The evolution of BIR domain and its containing proteins

AbstractBIR domain and its containing proteins play critical roles in cell apoptosis and cell division. Here several lines of novelty were revealed based on a comprehensive evolutionary analysis of BIR domains in 11 representative organisms. First, the type II BIR domains in Survivin and Bruce showed more conservation compared with the type I BIR domains in the inhibitors of apoptosis proteins (IAPs). Second, cIAP was derived from a XIAP duplicate and emerged just after the divergence of invertebrates and vertebrates. Third, the three BIR domains of NAIP displayed significantly elevated evolutionary rates compared with the BIR domains in other IAPs

The Development and Application of Simulation Studio Teaching Experiment System in Colleges and Universities

AbstractBeing established in the personnel training of the directing and producing of film and television program in our university, considering the problems and dilemma that our university is faced with, we plan to construct a simulation studio. The paper elaborates the whole design and functional components of simulation studio, describes specific realization flow, and accomplishes a simulation studio system applied in teaching. Now, the simulation studio has applied in teaching, and has acquires well teaching effect. The simulation studio has definite promotional value, can be used in the education and teaching of film and television producing extensivel

Phylogenetic and evolutionary analysis of the septin protein family in metazoan

AbstractSeptins, a conserved family of cytoskeletal GTP-binding proteins, were presented in diverse eukaryotes. Here, a comprehensive phylogenetic and evolutionary analysis for septin proteins in metazoan was carried out. First, we demonstrated that all septin proteins in metazoan could be clustered into four subgroups, and the representative homologue of every subgroup was presented in the non-vertebrate chordate Ciona intestinalis, indicating that the emergence of the four septin subgroups should have occurred prior to divergence of vertebrates and invertebrates, and the expansion of the septin gene number in vertebrates was mainly by the duplication of pre-existing genes rather than by the appearance of new septin subgroup. Second, the direct orthologues of most human septins existed in zebrafish, which suggested that human septin gene repertoire was mainly formed by as far as before the split between fishes and land vertebrates. Third, we found that the evolutionary rate within septin family in mammalian lineage varies significantly, human SEPT1, SEPT 10, SEPT 12, and SEPT 14 displayed a relative elevated evolutionary rate compared with other septin members. Our data will provide new insights for the further function study of this protein family

The ancient function of RB-E2F Pathway: insights from its evolutionary history

<p>Abstract</p> <p>Background</p> <p>The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored.</p> <p>Results</p> <p>We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs) protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5) and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3), RB family was divided into RB1 subgroup (including RB1) and RBL subgroup (including RBL1 and RBL2). Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates,</p> <p>Conclusions</p> <p>Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F pathway. Our results will enhance the current understanding of RB-E2F pathway and will also be useful to further functional studies in human and other model organisms.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Pierre Pontarotti, Dr. Arcady Mushegian and Dr. Zhenguo Lin (nominated by Dr. Neil Smalheiser).</p

Bioactivity-guided fractionation of the triglyceride-lowering component and in vivo and in vitro evaluation of hypolipidemic effects of Calyx seu Fructus Physalis

<p>Abstract</p> <p>Background</p> <p>In folklore, some people take the decoction of <it>Calyx seu Fructus Physalis </it>(CSFP) for lowering blood lipids. The present study is designed to evaluate the lipid-lowering activities of CSFP, and search for its pharmacodynamical material.</p> <p>Methods</p> <p>CSFP was extracted by water and 75% ethanol, respectively. The extracts of CSFP for reducing serum lipid levels were evaluated on mouse model of hyperlipidemia. The optimized extract was subjected to the bioactivity-guided fractionation in which the liquid-liquid extraction, collumn chromatography, the <it>in vivo </it>and <it>in vitro </it>models of hyperlipidemia were utilized. The structure of active component was determined by ¹³C-NMR and ¹H-NMR.</p> <p>Results</p> <p>The 75% ethanol extract of CSFP decreased the serum total cholesterol (TC) and triglyceride (TG) levels in mouse model of hyperlipidemia. Followed a separation process for the 75% ethanol extract of CSFP, the fraction B was proved to be an active fraction for lowering lipid <it>in vivo </it>and <it>in vitro </it>experiments, which could significantly decrease the serum TC and TG levels in mouse model of hyperlipidemia, and remarkably decrease the increase of TG in primary mouse hepatocytes induced by high glucose and the increase of TG in HepG2 cells induced by oleic acid. The fraction B2, isolated from B on bioactivity-guided fractionation, could significantly decrease TG level in HepG2 cells. One compound with the highest content in B2 was isolated and determined as luteolin-7-O-beta-D-glucopyranoside by NMR spectra. It could significantly reduce the TG level in HepG2 cells, and inhibited the accumulation of lipids by oil red O stain.</p> <p>Conclusion</p> <p>Our results demonstrated that the 75% ethanol extract of CSFP could improve <it>in vitro </it>and <it>in vivo </it>lipid accumulation. Luteolin-7-O-beta-D-glucopyranoside might be a leading pharmacodynamical material of CSFP for lowering lipids.</p

A high-resolution haplotype-resolved Reference panel constructed from the China Kadoorie Biobank Study

Precision medicine depends on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is still not suitable for gigantic studies due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we used 10 000 samples with medium-depth WGS to construct a reference panel that we named the CKB reference panel. By imputing microarray datasets, it showed that the CKB panel outperformed compared panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of 100 706 microarrays with the CKB panel, and the after-imputed data is the hitherto largest whole genome data of the Chinese population. Furthermore, in the GWAS analysis of real phenotype height, the number of tested SNPs tripled and the number of significant SNPs doubled after imputation. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the CKB panel is of great value for imputing microarray or low-coverage genotype data of Chinese population, and potentially mixed populations. The imputation-completed 100 706 microarray data are enormous and precious resources of population genetic studies for complex traits and diseases

Prevalence of violence to others among individuals with schizophrenia in China: A systematic review and meta-analysis

BackgroundViolence to others (hereinafter referred to as “violence-TO”) is common in individuals with schizophrenia. The reported prevalence of violence-TO among schizophrenics ranges widely in existing studies. Improved prevalence estimates and identification of moderators are needed to guide future management and research.MethodsWe searched EBSCO, EMBASE, Medline, PubMed, Science Direct, Web of Science, CNKI, VIP, WANFANG data, and CBM for relevant articles published before June 5, 2022. Meanwhile, violence-TO was summarized into four categories: (a) violence-TO on the reviews of official criminal or psychiatric records (type I); (b) less serious forms of violence-TO (type II); (c) physical acts causing demonstrable harm to victims (type III); (d) homicide (type IV). We did meta-analysis for the above types of violence-TO, respectively, and applied subgroup analyses and meta-regression analyses to investigate the source of heterogeneity.ResultsA total of 56 studies were eligible in this study and 34 of them were high-quality. The prevalence of type I to type IV in individuals with schizophrenia in China was 23.83% (95% CI: 18.38–29.75%), 23.16% (95% CI: 8.04–42.97%), 17.19% (95%CI: 8.52–28.04%), and 0.62% (95% CI: 0.08–1.54%) respectively. The results of the subgroup analysis showed that the prevalence of type I was higher among subjects in the inland than in the coastal non-economic zone, while the prevalence of type III was the highest in the coastal economic zone, followed by the inland region and the lowest in the coastal non-economic zone. The results of multivariate meta-regression analyses showed that: patient source in type I (β = 0.15, P &lt; 0.01), patient source (β = 0.47, P &lt; 0.01), and proportion of male (β = 0.19, P &lt; 0.01) in type II, age (β = 0.25, P &lt; 0.01), and GDP per capita (β = 0.05, P = 0.01) in type III were statistically significant.ConclusionThe prevalence of different types of violence-TO and their influencing factors varied. Therefore, the authorities should take different management measures. In addition to individual factors, regional factors may also affect violence-TO, which suggests the need for a multi-sectorial approach to prevention and treatment for subjects in different regions and adopting targeted control strategies.Systematic Review Registration[www.ClinicalTrials.gov], identifier [CRD42021269767]

An Inhibitory Effect of Dryocrassin ABBA on Staphylococcus aureus vWbp That Protects Mice From Pneumonia

Von Willebrand factor-binding protein (vWbp), secreted by Staphylococcus aureus (S. aureus), can activate host prothrombin, convert fibrinogen to fibrin clots, induce blood clotting, and contribute to pathophysiology of S. aureus-related diseases, including infective endocarditis, staphylococcal sepsis and pneumonia. Therefore, vWbp is an promising drug target in the treatment of S. aureus-related infections. Here, we report that dryocrassin ABBA (ABBA), a natural compound derived from Dryopteris crassirhizoma, can significantly inhibit the coagulase activity of vWbp in vitro by directly interacting with vWbp without killing the bacteria or inhibiting the expression of the vWbp. Using molecular dynamics simulations, we demonstrate that ABBA binds to the “central cavity” in the elbow of vWbp by interacting with Arg-70, His-71, Ala-72, Gly-73, Tyr-74, Glu-75, Tyr-83, and Gln-87 in vWbp, thus interfering with the binding of vWbp to prothrombin. Furthermore, in vivo studies demonstrated that ABBA can attenuate injury and inflammation of mouse lung tissues caused by S. aureus and increase survival of mice. Together these findings indicate that ABBA is a promising lead drug for the treatment of S. aureus-related infections. This is the first report of potential inhibitor which inhibit the coagulase activity of vWbp by directly interacting with vWbp

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules