PRG3 and PRG5 C-Termini: Important Players in Early Neuronal Differentiation

The functional importance of neuronal differentiation of the transmembrane proteins’ plasticity-related genes 3 (PRG3) and 5 (PRG5) has been shown. Although their sequence is closely related, they promote different morphological changes in neurons. PRG3 was shown to promote neuritogenesis in primary neurons; PRG5 contributes to spine induction in immature neurons and the regulation of spine density and morphology in mature neurons. Both exhibit intracellularly located C-termini of less than 50 amino acids. Varying C-termini suggested that these domains shape neuronal morphology differently. We generated mutant EGFP-fusion proteins in which the C-termini were either swapped between PRG3 and PRG5, deleted, or fused to another family member, plasticity-related gene 4 (PRG4), that was recently shown to be expressed in different brain regions. We subsequently analyzed the influence of overexpression in immature neurons. Our results point to a critical role of the PRG3 and PRG5 C-termini in shaping early neuronal morphology. However, the results suggest that the C-terminus alone might not be sufficient for promoting the morphological effects induced by PRG3 and PRG5.     

LPPR5 Expression in Glioma Affects Growth,Vascular Architecture,and Sunitinib Resistance

Despite intensive research, glioblastoma remains almost invariably fatal. Various promising drugs targeting specific aspects of glioma biology, in addition to or as an alternative to antiproliferative chemotherapy, were not successful in larger clinical trials. Further insights into the biology of glioma and the mechanisms behind the evasive-adaptive response to targeted therapies is needed to help identify new therapeutic targets, prognostics, or predictive biomarkers. As a modulator of the canonically oncogenic Rho-GTPase pathway, Lipid phosphate phosphatase-related protein type 5 (LPPR5) is pivotal in influencing growth, angiogenesis, and therapeutic resistance. We used a GL261 murine orthotopic allograft glioma model to quantify the tumor growth and to obtain tissue for histological and molecular analysis. Epicortical intravital epi-illumination fluorescence video microscopy of the tumor cell spheroids was used to characterize the neovascular architecture and hemodynamics. GL261-glioma growth was delayed and decelerated after LPPR5 overexpression (LPPR5^OE). We observed increased tumor cell apoptosis and decreased expression and secretion of vascular endothelial growth factor A in LPPR5^OE glioma. Hence, an altered micro-angioarchitecture consisting of dysfunctional small blood vessels was discovered in the LPPR5^OE tumors. Sunitinib therapy eliminated these vessels but had no effect on tumor growth or apoptosis. In general, LPPR5 overexpression generated a more benign, proapoptotic glioma phenotype with delayed growth and a dysfunctional vascular architecture.     

Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection in Prg4 Null Mice

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4—PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4^−/− (N = 44) mice of both sexes were injected with rhPRG4 and gait alterations were studied at post-injection day 3 and 6, before joints were harvested for immunohistochemistry for caspase-3 activation. Increased stance and propulsion was shown at 3 days post-injection in male mice. There were significantly fewer caspase-3-positive chondrocytes in tibiofemoral cartilage from rhPRG4-injected mice. The mitochondrial gene Mt-tn, and myosin heavy (Myh7) and light chains (Myl2 and Myl3), known to play a cytoskeletal stabilizing role, were significantly upregulated in both sexes (RNA-Seq) following IA rhPRG4. Chondrocyte mitochondrial dyscrasias attributable to the arthrosis in CACP may be mitigated by IA rhPRG4. In a supporting in vitro crystal microbalance experiment, molecular fouling by albumin did not block the surface activity of rhPRG4.     

Evaluation of antioxidant and immune activity of Phellinus ribis glucan in mice

The potential protective effects of Phellinus ribis glucan (PRG) administration against immune injury due to free radical formation were evaluated in mice. The results showed that glucan administration significantly increased thymus and spleen indices, spleen lymphocyte proliferation and NK cells activity, as well as CD8 T cell numbers, and decreased CD4+/CD8+. In accordance with a previous study, glucan administration significantly enhanced plasma glutathione peroxidase, superoxide dismutases activity and reduced plasma thiobarbituric acid reactive species level. In conclusion, our results indicate that glucan administration improve immune function by its free radicals scavenging activity and reducing oxidative stress in mice.     

低密度无固相海水钻井液在南海西部D气田的应用

南海西部D气田目前在生产的浅层气藏,属上第三系莺歌海组地层,是中孔中渗的泥岩储层,该地层较复杂,钻进时易发生掉块、井塌、卡钻等井下复杂。在研究储层岩石性质及现有钻井液性能存在问题基础上,提出应提高体系的封堵性能以及抑制性能,措施为:在φ311.1 mm井段原PRG钻井液配方中增加VIS,降低滤液侵入速度,降低钻井液对于井壁的冲刷作用;降低PLUS的含量和增加PF-FLOTROL,降低黏度并增强降滤失性能;在φ215.9 mm井段原PRF钻井液配方中增加Greenseal,形成致密隔离层带,封堵微裂缝和孔喉,降低滤液渗透,延长井壁稳定时间;增加EZCARB的含量并且使用KCl加重,增加抑制性能。评价结果表明,PRG和PRF钻井液具有滤失量低（API滤失量为2.1 mL,高温高压滤失量约为4.3 mL）、流变性好、抑制性强（滚动回收率约为90%）和抗污染能力强（抗盐达10%,抗钙达2%）等特点。在D气田P3H井和D4H井的现场应用表明,使用PRG和PRF钻井液,有效抑制了泥包卡钻、井漏等井下复杂的发生,使用效果良好。