bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA mis-splicing in children with myotonic dystrophy is associated with physical function
Authors: Hartman Julia M. , Ikegami Kobe , Provenzano Marina , Bates Kameron , Butler Amanda , Jones Aileen S. , Berggren Kiera N. , Dekdebrun Jeanne , McKay Marnee J. , Baldwin Jennifer N. , Cornett Kayla M.D. , Burns Joshua , Kiefer Michael , Johnson Nicholas E. , Hale Melissa A. 
Published: July 2024

AbstractObjectivesDysregulated RNA alternative splicing is the hallmark of myotonic dystrophy type 1 (DM1). However, the association between RNA mis-splicing and physical function in children with the most severe form of disease, congenital myotonic dystrophy (CDM), is unknown.Methods82 participants (42 DM1 adults & 40 CDM children) with muscle biopsies and measures of myotonia, motor function, and strength were combined from five observational studies. Data were normalized and correlated with an aggregate measure of alternative splicing dysregulation, [MBNL]inferredin skeletal muscle biopsies. Multiple linear regression analysis was performed to predict [MBNL]inferredusing clinical outcome measures alone. Similar analyses were performed to predict 12-month physical function using baseline metrics.ResultsMyotonia (measured via vHOT) was significantly correlated with RNA mis-splicing in our cross-sectional population of all DM1 individuals; CDM participants alone displayed no myotonia despite a similar range of RNA mis-splicing. Measures of motor performance and muscle strength were significantly associated with [MBNL]inferredin our cohort of all DM1 individuals and when assessing CDM children independently. Multiple linear regression analyses yielded two models capable of predicting [MBNL]inferredfrom select clinical outcome assessments alone in all subjects (adjusted R2= 0.6723) or exclusively in CDM children (adjusted R2= 0.5875).InterpretationOur findings establish significant correlations between skeletal muscle performance and a composite measure of alternative splicing dysregulation, [MBNL]inferred,in DM1. The strength of these correlations and the development of the predictive models will assist in designing efficacious clinical trials for individuals with DM1, particularly CDM.
Ambivalent partnership of the Drosophila posterior class Hox protein Abdominal-B with the Extradenticle and Homothorax cofactors
Authors: Curt Jesús R. , Martín Paloma , Foronda David , Hudry Bruno , Kannan Ramakrishnan , Shetty Srividya , Merabet Samir , Saurin Andrew , Graba Yacine , Herrero Ernesto Sanchez 
Published: July 2024

ABSTRACTHox proteins, a sub-group of the homeodomain (HD) transcription factor family, provide positional information for axial patterning in development and evolution. Hox protein functional specificity is reached, at least in part, through Pbc (Extradenticle (Exd) in Drosophila) and Meis/Prep (Homothorax (Hth) in Drosophila) cofactor interactions. Most of our current knowledge of Hox protein specificity stems from the study of anterior and central Hox proteins, identifying the molecular and structural bases for Hox/Pbc/Meis-Prep cooperative action. Posterior Hox class proteins, Abd-B in Drosophila and Hox9-13 in vertebrates, have been comparatively less studied. They strongly diverge from anterior and central class Hox proteins, with a low degree of HD sequence conservation and the absence of a core canonical Pbc interaction motif. Here we explore how Abd-B function interface with that of Exd/Hth using several developmental contexts, studying mutual expression control, functional dependency and intrinsic protein requirements. Results identify cross regulatory interactions setting relative expression and activity levels required for proper development. They also reveal organ-specific requirement and a binary functional interplay with Exd and Hth, either synergistic or antagonistic. This highlights context specific use of Exd/Hth cofactors, and a similar context specific use of Abd-B protein intrinsic protein requirements.
A flexible framework for minimal biomarker signature discovery from clinical omics studies without library size normalisation
Authors: Rawlinson Daniel , Zhou Chenxi , Lê Cao Kim-Anh , Coin Lachlan J.M. 
Published: July 2024

AbstractApplication of transcriptomics, proteomics and metabolomics technologies to clinical cohorts has uncovered a variety of signatures for predicting disease. Many of these signatures require the full ‘omics data for evaluation on unseen samples, either explicitly or implicitly through library size normalisation. Translation to low-cost point-of-care tests requires development of signatures which measure as few analytes as possible without relying on direct measurement of library size.To achieve this, we have developed a feature selection method (Forward Selection-Partial Least Squares) which generates minimal disease signatures from high-dimensional omics datasets with applicability to continuous, binary or multi-class outcomes. Through extensive benchmarking, we show that FS-PLS has comparable performance to commonly used signature discovery methods while delivering signatures which are an order of magnitude smaller. We show that FS-PLS can be used to select features predictive of library size, and that these features can be used to normalize unseen samples, meaning that the features in the complete model can be measured in isolation for making new predictions.By enabling discovery of small, high-performance signatures, FS-PLS addresses an important impediment for the further development of precision medical care.
Tsa1 is the dominant peroxide scavenger and a source of H2O2-dependent GSSG production in yeast
Authors: Zimmermann Jannik , Lang Lukas , Calabrese Gaetano , Laporte Hugo , Amponsah Prince S , Michalk Christoph , Sukmann Tobias , Oestreicher Julian , Tursch Anja , Peker Esra , Owusu Theresa N E , Weith Matthias , Roma Leticia Prates , Deponte Marcel , Riemer Jan , Morgan Bruce 
Published: July 2024

AbstractHydrogen peroxide (H2O2) is an important biological molecule, functioning both as a second messenger in cell signaling and, especially at higher concentrations, as a cause of cell damage. Cells harbor multiple enzymes that have peroxide reducing activityin vitro. However, the contribution of each of these enzymes towards peroxide scavengingin vivois less clear. Therefore, to directly investigatein vivoperoxide scavenging, we used the genetically encoded peroxide sensors, roGFP2-Tsa2ΔCRand HyPer7, to systematically screen the peroxide scavenging capacity of yeast thiol and heme peroxidase mutants. We show that the 2-Cys peroxiredoxin Tsa1 alone is responsible for almost all exogenous H2O2andtert-butyl hydroperoxide scavenging. The two catalases and cytochromecperoxidase only produce observable scavenging defects at higher H2O2concentrations when these three heme peroxidases are deleted in combination. We also analyzed the reduction of Tsa1in vitro, revealing that the enzyme is efficiently reduced by thioredoxin 1 with a rate constant of 2.8×106M−1s−1. When thioredoxins are oxidized, Tsa1 can become an important source of H2O2-dependent cytosolic glutathione disulfide production in yeast. Our findings clarify the importance of the various thiol and heme peroxidases for peroxide removal and suggest that most thiol peroxidases have alternative or specialized functions in specific subcellular compartments.
Developing, characterizing and modeling CRISPR-based point-of-use pathogen diagnostics
Authors: Jung Jaeyoung K. , Dreyer Kathleen S. , Dray Kate E. , Muldoon Joseph J. , George Jithin , Shirman Sasha , Cabezas Maria D. , D’Aquino Anne E. , Verosloff Matthew S. , Seki Kosuke , Rybnicky Grant A. , Alam Khalid K. , Bagheri Neda , Jewett Michael C. , Leonard Joshua N. , Mangan Niall M. , Lucks Julius B. 
Published: July 2024

ABSTRACTRecent years have seen intense interest in the development of point-of-care nucleic acid diagnostic technologies to address the scaling limitations of laboratory-based approaches. Chief among these are combinations of isothermal amplification approaches with CRISPR-based detection and readouts of target products. Here, we contribute to the growing body of rapid, programmable point-of-care pathogen tests by developing and optimizing a one-pot NASBA-Cas13a nucleic acid detection assay. This test uses the isothermal amplification technique NASBA to amplify target viral nucleic acids, followed by Cas13a-based detection of amplified sequences. We first demonstrate an in-house formulation of NASBA that enables optimization of individual NASBA components. We then present design rules for NASBA primer sets and LbuCas13a guide RNAs for fast and sensitive detection of SARS-CoV-2 viral RNA fragments, resulting in 20 – 200 aM sensitivity without any specialized equipment. Finally, we explore the combination of high-throughput assay condition screening with mechanistic ordinary differential equation modeling of the reaction scheme to gain a deeper understanding of the NASBA-Cas13a system. This work presents a framework for developing a mechanistic understanding of reaction performance and optimization that uses both experiments and modeling, which we anticipate will be useful in developing future nucleic acid detection technologies.
A novel infective endocarditis virulence factor related to multiple functions for bacterial survival in blood was discovered inStreptococcus sanguinis
Authors: Anandan Vysakh , Bao Liang , Zhu Zan , Bradley Jennifer , Assi Valery-Francine , Chavda Henna , Kitten Todd , Xu Ping 
Published: July 2024

AbstractWe identified the role of a conserved hypothetical protein (SSA_0451) inS. sanguinisthat is involved in the virulence of infective endocarditis. Anin vitrowhole blood killing assay and rabbit endocarditis model studies revealed that the SSA_0451 mutant (ΔSSA_0451) was significantly less virulent than the wild-type (SK36) and its complementation mutant (ΔSSA_0451C). The mechanism underlying the SSA_0451 mutant’s reduced virulence in infective endocarditis was evidentially linked to oxidative stress and environmental stress. The genes related to the survival ofS. sanguinisin an oxidative stress environment were downregulated in ΔSSA_0451, which affected its survival in blood. Our findings suggest that SSA_0451 is a novel IE virulence factor and a new target for drug discovery against IE.Author summaryThis study focused on SSA_0451, a conserved hypothetical protein inS. sanguinis, to explore its potential role as a virulence factor. Throughin vitrowhole blood killing assays and rabbit IE models, it was found that the SSA_0451 mutant exhibited reduced virulence compared to the wild-type and a complemented mutant. The study linked the mutant’s diminished virulence in IE to heightened susceptibility to oxidative and environmental stresses, supported by downregulation of genes crucial for oxidative stress survival inS. sanguinis. These findings identify SSA_0451 as a novel virulence factor in IE and propose it as a promising target for future drug development against this condition.
Profiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries
Authors: Comstock Will , Sanford Ethan , Navarro Marcos , Smolka Marcus B 
Published: July 2024

AbstractThe stability of the genome relies on Phosphatidyl Inositol 3-Kinase-related Kinases (PIKKs) that sense DNA damage and trigger elaborate downstream signaling responses. InS. cerevisiae, the Tel1 kinase (ortholog of human ATM) is activated at DNA double strand breaks (DSBs) and short telomeres. Despite the well-established roles of Tel1 in the control of telomere maintenance, suppression of chromosomal rearrangements, activation of cell cycle checkpoints, and repair of DSBs, the substrates through which Tel1 controls these processes remain incompletely understood. Here we performed an in depth phosphoproteomic screen for Tel1-dependent phosphorylation events. To achieve maximal coverage of the phosphoproteome, we developed a scaled-up approach that accommodates large amounts of protein extracts and chromatographic fractions. Compared to previous reports, we expanded the number of detected Tel1-dependent phosphorylation events by over 10-fold. Surprisingly, in addition to the identification of phosphorylation sites featuring the canonical motif for Tel1 phosphorylation (S/T-Q), the results revealed a novel motif (D/E-S/T) highly prevalent and enriched in the set of Tel1-dependent events. This motif is unique to Tel1 signaling and not shared with the Mec1 kinase, providing clues to how Tel1 plays specialized roles in DNA repair and telomere length control. Overall, these findings define a Tel1-signaling network targeting numerous proteins involved in DNA repair, chromatin regulation, and telomere maintenance that represents a framework for dissecting the molecular mechanisms of Tel1 action.
Ecology of prophage-like elements inBacillus subtilisat global and local geographical scale
Authors: Stefanič Polonca , Stare Eva , Floccari Valentina A. , Kovac Jasna , Hertel Robert , Rocha Ulisses , Kovács Ákos T. , Mandić-Mulec Ines , Strube Mikael Lenz , Dragoš Anna 
Published: July 2024

SummaryProphages account for a substantial part of most bacterial genomes, but the impacts on hosts remain poorly understood. Here, we combined computational and laboratory experiments to explore the abundance, distribution, and activity of prophage elements inBacillus subtilis. NCBI database genome sequences and isolates from 1 cm3riverbank soil samples were analyzed to provide insights at global and local geographical scales, respectively. Most prophages in wildB. subtilisisolates were related to mobile genetic elements previously identified in laboratory strains. Some large groups of prophages were closely related to completely uncharacterized yet functional Bacillus phages, or completely unknown. As certain prophage groups were unique to local isolates, we explored factors influencing prophages within a single genome. Phylogenetic relatedness was a slightly better predictor of host prophage repertoire than geographical origin. We show that cryptic phages can play a major role in acquisition and/or maintenance of other prophage elements both via strong antagonism or by co-dependence. Laboratory experiments showed that most predicted prophages may be cryptic, since they failed to induce under DNA-damaging stress conditions. Interestingly, the magnitude of stress responses remained proportional to the total number of prophage elements predicted, suggesting their importance in host physiology. This study highlights the diversity, integration patterns, and co-occurrence of prophages inB. subtilisand their potential impact on host evolution and physiology. Understanding these dynamics provides insight into bacterial genome evolution and prophage-host interactions, laying the groundwork for future experimental studies on the roles of phages in the ecology and evolution of this bacterial species.
Promoted Read-through and Mutation Against Pseudouridine-CMC by an Evolved Reverse Transcriptase
Authors: He Zhiyong , Qiu Weiqi , Zhou Huiqing 
Published: July 2024

ABSTRACTPseudouridine (Ψ) is an abundant RNA chemical modification that can play critical roles in the biological functions of RNA, and RNA-therapeutic applications. Current Ψ detection methods are limited in identifying Ψs at base-resolution in U-rich sequence contexts, where Ψ occurs frequently. The N-cyclohexyl N’-(2-morpholinoethyl)carbodiimide (CMC) can selectively label Ψ in RNA by forming the CMC-Ψ adduct. Here we report that an evolved reverse transcriptase (“RT-1306”) shows promoted read-through and mutation against the CMC-Ψ. The mutation signature can resolve the occurrence of Ψs within UU-containing sequences. We developed “Mut-Ψ-seq” utilizing CMC and RT-1306 for transcriptome-wide mapping of Ψ at base-resolution. The mutation signatures robustly identify reported Ψs in human rRNAs via the ROC analysis, and elongated CMC reaction duration increases the detection sensitivity of Ψ. We report a high-confidence list of Ψ sites in polyA-enriched RNAs from HEK-293T cells identified by orthogonal chemical treatments (CMC and bisulfite). The mutation signatures resolve the position of Ψ in UU-containing sequences, revealing diverse occurrence of Ψs in such sequences. This work provides new methods and datasets for biological research of Ψ, and demonstrates the potential of combining the reverse transcriptase engineering and selective chemical labeling to expand the toolkit for RNA chemical modifications studies.
Legal nature of the court’s discretionary power in business contract revocation
Authors: Khawaldeh Ahmed M. 
Published: July 2024

Purpose
This paper aims to know the legal nature of the court’s discretionary power in business contract revocation.

Design/methodology/approach
Following the normative method that analyzes legislation using secondary data consisting of primary, secondary and tertiary legal materials, this research was conducted during the period November, 2023 – February, 2024. Moreover, studies that addressed the legal nature of the court’s discretionary power in business contract revocation and published since 2000 were included. The focus was made upon the business contract’s retroactive effect in relation to the Court’s discretionary power.

Findings
From the initial 312 studies reviewed, 20 met the inclusion criteria. The business contract's retroactive effect in relation to the Court’s discretionary power has been considered by the relatively small number of studies included in the review. Researchers from different countries explored the phenomenon, using different approaches to explore the topic. However, none of these researchers has examined the phenomenon in the Jordanian Context.

Research limitations/implications
This research is unique, as it examines the legal nature of the court’s discretionary power in business contract revocation, which has not been investigated in the Jordanian context. The previous researches on business contract revocation have addressed laws other than the Jordanian law.

Practical implications
This research will be a guide for the Jordanian legislation to draft a business contract law that regulates the court's interference in cases of business contract revocation and clearly specify its role in this regard.

Social implications
This research will increase the Jordanian people's awareness of the legal nature of court in cases of business contract revocation. Moreover, it will make them familiar with the current laws so that they will legally deal with cases of this kind.

Originality/value
It is very important to conduct this research to review the papers and laws related to business contract revocation in Jordan since this issue has not been investigated.
The emergence of discrimination due to miscategorization
Authors: Yasar M. Alperen 
Published: July 2024

PurposeThis study explores the emergence of discrimination based on observable characteristics. In many instances, agents presume differences arising from traits such as race or gender, even when these parameters are irrelevant to the situation at hand. This paper intends to reveal an emergent behavior and a persistent culture of discrimination caused by miscategorization in strategic interactions.Design/methodology/approachWe assume that agents occasionally engage in conflicts modeled as asymmetric hawk and dove games, where boundedly rational agents may categorize their opponents based on observable traits to make effective decisions. Three categorization strategies are considered: fine-grained, regular, and coarse-grained. Subsequently, an evolutionary agent-based model is employed to examine the performance of these strategies in a dynamic environment.FindingsThe results demonstrate that fine-grained categorization provides an advantage when the cost of fighting is low, while coarse-grained categorizers exhibit more peaceful behavior, gaining an advantage when the cost of conflict is high. Our primary finding indicates the emergence of discrimination based on non-relevant traits, manifested through consistent aggressive behavior towards individuals possessing these traits.Originality/valueThis paper is the first to investigate the emergence of discrimination without assuming prior differences between groups. Previous studies have assumed either an initial population difference or a homophily-based approach. In contrast, we demonstrate that discrimination can emerge even in the absence of such assumptions. Discrimination between two groups may arise as long as there are agents who label these categories.
The relationship between low-consumption single-use plastic awareness and behaviour: a case study of FPT University students (Ho Chi Minh Branch)
Authors: Nguyen Nhi Yen , Tran Hao Gia , Tra Dang Thanh , Le Nhung Tuyet , Nguyen Hien Thi Thuy 
Published: July 2024

Purpose
This study aims to combine two theories, the Theory of Planned Behaviour (TPB) and the Norm Activation Model (NAM), to investigate the relationship between the awareness of reducing single-use plastic waste's environmental cost and the behaviour to limit the use of single-use plastic products (SUPPs) by FPT university students.

Design/methodology/approach
Quantitative research methodologies were employed on a sample of 506 university students. The survey data was then examined using SPSS, SPSS AMOS and SmartPLS software.

Findings
The overarching conclusion of the study is that awareness of reducing single-use plastic waste's environmental cost has a positive impact on FPT university students' behaviour to reduce their use of single-use plastic products. Another intriguing discovery is how socialisation of responsibility affects pro-environmental behaviour through the interplay between personal norms, subjective norms and behavioural intention.

Originality/value
This study on the relationship between SUPP low-consumption awareness and behaviour and mediating factors is a necessary foundation for future studies related to changing the behaviour of students using SUPPs. That will also be a solid foundation for practical plans to change behaviour using SUPPs through communication campaigns to increase awareness.
Sustainability in (engineering) education through reclaiming and reusing electronic components from e-waste: a last decade research review
Authors: Nikoloudakis Nikolaos , Rangoussi Maria 
Published: July 2024

Purpose
This paper aims to investigate the e-waste aspect of sustainability in education, with a specific interest in engineering education. Specifically, it focuses on recycling through reclaiming electronic components from e-waste and reusing them in repairs or in the design and construction of new devices.

Design/methodology/approach
A systematic literature review is performed according to the PRISMA methodology. In total, 27 articles are analysed as to publication parameters, characteristics and evaluation of educational interventions on e-waste and evaluation results across major domains of learning (cognitive, affective and 21st century skills).

Findings
The reviewed subject is under-research; publications are rare and mostly in conference proceedings. The majority of interventions take place at university level, in face-to-face mode, using a practical approach in hands-on labs. Educational methods draw from modern, learner-centred pedagogies such as collaborative learning and constructionism. Topics focus on innovative design and construction, while interventions tend to become embedded in engineering curricula/courses. Evaluation of learners’ gains across domains of learning is rare and follows informal procedures that shake the reliability of results. Domains other than the cognitive are scarcely and subjectively evaluated.

Originality/value
Contrary to other aspects of sustainability, the aspect of e-waste has not been reviewed. The applied, hands-on approach and the analytic, synthetic, collaboration and creativity skills it requires are all much valued in education. The current review, therefore, comes to inform, inspire and guide educators and researchers in planning and implementing activities on this subject.