β-aminoisobutyric Acid,l-BAIBA,Is a Muscle-Derived Osteocyte Survival Factor

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Intracameral Interleukin 1β, 6, 8, 10, 12p,Tumor Necrosis Factor α and Vascular Endothelial Growth Factor and Axial Length in Patients with Cataract

ObjectiveTo assess associations between the aqueous humour concentration of interleukin IL-1β, IL-6, IL-8, IL-10 and IL-12p, tumor necrosis factor α (TNF-α) and vascular endothelial growth factor (VEGF) and axial length in eyes with cataract.MethodsThe hospital-based investigation included patients who underwent cataract surgery between March 2014 and April 2014. Using aqueous humour collected at the start of cataract surgery, the interleukins IL-1β, IL-6, IL-8, IL-10 and IL-12p, TNF-α and VEGF were examined using a cytometric bead array. Axial length was determined by partial coherence laser interferometry (IOL Master).ResultsThe study included 33 patients with cataract (33 eyes) with a mean age of 69.2±10.8 years (range:50–87 years) and a mean axial length of 24.7±1.9 mm (range:22.6–31.5 mm). Lower aqueous concentration of VEGF was significantly associated with longer axial length (VEGF concentration (pg/mL) = -5.12 x Axial Length (mm) + 163; correlation coefficient r = -0.41; P<0.001) and more myopic refractive error (VEGF concentration (pg/mL) = 1.27xspherical equivalent (diopters)+44.8; r = 0.383; P = 0.002). The aqueous concentrations of all other substances were not significantly (all P>0.10) associated with axial length or refractive error.ConclusionsHigher intravitreal concentrations of VEGF were measured in eyes with a longer axial length, while the intraocular concentrations of IL-1β, IL-6, IL-8, IL-10, IL-12p and TNF-α were not correlated with axial length. The lower concentration of VEGF in axially elongated eyes may be one of the reasons for the lower prevalence of age-related macular degeneration and diabetic retinopathy in myopic eyes.     

Platelet-derived Growth Factor β-Receptor,Transforming Growth Factor β Type I Receptor,and CD44 Protein Modulate Each Other's Signaling and Stability

Growth factors, such as platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ), are key regulators of cellular functions, including proliferation, migration, and differentiation. Growth factor signaling is modulated by context-dependent cross-talk between different signaling pathways. We demonstrate in this study that PDGF-BB induces phosphorylation of Smad2, a downstream mediator of the canonical TGFβ pathway, in primary dermal fibroblasts. The PDGF-BB-mediated Smad2 phosphorylation was dependent on the kinase activities of both TGFβ type I receptor (TβRI) and PDGF β-receptor (PDGFRβ), and it was prevented by inhibitory antibodies against TGFβ. Inhibition of the activity of the TβRI kinase greatly reduced the PDGF-BB-dependent migration in dermal fibroblasts. Moreover, we demonstrate that the receptors for PDGF-BB and TGFβ interact physically in primary dermal fibroblasts and that stimulation with PDGF-BB induces internalization not only of PDGFRβ but also of TβRI. In addition, silencing of PDGFRβ by siRNA decreased the stability of TβRI and delayed TGFβ-induced signaling. We further show that the hyaluronan receptor CD44 interacts with both PDGFRβ and TβRI. Depletion of CD44 by siRNA increased signaling via PDGFRβ and TβRI by stabilizing the receptor proteins. Our data suggest that cross-talk between PDGFRβ and TβRI occurs in dermal fibroblasts and that CD44 negatively modulates signaling via these receptors.     

The Activity of σV,an Extracytoplasmic Function σ Factor of Bacillus subtilis,Is Controlled by Regulated Proteolysis of the Anti-σ Factor RsiV

During growth in the environment, bacteria encounter stresses which can delay or inhibit their growth. To defend against these stresses, bacteria induce both resistance and repair mechanisms. Many bacteria regulate these resistance mechanisms using a group of alternative σ factors called extracytoplasmic function (ECF) σ factors. ECF σ factors represent the largest and most diverse family of σ factors. Here, we demonstrate that the activation of a member of the ECF30 subfamily of ECF σ factors, σ^V in Bacillus subtilis, is controlled by the proteolytic destruction of the anti-σ factor RsiV. We will demonstrate that the degradation of RsiV and, thus, the activation of σ^V requires multiple proteolytic steps. Upon exposure to the inducer lysozyme, the extracellular domain of RsiV is removed by an unknown protease, which cleaves at site 1. This cleavage is independent of PrsW, the B. subtilis site 1 protease, which cleaves the anti-σ factor RsiW. Following cleavage by the unknown protease, the N-terminal portion of RsiV requires further processing, which requires the site 2 intramembrane protease RasP. Our data indicate that the N-terminal portion of RsiV from amino acid 1 to 60, which lacks the extracellular domain, is constitutively degraded unless RasP is absent, indicating that RasP cleavage is constitutive. This suggests that the regulatory step in RsiV degradation and, thus, σ^V activation are controlled at the level of the site 1 cleavage. Finally, we provide evidence that increased resistance to lysozyme decreases σ^V activation. Collectively, these data provide evidence that the mechanism for σ^V activation in B. subtilis is controlled by regulated intramembrane proteolysis (RIP) and requires the site 2 protease RasP.     

Isolation of a Peptidyl Factor, α Substance-IA,Inducing Sexual Agglutinability in Saccharomyces cerevisiae

After a eleven-steps purification, a peptidyl factor named α substance-Ia was isolated in pure form from a culture filtrate of α type cells of the heterothallic Saccharomyces cerevisiae. The substance induced the sexual agglutinability in a haploid cells belonging to the opposite mating type at concentrations from 0.4 to 0.8 ng/ml.     

Transforming Growth Factor β Regulates P-Body Formation through Induction of the mRNA Decay Factor Tristetraprolin

Transforming growth factor β (TGF-β) is a potent growth regulator and tumor suppressor in normal intestinal epithelium. Likewise, epithelial cell growth is controlled by rapid decay of growth-related mRNAs mediated through 3′ untranslated region (UTR) AU-rich element (ARE) motifs. We demonstrate that treatment of nontransformed intestinal epithelial cells with TGF-β inhibited ARE-mRNA expression. This effect of TGF-β was promoted through increased assembly of cytoplasmic RNA processing (P) bodies where ARE-mRNA localization was observed. P-body formation was dependent on TGF-β/Smad signaling, as Smad3 deletion abrogated P-body formation. In concert with increased P-body formation, TGF-β induced expression of the ARE-binding protein tristetraprolin (TTP), which colocalized to P bodies. TTP expression was necessary for TGF-β-dependent P-body formation and promoted growth inhibition by TGF-β. The significance of this was observed in vivo, where colonic epithelium deficient in TGF-β/Smad signaling or TTP expression showed attenuated P-body levels. These results provide new insight into TGF-β''s antiproliferative properties and identify TGF-β as a novel mRNA stability regulator in intestinal epithelium through its ability to promote TTP expression and subsequent P-body formation.     

Polo-like Kinase 2, a Novel ADAM17 Signaling Component,Regulates Tumor Necrosis Factor α Ectodomain Shedding

ADAM17 (a disintegrin and metalloprotease 17) controls pro- and anti-inflammatory signaling events by promoting ectodomain shedding of cytokine precursors and cytokine receptors. Despite the well documented substrate repertoire of ADAM17, little is known about regulatory mechanisms, leading to substrate recognition and catalytic activation. Here we report a direct interaction of the acidophilic kinase Polo-like kinase 2 (PLK2, also known as SNK) with the cytoplasmic portion of ADAM17 through the C-terminal noncatalytic region of PLK2 containing the Polo box domains. PLK2 activity leads to ADAM17 phosphorylation at serine 794, which represents a novel phosphorylation site. Activation of ADAM17 by PLK2 results in the release of pro-TNFα and TNF receptors from the cell surface, and pharmacological inhibition of PLK2 leads to down-regulation of LPS-induced ADAM17-mediated shedding on primary macrophages and dendritic cells. Importantly, PLK2 expression is up-regulated during inflammatory conditions increasing ADAM17-mediated proteolytic events. Our findings suggest a new role for PLK2 in the regulation of inflammatory diseases by modulating ADAM17 activity.     

JIPB’s 2016 Impact Factor

正We are delighted to announce that JIPB's 2-year SCI impact factor(IF)has reached 3.962(8%increase as compared to last year,Fig.1),and 5-year IF is 3.956,according to 2016 Journal Citation Report.Among 211 SCI-indexed Plant Science journals in the world,JIPB ranks 24th(top 9.95%,Q1 category).The total citations of JIPB in 2016 are 3,773(12%increase as compared     

Engineering of Substrate Selectivity for Tissue Factor·Factor VIIa Complex Signaling through Protease-activated Receptor 2

The complex of factor VIIa (FVIIa) with tissue factor (TF) triggers coagulation by recognizing its macromolecular substrate factors IX (FIX) and X (FX) predominantly through extended exosite interactions. In addition, TF mediates unique cell-signaling properties in cancer, angiogenesis, and inflammation that involve proteolytic cleavage of protease-activated receptor 2 (PAR2). PAR2 is cleaved by FVIIa in the binary TF·FVIIa complex and by FXa in the ternary TF·FVIIa·FXa complex, but physiological roles of these signaling complexes are incompletely understood. In a screen of FVIIa protease domain mutants, three variants (Q40A, Q143N, and T151S) activated macromolecular coagulation substrates and supported signaling of the ternary TF·FVIIa-Xa complex normally but were severely impaired in binary TF·FVIIa·PAR2 signaling. The residues identified were located in the model-predicted S2′ pocket of FVIIa, and complementary PAR2 P2′ Leu-38 replacements demonstrated that the P2′ side chain was indeed crucial for PAR2 cleavage by TF·FVIIa. In addition, PAR2 was activated more efficiently by FVIIa T99Y, consistent with further contributions from the S2 subsite. The P2 residue preference of FVIIa and FXa predicted additional PAR2 mutants that were efficiently activated by TF·FVIIa but resistant to cleavage by the alternative PAR2 activator FXa. Thus, contrary to the paradigm of exosite-assisted cleavage of PAR1 by thrombin, the cofactor-associated protease FVIIa recognizes PAR2 predominantly by catalytic cleft interactions. Furthermore, the delineated molecular details of this substrate interaction enabled protein engineering of protease-selective PAR2 receptors that will aid further studies to dissect the roles of TF signaling complexes in vivo.