Biology subjects

Liu, H.

Publications and source records attributed to Liu, H..

At least 613 records · Page 34Linked to original sources

bioRxiv2022

Preference of CAMSAP3 for microtubules with expanded lattice contributes to stabilization of the minus end

CAMSAPs are proteins that show microtubule minus-end-specific localization, decoration and stabilization. Although the mechanism for minus-end recognition via their C-terminal CKK domain has been well described in recent studies, it is unclear how CAMSAPs stabilize microtubules. Our several binding assays revealed that D2 region of CAMSAP3 specifically binds to microtubules with the expanded lattice. To investigate the relationship between this preference and the stabilization effect of CAMSAP3, we precisely measured individual microtubule lengths and found that D2-binding expanded the microtubule lattice by [~]3%. Consistent with the notion that the expanded lattice is a common feature of stable microtubules, the presence of D2 slowed the microtubule depolymerization rate to approximately 1/20, suggesting that the D2-triggered lattice expansion stabilizes microtubules. Combining these results, we propose that CAMSAP3 stabilizes microtubules by lattice expansion upon D2-binding, which further accelerates the recruitment of other CAMSAP3 molecules. Since only CAMSAP3 has D2 and the highest microtubule stabilizing effect among mammalian CAMSAPs, our model also explains the molecular basis for the functional diversity of CAMSAP family members. Summary blurbD2 region in CAMSAP3 preferentially bound to expanded microtubule lattices and also induced lattice expansion, explaining the molecular functions of CAMSAP3.

biophysics↗

bioRxiv2022

Detection of Frog virus 3 via the system integrating RPA-CRISPR/Cas12a-SPM with deep learning

Frog virus 3 (FV3, genera Ranavirus, family Iridoviridae), a double-stranded DNA virus, results in irreparable damage to biodiversity and significant economic losses to aquaculture. Although the existing FV3 detection methods are of high sensitivity and specificity, the complex procedure and requirement of expensive instruments limit their practical implantation. Herein, we develop a fast, easy-to-implement, highly sensitive, and point-of-care (POC) detection system for FV3. Combining recombinase polymerase amplification (RPA) and CRISPR/Cas12a, we achieve a limit of detection (LoD) of 100 aM (60.2 copies/L) by optimizing RPA primers and CRISPR RNAs (crRNAs). For POC detection, we build a smartphone microscopy (SPM) and achieve an LoD of 10 aM within 40 minutes. Four positive animal-derived samples with a quantitation cycle (Cq) value of quantitative PCR (qPCR) in the range of 13 to 32 are detectable by the proposed system. In addition, we deploy deep learning models for binary classification (positive or negative samples) and multiclass classification (different concentrations of FV3 and negative samples), achieving 100% and 98.75% accuracy, respectively. Without temperature regulation and expensive equipment, RPA-CRISPR/Cas12a combined with a smartphone readout and artificial intelligence (AI) assisted classification shows great potential for FV3 detection. This integrated system holds great promise for POC detection of aquatic DNA pathogens. HighlightsO_LIAn integrated DNA detection system is developed by combining RPA, CRISPR/Cas12a, smartphone microscopy, and deep learning. C_LIO_LIThe LoD of frog virus 3 is 10 aM within 40 min. C_LIO_LIThe detection system shows good performance on animal-derived samples. C_LI

molecular biology↗

bioRxiv2022

Pre-symptomatic reduction of individuality in the App NL-F knock-in model of Alzheimer's disease

While one third of the risk for Alzheimers disease (AD) is explained by environment and lifestyle, AD pathology also affects individual lifestyle, possibly long before clinical manifestation of dementia. To study this hidden disease effect with its potentially large impact on coping with AD, we examined in mice how the AppNL-F/NL-F (NL-F) knock-in mutation affects the pre-symptomatic response to environmental enrichment (ENR). We assessed the emergence of inter-individual phenotypic variation while both genetic background and the shared environment were held constant, thereby isolating the contribution of individual behavior ( non-shared environment). After 4 months of ENR, in NL-F both mean and variability of plasma ApoE were increased, suggesting a pre-symptomatic variation in pathogenic processes. Roaming entropy (RE) as a measure of behavioral activity was continuously assessed with radiofrequency identification (RFID) technology and revealed reduced habituation and variance in NL-F compared to controls. Intra-individual variation decreased but behavioral predictability and stability were reduced in NL-F. Seven months after discontinuation of ENR we found no difference in plaque size and number, but ENR increased variance in hippocampal plaque counts in NL-F. A reactive increase in adult hippocampal neurogenesis in NL-F, known from other models, was normalized by ENR. Our data suggest that, while NL-F has early effects on individual behavioral patterns in response to ENR, there are lasting effects at the level of cellular plasticity even after discontinuation of ENR. Hence, early behavior matters for maintaining individual behavioral trajectories and brain plasticity even under maximally constraint conditions.

neuroscience↗

bioRxiv2022

Dynamics, signals and influencing factors of CD4 T cell activation revealed by single cell RNA-seq

T cell activation is a key event in adaptive immunity. However, factors affecting T cell activation have not been systematically analyzed. Here, we analyzed stimulated CD4 T cells with anti-CD3/CD28 under several conditions to explore the factors affecting T cell activation. We defined stimulated T overlapped with resting T on UMAP as inert T. Inert T expressed activated T specific genes and cytokines, indicating it is a special functional state. Stimulated T derived from peripheral CD4 T has higher fraction of effector T (TEFF) while stimulated T derived from CD4 TN has higher fraction of proliferation T and interferon highly expressed T (IFNhi T). CD4 T was more likely to differentiate into TEFF and less likely to differentiate into heat shock protein specific T (HSPhi T) and IFNhi T in the presence of CD8 T. Interestingly, CXCR4low T responded to stimulation more efficiently than CXCR4hi T. These information facilitates we design stimulation to obtain ideal activated T.

immunology↗

bioRxiv2022

IL-12/18/21 pre-activation enhances the anti-tumor efficacy of expanded γδT cells and overcomes resistance to anti-PD-L1 treatment

{gamma}{delta}T cells are promising candidates for cellular immunotherapy due to their immune regulation through cytokine production and MHC-independent direct cytotoxicity against a broad spectrum of tumors. However, current {gamma}{delta}T cell-based cancer immunotherapy has limited efficacies and novel strategies are needed to improve its clinical outcomes. Here, we report that cytokine pre-treatment with IL-12/18, IL-12/15/18, IL-12/18/21 and IL-12/15/18/21 could effectively enhance the activation and cytotoxicity of in vitro expanded murine and human {gamma}{delta}T cells. However, only adoptive transfer of IL-12/18/21 pre-activated {gamma}{delta}T cells significantly inhibited tumor growth in a murine melanoma model and a hepatocellular carcinoma model. Both IL-12/18/21 pre-activated antibody-expanded and zoledronate-expanded human {gamma}{delta}T cells effectively controlled tumor growth in a humanized mouse model. IL-12/18/21 pre-activation promoted {gamma}{delta}T cell proliferation and cytokine production in vivo and enhanced IFN-{gamma} and TNF- production, as well as granzyme B expression by endogenous CD8+ T cells in a cell-cell contact dependent manner. Furthermore, the adoptive transfer of IL-12/18/21 pre-activated {gamma}{delta}T cells could overcome the resistance to anti-PD-L1 therapy, and the combination therapy had a synergistic effect on the therapeutic outcomes. Moreover, the enhanced anti-tumor function of adoptively transferred IL-12/18/21 pre-activated {gamma}{delta}T cells was largely diminished in the absent of endogenous CD8+T cells when administered alone or in combination with anti-PD-L1, suggesting a CD8+T cell-dependent mechanism. Taken together, IL-12/18/21 pre-activation could promote {gamma}{delta}T cell anti-tumor function and overcome the resistance to checkpoint blockade therapy, indicating an effective combinational cancer immunotherapeutic strategy. SynopsisO_LIIL-12/18/21 pre-activation enhances the anti-tumor efficacy of adoptively transferred {gamma}{delta}T cells by promoting its proliferation, activation, and cytotoxicity, as well as activating endogenous CD8+ T cells. C_LIO_LIAdoptive transfer of IL-12/18/21 pre-activated {gamma}{delta}T cells could overcome the resistance to anti-PD-L1 therapy, indicating an effective combinational cancer immunotherapeutic strategy. C_LI

immunology↗

bioRxiv2022

A unique peptide recognition mechanism by the human relaxin family peptide receptor 4 (RXFP4)

Members of the insulin superfamily regulate a variety of biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and relaxin/insulin-like peptides. The latter bind to the human relaxin family peptide receptors (RXFPs), which are class A G protein-coupled receptors (GPCRs), to exert pleiotropic actions. Here, we report three cryo-electron microscopy structures of RXFP4-Gi protein complexes in the presence of the endogenous ligand insulin-like peptide 5 (INSL5) or one of the two small molecule agonists, compound 4 and DC591053, both were discovered through medicinal chemistry efforts. The B chain of INSL5 adopts a single -helix that penetrates into the orthostatic pocket, while the A chain sits above the orthosteric pocket to interact with the extracellular surface of RXFP4, revealing a unique peptide-binding mode previously unknown. Together with mutagenesis and functional analyses, the key determinants responsible for the peptidomimetic agonism and subtype selectivity were identified. DC591053 selectively mimicked the action of INSL5 at RXFP4 whereas compound 4 activated both RXFP3 and RXFP4. Comparison of peptide binding modes within the insulin superfamily displayed diverse interaction mechanisms distinct to each type of the peptides. Our findings not only provide valuable insights into ligand recognition and subtype selectivity among class A GPCRs, but also expand the knowledge of signaling mechanisms in the insulin superfamily.

molecular biology↗

bioRxiv2022

Myostatin gene deletion alters gut microbiota stimulating fast-twitch glycolytic muscle growth

The host genome may influence the composition of the intestinal microbiota, and intestinal microbiota performs an important role in muscle growth and development. Here, we showed that Myostatin (MSTN), a key factor for muscle growth, deletion alters muscularis, plica, and intestinal barrier in pigs. Mice transplanted with MSTN-/- pig intestinal flora showed increase in the cross-sectional area of myofibers and fast-twitch glycolytic muscle mass. The microbes responsible for the production of short chain fatty acids (SCFAs) were enriched in both MSTN-/- pigs and recipient mice, and SCFAs levels were elevated in the colon contents. We demonstrated that valeric acid can stimulate type IIb myofiber growth by activation of the Akt/mTOR pathway via GPR43 and improve muscle atrophy induced by dexamethasone. This is the first study to identify the MSTN gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.

microbiology↗

bioRxiv2022

Structural basis of a high-affinity antibody binding to glycoprotein region with consecutive glycosylation sites

Consecutive glycosylation sites occur in both self and viral proteins. Glycan-shielding of underneath peptide region is a double-edged sword, that avoids immune attack to self-proteins, but helps viruses including HIV-1 and SARS-CoV2 to escape antibody binding. Here we report a high-affinity antibody, 16A, binding to linear peptide containing consecutive glycosylation sites. Co-crystallization of 16A Fab and glycopeptides with GalNAc modifications at different sites showed that STAPPAHG is the sequence recognized by 16A antibody. GalNAc modification at Threonine site on STAPPAHG sequence significantly increased the affinity of Fab binding by 30.6 fold (KD=6.7nM). The increased affinity is conferred by hydrophilic and pi-stacking interactions between the GalNAc residue on Threonine site and a Trp residue from the CDR1 region of the heavy chain. Furthermore, molecular modeling suggested that GalNAc on T site causes more favorable conformation for antibody binding. These results showed that glycan modification most proximal to linear peptide core epitope significantly increases antigenicity of a glycopeptide epitope. The antibody recognition mode by peptide-binding CDR groove with a glycan-binding edge, may shed light on designing of linear glycopeptide-based vaccines for cancer and viral diseases. TeaserA high-affinity antibody was found to bind densely glycosylated glycoprotein region by a peptide binding groove of the antibodys variant region, with a glycan-binding edge specific to glycosylation site most proximal to core peptide epitope.

immunology↗

bioRxiv2022

Three-dimensional structured illumination microscopy with enhanced axial resolution

We present two distinct, complementary methods for improving axial resolution in three-dimensional structured illumination microscopy (3D SIM) with minimal or no modification to the optical system. First, we show that placing a mirror directly opposite the sample enables 4-beam interference with higher spatial frequency content than 3D SIM illumination, offering near-isotropic imaging with [~]120 nm lateral and 160 nm axial resolution. Second, we develop an improved deep learning method that can be directly applied to 3D SIM data, obviating the need for additional hardware. This procedure results in [~]120 nm isotropic resolution and can be combined with denoising to facilitate volumetric imaging spanning dozens of time points. We demonstrate the potential of these advances by imaging a variety of cellular samples, delineating the nanoscale distribution of vimentin and microtubule filaments, observing the relative positions of caveolar coat proteins and lysosomal markers, and visualizing rich cytoskeletal dynamics within T-cells in the early stages of immune synapse formation.

cell biology↗

bioRxiv2022

Brassinosteroids signaling component SlBZR1 promotes fruit ripening in tomato

Fruit ripening evolved to be attractive to frugivores that derive energy and nutrition from the fruits in exchange for assisting seed dispersal, which is accompanied by the dramatically change of fruit characteristics, including color, aroma, and texture. The plant hormone ethylene plays a key role in climacteric fruit ripening, while the role of other phytohormones as well as their cross talk with ethylene in modulating fruit ripening remains elusive. Here, we report growth-promoting phytohormone brassinosteroids promote fruit ripening in tomato through regulation of ethylene biosynthesis. Exogenous BR treatment and the increase of endogenous BR content in SlCYP90B3-OE promoted ethylene production and fruit ripening. SlBZR1, a central component and positive regulator of BR signaling pathway, promotes ethylene production and carotenoid accumulation through direct transcriptional regulation of SlACO1, SlACO3 and SlPSY1. Furthermore, SlBIN2, a negative regulator of BR signaling upstream of SlBZR1, decreases ethylene production and carotenoid accumulation. Together, our results demonstrate that BR signaling integrates ethylene and carotenoid biosynthetic pathway to regulate fruit ripening.

plant biology↗

bioRxiv2022

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic pathways, Inflammation, and Atherosclerosis

BACKGROUNDAtherosclerosis is an inflammatory vascular disease marked by hyperlipidemia and hematopoietic stem cell (HSC) expansion. Activin A, a member of the Activin/GDF/TGF{beta}/BMP family is broadly expressed and increases in human atherosclerosis, but its functional effects in vivo in this context remain unclear. METHODSWe studied LDLR-/- mice on a Western diet for 12 weeks and used adeno-associated viral vectors with a liver-specific thyroxine binding globulin (TBG) promoter to express Activin A or GFP (control). Atherosclerotic lesions were analyzed by oil red staining. Blood lipid profiling was performed by HPLC (High Performance Liquid Chromatography), and immune cells were evaluated by flow cytometry. Liver RNA-sequencing was performed to explore the underlying mechanisms. RESULTSActivin A expression decreased in both livers and aortae from LDLR-/- mice fed a Western diet compared with chow. AAV-TBG-Activin A increased Activin A hepatic expression ([~]10-fold at 12-weeks, p<0.0001) and circulating Activin A levels ([~]2000pg/ml vs [~]50pg/ml, p<0.001, compared with controls). Hepatic Activin A expression decreased plasma total and low-density lipoprotein (LDL) cholesterol ([~]60% and [~]40%, respectively), reduced inflammatory cells in aortae and proliferating hematopoietic stem cells (HSC) in bone marrow, and reduced atherosclerotic lesion area in the aortic arch by [~]60%. Activin A also attenuated liver steatosis and expression of the lipogenesis genes, Srebp1 and Srebp2. RNA sequencing revealed Activin A not only blocked expression of genes involved in hepatic de novo lipogenesis but also fatty acid uptake, and liver inflammation. In addition, Activin A expressed in the liver also reduced white fat tissue accumulation, decreased adipocyte size, and improved glucose tolerance. CONCLUSIONSOur studies reveal hepatic Activin A expression reduces inflammation, HSC expansion, liver steatosis, circulating cholesterol, and fat accumulation, which likely all contribute to the observed protection against atherosclerosis. The reduced Activin A observed in LDLR-/- mice on a Western diet appears maladaptive and deleterious for atherogenesis.

pathology↗

bioRxiv2022

Small cytosolic dsDNAs repress cGAS activation and induce autophagy

Cyclic GMP-AMP (cGAMP) synthase (cGAS), a major cytosolic DNA sensor, activates innate immune responses by producing cGAMP, which activates stimulator of interferon genes (STING)1. Cytosolic DNA induces autophagy in a cGAS-dependent manner to avoid persistent immune stimulation. Although dsDNAs < 20 bp can bind to cGAS, robust cGAS activation requires dsDNAs > 45 bp 2-4. However, whether cytosolic dsDNAs < 45 bp exist in mammalian cells remains unclear. Here, we identified a class of small cytosolic DNAs (scDNAs) of [~]20-40 bp in human and mouse cell lines. scDNAs competed with herring testis DNA (HT-DNA, [~]200-1500 bp) for binding to cGAS, and repressing HT-DNA-induced cGAS activation and the associated interferon {beta} (IFN{beta}) production. Moreover, scDNAs promoted cGAS and Beclin-1 interaction, triggering the release of Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3)5,6, from the Beclin-1-PI3KC3 complex, activating PI3KC3 and inducing autophagy. DNA damage decreased and autophagy inducers increased scDNA levels. scDNA transfection or autophagy induction attenuated DNA damage-induced cGAS-STING activation and IFN{beta} expression. Thus, scDNAs acted as molecular brakes of cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings lay foundations for understanding the physiological and pathological functions of scDNAs.

molecular biology↗

bioRxiv2022

Renal ischemia-reperfusion injury attenuated by exosomes extracted from splenic ischemic preconditioning

ObjectiveTo investigate the protective effects of the exosomes extracted from splenic ischemic preconditioning (sIPC) on renal ischemia-reperfusion (IR) injury. Materials and methodsSplenic ischemic preconditioning(sIPC)was conducted on mice in vivo 24 hours before the start of renal ischemia-reperfusion (IR) injury experiment, and serum exosomes derived from sIPC mice were infused into the mice model of renal ischemia-reperfusion injury. The kidney tissue and serum were collected 24 hours later. The morphological changes and inflammation in ischemia-reperfusion kidneys were determined by hematoxylin-eosin (HE) staining.Then the apoptosis of kidney tissue sections were detected by TUNEL staining, Ki-67 immunohistochemical staining was used to assess the proliferation.In addition, the levels of pro-inflammatory cytokines including TNF-, IL-1{beta} and SCr in serum were measured by ELISA. In vitro, we extracted exosomes from mouse spleen fibroblasts pretreated with hypoxia and reoxygenation (H/R) and administered them to mouse renal epithelial cells.Furthermore, for the hypoxia-reoxygenation model of renal epithelial cells, TUNEL and flow cytometry were used to evalutaed cell apoptosis;Then ELISA was used to measure the levels of TNF- and IL-1{beta} in the cell supernatant, Bax and Bcl-2 were measured by Western Blotting. ResultsHE staining showed that the renal injury caused by ischemia-reperfusion attenuated after sIPC. TUNEL staining showed that renal tissue apoptosis was greatly reduced after sIPC or injection of exosomes extracted from splenic fibroblast hypoxia-reoxygenation model. Ki-67 staining showed that the positive rates of IRI+sIPC group, IRI+mSF(H/R)-exo group, IRI+mSF(H/R+PBS)-exo group were close, higher than IRI group but lower than sham group. ELISA test of kidney tissue showed that the serum creatinine, TNF- and IL-1{beta} induced by IRI decreased with sIPC and addition of the above-mentioned exosomes.In vitro, the exosomes extracted from the hypoxia-reoxygenation model of splenic fibroblasts had the same protective effect on hypoxia-reoxygenated mouse renal epithelial cells model, and this protective effect disappears after the addition of exosome inhibitors.TUNEL and flow cytometry showed that the exosomes reduced the apoptosis. The ELISA test results showed that the levels of TNF- and IL-1{beta} in the H/R group increased significantly, but decreased due to the splenic fibroblast exosomes treated with starvation.While the exosome inhibitors inhibited the effects of exosomes.Western blot results showed that the Bax expression level of the H/R group increased, and the Bcl-2 decreased.While the starvation-treated splenic fibroblast exosomes decreased the Bax level and increased the Bcl-2 level. ConclusionsThe exosomes extracted from splenic ischemic preconditioning exerted a protective capacity to attenuate renal IR injury.

pathology↗

bioRxiv2022

Phase separation of Myc differentially regulates gene transcription

Dysregulation and enhanced expression of MYC transcription factors (TFs) including MYC and MYCN contribute to the majority of human cancers. For example, MYCN is amplified up to several hundred-fold in high-risk neuroblastoma. The resulting overexpression of N-myc aberrantly activates genes that are not activated at low N-myc levels and drives proliferation and cell survival. Whether increasing N-myc levels simply mediate binding to lower-affinity binding sites in the genome or fundamentally changes the activation process remains unclear. One such activation mechanism that could become important above threshold levels of N-myc is the formation of aberrant transcriptional condensates through phase separation. Phase separation has recently been linked to transcriptional regulation, but how strongly it contributes to gene activation remains unclear. Here we characterized the phase behavior of N-myc and showed that it can form dynamic condensates that bear the hallmarks of transcriptional activity. We tested the contribution of phase separation to N-myc-mediated gene expression by using a chemogenetic tool that allowed us to compare non-phase-separated and phase-separated conditions at identical N-myc levels, which both showed a strong impact on gene expression compared to no N-myc expression. However, we found that only a small fraction of <3% of N-myc-regulated genes is further affected by phase separation, but that these events include the activation of key oncogenes and the repression of tumor suppressors. Indeed, phase separation increases cell survival by [~]15% corroborating the biological effects of the transcriptional changes. However, our results also show that >97% of N-myc-regulated genes are not affected by N-myc phase separation, highlighting that transcription can be activated effectively by diffuse complexes of TFs with the transcriptional machinery.

cell biology↗

bioRxiv2022

CARD8 negatively regulates NLRP1 inflammasome activation level by interaction with NLRP1

NLRP1 inflammasome functions as canonical cytosolic sensor in response to intracellular infections and is implicated in auto-inflammatory diseases. But the regulation and signal transduction mechanisms of NLRP1 are incompletely understood. Here, we show that the T60 variant of CARD8, but not the canonical T48 isoform, negatively regulates NLRP1 inflammasome activation by directly interacting with the receptor molecule NLRP1 and inhibiting inflammasome assembly. Furthermore, our results suggest that the different ASC preference in three types of inflammasomes, namely ASC-indispensable NLRP1 inflammasome, ASC-dispensable mNLRP1b inflammasome and ASC-independent CARD8 inflammasome, is mainly caused by the CARD domain, not the UPA subdomain. Based on the systematic site-directed mutagenesis and structural analysis, we find that the signal transduction of NLRP1 inflammasome relies on multiple interaction surfaces on its death domain superfamily member CARD domain. Finally, our results partly explain the mechanism of the NLRP1 mutation-derived auto-inflammatory diseases caused by the overactivation of the NLRP1 inflammasome. In conclusion, our study not only reveals how CARD8 downregulates NLRP1 inflammasome activation, but also provides insights into the mechanisms of CARD-containing inflammasome assembly.

immunology↗

bioRxiv2022

EZH2 inhibition remodels the inflammatory senescence-associated secretory phenotype to potentiate pancreatic cancer immune surveillance

T cell-activating immunotherapies that produce durable and even curative responses in some malignancies have failed in pancreatic ductal adenocarcinoma (PDAC) due to rampant immune suppression and poor tumor immunogenicity. We and others have demonstrated that induction of cellular senescence and its accompanying senescence-associated secretory phenotype (SASP) can be an effective approach to activate not only T cell but also cytotoxic Natural Killer (NK) cell-mediated anti-tumor immunity. Here we found that the pancreas tumor microenvironment (TME) suppresses NK and T cell surveillance following therapy-induced senescence through EZH2-mediated repression of pro-inflammatory SASP genes. Genetic or pharmacological inhibition of EZH2 or its methyltransferase activity stimulated the production of pro-inflammatory SASP chemokines CCL2 and CXCL9/10 that led to enhanced NK and T cell infiltration and tumor eradication in preclinical PDAC mouse models. EZH2 activity was also associated with suppression of SASP-associated inflammatory chemokines and cytotoxic lymphocyte immunity and reduced overall survival in a PDAC patient cohort. These results demonstrate that EZH2 mediates epigenetic repression of the pro-inflammatory SASP in the pancreas TME, and that EZH2 blockade in combination with senescence-inducing therapies could be a powerful means to potentiate NK and T cell surveillance in PDAC to achieve immune-mediated tumor control.

cancer biology↗

bioRxiv2022

Rotations improve the diversity of rhizosphere soil bacterial communities, enzyme activities and tomato yield

The use of rotations is an effective strategy to control crop diseases and improve plant health. The soil bacterial communities in the rhizosphere are highly important for maintaining soil productivity. However, the composition and structure of soil bacterial communities in the rotations of vegetable crops remain unclear. In this study, we explored the bacterial diversity and community structure of the tomato rhizosphere, including enzyme activities, yield, and fruit quality, under three different cropping systems: tomato-tomato continuous cropping (TY1), eggplant-tomato (S. melongena) rotation (TY2) and arrowhead-tomato (Sagittaria trifolia-Solanum lycopersicum) rotation (TY3). The composition and diversity of the rhizosphere bacterial communities differed significantly. The diversity was more in the TY2 and TY3 treatments than those in the TY1 treatment. Chujaibacter and Rhodanobacter were two predominant and unique strains detected only in TY1, while the relative abundances of Curvibacter and Luteimonas were the highest in TY2 and TY3, respectively. Moreover, Lysobacterium was a relatively abundant type of biocontrol bacterium found only in the TY3 treatment, which could contribute to alleviating the obstacle of tomato continuous cropping. Compared with the TY1 treatment, the activities of catalase were significantly higher in the TY2 and TY3 treatments. In addition, compared with TY1, the TY2 and TY3 plots increased the following parameters: tomato yields by 24-46%, total soluble solids by 37-93%, total organic acid by 10-15.7% and soluble protein by 10-21%, while the content of nitrate was significantly reduced by 23%. Altogether, compared with the tomato monoculture, the rotations of tomato with eggplant and arrowhead shifted the rhizosphere bacterial communities and improved the yield and quality of the vegetables. Moreover, a tomato rotation, particularly with arrowhead, was an effective way to alleviate the obstacles of continuous cropping.

microbiology↗

bioRxiv2022

A wealth of novel cell-specific expressed SNVs from tumor and normal scRNA-seq datasets

We demonstrate a novel variant calling strategy using barcode-stratified alignments on 25 tumor and normal 10XGenomics scRNA-seq datasets (>200,000 cells). Our approach identified 24,528 exonic non-dbSNP single cell expressed (sce)SNVs, a third of which are shared across multiple samples. The novel sceSNVs include unreported somatic and germline variants, as well as RNA-originating variants; some are expressed in up to 17% of the cells, and many are found in known cancer genes. Our findings suggest that there is an unacknowledged repertoire of expressed genetic variants, possibly recurrent and common across samples, in the normal and cancer transcriptome.

genomics↗