bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation signatures of early life adversity are exposure-dependent in wild baboons
Authors: Anderson Jordan A. , Lin Dana , Lea Amanda J. , Johnston Rachel A. , Voyles Tawni , Akinyi Mercy Y. , Archie Elizabeth A. , Alberts Susan C. , Tung Jenny 
Published: June 2023

AbstractThe early life environment can profoundly shape the trajectory of an animal’s life, even years or decades later. One mechanism proposed to contribute to these early life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early life effects on fitness-related traits.Significance statementThe environment animals face when young can affect how they function throughout life. Long-lasting changes in DNA methylation—a chemical mark deposited on DNA that can affect gene activity—have been hypothesized to contribute to early life effects. But evidence for persistent, early environment-associated differences in DNA methylation is lacking in wild animals. Here, we show that early life adversity in wild baboons predicts DNA methylation levels in adulthood, especially for animals born in low resource environments and drought conditions. We also show that some of the changes we observe in DNA methylation have the capacity to influence gene activity levels. Together, our results support the idea that early experiences can become biologically embedded in the genomes of wild animals.
Biochemical characterization of mRNA capping enzyme from Faustovirus
Authors: Chan S. Hong , Molé Christa N. , Nye Dillon , Mitchell Lili , Dai Nan , Buss Jackson , Kneller Daniel W. , Whipple Joseph M. , Robb G. Brett 
Published: June 2023

AbstractThe mammalian mRNA 5’ cap structures play important roles in cellular processes such as nuclear export, efficient translation, and evading cellular innate immune surveillance and regulating 5’- mediated mRNA turnover. Hence, installation of the proper 5’ cap is crucial in therapeutic applications of synthetic mRNA. The core 5’ cap structure, Cap-0, is generated by three sequential enzymatic activities: RNA 5’ triphosphatase, RNA guanylyltransferase, and cap N7-guanine methyltransferase. Vaccinia virus RNA capping enzyme (VCE) is a heterodimeric enzyme that has been widely used in synthetic mRNA research and manufacturing. The large subunit of VCE D1R exhibits a modular structure where each of the three structural domains possesses one of the three enzyme activities, whereas the small subunit D12L is required to activate the N7-guanine methyltransferase activity. Here we report the characterization of a single-subunit RNA capping enzyme from an amoeba giant virus. Faustovirus RNA capping enzyme (FCE) exhibits a modular array of catalytic domains in common with VCE and is highly efficient in generating the Cap-0 structure without an activation subunit. Phylogenetic analysis suggests that FCE and VCE are descended from a common ancestral capping enzyme. We found that compared to VCE, FCE exhibits higher specific activity, higher activity towards RNA containing secondary structures, and broader temperature range, properties favorable for synthetic mRNA manufacturing workflows.
NEMO reshapes the protein aggregate interface and promotes aggrephagy by co-condensation with p62
Authors: Furthmann Nikolas , Angersbach Lena , Bader Verian , Blusch Alina , Goel Simran , Sánchez-Vicente Ana , Krause Laura J. , Grover Prerna , Trinkaus Victoria A. , van Well Eva M. , Jaugstetter Maximilian , Tschulik Kristina , Damgaard Rune Busk , Saft Carsten , Ellrichmann Gisa , Gold Ralf , Koch Arend , Englert Benjamin , Glatzel Markus , Hartl F. Ulrich , Nakamura Ken , Christine Chadwick W. , Huang Eric J. , Tatzelt Jörg , Winklhofer Konstanze F. 
Published: June 2023

ABSTRACTNEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identified an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62.
Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference
Authors: Lobo Vivian , Nowak Iwona , Fernandez Carola , Correa Muler Ana Iris , Westholm Jakub O. , Huang Hsiang-Chi , Fabrik Ivo , Huynh Hang Thuy , Shcherbinina Evgeniia , Poyraz Melis , Härtlova Anetta , Benhalevy Daniel , Angeletti Davide , Sarshad Aishe A. 
Published: June 2023

ABSTRACTIn mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. Lamin A KO manifested a more pronounced effect in SHSY5Y cells compared to A375 cells, evident by changes in cell morphology, increased cell proliferation, and oncogenic miRNA expression. Furthermore, in SHSY5Y cells, AGO fPAR-CLIP in Lamin A KO cells revealed significantly reduced activity of RNAi. Further exploration of the nuclear AGO interactome by mass spectrometry indicated that AGO2 is in complex with FAM120A, an RNA-binding protein and known interactor of AGO2. By performing FAM120A fPAR-CLIP, we discovered that FAM120A co-binds AGO targets and that this competition reduces the activity of RNAi. Therefore, loss of Lamin A triggers nuclear AGO2 translocation, RNAi impairment, and selective upregulation of oncogenic miRNAs, facilitating cancer cell proliferation.
Oatmeal and wheat flour as the sources of thyroid peroxidase (TPO), lipoxygenase (LOX) and xanthine oxidase (XO) modulators potentially applicable in the prevention of inflammatory thyroid diseases
Authors: Habza - Kowalska Ewa , Piwowarczyk Katarzyna , Czyż Jarosław , Gawlik - Dziki Urszula 
Published: June 2023

AbstractDespite the widespread potential pro-health effects of ferulic acid (FA), their interference in the progression of thyroid dysfunction has mainly remained unresolved. Here, we combined in vitro enzyme studies with the in vitro cellular approach to investigate the potential of main dietary sources of FA - the oatmeal (OM) and wheat flour (WF) compounds for the prophylactics of inflammatory thyroid diseases. Potentially bioaccessible OM and WF compounds activated thyroid peroxidase (TPO), while inhibiting the activity of lipoxygenase (LOX) and xanthine oxidase (XO). Isobolographic studies revealed cooperation between them. Relatively strong inhibitory activity of bioaccessible OM compounds on LOX activity correlated with their cytostatic and pro-invasive effects in thyroid cancer model in vitro. These data indicate the potential of OM and WF products for the prophylactics of inflammatory thyroid diseases (incl. hypothyroidism). However, it should be considered with care, especially in the context of the oncological status of the patient.
RNA-RNA interactions between Respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity
Authors: Ressel Sarah , Kumar Sujai , Bermúdez-Barrientos Jose Roberto , Gordon Katrina , Lane Julia , Wu Jin , Abreu-Goodger Cei , Schwarze Jürgen , Buck Amy H. 
Published: June 2023

AbstractmicroRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of viral infections. Here we adapt a biochemical method (CLEAR-CLIP) and analysis pipeline to identify targets of miRNAs in lung cells infected with Respiratory syncytial virus (RSV). We show that RSV binds directly to miR-26 and miR-27 through seed pairing and demonstrate that these miRNAs target distinct gene networks associated with cell cycle and metabolism (miR-27) and antiviral immunity (miR-26). Many of the targets are de-repressed upon infection and we show that the miR-27 targets most sensitive to miRNA inhibition are those associated with cell cycle. Finally, we demonstrate that high confidence chimeras for miR-26 and miR-27 also map to regulatory regions. We validate that a proportion of miR-27 and Argonaute 2 (AGO2) is nuclear in infected cells and identify a long non-coding RNA (lncRNA) as a miR-27 target that is linked to transcriptional regulation of nearby genes. This work expands the target networks of miR-26 and miR-27 to include direct interactions with RSV and lncRNAs and implicate these miRNAs in regulation of key genes that impact the viral life cycle associated with cell cycle, metabolism, and antiviral immunity.
The TRIP6/LATS1 complex constitutes the tension sensor of α-catenin/vinculin at both bicellular and tricellular junctions
Authors: Xie Lin , Wu Gangyun , Liu Xiayu , Duan Xiufen , Zhou Kaiyao , Li Hua , Ning Wenxiu 
Published: June 2023

AbstractCell-cell mechanotransduction regulates tissue development and homeostasis. α-catenin, the core component of adherens junctions, functions as a tension sensor and transducer by recruiting vinculin and transducing the signals to influence cell behaviors. However, little is known about the components, distributions, and dynamics of the α-catenin based tension sensors at the cell junctions. Here, we uncovered the TRIP6/LATS1 complex locates at the tension sites where α-catenin/vinculin is at both the bicellular junctions (BCJs) and tricellular junctions (TCJs). Vinculin/TRIP6/LATS1 are prone to form as puncta in the cytoplasm without α-catenin participation. Furthermore, the tension sensing complex distributed stronger at TCJs and exhibited a discontinuously button-like pattern on BCJs. The α-catenin/vinculin BiFC-based mechanosensor further proved the discontinuous distribution of the tension at BCJs, and was more motile than the TCJs. In summary, our study revealed that TRIP6 and LATS1 are novel compositions of the tension sensor, together with the core complex of α-catenin/vinculin, at both the BCJs and TCJs. This work gives insights and improvements in exploring the molecular mechanism that mediates cell-cell mechanotransduction at cell junctions.
Apical polarity and actomyosin dynamics regulate Hippo signaling by controlling Kibra subcellular localization
Authors: Tokamov Sherzod A. , Nouri Nicki , Rich Ashley , Buiter Stephan , Glotzer Michael , Fehon Richard G. 
Published: June 2023

AbstractCell polarity and actomyosin networks are key features that organize cells of epithelial tissues and are known to regulate tissue growth. However, the mechanisms by which polarity cues and actomyosin cytoskeleton influence intracellular signaling cascades that control growth remain poorly understood. The Hippo pathway is an evolutionarily conserved regulator of tissue growth and is known to integrate inputs from both polarity and actomyosin components. An upstream activator of the Hippo pathway, Kibra, localizes into distinct pools at the junctional and medial regions of the apical cortex in epithelial cells, and medial accumulation was shown to promote Kibra activity. Here, we demonstrate that cortical Kibra distribution is controlled by a tug of war between apical polarity and actomyosin dynamics. We show that while the apical polarity network, in part via aPKC, tethers Kibra at the junctional cortex to silence its activity, medial actomyosin flows promote Kibra-mediated Hippo complex formation at the medial cortex, thereby activating the Hippo pathway. This study provides a mechanistic understanding of the relationship between the Hippo pathway, polarity, and actomyosin cytoskeleton and offers novel insights into how fundamental features of epithelial tissue architecture can serve as inputs into signaling cascades that control tissue growth, patterning, and morphogenesis.
PRIMARY HEALTH CARE PERFORMANCE INDICATORS MODEL IN A PERFORMANCE-BASED CAPITATION SCHEME TO MEASURE NATIONAL HEALTH INSURANCE HEALTH SERVICE EQUITY (PROTOCOL STUDY)
Authors: Aryani Ari Dwi , Bachtiar Adang , Candi Cicilya 
Published: June 2023

AbstractThe inequity of health services still occurs after the implementation of the National Health Insurance (JKN). Regular monitoring of the Performance of Primary Health Care is the key to reducing the inequity of health services as the main goal of JKN. The application of Performance-Based Capitation (KBK) with three indicators since 2016, shows an improvement in Primary Health Care’s performance in improving quality and efficiency in the first level of service in comparison. Primary Health Care performance is influenced by Primary Health Care capacity and has an impact on the output of primary service performance (Health Service Equity). This study aims to develop a model of performance indicators, Primary Health Care capacity and equity indicators, in order to measure healthcare equity. The research design used an exploratory sequential-mixed method. The research is divided into three stages. Phase one is a systematic review to identify indicators that can be used in measuring the capacity, the performance of Primary Health Care and healthcare equity. Phase two is carried out with a qualitative approach with the Consensus Decision Making Group (CDMG) to determine indicators that can be used in measuring the capacity and performance of Primary Health Care as well as measuring health service equity with experts. Phase three is to develop a model of Primary Health Care performance indicators based on a capitation scheme that can measure the equity of healthcare access. This stage is carried out using Multilevel Structural Equation Modeling (MSEM) analysis. It is hoped that this model can be used by Social Security Administrator for Health (BPJS Kesehatan) and the Ministry of Health to measure the performance of Primary Health Care and health service equity.
GENDER DIFFERENCES IN ANTIBIOTICS USE BEHAVIOUR AND ACCESS TO ANTIBIOTICS IN LOW- AND MIDDLE-INCOME COUNTRIES: A SCOPING REVIEW PROTOCOL
Authors: Adewusi Oluwafemi J. , Cassidy Rebecca , Aboderin Aaron O. , Bailey Simon , Hotham Sarah 
Published: June 2023

ABSTRACTBackgroundIn low-and middle-income countries (LMICs), the persistent lack of access and high inappropriate use of antibiotics, which are fuelled by gender-related factors continue to facilitate antimicrobial resistance which in turn reduces the capacity to treat infectious diseases. However, there is lack of sufficient clarity on the nature and extent of gender influence on access to antibiotics and antibiotic use behaviour. This proposed study aims to systematically review available literature in order to map out the nature and extent of evidence on gender differences and related factors influencing antibiotics use behaviour and access to antibiotics in LMICs.MethodsThis scoping review will be conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews. The MEDLINE, PsycINFO, African Journal Online (AJOL), Web of Science and CINAHL databases will be searched for peer-reviewed articles and relevant electronic grey literature will also be included in the study. A predefined excel spreadsheet will be utilized for data extraction and analysis. Findings will be presented in narrative summary and tables.ConclusionIt is expected that this study will identify knowledge and gaps on gender contributory factors to antibiotics use and access to antibiotics. These will contribute to understanding gender health inequalities and areas for further research on gender mainstreaming in antimicrobial stewardship efforts in the LMICs. This study findings will be disseminated through presentations in scientific conferences and publications in peer-reviewed journals.Scoping review registration with Open Science FrameworkRegistration DOI:https://doi.org/10.17605/OSF.IO/N5W8E
The impacts of the wind on GPS of quadrotors
Authors: Ercan Hamdi , Ulucan Hamdi 
Published: June 2023

Purpose
The Global Positioning System (GPS) is crucial for determining the positions of quadrotors, enabling safe flight and maintaining stability against environmental conditions. This study aims to investigate the effect of wind on the GPS of quadrotors experimentally.

Design/methodology/approach
This experimental study was conducted using an F450 frame, 980 kV motors and a Pixhawk flight controller to manage the quadrotor’s flight. To investigate the effects of wind on the quadrotor’s GPS during flight, a Pixhawk 4 Holybro flight controller was used. The experimental tests were performed on a predetermined route at different wind speeds.

Findings
Analysis of the data obtained from the flight tests showed that GPS signals were more affected as the wind speed increased. The percentage of GPS jamming levels reached 18% at high wind speeds.

Practical implications
Positioning services will be even more critical for quadrotors, which are expected to be used more frequently in public areas. This study is expected to be a reference for GPS-related research.

Originality/value
Winds pose a significant threat to the safe flight of quadrotors in many ways. This study experimentally investigates the effects of wind on the GPSs of quadrotors and to what extent it affects them at different wind speeds under real weather conditions. The obtained data shows that wind has a significant impact on GPS jamming.
Influence of drop test impact on the physiochemical attributes of tomatoes
Authors: Pathare Pankaj B. , AL-Dairi Mai , Al Mahdouri Adil 
Published: June 2023

Purpose This study aims to determine the influence of bruise damage generated from the impact test on the physical, chemical and nutritional responses of tomato fruit.Design/methodology/approach The impact loading was applied from different heights. The impact energies for 20, 40 and 60 cm drop heights were 129.59, 259.18 and 388.77 mJ, respectively. The injured samples were kept for 48 hours at low (10 °C) and ambient (22 °C) storage temperatures. Weight loss, firmness, color, total soluble solids (TSS), lycopene and carotenoids were measured before the impact test (day 0) and after 48 hours of the impact and storage.Findings The drop height of 60 cm and storage at 22 °C showed the highest values in the bruised area. The impact from the 60 cm drop height significantly reduced weight, lightness, yellowness, hue, firmness, lycopene and carotenoids, particularly at 22 °C storage condition. Redness (a*) and color index (CI) showed a remarkable increase (p < 0.05) at 22 °C on tomatoes affected from the highest impact level (388.77 mJ) after 48 hours of storage. No pronounced significance was seen between TSS and drop heights. This study has confirmed that tomato bruising for a short-term storage period induces physiological changes at different storage temperature conditions.Originality/value The study can confirm the crucial role of inappropriate handling in increasing fresh produce loss within short-term storage. Also, this research can be considered as a guideline for transporters, handlers, processors, distributors and horticulture researchers in the fresh produce supply chain during postharvest operations.
Understanding railway passengers’ E-ticketing usage intention in an emerging economic context: application of an extended technology acceptance model
Authors: Awal Md. Rabiul , Arzin Tahmina Akter , Islam Md. Mirajul , Hasan Md. Tareq 
Published: June 2023

PurposeThis techno-centric and too much busy day-to-day living style of citizens pressurizes the implementation of E-ticketing service to adapt with change. Thus, this study aims to examine the factors influencing railway passengers’ E-ticketing service acceptance and usage intention in Bangladesh and to extend the widely used Technology Acceptance Model through inserting two new constructs.Design/methodology/approachThis paper employs structural equation modeling to test model’s paths developed through theoretical research framework. Moreover, a structured questionnaire was administered at different railway stations in northern and western parts of Bangladesh to collect data. Total of 302 responses were considered for statistical analysis to test hypotheses after considering anomalies and outliers in raw data.FindingsThe study results show that technology trust (TT) has the strongest impact on passengers’ E-ticketing usage intention rather than perceived ease of use and perceived usefulness (PU). Meanwhile, the easiness of using technology to reserve tickets does matter to female passengers rather than male passengers wherein PU and TT do not do that.Originality/valueThe findings of this study might be helpful for the railway authorities to improve the ticket reservation service quality online by developing the advanced booking application and minimizing the pressure on other transportation. Therefore, this empirical study will contribute to this domain for further study that ensures full satisfaction of passengers and uplift the railway passengers’ usage intention for E-ticketing which then helps the government to implement the digitization slogan with efficiency and effectiveness.