Biology subjects

Lv, Y.

Publications and source records attributed to Lv, Y..

52 records · Page 3Linked to original sources

bioRxiv2021

The creation of functioning gastrojejunostomy following magnetic compression

BackgroundMagnetic compression for creating gastrojejunostomy has many advantages according to previous studies. However, following mechanical device release after healing, the anastomotic stenosis becomes the pivotal point. MethodsRectangle-shaped magnets were used for magnetic compression in rabbits. Both paclitaxel-loaded magnets and a strategy of pyloric ligation were chosen to improve the gastrojejunostomy. Based on these choices, the half-capsule was applied to occlude the pylorus after anastomotic formation. The size and patency of the anastomoses were analyzed to evaluate the efficacy of these approaches. A histological examination was also performed. ResultsThe positive effect of ligating the pylorus on gastrojejunostomy was significantly greater than that achieved using paclitaxel-loaded magnets during either short- or long-term follow-up. There were fewer scar tissue and collagen fibers at the anastomotic site in the treatment group than in the control group. The anastomotic aperture was of great interest at 9 months after the ligation of the pylorus following magnetic compression. In the view of the jejunum, although the aperture was barely visible, gastric juice was continuously spilling through it like a spring, and the aperture was clearly visible from the stomach side. All half-capsules failed to block the pylorus. ConclusionThe effect of paclitaxel on maintaining gastrojejunostomy patency was temporary. The ligation of the pylorus ensured the long-term patency of gastrojejunostomy, and the aperture was comparable to the pylorus which could play an anti-reflux role. Further studies for the sort of gastrointestinal aperture are being planned.

physiology↗

bioRxiv2021

Altered effective connectivity from the posterior insula to the amygdala mediates the relationship between psychopathic traits and concern with the Harm foundation

Psychopathic traits have been demonstrated to be associated with different types of morality; however, the neuropsychological mechanism underlying the relationship between psychopathic traits and morality remains unclear. Our study examined the effective connectivity (EC) of psychopathic traits-related brain regions and its association to concern with different moral foundations by combining behavioral measures with resting-state fMRI. We administered the Levenson Self-Report Psychopathy Scale (LSRP) and Moral Foundation Questionnaire (MFQ) to 78 college students after resting-state fMRI scanning. Our results showed that total and primary psychopathic traits score predicted concern with the Harm foundation. The EC from the posterior insula to the amygdala was negatively correlated with psychopathic traits and positively with concern with the Harm foundation. Altered posterior insula-amygdala EC partially mediated the relationship between psychopathic traits and concern with the Harm foundation. Our findings indicated that individuals with elevated psychopathic traits may have atypical processes in recognizing and integrating bodily state information into emotional responses, leading to less concern for harm-related morality. The study deepened our understanding of the neuropsychological mechanism underlying the relationship between psychopathic traits and morality and may have implications for the prevention of higher psychopathic traits individuals from committing serious transgressions.

neuroscience↗

bioRxiv2021

Surface-based Single-subject Morphological Brain Networks: Effects of Morphological Index, Brain Parcellation and Similarity Measure, Sample Size-varying Stability and Test-retest Reliability

Morphological brain networks, in particular those at the individual level, have become an important approach for studying the human brain connectome; however, relevant methodology is far from being well-established in their formation, description and reproducibility. Here, we extended our previous study by constructing and characterizing single-subject morphological similarity networks from brain volume to surface space and systematically evaluated their reproducibility with respect to effects of different choices of morphological index, brain parcellation atlas and similarity measure, sample size-varying stability and test-retest reliability. Using the Human Connectome Project dataset, we found that surface-based single-subject morphological similarity networks shared common small-world organization, high parallel efficiency, modular architecture and bilaterally distributed hubs regardless of different analytical strategies. Nevertheless, quantitative values of all interregional similarities, global network measures and nodal centralities were significantly affected by choices of morphological index, brain parcellation atlas and similarity measure. Moreover, the morphological similarity networks varied along with the number of participants and approached stability until the sample size exceeded [~]70. Using an independent test-retest dataset, we found fair to good, even excellent, reliability for most interregional similarities and network measures, which were also modulated by different analytical strategies, in particular choices of morphological index. Specifically, fractal dimension and sulcal depth outperformed gyrification index and cortical thickness, higher-resolution atlases outperformed lower-resolution atlases, and Jensen-Shannon divergence-based similarity outperformed Kullback-Leibler divergence-based similarity. Altogether, our findings propose surface-based single-subject morphological similarity networks as a reliable method to characterize the human brain connectome and provide methodological recommendations and guidance for future research.

neuroscience↗

bioRxiv2020

Regulation of cGAS activity through RNA-mediated phase separation

Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA (dsDNA) sensor that functions in the innate immune system. Upon binding dsDNA in the cytoplasm, cGAS and dsDNA form phase-separated aggregates in which cGAS catalyzes synthesis of 23-cyclic GMP-AMP that subsequently triggers a STING-dependent, type I IFN response. Here, we showed that cytoplasmic RNAs, especially tRNAs, regulate cGAS activity. We discovered that RNAs did not activate cGAS but rather promoted phase separation in vitro. In cells, cGAS colocalized with RNAs and formed phase-separated granules even in the absence of cytoplasmic dsDNA. An Opti-prep gradient analysis of cell lysates showed that the endogenous cGAS was associated with cytoplasmic RNAs in an aggregative form. Further in vitro assays showed that RNAs compete for binding of cGAS with dsDNA and inhibit cGAS activity when the dsDNA concentration is high and promote the formation of phase separations and enhance cGAS activity when the dsDNA concentration is low. Thus, cytoplasmic RNAs regulate cGAS activity by interfering with formation of cGAS-containing aggregates.

biochemistry↗

bioRxiv2020

Global Profiling of the Lysine Crotonylome in Different Pluripotent States

Pluripotent stem cells (PSCs) can be expanded in vitro in different culture conditions, resulting in a spectrum of cell states with distinct properties. Understanding how PSCs transition from one state to another, ultimately leading to lineage-specific differentiation, is important for developmental biology and regenerative medicine. Although there is significant information regarding gene expression changes controlling these transitions, less is known about post-translational modifications of proteins. Protein crotonylation is a newly discovered post-translational modification where lysine residues are modified with a crotonyl group. Here, we employed affinity purification of crotonylated peptides and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to systematically profile protein crotonylation in mouse PSCs in different states including ground, metastable and primed state, as well as metastable PSCs undergoing early pluripotency exit. We successfully identified 3628 high-confidence sites in 1426 proteins. These crotonylated proteins are enriched for factors involved in functions related to pluripotency such as RNA biogenesis, central carbon metabolism and proteasome function. Moreover, we found that increasing the cellular levels of crotonyl-CoA through crotonic acid treatment promotes proteasome activity in metastable PSCs and delays their differentiation, consistent with previous observations showing that enhanced proteasomal activity helps to sustain pluripotency. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of metabolism in other cell fate transitions.

cell biology↗

bioRxiv2020

Integrative Proteomic Analysis of Posttranslational Modification in The Inflammatory Response

The posttranslational modification (PTM) of proteins, particularly acetylation, phosphorylation and ubiquitination, plays a critical role in the host innate immune response. PTMs dynamic changes and the crosstalk among them are complicated. To build a comprehensive dynamic network of inflammation related proteins, we integrated data from the whole cell proteome (WCP), acetylome, phosphoproteome and ubiquitinome of human and mouse macrophages. Our datasets of acetylation, phosphorylation and ubiquitination sites helped identify PTM crosstalk within and across proteins involved in the inflammatory response. Stimulation of macrophages by lipopolysaccharide (LPS) resulted in both degradative and non-degradative ubiquitination. Moreover, this study contributes to the interpretation of the roles of known inflammatory molecules and the discovery of novel inflammatory proteins.

immunology↗

bioRxiv2020

Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike psedotype virus

BackgroundThe novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019 and there is no sign that the epidemic is abating. The major issue for controlling the infectious is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been reported to treat the disease, but the underlying mechanism remains controversial. PurposeThe objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. MethodsIn our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. ResultsResults showed that HCQ is slightly more toxic to ACE2h cells than CQ. Both CQ and HCQ could bind to ACE2 with KD =(7.31{+/-}0.62)e-7 M and (4.82{+/-}0.87)e-7 M, respectively. They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2h cells. ConclusionsCQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. Our findings provide novel insights into the molecular mechanism of CQ and HCQ treatment effect on virus infection.

biochemistry↗

bioRxiv2020

Identification a novel subset of alveolar type 2 cells expanding following pneumonectomy and enriched in PD-L1

Alveolar type 2 (AT2) cells are heterogeneous cells; where specialized AT2 subpopulations within this lineage exhibit stem cell properties. However, the existence of quiescent, immature cells within the AT2 lineage, which get activated during lung regeneration, is unknown. SftpcCreERT2/+; tdTomatoflox/flox mice were used for the labelling of AT2 cells and labeled subpopulations were analyzed by flow cytometry, qPCR, ATAC-seq, gene arrays, pneumonectomy, and culture of precision-cut lung slides. Human lungs from donor and IPF were also analyzed. In mice, we detected two distinct AT2 subpopulations with low tdTomato level (TomLow) and high tdTomato level (TomHigh). TomLow express lower level of AT2 differentiation markers, Fgfr2b and Etv5, while TomHigh, as bona fide mature AT2 cells, show higher level of Sftpc, Sftpb, Sftpa1, Fgfr2b, and Etv5. ATAC-seq analysis indicates that TomLow and TomHigh constitute two distinct cell populations with specific silencing of Sftpc, Rosa26 and cell cycle gene loci in TomLow. Upon pneumonectomy, TomLow but not TomHigh cells proliferate and upregulate the expression of Fgfr2b, Etv5, Sftpc, Ccnd1 and Ccnd2 compared to sham. TomLow cells overexpress PD-L1, an immune inhibitory membrane receptor ligand, which is used by flow cytometry to differentially isolate these two sub-populations. In the human lung, PD-L1 and HTII-280 antibodies are used by flow cytometry to differentially sort mature AT2 (HTII-280-high, PD-L1-low) as well as an additional subpopulation of epithelial cells characterized by HTII-280-Low and PD-L1-high. We have identified a novel population of AT2 quiescent immature progenitor cells in mouse that proliferate upon pneumonectomy and provided evidence for the existence of such cells in human. Significance of the workThe characterization and mechanism of the proliferation of a novel and relevant pool of AT2 progenitor cells for the repair/regeneration process after injury are critical to improving respiratory function in patients with lung disease.

cell biology↗

bioRxiv2020

Coupling metabolic addiction with negative autoregulation to improve strain stability and pathway yield

Metabolic addiction, an organism that is metabolically addicted with a compound to maintain its growth fitness, is an underexplored area in metabolic engineering. Microbes with heavily engineered pathways or genetic circuits tend to experience metabolic burden leading to degenerated or abortive production phenotype during long-term cultivation or scale-up. A promising solution to combat metabolic instability is to tie up the end-product with an intermediary metabolite that is essential to the growth of the producing host. Here we present a simple strategy to improve both metabolic stability and pathway yield by coupling chemical addiction with negative autoregulatory genetic circuits. Naringenin and lipids compete for the same precursor with inversed pathway yield in oleaginous yeast. Negative autoregulation of the lipogenic pathways, enabled by CRISPRi and fatty acid-inducible promoters, repartitioned malonyl-CoA to favor flavonoid synthesis and increased naringenin production by 74.8%. With flavonoid-sensing hybrid promoters to control leucine synthesis, this flavonoid addiction phenotype confers a selective growth advantage to the naringenin-producing cell. The engineered yeast persisted 90.9% of naringenin titer up to 324 generations. Cells without flavonoid addiction regained growth fitness but lost 94.5% of the naringenin titer after cell passage beyond 300 generations. Metabolic addiction and negative autoregulation may be generalized as basic tools to eliminate metabolic heterogeneity, improve strain stability and pathway yield.

synthetic biology↗

bioRxiv2020

WISP2/CCN5 gene knockdown in vitro and in vivo exhibits proliferation promotion of breast cancer through targeting Skp2 and p27Kip1

BackgroundEmerging evidence has demonstrated that WISP2/CCN5 is critically involved in tumorigenesis. However, the function of WISP2/CCN5 in breast cancer carcinogenesis is largely unclear. Methodswe aim to explore the effects and potential mechanisms of WISP2/CCN5 on proliferation of breast cancer cells and carcinogenesis of breast cancer xenograft. Lentivirus vector with WISP2/CCN5shRNA was transfected into MCF-7, and breast cancer cells and xenograft were conducted. Effect of WISP2/CCN5 on growth and carcinogenesis of breast cancer cells and xenografts was evaluated by MTT assay and tumor volume. The relationship between WISP2/CCN5, Skp2 and p27Kip1 was detected in vitro and in vivo by RT-PCR at mRNA level and Western blotting at protein level. ResultsThe result of MTT assay indicated that MCF-7 cell growth viability in WISP2/CCN5 gene knockdown group was significantly higher than negative vector group(P<0.05) or control group (P<0.05). It suggested that knockdown of WISP2/CCN5 gene by shRNA lentivirus plasmid promoted proliferation of MCF-7 cells. The growth curves of breast cancer xenograft showed that xenografts in WISP2/CCN5 knockdown group grew more quickly than negative vector group(P< 0.05) or control group (P< 0.05). Subsequently, the results of RT-PCR and Western blotting revealed that WISP2/CCN5 gene knockdown led to increased Skp2 and decreased p27Kip1 at mRNA and protein levels. WISP2/CCN5 exerts its inhibition on proliferation of MCF-7 cell line and suppressive functions on growth of breast carcinoma via regulation of Skp2 and p27Kip1at mRNA and protein levels. However, WISP2/CCN5 gene knockdown resulted in loss of inhibition effect on MCF-7 and breast cancer. ConclusionsOur findings suggest that WISP2/CCN5 could be a useful therapeutic strategy for the treatment of breast cancer through targeting Skp2 and p27Kip1.

molecular biology↗

bioRxiv2019

Evolutionary genomics of structural variation in Asian rice (Oryza sativa) and its wild progenitor (O. rufipogon)

Structural variants (SVs) are a largely unstudied feature of plant genome evolution, despite the fact that SVs contribute substantially to phenotypes. In this study, we discovered structural variants (SVs) across a population sample of 358 high-coverage, resequenced genomes of Asian rice (Oryza sativa) and its wild ancestor (O. rufipogon). In addition to this short-read dataset, we also inferred SVs from whole-genome assemblies and long-read data. Comparisons among datasets revealed different features of genome variability. For example, genome alignment identified a large (~4.3 Mb) inversion in indica rice varieties relative to an outgroup, and long-read analyses suggest that ~9% of genes from this outgroup are hemizygous. We focused, however, on the resequencing sample to investigate the population genomics of SVs. Clustering analyses with SVs recapitulated the rice cultivar groups that were also inferred from SNPs. However, the site-frequency spectrum of each SV type -- which included inversions, duplications, deletions, translocations and mobile element insertions -- was skewed toward lower frequency variants than synonymous SNPs, suggesting that SVs are predominantly deleterious. The strength of these deleterious effects varied among SV types, with inversions especially deleterious, and across transposable element (TE) families. Among TEs SINE and mariner insertions were especially deleterious, due to stronger selection against their insertions. We also used SVs to study domestication by contrasting between rice and O. rufipogon. Cultivated genomes contained ~25% more derived SVs than O. rufipogon, suggesting these deleterious SVs contribute to the cost of domestication. We also used SVs to study the effects of positive selection on the rice genome. Generally, the search for domestication genes were enriched for known candidates, suggesting some utility for SVs towards this purpose. More importantly, we detected hundreds to thousands of genes gained and lost during domestication, many of which are predicted to contribute to traits of agronomic interest.

evolutionary biology↗

bioRxiv2019

Transposable elements contribute to regulatory hubs stress-related long noncoding RNAs in Maize

Several studies have mined short-read RNA sequencing datasets to identify lncRNAs, and others have focused on the function of individual lncRNA in abiotic stress response. However, our understanding of the complement, function and origin of long-non-coding RNA (lncRNAs) response to abiotic stress, especially transposon derived lncRNA (TE-lncRNA), is still in its infancy. To discover and study lncRNAs in maize (Zea mays ssp. mays), we utilized a dataset of 127 RNA sequencing samples that included PacBio fl-cDNA and total RNA-Seq datasets. Overall, we identified 23,309 candidate lncRNAs, 60% of which were identified in polyadenylated (polyA+) samples. The majority (65%) of the 23,309 lncRNAs had sequence similarity to transposable elements (TEs). Most had similarity to long-terminal-repeat retrotransposons from the Copia and Gypsy superfamilies, representing the high proportion of these elements in the genome, but class II, DNA transposons were enriched for lncRNAs relative to their genomic representation by 2-fold. By assessing the fraction of lncRNAs that respond to abiotic stresses like heat, cold, salt and drought, we identified 1,077 differentially expressed lncRNA transcripts. Their expression was correlated (r2=0.48) with their nearest gene, suggesting that lncRNAs are subject to some of the cis regulatory features as neighboring genes. By inferring co-expression networks across our large dataset, we found that 39 lncRNAs act as major hubs in co-expression networks, of which 18 appeared to be derived from TEs. These results suggest that lncRNAs, especially TE-lncRNAs, may play key regulatory roles in moderating abiotic responses.

plant biology↗

bioRxiv2019

A unified neurocognitive model of the anterior temporal lobe contributions to semantics, language, social behaviour & face recognition

AbstractThe anterior temporal lobes (ATL) have become a key brain region of interest in cognitive and clinical neuroscience. Contemporary explorations are founded upon neuropsychological investigations of semantic dementia (SD) that describe the patients selective semantic impairment and the variations in their language, behavioural and face recognition abilities. The purpose of this investigation was to generate a single unified model which captures the known cognitive-behavioural variations in SD, and integrates with the considerable database on healthy semantic function and other patient groups. A new analytical approach was able to capture the graded neuropsychological differences and map these to the patients distribution of frontotemporal atrophy. Multiple regression and principal component analyses confirmed that the degree of generalised semantic impairment was related to the patients total, bilateral ATL atrophy. Verbal production and word-finding abilities were related to total ATL atrophy as well as to the balance of left>right ATL atrophy. Behavioural apathy was found to relate positively to the degree of orbitofrontal atrophy and negatively to total temporal volumes. Disinhibited behaviour was related to right ATL and orbitofrontal atrophy and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.

neuroscience↗

bioRxiv2019

Optimizing oleaginous yeast cell factories for flavonoids and hydroxylated flavonoids biosynthesis

Plants possess myriads of secondary metabolites with a broad spectrum of health-promoting benefits. Up to date, plant extraction is still the primary route to produce high-value natural products, which inherently suffers from economics and scalability issues. Heterologous production in microbial host is considered as a feasible approach to overcoming these limitations. Flavonoid and its hydroxylated derivatives represent a diversified family of bioactive compounds, most prominently known as antioxidant and anti-aging agents. Oleaginous yeast is rich in hydrophobic lipid bodies and spatially-organized organelles, which provides the ideal environment for the regioselectivity and stereoselectivity of many plant-specific enzymes. In this report, we validated that Y. lipolytica is a superior platform for heterologous production of high-value flavonoids and hydroxylated flavonoids. By modular construction and characterization, we determined the rate-limiting steps for efficient flavonoids biosynthesis in Y. lipolytica. We evaluated various precursor pathways and unleashed the metabolic potential of Y. lipolytica to produce flavonoids, including the supply of acetyl-CoA, malonyl-CoA and chorismate. Coupled with the optimized chalcone synthase module and the hydroxylation module, our engineered strain produced 252.4 mg/L naringenin, 134.2 mg/L eriodictyol and 110.5 mg/L taxifolin from glucose. Collectively, these findings demonstrate our ability to harness oleaginous yeast as microbial workhorse to expand natures biosynthetic potential, enabling us to bridge the gap between drug discovery and natural product manufacturing.

synthetic biology↗

bioRxiv2019

3D association of ER, PR and Her2 at protein levels to aid sub-grouping of breast cancer patients in routine clinical practice

Treatments of patients with solid tumors frequently rely on the relative and semi-quantitative assessment of tissue protein biomarkers by immunohistochemistry (IHC). The perspective of transition to absolute and quantitative assessment of tissue biomarkers is hindered by lack of a suitable method, especially for Formalin Fixed Paraffin Embedded (FFPE) tissues. In this study, we explored the feasibility of Quantitative Dot Blot (QDB) method as a universal platform to quantitate tissue biomarkers as absolute and continuous variables in FFPE samples by measuring unprecedentedly the protein levels of Estrogen Receptor (ER), Progesterone Receptor (PR), Her2 and Ki67 simultaneously in 1048 FFPE samples. When using measured Her2, ER and PR levels as coordinates to develop 3D scatterplot, we observed a distinct distribution pattern of the samples with natural segregation of three groups as the likely phenotypical projection of known intrinsic subtypes. Thus, we have achieved a major milestone in this transition by identifying the first practice method for daily clinical practice, and one clinical usage in 3D subtyping of samples for prediction and prognosis. This study may serve as basis for a new field of Quantitative Diagnosis where diagnosis, prognosis and prediction are derived from database analysis of protein biomarkers as absolute and continuous variables.

pathology↗

bioRxiv2018

JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke

c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated in ischemia brain injury and plays an important role in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a specific JNK inhibitor) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the role of JNK-IN-8 in ischemic stroke and the underlying mechanisms of JNK-IN-8 involving neuroprotection remain poorly understood. In the present study, male rats were subjected to tMCAO (transient middle cerebral artery occlusion) followed by treatment with JNK-IN-8, and then the modified improved neurological function score (mNSS), the Foot-fault test and the level of inflammatory cytokines (IL-1{beta}, IL-6 and TNF-) were assessed. We found that JNK-IN-8-treated rats with MCAO exerted a significant improvement in spatial learning as measured by the improved mNSS, and showed sensorimotor functional recovery as measured by the Foot-fault test. JNK-IN-8 also exerted anti-inflammatory effects as indicated by decreased activation of microglia and the decreased expresson of IL-6, IL-1{beta} and TNF-. Furthermore, JNK-IN-8 suppressed the activation of JNK and subsequent activation of NF-{kappa}B signaling as indicated by the decreased level of phosphorylated JNK (p-JNK) and p65. These data suggest that JNK-IN-8 suppressed neuroinflammation and improved neurological function by inhibiting JNK/NF-{kappa}B pathway after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.

cancer biology↗