Biology subjects

Tan, X.

Publications and source records attributed to Tan, X..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Generation of a biosafety mouse model infection for SARS-CoV-2 replicon delivery particles

Animal models are essential for understanding the pathogenesis of SARS-CoV-2 and for developing therapeutic strategies. Replicon delivery particles (RDPs) were a component of trans-complementary systems for SARS-CoV-2, which is a safe and convenient tool in researching SARS-CoV-2 in animal biosafety level-II laboratory (ABSL-2). Here, we constructed a mouse model that conditional expressing SARS-CoV-2 N on the background of the K18-hACE2 KI mice. The SARS-CoV-2 N with flanked loxP-stop-loxP sequence was under the CAG promoter, and this cassette was knocked into the Tiger locus of mouse by CRISPR-Cas9 (K18-hACE2-N KI). By mating K18-hACE2-N KI mice with Cre tool mice, the offspring can express SARS-CoV-2 N (Cre-N-hACE2 KI) systemically and in a tissue-specific manner. Cre-N-hACE2 KI exhibited susceptibility to the SARS-CoV-2 {Delta}N-GFP/HBiT infection. The viral loads in lung exhibited a mountain-like trend, peaking at 4 days post-infection, and lung injuries can be observed. Overall, we demonstrated a mouse model infection for SARS-CoV-2 {Delta}N-GFP/HBiT to understand SARS-CoV-2 pathogenesis.

microbiology↗

bioRxiv2024

TomoScore: A Neural Network Approach for Quality Assessment of Cellular cryo-ET

Electron cryo-tomography (cryoET) is a powerful imaging tool that allows three-dimensional visualization of subcellular and molecular architecture without chemical fixation. Tomogram quality varies widely, particularly during large high-throughput data collections, and the most common strategy for initial quality assessment is empirical judgment by an expert. Tomograms are collected for two distinct purposes: 1) Annotation of subcellular features and cellular morphology, typically performed at lower magnifications and higher defocus. 2) Subtomogram averaging, generally at higher magnifications and closer to focus. For the first purpose, contrast and the ability to distinguish cellular features of interest are key, whereas for subtomogram averaging, recoverable signal at high resolution is the key factor. We have developed "TomoScore" a deep-learning based tomogram quality metric to assess the suitability of individual tomograms for cellular annotation based on the scale of features which can be distinguished. We further explore the relationship between accumulated electron dose and resulting quality, suggesting an optimum dose range for cryoET data collection. Overall, our study streamlines data processing and reduces the need for human involvement during pre-selection for tomogram segmentation.

biophysics↗

bioRxiv2024

Microglia modulate cerebral blood flow and neurovascular coupling through ectonucleotidase CD39

Microglia and the border-associated macrophages (BAMs) contribute to the modulation of cerebral blood flow (CBF), but the mechanisms have remained ill-defined. Here, we show that microglia regulate the CBF baseline and upsurges after whisker stimulation or intracisternal magna injection of adenosine triphosphate (ATP). Genetic or pharmacological depletion of microglia reduces the activity-dependent hyperemia but not the cerebrovascular responses to adenosine stimulation. Notably, microglia repopulation corrects these CBF reactivity deficits. The microglial-dependent regulation of CBF requires the ATP-sensing P2ry12 receptor and the ectonucleotidase CD39 that initiates the breakdown of extracellular ATP. Pharmacological inhibition or microglia-specific deletion of CD39 simulates the CBF anomalies detected in microglia-deficient mice and reduces the rise of extracellular adenosine after whisker stimulation. Together, these results suggest that the microglial CD39-initiated conversion of extracellular ATP to adenosine is an important step in neurovascular coupling and the regulation of cerebrovascular reactivity.

neuroscience↗

bioRxiv2024

SpaMTP: Integrative Statistical Analysis and Visualisation of Spatial Metabolomics and Transcriptomics data.

The ability to spatially measure multi-modal data provides an unprecedented opportunity to comprehensively explore molecular regulation at transcriptional, translational and metabolic levels to acquire insights on cellular activities underpinning health and disease. However, there is currently a lack of analytical tools to integrate complementary information across different spatial-omics data modalities, particularly with respect to spatial metabolomics data, which is becoming increasingly invaluable. We introduce SpaMTP, a versatile software that implements an end-to-end integrative analysis of spatial metabolomics and transcriptomics data. Based in R, SpaMTP bridges processing functionalities for metabolomics data from Cardinal with user-friendly cell-centric analyses implemented in Seurat. Furthermore, SpaMTPs comprehensive analysis pipeline covers (1) automated mass-to-charge ratio (m/z) metabolite annotation; (2) a wide range of metabolite-gene based downstream statistical analyses including differential expression, pathway analysis, and correlation analysis; (3) integrative spatial-omics analysis; and (4) a suite of visualisation functions. For flexibility and interoperability, SpaMTP includes various functions for data import/export and object conversion, enabling seamless integration with other R and Python packages. We demonstrated the utility of SpaMTP to draw new biological understandings through analysing two biological system. We believe this software and implemented methods will be broadly utilised in spatial multi-omics and spatial metabolomics analyses.

bioinformatics↗

bioRxiv2024

Early-life antibiotic exposure leads to gut microbial dysbiosis associated with neurodevelopment and neuroregeneration

Early-life is a critical period for neurodevelopment and establishment of gut microbiota, which are highly susceptible to antibiotic exposure. Here, we aimed to investigate association between gut microbiota and metabolites with neurodevelopment and neuroregeneration in early-life after antibiotic exposure. To induce microbial dysbiosis in offspring, a broad-spectrum antibiotic cocktail was administered to mice dams. The prefrontal lobe, spinal cord tissues and gut sample of offspring were collected at different time with or without spinal cord crush injury. 16S rRNA sequencing and metabolomics were performed to analyze the gut microbiota and metabolites. NG2 glia were cultured and treated by mitochondrial fusion and fission compounds and metabolites. Maternal antibiotic exposure significantly affected neuronal maturation, NG2 glia proliferation, prefrontal cortex myelination and injured spinal cord neuroregeneration of offspring. Mice in antibiotic exposure group exhibited disruption of gut microbiota and metabolites, along with lower Ace, Chao and Shannon indexes, higher relative abundance of Enterobacter and Escherichia_Shigella, lower lactobacillus and Streptococcus genus, and downregulated Cyclo(Arg-Gly-Asp-D-Phe-Val), Ampicilloyl, DG(8:0/i-19:0/0:0), Petasinine and 6-Hydroxymelatonin glucuronide. These metabolites were enriched in alpha-Linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism. 6-Hydroxymelatonin glucuronide, PC(20:3/0:0), PC(20:2/0:0), Ameltolide, DG(8:0/i-19:0/0:0), Inproquone, and Chorismate were the cores of networks between gut microbiota and metabolites and negatively associated with neurodevelopment and neuroregeneration. Additionally, gut microbiota metabolites promoted NG2 glia differentiation, partly through reversing the effects of mitochondrial fusion/fission compounds. Totally, antibiotic exposure in early-life changed the composition, abundance, and metabolites of gut microbiota in offspring, which was associated with neurodevelopment and neuroregeneration.

microbiology↗

bioRxiv2024

Fatty acid desaturation guides cellular decisions between ferroptosis and cellular senescence

When subject to damage or stress, cells develop responses in order to maintain tissue homeostasis. Two such decisions are ferroptosis and cellular senescence, but how cells decide between these outcomes remains unclear. Here we show that senescent cells increase levels of multiple membrane-bound polyunsaturated fatty acids (PUFAs), but a specific PUFA, dihomo-gamma-linolenic acid (DGLA, 20:3{omega}-3) is reduced. Exogenous repletion of DGLA or inhibition of delta-5-desaturase, the enzyme that metabolizes DGLA, instead results in cell death by ferroptosis. Senescent cells had elevated levels of other fezzroptosis sensitizers, including labile iron and expression of lipoxygenases - but also increased Gpx4 levels to prevent ferroptosis. Oral DGLA lowered senescent cell burden in aged mice and improved age-related functional outcomes. Finally, obese humans with lowered DGLA desaturation rates showed lower markers of adipose tissue senescence. Together, our data implicate DGLA and its desaturation as a major driver of decisions between senescence and ferroptosis.

cell biology↗

bioRxiv2024

Hypomorphic NOTCH1 Expression Alters Cardiomyocyte Cellular Architecture in Hypoplastic Left Heart Syndrome

NOTCH1 is a protein involved in cardiac development and mutations in NOTCH1 are implicated in left sided congenital heart disease, including hypoplastic left heart syndrome (HLHS). Therapeutic advances for HLHS patients have been hampered by the absence of suitable experimental models. Here, using human induced pluripotent stem cells (hiPSCs), we have generated a series of CRISPR-edited complex heterozygous hypomorphic mutations in NOTCH1 that recapitulate mutations seen in HLHS patients. These cells demonstrate the downregulation of genes associated with mitochondria, the actin cytoskeleton, and cardiomyocyte development. In addition, these hypomorphic NOTCH1 hiPSCs cells showed an increased propensity to differentiate towards non-cardiomyocyte lineages such as fibroblasts and smooth muscle cells, a finding confirmed in HLHS patient-derived myocardial tissue. Abnormalities in sarcomeric and mitochondrial architecture contributed to decreased ATP production, abnormal calcium transients, and reduced contractility. Using a split nano-luciferase system as a NOTCH1 intracellular reporter, we screened a library of FDA-approved compounds. Auranofin, an agent currently employed for rheumatoid arthritis, was identified as a candidate drug that could rescue impaired differentiation and contractility seen in the hypomorphic NOTCH1 model. These findings point to cell-autonomous abnormalities in hypomorphic NOTCH1 pre-cardiomyocyte cells that can be leveraged to identify potential therapeutic strategies for patients with severe congenital cardiac abnormalities. HighlightsO_LICRISPR edited and patient-derived iPSCs with hypomorphic NOTCH1 expression were used to characterize a cell-based model of hypoplastic left heart syndrome. C_LIO_LIHypomorphic NOTCH1 iPSCs have abnormalities in pathways associated with mitochondrial function, actin cytoskeleton, and cardiomyocyte development. C_LIO_LIHypomorphic NOTCH1 iPSCs have less pluripotency and tend to skew differentiation away from cardiomyocytes and towards fibroblasts and smooth muscle cells. C_LIO_LINOTCH1 is required for cardiac cytoskeletal and mitochondrial architecture, and to preserve contractility and ATP production. C_LIO_LIA high-throughput drug screen identified auranofin as an agent that may benefit patients with hypoplastic left heart syndrome. C_LI

cell biology↗

bioRxiv2024

O-glycosylation contributes to mammalian glycoRNA biogenesis

There is an increasing appreciation for the role of cell surface glycans in modulating interactions with extracellular ligands and participating in intercellular communication. We recently reported the existence of sialoglycoRNAs, where mammalian small RNAs are covalently linked to N-glycans through the modified base acp3U and trafficked to the cell surface. However, little is currently known about the role for O-glycosylation, another major class of carbohydrate polymer modifications. Here, we use parallel genetic, enzymatic, and mass spectrometry approaches to demonstrate that O-linked glycan biosynthesis is responsible for the majority of sialoglycoRNA levels. By examining the O-glycans associated with RNA from cell lines and colon organoids we find known and previously unreported O-linked glycan structures. Further, we find that O-linked glycans released from small RNA from organoids derived from ulcerative colitis patients exhibit higher levels of sialylation than glycans from healthy organoids. Together, our work provides flexible tools to interrogate O-linked glycoRNAs (O-glycoRNA) and suggests that they may be modulated in human disease.

molecular biology↗

bioRxiv2024

CD131 Contributes to Ulcerative Colitis Pathogenesis by Promoting Macrophage Infiltration

BackgroundUlcerative colitis (UC) is a group of chronic inflammatory bowel disease (IBD) mainly affecting the colon. The exact etiology of ulcerative colitis remains elusive. CD131 is a receptor subunit mediating the effects of hematopoietic growth factors GM-CSF and IL-3, which regulate various inflammatory responses. The pleiotropic effects of the cytokines on intestinal inflammation suggest that additional factors influence their overall function, where the receptor may play a role. MethodsIn the present study, we investigated the role of CD131 in the pathogenesis of ulcerative colitis, with the use of murine colitis model established by administration of DSS in the drinking water. ResultsBy comparing the immune and inflammatory responses between wt and CD131-deficient mice, we found that CD131 contributed to DSS-induced murine colitis, which functioned in synergy with tissue- infiltrating macrophages. Besides, CD131 may have promoted the chemotaxis of macrophages and T cells into the colon through CCL4. In addition, we analyzed clinical data and pathology specimens from ulcerative colitis patients and found that CD131 was associated with the endoscopic and pathological severity of intestinal inflammation. ConclusionsThe present study provides a novel way to the understanding of the mechanisms of GM-CSF and IL-3 effects in the intestine, which will benefit the development of therapeutic approaches.

immunology↗

bioRxiv2024

IGF-1 Peptide Mimetic-functionalized Hydrogels Enhance MSC Survival and Immunomodulatory Activity

Human mesenchymal stem cells (MSCs) have demonstrated promise when delivered to damaged tissue or tissue defects for their cytokine secretion and inflammation modulation behaviors that can promote repair. Insulin-like growth factor 1 (IGF-1) has been shown to augment MSCs viability and survival and promote their secretion of cytokines that signal to endogenous cells, in the treatment of myocardial infarction, wound healing, and age-related diseases. Biomaterial cell carriers can be functionalized with growth factor-mimetic peptides (i.e. IGF-1 mimicking peptides) to enhance MSC function while promoting cell retention and minimizing off-target effects seen with direct administration of soluble growth factors. Here, we functionalized alginate hydrogels with three distinct IGF-1 peptide mimetics and the integrin-binding peptide, cyclic RGD. One IGF-1 peptide mimetic (IGM-3) in combination with integrin ligand was found to activate Akt and ERK1/2 signaling and support survival of serum-deprived MSCs. MSCs encapsulated in alginate hydrogels that presented both IGM-3 and cRGD showed a significant reduction in pro-inflammatory cytokine secretion when challenged with interleukin-1{beta}. Finally, MSCs cultured within the cRGD/IGM-3 hydrogels were able to blunt pro-inflammatory gene expression of human primary cells from degenerated intervertebral discs. These studies indicate the potential to leverage cell adhesive and IGF-1 growth factor peptide mimetics together to control therapeutic secretory behavior of MSCs. Significance StatementInsulin-like growth factor 1 (IGF-1) plays a multifaceted role in stem cell biology and may promote proliferation, survival, migration, and immunomodulation for MSCs. In this study, we functionalized alginate hydrogels with integrin-binding and IGF-1 peptide mimetics to investigate their impact on MSC function. Encapsulating MSCs in the dual peptide (cRGD/IGM-3) hydrogels enhanced their ability to reduce inflammatory cytokine production and promote anti-inflammatory gene expression in cells from degenerative human intervertebral discs exposed to proteins secreted by the MSC. This approach suggests a new way to retain and augment MSC functionality using IGF-1 peptide mimetics, offering an alternative to co-delivery of cells and high dose soluble growth factors for tissue repair and immune-system modulation.

bioengineering↗

bioRxiv2024

Spatial Transcriptomic Sequencing of a DIPG-infiltrated Brainstem reveals Key Invasion Markers and Novel Ligand-Receptor Pairs contributing to Tumour to TME Crosstalk

Emerging spatially-resolved sequencing technologies offer unprecedented possibilities to study cellular functionality and organisation, transforming our understanding of health and disease. The necessity to understand healthy and diseased tissues in its entirety becomes even more evident for the human brain, the most complex organ in the body. The brains cellular architecture and corresponding functions are tightly regulated. However, when intercellular communications are altered by pathologies, such as brain cancer, these microenvironmental interactions are disrupted. DIPG is a brainstem high-grade glioma arising in young children and is universally fatal. Major disease obstacles include intratumoural genetic and cellular heterogeneity as well as a highly invasive phenotype. Recent breakthrough studies have highlighted the vital oncogenic capacity of brain cancer cells to functionally interact with the central nervous system (CNS). This CNS-crosstalk crucially contributes to tumour cell invasion and disease progression. Ongoing worldwide efforts seek to better understand these cancer-promoting CNS interactions to develop more effective DIPG anti-cancer therapies. In this study, we performed spatial transcriptomic analysis of a complete tumour-infiltrated brainstem from a single DIPG patient. Gene signatures from ten sequential tumour regions were analysed to assess disease progression and to study DIPG cell interactions with the tumour microenvironment (TME). We leveraged this unique DIPG dataset to evaluate genes significantly correlated with invasive tumour distal regions versus the proximal tumour initiation site. Furthermore, we assessed novel ligand-receptor pairs that actively promote DIPG tumour progression via crosstalk with endothelial, neuronal and immune cell communities, which can be utilised to support future research efforts in this area of high unmet need.

cancer biology↗

bioRxiv2024

A Vascular Dissection and Rupture Linked Metabolite Acts Via BLT2 Receptor

BACKGROUNDThoracic aortic dissection (TAD) is a life-threatening vascular disease that requires effective drug treatment to prevent progression and rupture. Because arachidonic acid metabolism is involved in inflammation and vascular homeostasis, we investigated the roles of arachidonic acid metabolites in TAD pathogenesis and their utility as therapeutic targets. METHODSSerum metabolomics analysis was performed to characterize arachidonic acid metabolites in TAD patients and a TAD mouse model. 12/15-LOX expression was profiled in the aortic tissues of TAD patients and the TAD mouse model. Four-week-old male Alox15 knockout mice (Alox15-/-), 12-HETE-treated mice, ML351 (12/15-LOX inhibitor)-treated mice, and LY255283 (leukotriene B 4 receptor 2 [BLT2] antagonist)-treated mice received {beta}-aminopropionitrile monofumarate (BAPN, 1 g/kg/day) for 4 weeks to model TAD, then underwent assessment of TAD progression. Interaction of 12-HETE produced by macrophages with BLT2 receptor-expressing cells was detected by molecular docking and immunoblotting. RESULTSSerum levels of 12-HETE and the expression of 12/15-LOX in aortic tissue were significantly increased in TAD patients and BAPN-treated TAD mice. BAPN-induced TAD progression was significantly ameliorated in Alox15-deficient or -suppressed mice. 12-HETE directly interacted with BLT2 receptors on macrophages, activating the downstream NOX-1/ROS/NF-{kappa}B signaling pathway to induce inflammatory cytokine release. This initiated inflammatory cell recruitment and exacerbated extracellular matrix degradation, leading to phenotype switching in vascular smooth muscle cells (VSMCs). Additionally, treatment with ML351 and LY255283 significantly reduced the rates of dissection rupture and combined treatment could maximize the curative effect. CONCLUSIONS12-HETE may amplify the inflammatory cascade and trigger aberrant phenotype switching in VSMCs during TAD development. The reduction of circulating 12-HETE or antagonism of its receptor may be new targets for TAD prevention and treatment. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIThe expression levels of 12/15-LOX and its metabolite 12-HETE were elevated in TAD patients and TAD mice. C_LIO_LIIncreased levels of 12-HETE directly bind to BLT2 receptors in macrophages, thereby initiating inflammatory cascades that downregulate VSMC differentiation markers through the suppression of IL-6. C_LIO_LIDeletion or pharmacologic inhibition of 12/15-LOX and suppression of BLT2 mitigated TAD development by alleviating inflammation and VSMC phenotype switching. C_LI What Are the Clinical Implications?O_LIThe inhibition of 12-HETE-related pathways, through mechanisms such as reducing the plasma 12-HETE content or blocking its receptor, may represent a novel therapeutic strategy for TAD. C_LIO_LIFurther studies are needed to explore the diagnostic value of serum 12-HETE as a novel biomarker for TAD. C_LI

cell biology↗

bioRxiv2024

Shift in cellular crosstalk reveals the immunosuppressive environment in cholangiocarcinoma patients.

Background and aimsCholangiocarcinoma (CCA) is a deadly disease, and this cancer entity is characterized by an abundant stroma. The tumor microenvironment (TME) plays an important role in aggressive behavior and poor response to therapeutics; however, underlying pathways are unknown. MethodsTo fill this gap, we used multiplexed immunohistochemistry, high-dimensional phenotyping, and transcriptomics to analyze human CCA samples and identify cell cluster crosstalk in patients with a poor prognosis. ResultsOur findings confirmed the presence of Tregs and the lack of effector memory cells in the tumor. New findings are the spatiality of the effector memory cells being more present in the peripheral tissue, for some reason these immune cells fail to reach the tumor niche. We revealed cancer crosstalk with macrophages and stromal cells and identified responsible genes in the poor prognosis group. Amongst the responsible ligand pairs are GAS6-AXL belonging to the TAM family. We then identified VCAN-TLR2 to be present and influencing the ECM in a way to supports immune exhaustion. Last, EGFR-TGF-{beta} is expressed in macrophages and this finding is important in Tregs induction and blocking cytotoxic T cell function. ConclusionsThe multiple mechanisms leading to the exclusion of relevant immune cells needed for an anti-cancer response and mechanisms leading to active immune suppression are part of complex cell-cell crosstalk. This study provides a deeper insight into the immune exhausted phenotype in CCA.

cancer biology↗

bioRxiv2024

Characterization of RNA editing profiles in rice endosperm development

Rice (Oryza sativa L.) endosperm provides nutrients for seed germination and determines grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we conduct genome re-sequencing and RNA sequencing for rice endosperms across five successive developmental stages and perform systematic analyses to characterize RNA editing profiles during rice endosperm development. We find that the majority of their editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids, and affecting structures and functions of mitochondrial proteins. Comparative analysis of RNA editing profiles across the five developmental stages reveals that CDS-recoding sites present higher editing frequencies with lower variabilities, and recoded amino acids, particularly caused by these sites with higher editing frequencies, tend to exhibit stronger evolutionary conservation across many land plants. Based on these results, we further classify mitochondrial genes into three groups that present distinct patterns in terms of editing frequency and variability of CDS-recoding sites. Besides, we identify a series of P- and PLS-class pentatricopeptide repeat (PPR) proteins with editing potential and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery. Author summaryRice endosperm development, a critical process determining quality and yield of our mankinds essential food, is regulated by RNA editing that provokes RNA base alterations by protein factors. However, our understanding of this regulation is incomplete. Hence, we systematically characterize RNA editing profiles during rice endosperm development. We find that editing sites resulting in amino acid changes, called "CDS-recoding", predominate in mitochondria, leading to increased hydrophobic amino acids and affecting structures and functions of proteins. Comparative analysis of RNA editing profiles during rice endosperm development reveals that CDS-recoding sites present higher editing frequencies with lower variabilities. Furthermore, evolutionary conservation of recoded amino acids caused by these CDS-recoding sites is positively correlated with editing frequency across many land plants. We classify mitochondrial genes into three groups that present distinct patterns in terms of editing frequency and variability of CDS-recoding sites, indicating different effects of these genes on rice endosperm development. In addition, we identify candidate protein factors associated closely with RNA editing regulation. To sum up, our findings provide valuable insights for fully understanding the role of RNA editing during rice endosperm development.

bioinformatics↗

bioRxiv2023

Allocator is a graph neural network-based framework for mRNA subcellular localization prediction

MotivationThe asymmetrical distribution of expressed mRNAs tightly controls the precise synthesis of proteins within human cells. This non-uniform distribution, a cornerstone of developmental biology, plays a pivotal role in numerous cellular processes. To advance our comprehension of gene regulatory networks, it is essential to develop computational tools for accurately identifying the subcellular localizations of mRNAs. However, considering multi-localization phenomena remains limited in existing approaches, with none considering the influence of RNAs secondary structure. ResultsIn this study, we propose Allocator, a multi-view parallel deep learning framework that seamlessly integrates the RNA sequence-level and structure-level information, enhancing the prediction of mRNA multi-localization. The Allocator models equip four efficient feature extractors, each designed to handle different inputs. Two are tailored for sequence-based inputs, incorporating multilayer perceptron and multi-head self-attention mechanisms. The other two are specialized in processing structure-based inputs, employing graph neural networks. Benchmarking results underscore Allocators superiority over state-of-the-art methods, showcasing its strength in revealing intricate localization associations. AvailabilityThe webserver of Allocator is available at http://Allocator.unimelb-biotools.cloud.edu.au; the source code and datasets are available at https://github.com/lifuyi774/Allocator

bioinformatics↗

bioRxiv2023

Unveiling interactions of spatial-temporal information in tactile motion perception

The intricate interplay of spatial and temporal information in tactile-motion perception remains elusive. Despite strides in decoding neural signals for direction, speed and texture in tactile perception, nuanced interactions persist as challenges. Addressing this, we investigated direction and speed tactile perception, exploring the intricate spatial-temporal dynamics. Psychophysical experiments manipulated direction and speed parameters using a laboratory-designed fingerpad ball-stimulator. A pivotal discovery includes quadrant-dependent anisotropic distortion in perceived motion direction, expanding the well-known notion of a specific preferred orientation. Spatial features primarily influence inherent responses, while temporal features impact stimulus-specific responses, shedding light on dynamic directional perception. The introduction of a psychometric function improved the modeling of tactile-motion speed perception, incorporating both linear and nonlinear components for a more accurate representation. This study provides intriguing insights into the neural mechanisms in tactile-motion perception, with potential applications for somatosensation in brain-machine interfaces. TeaserThis study unveils the intricate interplay of perceiving tactile motion, shedding light on the mysteries of tactile sensations.

neuroscience↗

bioRxiv2023

Spatially resolved molecular and cellular atlas of the mouse brain

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.

neuroscience↗

bioRxiv2023

Polygonum Cillinerve polysaccharide inhibits Transmissible gastroenteritis virus by regulating microRNA-181

Transmissible gastroenteritis virus (TGEV) is an important pathogen that can cause changes in the expression profile of cell miRNA. In this study, PCP could treat piglets infected with TGEV by in vivo experiment. High-throughput sequencing technology was used to detect that 9 miRNAs were up-regulated and 17 miRNAs were down-regulated during PCP inhibition of TGEV infection in PK15 cells. Meanwhile, miR-181 was related to the target genes of key proteins of apoptosis pathway. PK15 was treated with different PCP after transfection of miR-181 mimic or inhibitor. Real-time PCR was used to detect the effect of TGEV replication, electron microscopy, TEM and Hoechst fluorescence staining were used to detect the biological function of the treated cells, and western blot (WB) was used to detect the expression of key signaling factors cyt C, caspase 9 and P53 in the apoptotic signaling pathway. The results showed that compared with the control group, 250 g/mL PCP significantly inhibited the replication of TGEV gRNA and gene N (P < 0.01). PK15 cells in PCP groups (250 and 125 g/mL) had uniform cell morphology and a small number of floating cells by microscopic, no typical virus structure was observed in 250 g/mL PCP group under TEM, and apoptosis staining showed that 250 g/mL PCP significantly reduced the number of apoptotic cells. PCP may inhibit TGEV-induced apoptosis through Caspase-dependent mitochondrial pathway after transfection of miR-181. The above results provided a theoretical basis for further research on the mechanism of PCP anti-TGEV.

pharmacology and toxicology↗