bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid and Sensitive Detection ofFusarium oxysporumf. sp.cubenseTropical Race 4 Using a RPA-DETECTR Assay
Authors: Venkatesh Jelli , Jankowicz-Cieslak Joanna , Mduma Hassan , Matijevic Mirta , Ali Adel , Balbin Isabel Cristina Calle , Soto-Suárez Mauricio , Zorrilla Cinthya , Mathur Pooja Bhatnagar- 
Published: August 2024

AbstractEarly and prompt detection of banana wilt pathogenFusarium oxysporumf. sp.cubense(Foc), tropical race 4 (Foc TR4), causing global banana crop losses is crucial to curtail the disease spread, minimize damage and implement quarantine measures. We report the first successfully developed DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) assay for the highly sensitive and specific detection of Foc TR4, validated across several isolates. Notably, specific crRNA spacer sequences and recombinant polymerase amplification (RPA) primers designed and evaluated for the DETECTR assay exhibited exceptional sensitivity, detecting Foc TR4 with genomic DNA as low as 0.005 ng, and demonstrated a very high specificity, and reproducibility. The RPA-DETECTR assay was validated using a diverse panel of samples, including both target and non-target pathogens confirming its robustness and reliability across different types of samples, ensuring practical application under varied conditions. In terms of throughput, the RPA-DETECTR assays enabled faster detection of Foc TR4 than other molecular diagnostics including PCR, quantitative PCR (qPCR) and droplet digital PCR (ddPCR) analyses, making this assay suitable for point-of-care (POC) detection of Foc TR4, and facilitating rapid decision-making and immediate response. This rapid detection capability is crucial in restricting any potential transboundary movement as part of ongoing disease management efforts.
Combining Gamma Neuromodulation and Robotic Rehabilitation Restores Parvalbimin-mediated Gamma Function and Boosts Motor Recovery in Stroke Mice
Authors: Vignozzi Livia , Macchi Francesca , Montagni Elena , Pasquini Maria , Martello Alessandra , Minetti Antea , Coulomb Éléa , Allegra Mascaro Anna Letizia , Micera Silvestro , Caleo Matteo , Spalletti Cristina 
Published: August 2024

ABSTRACTStroke is a leading cause of long-term disability, often characterized by compromised motor function. Gamma band is known to be related to Parvalbumin interneurons (PV-IN) synchronous discharge and it has been found to be affected after stroke in humans and animals. Both Gamma band and PV-IN also play a key role in motor function, thus representing a promising target for post-stroke neurorehabilitation. Non-Invasive neuromodulatory approaches are considered a safe intervention and can be used for this purpose. This study presents a novel, clinically relevant, non-invasive and well-tolerated sub-acute treatment combining robotic rehabilitation with advanced neuromodulation techniques, validated in a mouse model of ischemic injury. In the sub-acute phase after stroke, we scored profound deficits in motor-related Gamma band regulation on the perilesional cortex. Accordingly, both at the perilesional and at the whole-cortex levels, the damage results in impaired PV-IN activity, with reduced firing rate and increased functional connectivity levels. Therefore, we tested the therapeutic potential of coupling robotic rehabilitation with optogenetic PV-driven Gamma band stimulation in a subacute post-stroke phase during motor training to reinforce the efficacy of the treatment. Frequency-specific movement-related Gamma band stimulation, when combined with physical training, significantly improved forelimb motor function. More importantly, by pairing robotic rehabilitation with a clinical-like non-invasive 40 Hz transcranial Alternating Current Stimulation, we achieved similar motor improvements mediated by the effective restoring of movement-related Gamma band power and increased PV-IN connections in premotor cortex. Our research introduces a new understanding of the role of parvalbumin-interneurons in post-stroke impairment and recovery. These results highlight the synergistic potential of combining perilesional Gamma band stimulation with robotic rehabilitation as a promising and realistic therapeutic approach for stroke patients.SummaryStroke-induced motor deficits are accompanied by alteration of Gamma modulation and PV-interneurons activity and restored by a combination of non-invasive Gamma stimulation and robotic therapy.
Novel use of global occurrence data to indirectly predict suitable habitats for widely distributed marine species in data-scarce regions
Authors: De Wysiecki Agustín M. , Barnett Adam , Sánchez-Carnero Noela , Cortés Federico , Milessi Andrés C. , Trobbiani Gastón A. , Jaureguizar Andrés J. 
Published: August 2024

AbstractThis study addresses the challenge of advancing habitat use knowledge of widely distributed marine species populations when regional data is scarce. To achieve this, we use an innovative approach based on ecological niche models (ENMs) calibrated with global presence data to estimate the global niche of species, allowing for indirect predictions of suitable habitats and potential distribution in one or more regions of interest. The method leverages a range of global occurrence records, including scientific papers, government data, biodiversity repositories, and citizen science contributions, to overcome regional data scarcity, which are then integrated with environmental variables to predict habitat suitability. As a case study, we apply this method to predict suitable habitats of copper (Carcharhinus brachyurus) and sand tiger (Carcharias taurus) sharks in the Southwest Atlantic, two species of conservation concern in a region with limited data. Suitable habitats for both species were predicted, information required to guide conservation efforts. Environmental factors were key to shaping predicted distribution patterns of these large predatory sharks, aligning with previous knowledge and historical records of their latitudinal ranges. The results have significant implications for the conservation planning and sustainable management of shark populations in the Southwest Atlantic, contributing to broader efforts of marine biodiversity preservation. Additionally, the study highlights the potential of ENMs to identify essential habitats even in the absence of effort data, underscoring their value in marine conservation. This study not only advances the use of niche modelling in marine systems but also demonstrates its applicability for area-based conservation initiatives, particularly in data-poor regions.
The combined impact of climate change, pesticides and pharmaceuticals on life history and behaviour in killifish (Nothobranchius furzeri)
Authors: Kim Dongjin 
Published: August 2024

SummaryAnimals in nature are confronted simultaneously with multiple stressors of both natural and anthropogenic origin including temperature stress, pollutants, predators and parasites. The overall goal of this study was to assess the sensitivity of fish to climate change in combination with both classic pollutants (pesticides) and emerging contaminants (pharmaceuticals). Specifically, we exposed individuals of the model fish speciesNothobranchius furzerito combinations of temperature fluctuation, 3,4-DCA and FLX. Our results indicate that both traditional endpoints such as body size and fecundity as well as behavioural endpoints are affected by daily temperature variation and by the tested pollutants. The fact that certain effects were much more prominent when pollutants were combined illustrates the relevance of stressor combination studies. Also, while the tested concentrations of pollutants did not cause excess mortality, they did induce significant behavioural changes which may carry serious fitness consequences. Ultimately, our study provides an effective illustration of the need for performing stressor combination studies and for including behavioural endpoints in ecotoxicological testing.
Gut Microbiota and DTI Microstructural Brain Alterations in Rodents Due to Morphine Self-Administration
Authors: Brunetti Kaylee , Zhou Zicong , Shuchi Samia , Berry Raymond , Zhang Yan , Allen Michael S. , Yang Shaohua , Figueroa Johnny , Colon-Perez Luis 
Published: August 2024

AbstractThe opioid epidemic is an evolving health crisis in need of interventions that target all domains of maladaptive changes due to chronic use and abuse. Opioids are known for their effects on the opioid and dopaminergic systems, in addition to neurocircuitry changes that mediate changes in behavior; however, new research lines are looking at complementary changes in the brain and gut. The gut-brain axis (GBA) is a bidirectional signaling process that permits feedback between the brain and gut and is altered in subjects with opioid use disorders. In this work, we determine longitudinal, non-invasive, and in-vivo complementary changes in the brain and gut in rodents trained to self-administer morphine for two weeks using MRI and 16S rDNA analysis of fecal matter. We assess the changes occurring during both an acute phase (early in the self-administration process, after two days of self-administration) and a chronic phase (late in the self-administration process, after two weeks of self-administration), with all measurements benchmarked against baseline (naïve, non-drug state). Rats were surgically implanted with an intravenous jugular catheter for self-administration of morphine. Rats were allowed to choose between an active lever, which delivers a single infusion of morphine (0.4 mg/kg/infusion), or an inactive lever, which had no consequence upon pressing. Animals were scanned in a 7T MRI scanner three times (baseline, acute, and chronic), and before scanning, fecal matter was collected from each rat. After the last scan session, a subset of animals was euthanized, and brains were preserved for immunohistochemistry analysis. We found early changes in gut microbiota diversity and specific abundance as early as the acute phase that persisted into the chronic phase. In MRI, we identified alterations in diffusivity indices both within subjects and between groups, showing a main effect in the striatum, thalamus, and somatosensory cortex. Finally, immunohistochemistry analyses revealed increased neuroinflammatory markers in the thalamus of rats exposed to morphine. Overall, we demonstrate that morphine self-administration shapes the brain and gut microbiota. In conclusion, gut changes precede the anatomical effects observed in MRI features, with neuroinflammation emerging as a crucial link mediating communication between the gut and the brain. This highlights neuroinflammation as a potential target in addressing the impacts of opioid use.
Ribosomal RNA transcription governs splicing through ribosomal protein RPL22
Authors: Fan Wenjun , Liu Hester , Stachelek Gregory C. , Begum Asma , Davis Catherine E. , Dorado Tony E. , Ernst Glen , Reinhold William C. , Ozbek Busra , Zheng Qizhi , De Marzo Angelo M. , Rajeshkumar N.V. , Barrow James C. , Laiho Marikki 
Published: August 2024

AbstractRibosome biosynthesis is a cancer vulnerability executed by targeting RNA polymerase I (Pol I) transcription. We developed advanced, specific Pol I inhibitors to identify drivers of this sensitivity. By integrating multi-omics features and drug sensitivity data from a large cancer cell panel, we discovered thatRPL22frameshift mutation conferred Pol I inhibitor sensitivity in microsatellite instable cancers. Mechanistically, RPL22 directly interacts with 28S rRNA and mRNA splice junctions, functioning as a splicing regulator. RPL22 deficiency, intensified by 28S rRNA sequestration, promoted the splicing of its paralog RPL22L1 and p53 negative regulator MDM4. Chemical and genetic inhibition of rRNA synthesis broadly remodeled mRNA splicing controlling hundreds of targets. Strikingly, RPL22-dependent alternative splicing was reversed by Pol I inhibition revealing a ribotoxic stress-initiated tumor suppressive pathway. We identify a mechanism that robustly connects rRNA synthesis activity to splicing and reveals their coordination by ribosomal protein RPL22.
PanKB: An interactive microbial pangenome knowledgebase for research, biotechnological innovation, and knowledge mining
Authors: Sun B , Pashkova L , Pieters PA , Harke AS , Mohite OS , Palsson BO , Phaneuf PV 
Published: August 2024

AbstractThe exponential growth of microbial genome data presents unprecedented opportunities for mining the potential of microorganisms. The burgeoning field of pangenomics offers a framework for extracting insights from this big biological data. Recent advances in microbial pangenomic research have generated substantial data and literature, yielding valuable knowledge across diverse microbial species. PanKB (pankb.org), a knowledgebase designed for microbial pangenomics research and biotechnological applications, was built to capitalize on this wealth of information. PanKB currently includes 51 pangenomes on 8 industrially relevant microbial families, comprising 8, 402 genomes, over 500, 000 genes, and over 7M mutations. To describe this data, PanKB implements four main components: 1) Interactive pangenomic analytics to facilitate exploration, intuition, and potential discoveries; 2) Alleleomic analytics, a pangenomic- scale analysis of variants, providing insights into intra-species sequence variation and potential mutations for applications; 3) A global search function enabling broad and deep investigations across pangenomes to power research and bioengineering workflows; 4) A bibliome of 833 open- access pangenomic papers and an interface with an LLM that can answer in-depth questions using their knowledge. PanKB empowers researchers and bioengineers to harness the full potential of microbial pangenomics and serves as a valuable resource bridging the gap between pangenomic data and practical applications.Graphical Abstract
FindingNemo: A Toolkit for DNA Extraction, Library Preparation and Purification for Ultra Long Nanopore Sequencing
Authors: Cahyani Inswasti , Tyson John , Holmes Nadine , Quick Josh , Moore Chris , Loman Nick , Loose Matthew 
Published: August 2024

AbstractSince the advent of long read sequencing, achieving longer read lengths has been a key goal for many users. Ultra-long read sets (N50 ≥ 100 kb) produced from Oxford Nanopore sequencers have improved genome assemblies in recent years. However, despite progress in extraction protocols and library preparation methods, ultra-long sequencing remains challenging for many sample types. Here we compare various methods and introduce theFindingNemoprotocol that: (1) optimises ultra-high molecular weight (UHMW) DNA extraction and library clean-up by using glass beads and Hexamminecobalt(III) chloride (CoHex), (2) can deliver high ultra-long sequencing yield of >20 Gb of reads from a single MinION flow cell or >100 Gb from PromethION devices (R9.4 to R10.4 pore variants), and (3) is scalable to using fewer input cells or lower DNA amounts, with extraction to sequencing possible in a single working day. By comparison, we show this protocol is superior to previous ones due to precise determination of input DNA quantity and quality by cell count, sample dilution and homogenization approaches.
Direction and modality of transcription changes caused by TAD boundary disruption inSlc29a3/Unc5blocus depends on tissue-specific epigenetic context
Authors: Salnikov Paul , Belokopytova Polina , Yan Alexandra , Viesná Emil , Korablev Alexey , Serova Irina , Lukyanchikova Varvara , Stepanchuk Yana , Torgunakov Nikita , Tikhomirov Savelii , Fishman Veniamin 
Published: August 2024

AbstractTopologically associated domains (TADs) are believed to be involved in the regulation of gene expression. While the impact of TAD perturbations is usually studied in developmental genes with highly cell-type-specific expression patterns, this study examines genes with broad expression profiles divided by a strong insulatory boundary. We focused on mouseSlc29a3/Unc5blocus, which encompasses two distinct TADs. Our analysis demonstrates that deletions of CTCF binding sites within this locus lead to alterations in local chromatin architecture, disrupting existing loops and forming novel long-range interactions. We evaluated the transcription changes ofUnc5b, Slc29a3, Psap, Vsir, Cdh23, andSgpl1genes across various organs, finding that TAD boundary disruption results in variable transcriptional responses, where not only magnitude, but also direction of gene expression changes are tissue-specific. Current models of genome architecture, including enhancer competition and hijacking, only partially account for these transcriptional changes, indicating the need for further investigation into the mechanisms underlying TAD function and gene regulation.
Xylazine Exacerbates Fentanyl-Induced Respiratory Depression and Bradycardia
Authors: Demery-Poulos Catherine , Moore Sierra C. , Levitt Erica S. , Anand Jessica P. , Traynor John R. 
Published: August 2024

ABSTRACTFatal opioid overdoses in the United States have nearly tripled during the past decade, with greater than 92% involving a synthetic opioid like fentanyl. Fentanyl potently activates the μ-opioid receptor to induce both analgesia and respiratory depression. The danger of illicit fentanyl has recently been exacerbated by adulteration with xylazine, an α2-adrenergic receptor agonist typically used as a veterinary anesthetic. In 2023, over a 1,000% increase in xylazine-positive overdoses was reported in some regions of the U.S. Xylazine has been shown to potentiate the lethality of fentanyl in mice, yet a mechanistic underpinning for this effect has not been defined. Herein, we evaluate fentanyl, xylazine, and their combination in whole-body plethysmography (to measure respiration) and pulse oximetry (to measure blood oxygen saturation and heart rate) in male and female CD-1 mice. We show that xylazine decreases breathing rate more than fentanyl by increasing the expiration time. In contrast, fentanyl primarily reduces breathing by inhibiting inspiration, and xylazine exacerbates these effects. Fentanyl but not xylazine decreased blood oxygen saturation, and when combined, xylazine did not change the maximum level of fentanyl-induced hypoxia. Xylazine also reduced heart rate more than fentanyl. Finally, loss in blood oxygen saturation correlated with the frequency of fentanyl-induced apneas, but not breathing rate. Together, these findings provide insight into how the addition of xylazine to illicit fentanyl may increase the risk of overdose.Graphical Abstract
Classifying epithelial-mesenchymal transition states in single cell cancer data using large language models
Authors: Pan Shi , Withnell Eloise , Secrier Maria 
Published: August 2024

AbstractEpithelial–mesenchymal plasticity plays a significant role in various biological processes including tumour progression and chemoresistance. However, the expression programmes underlying the epithelial–mesenchymal transition (EMT) in cancer are diverse, and accurately defining the EMT status of tumour cells remains a challenging task. In this study, we employed a pre-trained single-cell large language model (LLM) to develop an EMT-language model (EMT-LM) that allows us to capture discrete states within the EMT continuum in single cell cancer data. In capturing EMT states, we achieved an average Area Under the Receiver Operating Characteristic curve (AUROC) of 90% across multiple cancer types. We propose a new metric, ADESI, to aid the biological interpretability of our model, and derive EMT signatures liked with energy metabolism and motility reprogramming underlying these state switches. We further employ our model to explore the emergence of EMT states in spatial transcriptomics data, uncovering hybrid EMT niches with contrasting potential for antitumour immunity or immune evasion. Our study provides a proof of concept that LLMs can be applied to characterise cell states in single cell data, and proposes a generalisable framework to predict EMT in single cell RNA-seq that can be adapted and expanded to characterise other cellular states.
MiniXL: An open-source, large field-of-view epifluorescence miniature microscope for mice capable of single-cell resolution and multi-brain region imaging
Authors: Zhao Pingping , Guo Changliang , Xie Mian , Chen Liangyi , Golshani Peyman , Aharoni Daniel 
Published: August 2024

AbstractCapturing the intricate dynamics of neural activity in freely behaving animals is essential for understanding the neural mechanisms underpinning specific behaviors. Miniaturized microscopy enables investigators to track population activity at cellular level, but the field of view (FOV) of these microscopes have been limited and does not allow multiple-brain region imaging. To fill this technological gap, we have developed the eXtra Large field-of-view Miniscope (MiniXL), a 3.5g lightweight miniaturized microscope with an FOV measuring 3.5 mm in diameter and an electrically adjustable working distance of 1.9 mm ± 200 μm. We demonstrated the capability of MiniXL recording the activity of large neuronal population in both subcortical area (hippocampal dorsal CA1) and deep brain regions (medial prefrontal cortex, mPFC and nucleus accumbens, NAc). The large FOV allows simultaneous imaging of multiple brain regions such as bilateral mPFCs or mPFC and NAc during complex social behavior and tracking cells across multiple sessions. As with all microscopes in the UCLA Miniscope ecosystem, the MiniXL is fully open-source and will be shared with the neuroscience community to lower the barriers for adoption of this technology.
Enhanced Piezoelectric Performance of PVDF-TrFE Nanofibers through Annealing for Tissue Engineering Applications
Authors: Krutko Maksym , Poling Holly M. , Bryan Andrew E. , Sharma Manju , Singh Akaljot , Reza Hasan A. , Wikenheiser-Brokamp Kathryn A. , Takebe Takanori , Helmrath Michael A. , Harris Greg M. , Esfandiari Leyla 
Published: August 2024

AbstractThis study investigates bioelectric stimulation’s role in tissue regeneration by enhancing the piezoelectric properties of tissue-engineered grafts using annealed poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) scaffolds. Annealing at temperatures of 80°C, 100°C, 120°C, and 140°C was assessed for its impact on material properties and physiological utility. Analytical techniques such as Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) revealed increased crystallinity with higher annealing temperatures, peaking in β-phase content and crystallinity at 140°C. Scanning Electron Microscopy (SEM) showed that 140°C annealed scaffolds had enhanced lamellar structures, increased porosity, and maximum piezoelectric response. Mechanical tests indicated that 140°C annealing improved elastic modulus, tensile strength, and substrate stiffness, aligning these properties with physiological soft tissues. In vitro assessments in Schwann cells demonstrated favorable responses, with increased cell proliferation, contraction, and extracellular matrix attachment. Additionally, genes linked to extracellular matrix production, vascularization, and calcium signaling were upregulated. The foreign body response in C57BL/6 mice, evaluated through Hematoxylin and Eosin (H&E) and Picrosirius Red staining, showed no differences between scaffold groups, supporting the potential for future functional evaluation of the annealed group in tissue repair.