Bone marrow-derived mesenchymal stem cells improve post-ischemia neurological function in rats via the PI3K/AKT/GSK-3β/CRMP-2 pathway

Background: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. However, the underlying protective mechanism remains undetermined. Here, we tested the hypothesis that transplantation of BMSCs via intravenous injection can alleviate neurological functional deficits through activating PI3K/AKT signaling pathway after cerebral ischemia in rats.

Methods: A cerebral ischemic rat model was established by the 2 h middle cerebral artery occlusion (MCAO). Twenty-four hours later, BMSCs (1?×?10⁶ in 1 ml PBS) from SD rats were injected into the tail vein. Neurological function was evaluated by modified neurological severity score (mNSS) and modified adhesive removal test before and on d1, d3, d7, d10 and d14 after MCAO. Protein expressions of AKT, GSK-3β, CRMP-2 and GAP-43 were detected by Western-bolt. NF-200 was detected by immunofluorescence.

Results: BMSCs transplantation did not only significantly improve the mNSS score and the adhesive-removal somatosensory test after MCAO, but also increase the density of NF-200 and the expression of p-AKT, pGSK-3β and GAP-43, while decrease the expression of pCRMP-2. Meanwhile, these effects can be suppressed by LY294002, a specific inhibitor of PI3K/AKT.

Conclusion: These data suggest that transplantation of BMSCs could promote axon growth and neurological deficit recovery after MCAO, which was associated with activation of PI3K/AKT /GSK-3β/CRMP-2 signaling pathway.

     

Consumer-driven nutrient release to the water by a small omnivorous fish enhanced ramet production but reduced the growth rate of the submerged macrophyte Vallisneria denseserrulata (Makino) Makino

Small fish are highly associated with submerged macrophytes but may potentially hamper their growth due to nutrient excretion that stimulate growth of phytoplankton and periphyton growth. We conducted a mesocosm experiment to elucidate the effects of the small omnivore Chinese bitterling Acheilognathus macropterus on the growth of phytoplankton, periphyton and the submerged macrophyte Vallisneria denseserrulata. The treatments were fishless as well as low (LF) and high (HF) fish density. We found that the concentrations of nutrients and the phytoplankton biomass increased substantially in both fish treatments, leading to a significantly higher light attenuation compared with the control. Moreover, bitterling substantially enhanced the biomass of periphyton on plant leaves. Consequently, the relative growth rate (RGR) of V. denseserrulata was significantly suppressed in HF, while RGR in the LF treatment did not differ significantly from the controls. However, the bitterling also stimulated the ramet production of V. denseserrulata, significantly. Our results indicate that Chinese bitterling reduce the RGR of V. denseserrulata under high fish density condition. Therefore, the density of Chinese bitterling should be kept low in order to reduce the negative effects of the fish on the RGR of submerged macrophytes (e.g. V. denseserrulata), when restoring lakes by plant transplantation.

     

Valproic Acid Causes Proteasomal Degradation of DICER and Influences miRNA Expression

Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA’s clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER.     

Association of Cerebral Networks in Resting State with Sexual Preference of Homosexual Men: A Study of Regional Homogeneity and Functional Connectivity

Recent imaging studies have shown that brain morphology and neural activity during sexual arousal differ between homosexual and heterosexual men. However, functional differences in neural networks at the resting state is unknown. The study is to characterize the association of homosexual preference with measures of regional homogeneity and functional connectivity in the resting state. Participants were 26 healthy homosexual men and 26 age-matched healthy heterosexual men in whom we collected echo planar magnetic resonance imaging data in the resting state. The sexual orientation was evaluated using the Kinsey Scale. We first assessed group differences in regional homogeneity and then, taking the identified differences as seed regions, we compared groups in measures of functional connectivity from those seeds. The behavioral significances of the differences in regional homogeneity and functional connectivity were assessed by examining their associations with Kinsey Scores. Homosexual participants showed significantly reduced regional homogeneity in the left inferior occipital gyrus, right middle occipital gyrus, right superior occipital gyrus, left cuneus, right precuneus, and increased regional homogeneity in rectal gyrus, bilateral midbrain, and left temporal lobe. Regional homogeneity correlated positively with Kinsey scores in the left inferior occipital gyrus. The homosexual group also showed reduced functional connectivity between left middle temporal gyrus, left supra-marginal gyrus, right cuneus and the seed region, i.e. left inferior occipital gyrus. Additionly, the connection between the left inferior occipital gyrus and right thalamus correlated positively with Kinsey scores. These differences in regional homogeneity and functional connectivity may contribute to a better understanding of the neural basis of male sexual orientation.     

Characterization of two monoclonal antibodies, 38F10 and 44D11,against the major envelope fusion protein of Helicoverpa armigera nucleopolyhedrovirus

The envelope fusion protein F of baculoviruses is a class I viral fusion protein which play a significant role during virus entry into insect cells. F is initially synthesized as a precursor(F_0) and then cleaved into a disulfide-linked F_1 and F_2 subunits during the process of protein maturation and secretion. To facilitate further investigation into the structure and function of F protein during virus infection, monoclonal antibodies(mAbs) against the F_2 subunit of Helicoverpa armigera nucleopolyhedrovirus(HearNPV)(Ha F) were generated. Two kinds of mAbs were obtained according to their different recognition epitopes: one kind of mAbs, as represented by 38F10,recognizes amino acid(aa) 85 to 123 of F_2 and the other kind, represented by 44D11, recognizes aa148 to 173 of F_2. Western blot and immunofluorescence assay confirmed that both of the mAbs recognized the F protein expressed in HearNPV infected cells, however, only 44D11 could neutralize HearNPV infection. The results further showed that 44D11 may not interact with a receptor binding epitope, rather it was demonstrated to inhibit syncytium formation in cells expressing the Ha F protein. The results imply that the monoclonal antibody 44D11 recognizes a region within HaF_2 that may be involved in the F-mediated membrane fusion process.     

Proper autophagy is indispensable for angiogenesis during chick embryo development

People have known that autophagy plays a very important role in many physiological and pathological events. But the role of autophagy on embryonic angiogenesis still remains obscure. In this study, we demonstrated that Atg7, Atg8 and Beclin1 were expressed in the plexus vessels of angiogenesis at chick yolk sac membrane and chorioallantoic membrane. Interfering in autophagy with autophagy inducer or inhibitor could restrict the angiogenesis in vivo, which might be driven by the disorder of angiogenesis-related gene expressions, and also lead to embryonic hemorrhage, which was due to imperfection cell junctions in endothelial cells including abnormal expressions of tight junction, adheren junction and desmosome genes. Using HUVECs, we revealed that cell viability and migration ability changed with the alteration of cell autophagy exposed to RAPA or 3-MA. Interestingly, tube formation assay showed that HUVECs ability of tube formation altered with the change of Atg5, Atg7 and Atg8 manipulated by the transfection of their corresponding siRNA or plasmids. Moreover, the lost cell polarity labeled by F-actin and the absenced β-catenin in RAPA-treated and 3-MA-treated cell membrane implied intracellular cytoskeleton alteration was induced by the activation and depression of autophagy. Taken together, our current experimental data reveal that autophagy is really involved in regulating angiogenesis during embryo development.     

线粒体蛋白质组及蛋白质量控制

线粒体是哺乳动物细胞内重要细胞器,不仅通过氧化磷酸化产生ATP为细胞提供能量,也参与调节钙离子稳态、活性氧(reactive oxygen species,ROS)的产生、细胞应激反应和细胞死亡等过程,其功能障碍不仅导致多种人类疾病的发生,而且也能降低动物卵母细胞质量和早期胚胎发育能力.大量证据表明,线粒体的功能依赖于...