Biology subjects

Yang, Q.

Publications and source records attributed to Yang, Q..

At least 271 records · Page 15Linked to original sources

bioRxiv2022

Novel leaf-root coordination driven by leaf water storage tissues in mangroves

Interactions among root and leaf traits (in particular, leaf hydraulic and leaf economics traits) are fundamental in generating diverse strategies in land plants, yet it remains a knowledge gap in mangrove plants that experiences saline stress distinct from most other vascular plants. Here, we tested the trait relationships in mangrove plants and compared them with typical land plants (non-mangrove). Consistent with non-mangrove plants, leaf hydraulic and economics traits were decoupled in mangrove plants. However, mangrove leaf economics traits correlated strongly with root hydraulic traits, which are normally decoupled in non-mangrove plants. Moreover, we observed a unique scaling relationship between leaf dry mass per area and root hydraulic traits in mangroves. The novel coordination between leaves and roots arises from the wide-presence of leaf water storage tissues in mangroves, and this potentially represents a new paradigm with which we look into the ecology, physiology and evolution of this important vegetation.

ecology↗

bioRxiv2022

ADOLESCENT EXPOSURE TO LOW-DOSE THC DISRUPTS ENERGY BALANCE AND ADIPOSE ORGAN HOMEOSTASIS IN ADULTHOOD

One of cannabis most iconic effects is the stimulation of hedonic high-calorie eating - the munchies - yet habitual cannabis users are on average leaner than non-users. We asked whether this unexpected phenotype might result from lasting changes in energy balance established during adolescence, when habitual use of the drug often begins. We found that daily low-dose administration of cannabis intoxicating constituent, {Delta}9-tetrahydrocannabinol (THC), to adolescent mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, and enhanced thermogenesis. Multi-omics analyses revealed that this phenotype is associated with multiple molecular anomalies in the adipose organ, which include ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring pseudo-lean state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.

pharmacology and toxicology↗

bioRxiv2022

Canonical Wnt Signaling Maintains Human Mesenchymal Progenitor Cell Multipotency During Adipose Tissue Development

Tissue development and repair throughout life depends on the availability of multipotent mesenchymal stem/progenitor cells capable of differentiating into specialized cell types. How an appropriately sized pool of such multipotent progenitors is maintained under varied signals for tissue growth and repair is unknown. We addressed this question by monitoring fate trajectories of human adipose tissue-derived multipotent progenitor cells using single-cell transcriptomics. Homogenous multipotent progenitors underwent two distinct fate trajectories rapidly upon induction of adipose differentiation- one toward the adipocyte fate, and the other towards a distinct, non-differentiated state characterized by up-regulation of canonical Wnt target genes. Upon isolation, this latter cell population was able to resume proliferation and display multipotency. Using canonical Wnt agonists and antagonists we find Wnt signaling is required for the maintenance of this multipotent pool under differentiation stimulus. In vivo, these cells are retained in adipose tissue developed from human multipotent progenitor cells in immunocompromised mice, and their transcriptomic signature is detected in human adult adipose tissue. Our study reveals a previously unrecognized mechanism for maintaining a functional pool of human mesenchymal progenitor cells under conditions of differentiation pressure, driven by Wnt signaling.

developmental biology↗

bioRxiv2022

Integrated microprism and micro-electrode array for chronic in vivo two-photon imaging and electrophysiology across all cortical layers

Electrophysiology is a vital tool in neuroscience research with increasing translational value. It is used to record or modulate neuronal activity with high temporal but lower spatial resolution. Optical technologies, such as two-photon microscopy (TPM) can complement electrophysiological recordings with large-scale imaging at cellular resolution. Combining these two provides a powerful platform to elucidate and coordinate multimodal functions. Prior attempts have been limited to the superficial brain from a top-down optical view. Here, we describe a novel combination of transparent microelectrode arrays (MEAs) with glass microprisms for simultaneous electrophysiology and optical imaging of all cortical layers in a vertical plane. We tested our device in Thy1-GCaMP6 mice for over 4 months and demonstrated its capability for multisite single-unit recording, microstimulation, and simultaneous TPM calcium imaging. Using this setup, we reveal how amplitude, frequency, and depth of microstimulation impact neural activation patterns across the cortical column. This work presents a multimodal tool that extends integrated electrophysiology and optical imaging from the superficial brain to the whole cortical column, opening new avenues of neuroscience research and neurotechnology development.

bioengineering↗

bioRxiv2022

Neutrophils reprograms the bone marrow to impair T-cell immunity during tuberculosis

Mycobacterium tuberculosis (Mtb) infection induces persistent influx of neutrophils that associates with poor bacterial control and clinical outcome from tuberculosis (TB). Although implicated in TB pathology, the mechanism by which these cells contribute to pathogenesis is poorly understood. Using Cell-DIVE multiplexed immunofluorescence imaging and spatial analysis of inflammatory TB lesions, we demonstrated that persistent neutrophil infiltration affects the spatiotemporal organization of T-lymphocytes and impairs their function. Instead of directly suppressing T-cells, neutrophils produce granulocyte colony stimulating factor (CSF3/G-CSF) that collaborates with type I interferon (IFN-I) to promote a granulocyte-skewed hematopoiesis impacting T-lymphocyte production. Importantly, neutrophil-intrinsic IFN-I receptor 1 (IFNAR1) is both necessary and sufficient to promote pathologic granulopoiesis. Finally, inhibition of IFNAR1-signaling alone mitigates immunopathogenesis by restoring hematopoietic equilibrium. Collectively, our work uncovers a potential immunevasion strategy by which virulent Mtb strains induce IFN-I to generate pathogen-permissive neutrophils that produce G-CSF and sustain pathogenic hematopoiesis to impair T-cell immunity during TB.

immunology↗

bioRxiv2022

Single-shot Volumetric Chemical Imaging by Mid- Infrared Photothermal Fourier Light Field Microscopy

Three-dimensional molecular imaging of living organisms and cells plays a significant role in modern biology. Yet, current volumetric imaging modalities are largely fluorescence-based and thus lack chemical content information. Mid-infrared photothermal microscopy as a new chemical imaging technology provides infrared spectroscopic information at sub-micrometer spatial resolution. Here, by harnessing thermosensitive fluorescent dyes to sense the mid-infrared photothermal effect, we demonstrate mid-infrared photothermal Fourier light field (MIP-FLF) microscopy for single-shot volumetric infrared spectroscopic imaging at the speed of 8 volumes per second and sub-micron spatial resolution. Protein contents in bacteria and lipid droplets in living pancreatic cancer cells are visualized. Altered lipid metabolism in drug-resistant pancreatic cancer cells is observed with the MIP-FLF microscope.

biochemistry↗

bioRxiv2022

Nanotopography modulates intracellular excitable systems through cytoskeleton actuation

Cellular sensing of most environmental cues involves receptors that affect a signal-transduction excitable network (STEN), which is coupled to a cytoskeletal excitable network (CEN). We show that the mechanism of sensing of nanoridges is fundamentally different. CEN activity occurs preferentially on nanoridges, whereas STEN activity is constrained between nanoridges. In the absence of STEN, waves disappear, but long-lasting F-actin puncta persist along the ridges. When CEN is suppressed, wave propagation is no longer constrained by nanoridges. A computational model reproduces these experimental observations. Our findings indicate that nanotopography is sensed directly by CEN, whereas STEN is only indirectly affected due to a CEN-STEN feedback loop. These results explain why texture sensing is robust, and acts cooperatively with multiple other guidance cues in complex microenvironments. One-Sentence SummaryCells sense nanotopography directly through their cytoskeletal dynamics, in a reversal of traditional signaling pathway hierarchies.

biophysics↗

bioRxiv2022

Neutralization of Omicron sublineages and Deltacron SARS-CoV-2 by 3 doses of BNT162b2 vaccine or BA.1 infection

Distinct SARS-CoV-2 Omicron sublineages have evolved showing increased fitness and immune evasion than the original Omicron variant BA.1. Here we report the neutralization activity of sera from BNT162b2 vaccinated individuals or unimmunized Omicron BA.1-infected individuals against Omicron sublineages and "Deltacron" variant (XD). BNT162b2 post-dose 3 immune sera neutralized USA-WA1/2020, Omicron BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and XD-spike SARS-CoV-2s with geometric mean titers (GMTs) of 1335, 393, 298, 315, 216, 103, and 301, respectively; thus, BA.4/5 SARS-CoV-2 spike variant showed the highest propensity to evade vaccine neutralization compared to the original Omicron variants BA.1. BA.1-convalescent sera neutralized USA-WA1/2020, BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and Deltacron-spike SARS-CoV-2s with GMTs of 15, 430, 110, 109, 102, 25, and 284, respectively. The low neutralization titers of vaccinated sera or convalescent sera from BA. 1 infected individuals against the emerging and rapidly spreading Omicron BA.4/5 variants provide important results for consideration in the selection of an updated vaccine in the current Omicron wave.

microbiology↗

bioRxiv2022

Privacy-preserving integration of multiple institutional data for single-cell type identification with scPrivacy

The rapid accumulation of large-scale single-cell RNA-seq datasets from multiple institutions presents remarkable opportunities for automatically cell annotations through integrative analyses. However, the privacy issue has existed but being ignored, since we are limited to access and utilize all the reference datasets distributed in different institutions globally due to the prohibited data transmission across institutions by data regulation laws. To this end, we present scPrivacy, which is the first and generalized automatically single-cell type identification prototype to facilitate single cell annotations in a data privacy-preserving collaboration manner. We evaluated scPrivacy on a comprehensive set of publicly available benchmark datasets for single-cell type identification to stimulate the scenario that the reference datasets are rapidly generated and distributed in multiple institutions, while they are prohibited to be integrated directly or exposed to each other due to the data privacy regulations, demonstrating its effectiveness, time efficiency and robustness for privacy-preserving integration of multiple institutional datasets in single cell annotations.

bioinformatics↗

bioRxiv2022

Mitochondrial genome recovery by ATFS-1 is essential for development following starvation

Nutrient availability regulates the C. elegans life cycle as well as mitochondrial physiology. Food deprivation significantly reduces mitochondrial genome (mtDNA) number and leads to aging-related phenotypes. Here, we demonstrate that the bZIP protein ATFS-1, a mediator of the mitochondrial unfolded protein response (UPRmt), is required to promote growth and establish a functional germline following prolonged starvation. Surprisingly, we found that the recovery of mtDNA copy number and development following starvation required mitochondrial-localized ATFS-1 but not its nuclear transcription activity. Lastly, we found that the insulin-like receptor DAF-2, functions upstream of ATFS-1 to modulate mtDNA content. We demonstrate that reducing DAF-2 activity represses ATFS-1 nuclear function while causing an increase in mtDNA content partly mediated by mitochondrial-localized ATFS-1. Combined, our data indicate the importance of the UPRmt in recovering mitochondrial mass and suggests that atfs-1-dependent mtDNA replication precedes mitochondrial network expansion following starvation.

cell biology↗

bioRxiv2022

Dendritic cell Piezo1 integrating mechanical stiffness and inflammatory signals directs the differentiation of TH1 and Treg cells in cancer

Dendritic cells (DCs) play an important role in anti-tumor immunity by inducing T cell differentiation. Herein, we found that the mechanical sensor Piezo1 expressed by DCs integrates innate inflammatory stimuli and stiffness signals and directs the reciprocal differentiation of TH1 and regulatory T (Treg) cells in cancer. Genetic deletion of Piezo1 in DCs inhibited the generation of TH1 cells while driving the development of Treg cells in promoting cancer growth. Mechanistically, Piezo1-deficient DCs regulated the secretion of the polarizing cytokines TGF{beta}1 and IL-12, leading to increased TGF{beta}R2-p-Smad3 activity and decreased IL-12R{beta}2-p-STAT4 activity while inducing the reciprocal differentiation of Treg and TH1 cells. In addition, Piezo1 integrated the SIRT1-hypoxia-inducible factor-1 alpha (HIF1)-dependent metabolic pathway and calcium-calcineurin-NFAT signaling pathway to orchestrate reciprocal TH1 and Treg lineage commitment through DC-derived IL-12 and TGF{beta}1. Our studies provide critical insight for understanding the role of the DC-based mechanical regulation of immunopathology in directing T cell lineage commitment in tumor microenvironments.

immunology↗

bioRxiv2022

Lipidomic change in Aedes aegypti female following blood feeding reveals similar changes in functionally related lipids

We conducted a lipidomic analysis of the whole body of female Aedes aegypti mosquitoes at different time points over the course of feeding and reproduction. There were temporal biphasic increases of more than 80% of lipids identified at the time of feeding and from 16 h to 30 h post blood meal. During these two increases, the abundance of many lipids dropped while body weight remained stable, probably reflecting blood lipid digestion and the synthesis of vitellogenin in this period. A concerted temporal pattern was particularly strong at the second peak for membrane and signalling lipids such as PE, PI, CL, HexCer and LPA. Lyso-glycerophospholipids showed three distinct change patterns which are functionally related: LPE and LPC, which are membrane lipids, showed little change; LPA, a signalling lipid, showed a dramatic increase from 16 to 30 h PBM; LPI, a bioactive lipid, and both LPG and LPS which are bacterial membrane lipids, showed one significant increase from the time of feeding to 16 hours post blood meal. The result of our study on the anautogenous insect Ae. aegypti point to specific lipids likely to be important in the reproductive process with a role in the formation and growth of ovarian follicles.

biochemistry↗

bioRxiv2022

Wolbachia inhibits ovarian formation and increases blood avidity in female Aedes aegypti-a novel time-specific reproductive alteration

Wolbachia, a gram-negative endosymbiotic bacterium widespread in arthropods, is well-known for changing the reproduction of its host in ways that increase its rate of spread, but there are also costs to hosts that can reduce this. Here we investigated a novel reproductive alteration of Wolbachia wAlbB on its mosquito host Aedes aegypti, based on studies of mosquito life history traits, ovarian dissections and gene expression assays. We found that an extended period of the larval stage as well as the egg stage, as previously shown, can increase the proportion of Wolbachia-infected females that become infertile; the impact of Wolbachia on infertility therefore accumulated before pupation. We found that ovarian formation was blocked in infertile females, even though infected females had relatively lower Wolbachia densities than fertile infected females. Infertile females also showed a higher frequency of blood feeding following a prior blood meal, indicating that they do not enter a complete gonotrophic cycle. Treatments leading to infertility decreased expression of genes related to reproduction. Our results demonstrate effects related to the causes and consequences of infertile wAlbB-infected Ae. aegypti females with implications for Wolbachia releases and have evolutionary implications for Wolbachia infections in novel hosts.

microbiology↗

bioRxiv2022

The senescence regulator S40 family members from Caragana intermedia and Arabidopsis thaliana inhibit leaf senescence via promoting cytokinins synthesis

Leaf senescence is regulated by both endogenous hormones and environmental stimuli in a programmed and concerted way. The members of the S40 family have been reported to play roles in leaf senescence. Here we report that overexpression of an S40 family member from Caragana intermedia, CiS40-11, delayed the leaf senescence. Phylogenetic analysis revealed that the CiS40-11 protein had the highest identity with AtS40-5 and AtS40-6 of A. thaliana. CiS40-11 was highly expressed in leaves and was down-regulated after dark treatment. The subcellular localization analysis showed that CiS40-11 was a cytoplasm-nucleus dual-localized protein. Leaf senescence was delayed in CiS40-11 transgenic A. thaliana or by its transient expression in C. intermedia. Transcriptomic analysis and endogenous hormones assay revealed that CiS40-11 inhibited leaf senescence via promoting the biosynthesis of cytokinins, through blocking AtMYB2 expression in CiS40-11 overexpression lines. Furthermore, in the ats40-5a and ats40-6a mutants, AtMYB2 expression was increased and their leaves exhibited a premature senescence phenotype. Our results show that CiS40-11 (and its orthologs, AtS40-5 and AtS40-6) promoted cytokinin synthesis by inhibiting the expression of MYB2 and releasing its negative regulation on the expression of IPTs to inhabit leaf senescence. HighlightThe senescence regulator S40 family members CiS40-11, AtS40-5 and AtS40-6 are induced by light and inhibition leaf senescence by promoting cytokinin synthesis.

plant biology↗

bioRxiv2022

Genetic surveillance of SARS-CoV-2 Mpro reveals high sequence and structural conservation prior to the introduction of protease inhibitor Paxlovid

SARS-CoV-2 continues to represent a global health emergency as a highly transmissible, airborne virus. An important coronaviral drug target for treatment of COVID-19 is the conserved main protease (Mpro). Nirmatrelvir is a potent Mpro inhibitor and the antiviral component of Paxlovid. The significant viral sequencing effort during the ongoing COVID-19 pandemic represented a unique opportunity to assess potential nirmatrelvir escape mutations from emerging variants of SARS-CoV-2. To establish the baseline mutational landscape of Mpro prior to the introduction of Mpro inhibitors, Mpro sequences and its cleavage junction regions were retrieved from [~]4,892,000 high-quality SARS-CoV-2 genomes in GISAID. Any mutations identified from comparison to the reference sequence (Wuhan-hu-1) were cataloged and analyzed. Mutations at sites key to nirmatrelvir binding and protease functionality (e.g., dimerization sites) were still rare. Structural comparison of Mpro also showed conservation of key nirmatrelvir contact residues across the extended Coronaviridae family (alpha-, beta-, and gamma-coronaviruses). Additionally, we showed that over time the SARS-CoV-2 Mpro enzyme remained under purifying selection and was highly conserved relative to the spike protein. Now, with the EUA approval of Paxlovid and its expected widespread use across the globe, it is essential to continue large-scale genomic surveillance of SARS-CoV-2 Mpro evolution. This study establishes a robust analysis framework for monitoring emergent mutations in millions of virus isolates, with the goal of identifying potential resistance to present and future SARS-CoV-2 antivirals. ImportanceThe recent authorization of oral SARS-CoV-2 antivirals, such as Paxlovid, has ushered in a new era of the COVID-19 pandemic. Emergence of new variants, as well as selective pressure imposed by antiviral drugs themselves, raise concern for potential escape mutations in key drug binding motifs. To determine the potential emergence of antiviral resistance in globally circulating isolates and its implications for the clinical response to the COVID-19 pandemic, sequencing of SARS-CoV-2 viral isolates before, during, and after the introduction of new antiviral treatments is critical. The infrastructure built herein for active genetic surveillance of Mpro evolution and emergent mutations will play an important role in assessing potential antiviral resistance as the pandemic progresses and Mpro inhibitors are introduced. We anticipate our framework to be the starting point in a larger effort for global monitoring of the SARS-CoV-2 Mpro mutational landscape.

genomics↗

bioRxiv2022

Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine

The newly emerged Omicron SARS-CoV-2 has 3 distinct sublineages: BA.1, BA.2, and BA.3. BA.1 accounts for the initial surge and is being replaced by BA.2, whereas BA.3 is at a low prevalence at this time. Here we report the neutralization of BNT162b2-vaccinated sera (collected at 1 month after dose 3) against the three Omicron sublineages. To facilitate the neutralization testing, we engineered the complete BA.1, BA.2, or BA.3 spike into an mNeonGreen USA-WA1/2020 SRAS-CoV-2. All BNT162b2-vaccinated sera neutralized USA-WA1/2020, BA.1-, BA.2-, and BA.3-spike SARS-CoV-2s with titers of >20; the neutralization geometric mean titers (GMTs) against the four viruses were 1211, 336, 300, and 190, respectively. Thus, the BA.1-, BA.2-, and BA.3-spike SARS-CoV-2s were 3.6-, 4.0-, and 6.4-fold less efficiently neutralized than the USA-WA1/2020, respectively. Our data have implications in vaccine strategy and understanding the biology of Omicron sublineages.

microbiology↗

bioRxiv2022

Microglial Piezo1 senses Aβ fibrils stiffness to restrict Alzheimer's disease

The pathology of Alzheimers disease (AD) is associated with the extracellular amyloid-{beta} (A{beta}) plaques that perturb the mechanical properties of brain tissue. Microglia sense and integrate biochemical cues in their local microenvironment, intimate linking with AD progress. However, neither the microglial mechanosensing pathway nor its impact on AD pathogenesis is well studied. Here, we showed that the mechanosensitive ion channel Piezo1 is increased in microglia upon stiffness stimuli of A{beta} fibrils. The upregulation of Piezo1 in A{beta} plaque-associated microglia was observed in AD mouse models and human patients. Microglia lacking Piezo1 disturbed microglial clustering, phagocytosis, and compaction of A{beta} plaques, resulting in the exacerbation of A{beta} and neurodegenerative pathologies in AD. Conversely, pharmacological activation of Piezo1 ameliorated brain A{beta} burden and cognitive impairment in the 5xFAD mouse. Together, our results reveal Piezo1, as a mechanosensor of A{beta} fibrils stiffness in microglia, could represent a promising therapeutic target for AD.

neuroscience↗

bioRxiv2022

Temporal and spatial dynamics mapping reveals follicle development regulated by different stromal cell populations

Follicle development is a complex dynamic process. The follicles are encapsulated in the stroma, and once the follicle develops, the follicle moves from the cortex to the medulla and finally to the cortex to ovulate in the process of continuous growth. Many of these processes cannot be explained with the follicle alone. Through single-cell and spatial transcriptome sequencing at key time points of follicular development in mice after birth, we found that ovarian stromal cells are not only one of the main cell groups that make up the ovary but that their cell population and spatial location are also closely related to follicular development. Through analysis of cell communication, it was found that ovarian stromal cells were the main transmitters of intercellular communication, and many of the signals they sent were received by granulosa cells and oocytes to participate in follicle development. Ovarian stromal cells are not a homogeneous cell population. We combined single cell types with their spatial location information to divide ovarian stromal cells into four types, namely, structural stromal cells, perifollicular stromal cells, stromal progenitor cells, and steroidogenic stromal cells, each of which plays a different function in follicle development. Indepth studies of the different spatial locations and different types of stromal cells will expand our understanding of follicle development dynamics, leading to new targets and novel approaches for the treatment of ovarian-related diseases.

developmental biology↗