Biology subjects

Tang, W.

Publications and source records attributed to Tang, W..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Dnmt3b deficiency in adipocyte progenitor cells ameliorates obesity in female mice

Obesity arises from chronic energy imbalance where energy intake exceeds energy expenditure. Emerging evidence supports a key role of DNA methylation in the regulation of adipose tissue development and metabolism. We recently discovered a key role of DNA methylation, catalyzed by DNA methyltransferase 1 or 3a (Dnmt1 or 3a), in the regulation of adipocyte differentiation and metabolism. Here, we aimed to investigate the role of adipocyte progenitor cell Dnmt3b, an enzyme mediating de novo DNA methylation, in energy metabolism and obesity. We generated a genetic model with Dnmt3b knockout in adipocyte progenitor cells (PD3bKO) by crossing Dnmt3b-floxed mice with platelet-derived growth factor receptor alpha (Pdgfr)-Cre mice. Dnmt3b gene deletion in adipocyte progenitors enhanced thermogenic gene expression in brown adipose tissue, increased overall energy expenditure, and mitigated high-fat diet (HFD)-induced obesity in female mice. PD3bKO mice also displayed a lower respiratory exchange ratio (RER), indicative of a metabolic shift favoring fat utilization as an energy source. Furthermore, female PD3bKO mice exhibited improved insulin sensitivity alongside their lean phenotype. In contrast, male PD3bKO mice showed no changes in body weight but demonstrated decreased insulin sensitivity, revealing a sexually dimorphic metabolic response to Dnmt3b deletion in adipocyte progenitor cells. These findings underscore the critical role of Dnmt3b in regulating energy homeostasis, body weight, and metabolic health, with significant implications for understanding sex-specific mechanisms of obesity and metabolism.

systems biology↗

bioRxiv2025

Integrating transcriptomic data with metabolic model unravels the electron transfer mechanisms of Methanosarcina barkeri

Methanogenic archaea, particularly Methanosarcina, are pivotal to the global carbon cycle and renewable energy production due to their versatile metabolic capabilities. Although transcriptomic analysis is widely employed to identify key genes and pathways in Methanosarcina under various methanogenic conditions--including the emerging direct interspecies electron transfer (DIET)-based methanogenesis--the weak correlation between gene expression levels and protein abundances poses challenges for interpreting transcriptomic data. To address this, we integrated transcriptomic data into a metabolic model of Methanosarcina barkeri for the first time, enabling more refined predictions and enhancing the interpretability of transcriptomic insights. This novel integrated model was subsequently utilized to simulate aceticlastic, hydrogenotrophic, and DIET-based methanogenesis. The results revealed that previous assumptions failed to account for the role of the CO2 reduction pathway in aceticlastic methanogenesis. The model also successfully captured key transcriptomic features of DIET-based methanogenesis, clarifying the functional roles of crucial enzymes like the F420H2 dehydrogenase Fpo and the transmembrane hydrogenase Vht in electron transfer. This integrative approach provided a deeper understanding of electron transfer mechanisms in M. barkeri and offered valuable insights for advancing methanogen-based biotechnologies. Moreover, the study critically evaluated the relationship between gene expression and metabolic flux, establishing a practical framework for deriving meaningful insights from the growing volume of transcriptomic data.

bioengineering↗

bioRxiv2024

Reshaping epigenomic landscapes in facilitating the speciation of bread wheat

Polyploidization is a driving force of wheat evolution and speciation, yet its impact on epigenetic regulation and gene expression remains unclear. Here, we constructed a high-resolution epigenetic landscape across leaves, spikes, and roots of hexaploidy wheat and its tetraploid and diploid relatives. Inter-species stable-expression genes exhibited conserved amino acid sequences under strong purifying selection, while dynamic-expression genes were linked to species-specific adaptation. During hexaploidization, dominant D-subgenome homoeolog expression was suppressed via reduced activating epigenetic signals, converging expression with the A and B subgenomes. Proximal chromatin regions near genes were more stable, whereas distal regions, particularly enhancer-like elements mediated by H3K27ac and H3K4me3, exhibit higher dynamism. Sequence variations in these enhancers lead to differential gene regulation, influencing traits such as spike development. For instance, the two haplotypes of dCRE region of TaDEP-B1 resulted in significant differences in its expression and spikelet numbers. We also observed a coevolution of transcription factors and their binding sites, particularly within the expanded ERF family, which regulates spike morphology. This study highlights the interplay between sequence variation and epigenetic modifications in shaping transcriptional regulation during wheat speciation, offering valuable insights for genetic improvement.

plant biology↗

bioRxiv2024

Vascular endothelial growth factor-D improves lung vascular integrity during acute lung injury

Disorders in pulmonary vascular integrity are a prominent feature in many lung diseases. Paracrine signaling is highly enriched in the lung and plays a crucial role in regulating vascular homeostasis. However, the specific local cell-cell crosstalk signals that maintain pulmonary microvascular stability in adult animals and humans remain largely unexplored. In this study, we employed single-cell RNA-sequencing (scRNAseq)-based computational pipelines to systematically profile ligand-receptor (L/R) interactions within the lung microvascular niche and identified vascular endothelial growth factor-D (VEGF-D) as a key local factor with previously unrecognized barrier-protective properties in models of acute lung injury. Our scRNAseq data revealed that, under physiological conditions, soluble L/R interactions between mesenchymal cells, in particular alveolar fibroblast, and microvascular endothelial cells are predominantly associated with pathways involved in maintaining vascular integrity as compared to all other cells. Upon treatment with top identified ligands, we found that VEGF-D significantly enhanced endothelial barrier function and conferred protection against inflammatory challenges induced by tumor necrosis factor- (TNF-), interleukin-1{beta} (IL-1{beta}), and thrombin. This barrier-protective effect of VEGF-D was significantly attenuated by inhibition of VEGFR2, either through siRNA knockdown or pharmacological blockade using specific VEGFR2 inhibitors. Intravenous administration of recombinant VEGF-D in lipopolysaccharides (LPS)-induced acute lung injury models significantly reduced vascular permeability (7339 {+/-} 2510 (LPS) v.s. 5350 {+/-} 1821 (LPS + VEGF-D), p < 0.05), immune cell infiltration (0.791 {+/-} 0.199 x 106 WBC/mL (LPS) v.s. 0.540 {+/-} 0.190 x 106 WBC/mL (LPS + VEGF-D), p < 0.01), and the expression of pro-inflammatory markers TNF- and IL-6 in the lung tissue. This effect was abolished in VEGFR2iECKO mice, confirming that VEGF-D mediates its effects via VEGFR2-dependent signaling. This study demonstrates an unexpected protective role for VEGF-D in promoting lung endothelial barrier integrity and suggests that paracrine signaling from the alveolar fibroblast niche contributes critically to lung capillary homeostasis.

molecular biology↗

bioRxiv2024

Upstream open reading frames buffer translational variability during Drosophila evolution and development

Protein abundance tends to be more evolutionarily conserved than mRNA levels both within and between species, yet the mechanisms underlying this phenomenon remain largely unknown. Upstream open reading frames (uORFs) are widespread cis-regulatory elements in eukaryotic genomes that regulate translation, but it remains unclear whether and how uORFs contribute to stabilizing protein levels. In this study, we performed ribosome translation simulations on mRNA to quantitatively assess the extent to which uORF translation influences the translational variability of downstream coding sequences (CDSs) across varying contexts. Our simulations revealed that uORF translation dampens CDS translational variability, with buffering capacity increasing in proportion to uORF efficiency, length, and number. We then compared the translatomes at different developmental stages of two Drosophila species, demonstrating that uORFs buffer mRNA translation fluctuations during both evolution and development. Experimentally, deleting a uORF in the bicoid (bcd) gene--a prominent example of translational buffering--resulted in extensive changes in gene expression and phenotypes in Drosophila melanogaster. Additionally, we observed uORF-mediated buffering between primates and within human populations. Together, our results reveal a novel regulatory mechanism by which uORFs stabilize gene translation during development and across evolutionary time.

evolutionary biology↗

bioRxiv2024

Molecular Signatures of Resilience to Alzheimer's Disease in Neocortical Layer 4 Neurons

Single-cell omics is advancing our understanding of selective neuronal vulnerability in Alzheimers disease (AD), revealing specific subtypes that are either susceptible or resilient to neurodegeneration. Using single-nucleus and spatial transcriptomics to compare neocortical regions affected early (prefrontal cortex and precuneus) or late (primary visual cortex) in AD, we identified a resilient excitatory population in layer 4 of the primary visual cortex expressing RORB, CUX2, and EYA4. Layer 4 neurons in association neocortex also remained relatively preserved as AD progressed and shared overlapping molecular signatures of resilience. Early in the disease, resilient neurons upregulated genes associated with synapse maintenance, synaptic plasticity, calcium homeostasis, and neuroprotective factors, including GRIN2A, RORA, NRXN1, NLGN1, NCAM2, FGF14, NRG3, NEGR1, and CSMD1. We also identified KCNIP4, which encodes a voltage-gated potassium (Kv) channel-interacting protein that interacts with Kv4.2 channels and presenilins, as a key factor linked to resilience. KCNIP4 was consistently upregulated in the early stages of pathology. Furthermore, AAV-mediated overexpression of Kcnip4 in a humanized AD mouse model reduced the expression of the activity-dependent genes Arc and c-Fos, suggesting compensatory mechanisms against neuronal hyperexcitability. Our dataset provides a valuable resource for investigating mechanisms underlying resilience to neurodegeneration.

neuroscience↗

bioRxiv2024

Multigenerational Proteolytic Inactivation of Restriction Upon Subtle Genomic Hypomethylation

Restriction-modification (R-M) systems, present in most bacterial genomes, protect against phage infection by detecting and degrading invading foreign DNA. However, like many prokaryotic anti-phage systems, R-M systems pose a significant risk of auto-immunity, exacerbated by the presence of hundreds to thousands of potential cleavage sites in the bacterial genome. In Pseudomonas aeruginosa, restriction inactivation upon growth at high temperatures was previously described, however, which system is being inactivated, the underlying mechanism, as well as the timing of recovery, remain unknown. Here, we report that P. aeruginosa Type I methyltransferase (HsdMS) and restriction endonuclease (HsdR) components are degraded by two Lon-like proteases when replicating above 41 {degrees}C, which induces partial genome hypomethylation and simultaneously prevents self-targeting, respectively. Interestingly, upon return to 37 {degrees}C, methyltransferase activity returns gradually, with restriction activity not fully recovering for over 60 bacterial generations, representing the longest bacterial memory to our knowledge. Forced expression of HsdR over the first 45 generations is toxic, demonstrating the fitness benefit of HsdR inactivation. Our findings demonstrate that type I R-M is tightly regulated post-translationally with a remarkable memory effect to ensure genomic stability and emphasize the importance of mitigating auto-toxicity for bacterial defense systems.

microbiology↗

bioRxiv2024

Identification and predictive machine learning models construction of gut microbiota associated with lymph node metastasis in colorectal cancer

This study focuses on the significant role between gut microbiota and lymph node metastasis (LNM) in colorectal cancer (CRC). By conducting 16S rRNA sequencing on fecal samples from 147 CRC patients and combining it with the linear discriminant analysis effect size (LEfSe) algorithm, we successfully identified significant differences in the gut microbiota between patients with LNM and those with none lymph node metastasis (NLNM). Furthermore, using transcriptome data from 9 CRC patients, we constructed an immune cell infiltration matrix to deeply explore the biological functions associated with LNM. Eventually, using the characteristics of the gut microbiota associated with LNM, we developed random forest (RF) and multilayer perceptron (MLP) machine learning models to predict the lymph node metastasis status of CRC patients. We identified 21 differentially abundant gut microbes between the two groups, among which Bacteroides plebeius, significantly enriched in LNM group, is closely related to the upregulation of resting NK cells and chemokine CXCL8 expression, and this bacterial species is also positively correlated with the enhancement of fructose metabolism. The RF and MLP models constructed based on the LNM-associated gut microbiota showed good predictive efficacy in predicting LNM status in CRC. This study reveals that Bacteroides plebeius may play an important role in the progression of CRC, with its mechanism potentially involving changes in immune modulation and metabolic pathways. The classification model constructed based on gut microbiota characteristics can predict LNM status of CRC, providing a new perspective for personalized and precision treatment of CRC patients. ImportanceThis study highlights the pivotal role of gut microbiota in lymph node metastasis (LNM) of CRC, identifying key microbial differences between LNM and NLNM patients. Our findings implicate Bacteroides plebeius in CRC progression via immune modulation and metabolic alterations. Moreover, machine learning models based on gut microbiota predict LNM status accurately, offering a novel approach for personalized CRC treatment.

microbiology↗

bioRxiv2024

Sm-site containing mRNAs can accept Sm-rings and are downregulated in Spinal Muscular Atrophy

Sm-ring assembly is important for the biogenesis, stability, and function of uridine-rich small nuclear RNAs (U snRNAs) involved in pre-mRNA splicing and histone pre-mRNA processing. Sm-ring assembly is cytoplasmic and dependent upon the Sm-site sequence and structural motif, ATP, and Survival motor neuron (SMN) protein complex. While RNAs other than U snRNAs were previously shown to associate with Sm proteins, whether this association follows Sm-ring assembly requirements is unknown. We systematically identified Sm-sites within the human and mouse transcriptomes and assessed whether these sites can accept Sm-rings. In addition to snRNAs, Sm-sites are highly prevalent in the 3 untranslated regions of long messenger RNAs. RNA immunoprecipitation experiments confirm that Sm-site containing mRNAs associate with Sm proteins in the cytoplasm. In modified Sm-ring assembly assays, Sm-site containing RNAs, from either bulk polyadenylated RNAs or those transcribed in vitro, specifically associate with Sm proteins in an Sm-site and ATP-dependent manner. In cell and animal models of Spinal Muscular Atrophy (SMA), mRNAs containing Sm-sites are downregulated, suggesting reduced Sm-ring assembly on these mRNAs may contribute to SMA pathogenesis. Together, this study establishes that Sm-site containing mRNAs can accept Sm-rings and identifies a novel mechanism for Sm proteins in regulation of cytoplasmic mRNAs. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/617433v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@d50f03org.highwire.dtl.DTLVardef@1cca1dforg.highwire.dtl.DTLVardef@1976fcaorg.highwire.dtl.DTLVardef@12c41d9_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

Genetic variation in the activity of a TREM2-p53 signaling axis determines oxygen-inducedlung injury

Bronchopulmonary dysplasia (BPD), a chronic lung disease, is the most common major complication of preterm birth. Supplemental oxygen administration, while lifesaving in the neonatal period, remains a key determinant of BPD pathophysiology. Exposure of the immature lung to increased levels of oxygen elicits an inflammatory response resulting in abnormal lung development. However, not every premature infant is equally sensitive to develop BPD. Using genetically diverse mouse strains, we show that the innate immune response activated in the lungs of mice sensitive to hyperoxia that develop BPD-like lung injury differs from mice resilient to disease. Specifically, we identified a selective upregulation of triggering receptor expressed on myeloid cells 2 (TREM2) on lung macrophages and monocytes in the hyperoxia-sensitive C57BL/6J mouse strain. We show that loss of function of TREM2 signaling in myeloid cells resulted in a dramatically improved phenotype after neonatal hyperoxia exposure characterized by a dampened immune response, preserved alveolar structure, and preserved cell proliferative potential supporting normal lung development. At the molecular level, inhibition of TREM2 signaling dampened the magnitude of p53 activation and resulted in cell cycle arrest instead of apoptosis. These findings show that TREM2 is a critical regulator of the pathogenic innate immune response to hyperoxia and highlight its importance as a potential therapeutic target for mitigating injury in the hyperoxia-exposed developing lung.

immunology↗

bioRxiv2024

Analysis of hepatic lentiviral vector transduction; implications on preclinical studies and clinical gene therapy protocols.

Lentiviral vector-transduced T-cells were approved by the FDA as gene therapy anti-cancer medications. Little is known about the host genetic variation effects on the safety and efficacy of the lentiviral vector gene delivery system. To narrow this knowledge-gap, we characterized hepatic gene delivery by lentiviral vectors across the Collaborative Cross (CC) mouse genetic reference population. For 24 weeks, we periodically measured hepatic luciferase expression from lentiviral vectors in 41 CC mouse strains. Hepatic and splenic vector copy numbers were determined. We report that CC mouse strains showed highly diverse outcomes following lentiviral gene delivery. For the first time, moderate correlation between mouse strain-specific sleeping patterns and transduction efficiency was observed. We associated two quantitative trait loci (QTLs) with intra-strain variations in transduction phenotypes, which mechanistically relates to the phenomenon of metastable epialleles. An additional QTL was associated with the kinetics of hepatic transgene expression. Genes comprised in the above QTLs are potential targets to personalize gene therapy protocols. Importantly, we identified two mouse strains that open new directions in characterizing continuous viral vector silencing and HIV latency. Our findings suggest that wide-range patient-specific outcomes of viral vector-based gene therapy should be expected. Thus, novel escalating dose-based clinical protocols should be considered.

genetics↗

bioRxiv2024

FLASH radiotherapy using high-energy X-rays: validation of the FLASH effect triggered by a compact single high-energy X-ray source device

PurposeThis preclinical study aimed to verify the FLASH effect of compact single high-energy X-ray source (CHEXs) and to explore whether three irradiations with single-gantry rotation two 30 s pauses can generate FLASH effect in mice. Materials and methodsThe absolute dose and pulsed beam of the CHEXs were measured using an EBTXD radiochromic film and fast current transformer. Healthy C57BL/6J female mice and a subcutaneous tumor model were irradiated under different conditions: sham (control), FLASH-RT (FLASH1: delivering the total dose in 1 fraction; FLASH3: delivering the total dose with two 30 second pauses to simulate a three-field delivery where the gantry rotation is occurring within 30 seconds), and conventional dose rate radiotherapy (CONV-RT). Various total doses were administered to the corresponding normal tissues (whole thorax, 30 Gy; whole abdomen, 12 Gy; and skin, 36 Gy) and tumors (CT26, 16.5 Gy; and LLC, 18 Gy). Survival status, normal tissue damage, and tumor growth suppression were recorded in each group. ResultsThe average dose rate of the CHEXs exceeded 40 Gy/s. For whole-thorax and skin irradiation, both FLASH1 and FLASH3 demonstrated protective effects. For whole-abdomen irradiation, FLASH1 exhibited a superior protective effect. No significant differences in tumor growth responses were observed between the FLASH1, FLASH3, and CONV-RT groups (P>0.05). ConclusionThis study confirmed that the FLASH effect could be triggered using CHEXs FLASH radiotherapy, and demonstrated that three irradiations with single gantry rotation two 30 s pauses can trigger the FLASH effect, indicating the potential benefit of CHEXs 3D conformal radiotherapy. Our findings indicate that further clinical trials on CHEXs are warranted.

cancer biology↗

bioRxiv2024

PIN2-mediated self-organizing transient auxin flow contributes to auxin maxima at the tip of Arabidopsis cotyledons

Directional auxin transport and formation of auxin maxima are critical for embryogenesis, organogenesis, pattern formation, and growth coordination in plants, but the mechanisms underpinning the initiation and establishment of these auxin dynamics are not fully understood. Here we show that a self-initiating and - terminating transient auxin flow along the marginal cells (MCs) contributes to the formation of an auxin maximum at the tip of Arabidopsis cotyledon that globally coordinates the interdigitation of puzzle-shaped pavement cells in the cotyledon epidermis. Prior to the interdigitation, indole butyric acid (IBA) is converted to indole acetic acid (IAA) to induce PIN2 accumulation and polarization in the marginal cells, leading to auxin flow toward and accumulation at the cotyledon tip. When IAA levels at the cotyledon tip reaches a maximum, it activates pavement cell interdigitation as well as the accumulation of the IBA transporter TOB1 in MCs, which sequesters IBA to the vacuole and reduces IBA availability and IAA levels. The reduction of IAA levels results in PIN2 down-regulation and cessation of the auxin flow. Hence, our results elucidate a self-activating and self-terminating transient polar auxin transport system in cotyledons, contributing to the formation of localized auxin maxima that spatiotemporally coordinate pavement cell interdigitation.

plant biology↗

bioRxiv2024

Hierarchical global and local auxin signals coordinate cellular interdigitation in Arabidopsis

The development of multicellular tissues requires both local and global coordination of cell polarization, however, the mechanisms underlying their interplay are poorly understood. In Arabidopsis, leaf epidermal pavement cells (PC) develop a puzzle-piece shape locally coordinated through apoplastic auxin signaling. Here we show auxin also globally coordinates interdigitation by activating the TIR1/AFB-dependent nuclear signaling pathway. This pathway promotes a transient maximum of auxin at the cotyledon tip, which then moves across the leaf activating local PC polarization, as demonstrated by locally uncaged auxin globally rescuing defects in tir1;afb1;afb2;afb4;afb5 mutant but not in tmk1;tmk2;tmk3;tmk4 mutants. Our findings show that hierarchically integrated global and local auxin signaling systems, which respectively depend on TIR1/AFB-dependent gene transcription in the nucleus and TMK-mediated rapid activation of ROP GTPases at the cell surface, control PC interdigitation patterns in Arabidopsis cotyledons, revealing a mechanism for coordinating a local cellular process with the development of whole tissues.

plant biology↗

bioRxiv2024

Prime editor-based high-throughput screening reveals functional synonymous mutations in the human genome

Synonymous mutations are generally considered neutral, while their roles in the human genome remain largely unexplored. Herein, we employed the PEmax system to create a library of 297,900 epegRNAs and performed extensive screening to identify synonymous mutations that impact cell fitness. While most synonymous mutations are neutral, we found that some can elicit phenotypic effects. By developing a specialized machine learning tool, we uncovered their impact on various biological processes such as mRNA splicing and transcription, supported by multifaceted experimental evidence. Notably, synonymous mutations can alter RNA folding and affect translation, as demonstrated by PLK1_S2. By integrating screening data with our model, we successfully predicted clinically deleterious synonymous mutations. This research deepens our understanding of synonymous mutations and provides insights for clinical disease studies.

genetics↗

bioRxiv2024

Deciphering the Immune Subtypes and Signature Genes: A Novel Approach Towards Diagnosing and Prognosticating Severe Asthma through Interpretable Machine Learning.

Asthma, a pervasive pulmonary disorder, affects countless individuals globally. Characterized by chronic inflammation of the bronchial passages, its symptoms include cough, wheezing, dyspnea, and chest tightness. While many manage their symptoms through pharmaceutical interventions and self-care, a significant subset grapples with severe asthma, posing therapeutic challenges. This study delves into the intricate etiology of asthma, emphasizing the pivotal roles of immune cells such as T cells, eosinophils, and mast cells in its pathogenesis. The recent emergence of monoclonal antibodies, including Mepolizumab, Reslizumab, and Benralizumab, offers therapeutic promise, yet their efficacy varies due to the heterogeneous nature of asthma. Recognizing the potential of personalized medicine, this research underscores the need for a comprehensive understanding of asthmas immunological diversity. We employ ssGSEA and LASSO algorithms to identify differentially expressed immune cells and utilize machine learning techniques, including XGBoost and Random Forest, to predict severe asthma outcomes and identify key genes associated with immune cells. Using a murine asthma model and an online database, we aim to elucidate distinct immune-centric asthma subtypes. This study seeks to provide novel insights into the diagnosis and classification of severe asthma through a transcriptomic lens.

bioinformatics↗

bioRxiv2024

Nuclear size-regulated emergence of topological packing order on growing human lung alveolospheres

Within multicellular living systems, cells coordinate their positions with spatiotemporal accuracy to form various structures, setting the clock to control developmental processes and trigger maturation. These arrangements can be regulated by tissue topology, biochemical cues, as well as mechanical perturbations. However, the fundamental rules of how local cell packing order is regulated in forming three-dimensional (3D) multicellular architectures remain unclear. Furthermore, how cellular coordination evolves during developmental processes, and whether this cell patterning behavior is indicative of more complex biological functions, is largely unknown. Here, using human lung alveolospheres as a model system, by combining experiments and numerical simulations, we find that, surprisingly, cell packing behavior on alveolospheres resembles hard-disk packing but with increased randomness; the stiffer cell nuclei act as the hard disks surrounded by deformable cell bodies. Interestingly, we observe the emergence of topological packing order during alveolosphere growth, as a result of increasing nucleus-to-cell size ratio. Specifically, we find more hexagon-concentrated cellular packing with increasing bond orientational order, indicating a topological gas-to-liquid transition. Additionally, by osmotically changing the compactness of cells on alveolospheres, we observe that the variations in packing order align with the change of nucleus-to-cell size ratio. Together, our findings reveal the underlying rules of cell coordination and topological phases during human lung alveolosphere growth. These static packing characteristics are consistent with cell dynamics, together suggesting that better cellular packing stabilizes local cell neighborhoods and may regulate more complex biological functions such as organ development and cellular maturation.

biophysics↗

bioRxiv2024

The evolutionary history of the ancient weevil family Belidae (Coleoptera: Curculionoidea) reveals the marks of Gondwana breakup and major floristic turnovers, including the rise of angiosperms

The rise of angiosperms to ecological dominance and the breakup of Gondwana during the Mesozoic marked major transitions in the evolutionary history of insect-plant interactions. To elucidate how contemporary trophic interactions were influenced by host plant shifts and palaeogeographical events, we integrated molecular data with information from the fossil record to construct a timetree for ancient phytophagous weevils of the beetle family Belidae. Our analyses indicate that crown-group Belidae originated approximately 138 Ma ago in Gondwana, associated with Pinopsida (conifer) host plants, with larvae likely developing in dead/decaying branches. Belids tracked their host plants as major plate movements occurred during Gondwanas breakup, surviving on distant, disjunct landmasses. Some belids shifted to Angiospermae and Cycadopsida when and where conifers declined, evolving new trophic interactions, including brood-pollination mutualisms with cycads and associations with achlorophyllous parasitic angiosperms. Extant radiations of belids in the genera Rhinotia (Australian region) and Proterhinus (Hawaiian Islands) have relatively recent origins.

evolutionary biology↗