Chau Keng Fong 
Published: April 2024

PurposeThis study aims to provide new insights into the relationship between individual characteristics, particularly personality traits and mature students' intention to use (ITU) mobile learning (m-learning).Design/methodology/approachThe research model was constructed by integrating the Big Five personality traits into the unified theory of acceptance and use of technology (UTAUT) model. The data were collected from mature students at a university research center in Macau. Partial least squares structural equation modeling (PLS-SEM) was used to analyze the data and test the proposed hypotheses.FindingsThe results reveal that personality traits play a significant role in determining mature students' ITU m-learning technology. In particular, social influence (SI) mediates the relationship between agreeableness (AGB) and ITU.Originality/valueThis study examines how personality traits collectively influence mature students' receptiveness and intentions toward m-learning. As mature learners' motivations and preferences remain underexplored, insights into trait-technology links could address current gaps and optimize mobile educational support tailored to their distinct characteristics and needs.