bluuebunny/crossref_metadata_2025_split huggingface dataset:
ECT2 peptide sequences outside the YTH domain regulate its m6A-RNA binding
Authors: Seigneurin-Berny Daphné , Karczewski Claire , Delaforge Elise , Yaacoub Karen , Litholdo Celso Gaspar , Favory Jean-Jacques , Jensen Malene Ringkjøbing , Bousquet-Antonelli Cécile , Verdel André 
Published: August 2024

SummaryThe m6A epitranscriptomic mark is the most abundant and widespread internal RNA chemical modification, which through the control of RNA acts as an important actor of eukaryote reproduction, growth, morphogenesis and stress response. The main m6A readers constitute a super family of proteins with hundreds of members that share a so-called YTH RNA binding domain. The majority of YTH proteins carry no obvious additional domain except for an Intrinsically Disordered Region (IDR). InArabidopsis thalianaIDRs are important for the functional specialization among the different YTH proteins, known as Evolutionarily ConservedC-Terminal region, ECT 1 to 12. Here by studying the ECT2 protein and using anin vitrobiochemical characterization, we show that full length ECT2 and its YTH domain alone have a distinct ability to bind m6A, conversely to previously characterized YTH readers. We identify peptide regions outside of ECT2 YTH domain, in the N-terminal IDR, that regulate its binding to m6A-methylated RNA. Furthermore, we show that the selectivity of ECT2 binding for m6A is enhanced by a high uridine content within its neighboring sequence, where ECT2 N-terminal IDR is believed to contact the target RNAin vivo. Finally, we also identify small structural elements, located next to ECT2 YTH domain and conserved in a large set of YTH proteins, that enhance its binding to m6A-methylated RNA. We propose from these findings that some of these regulatory regions are not limited to ECT2 or YTH readers of the flowering plants but may be widespread among the eukaryotic YTH readers.
Structural and mechanistic diversity in p53-mediated regulation of organismal longevity across taxonomical orders
Authors: Osbourne Romani , Thayer Kelly M. 
Published: August 2024

AbstractThe accumulation of senescent cells induces several aging phenotypes, and the p53 tumor suppressor protein regulates one of the two known cellular senescence pathways. p53’s regulation of senescence is however not clear. For example, p53 deficiency in some mice has been shown to rescue premature aging while others display significant aging phenotype when p53-deficient. This study seeks to elucidate, structurally and mechanistically, p53’s roles in longevity. Through a relative evolutionary scoring (RES) algorithm, we quantify the level of evolutionary change in the residues of p53 across organisms of varying average lifespans in six taxonomic orders. Secondly, we used PEPPI to assess the likelihood of interaction between p53–or p53-linked proteins–and known senescence-regulating proteins across organisms in the orders Primates and Perciformes. Our RES algorithm found variations in the alignments within and across orders, suggesting that mechanisms of p53-mediated regulation of longevity may vary. PEPPI results suggest that longer-lived species may have evolved to regulate induction and inhibition of cellular senescence better than their shorter-lived counterparts. With experimental verification, these predictions could help elucidate the mechanisms of p53-mediated cellular senescence, ultimately clarifying our understanding of p53’s connection to aging in a multiple-species context.Author summaryThe p53 tumor suppressor protein protects our genome from cancers by repairing DNA damage, regulating cell death and/or pushing cells to a state where they become permanently unable to divide (known as cellular senescence). An accumulation of senescent cells produces various molecular features of aging in both mouse and human cellular models–thus linking p53 to the aging process. However, the molecular mechanism by which p53 regulates aging and its structural implications on this regulation are not clear. In this study, we assessed quantitatively the evolutionary differences in p53 sequences of organisms across several taxonomical orders to determine if there is a relationship between average lifespan and sequence evolution. In addition, we used a protein-protein interaction tool to assess the likelihood of interaction between p53, or p53-associated protein, and various senescence-associated proteins across organisms of various lifespans in two taxonomic orders: Primates and Perciformes. An elucidation of p53 structural difference and mechanistic proteomic network linked to p53 regulation of cellular senescence could advance therapeutics targeting abnormal aging.
Context effects on repair of 5’-overhang DSB induced by Cas12a in Arabidopsis
Authors: Lageix Sébastien , Sanchez-Rebato Miguel Hernandez , Gallego Maria E. , Verbeke Jérémy , Bidet Yannick , Viala Sandrine , White Charles I. 
Published: August 2024

AbstractSequence-specific endonucleases have been key to the study of the mechanisms and control of DNA double-strand break (DSB) repair and recombination and the availability of CRISPR-Cas nucleases over the last decade has driven rapid progress in understanding and application of targeted recombination in many organisms, including plants. We present here an analysis of recombination at targeted chromosomal 5’overhang DSB generated by the FnCas12a endonuclease in the plant,Arabidopsis thaliana. The much-studied Cas9 nuclease cleaves DNA to generate blunt-ended, double-strand breaks (DSB), but relatively less is known about the repair of other types of breaks, such as those with 5’-overhanging ends. Sequencing the repaired breaks clearly shows that the majority of repaired DSB carry small deletions and are thus repaired locally by End-Joining recombination, confirmed by Nanopore sequencing of larger amplicons. Paired DSB generate deletions at one or both cut-sites, as well as deletions and reinsertions of the deleted segment between the two cuts, visible as inversions. While differences are seen in the details, overall the deletion patterns are similar between repair at single-cut and double-cut events, notwithstanding the fact that only the former involve cohesive DNA overhangs. A strikingly different repair pattern is however observed at breaks flanked by direct repeats. This change in sequence context results in the presence of an alternative class of repair events, corresponding to highly efficient repair by Single-strand Annealing recombination.
Rational design paving the way for improving glucose tolerance and catalytic properties of a β-glucosidase fromAcetivibrio thermocellus
Authors: Kamale Chinmay , Rauniyar Abhishek , Bhaumik Prasenjit 
Published: August 2024

AbstractCellulases are an ensemble of enzymes that hydrolyse cellulose chains to fermentable glucose, hence, are widely used in bioethanol production. The last enzyme of the cellulose degradation pathway - β-glucosidase, is inhibited by its product – glucose. The product inhibition by glucose hinders cellulose hydrolysis limiting the saccharification during bioethanol production. Therefore, engineered β-glucosidases with improved glucose tolerance along with the catalytic efficiency are the need of the hour. This study focuses on the rational engineering of β-glucosidase fromAcetivibrio thermocellus(WT-AtGH1). Recombinant WT-AtGH1 exhibited activity on cellobiose and p-nitrophenyl-β-D-glucosidase as substrates and retained around 80% of its activity over 48 hours at 55°C, pH 5.5. However, WT-AtGH1 showed low glucose tolerance of 380 mM as compared to the requiredIC50value of > 800 mM for industrial use. Therefore, the rational design approach was applied for improving the glucose tolerance of this enzyme. We determined 3 Å resolution crystal structure of WT-AtGH1. The structure-based engineered G168W-AtGH1 and S242W-AtGH1 mutants exhibited improved glucose tolerance of 840 mM and 612 mM, respectively. Surprisingly, S242L-AtGH1 mutant showed ∼ 2.5-fold increase in the catalytic efficiency as compared to WT-AtGH1. A combinatorial effect of improved glucose tolerance, as well as enhanced catalytic efficiency, was observed for the G168W-S242L-AtGH1 mutant. All the mutants with enhanced properties showed considerable stability at industrial operating conditions of 55°C and pH 5.5. Thus, we present the next-generation mutants of WT-AtGH1 with improved glucose tolerance and kinetic properties that have the potential to increase the efficiency of the saccharification process for second generation bioethanol production.
The influence of the head model on magnetoencephalography-derived functional connectivity fingerprinting
Authors: Schelfhout Matthias , Hinault Thomas , Lago Sara , Arcara Giorgio , Amico Enrico , Fraschini Matteo , Marinazzo Daniele 
Published: August 2024

AbstractFunctional connectivity (FC)-based neural fingerprinting is an approach that promises to distinguish subjects within a cohort on the basis of the patterns of statistical dependencies between time series recorded mostly if not always noninvasively, with electroencephalography (EEG), magnetoencephalography (MEG), or functional magnetic resonance imaging (fMRI). The message is that brain activity is what differentiates subjects, or in other words, what makes a neural fingerprint “unique”. In EEG- and MEG-derived FC fingerprinting, the activity recorded at the sensors is projected back into cortical sources by means of an inverse model containing the shape of the head and its conductivity, and further averaged to obtain time series of regional activity, used to compute FC. In this study we investigated the role of the head model in fingerprinting. Through a set of experiments aimed to decouple recorded activity and head model for each subject, we found that the head model has a strong influence on the fingerprinting performance, according to two different sets of metrics.
C-COMPASS: A Neural Network Tool for Multi-Omic Classification of Cell Compartments
Authors: Haas Daniel Thomas , Trautmann Eva-Maria , Mao Xia , Gerl Mathias J. , Klose Christian , Cheng Xiping , Hasenauer Jan , Krahmer Natalie 
Published: August 2024

AbstractFunctional compartmentalization in eukaryotic cells is essential for maintaining physiological processes. The development of systematic organelle proteomic techniques, such as Protein Correlation Profiling (PCP) and Localization of Organelle Proteins by Isotope Tagging (LOPIT), has enhanced our understanding of organelle dynamics and protein localization. However, the complexity of the data and the need for advanced computational skills limit their accessibility. To address this, we introduce C-COMPASS, an open-source software featuring a user-friendly interface that utilizes a neural network-based regression model to predict the spatial distribution of proteins across cellular compartments. C-COMPASS manages complex multilocalization patterns and integrates protein abundance information to model organelle composition changes under various biological conditions. Using C-COMPASS, we mapped the organelle proteomic landscapes of humanized liver mice in different metabolic states and modeled changes in organelle composition to provide insights into cellular adaptations. Additionally, we extended cellular maps to the lipid level by co-generating protein and lipid profiles. C-COMPASS trains neural networks with marker protein profiles to predict lipid localizations, enabling parallel mapping of lipid and protein localization. This approach overcomes the lack of knowledge of organelle-specific lipid markers and identifies previously unknown organelle-specific lipid species. C-COMPASS offers a comprehensive solution for studying organelle dynamics at the multi-omics level, designed to be accessible without requiring extensive computational expertise or specialized high-performance computing equipment.
DNA spontaneously wrapping around a histone core prefers negative supercoiling: A Brownian dynamics study
Authors: Long Chunhong , Liang Hongqiong , Wan Biao 
Published: August 2024

AbstractIn eukaryotes, DNA achieves a highly compact structure primarily due to its winding around the histone cores. The nature wrapping of DNA around histone core form a 1.7 left-handed superhelical turns, contributing to negative supercoiling in chromatin. On the contrary, negative supercoils generated behind the polymerase during transcription may play a role in triggering nucleosome reassembly. To elucidate how supercoils influence the dynamics of wrapping of DNA around the histone cores, we developed a novel model to simulate the intricate interplay between DNA and histone. Our simulations revealed that both positively and negatively supercoiled DNAs are capable of wrapping around histone cores to adopt the nucleosome conformation. Most of all, our findings confirmed a preference for negative supercoiled DNA during nucleosome wrapping, and revealed that the both of the negative writhe and twist are comparatively beneficial to the formation of the DNA wrapping around histone. This advancement in the understanding of spontaneously nucleosome formation may provide insights into the intricate dynamics of chromatin assembly and its diverse functions. Our model thus can be further utilized to simulate the formations of multi-nucleosomes during re-assembling of the chromatin fiber, which will significantly enhance the understanding of the fundamental mechanisms governing the structure and function of chromatin.Author summaryThe compacted organization of DNA within chromatin is primarily attributed to its intricate winding around histone cores. This winding process involves 1.7 left-handed superhelical turns around the histone core, contributing to the negative supercoiling within chromatin fibers. To gain deeper insights into how DNA supercoiling impacts the dynamics of DNA wrapping around histone cores, we devised a novel computational model that simulates the intricate interplay between DNA and histone cores. Additionally, our simulations revealed that both of the positively and negatively supercoiled DNA can spontaneously adopt the nucleosome conformation upon wrapping around the histone core, and demonstrated a preferential tendency for negative supercoiling during nucleosome wrapping. Finally, we examined that both the negative writhe and twist components are comparatively advantageous for the formation of the nucleosome. The studies shed light on the intricate dynamics underlying chromatin assembly and its functional implications.
The challenges of replication: a worked example of methods reproducibility using electronic health record data
Authors: Williams Richard , Bolton Thomas , Jenkins David , Mizani Mehrdad A , Sperrin Matthew , FMedSci Cathie Sudlow , Wood Angela , Heald Adrian , Peek Niels 
Published: August 2024

AbstractObjectiveThe ability to reproduce the work of others is an essential part of the scientific disciplines. Replicating observational studies using electronic health record (EHR) data can be challenging due to complexities in data access, variations in EHR systems across institutions, and the potential for unaccounted confounding variables. Our aim is to identify the barriers to methods reproducibility for replication studies using EHR data.MethodsWe replicated a study that examined the risk of hospitalisation following a positive COVID-19 test in individuals with diabetes. Using EHR data from the NHS England’s Secure Data Environment (SDE) covering the whole of England, UK (population 57m), we sought to replicate findings from the original study, which used data from Greater Manchester (a large urban region in the UK, population 2.9m). Both analyses were conducted in Trusted Research Environments (TREs) or SDEs, containing linked primary and secondary care data, however methods reproducibility was not straightforward. Differences between the environments that contributed to the difficulties were documented, categorized into themes, and converted into a list of recommendations for TRE/SDEs.ResultsSmall differences between the environments and the data sources led to several challenges in methods reproducibility. Our recommendations of TRE/SDEs should facilitate future replication studies. The recommendations include: a need for improved machine-readable metadata for EHR data; standardization of governance processes to facilitate federated analysis; mandating of code sharing; and for environments to have a support structure for data engineers and analysts. We also propose a new theme for research, “data reproducibility”, as the ability to prepare, extract and clean data from a different database for a replication study.ConclusionEven with perfect code sharing, data reproducibility remains a challenge. Our recommendations have the potential to reduce the barriers to replication studies and therefore enhance the potential of observational studies using EHR data.
Generative artificial intelligence: opportunities, challenges and future avenues for organizational learning
Authors: Rahman Hanfia , Singh Tripti 
Published: August 2024

Purpose
This study provides a comprehensive investigation of the opportunities and challenges associated with generative artificial intelligence (GAI) use in development and learning in organizations. Additionally, it highlights the future avenues in GAI research and provides practical recommendations for policymakers.

Design/methodology/approach
Data for the review was collected from the Web of Science database using the search criteria (“Generative artificial intelligence” OR “artificial intelligence”) AND (“human resource management” OR “human resource development” OR “workplace learning” OR “organizational learning” OR “organizational development” OR “learning organization”) on March 6th, 2024. Filtering results to Management and Business categories yielded 71 articles. After abstract review, 6 unrelated articles were excluded, leaving 65 articles for final analysis.

Findings
The study presents several opportunities of GAI such as applications in personal learning and content generation. Moreover, it unravels several potential challenges of GAI such as quality and accuracy issues and elucidates several future research directions.

Originality/value
Our study is the first literature review that provides and a comprehensive overview of generative artificial intelligence in the context of organizational learning.
ESG performance, corporate innovation and downside risk: empirical evidence from China
Authors: Lin Binghong , Li Bingxiang 
Published: August 2024

PurposeThis study mainly explores how ESG performance (ESG stands for Environment, Social, and Governance) affects corporate downside risk through innovation input and innovation output, thereby promoting sustainable development of enterprises.Design/methodology/approachUsing Chinese A-share listed companies from 2014 to 2022 as research samples, a stepwise regression method is used to empirically test the impact of ESG performance on corporate innovation and downside risk by constructing multiple multivariate primary regression models.FindingsESG performance is beneficial for obtaining external resources and alleviating principal-agent problems. It can promote enterprises to increase innovation input and improve innovation output, thereby enhancing their core competitiveness, and suppressing their downside risk. This inhibitory effect is more significant in non-state-owned enterprises, non-high-tech enterprises, and enterprises where the chairman and the general manager are not combined in one. Further additional analysis has found that equity concentration weakens the inhibitory effect of ESG performance on corporate downside risk, equity balance strengthens the inhibitory effect of ESG performance on corporate downside risk, indicating that a mutually restrictive equity structure is conducive to promoting enterprises to actively fulfill ESG responsibility, thereby improving corporate innovation level and resolving their downside risk.Practical implicationsEnterprise managers, policy makers, and other practitioners can clearly see the benefits of implementing ESG measures, further strengthen their confidence in sustainable development, actively apply ESG concepts to the entire production and operation process of enterprises, increase attention and implementation of ESG elements, and promote the healthy and vigorous development of enterprises and macroeconomics.Originality/valueThe research conclusions reveal the inherent mechanism by which ESG performance empowers enterprises to improve their innovation level and reverse their performance decline, effectively expanding the theoretical achievements of ESG performance in enterprise innovation and risk management.
Blockchain for the circular economy, implications for public governance
Authors: Acosta Llano Eduardo , Hurmelinna-Laukkanen Pia , Haapanen Lauri 
Published: August 2024

Purpose This study examines the intricate interplay of blockchain, public governance and the circular economy (CE), aiming to assess the potential of blockchain technology (BT) in addressing challenges associated with the adoption of CE principles, particularly in the public sector.Design/methodology/approach Focused on public governance, the research employs in-depth interviews with Finnish policymakers actively engaged in CE initiatives. Qualitative analysis is applied to derive insights and patterns from the gathered data, providing a nuanced understanding of blockchain’s transformative role.Findings The study uncovers key dimensions for leveraging blockchain in the CE within the public sector. Notable findings include the significance of contextual transparency, the use of incentivization as a regulatory tool, the role of standardization through strategic autonomy and the importance of public engagement and participation.Originality/value This research contributes a unique framework that illuminates the transformative potential of blockchain within the CE, emphasizing its relevance to public governance. The identified dimensions offer practical insights for policymakers and practitioners seeking to navigate the complexities of circular transitions in the public sector.
Constructing Sukuk-linked Awqaf (endowment) model
Authors: Ismal Rifki 
Published: August 2024

Purpose
Islamic endowment (awqaf), particularly awqaf land, is one of the potential Islamic social assets to serve the public interest, particularly to provide public infrastructures such as business centers, public hospitals and airports. However, unfortunately, most of them are still unproductive lands, especially in the form of idle lands. One problem to use such unproductive awqaf lands is the lack of awqaf land model as the platform to use such awqaf lands. This paper aims to construct and propose a model called Sukuk-linked Awqaf (SLA) to use awqaf lands as an underlying for Sukuk issuance.

Design/methodology/approach
This paper constructs mechanisms and formulas of SLA by involving Sukuk issuer, awqaf management (Nadzhir), Sukuk investors and tenants of the infrastructure. In particular, the SLA model is proposed based on the unique characteristics of both awqaf asset and Ijarah (leasing) Sukuk, considers the intention of state-owned enterprise (SOE) to construct buildings to be rented to the tenant and to be owned by the awqaf manager and formulates equations and uses net present value theory to determine Nadzhir and Sukuk investors’ investment decisions.

Findings
Engaging awqaf land with SLA model can ease its benefit for the society. The model addresses the strategic roles of Nadzhir, SOE, investors and contractor in using awqaf land.

Research limitations/implications
The SLA model could ease related parties to use the awqaf land for the sake of public benefits.

Originality/value
To the best of the author’s knowledge, this is the first assessment on the potential implementation of Islamic hedging with a commodity as an alternative hedging in Indonesia.