bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical activity increases neuronal activity in the circadian clock of diurnalArvicanthis ansorgei
Authors: Caputo Rosanna , Schoonderwoerd Robin A. , Ramkisoensing Ashna , Janse Jan A.M. , van Diepen Hester C. , Raison Sylvie , Pévet Paul , Derks Nienke A.V. , Sage-Ciocca Dominique , Deboer Tom , Challet Etienne , Meijer Johanna H. 
Published: June 2022

2.AbstractThe central circadian clock, located in the suprachiasmatic nucleus (SCN) within the brain, regulates daily patterns of activity and physiology. Many studies indicate that exercise at specific times throughout the day can help maintain proper circadian rhythms. In nocturnal animals, even moderate levels of physical activity suppress the neuronal discharge rate of the SCN. Given that such a mechanism would likely be counter-effective in diurnal animals, we measured the firing rate of SCN neurons in freely moving diurnalArvicanthis ansorgeiusing implanted microelectrodes. We found that SCN firing was acutely increased rather than decreased both during brief (seconds) and long (hours) bouts of activity, and returned to baseline levels after behavioral activity ceased. We also found that daytime activity increases the strength of the SCN rhythm, as expected for day-active animals. To determine whether the acute increases in firing are produced within the SCN or in response to input from outside the SCN, we performedex vivorecordings in which afferent inputs are severed. We found no intrinsic increment occurring in the isolated SCN. These findings suggest that the excitatory effect on the SCN’s neuronal firing rate comes from areas that lie outside the SCN, presumably those that are affected by the animal’s activity. We conclude that exercise has opposite effects on the clock between nocturnal and diurnal rodents, and identified how exercise strengthens the neuronal discharge rhythm in the clock of a diurnal animal.3.Significance statementOur biological clock controls behavioral activity rhythms by generating a 24-pattern of electrical activity. The electrical activity serves as output of the clock and is high during the day and low during the night. Physical activity, being under strong control of the clock, acts vice versa, and affects the electrical activity of the clock. In nocturnal animals, behavioral activity inhibits the clock’s firing rate. Here, we examined the effect of behavioral activity on the brain’s clock in the diurnal rodent,Arvicanthis. When the animal is active, the clock’s electrical activity is enhanced, rather than decreased. Thus, a diurnal animal can increase the strength of its own clock, by being active during the day.Preprint ServersThe manuscript was deposited as a preprint in bioRxiv preprint doi:https://doi.org/10.1101/2022.05.31.493966; this version posted June 1, 2022. The copyright holder for this preprintin bioRxiv, made available under aCC-BY-NC-ND 4.0 International license (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.ClassificationBiological Sciences, Physiology
A novel 3-miRNA network regulates tumour progression in oral squamous cell carcinoma
Authors: Patel Aditi , Patel Parina , Mandlik Dushyant , Patel Kaustubh , Malaviya Pooja , Johar Kaid , Swamy Krishna B.S , Patel Shanaya , Tanavde Vivek 
Published: June 2022

AbstractOral squamous cell carcinoma (OSCC) is often diagnosed late, leading to poor patient outcomes. This study aims to identify potential miRNA-based biomarkers for predicting disease progression using salivary exosomes derived from OSCC patients. Further, we identify crucial miRNA-mRNA networks involved in tumorigenesis and uncover the underlying mechanism responsible for OSCC progression.Small RNA (n=23) sequencing analysis along with data available from The Cancer Genome Atlas (TCGA) (n=114) identified 12 differentially expressed miRNAs in OSCC patients as compared to controls. Validating these findings, miR-140-5p, miR-143-5p, and miR-145-5p were significantly downregulated in a larger cohort of OSCC patients (n=70). This 3-miRNA signature demonstrated higher efficacy of salivary exosomes (p<0.0001) in early detection and clinically correlated with disease progression and overall survival of OSCC patients (p<0.05). Further, analysis of the transcriptome, TCGA datasets and miRNA-mRNA networks, identified top hub genes (HIF1a,CDH1,CD44,EGFR, andCCND1) which were regulated by a 3-miRNA signature. Based on pathway analysis, these miRNA-mRNA interactions were found to be involved in regulating epithelial-mesenchymal transition (EMT). Further, transfection-mediated upregulation of the 3-miRNA signature significantly decreased cell proliferation, induced apoptosis, resulted in G2/M phase cell cycle arrest and reduced the invasive and migratory potential by reversing the EMT process in OECM-1 cell line.Thus, this study identifies a 3-miRNA signature that can be utilized as a potential biomarker for early detection of OSCC and uncovers the underlying mechanisms responsible for converting a normal epithelial cell into a malignant phenotype.
A flexible, efficient, and scalable platform to produce circular RNAs as new therapeutics
Authors: Chen Chuyun , Wei Huanhuan , Zhang Kai , Li Zeyang , Wei Tong , Tang Chenxiang , Yang Yun , Wang Zefeng 
Published: June 2022

AbstractMessenger RNA (mRNA) has recently emerged as a new drug modality with great therapeutic potential. However, linear mRNAs are relatively unstable and also require base modification to reduce their immunogenicity, imposing a limitation to the broad application. With improved stability, the circular RNA (circRNA) presents a better alternative for prolonged expression of the proteins, however the in vitro circularization of RNA at a large scale is technically challenging. Here we developed a new self-catalyzed system to efficiently produce circRNAs in a co-transcriptional fashion. By rational sequence design, we can efficiently produce scarless circRNAs that do not contain foreign sequences. The resulting circRNAs are very stable and have low immunogenicity, enabling prolonged protein translation in different cells without cellular toxicity. The circRNAs generated from this platform can be encapsulated in lipid nanoparticles and efficiently delivered into mice to direct robust protein expression. Finally, the circRNAs encoding RBD of SARS-CoV-2 S protein induced strong antibody productions, with neutralization antibody titers higher than the preclinical data from the linear mRNAs. Collectively, this study provided a general platform for efficient production of circRNAs, demonstrating the potential of circRNAs as the new generation of mRNA therapy.
The Value of Zero-filling in In Vivo MRS
Authors: Murali-Manohar Saipavitra , Oeltzschner Georg , Barker Peter B. , Edden Richard A.E. 
Published: June 2022

AbstractTwo opinions currently exist on the role of zero-filling in data processing for in vivo MRS: that it results in a purely cosmetic interpolation; or that it confers a benefit. Most commonly, in vivo MRS data are acquired as complex time-domain half-echoes, that are Fourier transformed to the give a real spectrum that is modeled for quantification. In this manuscript, we highlight that performing zero-filling draws the independent information from the imaginary part of the spectrum into the real spectrum, improving modeling accuracy. In order to demonstrate this, 10,000 time-domain datasets were simulated as decaying exponentials and noise was added. Data were then Fourier transformed with no-zero filling, 2x, 4x and 8x zero-filling. All spectra were then modeled using a simple single-Lorentzian frequency-domain model. It was demonstrated that 2x zero-filling results in a ∼√2 benefit in modeling accuracy, compared to no zero-filling. There was no additional advantage for further zero-filling.
Multiple Cullin-Associated E3 Ligases Regulate Cyclin D1 Protein Stability
Authors: Lu Ke , Zhang Ming , Xiao Guozhi , Tong Liping , Chen Di 
Published: June 2022

AbstractCyclin D1 is a key regulator of cell cycle progression, which forms a complex with CDK4/6 to regulate G1/S phase transition during cell cycle progression. Cyclin D1 has been recognized as an oncogene since it was upregulated in several different types of cancers. It is known that the post-translational regulation of cyclin D1 is controlled by ubiquitination/ proteasome degradation system in a phosphorylation-dependent manner. A few cullin-associated F-box E3 ligases have been shown to regulate cyclin D1 degradation; however, it is not known if additional cullin-associated E3 ligases participate in the regulation of cyclin D1 protein stability. In this study, we have screened a siRNA library containing siRNAs specific for 154 ligase subunits, including F-box, SOCS, BTB-containing proteins and DDB proteins. We found that multiple cullin-associated E3 ligases regulate cyclin D1 activity, including Keap1, DDB2, WSB2 and Rbx1. We found that these E3 ligases directly interact with cyclin D1, regulate cyclin D1 ubiquitination and proteasome degradation in a phosphorylation-dependent manner. These E3 ligases also control cell cycle progression and cell proliferation through regulation of cyclin D1 protein stability. Our study provides novel insights into regulatory mechanisms of cyclin D1 protein stability and function.
BirdVox: Machine listening for bird migration monitoring
Authors: Lostanlen Vincent , Cramer Aurora , Salamon Justin , Farnsworth Andrew , Van Doren Benjamin M. , Kelling Steve , Bello Juan Pablo 
Published: June 2022

AbstractThe steady decline of avian populations worldwide urgently calls for a cyber-physical system to monitor bird migration at the continental scale. Compared to other sources of information (radar and crowdsourced observations), bioacoustic sensor networks combine low latency with a high taxonomic specificity. However, the scarcity of flight calls in bioacoustic monitoring scenes (below 0.1% of total recording time) requires the automation of audio content analysis. In this article, we address the problem of scaling up the detection and classification of flight calls to a full-season dataset: 6672 hours across nine sensors, yielding around 480 million neural network predictions. Our proposed pipeline, BirdVox, combines multiple machine learning modules to produce per-species flight call counts. We evaluate BirdVox on an annotated subset of the full season (296 hours) and discuss the main sources of estimation error which are inherent to a real-world deployment: mechanical sensor failures, sensitivity to background noise, misdetection, and taxonomic confusion. After developing dedicated solutions to mitigate these sources of error, we demonstrate the usability of BirdVox by reporting a species-specific temporal estimate of flight call activity for the Swainson’s Thrush(Catharus ustulatus).
R/LinkedCharts: A novel approach for simple but powerful interactive data analysis
Authors: Ovchinnikova Svetlana , Anders Simon 
Published: June 2022

AbstractIn any research project involving data-rich assays, exploratory data analysis is a crucial step. Typically, this involves jumping back and forth between visualizations that provide overview of the whole data and others that dive into details. In data quality assessment, for example, it might be very helpful to have one chart showing a summary statistic for all samples, and clicking on one of the data points would display details on this sample in a second plot. Setting up such interactively linked charts is usually too cumbersome and time-consuming to use them inad hocanalysis. We present R/LinkedCharts, a framework that renders this task radically simple: Producing linked charts is as quickly done as is producing conventional static plots in R, requiring a data scientist to write only very few lines of simple R code to obtain complex and general visualization. We expect that the convenience of our new tool will enable data scientists and bioinformaticians to perform much deeper and more thorough EDA with much less effort. Furthermore, R/LinkedCharts apps, typically first written as quick-and-dirty hacks, can also later be polished to provide interactive data access in publication quality, thus contributing to open science.
Preparing glycomics data for robust statistical analysis with GlyCompareCT
Authors: Zhang Yujie , Krishnan Sridevi , Bao Bokan , Chiang Austin W.T. , Sorrentino James T. , Schinn Song-Min , Kellman Benjamin P. , Lewis Nathan E. 
Published: June 2022

AbstractSummaryGlycomics data are rapidly increasing in scale and diversity. Complexities in glycan biosynthesis (hierarchy, competition, and compartmentalization) make preprocessing critical to address resulting sparsity (many similar glycosylation profiles may share few common glycans) and non-independence (substrate-competition in glycan biosynthesis results in non-independence incompatible with many statistical methods). Here, we present GlyCompareCT, a portable command-line tool, to address these challenges thereby facilitating downstream analyses. Given glycan abundances, GlyCompareCT conducts substructure decomposition to quantify hidden biosynthetic intermediate abundance and relationships between measured glycans. Thus, GlyComparCT mitigates sparsity and makes interdependence explicit thereby increasing statistical power. Ultimately, GlyComparCT is a user-friendly implementation of substructure analysis designed to increase accessibility, interoperability, and scope and consistency in glycomics analysis.Availability and implementationSource code, test data, and instructions for GlyCompareCT v1.1.0 are available at: https://github.com/LewisLabUCSD/GlyCompareCTSupplementary informationhttps://github.com/LewisLabUCSD/GlyCompareCT/raw/main/Supplementary%20Material.pdf
Time-lapse Imaging of Microglial Activity and Astrocytic Calcium Signaling Reveals a Neuroprotective Effect of Cannabidiol in the Subacute Phase of Stroke
Authors: Meyer Erika , Rieder Phillip , Gobbo Davide , Cândido Gabriela , Scheller Anja , de Oliveira Rúbia Maria Weffort , Kirchhoff Frank 
Published: June 2022

AbstractPharmacological agents that limit secondary tissue loss and/or improve functional outcomes after stroke are still limited. Cannabidiol, the major non-psychoactive component of Cannabis sativa, has been proposed as a neuroprotective agent against experimental focal cerebral ischemia. The effects of cannabidiol have generally been related to the modulation of neuroinflammation, including the control of glial activation and the toxicity exerted by pro-inflammatory mediators. However, so far, most information concerning cannabidiol neuroprotective effects was obtained from histological and biochemical post-mortem assays. To test whether the effects of cannabidiol on glial cells could be also detected in vivo, we performed time-lapse imaging of microglial activity and astrocytic calcium signaling in the subacute phase of stroke using two-photon laser-scanning microscopy. First, C57BL/6N wild-type mice underwent either sham or transient middle cerebral artery occlusion surgery. The animals received intraperitoneal injection of vehicle or cannabidiol (10 mg/kg) 30 min, 24 h, and 48 h after surgery. One day later the neurological score test was performed. Brain tissue was processed to evaluate the neuronal loss and microglial activation. Transgenic mice with microglial expression of the enhanced green fluorescent protein and astrocyte-specific expression of the calcium sensor GCaMP3 were used to access in vivo microglial activity and astrocytic calcium signaling, respectively. The animals were submitted to the same experimental design described above and to imaging sessions before, 30 min, 24 h and, 48 h after surgery. Astrocytic calcium signaling was also assessed in acutely isolated slices 5 h after transient middle cerebral artery occlusion surgery in the presence of perfusion or cannabidiol solution. Cannabidiol prevented ischemia-induced neurological impairments as well as protected against neuronal loss in ischemic mice. Cannabidiol also reduced ischemia-induced microglial activation, as demonstrated in fixed tissue as well in in vivo conditions. No difference in the amplitude and duration of astrocytic calcium signals was detected before and after the middle cerebral artery occlusion in vivo. Similarly, no significant difference was found in the astrocytic calcium signals between contra and ipsilateral side of acutely isolated brain slices. The present results suggest that the neuroprotective effects of cannabidiol after stroke may occur in the subacute phase of ischemia and reinforce the strong anti-inflammatory property of this compound.
Within-species control reveals novel immune response genes in Caenorhabditis elegans
Authors: Ranawade Ayush , Hartman Emma , Levine Erel 
Published: June 2022

AbstractThe nematode Caenorhabditis elegans is a simple model host for studying the interaction between bacterial pathogens and the metazoan innate immune system. In the last two decades, much focus has been given to studying intestinal infection in the worm by the clinical strain Pseudomonas aeruginosa PA14. Powerful genetic and molecular tools in both species facilitate the identification and analysis of bacterial virulence factors as well as host defense factors.However, findings from these studies are confounded by the use of the genetically, metabolically, and physiologically divergent E. coli OP50 as a food source and as the non-virulent control. Here we report the use of P. aeruginosa z11 strain as a preferable control for PA14 infection studies. We demonstrate that many aspects of worm behavior, health-span, longevity, food attraction, brood size, lifespan, and pathogen avoidance and survival are not affected in z11. We show that the use of z11 as a control for transcriptomics analysis can increase the discovery power. In particular, we identified three novel pathogenesis-related genes in C. elegans. Our findings accentuate the importance of choosing an appropriate control environment for host-pathogen studies.
Whole-genome sequencing identifies interferon induced protein IFI6 as a strong candidate gene for VNN resistance in European sea bass
Authors: Delpuech Emilie , Vandeputte Marc , Morvezen Romain , Bestin Anastasia , Besson Mathieu , Brunier Joseph , Bajek Aline , Imarazene Boudjema , François Yoannah , Bouchez Olivier , Cousin Xavier , Poncet Charles , Morin Thierry , Bruant Jean-Sébastien , Chatain Béatrice , Haffray Pierrick , Phocas Florence , Allal François 
Published: June 2022

AbstractBackgroundViral Nervous Necrosis (VNN) is major disease affecting of European sea bass. Understanding the biological mechanisms that underlie VNN resistance is thus important for the welfare of farmed fish and the sustainability of production systems. This study aimed at identifying key genomic regions and genes that determine VNN resistance in sea bass.ResultsWe generated a dataset of around 900,000 single nucleotide polymorphisms (SNPs) identified from whole-genome sequencing (WGS) in the parental generation in two different commercial populations (pop A and pop B) comprising 2371 and 3428 European sea bass with phenotypic records for binary survival in a VNN challenge. In each commercial population, three cohorts were submitted to the redspotted grouper nervous necrosis virus (RGNNV) challenge by immersion and genotyped on a 57K SNP chip. After imputation of WGS SNPs from their parents, QTL mapping was performed using a Bayesian Sparse Linear Mixed Model (BSLMM). We found several QTL regions on different linkage groups (LG), most of which are specific to a single population, but a QTL region on LG12 was shared by both commercial populations. This QTL region is only 127 kB wide, and we identified IFI6, an interferon induced protein at only 1.9 kB of the most significant SNP. An unrelated validation population with 4 large families was used to validate the effect of the QTL, for which the survival of the susceptible genotype ranges from 39.8 to 45.4%, while that of the resistant genotype ranges from 63.8 to 70.8%.ConclusionsWe could precisely locate the genomic region implied in the main resistance QTL at less than 1.9 kb of the interferon alpha inducible protein 6 (IFI6), which has already been identified as a key player for other viral infections such as hepatitis B and C. This will lead to major improvements for sea bass breeding programs, allowing for greater genetic gain by using marker-assisted genomic selection to obtain more resistant fish. Further functional analyses are needed to evaluate the impact of the variant on the expression of this gene.
Incubation of palatable food craving is associated with brain-wide neuronal activation in mice
Authors: Madangopal Rajtarun , Szelenyi Eric R. , Nguyen Joseph , Brenner Megan B. , Drake Olivia R. , Pham Diana , Shekara Aniruddha , Jin Michelle , Choong Jia Jie , Heins Connor , Komer Lauren E. , Weber Sophia J. , Hope Bruce T. , Shaham Yavin , Golden Sam A. 
Published: June 2022

AbstractStudies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a phenomenon termed ‘incubation of craving’. Mechanistic studies of incubation of craving have focused on specific neurobiological targets within pre- selected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now enable unbiased brain-wide cellular resolution mapping of regions and circuits engaged during learned behaviors. However, these whole brain imaging approaches were developed for mouse brains while incubation of drug craving has primarily been studied in rats and incubation of food craving has not been demonstrated in mice. Here, we established a mouse model of incubation of palatable food craving and examined food reward seeking after 1, 15, and 60 abstinence days. We then used the neuronal activity marker Fos with intact brain mapping procedures to identify corresponding patterns of brain-wide activation. Relapse to food seeking was significantly higher after 60 abstinence days than after 1 or 15 days. Using unbiased ClearMap analysis, we identified increased activation of multiple brain regions, particularly corticostriatal structures, following 60, but not 15 abstinence days. We used orthogonal SMART2 analysis to confirm these findings within corticostriatal and thalamocortical subvolumes and applied expert-guided registration to investigate subdivision and layer-specific activation patterns. Overall, we (1) identified novel brain-wide activity patterns during incubation of food seeking using complementary analytical approaches, and (2) provide a single-cell resolution whole-brain atlas that can be used to identify functional networks and global architecture underlying incubation of food craving.Significance StatementRelapse to reward seeking progressively increases during abstinence, a phenomenon termed incubation of craving. Mechanistic studies of incubation can lead to novel relapse treatments. However, previous studies have primarily used rat models and targeted region-by-region analyses and a brain-wide functional atlas of incubation of reward seeking is lacking. We established a behavioral procedure for incubation of palatable food seeking in mice and applied whole-brain activity mapping with Fos as a neuronal activity marker to identify the functional connectome of this incubation. Like rats, mice showed incubation of food seeking during abstinence. Using two complementary activity mapping approaches, we identified a brain-wide pattern of increased neural activation that mirrored incubation of food seeking after 60, but not 15, days of abstinence.