150 research outputs found

    Simulation of Fluctuating Wind Speed Fields by Stochastic Harmonic Function Representation Method Based on Joint Wavenumber-Frequency Power Spectrum

    Get PDF
    Simulation of wind speed fields usually plays a crucial role in the reliability analysis of large-size and high-rise structures such as tall buildings, long-span bridges and offshore wind turbines. To simulate a fluctuating wind speed field by the spectral representation method (SRM), two schemes can be adopted: (1) the conventional SRM, involving the decomposition of the cross power spectrum density (XPSD) matrix of fluctuating wind speed inevitablyand (2) the joint wavenumber-frequency spectrum based SRM, where a series of trigonometric functions are directly superimposed without any decompositions of XPSD matrix. However, both the two approaches involve large amounts of random variables, which hinder the reliability analysis of structures. In this paper, the stochastic harmonic function (SHF) representation method is extended and integrated with the joint wavenumber-frequency power spectrum to simulate fluctuating wind speed fields in one spatial dimension. Further, an efficient non-uniformly discretized scheme in wavenumber and frequency directions is suggested such that the number of random variables is dramatically reduced. Simulation results demonstrate the efficiency and validity of the proposed method.Financial supports from the National Natural Science Foundation of China (Grant Nos. 51725804, 11672209, and 11761131014) and the International Joint Research Program of Shanghai Municipal Government (Grant No. 18160712800) are highly appreciated

    SOHLHs Might Be Gametogenesis-Specific bHLH Transcriptional Regulation Factors in Crassostrea gigas

    Get PDF
    The self-renewal and differentiation of germ cells are essential for gametogenesis and reproduction. In mammals, the transcription factors SOHLH1 and SOHLH2, two members of the bHLH family, are specifically expressed in the gonads, and play an important role in spermatocyte and oocyte differentiation. In our previous study, we performed a phylogenetic analysis of the Lophotrochozoa bHLH genes, and two Sohlh were identified in the Pacific oyster Crassostrea gigas. Based on the genomes of other species that have complete genomic information, we further analyzed the phylogenetics of the Sohlh in this study. The results indicate that the Sohlh are ancient genes that were lost in many species during evolution, including in some invertebrates, and lower vertebrates. The phylogenetic tree shows that Sohlh1 and Sohlh2 are located in different scaffolds and that they have low similarity, suggesting early separation in invertebrates. We used RNA-seq and RT-PCR to examine the mRNA expression of the Sohlh in C. gigas (termed Cg-Sohlh), we found that Cg-Sohlh1, and Cg-Sohlh2 are specifically expressed in the gonads. During gonadal development, the mRNA expression levels of both genes increased from the proliferative stage and reached the highest level at the growth stage (P < 0.05). Then, the expression level decreased until the resting stage. In addition, immunohistochemistry was used to determine that the Cg-SOHLH1 protein was specifically expressed in the spermatogonia and spermatocytes. Cg-Sohlh2 mRNA was expressed in both the male and female gonads, while Cg-Sohlh1 mRNA was highly expressed in the female gonads at all developmental stages except for the resting stage. These data indicate that Cg-SOHLH might be gonad-specific regulatory factors, similar to mammalian SOHLH, and that Cg-SOHLH1 might be involved in spermatogonial differentiation. This study lays the foundation to further determine the functional role of SOHLH in mollusk gametogenesis and provides a foundation to better understand the regulatory mechanism of gametogenesis in invertebrates

    Blood-Stage Plasmodium Berghei ANKA Infection Promotes Hepatic Fibrosis by Enhancing Hedgehog Signaling in Mice

    Get PDF
    Background/Aims: Malaria is the most deadly parasitic infection in the world, resulting in damage to various organs, including the liver, of the infected organism; however, the mechanism causing this damage in the liver remains unclear. Liver fibrosis, a major characteristic of liver diseases, occurs in response to liver injury and is regulated by a complex network of signaling pathways. Hedgehog (Hh) signaling orchestrates a number of hepatic responses including hepatic fibrogenesis. Therefore, we investigated whether Hh signaling influenced the liver’s response to malarial infection. Methods: Eight-week-old male C57BL/6 mice inoculated with blood containing Plasmodium berghei ANKA (PbA)-infected erythrocytes were sacrificed when the level of parasitemia in the blood reached 10% or 30%, and the livers were collected for biochemical analysis. Liver responses to PbA infection were examined by hematoxylin and eosin staining, real-time polymerase chain reaction, immunohistochemistry and western blot. Results: Severe hepatic injury, such as ballooned hepatocytes, sinusoidal dilatation, and infiltrated leukocytes, was evident in the livers of the malaria-infected mice. Hypoxia was also induced in 30% parasitemia group. With the accumulation of Kupffer cells, inflammation markers, TNF-α, interleukin-1β, and chemokine (C-X-C motif) ligand 1, were significantly upregulated in the infected group compared with the control group. Expression of fibrotic markers, including transforming growth factor-β, α-smooth muscle actin (α-SMA), collagen 1a1, thymosin β4, and vimentin, were significantly higher in the infected groups than in the control group. With increased collagen deposition, hepatic stellate cells expressing α-SMA accumulated in the liver of the PbA-infected mice, whereas those cells were rarely detected in the livers of the control mice. The levels of Hh signaling and Yes-associated protein (YAP), two key regulators for hepatic fibrogenesis, were significantly elevated in the infected groups compared with the control group. Treatment of mice with Hh inhibitor, GDC-0449, reduced hepatic inflammation and fibrogenesis with Hh suppression in PbA-infected mice. Conclusion: Our results demonstrate that HSCs are activated in and Hh and YAP signaling are associated with this process, contributing to increased hepatic fibrosis in malaria-infected livers

    Mapping QTLs for the tissue culture performance of rice mature embryo using indica-japonica recombinant inbred lines

    Get PDF
    Abstract The tissue culture performance is the determinant factor of genetic transformation in indica rice (Oryza sativa L.). Quantitative trait loci (QTLs) associated with the tissue culture performance of mature embryo were detected by 202 genetic markers and 190 recombinant inbred lines (RILs) derived from the cross between two rice varieties, 93-11 (indica) as female parent and Nipponbare (japonica) as male parent. A composite interval mapping (CIM) was used to identify the QTLs for the tissue culture performance. The tissue culture performance of rice mature embryo were evaluated by six parameters, embryogenic calli induction rate (ECR), callus subculture capability (CSC), plantlet regeneration rate (RR), average number of regenerated shoots per callus (NRS), green plantlet regeneration rate (GRR) and average number of regenerated green shoots per callus (NRGS). Nipponbare has better tissue culture response than 93-11 because all indicators were higher in Nipponbare except CSC. Four QTLs for ECR, five QTLs for CSC, three QTLs for RR, two QTLs for NRS, four QTLs for GRR and three QTLs for NRGS were detected. These putative QTLs associated with tissue culture performance were distributed on eight rice chromosomes. These results demonstrated the possibilities of improving the tissue culture performance of indica rice by marker assisted selection (MAS) with those desirable alleles of japonica rice. Keywords: mature embryo; quantitative trait loci (QTLs); rice; recombinant inbred lines (RILs); tissue culture performance. Abbreviations: CAPS-cleaved amplified polymorphic sequence; CIM-composite interval mapping; CSC-callus subculture capability; DH-doubled haploid; ECR-embryogenic calli induction rate; GRR-green plantlet regeneration rate; LOD-logarithm of odds; MAS-marker assisted selection; NRGS-average number of regenerated green shoots per callus; NRS-average number of regenerated shoots per callus; QTLs-quantitative trait loci; RILs-recombinant inbred lines; RR-plantlet regeneration rate; SSRsimple sequence repeats; STS-sequence-tagged site

    Hippo dictates signaling for cellular homeostasis and immune defense in Crassostrea hongkongensis hemocytes

    Get PDF
    IntroductionThe Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution.MethodThe complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes.ResultThe results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis.DiscussionThis study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution

    Sphingosine Kinase 1 Regulates the Akt/FOXO3a/Bim Pathway and Contributes to Apoptosis Resistance in Glioma Cells

    Get PDF
    The aim of this study was to investigate the mechanism through which Sphingosine kinase-1 (SPHK1) exerts its anti-apoptosis activity in glioma cancer cells. We here report that dysregulation of SPHK1 alters the sensitivity of glioma to apoptosis both in vitro and in vivo. Further mechanistic study examined the expression of Bcl-2 family members, including Bcl-2, Mcl-1, Bax and Bim, in SPHK1-overexpressing glioma cells and revealed that only pro-apoptotic Bim was downregulated by SPHK1. Moreover, the transcriptional level of Bim was also altered by SPHK1 in glioma cells. We next confirmed the correlation between SPHK1 and Bim expression in primary glioma specimens. Importantly, increasing SPHK1 expression in glioma cells markedly elevated Akt activity and phosphorylated inactivation of FOXO3a, which led to downregulation of Bim. A pharmacological approach showed that these effects of SPHK1 were dependent on phosphatidylinositol 3-kinase (PI3K). Furthermore, effects of SPHK1 on Akt/FOXO3a/Bim pathway could be reversed by SPHK1 specific RNA interference or SPHK1 inhibitor. Collectively, our results indicate that regulation of the Akt/FOXO3a/Bim pathway may be a novel mechanism by which SPHK1 protects glioma cells from apoptosis, thereby involved in glioma tumorigenesis

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

    Get PDF
    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
    corecore