Phospholipase C-related catalytically inactive protein acts as a positive regulator for insulin signalling in adipocytes

Insulin signalling is tightly controlled by various factors, but the exact molecular mechanism remains incompletely understood. We previously reported that phospholipase C-related but catalytically inactive protein (PRIP) interacts with Akt, the central molecule in insulin signalling. Here, we investigated whether PRIP is involved in the regulation of insulin signalling in adipocytes. We found that insulin signalling including insulin-stimulated phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), Akt, and glucose uptake, were impaired in adipocytes from PRIP-knockout (KO) mice compared with those from wild-type (WT) mice. The amount of IR expressed on the cell-surface was decreased in PRIP-KO adipocytes. Immunoprecipitation assay showed that PRIP interacted with IR. The reduced cell-surface IR in PRIP-KO adipocytes was comparable with that in WT cells when Rab5 expression was silenced using specific siRNA. In contrast, the dephosphorylation of IRS-1 at serine residues, some of which were reported to be involved in the internalisation of IR, was impaired in cells from PRIP-KO mice. These results suggest that PRIP facilitates insulin signalling by modulating the internalisation of IR in adipocytes.

sMEK1 promotes crosstalk between IRE1 and Akt signaling pathway: Evidence for a novel IRE1/sMEK1/Akt complex

ER is facilitated with a dynamic cellular pathway namely Unfolded Protein Response (UPR): an adaptive signalling mechanism that maintains proteostasis in response to ER stress. IRE1 is one of the three transmembrane sensors of UPR with dual protein kinase and ribonuclease activities. IRE1 acts as a central molecule of UPR, which associates with a number of proteins that either regulate its activity or connect it to other pathways. Here, we report sMEK1 and Akt as novel interacting partners of IRE1 which associate to orchestrate the IRE1 and Akt signalling networks. Our study revealed that ER stress negatively regulates Akt through IRE1 protein. We found that IRE1/sMEK1/Akt form a ternary complex, which results in the dephosphorylation of Akt by protein phosphotase sMEK1 in presence of activated IRE1. Together, this study highlights the UPR/Akt link by delineating the molecular mechanism along with giving insights into the overall impact of this interaction.

Significantly enhanced thermoelectric performance in intermediate weak-coupling C8-BTBT molecular junction with p/n type electrode doping

For single-molecular junction, inherent energy mismatch between central molecule and electrodes requires a delicate balance between electronic and phonon transport properties. Based on a combination of density functional theory and...

Tumor ferroptosis status demonstrated vulnerability to chemotherapy and reflected immune-activation in colorectal cancer

Background: Existing studies for ferroptosis and prognosis in colorectal cancer (CRC) were limited. In this study, we aim to investigate the prognostic role of ferroptosis markers in patients with CRC and exploration of its micro-environmental distributions. Methods: A total of 911 patients from 2008 to 2013 with CRC were enrolled. Immunohistochemical staining was performed for CRC patients’ tissue microarray. Selection and prognostic validation of markers were based on mRNA data from the cancer genome atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed to indicate relative immune landmarks and hallmarks. Ferroptosis and immune contexture were examined by CIBERSORT. Survival outcomes were analyzed by Kaplan-meier analysis and cox analysis.Results: A panel of 42 genes was selected. Through mRNA expression difference and prognosis analysis, GPX4, NOX1 and ACSL4 were selected as candidate markers. By IHC, increased GPX4, decreased NOX1 and decreased FACL4 indicate poor prognosis and worse clinical characteristics. Ferroptosis score based on GPX4, NOX1 and ACSL4 was constructed and validated with high C-index. Low ferroptosis score can also demonstrate the better progression free survival and better adjuvant chemotherapy (ACT) responsiveness. Moreover, tumor with low ferroptosis score tend to be infiltrated with more CD4+ T cells, CD8+ T cells and less M1 macrophage. Finally, we found that IFN-γ was potentially the central molecule at the crossroad between ferroptosis and onco-immune response. Conclusion: Ferroptosis plays important role on CRC tumor progression, ACT response and prognosis. Ferroptosis contributes to immune-supportive responses and IFN-γ was the central molecule for this process.

Energetics competition in centrally four-coordinated water clusters and Raman spectroscopic signature for hydrogen bonding

Viaseparating the H-bonded neighbour molecules of centrally four-coordinated water molecules from other molecules in outer cages, the calculations discover these two regions interact competitively with the central molecule.

A comparison of colorimetric assays detecting hydrogen peroxide in leaf extracts

Hydrogen peroxide (H2O2) is a central molecule in plant stress responses as a potential oxidizing agent or a signal molecule, depending on its localization and cellular concentrations. The work compares the versatility of three simple and rapid, potentially high through-put photometric assays to detect this reactive oxygen species in leaf extracts.