Amino acid residues 201-205 in C-terminal acidic tail region plays a crucial role in antibacterial activity of HMGB1

<p>Abstract</p> <p>Background</p> <p>Antibacterial activity is a novel function of high-mobility group box 1 (HMGB1). However, the functional site for this new effect is presently unknown.</p> <p>Methods and Results</p> <p>In this study, recombinant human HMGB1 A box and B box (rHMGB1 A box, rHMGB1 B box), recombinant human HMGB1 (rHMGB1) and the truncated C-terminal acidic tail mutant (tHMGB1) were prepared by the prokaryotic expression system. The C-terminal acidic tail (C peptide) was synthesized, which was composed of 30 amino acid residues. Antibacterial assays showed that both the full length rHMGB1 and the synthetic C peptide alone could efficiently inhibit bacteria proliferation, but rHMGB1 A box and B box, and tHMGB1 lacking the C-terminal acidic tail had no antibacterial function. These results suggest that C-terminal acidic tail is the key region for the antibacterial activity of HMGB1. Furthermore, we prepared eleven different deleted mutants lacking several amino acid residues in C-terminal acidic tail of HMGB1. Antibacterial assays of these mutants demonstrate that the amino acid residues 201-205 in C-terminal acidic tail region is the core functional site for the antibacterial activity of the molecule.</p> <p>Conclusion</p> <p>In sum, these results define the key region and the crucial site in HMGB1 for its antibacterial function, which is helpful to illustrating the antibacterial mechanisms of HMGB1.</p

Evaluation expérimentale des propriétés hydrodynamiques des matériaux cimentaires

Plusieurs expériences de séchage isotherme sur des échantillons de matériaux cimentaires de natures, de compositions et de tailles différentes sont réalisées afin d'étudier l'influence des paramètres intrinsèques du matériau sur les transferts hydriques diffusifs. La loi proposée par van Genuchten et Mualem pour les milieux poreux est identifiée à partir des valeurs expérimentales de l'évolution de la teneur en eau en fonction de la pression capillaire dans le matériau. Une modélisation de l'équation de diffusivité permet ensuite d'estimer la perméabilité intrinsèque. La relation de van Genuchten-Mualem ne s'ajuste qu'imparfaitement aux résultats et apparaît sensible à la nature du matériau et à la taille de l'éprouvette utilisée On met également en évidence une augmentation importante de la perméabilité intrinsèque du matériau au cours du séchage probablement due à l'apparition de microfissuration. Une modification de la formulation des propriétés hydrodynamiques est proposée pour permettre une meilleure représentation des ces expériences

The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence (Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box

Probing Primordial Gravitational Waves: Ali CMB Polarization Telescope

In this paper, we will give a general introduction to the project of Ali CMB Polarization Telescope (AliCPT), which is a Sino-US joint project led by the Institute of High Energy Physics (IHEP) and has involved many different institutes in China. It is the first ground-based Cosmic Microwave Background (CMB) polarization experiment in China and an integral part of China's Gravitational Waves Program. The main scientific goal of AliCPT project is to probe the primordial gravitational waves (PGWs) originated from the very early Universe. The AliCPT project includes two stages. The first stage referred to as AliCPT-1, is to build a telescope in the Ali region of Tibet with an altitude of 5,250 meters. Once completed, it will be the worldwide highest ground-based CMB observatory and open a new window for probing PGWs in northern hemisphere. AliCPT-1 telescope is designed to have about 7,000 TES detectors at 90GHz and 150GHz. The second stage is to have a more sensitive telescope (AliCPT-2) with the number of detectors more than 20,000. Our simulations show that AliCPT will improve the current constraint on the tensor-to-scalar ratio $r$ by one order of magnitude with 3 years' observation. Besides the PGWs, the AliCPT will also enable a precise measurement on the CMB rotation angle and provide a precise test on the CPT symmetry. We show 3 years' observation will improve the current limit by two order of magnitude.Comment: 11 pages, 7 figures, 2 table

Single-nucleotide polymorphism-gene intermixed networking reveals co-linkers connected to multiple gene expression phenotypes

Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges

Prevalence of Mycobacterium bovis in deer in mainland China: a systematic review and meta-analysis

BackgroundDeer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis.MethodologyThis study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran’s Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger’s test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses.ResultsIn this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0–21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2–53.0; 1557/4291). Elaphurus davidianus was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5–67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis.ConclusionDeer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis

The Role of Receptor for Advanced Glycation End Products (RAGE) in the Proliferation of Hepatocellular Carcinoma

The receptor for advanced glycation end products (RAGE) is oncogenic and overexpressed in human cancers, but its role in hepatocellular carcinoma remains unclear. Here we demonstrated that RAGE is overexpressed in primary hepatocellular carcinoma (PHC) compared to adjacent para-neoplastic liver samples. Serum endogenous secretory RAGE levels were also increased in PHC patients (p < 0.01). Moreover, we demonstrated that RAGE regulates cellular proliferation in Hepatocellular carcinoma (HCC). Knockdown of RAGE by specific siRNA inhibited cellular growth in the hepatocellular carcinoma cell line, Huh7, whereas the RAGE ligand, high mobility group box 1 protein (HMGB1) increased cellular proliferation. In addition, knockdown of RAGE by siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.01), while HMGB1 protein decreased the number of cells in the G1 phase and increased the number in the S phase (p < 0.05). Furthermore, quantitative real time RT-PCR (qRT-PCR) and Western Blot results demonstrated that RAGE and HMGB1 positively regulate NF-κB p65 expression in Huh7 cells. These studies suggest that RAGE and RAGE ligands are important targets for therapeutic intervention in hepatocellular carcinoma