bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex
Authors: Bloor Stuart , Wit Niek , Lehner Paul J. 
Published: July 2024

AbstractThe human silencing hub (HUSH) complex is a transcription-dependent, epigenetic repressor complex that provides a genome-wide immunosurveillance system for the recognition and silencing of newly-integrated retroelements. The core HUSH complex of TASOR, MPP8 and Periphilin, represses these retroelements through SETDB1-mediated H3K9me3 deposition and MORC2-dependent chromatin compaction. HUSH-dependent silencing is RNA-mediated, yet no HUSH components contain any RNA-binding domain. Here we used an unbiased approach to identify which HUSH component was able to bind RNA and determine whether RNA-binding was essential for HUSH function. We identify Periphilin as the major RNA-binding component of the HUSH complex and show that Periphilin’s N-terminal domain is essential for both RNA binding and HUSH function. Periphilin binding to RNA was independent of its interaction with TASOR or MPP8, as its N-terminal domain was sufficient for RNA targeting. The artificial tethering of Periphilin to a HUSH-insensitive, nascent transcript, enabled the HUSH-dependent silencing of the transcript. This tethering of Periphilin allowed the RNA-binding region of Periphilin to be removed such that only its C-terminal domain was required for oligomerisation and interaction with TASOR. We therefore show that Periphilin is the predominant RNA-binding protein of the HUSH complex and this RNA-binding is essential for HUSH activity.
Analysis of iPLA2-VIA Gene Expression in The CNS of Larvae and AdultDrosophila MelanogasterFlies
Authors: Moura Gabriel 
Published: July 2024

1AbstractThis study aimed to investigate the expression levels of the iPLA2-VIA gene (FlyBase: FBgn0035800) in the nervous tissue ofDrosophila melanogaster(FlyBase: FBsp00000008) larvae and adults. The gene was identified using the FlyBase database and the HGNC database. The results of our experiments indicated that the expression levels of the gene were consistent between the larval and adult stages, with higher expression of Larvae than of Adult. We also found that the gene was expressed in the CNS, digestive system, fat body, salivary glands, ovaries, and accessory glands. Furthermore, PLA2G6 (Gene ID: 8398) knockout resulted in lethality, fertility problems, tissue formation defects, and neurological abnormalities, highlighting its essential biological roles in neural health and disease. Our findings could inform future studies focused on the gene’s involvement in neural development and its potential as a therapeutic target for neurodegenerative diseases.
β3 accelerates microtubule plus end maturation through a divergent lateral interface
Authors: Wood Lisa M. , Moore Jeffrey K. 
Published: July 2024

Abstractβ-tubulin isotypes exhibit similar sequences but different activities, suggesting that limited sequence divergence is functionally important. We investigated this hypothesis for TUBB3/β3, a β-tubulin linked to aggressive cancers and chemoresistance in humans. We created mutant yeast strains with β-tubulin alleles that mimic variant residues in β3 and find that residues at the lateral interface are sufficient to alter microtubule dynamics and response to microtubule targeting agents. In HeLa cells, β3 overexpression decreases the lifetime of microtubule growth, and this requires residues at the lateral interface. These microtubules exhibit a shorter region of EB binding at the plus end, suggesting faster lattice maturation, and resist stabilization by paclitaxel. Resistance requires the H1-S2 and H2-S3 regions at the lateral interface of β3. Our results identify the mechanistic origins of the unique activity of β3 tubulin and suggest that tubulin isotype expression may tune the rate of lattice maturation at growing microtubule plus ends in cells.
Rapid protein evolution by few-shot learning with a protein language model
Authors: Jiang Kaiyi , Yan Zhaoqing , Bernardo Matteo Di , Sgrizzi Samantha R. , Villiger Lukas , Kayabolen Alisan , Kim Byungji , Carscadden Josephine K. , Hiraizumi Masahiro , Nishimasu Hiroshi , Gootenberg Jonathan S. , Abudayyeh Omar O. 
Published: July 2024

AbstractDirected evolution of proteins is critical for applications in basic biological research, therapeutics, diagnostics, and sustainability. However, directed evolution methods are labor intensive, cannot efficiently optimize over multiple protein properties, and are often trapped by local maxima.In silico-directed evolution methods incorporating protein language models (PLMs) have the potential to accelerate this engineering process, but current approaches fail to generalize across diverse protein families. We introduce EVOLVEpro, a few-shot active learning framework to rapidly improve protein activity using a combination of PLMs and protein activity predictors, achieving improved activity with as few as four rounds of evolution. EVOLVEpro substantially enhances the efficiency and effectiveness ofin silicoprotein evolution, surpassing current state-of-the-art methods and yielding proteins with up to 100-fold improvement of desired properties. We showcase EVOLVEpro for five proteins across three applications: T7 RNA polymerase for RNA production, a miniature CRISPR nuclease, a prime editor, and an integrase for genome editing, and a monoclonal antibody for epitope binding. These results demonstrate the advantages of few-shot active learning with small amounts of experimental data over zero-shot predictions. EVOLVEpro paves the way for broader applications of AI-guided protein engineering in biology and medicine.
Urinary Volatile Organic Compound Metabolites are Associated with High Blood Pressure Among Non-smoking Participants in the National Health and Nutrition Examination Survey (2011-2018)
Authors: McGraw Katlyn E. , Domingo-Relloso Arce , Riggs Daniel W. , Medgyesi Danielle N. , Neupane Raghavee , Stingone Jeanette A. , Sanchez Tiffany R. 
Published: July 2024

ABSTRACTBackgroundVolatile organic compounds (VOCs) are ubiquitous environmental pollutants. Exposure to VOCs is associated with cardiovascular disease (CVD) risk factors, including elevated blood pressure (BP) in susceptible populations. However, research in the general population, particularly among non-smoking adults, is limited. We hypothesized that higher VOC exposure is associated with higher BP and hypertension, among non-smokers.MethodsWe included four cycles of data (2011-2018) of non-smoking adults (n=4,430) from the National Health and Nutrition Examination Survey (NHANES). Urinary VOC metabolites were measured by ultra-performance liquid chromatography–mass spectrometry, adjusted for urine dilution, and log-transformed. We estimated mean differences in BP using linear models and prevalence ratio of stage 2 hypertension using modified Poisson models with robust standard errors. Models were adjusted for age, sex, race and ethnicity, education, body mass index, estimated glomerular filtration rate and NHANES cycle.ResultsParticipants were 54% female, with a median age of 48 years, 32.3% had hypertension, and 7.9% had diabetes. The mean differences (95% CI) in systolic BP were 1.61 (0.07, 3.15) and 2.46 (1.01, 3.92) mmHg when comparing the highest to lowest quartile of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA) metabolites. The prevalence ratios (PR) for hypertension were 1.06 (1.02, 1.09) and 1.05 (1.01, 1.09) when comparing the highest to lowest quartiles of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA), respectively.ConclusionsExposure to VOCs may be relevant yet understudied environmental contributors to CVD risk in the non-smoking, US population.
Induced degradation of SNAP-fusion proteins
Authors: Pol Savina Abraham , Liljenberg Sara , Barr Jack , Simon Gina , Wong-Dilworth Luis , Paterson Danielle L. , Berishvili Vladimir P. , Bottanelli Francesca , Kaschani Farnusch , Kaiser Markus , Pettersson Mariell , Hellerschmied Doris 
Published: July 2024

SUMMARYSelf-labeling protein tags are an efficient means to visualize, manipulate, and isolate engineered fusion proteins with suitable chemical probes. The SNAP-tag, which covalently conjugates to benzyl-guanine and -chloropyrimidine derivatives is used extensively in fluorescence microscopy, given the availability of suitable SNAP-ligand-based probes. Here, we extend the applicability of the SNAP-tag to targeted protein degradation. We developed a set of SNAP PROteolysis TArgeting Chimeras (SNAP-PROTACs), which recruit the VHL or CRBN-ubiquitin E3 ligases to induce the degradation of SNAP-fusion proteins. Endogenous tagging enabled the visualization and the selective depletion of a SNAP-clathrin light chain fusion protein using SNAP-PROTACs. The addition of PROTACs to the SNAP-tag reagent toolbox facilitates the comprehensive analysis of protein function with a single gene tagging event.
From spreadsheet lab data templates to knowledge graphs: A FAIR data journey in the domain of AMR research
Authors: Gadiya Yojana , Abbassi-Daloii Tooba , Ioannidis Vassilios , Juty Nick , Stie Kallesøe Claus , Attwood Marie , Kohler Manfred , Gribbon Philip , Witt Gesa 
Published: July 2024

AbstractWhile awareness of FAIR (Findable, Accessible, Interoperable, and Reusable) principles has expanded across diverse domains, there remains a notable absence of impactful narratives regarding the practical application of FAIR data. This gap is particularly evident in the context ofin-vitroandin-vivoexperimental studies associated with the drug discovery and development process. Despite the structured nature of these data, reliance on classic methods such as spreadsheet-based visualization and analysis has limited the long-term reuse opportunities for such datasets. In response to this challenge, our work presents a representative journey towards FAIR data, characterized by structured, conventional spreadsheet-based lab data templates and the adoption of a knowledge graph framework for breaking data silos in the field of early antimicrobial resistance research. Here, we illustrate a tailored application of a “FAIRification framework” facilitating the practical implementation of FAIR principles. By showcasing the feasibility and benefits of transitioning to FAIR data practices, our work aims to encourage broader adoption and integration of FAIR principles within a research lab setting.
Multiple clustered centrosomes in antigen-presenting cells foster T cell activation without MTOC polarization
Authors: Stötzel Isabel , Weier Ann-Kathrin , Sarkar Apurba , Som Subhendu , Konopka Peter , Miková Eliška , Böthling Jan , Homrich Mirka , Schaedel Laura , Kazmaier Uli , Symeonidis Konstantinos , Abdullah Zeinab , Uderhardt Stefan , Hons Miroslav , Paul Raja , Rieger Heiko , Kiermaier Eva 
Published: July 2024

AbstractCellular polarization plays a pivotal role in regulating immunological processes and is often associated with centrosome reorientation. During immune synapse (IS) formation centrosome repositioning in lymphocytes assists in T cell activation. While a single centrosome, consisting of two centrioles, is present in T cells, antigen-presenting cells (APCs) such as dendritic cells (DCs) amplify centrioles during maturation leading to increased centrosome numbers upon immune activation. How centrosome amplification in DCs affects IS formation and T cell activation is unclear. In this study, we combine experimental data with mathematical and computational modelling to provide evidence that centrosome amplification in DCs enhances antigen-specific T cell activation. Extra centrioles in DCs form active centrosomes, which cluster during DC-T cell interactions and unlike in T cells, localize close to the cell center. Perturbing either centriole numbers or centrosome configuration in DCs results in impaired T cell activation. Collectively, our results highlight a crucial role for centrosome amplification and optimal centrosome positioning in APCs for controlling T cell responses.
Sensitive detection and propagation of brain-derived tau assemblies in HEK293 based wild-type tau seeding assays
Authors: Huang Melissa , McEwan William A 
Published: July 2024

AbstractThe assembly of tau into filaments defines the tauopathies, a group of neurodegenerative diseases including Alzheimer’s disease (AD), Pick’s disease (PiD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The seeded aggregation of tau has been modelled in cell culture using pro-aggregant modifications such as truncation of the N- and C-termini and point-mutations within the tau microtubule-binding repeat domain. While providing experimental convenience, this limits the applicability of research findings to sporadic disease, where filaments contain wild-type, full-length tau isoforms. We therefore aimed to develop a sensitive and specific biosensor assay for the seeded aggregation of brain-derived tau species utilizing full-length, wild-type tau stably expressed in HEK293 cells. We show that addition of brain-derived tau extracted from cases of AD, PiD, CBD, or PSP induces the formation of HA- or GFP-tagged 0N3R or 0N4R tau aggregates. By isolating and expanding a single cell containing AD-seeded aggregates, we generated a cell line that propagates insoluble tau. We demonstrate that HEK293-propagated tau is hyperphosphorylated at disease relevant sites and retains a seeding profile similar to AD brain-derived material. We propose that these cell lines will aid pre-clinical, high-throughput screening for modifiers of seeded aggregation with greater conformational and strain specificity than existing cell-based biosensor assays.
DArTSNPbased genetic diversity analyses in cassava (Manihot esculenta) genotypes sourced from different regions revealed high level of diversity within population
Authors: NeimSemman A. , Abush Tesfaye A. , Ismael Rabbi Y. , Tewodros Mulualem B. , Abtew Wosene G. 
Published: July 2024

AbstractUnderstanding the extent of genetic diversity is a pre requisite in cassava breeding program due to its, available broad genetic base of the crop and have great opportunity for its genetic improvement. This study was designed to assess the genetic diversity of 184 cassava germplasm sourced from International Institute of Tropical Agriculture (IITA) and previous collection of Jimma Agricultural Research Center (JARC) by using DArTSNPs markers. The data were subjected to imputation and filtering for minor allele frequency of 0.01, 0.95 major allele frequency using TASSEL and Beagle. The resultants 9,310 informative SNPs were retained and used to perform analysis of molecular variance (AMOVA), genetic diversity, population structure, and dissimilarity-based clustering of the tested cassava germplasm. The results of AMOVA revealed higher variation within (91.3%) than between (8.7%) the study populations. The high average PIC (0.44), He (0.50), major allele (0.61) and minor allele (0.28) frequency showed the existence of high variation in the study populations. Population structure analysis grouped the panels into six structures with the existence of admixtures. Similarly, principal component analysis, factor analysis and cluster analysis apparently divided the panels into six clusters. Both the introduced and locally collected germplasm formed three clusters, each creating some mixes of genotypes, indicating that alleles sharing common ancestral background. The overall results, the studied genotypes showed significant variations, which can render opportunity for association mapping and technical conservation purposes.
Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA
Authors: Wisniewski Brett T. , Lackner Laura L. 
Published: July 2024

ABSTRACTMitochondria exist as dynamic tubular networks and the morphology of these networks impacts organelle function and cell health. Mitochondrial morphology is maintained in part by the opposing activities of mitochondrial fission and fusion. Mitochondrial fission and fusion are also required to maintain mitochondrial DNA (mtDNA) integrity. InSaccharomyces cerevisiae, the simultaneous inhibition of mitochondrial fission and fusion results in increased mtDNA mutation and the consequent loss of respiratory competence. The mechanism by which fission and fusion maintain mtDNA integrity is not fully understood. Previous work demonstrates that mtDNA is spatially linked to mitochondrial fission sites. Here, we extend this finding using live-cell imaging to localize mtDNA to mitochondrial fusion sites. While mtDNA is present at sites of mitochondrial fission and fusion, mitochondrial fission and fusion rates are not altered in cells lacking mtDNA. Using alleles that alter mitochondrial fission and fusion rates, we find that mtDNA integrity can be maintained in cells with significantly reduced, but balanced, rates of fission and fusion. In addition, we find that increasing mtDNA copy number reduces the loss of respiratory competence in double mitochondrial fission-fusion mutants. Our findings add novel insights into the relationship between mitochondrial dynamics and mtDNA integrity.
Thermal analysis of batteries and prediction with artificial neural networks
Authors: Yetik Ozge 
Published: July 2024

Purpose
In this study, it is aimed to develop cooling models for the efficient use of batteries and to show how important the busbar material is. Batteries, which are indispensable energy sources of electric aircraft, automobiles and portable devices, may eventually run out. Battery life decreases over time; the most critical factor is temperature. The temperature of batteries should not exceed the safe operating temperature of 313 K and it is recommended to have a balanced temperature distribution through the battery.

Design/methodology/approach
In this study, the effect on the battery temperature caused by using different busbar materials to connect batteries together was investigated. Gold, copper and titanium were chosen as the different busbar material. The Air velocities used were 1 m/s and 2 m/s, the air inlet temperatures were 295 and 300 K and the discharge rates 1.0–1.5–2.0–2.5C were chosen for cooling the batteries.

Findings
The best busbar material was identified as copper. Because these studies are long-term studies, it is also suggested to estimate the data obtained with ANN (Artificial Neural Networks). The purpose of ANN is to enable the solution of many different complex problems by creating systems that do not require human intelligence. Four different program (BR-LM-CGP-SCG) were used to estimate the data obtained with ANN. It was found that the most reliable algorithm was BR18. The R2 size of the BR18 algorithm in the test phase was 0.999552, the CoV size was 0.007697 and the RMSE size was 0.005076.

Originality/value
When the literature is considered, the cooling part of the battery modules has been taken into consideration during the temperature observation of the battery modules, but busbar materials connecting the batteries have always been ignored. In this study, various busbar materials were used and it was noticed how the temperature of the battery model changed under the same working conditions. These studies are very time-consuming and costly studies. Therefore, an estimation of the data obtained with artificial neural networks (ANN) was also evaluated.
Role of line managers in promoting DEI in higher education institution: an autoethnographic case study
Authors: Garg N. 
Published: July 2024

PurposeThe purpose of this study is to analyse the role of line management in promoting Diversity, Equity and Inclusion (DEI) in Higher Education Institutions (HEIs). Transformational leadership (TL) promotes DEI, and autocratic leadership curbs it.Design/methodology/approachThe research approach is deductive from existing literature followed by auto ethnographic case study.FindingsThe finding of this study is how the autocracy of a line manager can kill the enthusiasm of a team member. Cascuta theory, which has been introduced as a parasitic form of management in paper, will come into existence when a less qualified and closed mindset is supervising a highly qualified and performing team.Research limitations/implicationsThe research limitations included inadequate autoethnographic case studies on similar circumstances. Also, the literature is divisive over the topic of DEI. On paper, policies are very strong; however, the implementation is not so good in many academic departments at many universities. Here, the whole HEIs is not to blame. Rather, the line manager has a bigger role in acknowledging or rejecting DEI. This research has many implications for studying the Cascuta phenomenon amongst DEI students, DEI staff.Practical implicationsThe DEI colleagues in some academic departments of many universities in the UK are facing affinity biases. This study could be used to identify and remove the roadblocks in acknowledging the role of DEI in the UK HEIs. These remedies, though, might only be cosmetic. Persons who encourage affinity biases may also be the ones carrying out DEI programmes (Sodhi, 2024). Second, instead of taking concrete action to solve urgent social issues in the workplace, institutions may view DEI activities as regulatory mandates.Social implicationsRegional committees could be a good alternative to explore the success of implementing DEI on a wider scale. The members could be from HEIs, who are renowned for their DEI policy implementation. Their implementation process, roadblocks, and wider benefits could be studied on a wider scale. The DEI people should be able to contribute to society with ownership. If they are contributing to the economy, education, or health care, they are an asset and not a burden on society. If HEI is not recognising DEI now, they may find their way out to a more acceptable place.Originality/valueThis is a novel study to explore the role of line leadership in promoting DEI in HEI using the deductive method, supported with an autoethnographic case study.
Industry 4.0 readiness: the impact of effective implementation of I4.0 on marketing performance
Authors: Raj Rohit , Kumar Vimal , Sharma Nagendra Kumar , Verma Pratima 
Published: July 2024

Purpose
The purpose of this study is to examine how Industry 4.0 (I4.0) implementation might improve marketing performance (MP). Early adopters now have the chance to capitalize on the advantages of this successful implementation owing to the transition to I4.0. To improve MP, businesses must be able to identify and manage their effective implementation of I4.0 technologies, which are essential to improve industrial performance.

Design/methodology/approach
A survey was created and sent to 311 samples of manufacturing companies. To investigate the hypothesis created in this context, the study includes a survey-based analysis. To present the study’s findings, partial least squares-structural equation modeling has been used.

Findings
According to the findings, it can be concluded that an efficient implementation of Industry 4.0 (EII) can improve MP by positively impacting consumer loyalty and increasing customer loyalty (CL) positively enhancing by product customization (PC). The study’s key results, however, are how both PC and CL affect MP.

Research limitations/implications
The intensive production technologies that are at the center of I4.0 will be better understood by professionals thanks to this study. The Internet of Things, artificial intelligence, additive manufacturing, sophisticated robots and many more are examples of these technologies. I4.0’s application strengthens efficiency and high-quality production. The I4.0 concept is gaining popularity in both developed and emerging countries due to its higher performance. Additionally, business people are actively working to implement I4.0 and make it a big success.

Originality/value
The study identifies the successful adoption of I4.0 that has a substantial impact on businesses’ MP. However, there is a lack of noteworthy studies that can concentrate on the marketing reach with I4.0 deployment. As a result, the goal of the current research is to comprehend how I4.0 will affect MP.