Accumulating evidence shows that RAGE has an important function in the pathogenesis of sepsis. However, the mechanisms by which RAGE transduces signals to downstream kinase cascades during septic shock are not clear. ...
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Accumulating evidence shows that RAGE has an important function in the pathogenesis of sepsis. However, the mechanisms by which RAGE transduces signals to downstream kinase cascades during septic shock are not clear. Here, we identify SLP76 as a binding partner for the cytosolic tail of RAGE both in vitro and in vivo and demonstrate that SLP76 binds RAGE through its sterile alpha motif (SAM) to mediate downstream signaling. Genetic deficiency of RAGE or SLP76 reduces AGE-induced phosphorylation of p38 MAPK, ERK1/2 and IKK alpha/beta, as well as cytokine release. Delivery of the SAM domain into macrophages via the TAT cell-penetrating peptide blocks proinflammatory cytokine production. Furthermore, administration of TAT-SAM attenuates inflammatory cytokine release and tissue damage in mice subjected to cecal ligation and puncture (CLP) and protects these mice from the lethality of sepsis. These findings reveal an important function for SLP76 in RAGE-mediated pro-inflammatory signaling and shed light on the development of SLP76-targeted therapeutics for sepsis.
The Indo Pacific Convergence Zone (IPC) is recognized as an area of highest taxonomic and functional diversity. The polychaetes have garnered attention as their enormous functional trait diversity and their significan...
The Indo Pacific Convergence Zone (IPC) is recognized as an area of highest taxonomic and functional diversity. The polychaetes have garnered attention as their enormous functional trait diversity and their significant role in biomonitoring ecosystems. Here, we developed a comprehensive dataset for polychaetes in the IPC, encompassing information on species distribution, DNA barcodes, and functional traits. The species distribution data were collected from 39,310 occurrence records, with over 13% newly contributed from museum collections and 350 scientific papers. This dataset also provides 29% known species coverage in the IPC, 154 mitochondrial genomes (35.1% are new contributions), and 7,052 COI/18S/16S sequences (4.6% are new contributions). Our functional traits subdatabase comprises approximately 12,000 records and 2,831 species, belonging to 696 genera and 75 families, with 90% of which are new additions. The functional trait data were categorized into 13 traits spanning morphology, life history, physiology, and behavior. The datasetbase provide an unprecedented and original contribution for conservation and for studying the biogeography, evolution processes, and ecology of tropic organisms.
Precaution of classical swine fever (CSF) is an important mission for the worldwide swine industry. Glycoprotein E2 is the leading antigen candidate for subunit vaccine of classical swine fever virus (CSFV). In this s...
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Precaution of classical swine fever (CSF) is an important mission for the worldwide swine industry. Glycoprotein E2 is the leading antigen candidate for subunit vaccine of classical swine fever virus (CSFV). In this study, two Spy-tagged E2 genes were synthesized in vitro and subcloned into pMCO-AOX vector for intracellular expression in Pichia pastor-is after methanol induction. Western blot analysis and semi-quantitative analysis showed that the yield of recombinant E2 protein was improved 17.87 folds by using co-translocational signal peptide cSIG. After the construction of the tandem multiple copy expression vectors, further increase of E2 production was observed by repetitive transforming expression vectors into P. pastoris genome. Finally, the yeast transformants harboring 8 or 16 copies of cSIG-E2-Spy increased the E2 expression level by 27.01-fold or 30.72-fold, respectively. These results demonstrate that utilizing co-translocational signal peptide together with multi-copy integration strategy can increase the production of recombinant E2 protein efficiently.
In recent decades, NGS data analysis has become a major research field in bioinformatics, which presents great advantages in many application scenarios. Many algorithms and software were designed for analyzing the NGS...
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ISBN:
(纸本)9781728118673
In recent decades, NGS data analysis has become a major research field in bioinformatics, which presents great advantages in many application scenarios. Many algorithms and software were designed for analyzing the NGS data, while simulation datasets are urgently needed for testing software and optimizing their parameter configurations. Thus, a series of NGS data simulators have been published. However, the existing simulators cannot satisfy the requirements from many specific scenarios. First, they do not support many newly discovered variations. Second, complex structural variations are difficult to generate. In addition, along with the increase of population data, it is urgent to increase population information simulation. In this paper, we propose GSDcreator, a comprehensive NGS simulator that overcome the three weaknesses mentioned above. It can produce all known types of variation, where the complex of variations are also supported. Furthermore, it can capture many important real data features including population polymorphism, insert size distribution, adjacent site depth distribution, overall depth distribution, quality score distribution, amplification bias, sequencing errors and so on. It's highlighted that 1000 Genomes Project Database is taken as a reference and integrates population genetic information to simulate population polymorphism. To test the performance, we did a lot of experiments and found that simulated data produced by GSDcreator are quit mimic to the real sequencing data.
Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on beta-amyloid (A beta) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and ir...
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Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on beta-amyloid (A beta) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and irreversible impairment of the nervous system in the late stage of AD. Recently, inflammatory responses, manifested in oxidative stress and glial cell activation, have been reported as hallmarks in the early stages of AD. Based on the crosstalk between inflammatory response and brain cells, a reactive oxygen species (ROS)-responsive dendrimer-peptide conjugate (APBP) is devised to target the AD microenvironment and inhibit inflammatory responses at an early stage. With the modification of the targeting peptide, this nanoconjugate can efficiently deliver peptides to the infected regions and restore the antioxidant ability of neurons by activating the nuclear factor (erythroid-derived 2)-like 2 signaling pathway. Moreover, this multi-target strategy exhibits a synergistic function of ROS scavenging, promoting A beta phagocytosis, and normalizing the glial cell phenotype. As a result, the nanoconjugate can reduce ROS level, decrease A beta burden, alleviate glial cell activation, and eventually enhance cognitive functions in APPswe/PSEN1dE9 model mice. These results indicate that APBP can be a promising candidate for the multi-target treatment of AD.
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