eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells

ObjectiveWe investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs).MethodsCortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.ResultsMdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.ConclusionseEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.     

Post-translational modifications of protein in response to ionizing radiation

Based on central dogma of genetics, protein is the embodiment and executor of genetic function, post-translational modifications (PTMs) of protein are particularly important and involved in almost all aspects of cell biology and pathogenesis. Studies have shown that ionizing radiation (IR) alters gene expression much more profoundly and a broad variety of cell-process pathways, lots of proteins are modified and activated. Our understanding of the protein in response to ionizing radiation is steadily increasing. Among the various biological processes known to induce radioresistance, PTMs have attracted marked attention in recent years. The present review summarizes the latest knowledge about how PTMs response to ionizing radiation and pathway analysis were conducted. The data provided insights into biological effects of IR and contributing to the development of novel IR-based strategies.     

Genetic Variants Associated with Lipid Profiles in Chinese Patients with Type 2 Diabetes

Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (ABCA1, GCKR, BAZ1B, TOMM40, DOCK7, HNF1A, and HNF4A) were genotyped. After adjusting for multiple covariates, SNPs in ABCA1, GCKR, BAZ1B, TOMM40, and HNF1A were identified as significantly associated with triglyceride levels in T2D patients (P < 0.05). The associations between the SNPs in ABCA1 (rs3890182), GCKR (rs780094), and BAZ1B (rs2240466) remained significant even after correction for multiple testing (P = 8.85×10⁻³, 7.88×10⁻⁷, and 2.03×10⁻⁶, respectively). BAZ1B (rs2240466) also was associated with the total cholesterol level (P = 4.75×10⁻²). In addition, SNP rs157580 in TOMM40 was associated with the low-density lipoprotein cholesterol level (P = 6.94×10⁻³). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes.     

Potential natural vegetation and pre‐anthropic pollen records on the Azores Islands in a Macaronesian context

This paper discusses the concept of potential natural vegetation (PNV) in the light of the pollen records available to date for the Macaronesian biogeographical region, with emphasis on the Azores Islands. The classical debate on the convenience or not of the PNV concept has been recently revived in the Canary Islands, where pollen records of pre‐anthropic vegetation seemed to strongly disagree with the existing PNV reconstructions. Contrastingly, more recent PNV model outputs from the Azores Islands show outstanding parallelisms with pre‐anthropic pollen records, at least in qualitative terms. We suggest the development of more detailed quantitative studies to compare these methodologies as an opportunity for improving the performance of both. PNV modelling may benefit by incorporating empirical data on past vegetation useful for calibration and validation purposes, whereas palynology may improve past reconstructions by minimizing interpretative biases linked to differential pollen production, dispersal and preservation.     

Statures in Han populations of China

<正>Dear Editor,Shortly after initiating the"Physical Anthropological Research on Han Chinese"research project,we applied uniform sampling methods as well as methods and instruments of measurement to obtain a complete set of measurements of physical anthropological indicators among Han populations across China.Among these measurements,body stature was a key indicator.Currently,there should be reliable     

Probing the U-Shaped Conformation of Caveolin-1 in a Bilayer

Caveolin induces membrane curvature and drives the formation of caveolae that participate in many crucial cell functions such as endocytosis. The central portion of caveolin-1 contains two helices (H1 and H2) connected by a three-residue break with both N- and C-termini exposed to the cytoplasm. Although a U-shaped configuration is assumed based on its inaccessibility by extracellular matrix probes, caveolin structure in a bilayer remains elusive. This work aims to characterize the structure and dynamics of caveolin-1 (D82–S136; Cav1_82–136) in a DMPC bilayer using NMR, fluorescence emission measurements, and molecular dynamics simulations. The secondary structure of Cav1_82–136 from NMR chemical shift indexing analysis serves as a guideline for generating initial structural models. Fifty independent molecular dynamics simulations (100 ns each) are performed to identify its favorable conformation and orientation in the bilayer. A representative configuration was chosen from these multiple simulations and simulated for 1 μs to further explore its stability and dynamics. The results of these simulations mirror those from the tryptophan fluorescence measurements (i.e., Cav1_82–136 insertion depth in the bilayer), corroborate that Cav1_82–136 inserts in the membrane with U-shaped conformations, and show that the angle between H1 and H2 ranges from 35 to 69°, and the tilt angle of Cav1_82–136 is 27 ± 6°. The simulations also reveal that specific faces of H1 and H2 prefer to interact with each other and with lipid molecules, and these interactions stabilize the U-shaped conformation.     

Interactions between bacteria and fungi in macrophyte leaf litter decomposition

Microbes play an important role in decomposition of macrophytes in shallow lakes, and the process can be greatly affected by bacteria–fungi interactions in response to material composition and environmental conditions. In this study, microbes involved in the decomposition of leaf litter from three macrophyte species, Zizania latifolia, Hydrilla verticillata and Nymphoides peltata, were analysed at temperatures of 5, 15 and 25 °C. Results indicate that the decomposition rate was affected by temperature. Bacterial alpha diversity increased significantly along the time, while both temperature and plant species had a significant impact on the bacterial community, and plant type was shown to be the most important driving factor for the fungal community. The cosmopolitan bacterial taxa affiliated with Gammaproteobacteria, Bacteroidetes, Deltaproteobacteria, Firmicutes and Spirochaetes were key species in the investigated ecological networks, demonstrating significant co-occurrence or co-exclusion relationships with Basidiomycota and Ascomycota, according to different macrophyte species. This study indicates that bacteria involved in the decomposition of macrophyte leaf litter are more sensitive to temperature variance, and that fungi have a higher specificity to the composition of plant materials. The nutrient content of Hydrilla verticillata promoted a positive bacteria–fungi interaction, thereby accelerating the decomposition and re-circulation of leaf litter.