bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-125b differentially impacts mineralization in dexamethasone and calcium-treated human mesenchymal stem cells
Authors: Joris Virginie , Balmayor Elizabeth R. , van Griensven Martijn 
Published: August 2024

AbstractBone metabolism is highly regulated, and microRNAs (miR) can contribute to this process. Among them, miR-125b is well-known to enhance osteoporosis and reduce osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this work we aim to evaluate and understand how miR-125b modulates mineralization of hMSCs in two differentin vitromodels. Cells were cultured in dexamethasone or calcium medium and transfected with miR-125b mimic. Exposure to dexamethasone or calcium medium increased mineralization of hMSCs and was associated with decreased miR-125b expression. Transfection of miR-125b mimic in dexamethasone-treated cells increased mineralization while it decreased it in calcium-treated cells. Levels of osteogenic markers presented the same difference. We identified STAT3, p53 and RUNX2 as direct targets of miR-125b in hMSCs. While these targets remained identical in both treatments, their modulation after transfection was different. We showed that miR-125b mimicking differentially modulated the expression of the miR-199a/214 cluster, probably via STAT3/miR-199a/214, and p53/miR-214 pathways. In conclusion, miR-125b affinity for targets implicated in bone remodeling changed depending on thein vitromodels used to induce mineralization and led to opposite physiological effect. This works shows the complexity of drugs such as dexamethasone and opens the door for newin vitromodels of mineralization.
LDB1 establishes multi-enhancer networks to regulate gene expression
Authors: Aboreden Nicholas G. , Lam Jessica C. , Goel Viraat Y. , Wang Siqing , Wang Xiaokang , Midla Susannah C. , Quijano Alma , Keller Cheryl A. , Giardine Belinda M. , Hardison Ross C. , Zhang Haoyue , Hansen Anders S. , Blobel Gerd A. 
Published: August 2024

SUMMARYHow specific enhancer-promoter pairing is established is still mostly unclear. Besides the CTCF/cohesin machinery, only a few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Here, we show via acute degradation experiments that LDB1 directly and broadly promotes enhancer-promoter loops. Most LDB1-mediated contacts, even those spanning hundreds of kb, can form in the absence of CTCF, cohesin, or YY1 as determined via the use of multiple degron systems. Moreover, an engineered LDB1-driven chromatin loop is cohesin independent. Cohesin-driven loop extrusion does not stall at LDB1 occupied sites but may aid the formation of a subset of LDB1 anchored loops. Leveraging the dynamic reorganization of nuclear architecture during the transition from mitosis to G1-phase, we establish a relationship between LDB1-dependent interactions in the context of TAD organization and gene activation. Lastly, Tri-C and Region Capture Micro-C reveal that LDB1 organizes multi-enhancer networks to activate transcription. This establishes LDB1 as a direct driver of regulatory network inter-connectivity.
Efflux pumps and membrane permeability contribute to intrinsic antibiotic resistance inMycobacterium abscessus
Authors: McGowen Kerry , Funck Tobias , Wang Xin , Zinga Samuel , Wolf Ian D. , Akusobi Chidiebere C. , Denkinger Claudia M. , Rubin Eric J. , Sullivan Mark R. 
Published: August 2024

AbstractMycobacterium abscessusis a pulmonary pathogen that exhibits intrinsic resistance to antibiotics, but the factors driving this resistance are incompletely understood. Insufficient intracellular drug accumulation could explain broad-spectrum resistance, but whether antibiotics fail to accumulate inM. abscessusand the mechanisms required for drug exclusion remain poorly understood. We measured antibiotic accumulation inM. abscessususing mass spectrometry and found a wide range of drug accumulation across clinically relevant antibiotics. Of these compounds, linezolid accumulates the least, suggesting that inadequate uptake impacts its efficacy. We utilized transposon mutagenesis screening to identify genes that cause linezolid resistance and found multiple transporters that promote membrane permeability or efflux, including an uncharacterized,M. abscessus-specific protein that effluxes linezolid and several chemically related antibiotics. This demonstrates that membrane permeability and drug efflux are critical mechanisms of antibiotic resistance inM. abscessusand suggests that targeting membrane transporters could potentiate the efficacy of certain antibiotics.
Evolutionary adaptation under climate change:Aedessp. demonstrates potential to adapt to warming
Authors: Couper Lisa I. , Dodge Tristram O. , Hemker James A. , Kim Bernard Y. , Exposito-Alonso Moi , Brem Rachel B. , Mordecai Erin A. , Bitter Mark C. 
Published: August 2024

AbstractClimate warming is expected to shift the distributions of mosquitoes and mosquito-borne diseases, facilitating expansions at cool range edges and contractions at warm range edges. However, whether mosquito populations could maintain their warm edges through evolutionary adaptation remains unknown. Here, we investigate the potential for thermal adaptation inAedes sierrensis, a congener of the major disease vector species that experiences large thermal gradients in its native range, by assaying tolerance to prolonged and acute heat exposure, and its genetic basis in a diverse, field-derived population. We found pervasive evidence of heritable genetic variation in acute heat tolerance, which phenotypically trades off with tolerance to prolonged heat exposure. A simple evolutionary model based on our data shows that the estimated maximum rate of evolutionary adaptation in mosquito heat tolerance typically exceeds that of projected climate warming under idealized conditions. Our findings indicate that natural mosquito populations may have the potential to track projected warming via genetic adaptation. Prior climate-based projections may thus underestimate the range of mosquito and mosquito-borne disease distributions under future climate conditions.Significance StatementGlobal change may have profound impacts on the distribution of mosquito-borne diseases, which collectively cause nearly one million deaths each year. Accurately predicting these impacts is critical for disease control preparedness, and will depend, in part, on whether mosquitoes can adapt to warming—a key open question. Using experimental and genomic data from a relative of major vector species that already experiences a wide thermal gradient, we find that natural mosquito populations have high levels of genetically-based variation in heat tolerance that could enable adaptation on pace with warming. Incorporating the potential for adaptive responses may therefore be necessary for accurate predictions of mosquito-borne disease distributions under warming, which is critical for preparing mosquito control interventions.
Large Serine Integrase Off-target Discovery and Validation for Therapeutic Genome Editing
Authors: Hazelbaker Dane Z. , Mehta Japan B. , McGinnis Connor , Santesmasses Didac , Bara Anne M. , Liang Xiaoyu , Biondi Thomas , Fennell Tim , Homer Nils , Estes Brett , Xie Jenny , Norouzi Davood , Molugu Kaivalya , Amunugama Ravindra , Luo Chong , Amin Parth , Shi Xiarong , Cochrane Jesse , Kumar Sandeep , Wang Jie , Bakalar Matthew H. , Finn Jonathan D. , O’Connell Daniel J. 
Published: August 2024

SUMMARYWhile numerous technologies for the characterization of potential off-target editing by CRISPR/Cas9 have been described, the development of new technologies and analytical methods for off-target recombination by Large Serine Integrases (LSIs) are required to advance the application of LSIs for therapeutic gene integration. Here we describe a suite of off-target recombination discovery technologies and a hybrid capture validation approach as a comprehensive framework for off-target characterization of LSIs. HIDE- Seq (High-throughput Integrase-mediated DNA Event Sequencing) is a PCR-free unbiased genome-wide biochemical assay capable of discovering sites with LSI- mediated free DNA ends (FDEs) and off-target recombination events. Cryptic-Seq is a PCR-based unbiased genome-wide biochemical or cellular-based assay that is more sensitive than HIDE-Seq but is limited to the discovery of sites with off-target recombination. HIDE-Seq and Cryptic-Seq discovered 38 and 44,311 potential off-target sites respectively. 2,455 sites were prioritized for validation by hybrid capture NGS in LSI- edited K562 cells and off-target integration was detected at 52 of the sites. We benchmarked the sensitivity of our LSI off-target characterization framework against unbiased whole genome sequencing (WGS) on LSI-edited samples, and off-target integration was detected at 5 sites with an average genome coverage of 40x. This reflects a greater than 10-fold increase in sensitivity for off-target detection compared to WGS, however only 4 of the 5 sites detected by WGS were also validated by hybrid capture NGS. The dissemination of these technologies will help advance the application of LSIs in therapeutic genome editing by establishing methods and benchmarks for the sensitivity of off-target detection.
Robustness and reliability of single-cell regulatory multi-omics with deep mitochondrial mutation profiling
Authors: Weng Chen , Weissman Jonathan S. , Sankaran Vijay G. 
Published: August 2024

AbstractThe detection of mitochondrial DNA (mtDNA) mutations in single cells holds considerable potential to define clonal relationships coupled with information on cell state in humans. Previous methods focused on higher heteroplasmy mutations that are limited in number and can be influenced by functional selection, introducing biases for lineage tracing. Although more challenging to detect, intermediate to low heteroplasmy mtDNA mutations are valuable due to their high diversity, abundance, and lower propensity to selection. To enhance mtDNA mutation detection and facilitate fine-scale lineage tracing, we developed the single-cell Regulatory multi-omics with Deep Mitochondrial mutation profiling (ReDeeM) approach, an integrated experimental and computational framework. Recently, some concerns have been raised about the analytical workflow in the ReDeeM framework. Specifically, it was noted that the mutations detected in a single molecule per cell are enriched on edges of mtDNA molecules, suggesting they resemble artifacts reported in other sequencing approaches. It was then proposed that all mutations found in one molecule per cell should be removed. We detail our error correction method, demonstrating that the observed edge mutations are distinct from previously reported sequencing artifacts. We further show that the proposed removal leads to massive elimination of bona fide and informative mutations. Indeed, mutations accumulating on edges impact a minority of all mutation calls (for example, in hematopoietic stem cells, the excess mutations on the edge account for only 4.3%-7.6% of the total). Recognizing the value of addressing edge mutations even after applying consensus correction, we provide an additional filtering option in the ReDeeM-R package. This approach effectively eliminates the position biases, leads to a mutational signature indistinguishable from bona fide mitochondrial mutations, and removes excess low molecule high connectedness mutations. Importantly, this option preserves the large majority of unique mutations identified by ReDeeM, maintaining the ability of ReDeeM to provide a more than 10-fold increase in variant detection compared to previous methods. Additionally, the cells remain well-connected. While there is room for further refinement in mutation calling strategies, the significant advances and biological insights provided by the ReDeeM framework are unique and remain intact. We hope that this detailed discussion and analysis enables the community to employ this approach and contribute to its further development.
Hydrogen Bonding Magnetic Resonance (HBMR)-based Cyclic Electromagnetic DNA Simulation (CEDS) can affect DNA Hybridization and Conformation
Authors: Lee Suk Keun , Lee Dae Gwan , Kim Yeon Sook 
Published: August 2024

AbstractThe proton magnetic resonance is commonly used in MRI machines with a strong magnetic field of over 1 T, while this study hypothesized that a weak magnetic field below 0.01 T can induce the proton magnetic resonance in hydrogen bonds of double-stranded DNA (dsDNA). This study found the hydrogen bonding magnetic resonance (HBMR) in dsDNA can modulate the conformations and functions of dsDNAs (1). Decagonal or dodecagonal cyclic electromagnetic DNA simulation (CEDS) was designed to target three-dimensional structures of randomly oriented dsDNAs with about 25% efficiency. This study found that the most effective magnetic exposure times for inducing an electric potential in A-T and G-C base pairs were 280 and 480 msec, respectively. Decagonal CEDS using a target sequence at 20-25 Gauss for 30 min was able to induce sequence-specific hybridization of target short oligo-dsDNAs in 0.005M NaCl solution and their unique conformation in 0.1M NaCl solution. There was a tendency that Pyu oligo-dsDNAs showed more hybridization and unique conformational changes by CEDS using a target sequence than Puy oligo-dsDNAs. This CEDS effect on Pyu ds6(2C2A) increased with CEDS time up to 90 min and gradually decreased to about half (51.8%) of the increase at 240 min resting time. CEDS influenced the oligo-dsDNAs to increase their infrared (IR) absorbance at approximately 3700-2800 cm-1band compared to the positive and negative controls, which was more dominant in Pyu oligo-dsDNAs than in Puy oligo-dsDNAs. Therefore, it is postulated that HBMR-based CEDS using a weak magnetic field can increase the hybridization potential of oligo-dsDNAs and subsequently lead to unique DNA conformation required for the initiation of various DNA functions. Therefore, it is suggested that decagonal CEDS play a role in regulating the function of target short oligo-dsDNA.
Single-cell analysis of the somatic mutational landscape in human chondrocytes during aging and in osteoarthritis
Authors: Ren Peijun , Zheng Chen , Pang Yidan , Sun Shixiang , Wang Qiyang , Xu Wanxing , Lee Moonsook , Qiang Yu , Lu Zhenzhen , Zhou Min , He Jian , Liu Ningning , Maslov Alexander Y. , Dong Xiao , Gao Junjie , Zhang Changqing , Vijg Jan 
Published: August 2024

AbstractSomatic mutation is now recognized as a cause of multiple human diseases other than cancer. Osteoarthritis (OA), a highly prevalent age-related disease, has been associated with increased chromosomal abnormalities in articular cartilage of OA patients. Thus far no systematic attempt has been made to characterize the somatic mutational landscape of chondrocytes during normal aging and in affected cartilage of OA patients. Here we used single-cell whole genome sequencing to quantitatively analyze single-nucleotide variants (SNVs) and small insertions and deletions (InDels) in 100 single chondrocytes isolated from the cartilage of hip femoral heads of 17 subjects aged from 26 to 90 years, including 9 OA patients and 8 non-OA donors. Both SNVs and InDels were found to accumulate with age in chondrocytes with a clock-like mutational signature. Surprisingly, the age-related accumulation rate of these mutations was found to be lower in OA chondrocytes compared with chondrocytes from non-OA control subjects.
Motivating factors of higher education institutions sustainable development goals online disclosure: a systematic literature review
Authors: Sawani Yussri , Joseph Corina , Leong Siow Hoo 
Published: August 2024

Purpose
This study aims to analyse the existing literature on factors motivating higher education institutions to disclose their Sustainability Development Goals initiatives.

Design/methodology/approach
This study used an interdisciplinary systematic review to develop a review protocol for Sustainability Development Goals and higher education institutions-related literature. Thematic analysis was performed using NVivo Release 1.4 to generate the theme related to the motivating factors of disclosure and further analysed using content analysis.

Findings
The study identified five clusters relating to Sustainability Development Goals and higher education institutions. The main subcategory consists solely of motivating factors as the main child note. The four main factors that motivate Higher Education Institutions to disclose their Sustainability Development Goals practices are the curriculum, research activities, human resource management and collaborations in research and operations.

Practical implications
This paper provides an overview of factors that contribute to Sustainable Development Goals disclosure among higher education institutions with regard to their primary functions of pioneering research, providing education, exercising governance and providing external leadership. Several implications in light of multiple stakeholders are provided in the paper.

Originality/value
This study is among the few studies that develop a review protocol for Sustainability Development Goals and higher education institutions-related literature. The review provides international overview of the current academic debate on the topic of Sustainability Development Goals disclosure.
Elder abuse risk factors: the interactive effect of cognition and functionality
Authors: Fundinho João F. , Ferreira-Alves José 
Published: August 2024

Purpose
Risk assessment in elder abuse is usually considered an additive process; risk factors are viewed as independent, and the higher the number of risk factors, the higher the risk. This study aims to explore the effect of the interaction between cognitive structures (episodic memory, perceptual speed, verbal fluency, executive function) and functional dependency on elder abuse.

Design/methodology/approach
The authors collected data from 62 participants, aged between 64 and 94 years old, in the Minho region of Portugal. Face-to-face interviews were conducted to apply the assessment procedures.

Findings
Results showed that emotional abuse is predicted by episodic memory and phonemic fluency, financial abuse by perceptual speed and phonemic fluency and neglect by perceptual speed. Moderation analysis showed that these effects were greater for older adults with higher dependence on movement and lower dependence on hygiene and daily organization. This study supports the hypothesis that the risk of elder abuse is interactive, highlighting a limitation of current risk assessment procedures.

Originality/value
The current study explores the possibility of risk factors for elder abuse interacting. Understanding how risk factors interact can help to design more accurate measures of the risk of elder abuse.
Make it unique! Why embossed product labels increase purchase intentions and willingness to pay
Authors: Favier Manon , Jaud David A. , Saintives Camille 
Published: August 2024

Purpose
This paper aims to explore the influence of a particular label surface texture, i.e. embossing, on consumer purchase intentions and willingness to pay. This paper further highlights the underlying mechanisms explaining this relationship by unveiling the mediating role of willingness to touch and perceived package uniqueness.

Design/methodology/approach
Based on the visual salience theory and the stimulus–organism–response (SOR) model, this paper tests mediations and serial mediations across two online experiments and evidence from a laboratory experiment.

Findings
Study 1 reveals perceived package uniqueness as the mediator, such that embossed elements on the label increase perceived uniqueness, hence leading to greater purchase intentions and willingness to pay. In addition, Study 2 replicates these results and goes further by demonstrating the positive effect of embossing on purchase intentions and willingness to pay through willingness to touch then perceived package uniqueness.

Practical implications
The findings provide insightful managerial implications by drawing attention to the importance of using embossed elements on packaging, particularly when companies seek to differentiate themselves from competitors by stimulating consumers to touch their product packaging and having them perceive their products as unique.

Originality/value
Using visual salience theory and the SOR model, this research is, to the best of the authors’ knowledge, the first to shed light on the effect of embossing as a visual element of the packaging design on willingness to touch the product (haptics) and perceived uniqueness, ultimately enhancing purchase intentions and willingness to pay.
Evaluation and total quality management: the case of primary education
Authors: Kaiseroglou Nikolaos , Sfakianaki Eleni , Siontorou Christina 
Published: August 2024

PurposeThe purpose of this paper is to investigate perceptions of primary education (PE) teachers with respect to evaluation within the framework of Total Quality Management (TQM) and their readiness to engage in the process of quality improvement. Within this context, a relevant measurement instrument is developed and empirically validated.Design/methodology/approachThe instrument developed herein included 30 items distributed across seven dimensions. It was disseminated among public PE units in Greece, yielding a substantial 2,088 responses. Several tests were performed, including principal component analysis, confirmatory factor analysis and structural equation modelling.FindingsThe findings supported the validity and reliability of the instrument, confirming that the proposed measures encapsulate actual dimensions that are most suitable for exploring evaluation perception and readiness in the context of TQM in PE. The study explored several correlations between the validated dimensions and independent variables such as gender, level of education, years of teaching experience and age. These analyses yielded additional valuable insights, enriching the depth of understanding provided by the present research.Practical implicationsThe fields of TQM and PE lack empirical evidence. However, this study offers valuable insights into teachers’ perceptions of evaluation and broader quality improvement efforts. This can help school managers, policymakers and practitioners refine their implementation strategies for educational excellence.Originality/valueTo the best of the authors’ knowledge, this study is the first to focus on the examination of evaluation as a key aspect of TQM within the context of PE. Through the development and validation of a real-time measurement instrument, it bridges a significant research gap, providing practitioners and researchers with a vital tool to understand and improve educators’ evaluation perceptions, enabling targeted interventions for enhanced performance.