A Proteomic Approach Identifies Isoform-Specific and Nucleotide-Dependent RAS Interactions

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Changes in concentrations of circulating heat‐shock proteins in House Finches in response to different environmental stressors

Heat‐shock proteins (HSP) are molecular chaperones that play key roles in the maintenance of cellular homeostasis under variable environmental conditions. Although HSP are frequently used in studies of wild vertebrates as indicators of stress, no one to date has assessed responses of HSP60, HSP70, and HSP90 in the same species to different environmental stressors. We studied changes in the circulating concentrations of HSP60, HSP70, and HSP90 in wild‐caught House Finches (Haemorhous mexicanus) in response to multiple and sequential stressful environments, including high temperatures, transportation, and pathogen exposure. House Finches sampled during a period of low‐environmental stress with moderate ambient temperatures had low levels of HSP60 and modest levels of HSP70 and HSP90 compared to birds sampled during a presumably more stressful period with high temperatures. After exposure to high‐ambient temperatures, transportation in a vehicle, and exposure to Mycoplasma gallisepticum, captive finches were found to have increasingly higher levels of HSP60. HSP70 tended to rise in response to each stressor, but to drop in the weeks between stress challenges. HSP90 levels increased significantly only in response to pathogen challenge. Our observations suggest that HSP60 and HSP70 are indices of a range of stressors in House Finches, whereas HSP90 primarily reflects health state.     

Retracted: Smad4 gene silencing enhances the chemosensitivity of human lymphoma cells to adriamycin via inhibition of the activation of transforming growth factor β signaling pathway

There are diverse investigations focused on the therapies of lymphoma. Our research was taken to identify the effects of lentiviral-mediated Smad4 gene silencing on chemosensitivity of human lymphoma cells to adriamycin (ADM) via transforming growth factor β (TGFβ) signaling pathway. Raji/ADM cells were cultured and infected with lentiviral particles Smad4-short hairpin (shRNA) and control-shRNA. Then, the messenger RNA (mRNA) and protein levels of TGFβ signaling pathway–related factors (Smad4, Smad3, cyclinE, cyclinD1, and p21) in Raji/ADM cells were determined. The effect of Smad4-shRNA on cell viability, invasion and migration, and apoptosis were also detected. Compared with the Raji group, increased mRNA and protein levels of Smad4, Smad3, cyclinE, cyclinD1, enhanced cell proliferation, migration and invasion as well as decreased mRNA, and protein levels of p21 and cell apoptosis rate were found in the Raji/ADM and control-shRNA groups. However, Smad4 gene silencing resulted in decreased mRNA and protein levels of Smad4, Smad3, cyclinE, and cyclinD1 along with inhibited cell proliferation, migration and invasion but increased expression of p21 together with cell apoptosis. Collectively, Smad4 gene silencing can inhibit the activation of TGFβ signaling pathway, thereby enhancing the chemosensitivity of human lymphoma cells to ADM.     

Microbial Products Induce Claudin-2 to Compromise Gut Epithelial Barrier Function

The epithelial barrier dysfunction is an important pathogenic feature in a number of diseases. The underlying mechanism is to be further investigated. The present study aims to investigate the role of tight junction protein claudin-2 (Cldn2) in the compromising epithelial barrier function. In this study, the expression of Cldn2 in the epithelial layer of mice and patients with food allergy was observed by immunohistochemistry. The induction of Cldn2 was carried out with a cell culture model. The Cldn2-facilitated antigen internalization was observed by confocal microscopy. The epithelial barrier function in the gut epithelial monolayer was assessed by recording the transepithelial resistance and assessing the permeability to a macromolecular tracer. The results showed that the positive immune staining of Cldn2 was observed in the epithelial layer of the small intestine that was weakly stained in naïve control mice, and strongly stained in sensitized mice as well as patients with food allergy. Exposure to cholera toxin or Staphylococcal enterotoxin B induced the expression of Cldn2 in HT-29 or T84 cells. Cldn2 could bind protein antigen to form complexes to facilitate the antigen transport across the epithelial barrier. Blocking Cldn2 prevented the allergen-related hypersensitivity the intestine. We conclude that the tight junction protein Cldn2 is involved in the epithelial barrier dysfunction.     

SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape

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Endocrine Control of Calcium Metabolism in Teleosts

It is evident that fishes regulate their serum calcium efficientlybut that endocrine systems involved may be different from thosein tetrapods. A functional parathyroid gland has not yet beendemonstrated in fishes. The majority of evidence indicates thatcalcitonin has little or no effect on fish calcium regulation.Instead, the corpuscles of Stannius and the pituitary glandare necessary for maintaining fish serum calcium levels. Inthe killifish, Fundulus heteroclitus, the removal of the corpusclesproduces hypercalcemia in sea water but not in artificial seawater deficient in calcium. Transplants of the corpuscles orthe administration of corpuscle homogenate corrects the increasein calcium. On the other hand, hypophysectomy elicits hypocalcemiaunder calcium deficient conditions but not in calcium rich seawater. Replacement therapy with pituitary homogenate or hypophysialtransplant prevents the fall in calcium. It is postulated thatthe hypocalcemic corpuscles of Stannius and the hypercalcemicpituitary gland enable the euryhaline killifish to regulateits serum calcium levels in high calcium sea water and low calciumfresh water, respectively.     

一株沙福芽胞杆菌生长及其产碳酸酐酶特性

为了探明一株沙福芽胞杆菌(Bacillus safensis)的生长与产碳酸酐酶(carbonic anhydrase,CA)特性,采用单因素实验,研究了培养基初始pH、接种量、温度、摇床转速及Zn2+、Co2+、Cd2+、Mn2+、Mg2+、Ca2+等金属离子对细菌生长及其产CA活性的影响.结果表明,该菌株的最佳生长...     

Label-retention expansion microscopy

Expansion microscopy (ExM) increases the effective resolving power of any microscope by expanding the sample with swellable hydrogel. Since its invention, ExM has been successfully applied to a wide range of cell, tissue, and animal samples. Still, fluorescence signal loss during polymerization and digestion limits molecular-scale imaging using ExM. Here, we report the development of label-retention ExM (LR-ExM) with a set of trifunctional anchors that not only prevent signal loss but also enable high-efficiency labeling using SNAP and CLIP tags. We have demonstrated multicolor LR-ExM for a variety of subcellular structures. Combining LR-ExM with superresolution stochastic optical reconstruction microscopy (STORM), we have achieved molecular resolution in the visualization of polyhedral lattice of clathrin-coated pits in situ.     

Replication potentials of HIV-1/HSIV in PBMCs from northern pigtailed macaque (Macaca leonina)

The northern pig-tailed macaque(Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1(HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-1NL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of vif-substituted HIV-1(HSIV) in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-1SV chimeras, two HIV-1NL4-3-derived viruses encoding the viral infectivity factor(Vif) protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.