Biology subjects

Jiang, H.

Publications and source records attributed to Jiang, H..

At least 181 records · Page 10Linked to original sources

bioRxiv2023

An ancient transcription activator is required for the multiciliogenesis program

Multiciliogenesis is an evolutionarily conserved process required a unique transcriptional program. The mechanisms governing multiciliogenesis are incompletely understood. Here we show that an ancient transcription activator, Edf1, is essential for the multiciliogenesis program. Mice lacking Edf1 exhibit postnatal hydrocephalus and delayed multiciliated cells (MCCs) differentiation. Functional studies reveal that MCCs in Edf1-/- mice have defects in tissue-level polarity and reduced motility. These defects result in abnormal cerebrospinal fluid (CSF) dynamics in vivo, potentially contributing to the development of hydrocephalus. Intriguingly, we found that the expression of pivotal ciliary transcription factors was decreased in Edf1-/- mice. Collectively, our data suggest that Edf1 modulates the multiciliogenesis by regulating the transcription of important ciliary transcription factors required for ciliary gene expression.

cell biology↗

bioRxiv2023

Dissecting the Impact of Maternal Androgen Exposure on Offspring Health through Targeting the Androgen Receptor in Developmental Programming

Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation in circulating androgens during pregnancy, an independent risk factor linked to pregnancy complications and adverse neonatal outcomes. Yet, further investigation is required to understand the precise mechanisms and the impact on cell-type specific placental dysfunction. To explore these dynamics, a PCOS-like mice model was induced with continuous androgen exposure throughout pregnancy, mimicking the human-PCOS. This resulted in impaired placental and embryonic development, leading to mid-gestation lethality. Co-treatment with the androgen receptor blocker, flutamide, prevented this lethality. Comprehensive analysis using whole-genome bisulfite and RNA sequencing revealed the diminished proportion of trophoblast precursors by downregulation of Cdx2. The absence of Gcm1, Synb, and Prl3b1 further resulted in decreased numbers of syncytiotrophoblasts and sinusoidal trophoblast giant cells, leading to observed compromised placenta labyrinth formation. Importantly, human trophoblast organoids exposed to androgens exhibited analogous alterations, highlighting impaired trophoblast differentiation as a key feature in PCOS-related pregnancy complications. Remarkably, all effects were mediated through the androgen receptor pathways, as demonstrated by comparable offspring phenotypes to controls when treated with flutamide. These findings provide novel insight into the PCOS-related pregnancy complications, and potential cellular targets for future treatment.

physiology↗

bioRxiv2023

Nuclear cytoophidia assembly represses transcriptional activity to control skeletal development and homeostasis

Compartmentation via filamentation is an evolutionarily conserved subcellular structure that fine-tunes the inherent activity of proteins. Cytoophidia represent a typical class of filamentous structures controlling enzymatic activities. Despite eukaryotic cells containing both cytoplasmic cytoophidia and nuclear cytoophidia, the physiological significance of nuclear cytoophidia is largely unknown. Here we show that nuclear filamentation inhibits the transcriptional activity of Impdh2 required for limb formation and bone resorption. Impdh2 deletion in mouse limb mesenchymal progenitors causes severe skeletal dysplasia by impairing endochondral ossification and chondrocyte differentiation. Additionally, Impdh2 deficiency in myeloid lineages leads to an increased bone mass via impeding osteoclast differentiation. Furthermore, Impdh2 regulates osteoclastic mitochondrial biogenesis and function. We propose that the nuclear compartmentalization of Impdh2 regulates the transcriptional activity during skeletal development and homeostasis.

cell biology↗

bioRxiv2023

Internal Dynamics Interact with Proprioceptive Feedback During Movement Execution in an RNN Model of Motor Cortex

Proprioceptive feedback provides the information about the state of the body, which is critical in motor control. However, the contribution of proprioceptive feedback to motor cortical activity during voluntary movement execution is unclear. Here, we built an recurrent neural network model of motor cortex that receives proprioceptive feedback, and optimized it to control a virtual arm to perform a delayed-reach task. Simulated neural activity is similar to real data, indicating that our model captures the motor cortical dynamics. We further disrupted recurrent connectivity and proprioceptive feedback to dissect their contribution, and found that internal dynamics dominate in neural population activity, while proprioceptive feedback controls movement termination. Moreover, proprioceptive feedback improves the networks robustness against noisy initial conditions. We further investigated the relative importance of the components in proprioceptive feedback and found that the feedback of hand velocity contributes most to the similarity between simulation and real data. Finally, we show that our motor cortex model can be implemented in the sensorimotor system, demonstrating our models biological plausibility. In summary, motor command may arise from the intersection between recurrent dynamics in motor cortex and proprioceptive feedback.

neuroscience↗

bioRxiv2023

Investigation of contributions from cortical and subcortical brain structures for speech decoding

Language impairments often arise from severe neurological disorders, prompting the development of neural prosthetics based on electrophysiological signals for the restoration of comprehensible language information. Previous decoding efforts have focused mainly on signals from the cerebral cortex, neglecting the potential contributions of subcortical brain structures to speech decoding in brain-computer interfaces (BCIs). This study aims to explore the role of subcortical structures for speech decoding by utilizing stereotactic electroencephalography (sEEG). Two native Mandarin Chinese speakers, who underwent sEEG implantation for pharmaco-resistant epilepsy, participated in this study. sEEG contacts were primarily located in the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, thalamus, hippocampus, insular gyrus, amygdala, and parahippocampal gyrus. The participants were asked to read Chinese text, which included 407 Chinese characters (covering all Chinese syllables), displayed on a screen after receiving prompts. 1-30, 30-70 and 70-150 Hz frequency band powers of sEEG signals were used as key features. A deep learning model based on long short-term memory (LSTM) was developed to evaluate the contribution of different brain structures during encoding of speech. Prediction of speech characteristics of consonants (articulatory place and manner) and tone within single words based on the selected features and electrode contact locations was made. Cortical signals were generally better at articulatory place prediction (86.5% accuracy, chance level = 12.5%), while cortical and subcortical signals predicted articulatory manner at similar level (51.5% vs 51.7% accuracy, respectively, chance level = 14.3%). Subcortical signals generated better prediction for tone (around 58.3% accuracy, chance level = 25%). Superior temporal gyrus remains highly relevant during speech decoding for both consonants and tone. Prediction reached the highest level when cortical and subcortical inputs were combined, especially for tone prediction. Our findings indicate that both cortical and subcortical structures can play crucial roles for speech decoding, each contributing to different aspects of speech.

neuroscience↗

bioRxiv2023

Mechanical Resistance to Micro-Heart Tissue Contractility unveils early Structural and Functional Pathology in iPSC Models of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is the most common cause of sudden death in the young. Because the disease exhibits variable penetrance, there are likely nongenetic factors that contribute to the manifestation of the disease phenotype. Clinically, hypertension is a major cause of morbidity and mortality in patients with HCM, suggesting a potential synergistic role for the sarcomeric mutations associated with HCM and mechanical stress on the heart. We developed an in vitro physiological model to investigate how the afterload that the heart muscle works against during contraction acts together with HCM-linked MYBPC3 mutations to trigger a disease phenotype. Micro-heart muscle arrays (HM) were engineered from iPSC-derived cardiomyocytes bearing MYBPC3 loss-of-function mutations and challenged to contract against mechanical resistance with substrates stiffnesses ranging from the of embryonic hearts (0.4 kPa) up to the stiffness of fibrotic adult hearts (114 kPa). Whereas MYBPC3+/- iPSC-cardiomyocytes showed little signs of disease pathology in standard 2D culture, HMs that included components of afterload revealed several hallmarks of HCM, including cellular hypertrophy, impaired contractile energetics, and maladaptive calcium handling. Remarkably, we discovered changes in troponin C and T localization in the MYBPC3+/- HM that were entirely absent in 2D culture. Pharmacologic studies suggested that excessive Ca2+ intake through membrane-embedded channels, rather than sarcoplasmic reticulum Ca2+ ATPase (SERCA) dysfunction or Ca2+ buffering at myofilaments underlie the observed electrophysiological abnormalities. These results illustrate the power of physiologically relevant engineered tissue models to study inherited disease mechanisms with iPSC technology.

bioengineering↗

bioRxiv2023

Functional Trait Variations in Zizania latifolia: Insights into Climate Adaptation

The global warming could have significant impact on plant adaptation to local environments. Widespread species provides a useful model to examine the population dynamic under climate change. However, it is still unclear how widespread aquatic species response to rapidly changing environments. Wild-rice Zizania latifolia is an emergent macrophyte widely distributed across East Asia. Here, 28 Z. latifolia natural populations covering above 30 latitudes were transplanted in a common garden. The growth, photosynthesis and reproduction traits were quantified and compared among populations, and pairwise relationships among geographic and genetic variables were estimated. Results showed that, in the common garden, the high-latitude populations grew in small size indicating weaker competitiveness in warmer temperatures; the low-latitude populations had no sexual reproduction, suggesting that low-latitude individuals stood little chance to migrate successfully to higher latitude. Significant positive correlations among the distances of genetic, geographic and morphological traits for populations indicated that both isolation by distance and isolation by environment models affected the genetic pattern of populations, and phenotypic traits of Z. latifolia populations might be genetically determined. All our data suggest that Z. latifolia would be inadaptable to the global warming, indicating that this species would be at least at risk of local extinction in the warmer future.

plant biology↗

bioRxiv2023

MIF Regulates M1 Macrophage Polarization via CD74/CXCR2/JNK Pathway and Mediates Aortic Dissection in Mice

BackgroundMacrophage polarization and vascular smooth muscle cell (VSMC) phenotypic switching are important features and critical targets in the progression of Aortic dissection (AD). High expression of macrophage migration inhibitory factor (MIF) in aortic and blood specimens has been observed in patients with aortic dissection, but its precise function and mechanism in AD are unknown. We aimed to clarify whether MIF mediates the development of aortic dissection via modulation of M1 macrophage polarization and its specific regulatory pathways. MethodsBased on the BAPN/Ang II-induced acute aortic dissection model and by intraperitoneal injection of the MIF antagonist ISO-1 to inhibit MIF activity in mice. We assayed macrophage infiltration, polarization, and VSMC phenotypic switching in the aorta of mice in each group. Further, we evaluated the polarizing effects of MIF on RAW264.7 cells directly or indirectly in vitro experiments and explored the specific cellular signaling pathways that mediate its function. At last, we evaluated the role and possible mechanisms of RAW264.7 cells with different degrees of polarization in inducing phenotypic switching of MOVAS cells based on a model of indirect co-culture of RAW264.7 cells with MOVAS cells. ResultsPharmacological inhibition of MIF decreased the incidence of BAPN/Ang II-induced aortic dissection and attenuated aortic vascular remodeling in mice by reducing M1 macrophage infiltration in mouse aorta. Through in vitro assays, we demonstrated that MIF could activate the intracellular JNK/c-Jun signaling pathway by targeting the CD74/CXCR2 receptor, promote M1 polarization and upregulate the expression of the M1 macrophage markers, iNOS, IL-18, and CD86 in RAW264.7 cells. Further experiments confirmed that upon co-culture with MIF-induced M1 macrophages, the NF-{kappa}B pathway was activated in MOVAS cells, inducing the onset of phenotypic switching and apoptosis. ConclusionsThe results indicated that MIF mediated macrophage polarization and regulated the progression of aortic dissection, which provided new scientific evidence for the pathogenesis of aortic dissection, and also suggested that MIF may be a potential preventive and therapeutic target for aortic dissection and aortic-related diseases.

molecular biology↗

bioRxiv2023

TCM-CMap: A Novel Computational Methodology to Link Gene Perturbation to Therapeutic Targets in Complex TCM Prescriptions

Herbal medicine, especially Traditional Chinese medicine (TCM), is a valuable resource of natural products for drug discovery with obvious therapeutic effects. However, the mechanisms of action (MOAs) of herbal medicine are often unknown due to limited target information and the complexity of multiple ingredients and targets. This study developed a Herb-CMap algorithm to prioritize active ingredients and targets within herbal medicine by integrating transcriptomics- based gene perturbation data with a random walk algorithm. This methodology bridges the gap between gene perturbation of herbal medicine and its therapeutic target. Using the Suhuang antitussive capsule (Suhuang) for treating cough variant asthma (CVA) as a case study, we identify and experimentally verify that quercetin and luteolin directly interact with Il17a, Pik3cb, Pik3cd, Akt1, and Tnf. These interactions inhibit the IL-17 signaling pathway and inactivate PI3K, Akt, and NF- {kappa}B, preventing lung inflammation and treating CVA. Our findings demonstrate the potential of the Herb-CMap methodology to provide insights into the molecular MOAs of herbal medicine, thereby advancing drug discovery from herbal medicine.

systems biology↗

bioRxiv2023

Integrin-like adhesin CglD confers traction and stabilizes bacterial focal adhesions involved in myxobacterial gliding motility

AO_SCPLOWBSTRACTC_SCPLOWIntegrins are crucial for eukaryotic cell attachment and motility within the extracellular matrix (ECM) via focal-adhesion formation, with their evolutionary emergence important for the development of multicellularity. Intriguingly, single gliding cells of the predatory deltaproteobacterium Myxococcus xanthus form bacterial focal-adhesion (bFA) sites; therein, helically-trafficked motors become immobilized at anchored locations through Glt apparatus association with cell-surface integrin I-domain-like adhesin CglB. Using traction-force, bead-force, and total internal reflection-fluorescence microscopies combined with biochemical approaches, we herein identify the von Willebrand A domain-containing cell-surface lipoprotein CglD to be a {beta}-integrin-like outer-membrane lipoprotein that functionally associates with and anchors the trans-envelope Glt-CglB gliding apparatus, stabilizing and efficiently anchoring this assembly at bFAs. Calcium dependence governs CglD importance, consistent with its integrated ECM eukaryotic cartilage oligomeric matrix protein domains. CglD thus confers mechanosensory and mechanotransductory capabilities to the gliding apparatus, helping explain bFA-mediated trans-envelope force transduction, from inner-membrane-embedded motors to the cell surface.

microbiology↗

bioRxiv2023

The role of immune inflammatory response and inflammatory infiltrates in major depression disorder and atopic dermatitis: new insights from machine learning

BackgroundMajor depression disorder (MDD) and atopic dermatitis (AD) are distinct disorders involving immune inflammatory responses. This study aimed to investigate the comorbid relationship between AD and MDD and to identify possible common mechanisms. MethodsWe obtained AD and MDD data from the Gene Expression Omnibus (GEO) database. Differential expression analysis and the Genecard database were employed to identify shared genes associated with inflammatory diseases. These shared genes were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Hub genes were selected based on the protein-protein interactions using CytoHubba, and key regulatory genes were identified through enrichment analysis. Subsequently, we conducted immune infiltration and correlation analyses of the shared genes in AD. Finally, we employed three machine learning models to predict the significance of shared genes. ResultsA total of 17 shared genes were identified in the AD_Inflammatory_MDD dataset (S100A9, PTGER2, PI3, SNCA, DAB2, PDGFA, FSTL1, CALD1, XK, UTS2, DHRS9, PARD3, NFIB,TMEM158, LIPH, RAB27B, and SH3BRL2). These genes were associated with biological processes such as the regulation of mesenchymal cell proliferation, mesenchymal cell proliferation, and glial cell differentiation. The neuroactive ligand-receptor interaction, IL-17 signaling, and Rap1 signaling pathways were significantly enriched in KEGG analysis. SNCA, S100A9, SH3BGRL2, RAB27B, TMEM158, DAB2, FSTL1, CALD1, and XK were identified as hub genes contributing to comorbid AD and MDD development. The three machine learning models consistently identified SNCA and PARD3 as important biomarkers. ConclusionSNCA, S100A9, SH3BGRL2, RAB27B, TMEM158, DAB2, FSTL1, CALD1, and XK were identified as significant genes contributing to the development of AD and MDD comorbidities. Immune infiltration analysis showed a notable increase in the infiltration of various subtypes of CD4+ T cells, suggesting a potential association between the development of skin inflammation and the immune response. Across different machine learning models, SNCA and PARD3 consistently emerged as important biomarkers.

genetics↗

bioRxiv2023

Deletion of CD44 promotes adipogenesis by regulating PPARγ and cell cycle-related pathways

CD44, a cell surface adhesion receptor and stem cell biomarker, is recently implicated in chronic metabolic diseases. Ablation of CD44 ameliorates adipose tissue inflammation and insulin resistance in obesity. Here, we investigated cell type specific CD44 expression in human and mouse adipose tissue and further studied how CD44 in preadipocytes regulates adipocyte function. Using Crispr Cas9-mdediated gene deletion and lentivirus-mediated gene re-expression, we discovered that deletion of CD44 promotes adipocyte differentiation and adipogenesis, whereas re-expression of CD44 abolishes this effect and decreases insulin responsiveness and adiponectin secretion in 3T3-L1 cells. Mechanistically, CD44 does so via suppressing Pparg expression. Using quantitative proteomics analysis, we further discovered that cell cycle-regulated pathways were mostly decreased by deletion of CD44. Indeed, re-expression of CD44 moderately restored expression of proteins involved in all phases of the cell cycle. Our data suggest that CD44 plays a crucial role in regulating adipogenesis and adipocyte function possibly through regulating PPAR{ballotbox} and cell cycle-related pathways. This study provides evidence for the first time that CD44 expressed in preadipocytes plays key roles in regulating adipocyte function outside immune cells where CD44 is primarily expressed. Therefore, targeting CD44 in (pre)adipocytes may provide therapeutic potential to treat obesity-associated metabolic complications.

cell biology↗

bioRxiv2023

Aquaporin 1 confers apoptosis resistance in pulmonary arterial smooth muscle cells from the SU5416 hypoxia rat model

Pulmonary arterial hypertension (PAH) is a deadly condition that arises from increased pulmonary vascular resistance due to contraction and remodeling of the pulmonary arteries. The structural changes that occur in the pulmonary arteries include thickening of the medial (smooth muscle) layer resulting from increased proliferation and resistance to apoptosis. The mechanisms underlying apoptosis resistance in PAH are not fully understood. In cancer cells, high expression of aquaporin 1 (AQP1), a water channel, is associated with apoptosis resistance. We previously showed functional AQP1 protein was expressed in pulmonary arterial smooth muscle cells (PASMCs) and was upregulated in pre-clinical models of pulmonary hypertension. Whether AQP1 controls susceptibility of PASMCs to apoptosis in pre-clinical models of PAH is unknown. In this study, we used PASMCs isolated from control rats and rats exposed to SU5416 plus hypoxia (SuHx) to test the role of AQP1 in modulating apoptosis in PASMCs. We found that elevated levels of AQP1 in PASMCs from pulmonary hypertensive rats were necessary for resistance to apoptosis, and that apoptosis resistance could be conferred by increasing expression of AQP1 in PASMCs from control rats. Moreover, in exploring the downstream pathways involved, we found AQP1 levels influence the expression of Bcl-2, with enhanced AQP1 levels corresponding to increased Bcl-2 expression, resulting in reductions in the ratio of BAX to Bcl-2 as are typically associated with apoptosis resistance. These early results provide a mechanism by which AQP1 can regulate PASMC fate and suggest further investigation could provide additional clues regarding whether AQP1-mediated apoptosis resistance contributes to PAH development or progression and whether AQP1 might be a suitable target for therapy.

cell biology↗

bioRxiv2023

Integrative analysis of multi-omics and machine learning highlighted an m6A-related mRNA signature as a robust AAA progression predictor

ObjectiveAbdominal aortic aneurysm (AAA) is a life-threatening disease in vascular surgery with significant morbidity and mortality rates upon rupture. Despite surgical interventions, effective targeted drugs for non-surgical candidates are lacking. M6A methylation, a dynamic RNA modification, has been implicated in various diseases, but its role in AAA remains poorly understood. In this study, we aimed to explore the participation of M6A in the progression of AAA progression through multi-omics and machine learning. Approach and Resultswe conducted methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) to profile the m6A methylome in AAA tissues, identifying differentially methylated genes (DMGs). Integrating multi-omics data from RNA-sequencing (RNA-seq) in GEO databases, we developed a machine learning-based AAA m6A-related mRNA signature (AMRMS) to predict AAA dilation risk. The AMRMS demonstrated robust predictive performance in distinguishing AAA patients with large AAA and small AAA. Notably, the AMRMS highlighted FKBP11 as a key gene with a significant impact on the predicted model. Subsequent single-cell RNA sequencing (ScRNA-seq) revealed the pivotal role of FKBP11-positive plasma cells in AAA progression. ConclusionsOur study provides novel insights into the regulatory role of m6A modification in AAA pathogenesis, and further develop a promising AMRMS for risk evaluation in AAA patients. Furthermore, the identification of FKBP11 positive plasma cells as significant contributors to AAA progression opens new avenues for targeted therapeutic interventions.

bioinformatics↗

bioRxiv2023

GeneCompass: Deciphering Universal Gene Regulatory Mechanisms with Knowledge-Informed Cross-Species Foundation Model

Deciphering the universal gene regulatory mechanisms in diverse organisms holds great potential to advance our knowledge of fundamental life process and facilitate research on clinical applications. However, the traditional research paradigm primarily focuses on individual model organisms, resulting in limited collection and integration of complex features on various cell types across species. Recent breakthroughs in single-cell sequencing and advancements in deep learning techniques present an unprecedented opportunity to tackle this challenge. In this study, we developed GeneCompass, the first knowledge-informed, cross-species foundation model pre-trained on an extensive dataset of over 120 million single-cell transcriptomes from human and mouse. During pre-training, GeneCompass effectively integrates four types of biological prior knowledge to enhance the understanding of gene regulatory mechanisms in a self-supervised manner. Fine-tuning towards multiple downstream tasks, GeneCompass outperforms competing state-of-the-art models in multiple tasks on single species and unlocks new realms of cross-species biological investigation. Overall, GeneCompass marks a milestone in advancing knowledge of universal gene regulatory mechanisms and accelerating the discovery of key cell fate regulators and candidate targets for drug development.

bioinformatics↗

bioRxiv2023

Integration of Patient-Derived Organoids and Organ-on-Chip Systems: Investigating Colorectal Cancer Invasion within the Mechanical and GABAergic Tumor Microenvironment

Three-dimensional (3D) in vitro models are essential in cancer research, but they often neglect physical forces. In our study, we combined patient-derived tumor organoids with a microfluidic organ-on-chip system to investigate colorectal cancer (CRC) invasion in the tumor microenvironment (TME). This allowed us to create patient-specific tumor models and assess the impact of physical forces on cancer biology. Our findings showed that the organoid-on-chip models more closely resembled patient tumors at the transcriptional level, surpassing organoids alone. Using omics methods and live-cell imaging, we observed heightened responsiveness of KRAS mutant tumors to TME mechanical forces. These tumors also utilized the {gamma}-aminobutyric acid (GABA) neurotransmitter as an energy source, increasing their invasiveness. This bioengineered model holds promise for advancing our understanding of cancer progression and improving CRC treatments. HighlightsO_LIMicrofluidic organ-on-chip system integrated with patient-derived CRC organoids C_LIO_LIPhysical forces influence invasion, particularly in KRAS mutant tumor cells C_LIO_LIGABAergic signaling contributes to increased invasion within a dynamic TME C_LIO_LIThis model explores patient heterogeneity, TME interactions, and cancer progression C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/557797v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1b181bborg.highwire.dtl.DTLVardef@bc5b6eorg.highwire.dtl.DTLVardef@16b4fcorg.highwire.dtl.DTLVardef@c43b9f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

Transcriptomic signatures of Abeta- and tau-induced neuronal dysfunction reveal inflammatory processes at the core of Alzheimer's disease pathophysiology

Molecular mechanisms enabling pathology-induced neuronal dysfunction in Alzheimers disease (AD) remain elusive. Here, we use mechanistic computational models to infer the combined influence of PET-measured A{beta} and tau burdens on fMRI-derived neuronal activity and to subsequently identify the transcriptomic spatial correlates of AD pathophysiology. Our results reveal overrepresented genes and biological processes that participate in synaptic degeneration and interact with A{beta} and tau deposits. Furthermore, we confirmed the central role of the immune system and neuroinflammatory pathways within AD pathogenesis; microglia were significantly enriched in the gene set associated with A{beta} and tau synergistic influences on neuronal activity. Lastly, our computational approach unveiled drug candidates with the potential to halt or reduce the observed pathological effects on neuronal activity, including existing medication for cancer, immune disorders, and cardiovascular diseases, many currently under clinical evaluation in AD. Overall, these findings support the notion that the AD brain experiences functional changes intricately associated with a diverse spectrum of molecular processes.

neuroscience↗

bioRxiv2023

Hormonal and transcriptomic analysis reveals the role of ABA and BR in breaking the barrier of inter-subgeneric hybridization in water lily (Nymphaea)

Understanding the process of signal communication between pollen and stigma is of significant importance for plant sexual reproduction. In the case of inter-subgeneric hybridization in water lily, there exists a pre-fertilization hybridization barrier, the regulatory mechanism of which remains unclear. In this study, we conducted hormone and transcriptome analyses of unpollinated stigmas (Mock), self-pollinated stigmas (SP), cross-pollinated stigmas within the same subgenus (CP), and inter-subgenus cross-pollination stigmas (ISCP) in water lily to elucidate the formation mechanism of the inter-subgeneric hybridization barrier. Our results indicated that the lack of ABA and BR in ISCP stigmas are key factors contributing to the formation of the inter-subgeneric hybridization barrier in water lily. Exogenous application of ABA and BR can help overcome the barrier between inter-subgeneric water lily crosses. Through transcriptome analysis, we identified nine candidate genes involved in regulating the inter-subgeneric hybridization barrier in water lily. In addition, we further demonstrated the importance of the NCED2-mediated ABA synthesis pathway in the hybridization process through AS-ODN technology. Our study confirms that ABA and BR are critical for breaking the inter-subgeneric hybridization barrier in water lily. The identification of the nine candidate genes provides important clues for further research on the hybridization recognition mechanism in water lily.

plant biology↗