bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the Effect of Local and Systemic Preoperative Dexamethasone Application on Bone Tissue Healing in Mandibular Bone Defects
Authors: Yavuz Gunay Yapici , Keskinruzgar Aydin , Bozdag Zehra , Bayazit Seyma 
Published: July 2024

Objectives:
The aim of this study was to investigate the effect of locally and systemically delivered single-dose corticosteroid injections on bone tissue.

Study Design:
A total of 84 Wistar albino rats were divided into 2 groups as local and systemic injection groups, and 2 groups as control and experiment among themselves. Before the procedure, dexamethasone was given to the experimental group and physiological saline was given to the control group. A defect was created in the jawbone. It was sacrificed on the third, seventh, and 40th days. The mandible bones of the sacrificed rats were removed and the healing of the bone tissue was examined histopathologically.

Results:
No significant difference was observed in the tissue sections of the subjects sacrificed after 40 days. However, the increase in fibroblastic connective tissue and the number of osteoblasts were less in the experimental local groups that were sacrificed after 7 days compared with the control groups (P=0.040 and 0.041). Again, it was determined that there was a statistically significant decrease in the experimental local group compared with the experimental systemic group (P=0.040 and 0.004).

Conclusions:
It can be said that single-dose corticosteroid applications cause a delay in bone healing in the early period.
Approximate Bayesian computation for inferring Waddington landscapes from single-cell data
Authors: Liu Yujing , Zhang Stephen Y. , Kleijn Istvan T. , Stumpf Michael P. H. 
Published: July 2024

Single-cell technologies allow us to gain insights into cellular processes at unprecedented resolution. In stem cell and developmental biology snapshot data allow us to characterize how the transcriptional states of cells change between successive cell types. Here, we show how approximate Bayesian computation (ABC) can be employed to calibrate mathematical models against single-cell data. In our simulation study, we demonstrate the pivotal role of the adequate choice of distance measures appropriate for single-cell data. We show that for good distance measures, notably optimal transport with the Sinkhorn divergence, we can infer parameters for mathematical models from simulated single-cell data. We show that the ABC posteriors can be used (i) to characterize parameter sensitivity and identify dependencies between different parameters and (ii) to construct representations of the Waddington or epigenetic landscape, which forms a popular and interpretable representation of the developmental dynamics. In summary, these results pave the way for fitting mechanistic models of stem cell differentiation to single-cell data.
Engineering of Transmembrane Alkane Monooxygenases to Improve a Key Reaction Step in the Synthesis of Polymer Precursor Tulipalin A
Authors: Nigl Andrea , Delsoglio Veronica , Grgić Marina , Malihan-Yap Lenny , Myrtollari Kamela , Spasic Jelena , Winkler Margit , Oberdorfer Gustav , Taden Andreas , Anić Iva , Kourist Robert 
Published: July 2024

AbstractThe α-methylene-γ-butyrolactone tulipalin A, naturally found in tulips can polymerize via addition at the vinyl group or via ring-opening polymerization, making it a highly promising monomer for biobased polymers. As tulipalin A biosynthesis in plants remains elusive, we propose a pathway for its synthesis starting from the metabolic intermediate isoprenol. For this, terminal hydroxylation of the α-methylene substrate isoprenyl acetate is a decisive step. While a panel of fungal unspecific peroxygenases showed a preference for the undesired epoxidation of theexo-olefin group, bacterial alkane monooxygenases were specific for terminal hydroxylation. A combination of protein engineering based onde novostructure prediction of the membrane enzymes with cell engineering allowed to increase the specific activity by 6-fold to 1.83 U gcdw-1, unlocking this reaction for the fermentative production of tulipalin A from renewable resources.
Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity
Authors: Sowton Alice P. , Holzner Lorenz M.W. , Krause Fynn N. , Baxter Ruby , Mocciaro Gabriele , Krzyzanska Dominika K. , Minnion Magdalena , O’Brien Katie A. , Harrop Matthew C. , Darwin Paula M. , Thackray Benjamin D. , Vacca Michele , Feelisch Martin , Griffin Julian L. , Murray Andrew J. 
Published: July 2024

AbstractInorganic nitrate (NO3-) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the Metabolic Syndrome (MetS), type-II diabetes and metabolic dysfunction associated steatotic liver disease (MASLD). Administration of NO3-to endothelial nitric oxide synthase-deficient mice reversed aspects of MetS, however the impact of NO3-supplementation in diet-induced obesity is not well understood. Here we investigated the whole-body metabolic phenotype and cardiac and hepatic metabolism in mice fed a high-fat high-sucrose (HFHS) diet for up to 12-months of age, supplemented with 1 mM NaNO3(or NaCl) in their drinking water. HFHS-feeding was associated with a progressive obesogenic and diabetogenic phenotype, which was not ameliorated by NO3-. Furthermore, HFHS-fed mice supplemented with NO3-showed elevated levels of cardiac fibrosis, and accelerated progression of MASLD including development of hepatocellular carcinoma in comparison with NaCl-supplemented mice. NO3-did not enhance mitochondrial β-oxidation capacity in any tissue assayed and did not suppress hepatic lipid accumulation, suggesting it does not prevent lipotoxicity. We conclude that NO3-is ineffective in preventing the metabolic consequences of an obesogenic diet and may instead be detrimental to metabolic health against the background of HFHS-feeding. This is the first report of an unfavorable effect of long-term nitrate supplementation in the context of the metabolic challenges of overfeeding, warranting urgent further investigation into the mechanism of this interaction.New & NoteworthyInorganic nitrate has been suggested to be of therapeutic benefit in obesity-related conditions as it increases nitric oxide bioavailability, enhances mitochondrial β-oxidation and reverses Metabolic Syndrome ineNOS-/-mice. However, we here show that over 12 months, nitrate was ineffective in preventing metabolic consequences in high-fat high-sucrose fed mice, and worsened aspects of metabolic health, impairing cholesterol handling, increasing cardiac fibrosis, and exacerbating steatotic liver disease progression, with acceleration to hepatocellular carcinoma.
Unraveling the Link between Nutrition and Metabolic Syndrome Risk through In Silico Dietary Interventions
Authors: Alessi Drew , McCreery Chloe , Zomorrodi Ali R. 
Published: July 2024

AbstractMetabolic Syndrome (MetS) is a cluster of metabolic disorders that substantially increases the risk of chronic metabolic diseases. Diet is known to play a crucial role in the progression of MetS, yet a mechanistic understanding of its impact on MetS risk remains elusive. To address this gap, we conducted a rigorous in silico diet intervention study by leveraging organ-resolved sex-specific whole-body models (WBMs) of metabolism. These models were utilized to computationally evaluate the effect of 12 diverse dietary regimens on key MetS biomarkers—glucose, triacylglycerides (TAG), LDL-C, and HDL-C—and fatty acid beta-oxidation in both males and females. Our analyses elucidated molecular mechanisms underlying the link between conventionally unhealthy diets and elevated MetS risk. Specifically, a typical Unhealthy or Keto diet indicated elevated TAG storage in the adipocytes and increased LDL-C to HDL-C ratios across both genders. Conversely, healthier dietary patterns like the Mediterranean and Vegan diets promoted favorable metabolic profiles, characterized by lower TAG storage and LDL-C to HDL-C ratios. Notably, plant-based (Vegan and Vegetarian) diets induced elevated fatty acid oxidation compared to high-fat regimens, suggesting their potential in mitigating MetS risk. Pronounced gender differences in metabolic responses to diets were also observed in our analyses, highlighting the need for gender-tailored dietary recommendations. Additionally, our study delineated organ-specific contributions to the MetS biomarkers, with the liver and lungs identified as major regulators of blood glucose homeostasis. Overall, this study contributes to a deeper understanding of the intricate interactions between diet and MetS risk.
The dynamic gene regulatory landscape of the mouse brain in response to sleep deprivation
Authors: Bafna Akanksha , Dang Quang , Taylor Lewis , Walsh Steven , Sims David , George Charlotte , Jagannath Aarti 
Published: July 2024

ABSTRACTSleep deprivation (SD) negatively impacts nearly all brain functions including cognition, memory consolidation and metabolism. However, the gene regulatory networks that underlie these biological effects are not well understood. In order to identify these networks, we conducted a multiomic analysis to analyse how gene expression, chromatin accessibility, enhancer activity and DNA methylation change with acute SD in mice. By studying three brain regions involved in different aspects of sleep - the cortex (CTX), dentate gyrus (DG), and suprachiasmatic nucleus (SCN) - we found that the effects of SD on the multiome varied widely, impacting physiological processes specific to each area, from spine formation in the dentate gyrus to neuropeptide release in the SCN. Our integrated analysis showed that distinct brain region-specific networks of regulatory factors dynamically alter the epigenomic landscape in response to SD to orchestrate transcriptional responses. These findings provide new understanding of the regulatory grammar encoded within the genome, which enables a general physiological signal like SD to produce unique effects in a tissue-specific context.
Infrared thermography for plant stress detection in vertical farms: Investigating spatiotemporal variations and exploring solutions via machine learning
Authors: Agarwal Avinash , de Jesus Colwell Filipe , Dinnis Rosalind , Correa Galvis Viviana Andrea , Hill Tom , Boonham Neil , Prashar Ankush 
Published: July 2024

AbstractApplication of infrared thermography (IRT) for real-time plant stress detection has grown rapidly in recent years. Although the technology has been well established for crops grown in fields and glasshouses, its feasibility for vertical farms has not been tested extensively. In this study, temporal monitoring of stress induced by root dehydration in purple basil plantlets inside a vertical farm was performed to identify bottlenecks in real-time stress detection via IRT. Subsequently, potential solutions were investigated via machine learning by implementing support vector machines for supervised classification. Edge effects as well as proximity to air vents were identified as the major causes of positional variation in plant temperature that could lead to misprediction of stress. Binary, ternary, and quaternary classification models were trained using thermal images from two, three, and four levels of stress, respectively, to assess model performance. Binary classification models trained with plants experiencing medial and high levels of stress were able to identify stressed plants with high accuracy (81–94%). Further, binary models trained using plants under medial levels of stress generated a continuous probability distribution for stress prediction when plotted against plant temperature. In contrast, models trained using samples experiencing high stress generated distinct probabilistic clusters for the unstressed and highly stressed plants, but were unable to classify medial stress samples reliably. Similarly, ternary and quaternary models were able to better predict very high and very low levels of stress than intermediate stress levels. Hence, our findings suggest that binary classification models trained using samples under medial levels of stress would be helpful in overcoming spatiotemporal variations in canopy thermal profile by providing reliable probabilistic estimates of plant stress within a vertical farming system.Key pointsPlant stress detection in vertical farms via thermal imaging may be challenging because perceptible plant temperature can be strongly influenced by its microenvironment.Thermal image analysis via supervised machine learning allows the development of robust prediction models that can overcome such factors to identify stressed plants.Binary classification machine learning models can reliably identify stressed plants as well as provide probabilistic estimates for the degree of stress.
Antimicrobial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase
Authors: Obeng Bright , Bennett Lucas J. , West Bailey E. , Wagner Dylan J. , Fleming Patrick J. , Tasker Morgan N. , Lorenger Madeleine K. , Smith Dorothy R. , Systuk Tetiana , Plummer Sydni M. , Eom Jeongwon , Paine Marissa D. , Frangos Collin T. , Wilczek Michael P. , Shim Juyoung K. , Maginnis Melissa S. , Gosse Julie A. 
Published: July 2024

AbstractCetylpyridinium chloride (CPC) is a quaternary ammonium antimicrobial used in numerous personal care products, human food, cosmetic products, and cleaning solutions. Yet, there is minimal published data on CPC effects on eukaryotes, immune signaling, and human health. Previously, we showed that low-micromolar CPC inhibits rat mast cell function by inhibiting antigen (Ag)-stimulated Ca2+mobilization, microtubule polymerization, and degranulation. In this study, we extend the findings to human mast cells (LAD2) and present data indicating that CPC’s mechanism of action centers on its positively-charged quaternary nitrogen in its pyridinium headgroup. CPC’s inhibitory effect is independent of signaling platform receptor architecture. Tyrosine phosphorylation events are a trigger of Ca2+mobilization necessary for degranulation. CPC inhibits global tyrosine phosphorylation in Ag-stimulated mast cells. Specifically, CPC inhibits tyrosine phosphorylation of specific key players Syk kinase and LAT, a substrate of Syk. In contrast, CPC does not affect Lyn kinase phosphorylation. Thus, CPC’s root mechanism is electrostatic disruption of particular tyrosine phosphorylation events essential for signaling. This work outlines the biochemical mechanisms underlying the effects of CPC on immune signaling and allows the prediction of CPC effects on cell types, like T cells, that share similar signaling elements.
Thickness and quality controlled fabrication of fluorescence-targeted frozen-hydrated lamellae
Authors: Boltje Daan B. , Skoupy Radim , Taisne Clémence , Evers Wiel H. , Jakobi Arjen J. , Hoogenboom Jacob P. 
Published: July 2024

AbstractCryogenic focused ion beam (FIB) milling is essential for fabricating thin lamella-shaped samples out of frozen-hydrated cells for high-resolution structure determination. Structural information can only be resolved at high resolution if the lamella thickness is between 100 and 200 nm. While the lamella fabrication workflow has undergone significant improvements since its conception, quantitative, live feedback on lamella thickness and quality is still lacking. Taking advantage of a coincident light microscopy integrated into the FIB-SEM, we present three different strategies that together allow accurate, live control during lamella fabrication. First, we combine 4D-STEM with fluorescence microscope (FM) targeting to determine the lamella thickness. Second, with reflected light microscopy (RLM) we screen target sites for ice contamination and monitor lamella thickness and integrity of the protective Pt coating during FIB milling. Third, we exploit thin-film interference to obtain fine-grained feedback on thickness uniformity below 500 nm. We finally present a full workflow for fluorescence-targeted and quality controlled fabrication of frozen-hydrated lamellae, benchmarked with excellent agreement to energy filtered transmision electron microscopy (EFTEM) measurements and reconstructed tomograms obtained with electron cryo-tomography.
A Systematic Review of the Distribution and Prevalence of Viruses Detected in thePeromyscus maniculatusSpecies Complex (Rodentia: Cricetidae)
Authors: Finkbeiner Ally , Khatib Ahmad , Upham Nathan , Sterner Beckett 
Published: July 2024

AbstractThe North American Deermouse,Peromyscus maniculatus, is one of the most widespread and abundant mammals on the continent. It is of public health interest as a known host of several viruses that are transmissible to humans and can cause illness, including the acute respiratory disease Hantavirus pulmonary syndrome (HPS). However, recent taxonomic studies indicate thatP. maniculatusis a complex of multiple species, raising questions about how to identify and interpret three decades of hantavirus monitoring data. We conducted a systematic review investigating the prevalence and spatial distribution of viral taxa detected in wild populations allocated toP. maniculatus. From the 49 relevant studies published from 2000 to 2022, we extracted and analyzed spatial occurrence data to calculate weighted populational prevalences for hantaviruses. We found that detection efforts have been concentrated in the Western United States and Mexico with a focus on the spread of Sin Nombre virus (Orthohantavirus sinnombreense), the primary causative agent of HPS. There are significant gaps in the existing literature both geographically and in regard to the types of viruses being sampled. These results are significantly impacted by a recent taxonomic split ofP. maniculatusinto four species, and we were able to update 94% of hantavirus observations to reflect this change. Investigating the uncertain, and likely multiple, phylogenetic histories of these viral hosts should be a key emphasis of future modeling efforts.Author SummaryUnderstanding the interactions of viruses with mammal hosts is critical for monitoring disease spread and identifying species or geographic areas at high risk for future zoonotic disease outbreaks. However, much of the data scientists have collected about viruses in mammals remains fragmented in published literature and is not available in an up-to-date, standardized format online. We conducted a systematic review of virus observations in one of the most abundant, widespread group of rodent species in North America, thePeromyscus maniculatus(North American Deermouse) species complex. We extracted and analyzed the spatial distribution of 62,421 observations reporting the results of tests for viruses in the Hantaviridae, Arenaviridae, and Flaviviridae families. We find that conclusions about reservoir host status may be impacted by recent taxonomic proposals that splitP. maniculatusinto four distinct species, and we show how the taxonomic identifications of 94% of the reported observations can be updated using expert-generated maps of the ranges for the proposed new species. We also highlight the uneven geographic sampling of viruses in the rodent populations and major gaps that remain in our knowledge.
Heli-SMACC: Helicase-targeting SMAll Molecule Compound Collection
Authors: Martin Holli-Joi , Hossain Mohammad A. , Wellnitz James , Kelestemur Enes , Hochuli Joshua E. , Parveen Sumera , Arrowsmith Cheryl , Willson Timothy M. , Muratov Eugene , Tropsha Alexander 
Published: July 2024

AbstractHelicases have emerged as promising targets for the development of antiviral drugs; however, the family remains largely undrugged. To support the focused development of viral helicase inhibitors we identified, collected, and integrated all chemogenomics data for all available helicases from the ChEMBL database. After thoroughly curating and enriching the data with relevant annotations we have created a derivative database of helicase inhibitors which we dubbed Heli-SMACC (Helicase-targetingSMAll MoleculeCompoundCollection). The current version of Heli-SMACC contains 20,432 bioactivity entries for viral, human, and bacterial helicases. We have selected 30 compounds with promising viral helicase activity and tested them in a SARS-CoV-2 NSP13 ATPase assay. Twelve compounds demonstrated ATPase inhibition and a consistent dose-response curve. The Heli-SMACC database may serve as a reference for virologists and medicinal chemists working on the development of novel helicase inhibitors. Heli-SMACC is publicly available athttps://smacc.mml.unc.edu.HighlightsWe created a curated Helicase-Targeting SMAll Molecule Compound Collection (Heli-SMACC).Heli-SMACC covers 29 human, viral, and bacterial helicases.Twelve of thirty selected compounds demonstrated inhibitory activity in a SARS-CoV-2 NSP13 ATPase Assay.Heli-SMACC is freely available online athttps://smacc.mml.unc.edu.TOC Graphic
LAG-3 blockade reactivates the CD8+T cell expansion program to re-expand contracted clones in the tumor
Authors: Takahashi Munetomo , Tsunoda Mikiya , Aoki Hiroyasu , Kurosu Masaki , Ogiwara Haru , Shichino Shigeyuki , Bending David , Ishikawa Shumpei , Thaventhiran James E.D. , Matsushima Kouji , Ueha Satoshi 
Published: July 2024

AbstractEffective cancer immunotherapy relies on the clonal proliferation and expansion of CD8+T cells in the tumor1,2. However, our insights into clonal expansions are limited, owing to an inability to track the same clones in tumors over time. Here, we developed a multi-tumor mouse model system to track hundreds of expanding and contracting CD8+T cell clones over multiple timepoints in tumors of the same individual. Through coupling of clonal expansion dynamics and single-cell RNA/TCR-seq data, we identified a transcriptomic signature in PD-1+Ly108+precursor exhausted cells3,4that strongly predicts rates of intratumoral clone expansion in mice and humans. We found that expression of the signature successfully stratifies melanoma patient outcomes to PD-1/PD-L1 blockade5,6. Downregulation of the signature precedes clone contraction – a phase in which clones contract but maintain revivable precursor exhausted cells in the tumor. LAG-3 blockade – an FDA-approved therapy whose effects on CD8+T cell responses are currently unclear7, re-activates the expansion signature, re-expanding pre-existing clones, including previously contracted clones. These findings reveal how the study of clonal expansion dynamics provide a powerful ‘pan-immunotherapy’ signature for monitoring immunotherapies, including PD-1/PD-L1 and LAG-3 blockade, with implications for their future development.