bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the PolyJet Printing Technology Affect Mechanical Properties of 3D Printed Synthetic Tissue?
Authors: Kohnle Samantha , Bermel Emily , Severseike Leah , Bhatia Varun 
Published: June 2024

AbstractWithin the medical field, there are multiple opportunities in which 3D printed anatomical models could be utilized such as physician training, surgical planning, education, and R&D testing. Because of this, it is vital to choose materials that most closely mechanically mimic the tissues that would be seen within the simulated model. Stratasys currently has a line of Digital Anatomy (DA) printers that contain predetermined compositions and mixtures called anatomical presets to mimic soft tissue materials such as liver, myocardium, aortic, and epicardium tissue. Different compositions of these printed materials have been previously printed on the J750 Digital Anatomy printer and have undergone mechanical testing. Stratasys is releasing a new printer called J5 Digital Anatomy printer that will also have the capabilities of printing anatomical presets. To compare any differences between the two printer sample types, these mechanical tests were repeated on the J5 DA printer.Mechanical testing included stiffness testing of printed liver samples, compliance testing of printed myocardium samples, and lubricity testing of printed cardiac tissue samples. Stiffness of J5 DA liver and J750 DA liver samples were similar with slight variation seen in more rigid J5 DA samples; however, both printer samples still fell within the stiffness range observed in porcine liver tissue. Compliance testing showed comparable stiffness between J5 DA and J750 DA myocardium samples; however, J5 DA samples tended to be slightly less stiff making them more similar to porcine myocardium stiffness. Thinner J5 DA samples were more variable when compared to J750 DA samples; however, this was minimal variability when compared to that experienced in porcine tissue. Lubricity testing showed comparable coefficients of friction between J5 DA and J750 DA samples with the exception of Mineral oil and Dry lubricants. J5 DA cardiac samples saw smaller coefficients of friction; however, these still fell within the range of aortic and epicardium coefficients of frictions. Because of these results, it can be concluded that the J5 DA printer samples are comparable to J750 DA printer samples and are alternatives to animal tissue benchtop testing depending on the application.
Functionally Adaptive Structural Basis Sets of the Brain: A Dynamic Fusion Approach
Authors: Duda Marlena , Chen Jiayu , Belger Aysenil , Ford Judith , Mathalon Daniel , Preda Adrian , Turner Jessica , Erp Theo Van , Pearlson Godfrey , Calhoun Vince D. 
Published: June 2024

AbstractThe precise relationship between brain structure and function has been investigated through a multitude of lenses, but one detail that is held constant across most neuroimaging studies in this space is the identification of a singular structural basis set of the brain, upon which functional activation signals can be reconstructed to examine the linkage between structure and function. Such basis sets can be considered “functionally independent”, as they are derived through structural data alone and have no explicit association to functional data. Recent work in multimodal fusion has facilitated a more integrated view of structure-function linkages by enabling the equal contribution of both modalities to the joint decomposition, resulting in components that are independent within modality but co-vary closely across modalities. These existing symmetric fusion approaches thus identify structural bases given an associated functional context. In this work we consider an additional layer of precision to the investigation of structure-function coupling by studying these context-dependent linkages in a time-resolved manner. In other words, we ask which features of brain structure become (or remain) salient given the dynamically changing functional contexts (i.e., dynamic functional connectivity states, task structure, etc.) the brain may pass through during a given fMRI scan. We introduce “dynamic fusion”, an ICA-based symmetric fusion approach that enables flexible, time-resolved linkages between brain structure and dynamic brain function. We show evidence that temporally resolved, and functionally contextualized, structural basis sets can accurately reflect dynamic functional processes and capture diagnostically relevant structure- functional coupling while detecting nuanced functionally-driven structural components that cannot be captured with traditionally computed structural bases. Lastly, differential analysis of component stability across repeated scans from a control cohort reveals organization of static and dynamic structure/function coupling falls along unimodal/transmodal hierarchical lines.
Quantum theory of a potential biological magnetic field sensor: radical pair mechanism in flavin adenine dinucleotide biradicals
Authors: Sotoodehfar Amirhosein , Rishabh  , Zadeh-Haghighi Hadi , Simon Christoph 
Published: June 2024

AbstractRecent studiesin vitroandin vivosuggest that flavin adenine dinucleotide (FAD) on its own might be able to act as a biological magnetic field sensor. Motivated by these observations, in this study, we develop a detailed quantum theoretical model for the radical pair mechanism (RPM) for the flavin adenine biradical within the FAD molecule. We perform molecular dynamics simulations to determine the distance between the radicals on FAD, which we then feed into a quantum master equation treatment of the RPM. In contrast to previous semi-classical models which are limited to the low-field and high-field cases, our quantum model can predict the full magnetic field dependence of the transient absorption signal. Our model’s predictions are consistent with experiments.
Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function
Authors: Loeb Gabriel B. , Kathail Pooja , Shuai Richard , Chung Ryan , Grona Reinier J. , Peddada Sailaja , Sevim Volkan , Federman Scot , Mader Karl , Chu Audrey , Davitte Jonathan , Du Juan , Gupta Alexander R. , Ye Chun Jimmie , Shafer Shawn , Przybyla Laralynne , Rapiteanu Radu , Ioannidis Nilah , Reiter Jeremy F. 
Published: June 2024

AbstractKidney disease is highly heritable; however, the causal genetic variants, the cell types in which these variants function, and the molecular mechanisms underlying kidney disease remain largely unknown. To identify genetic loci affecting kidney function, we performed a GWAS using multiple kidney function biomarkers and identified 462 loci. To begin to investigate how these loci affect kidney function, we generated single-cell chromatin accessibility (scATAC-seq) maps of the human kidney and identified candidatecis-regulatory elements (cCREs) for kidney podocytes, tubule epithelial cells, and kidney endothelial, stromal, and immune cells. Kidney tubule epithelial cCREs explained 58% of kidney function SNP-heritability and kidney podocyte cCREs explained an additional 6.5% of SNP-heritability. In contrast, little kidney function heritability was explained by kidney endothelial, stromal, or immune cell-specific cCREs. Through functionally informed fine-mapping, we identified putative causal kidney function variants and their corresponding cCREs. Using kidney scATAC-seq data, we created a deep learning model (which we named ChromKid) to predict kidney cell type-specific chromatin accessibility from sequence. ChromKid and allele specific kidney scATAC-seq revealed that many fine-mapped kidney function variants locally change chromatin accessibility in tubule epithelial cells. Enhancer assays confirmed that fine-mapped kidney function variants alter tubule epithelial regulatory element function. To map the genes which these regulatory elements control, we used CRISPR interference (CRISPRi) to target these regulatory elements in tubule epithelial cells and assessed changes in gene expression. CRISPRi of enhancers harboring kidney function variants regulatedNDRG1andRBPMSexpression. Thus, inherited differences in tubule epithelialNDRG1andRBPMSexpression may predispose to kidney disease in humans. We conclude that genetic variants affecting tubule epithelial regulatory element function account for most SNP-heritability of human kidney function. This work provides an experimental approach to identify the variants, regulatory elements, and genes involved in polygenic disease.
PathoLM: Identifying pathogenicity from the DNA sequence through the Genome Foundation Model
Authors: Dip Sajib Acharjee , Shuvo Uddip Acharjee , Chau Tran , Song Haoqiu , Choi Petra , Wang Xuan , Zhang Liqing 
Published: June 2024

AbstractPathogen identification is pivotal in diagnosing, treating, and preventing diseases, crucial for controlling infections and safeguarding public health. Traditional alignment-based methods, though widely used, are computationally intense and reliant on extensive reference databases, often failing to detect novel pathogens due to their low sensitivity and specificity. Similarly, conventional machine learning techniques, while promising, require large annotated datasets and extensive feature engineering and are prone to overfitting. Addressing these challenges, we introduce PathoLM, a cutting-edge pathogen language model optimized for the identification of pathogenicity in bacterial and viral sequences. Leveraging the strengths of pre-trained DNA models such as the Nucleotide Transformer, PathoLM requires minimal data for fine-tuning, thereby enhancing pathogen detection capabilities. It effectively captures a broader genomic context, significantly improving the identification of novel and divergent pathogens. We developed a comprehensive data set comprising approximately 30 species of viruses and bacteria, including ESKAPEE pathogens, seven notably virulent bacterial strains resistant to antibiotics. Additionally, we curated a species classification dataset centered specifically on the ESKAPEE group. In comparative assessments, PathoLM dramatically outperforms existing models like DciPatho, demonstrating robust zero-shot and few-shot capabilities. Furthermore, we expanded PathoLM-Sp for ESKAPEE species classification, where it showed superior performance compared to other advanced deep learning methods, despite the complexities of the task.
Full-length direct RNA sequencing reveals extensive remodeling of RNA expression, processing and modification in agingCaenorhabditis elegans
Authors: Schiksnis Erin C. , Nicastro Ian A. , Pasquinelli Amy E. 
Published: June 2024

SummaryOrganismal aging is marked by decline in cellular function and anatomy, ultimately resulting in death. To inform our understanding of the mechanisms underlying this degeneration, we performed standard RNA sequencing and Nanopore direct RNA sequencing over an adult time course inCaenorhabditis elegans.Long reads allowed for identification of hundreds of novel isoforms and age-associated differential isoform accumulation, resulting from alternative splicing and terminal exon choice. Genome-wide analysis reveals a decline in RNA processing fidelity and a rise in inosine and pseudouridine editing events in transcripts from older animals. In this first map of pseudouridine modifications forC. elegans, we find that they largely reside in coding sequences and that the number of genes with this modification increases with age. Collectively, this analysis discovers transcriptomic signatures associated with age and is a valuable resource to understand the many processes that dictate altered gene expression patterns and post-transcriptional regulation in aging.
Acute nicotine vapor normalizes sensorimotor gating and reduces locomotor activity deficits in HIV-1 transgenic rats
Authors: Jha Neal A. , Ayoub Samantha M. , Flesher M. Melissa , Morton Kathleen , Sikkink Megan , de Guglielmo Giordano , Khokhar Jibran Y. , Minassian Arpi , Brody Arthur L. , Young Jared W. 
Published: June 2024

AbstractRationaleDespite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication.ObjectivesHere, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV.MethodsMale and female HIV-1Tg and F344 control rats (n=57) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM).ResultsVehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV-1Tg rats, however. HIV-1Tg rats were hypoactive in the BPM relative to controls, whilst nicotine vapor increased activity and exploratory behavior across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes.ConclusionsPrevious findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. HIV-1Tg rats had reduced exploratory behavior compared to controls, attenuated by acute nicotine vapor. Therefore, acute nicotine may be beneficial for remediating sensorimotor and locomotor activity deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.
The Retrosplenial Cortical Role in Delayed Spatial Alternation
Authors: Subramanian Dev Laxman , Miller Adam M.P. , Smith David M. 
Published: June 2024

AbstractThe retrosplenial cortex (RSC) plays an important role in spatial cognition. RSC neurons exhibit a variety of spatial firing patterns and lesion studies have found that the RSC is necessary for spatial working memory tasks. However, little is known about how RSC neurons might encode spatial memory during a delay period. In the present study, we trained control rats and rats with excitotoxic lesions of the RSC on spatial alternation task with varying delay durations and in a separate group of rats, we recorded RSC neuronal activity as the rats performed the alternation task. We found that RSC lesions significantly impaired alternation performance, particularly at the longest delay duration. We also found that RSC neurons exhibited reliably different firing patterns throughout the delay periods preceding left and right trials, consistent with a working memory signal. These differential firing patterns were absent during the delay periods preceding errors. We also found that many RSC neurons exhibit a large spike in firing rate leading up to the start of the trial. Many of these trial start responses also differentiated left and right trials, suggesting that they could play a role in priming the ‘go left’ or ‘go right’ behavioral responses. Our results suggest that these firing patterns represent critical memory information that underlies the RSC role in spatial working memory.
O-Glycosylated RNA Identification and Site-specific Prediction by Solid-phase Chemoenzymatic TnORNA method and PONglyRNA tool
Authors: Li Jiajia , Wang Linshu , Chen Yan , Zhang Shaomei , Wen Zhongmin , Zhen Xuechu , Zhang Haiyun , Zhou Yuan , Xu Longjiang , Yang Shuang 
Published: June 2024

AbstractRecent studies have shown that the cell surface undergoes post-transcriptional modification by N-linked glycosylation. However, the question of whether RNA can be glycosylated by O-glycans remains to be explored. The presence of O-glycosylation in cells is indirectly revealed by the presence of O-glycans on RNAs following treatment with O-glycoproteases. To identify RNA O-glycosylation, we have developed a chemoenzymatic method for capturing and enriching O-glycosylated RNA (O-glycoRNA) using covalent immobilization on a solid support. GalNAcEXO selectively releases Tn-containing O-glycosylated RNAs (TnORNA). Using this method and SPCgRNA, we compared the expression of O-glycoRNAs and N-glycoRNAs in pancreatic cancer cell lines and tissues. We found that glycosylated miR-103a-3p, miR-122-5p, and miR-4492 regulate pancreatic cancer cell growth and proliferation through the PI3K-Akt pathway. In vitro assays and PDAC tissue analysis confirmed the potential regulatory roles of Tn-O-glycosylated miRNAs in pancreatic tumor growth and metastasis. Furthermore, a significant number (131) of miRNAs carrying both N- and Tn-O-glycosylation were identified, indicating the co-occurrence of N-linked and O-linked glycosylation on small RNAs. We have also developed PONglyRNA, an online bioinformatic tool for the site-specific prediction of RNA glycosylation. PONglyRNA identifies glycosylation motifs based on RNA sequence and has been validated using our glycoRNA data. In conclusion, this study establishes robust experimental and computational tools for identifying O-linked glycoRNAs. Additionally, it uncovers the novel role of glycosylation in PDAC development and progression through altered glycosylation of oncogenic miRNAs.Graphical Abstract
Label-free visualization of ciliary rootlets in mouse brain
Authors: Murakami Yusuke , Nuriya Mutsuo , Hu Zuliang , Tomioka Masaki , Oketani Ryosuke , Hiramatsu Kotaro , Leproux Philippe , Inoko Akihito , Honjoh Sakiko , Kano Hideaki 
Published: June 2024

AbstractNeuronal primary cilia are important role in brain development, sensory perception and neurogenesis. Rootletin, a fibrous protein composed of coiled-coil motifs, is a major structural component of ciliary rootlets and is essential for understanding ciliary functions. However, the precise mechanisms by which Rootletin influences ciliary dynamics and impacts neuronal function remain largely unknown, primarily due to the challenges in visualizing these structures. Here, we describe a label-free, rapid, and highly sensitive method to visualize Rootletin molecules in brain tissue. This platform integrates a second harmonic generation (SHG) microscope and background reduction by a one-step chemical pretreatment. Additionally, we employ coherent anti-Stokes Raman scattering imaging to simultaneously determine the cellular regions and intracellular locations of SHG signals. By applying this multimodal multiphoton imaging to mouse hippocampus, we found that neuronal ciliary rootlets were found to exhibit highly organized specific intracellular distributions. Moreover, the formation of ciliary rootlets precedes that of primary cilia. These findings highlight the utility of our label-free imaging platform in developmental and neuroscience research, providing a new tool to characterize ciliary dynamics and neuronal function.
Interaction between mitochondrial translocator protein and aging in inflammatory responses in mouse hippocampus
Authors: Lai Kei Onn , Tham Nevin , Fairley Lauren , Naik Roshan Ratnakar , Wang Yulan , Langley Sarah R. , Barron Anna M. 
Published: June 2024

AbstractThe mitochondrial translocator protein (TSPO) is a biomarker of inflammation which is upregulated in the brain in aging and associated neurodegenerative diseases, such as Alzheimer’s disease (AD). Here we investigated the interaction between aging and TSPO immunomodulatory function in mouse hippocampus, a region severely affected in AD. Aging resulted in a reversal of TSPO knockout transcriptional signatures following inflammatory insult, with TSPO deletion drastically exacerbating inflammatory transcriptional responses in the aging hippocampus whilst dampening inflammation in the young hippocampus. Drugs that disrupt cell cycle and induce DNA-damage such as heat shock protein and topoisomerase inhibitors were identified to mimic the inflammatory transcriptional signature characterizing TSPO-dependent aging most closely. This TSPO-aging interaction is an important consideration in the interpretation of TSPO-targeted biomarker and therapeutic studies, as well asin vitrostudies which cannot model the aging brain.
Integrated Movement Models for Individual Tracking and Species Distribution Data
Authors: Buderman Frances E. , Hanks Ephraim M. , Ruiz-Gutierrez Viviana , Shull Michael , Murphy Robert K. , Miller David A.W. 
Published: June 2024

AbstractWhile the quantity, quality, and variety of movement data has increased, methods that jointly allow for population- and species-level movement parameters to be estimated are still needed. We present a formal data integration approach to combine individual-level movement and population-level distribution data. We show how formal data integration can be used to improve precision of individual and population level movement parameters and allow additional population level metrics (e.g., connectivity) to be formally quantified.We describe three components needed for an Integrated Movement Model (IMM): a model for individual movement, a model for among-individual heterogeneity, and a model to quantify changes in species distribution. We outline a general IMM framework and develop and apply a specific stochastic differential equation model to a case study of telemetry and species distribution data for golden eagles in western North American during spring migration.We estimate eagle movements during spring migration from data collected between 2011 and 2019. Individual heterogeneity in migration behavior was modeled for two sub-populations, individuals that make significant northward migrations and those that remained in the southern Rocky Mountain region through the summer. As is the case with most tracking studies, the sample population of individual telemetered birds is not representative of the population, and underrepresents the proportion of long-distance migrants in. The IMM was able to provide a more biological accurate subpopulation structure by jointly estimating the structure using the species distribution data. In addition, the integrated approach a) improves accuracy of other estimated movement parameters, b) allows us to estimate the proportion of migratory and non-migratory birds in a given location and time, and c) estimate future spatio-temporal distributions of birds given a wintering location, which provide estimates of seasonal connectivity and migratory routes.We demonstrate how IMMs can be successfully used to address the challenge of estimating accurate population level movement parameters. Our approach can be generalized to a broad range of available movement models and data types, allowing us to significantly improve our knowledge of migration ecology across taxonomic groups, and address population and continental level information needs for conservation and management.