bluuebunny/crossref_metadata_2025_split huggingface dataset:
The P2 protein of wheat yellow mosaic virus acts as a viral suppressor of RNA silencing to facilitate virus infection in wheat plants
Authors: Chen Dao , Zhang Hui-Ying , Hu Shu-Ming , He Zheng , Wu Yong Qi , Zhang Zong-Ying , Wang Ying , Han Cheng-Gui 
Published: December 2023

AbstractWheat yellow mosaic virus (WYMV) causes severe viral wheat disease in Asia. The WYMV P1 protein encoded by RNA2 has viral suppressor of RNA silencing (VSR) activity to facilitate virus infection; however, VSR activity has not been identified for P2 protein encoded by RNA2. In this study, P2 protein exhibited strong VSR activity inNicotiana benthamianaat the four-leaf stage, and point mutants P70A and G230A lost VSR activity. Protein P2 interacted with calmodulin (CaM) protein, a gene-silencing associated protein, while point mutants P70A and G230A did not interact with it. Competitive bimolecular fluorescence complementation and competitive co-immunoprecipitation experiments showed that P2 interfered with the interaction between CaM and calmodulin-binding transcription activator 3 (CAMTA3), but the point mutants P70A and G230A could not. Mechanical inoculation of wheat within vitrotranscripts of WYMV infectious cDNA clone further confirmed that VSR-deficient mutants P70A and G230A decreased WYMV infection in wheat plants compared with the wild type. In addition, RNA silencing, temperature, and autophagy had significant effects on accumulation of P2 protein inN. benthamianaleaves. In conclusion, WYMV P2 plays a VSR role in wheat and promotes virus infection by interfering with calmodulin-related antiviral RNAi defense.One-sentence summaryWYMV P2 protein exerts VSR activity by interfering with the CaM–CAMTA3 interaction to facilitate virus efficient systemic infection in wheat plants.
Differential effects of MATR3 variants on its cryptic splicing repression function
Authors: Khan Mashiat , Chen Xiao Xiao Lily , Dias Michelle , Santos Jhune Rizsan , Kour Sukhleen , You Justin , van Bruggen Rebekah , Youssef Mohieldin M.M. , Wan Ying-Wooi , Liu Zhandong , Rosenfeld Jill A. , Tan Qiumin , Pandey Udai Bhan , Yalamanchili Hari Krishna , Park Jeehye 
Published: December 2023

AbstractMATR3 is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated variants impact this function. We show that loss of MATR3 leads to cryptic exon inclusion in many transcripts. We reveal that ALS-linked S85C pathogenic variant reduces MATR3 solubility but does not impair RNA binding. In parallel, we report a novel neurodevelopmental disease-associated M548T variant, located in the RRM2 domain, which reduces protein solubility and impairs RNA binding and cryptic splicing repression functions of MATR3. Altogether, our research identifies cryptic events within functional genes and demonstrates how disease-associated variants impact MATR3 cryptic splicing repression function.
Co-existence of synaptic plasticity and metastable dynamics in a spiking model of cortical circuits
Authors: Yang Xiaoyu , La Camera Giancarlo 
Published: December 2023

AbstractEvidence for metastable dynamics and its role in brain function is emerging at a fast pace and is changing our understanding of neural coding by putting an emphasis on hidden states of transient activity. Clustered networks of spiking neurons have enhanced synaptic connections among groups of neurons forming structures called cell assemblies; such networks are capable of producing metastable dynamics that is in agreement with many experimental results. However, it is unclear how a clustered network structure producing metastable dynamics may emerge from a fully local plasticity rule, i.e., a plasticity rule where each synapse has only access to the activity of the neurons it connects (as opposed to the activity of other neurons or other synapses). Here, we propose a local plasticity rule producing ongoing metastable dynamics in a deterministic, recurrent network of spiking neurons. The metastable dynamics co-exists with ongoing plasticity and is the consequence of a self-tuning mechanism that keeps the synaptic weights close to the instability line where memories are spontaneously reactivated. In turn, the synaptic structure is stable to ongoing dynamics and random perturbations, yet it remains sufficiently plastic to remap sensory representations to encode new sets of stimuli. Both the plasticity rule and the metastable dynamics scale well with network size, with synaptic stability increasing with the number of neurons. Overall, our results show that it is possible to generate metastable dynamics over meaningful hidden states using a simple but biologically plausible plasticity rule which co-exists with ongoing neural dynamics.
Approaching Maximum Resolution in Structured Illumination Microscopy via Accurate Noise Modeling
Authors: Saurabh Ayush , Brown Peter T. , Bryan J. Shepard , Fox Zachary R. , Kruithoff Rory , Thompson Cristopher , Kural Comert , Shepherd Douglas P. , Pressé Steve 
Published: December 2023

AbstractBiological images captured by microscopes are characterized by heterogeneous signal-to-noise ratios (SNRs) due to spatially varying photon emission across the field of view convoluted with camera noise. State-of-the-art unsupervised structured illumination microscopy (SIM) reconstruction algorithms, commonly implemented in the Fourier domain, do not accurately model this noise and suffer from high-frequency artifacts, user-dependent choices of smoothness constraints making assumptions on biological features, and unphysical negative values in the recovered fluorescence intensity map. On the other hand, supervised methods rely on large datasets for training, and often require retraining for new sample structures. Consequently, achieving high contrast near the maximum theoretical resolution in an unsupervised, physically principled, manner remains an open problem. Here, we propose Bayesian-SIM (B-SIM), an unsupervised Bayesian framework to quantitatively reconstruct SIM data, rectifying these shortcomings by accurately incorporating known noise sources in the spatial domain. To accelerate the reconstruction process, we use the finite extent of the point-spread-function to devise a parallelized Monte Carlo strategy involving chunking and restitching of the inferred fluorescence intensity. We benchmark our framework on both simulated and experimental images, and demonstrate improved contrast permitting feature recovery at up to 25% shorter length scales over state-of-the-art methods at both high- and low-SNR. B-SIM enables unsupervised, quantitative, physically accurate reconstruction without the need for labeled training data, democratizing high-quality SIM reconstruction and expands the capabilities of live-cell SIM to lower SNR, potentially revealing biological features in previously inaccessible regimes.
Low salinity destabilizes the bacterial community of sugar kelp,Saccharina latissima(Phaeophyceae)
Authors: Schenk Siobhan , Wardrop Connor Glen , Parfrey Laura Wegener 
Published: December 2023

AbstractAs climate change progresses, the intensity and variability of freshwater outflow into the ocean are predicted to increase. The resulting increase in low-salinity events will be a source of stress forSaccharina latissimaand potentiallySaccharina-associated bacteria. Bacteria influence host health and can facilitate or hinder host survival and acclimation to stressful abiotic conditions. Therefore, understanding how bacterial communities change under abiotic stress is critical to understand how abiotic stress will affect kelp physiology. We investigated the effect of low-salinity stress onSaccharina-associated bacteria and the host by surveying the bacterial community associated withSaccharinaand the surrounding environment across naturally occurring salinity gradients during the spring freshet across two years at four field sites with contrasting salinity profiles around Vancouver, Canada (519 samples), coupled with salinity manipulation experiments repeated eight times (269 samples). Overall,Saccharinaharbours a stable core bacterial community, which decreases in relative abundance under abiotic stress. In the field, both salinity and temperature shape the bacterial community, with temperature having higher explanatory power most of the time. In the lab, we confirm that the patterns observed in the field can be replicated by manipulating salinity alone. Decreased relative abundance of core bacteria and increased community dissimilarity in low salinity, in both the lab and field, suggest that host filtering is significantly impaired in low salinity. In the context of a stable host-associated core bacterial community during non-stressful conditions, the change in the community composition observed during conditions of abiotic stress indicates a host stress response.
Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models
Authors: Loh Liyen , Carcy Salomé , Krovi Harsha S. , Domenico Joanne , Spengler Andrea , Lin Yong , Torres Joshua , Palmer William , Norman Paul J. , Stone Matthew , Brunetti Tonya , Meyer Hannah V. , Gapin Laurent 
Published: December 2023

ABSTRACTThe “innate-like” T cell compartment, known as Tinn, represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity, having the ability to mount rapid responses following activation. In mice, this ability is acquired during thymic development. We explored the transcriptional landscape of Tinncompared to conventional T cells (Tconv) in the human thymus and blood using single cell RNA sequencing and flow cytometry. We reveal that in human blood, the majority of Tinncells, including iNKT, MAIT, and Vδ2+Vγ9+T cells, share an effector program characterized by the expression of unique chemokine and cytokine receptors, and cytotoxic molecules. This program is driven by specific transcription factors, distinct from those governing Tconvcells. Conversely, only a fraction of thymic Tinncells displays an effector phenotype, while others share transcriptional features with developing Tconvcells, indicating potential divergent developmental pathways. Unlike the mouse, human Tinncells do not differentiate into multiple effector subsets but develop a mixed type I/type III effector potential. To conduct a comprehensive cross-species analysis, we constructed a murine Tinndevelopmental atlas and uncovered additional species-specific distinctions, including the absence of type II Tinncells in humans, which implies distinct immune regulatory mechanisms across species. The study provides insights into the development and functionality of Tinncells, emphasizing their role in immune responses and their potential as targets for therapeutic interventions.
Not dasycladalean alga, but an Odyssey of the earliest Phanerozoic animal reef-builders
Authors: Yang Aihua , Luo Cui , Han Jian , Zhuravlev Andrey Yu. , Reitner Joachim , Sun Haijing , Zeng Han , Zhao Fangchen , Hu Shixue 
Published: December 2023

AbstractThe compacted macrofossilProtomelission? sp. from the early Cambrian Xiaoshiba Lagerstätte was recently ascribed to early dasycladalean green algae and used to disprove the bryozoan affinity of coeval phosphatized microfossils, which made the puzzling question whether the bryozoans originated in early Cambrian pending again. Our new analyses of multiple specimens which are conspecific withProtomelission? from the Chengjiang Lagerstätte indicate that they are not dasycladaleans but one of the three groups of archaeocyath-like sponges that atypically inhabited siliciclastic substrates. All the archaeocyath-like fossils share the same preservation mode and exhibit archaeocyath-type external skeletal features. Particularly, theProtomellision?-like fossils preserve structures indicative of archaeocyath aquiferous system and ontogeny. They represent the first recognized one-walled archaeocyath sponges in South China and evidence the niche expansion of archaeocyaths on their way of global radiation from Siberia, 518 million years ago. The origin of the bryozoans remains a mystery.
Reference-guided automatic assembly of genomic tandem repeats with only HiFi and Hi-C data enables population-level analysis
Authors: Wen Huaming , Pan Weihua 
Published: December 2023

AbstractThe existing de novo methods of complete genome assembly are not able to generate large-scale pangenomes with complete assemblies due to the shortcomings such as requiring multiple types of sequencing data of high price, requiring large amount of manual curation, and not being able to achieve haplotype-resolved complete assembly of long tandem repeats in most situations. To solve this problem, in this study, we propose a new genome assembly mode called reference-guided assembly which relies on the reference information to recall the reads for complex genomic regions of interest and assembles them inde novo-like way. As a proof-of-concept, we developed an algorithm TRFill which can reassemble or fill the gaps of tandem repeats in chromosome-level assembly in either haploid or diploid way using only HiFi and Hi-C data. The experimental results on human centromeres and tomato subtelomeres show that TRFill successfully improved the completeness and correctness of about two thirds of the tested tandem repeat sequences. Furthermore, TRFill improved the completeness of subtelomeric tandem repeats by 50% in a recently published tomato pangenome, enabling a population-level analysis of the subtelomeric tandem repeats, which found the ‘local law of sequence similarity of tandem repeats’ providing theoretical basis for reference-guided assembly in turn.
The myeloid cell-driven transdifferentiation of endothelial cells into pericytes promotes the restoration of BBB function and brain self-repair after stroke
Authors: Li Tingbo , Yang Ling , Tu Jiaqi , Hao Yufan , Zhu Zhu , Xiong Yingjie , Gao Qingzhu , Zhou Lili , Xie Guanglei , Zhang Dongdong , Li Xuzhao , Jin Yuxiao , Zhang Yiyi , Zhao Bingrui , Li Nan , Wang Xi , Jia Jie-Min 
Published: December 2023

AbstractIschemic stroke, one of the leading causes of death in the world, is accompanied by the dysfunction of the blood-brain barrier (BBB), which aggravates neuron damage. However, the mechanisms underlying the restoration of BBB in the chronic stage after stroke remain unclear. Here, we investigated the changes in the pericyte pool and their effects on BBB function and brain self-repair after stroke. Using lineage tracing, RNA-seq and immunofluorescence staining, we detected endothelial cells (ECs) transdifferentiated into pericytes (E-pericytes) after stroke in the MCAO model. E-pericytes depletion by diphtheria toxin A (DTA) aggravated BBB leakage and exacerbated neurological deficits in the MCAO model. The myeloid cell-driven transdifferentiation of ECs into pericytes accelerated BBB restoration and brain self-repair after stroke via endothelial-mesenchymal transformation (EndoMT). Decreasing the number of E-pericytes by specific knockout of theTgfbr2gene in ECs also aggravated BBB leakage and exacerbated neurological deficits. Specific-ECs overexpression of theTgfbr2gene promoting E-pericytes transdifferentiation reduced BBB leakage and exerted neuroprotective effects. Our findings solve a key question about how changes in the pericyte pool after stroke affect the restoration of BBB function and brain self-repair and may offer a new approach to therapy.
Low-Cost 3D-Printed Tools Towards Robust Longitudinal Multi-Modal Pre-Clinical Imaging
Authors: Allam Nader , Taylor Edward , Vitkin I. Alex 
Published: December 2023

1AbstractWindow chamber models enable a range of preclinicalin-vivooptical studies with high spatial resolution and contrast, most notably probing the tumour microenvironment (TME). However, there are multiple sources of experimental variability that can affect the quality of the resultant data, especially in the context of longitudinal data acquisition, where accurate registration between images acquired at different times is crucial to understanding changes to the spatially heterogeneous TME. Further, it is challenging to correlate the findings of these models to clinical imaging modalities such as magnetic resonance imaging (MRI), which typically have much lower resolution and derive contrast from different physical mechanisms; yet such correlations may assist in the translation of window-chamber-derived basic preclinical insights into the clinic. Here, we describe the development and construction of a low-cost 3D-printable window chambers and compatible toolset to improve the accuracy, precision, and repeatability of longitudinal pre-clinical imaging and inter-modality co-registration at different spatial resolution scales. Such improvements in our novel multi-modal experimental pipeline may assist researchers in the acquisition and translation of TME biomarkers and other pre-clinical measurements from the window chamber model into the clinic.
Large-Scale Information Retrieval and Correction of Noisy Pharmacogenomic Datasets through Residual Thresholded Deep Matrix Factorization
Authors: Hu Zhiyue Tom , Yu Yaodong , Chen Ruoqiao , Yeh Shan-Ju , Chen Bin , Huang Haiyan 
Published: December 2023

SummaryPharmacogenomics studies are attracting an increasing amount of interest from researchers in precision medicine. The advances in high-throughput experiments and multiplexed approaches allow the large-scale quantification of drug sensitivities in molecularly characterized cancer cell lines (CCLs), resulting in a number of open drug sensitivity datasets for drug biomarker discovery. However, a significant inconsistency in drug sensitivity values among these datasets has been noted. Such inconsistency indicates the presence of substantial noise, subsequently hindering downstream analyses. To address the noise in drug sensitivity data, we introduce a robust and scalable deep learning framework, Residual Thresholded Deep Matrix Factorization (RT-DMF). This method takes a single drug sensitivity data matrix as its sole input and outputs a corrected and imputed matrix. Deep Matrix Factorization (DMF) excels at uncovering subtle patterns, due to its minimal reliance on data structure assumptions. This attribute significantly boosts DMF’s ability to identify complex hidden patterns among nuisance effects in the data, thereby facilitating the detection of signals that are therapeutically relevant. Furthermore, RT-DMF incorporates an iterative residual thresholding (RT) procedure, which plays a crucial role in retaining signals more likely to hold therapeutic importance. Validation using simulated datasets and real pharmacogenomics datasets demonstrates the effectiveness of our approach in correcting noise and imputing missing data in drug sensitivity datasets (open source package available athttps://github.com/tomwhoooo/rtdmf).
Optimized Mass Spectrometry Detection of Thyroid Hormones and Polar Metabolites in Rodent Cerebrospinal Fluid
Authors: Fame Ryann M. , Ali Ilhan , Lehtinen Maria K. , Kanarek Naama , Petrova Boryana 
Published: December 2023

AbstractBackgroundThyroid hormones (TH) are required for brain development and function. Cerebrospinal fluid (CSF), which bathes the brain and spinal cord, contains TH as free or transthyretin (TTR)-bound. Tight thyroid hormone level regulation in the central nervous system is essential for developmental gene expression that governs neurogenesis, myelination, and synaptogenesis. This integrated function of TH highlights the importance of developing precise and reliable methods for assessing TH levels in CSF. Methods: we report an optimized LC-MS based method to measure thyroid hormones in rodent CSF and serum, applicable to both fresh and frozen samples. Results: We find distinct differences in CSF thyroid hormone in pregnant dams vs. non-pregnant adults and in embryonic vs. adult CSF. Further, targeted LC-MS metabolic profiling uncovers distinct central carbon metabolism in the CSF of these populations. Conclusions: TH detection and metabolite profiling of related metabolic pathways open new avenues of rigorous research into CSF thyroid hormone and will inform future studies on metabolic alterations in CSF during normal development.
Evaluation of the fitness benefit conferred by RNA cis-regulators toStreptococcus pneumoniaeduring infection
Authors: Warrier Indu , Perry Ariana , Hubbell Sara M. , Eichelman Matthew , van Opijnen Tim , Meyer Michelle M. 
Published: December 2023

AbstractBacteria have evolved complex transcriptional regulatory networks, as well as many diverse regulatory strategies at the RNA level, to enable more efficient use of metabolic resources and rapid response to changing conditions. However, most RNA-based regulatory mechanisms are not well conserved across different bacterial species despite controlling genes important for virulence or essential biosynthetic processes. Here, we characterize the activity of, and assess the fitness benefit conferred by, twelve cis-acting regulatory RNAs (including several riboswitches and a T-box), in the opportunistic pathogenStreptococcus pneumoniaeTIGR4. By evaluating native locus mutants of each regulator that result in constitutively active and repressed expression, we establish that growth defects in planktonic culture are associated with constitutive repression of gene expression, while constitutive activation of gene expression is rarely deleterious. In contrast, in mouse nasal carriage and pneumonia models, strains with both constitutively active and repressed gene expression are significantly less fit than matched control strains. Furthermore, two RNA-regulated pathways, FMN synthesis/transport and pyrimidine synthesis/transport display the greatest sensitivity to mis-regulation or constitutive gene repression in both planktonic culture andin vivoenvironments. Our findings suggest that despite lack of an obvious phenotypes associated with gene over-expressionin vitro, the fitness benefit conferred on bacteria via fine-tuned metabolic regulation through cis-acting regulatory RNAs is often substantialin vivo, and therefore easily sufficient to drive the evolution and maintenance of diverse RNA regulatory mechanisms.
The mutational landscape ofStaphylococcus aureusduring colonisation
Authors: Coll Francesc , Blane Beth , Bellis Katherine , Matuszewska Marta , Jamrozy Dorota , Toleman Michelle , Geoghegan Joan A , Parkhill Julian , Massey Ruth C , Peacock Sharon J , Harrison Ewan M 
Published: December 2023

AbstractStaphylococcus aureusis an important human pathogen but is primarily a commensal of the human nose and skin. Survival during colonisation is likely one of the major drivers ofS. aureusevolution. Here we use a genome-wide mutation enrichment approach to analyse a genomic dataset of 3,060S. aureusisolates from 791 individuals to show that despite limited within-host genetic diversity, an excess of protein-altering mutations can be found in genes encoding key metabolic pathways, in regulators of quorum-sensing and in known antibiotic targets. Nitrogen metabolism and riboflavin synthesis are the metabolic processes with strongest evidence of adaptation. Further evidence of adaptation to nitrogen availability was revealed by enrichment of mutations in the assimilatory nitrite reductase and urease, including mutations that enhance growth with urea as the sole nitrogen source. Inclusion of an additional 4,090 genomes from 802 individuals revealed eight additional genes includingsasA/sraP,pstA, andrsbUwith signals adaptive variation that warrant further characterisation. Our study provides the most comprehensive picture to date of the heterogeneity of adaptive changes that occur in the genomes ofS. aureusduring colonisation, revealing the likely importance of nitrogen metabolism, loss of quorum sensing and antibiotic resistance for successful human colonisation.