Economic policy uncertainty, political connections, and M&As: Evidence from China

Economic policy uncertainty, political connections, and M&As: Evidence from Chin

Initial Substrate Binding of γ‑Secretase: The Role of Substrate Flexibility

γ-Secretase cleaves transmembrane domains (TMD) of amyloid precursor protein (APP), producing pathologically relevant amyloid-β proteins. Initial substrate binding represents a key step of the γ-secretase cleavage whose mechanism remains elusive. Through long time scale coarse-grained and atomic simulations, we have found that the APP TMD can bind to the catalytic subunit presenilin 1 (PS1) on an extended surface covering PS1’s TMD2/6/9 and PAL motif that are all known to be essential for enzymatic activity. This initial substrate binding could lead to reduction in the vertical gap between APP’s ε-cleavage sites and γ-secretase’s active center, enhanced flexibility and hydration levels around the ε-sites, and the presentation of these sites to the enzyme. There are heterogeneous substrate binding poses in which the substrate is found to bind to either the N- or C-terminal parts of PS1, or both. Moreover, we also find that the stability of the binding poses can be modulated by the flexibility of substrate TMD. Especially, the APP substrate, when deprived of bending fluctuation, does not bind to TMD9 at PS1’s C-terminus. Our simulations have revealed further that another substrate of γ-secretase, namely, notch receptors, though bearing a rigid TMD, can still bind to PS1 TMD9, but by a different mechanism, suggesting that the influence of substrate flexibility is context-dependent. Together, these findings shed light on the mechanism of initial substrate docking of γ-secretase and the role of substrate flexibility in this process

DataSheet_1_TGIF2 is a potential biomarker for diagnosis and prognosis of glioma.docx

BackgroundTGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development remain elusive.MethodsThe expression of TGIF2 in various human normal tissues, normal brain tissues, and gliomas was investigated using HPA, TCGA, GTEx, and GEO databases. The study employed several approaches, including Kaplan-Meier analysis, ROC analysis, logistic regression, Cox regression, GO analysis, KEGG analysis, and GSEA, to explore the relationship between TGIF2 expression and clinicopathologic features, prognostic value, and potential biological functions in glioma patients. The impact of TGIF2 on tumor immune infiltration was assessed through Estimate, ssGSEA, and Spearman analysis. Genes coexpressed with TGIF2 were identified, and the protein-protein interaction (PPI) network of these coexpressed genes were constructed using the STRING database and Cytoscape software. Hub genes were identified using CytoHubba plugin, and their clinical predictive value was explored. Furthermore, in vitro experiments were performed by knocking down and knocking out TGIF2 using siRNA and CRISPR/Cas9 gene editing, and the role of TGIF2 in glioma cell invasion and migration was analyzed using transwell assay, scratch wound-healing assay, RT-qPCR, and Western blot.ResultsTGIF2 mRNA was found to be upregulated in 21 cancers, including glioma. High expression of TGIF2 was associated with malignant phenotypes and poor prognosis in glioma patients, indicating its potential as an independent prognostic factor. Furthermore, elevated TGIF2 expression positively correlated with cell cycle regulation, DNA synthesis and repair, extracellular matrix (ECM) components, immune response, and several signaling pathways that promote tumor progression. TGIF2 showed correlations with Th2 cells, macrophages, and various immunoregulatory genes. The hub genes coexpressed with TGIF2 demonstrated significant predictive value. Additionally, in vitro experiments revealed that knockdown and knockout of TGIF2 inhibited glioma cell invasion, migration and suppressed the epithelial-mesenchymal transition (EMT) phenotype.ConclusionTGIF2 emerges as a potential biomarker for glioma, possibly linked to tumor immune infiltration and EMT.</p

Additional file 1: Table S1. of FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients

siRNA used in this study. Table S2 Primers used in qPCR. Table S3 Primers used in ChIP analysis. Table S4 Correlation between clinical pathological factors and expression of FOXA1, PI3Kp85 in HCC Table S5 Specimens exhibit low or high FOXA1 expression in relation to PI3Kp85 expression. (DOCX 25 kb

Two Unprecedented Transition-Metal–Organic Frameworks Showing One Dimensional-Hexagonal Channel Open Network and Two-Dimensional Sheet Structures

Two new metal–organic frameworks, {[Co₃(μ₃-DMPhIDC)₂(H₂O)₆]·2H₂O}_<i>n</i> (<b>1</b>) and {[Mn₅(μ₃-DMPhIDC)₂(μ₂-HDMPhIDC)₂(Phen)₅]·2CH₃OH·3H₂O}_<i>n</i> (<b>2</b>) (H₃DMPhIDC = 2-(3,4-dimethylphenyl)-1<i>H</i>-imidazole-4,5-dicarboxylic acid, Phen = 1,10-phenanthroline), have been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction, elemental analyses, X-ray powder diffraction (XRPD), thermal analyses, and IR spectra. Polymer <b>1</b> is an enchanting three-dimensional network containing infinite one-dimensional-hexagonal channels and [Co₂(DMPhIDC)]₆ cages, which have two interpenetrating nets topology. Polymer <b>2</b> exhibits a two-dimensional framework, which is composed of left- and right-handed helices pillared by Mn²⁺ linkages. Antiferromagnetic coupling exists between the Co­(II) ions or Mn­(II) ions in <b>1</b> or <b>2</b>, respectively

Two Unprecedented Transition-Metal–Organic Frameworks Showing One Dimensional-Hexagonal Channel Open Network and Two-Dimensional Sheet Structures

Two new metal–organic frameworks, {[Co₃(μ₃-DMPhIDC)₂(H₂O)₆]·2H₂O}_<i>n</i> (<b>1</b>) and {[Mn₅(μ₃-DMPhIDC)₂(μ₂-HDMPhIDC)₂(Phen)₅]·2CH₃OH·3H₂O}_<i>n</i> (<b>2</b>) (H₃DMPhIDC = 2-(3,4-dimethylphenyl)-1<i>H</i>-imidazole-4,5-dicarboxylic acid, Phen = 1,10-phenanthroline), have been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction, elemental analyses, X-ray powder diffraction (XRPD), thermal analyses, and IR spectra. Polymer <b>1</b> is an enchanting three-dimensional network containing infinite one-dimensional-hexagonal channels and [Co₂(DMPhIDC)]₆ cages, which have two interpenetrating nets topology. Polymer <b>2</b> exhibits a two-dimensional framework, which is composed of left- and right-handed helices pillared by Mn²⁺ linkages. Antiferromagnetic coupling exists between the Co­(II) ions or Mn­(II) ions in <b>1</b> or <b>2</b>, respectively

Additional file 1: Table S1. of The walnut JrVHAG1 gene is involved in cadmium stress response through ABA-signal pathway and MYB transcription regulation

The primers used in qRT-PCR analysis. Table S2. The primers used in yeast one-hybrid assay and pCAMBIA1301 recombinant vector construction. Figure S1. The abiotic stress tolerance analysis of VHA-B, C, JrVHAG1, c1 and c4 in yeast expression system compared with empty pYES2 (CK) yeast. The six yeast cultures were independently grown in SC-Ura liquid medium containing 2% (w/v) galactose for 20 h at 30 °C to OD600 = 0.4, then collecting and adjusting the yeast with Sc-Ura including 2% galactose cultivated to OD600 = 1.6 for stress analysis. Yeast cell densities (OD600) of VHA-B, C, JrVHAG1, c1 and c4 transgenic yeasts and CK were treated with 50 μM ABA, or 150 μM CdCl2, or 150 μM CdCl2 plus 50 μM ABA (ABA+CdCl2) for 0 or 24 h (0 h was set as control) were tested. All data are displayed as the mean ± S.D. of three independent experiments, the significant differences among the six yeasts were compared under the same treatment and indicated by a, b, c (p < 0.05), respectively. Figure S2. Mapping the reconstruct of JrVHAG1 promoter that inserted into pCAMBIA1301 vector. Figure S3. The promoter and elements of JrVHAG1 promoter. The MBS means the ‘MYBCORE’ element. Figure S4. The binding analysis of JrMYB2 to the MYBCORE motif. (A) Diagram of the reportor and effector vectors. Three tandem copies of the MYBCORE were inserted into the pHIS2 vector as the reportor construct. (B)The CDS of JrMYB2 was cloned into pGADT7-Rec2 as the effector construct. The effector and reportor constructs were co-transformed into the yeast strain Y187. (C) Diagram of the reportors and effectors. Triple tandem copies of the W-box were fused with the 35S CaMV-46 minimal promoter and cloned into pCAMBIA1301 for driving the GUS gene as the reportor construct. The CDS of JrMYB2 was cloned into prokII under the control of the 35S promoter as the effector constructs. (DOC 1310 kb

Two Unprecedented Transition-Metal–Organic Frameworks Showing One Dimensional-Hexagonal Channel Open Network and Two-Dimensional Sheet Structures

Two new metal–organic frameworks, {[Co₃(μ₃-DMPhIDC)₂(H₂O)₆]·2H₂O}_<i>n</i> (<b>1</b>) and {[Mn₅(μ₃-DMPhIDC)₂(μ₂-HDMPhIDC)₂(Phen)₅]·2CH₃OH·3H₂O}_<i>n</i> (<b>2</b>) (H₃DMPhIDC = 2-(3,4-dimethylphenyl)-1<i>H</i>-imidazole-4,5-dicarboxylic acid, Phen = 1,10-phenanthroline), have been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction, elemental analyses, X-ray powder diffraction (XRPD), thermal analyses, and IR spectra. Polymer <b>1</b> is an enchanting three-dimensional network containing infinite one-dimensional-hexagonal channels and [Co₂(DMPhIDC)]₆ cages, which have two interpenetrating nets topology. Polymer <b>2</b> exhibits a two-dimensional framework, which is composed of left- and right-handed helices pillared by Mn²⁺ linkages. Antiferromagnetic coupling exists between the Co­(II) ions or Mn­(II) ions in <b>1</b> or <b>2</b>, respectively

OsNRAMP3 Is a Vascular Bundles-Specific Manganese Transporter That Is Responsible for Manganese Distribution in Rice

<div><p>Manganese (Mn) is an essential trace element for plants. Recently, the genes responsible for uptake of Mn in plants were identified in <i>Arabidopsis</i> and rice. However, the mechanism of Mn distribution in plants has not been clarified. In the present study we identified a natural resistance-associated macrophage protein (NRAMP) family gene in rice, <i>OsNRAMP3</i>, involved in Mn distribution. <i>OsNRAMP3</i> encodes a plasma membrane-localized protein and was specifically expressed in vascular bundles, especially in phloem cells. Yeast complementation assay showed that OsNRAMP3 is a functional Mn-influx transporter. When <i>OsNRAMP3</i> was absent, rice plants showed high sensitivity to Mn deficiency. Serious necrosis appeared on young leaves and root tips of the <i>OsNRAMP3</i> knockout line cultivated under low Mn conditions, and high Mn supplies could rescue this phenotype. However, the necrotic young leaves of the knockout line possessed similar levels of Mn to the wild type, suggesting that the necrotic appearance was caused by disturbed distribution of Mn but not a general Mn shortage. Additionally, compared with wild type, leaf Mn content in <i>osnramp3</i> plants was mostly in older leaves. We conclude that OsNRAMP3 is a vascular bundle-localized Mn-influx transporter involved in Mn distribution and contributes to remobilization of Mn from old to young leaves.</p></div

Subcellular localization of OsNRAMP3 protein.

<p>Subcellular localization of OsNRAMP3 protein was determined in <i>Arabidopsis</i> protoplasts. The confocal images were acquired using a confocal laser scanning microscope (TCS SP2; Leica).</p