Interleukin-22 protects rat PC12 pheochromocytoma cells from serum deprivation-induced cell death

Interleukin-22 (IL-22), an IL-10 family cytokine, mediates the crosstalk between leukocytes and epithelial cells. Previous studies reported that IL-22 expresses in mouse brain, and the rat PC12 cells are responsive to IL-22 stimulation. However, the biological roles of IL-22 in neuronal cells remain largely unknown. We show here that IL-22 activates Stat3, p38 mitogen-activated protein kinases (MAPK), and Akt pathways and inhibits Erk/MAPK pathway in na?ve PC12 cells. We further demonstrate that IL-22 protects na?ve PC12 cells from serum starvation-induced cell death via the Jak1/Stat3 and Akt pathways. We also show that IL-22 has no effects on na?ve PC12 cell proliferation and cannot protect na?ve PC12 cells from 1-methyl-4-phenylpyridinium (MPP⁺)-induced cytotoxicity. However, IL-22 exerts a dose-dependent protective effect on MPP⁺-induced neurodegeneration in nerve growth factor-differentiated PC12 cells. Overall, our data suggest that IL-22 might play a role in neurological processes. To our knowledge, this is the first report showing that IL-22 confers a neuroprotective function, which may provide a new therapeutic option for treatment of neurodegenerative diseases.     

Effects of TRIM on tension, intracellular calcium and nitrergic transmission in the rat anococcygeus muscle.

The effects of the putatively selective inhibitor of neuronal nitric oxide synthase (nNOS) 1-(2-trifluoromethylphenyl) imidazole (TRIM) were investigated on contractility, intracellular calcium and nitrergic relaxations in the rat anococcygeus muscle. TRIM (100-1000 microM) reduced the tension of rat anococcygeus muscles when contracted with guanethidine (10 microM) and clonidine (0.1 microM). Relaxations to TRIM persisted in the presence of the non-selective NOS inhibitor L-NAME (100 microM) and the inhibitor of soluble guanylate cyclase ODQ (1 microM). TRIM also reduced tension when muscles were contracted with phenylephrine (3 microM), noradrenaline (3 microM) or high K physiological salt solution (high KPSS; 60mM). Influx of calcium ([Ca(2+)](i)) in response to high KPSS was significantly reduced in the presence of TRIM (1mM). TRIM also inhibited the influx of (45)Ca(2+) induced by KPSS, but had no effect on the influx induced by phenylephrine (10 microM). TRIM (300 microM) had a modest, but significant, inhibitory effect on nitrergic relaxations that were evoked by electrical field stimulation (1-10 Hz, 15 V, 10s trains) in muscles contracted with guanethidine and clonidine. In contrast, L-NAME (1-100 microM) inhibited these nitrergic responses with an IC(50) of 9.31+/-0.87 microM (n=4). The results suggest that the smooth muscle relaxant effect of TRIM in the rat anococcygeus muscle may affect the entry of Ca(2+) possibly through voltage-operated calcium channels. Furthermore, the relatively modest effect of TRIM on nitrergic responses indicates that it is not a particularly reliable inhibitor of nNOS.     

Proton-conductivity assay of plugged and unplugged MotA/B proton channel by cytoplasmic pHluorin expressed in Salmonella

MotA and MotB form the proton-channel complex of the proton-driven bacterial flagellar motor. A plug segment of Escherichia coli MotB suppresses proton leakage through the MotA/B complex when it is not assembled into the motor. Using a ratiometric pH indicator protein, pHluorin, we show that the proton-conductivity of a Salmonella MotA/B complex not incorporated into the motor is two orders of magnitude lower than that of a complex that is incorporated and activated. This leakage is, however, significant enough to change the cytoplasmic pH to a level at which the chemotaxis signal transduction system responds.     

我国23个土壤磷素淋失风险评估Ⅱ.淋失临界值与土壤理化性质和磷吸附特性的关系

从13个省（市）采取23个耕地表层土壤,通过室内模拟试验测定其磷素淋失临界值和pH、有机质、＜0.01mm、＜0.002mm、交换性钙镁、活性铁铝、磷等温吸附特性等,以建立土壤磷素淋失临界值与土壤基本理化性质和磷吸附特性之间的关系.结果表明：土壤pH＜6.0时,随土壤pH提高临界值增加,土壤pH与临界值之间呈显著的指数关系;而当土壤pH＞6.0时,随土壤pH提高临界值减小,在pH6.5左右土壤磷素淋失临界值最高.土壤磷素淋失临界值与土壤有机质、活性铁（铝）、交换性钙之间存在显著的相关,而与交换性镁、CEC、＜0.01mm、＜0.002mm、K、Qm的相关性受土壤酸碱度影响.可以通过测定土壤有机质或活性铁的含量,来计算土壤磷素淋失临界值,评价土壤磷素淋失的风险.供试的23个土壤,除了采自湖北潜江的20号水稻土存在比较大的磷素淋失风险,其余土壤发生磷素淋失的风险很小.     

<Emphasis Type="Italic">Virgibacillus xinjiangensis</Emphasis> sp. nov., isolated from a Salt Lake of Xin-jiang Province in China

A strictly aerobic Gram-positive, moderately halophilic spore forming bacterium, designated strain SL6-1^T, was isolated from a salt lake in Xin-jiang province, China. Growth of strain SL6-1^T was observed at NaCl concentrations of 0∼20% (w/v) (the optimum being 5∼7%, w/v). The peptidoglycan type of strain SL6-1^T was Alγ-meso-diaminopimelic acid and its major cellular fatty acids were iso-C_14:0 and iso-C_16:0 and ante-iso-C_15:0. The major respiratory isoprenoid quinone was MK-7 and the G+C content of the genomic DNA was 44.5 mol%. The major cellular phospholipids were phosphatidylglycerol and diphosphatidylglycerol. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SL6-1^T formed a phylogenetic lineage within the genus Virgibacillus. Based on 16S rRNA gene sequence similarity, the strain was most closely related to Virgibacillus olivae E₃₀8^T, Virgibacillus kekensis YIM kkny16^T, Virgibacillus marismortui DSM 12325^T with 97.1%, 97.1%, and 97.0% gene sequence similarities, respectively and the sequence similarities to other related taxa were less than 96.7%. The DNA relatedness values between strain SL6-1^T and V. olivae E₃₀8^T, V. kekensis YIM kkny16^T, V. marismortui DSM 12325^T were 16.7%, 51.0%, and 22.8%, respectively. On the basis of physiological, biochemical and phylogenetic properties, strain SL6-1^T represents a novel species, for which the name Virgibacillus xinjiangensis sp. nov. is proposed. The type strain is SL6-1^T (=KCTC 13128^T =DSM 19031^T).     

The auxin-inducible phosphate transporter AsPT5 mediates phosphate transport and is indispensable for arbuscule formation in Chinese milk vetch at moderately high phosphate supply

Phosphorus is a macronutrient that is essential for plant survival. Most land plants have evolved the ability to form a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, which enhances phosphate (Pi) acquisition. Modulation of Pi transporter systems is the master strategy used by mycorrhizal plants to adapt to ambient Pi concentrations. However, the specific functions of PHOSPHATE TRANSPORTER 1 (PHT1) genes, which are Pi transporters that are responsive to high Pi availability, are largely unknown. Here, we report that AsPT5, an Astragalus sinicus (Chinese milk vetch) member of the PHT1 gene family, is conserved across dicotyledons and is constitutively expressed in a broad range of tissues independently of Pi supply, but is remarkably induced by indole-3-acetic acid (auxin) treatment under moderately high Pi conditions. Subcellular localization experiments indicated that AsPT5 localizes to the plasma membrane of plant cells. Using reverse genetics, we showed that AsPT5 not only mediates Pi transport and remodels root system architecture but is also essential for arbuscule formation in A. sinicus under moderately high Pi concentrations. Overall, our study provides insight into the function of AsPT5 in Pi transport, AM development and the cross-talk between Pi nutrition and auxin signalling in mycorrhizal plants.     

Fibroblast Activation Protein Overexpression and Clinical Implications in Solid Tumors: A Meta-Analysis

Objective

Fibroblast activation protein (FAP) plays a vital role in tumor invasion and metastasis. Previous studies have reported its prognostic value in different tumors. However, the results of these reports remain controversial. In this study, a meta-analysis was performed to clarify this issue.

Methods

A search of the PubMed, Embase and CNKI databases was conducted to analyze relevant articles. The outcomes included the relations between FAP expression and histological differentiation, tumor invasion, lymph node metastasis, distant metastasis and overall survival (OS). Sensitivity analysis by FAP expression in different cells and tumor types were further subjected to sensitivity analyses as subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using the random-effects model.

Results

The global analysis included 15 studies concerning various solid tumors. For global analysis, FAP overexpression in tumor tissue displayed significant associations with poor OS and tumor progression (OS: HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable results. First, the relation between FAP overexpression and poor OS and tumor lymph node metastasis was closer in the patients with FAP expression in tumor cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers all indicated that FAP overexpression was associated with a detrimental OS (HR: 1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect was not statistically significant compared with that in patients with non-colorectal cancers or non-pancreatic cancers. These analyses did not display a statistically significant correlation between FAP expression and histological differentiation and distant metastasis in all of the groups.

Conclusions

FAP expression is associated with worse prognosis in solid tumors, and this association is particularly pronounced if FAP overexpression is found in the tumor cells rather than the stroma.     

Receptor activator of NF-kappaB and podocytes: towards a function of a novel receptor-ligand pair in the survival response of podocyte injury

Background

Glomerulosclerosis correlates with reduction in podocyte number that occurs through mechanisms which include apoptosis. Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of glomerulosclerosis. However, the mechanism by which podocytes respond to injury is poorly understood. TNF and TNF receptor superfamilies are important in the pathogenesis of podocyte injury and apoptosis. The ligand of receptor activator of NF-kappaB (RANKL) and receptor activator of NF-kappaB (RANK) are members of the TNF and receptor superfamilies. We investigated whether RANK - RANKL is a receptor - ligand complex for podocytes responding to injury.

Methodology/Principal Findings

In this study, RANKL and RANK were examined in human podocyte diseases and a rat model of puromycin aminonucleoside nephrosis (PAN). Compared with controls, RANK and RANKL were increased in both human podocyte diseases and the rat PAN model; double immunofluorescence staining revealed that RANK protein expression was mainly attributed to podocytes. Immunoelectron microscopy showed that RANK was localized predominantly at the top of the foot process membrane and the cytoplasm of rat podocyte. In addition, RANK was upregulated in mouse podocytes in vitro after injury induced by puromycin aminonucleoside (PA). Knockdown of RANK expression by small interference RNA (siRNA) exacerbated podocyte apoptosis induced by PA. However, RANKL inhibited significantly the apoptosis of podocytes induced by PA.

Conclusions/Significance

These findings suggest the increase in RANK–RANKL expression is a response to podocyte injury, and RANK–RANKL may be a novel receptor–ligand complex for the survival response during podocyte injury.