Binding of human centrin 2 to the centrosomal protein hSfi1

hSfi1, a human centrosomal protein with homologs in other eukaryotic organisms, includes 23 repeats, each of 23 amino acids, separated by 10 residue linkers. The main molecular partner in the centrosome is a small, calcium-binding EF-hand protein, the human centrin 2. Using isothermal titration calorimetry experiments, we characterized the centrin-binding capacity of three isolated hSfi1 repeats, two exhibiting the general consensus motif and the third being the unique Pro-containing human repeat. The two standard peptides bind human centrin 2 and its isolated C-terminal domain with high affinity (approximately 10(7) M(-1)) by an enthalpy-driven mechanism, with a moderate Ca2+ dependence. The Pro-containing repeat shows a binding affinity that is two orders of magnitude lower. The target binding site is localized within the C-terminal domain of human centrin 2. Fluorescence titration and NMR spectroscopy show that the well-conserved Trp residue situated in the C-terminus of each repeat is deeply embedded in a protein hydrophobic cavity, indicating that the peptide direction is reversed relative to previously studied centrin targets. The present results suggest that almost all of the repeats of the Sfi1 protein may independently bind centrin molecules. On the basis of this hypothesis and previous studies on centrin self-assembly, we propose a working model for the role of centrin-Sfi1 interactions in the dynamic structure of centrosome-associated contractile fibers.     

Overexpression of EMMPRIN is associated with lymph node metastasis and advanced stage of non-small cell lung cancer: a retrospective study

Background

Previous studies show that overexpression of EMMPRIN involved in the malignant biological behavior of tumors. This investigation was to disclose the expression status of EMMPRIN in non-small cell lung cancer (NSCLC) and its clinical value for the diagnosis of NSCLC.

Methods

The expression of EMMPRIN was examined using immunohistochemistry and enzyme-linked immunosorbent assay. The clinical value of EMMPRIN was evaluated by drawing a receiver operating characteristic (ROC) curve.

Results

NSCLC tissues and serum exhibited higher expression levels of EMMPRIN than the normal control (p?<?0.05), and the expression of the EMMPRIN was significantly associated with lymphatic invasion and advanced stage of NSCLC (p?<?0.05). ROC curve suggested that the threshold level of serum EMMPRIN for distinguishing NSCLC from control group was 80.3 pg/mL, and displayed a sensitivity of 97.22% and a specificity of 95%. And higher EMMPRIN expression in serum and tissues appeared to be risk factors for NSCLC development (risk ratio =1.56 and 1.1).

Conclusion

Overexpression of EMMPRIN was associated with lymphatic metastasis and advanced stage of NSCLC and test of serum EMMPRIN contributes to the NSCLC diagnosis.

     

酵母菌的微生态调节作用

酵母菌能够产生大量的B族维生素和氨基酸,既可以帮助消化,促进营养物质的吸收,刺激有益菌的生长,又可为动物提供蛋白质.酵母菌直接参与生物屏障的构成,发挥对致病菌和条件致病菌的拮抗作用,促进优势种群生长,调整微生态平衡.     

A combined steepest descent and genetic algorithm (SD/GA) approach for the optimization of solvation parameters

An accurate solvation model is essential for computer modeling of protein folding and other biomolecular self-assembly processes. Compared to explicit solvent models, implicit solvent models, such as the Poisson-Boltzmann (PB) with solvent accessible surface area model (PB/SA), offer a much faster speed—the most compelling reason for the popularity of these implicit solvent models. Since these implicit solvent models typically use empirical parameters, such as atomic radii and the surface tensions, an optimal fit of these parameters is crucial for the final accuracy of properties such as solvation free energy and folding free energy. In this paper, we proposed a combined approach, namely SD/GA, which takes the advantage of both local optimization with the steepest descent (SD), and global optimization with the genetic algorithm (GA), for parameters optimization in multi-dimensional space. The SD/GA method is then applied to the optimization of solvation parameters in the non-polar cavity term of the PB/SA model. The results show that the newly optimized parameters from SD/GA not only increase the accuracy in the solvation free energies for ～200 organic molecules, but also significantly improve the free energy landscape of a β-hairpin folding. The current SD/GA method can be readily applied to other multi-dimensional parameter space optimization as well.     

Length–weight relationships for 15 fish species from the Three Gorges Reservoir

The length–weight relationships (LWRs) for 15 fish species from the Three Gorges Reservoir (TGR) were described in this paper. Specimens were collected using gill nets (mesh size: 6, 8, 10, 12 cm), cage net (mesh size: 1 cm), benthic fyke net (mesh size: 1 cm), hook longlines (80 m long, 3 barbless hooks per meter line) and electrofishing (power: 1,500 w; distance of electrodes: 1–2 m; water depth: 0.2–1.0 m; water area: 1–2 m²; catch by dip net [mesh size: 0.4 cm]) at four sections of the TGR, monthly in June–August and October–November in 2017 and 2018. The first LWR reference for Zacco acutipinnis (Bleeker, 1871), Discogobio brachyphysallidos Huang, 1989, Squalidus nitens (Günther, 1873), Leptobotia pellegrini Fang, 1936, Sinibotia reevesae (Chang, 1944), Pseudobagrus tenuifurcatus (Nichols, 1931), Pseudobagrus medianalis (Regan, 1904), Liobagrus marginatoides (Wu, 1930), Glyptothorax fokiensis (Rendahl, 1925), and Ctenogobius szechuanensis (Liu, 1940) and new maximum total length for 12 species are provided.     

Radiofrequency Ablation versus Resection for Colorectal Cancer Liver Metastases: A Meta-Analysis

Background

No randomized controlled trial (RCT) has yet been performed to provide the evidence to clarify the therapeutic debate on liver resection (LR) and radiofrequency ablation (RFA) in treating colorectal liver metastases (CLM). The meta-analysis was performed to summarize the evidence mostly from retrospective clinical trials and to investigate the effect of LR and RFA.

Methodology/Principal Findings

Systematic literature search of clinical studies was carried out to compare RFA and LR for CLM in Pubmed, Embase and the Cochrane Library Central databases. The meta-analysis was performed using risk ratio (RR) and random effect model, in which 95% confidence intervals (95% CI) for RR were calculated. Primary outcomes were the overall survival (OS) and disease-free survival (DFS) at 3 and 5 years plus mortality and morbidity. 1 prospective study and 12 retrospective studies were finally eligible for meta-analysis. LR was significantly superior to RFA in 3 -year OS (RR 1.377, 95% CI: 1.246–1.522); 5-year OS (RR: 1.474, 95%CI: 1.284–1.692); 3-year DFS (RR 1.735, 95% CI: 1.483–2.029) and 5-year DFS (RR 2.227, 95% CI: 1.823–2.720). The postoperative morbidity was higher in LR (RR: 2.495, 95% CI: 1.881–3.308), but no significant difference was found in mortality between LR and RFA. The data from the 3 subgroups (tumor<3 cm; solitary tumor; open surgery or laparoscopic approach) showed significantly better OS and DFS in patients who received surgical resection.

Conclusions/Significances

Although multiple confounders exist in the clinical trials especially the bias in patient selection, LR was significantly superior to RFA in the treatment of CLM, even when conditions limited to tumor<3 cm, solitary tumor and open surgery or laparoscopic (lap) approach. Therefore, caution should be taken when treating CLM with RFA before more supportive evidences for RFA from RCTs are obtained.     

Physical properties and biocompatibility of a porous chitosan-based fiber-reinforced conduit for nerve regeneration

Porous fiber-reinforced chitosan nerve conduits were fabricated from chitosan yarns and a chitosan solution by combining an industrial braiding method with a mold casting/lyophilization technique. The conduits were permeable to molecules ranging in molecular size from 180 Da (glucose) to 66,200 Da (BSA). The compressive load of the reinforced conduits was significantly higher than that of a non-reinforced control conduit at equal levels of strain. The tensile strength of the reinforced conduits was also increased from 0.41 ± 0.17 to 3.69 ± 0.64 MPa. An in vitro cytotoxicity test showed the conduits were not cytotoxic to Neuro-2a cells. Preliminary in vivo implantation testing indicated that the conduits were compatible with the surrounding tissue. Aijun Wang and Qiang Ao contributed equally to this work.     

Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas

Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations.     

Platelet-derived growth factor-induced disruption of gap junctional communication and phosphorylation of connexin43 involves protein kinase C and mitogen-activated protein kinase

Previously we showed a rapid and transient inhibition of gap junctional communication (GJC) by platelet-derived growth factor (PDGF) in T51B rat liver epithelial cells expressing wild-type platelet-derived growth factor β receptors (PDGFrβ). This action of PDGF correlated with the hyperphosphorylation of the gap junction protein connexin43 (Cx43) and required PDGFrβ tyrosine kinase activity, suggesting the participation of protein kinases and phosphatases many of which are activated by PDGF treatment. In the present study, two such kinases, namely protein kinase C (PKC) and mitogen-activated protein kinase (MAPK), are investigated for their possible involvement in PDGF-induced closure of junctional channels and Cx43-phosphorylation. Down-regulation of PKC-isoforms by 12-O-tetradecanoylphorbol-13-acetate or pretreatment with the PKC inhibitor calphostin C, completely blocked PDGF action on GJC and Cx43. Activation of MAPK correlated with PDGF-induced Cx43 phosphorylation, and prevention of MAPK activation by PD98059 eliminated the PDGF effects. Interestingly, elimination of GJC recovery by cycloheximide was associated with a sustained activated-MAPK level. Based on these results we postulate that the activation of PKC and MAPK are required in PDGF-mediated Cx43 phosphorylation and junctional closure. J. Cell. Physiol. 176:332–341, 1998. © 1998 Wiley-Liss, Inc.