A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart.

Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte, its inhibitory activity to SERCA is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in failing heart. The current study provided evidence at molecular, cellular and whole heart levels to implicate a sarcolemma membrane targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase. PP2Ce expression was elevated in failing human heart and induced acutely at protein level by β -adrenergic stimulation or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted β-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore, PP2Ce is a new regulator for cardiac function and pathogenesis

Strain Enhanced Visible–Ultraviolet Absorption of Blue Phosphorene/MoX2 (X = S,Se) Heterolayers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149231/1/pssr201800659.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149231/2/pssr201800659_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149231/3/pssr201800659-sup-0001-SuppFig-S1.pd

Highly Efficient Polarized GeS/MoSe2 van der Waals Heterostructure for Water Splitting from Ultraviolet to Near‐Infrared Light

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152744/1/pssr201900582.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152744/2/pssr201900582_am.pd

Activation of CXCL6/CXCR1/2 Axis Promotes the Growth and Metastasis of Osteosarcoma Cells in vitro and in vivo

Osteosarcoma (OS) is a malignant primary bone tumor with high metastatic rate. C-X-C motif chemokine ligand 6 (CXCL6) and its receptor C-X-C motif chemokine receptor 1/2 (CXCR1/2) have been found to participate in the process of carcinogenesis. In this study, we evaluated the role of CXCL6/CXCR1/2 axis in proliferation and metastasis of OS cells. According to our results, the mRNA and protein expressions of CXCL6, CXCR1, and CXCR2 in multiple OS cell lines were determined. Treatment with exogenous CXCL6 for more than 72 h significantly promoted the proliferation of OS cells. Blocking the effect of endogenous CXCL6 restrained the migration, invasion and epithelial-mesenchymal transition (EMT) as evidenced by increased E-cadherin level, decreased N-cadherin and Snail levels in OS cells. On the contrary, exogenous CXCL6 administration enhanced the migration and invasive abilities of OS cells. Moreover, silencing of CXCR1/2 suppressed migration, invasion and EMT of OS cells with or without treatment with exogenous CXCL6. In addition, exogenous CXCL6 promoted the activation of PI3K/AKT and β-catenin signaling pathways, which could be repressed by CXCR2 knockdown. Inactivation of PI3K/AKT or β-catenin pathway by specific inhibitors effectively suppressed CXCL6-induced migration, invasion and EMT of OS cells. Finally, overexpression of CXCL6 significantly contributed to tumor growth, pulmonary metastasis and activation of PI3K/AKT and β-catenin pathways in nude mice in vivo, which were repressed by treatment with CXCR2 antagonist. Our results suggest that CXCL6/CXCR1/2 axis promotes the proliferation and metastasis of OS cells

Visual characterization of associative quasitrivial nondecreasing operations on finite chains

In this paper we provide visual characterization of associative quasitrivial nondecreasing operations on finite chains. We also provide a characterization of bisymmetric quasitrivial nondecreasing binary operations on finite chains. Finally, we estimate the number of functions belonging to the previous classes.Comment: 25 pages, 18 Figure

Tyrosine Phosphatase PTPRO Deficiency in ERBB2-Positive Breast Cancer Contributes to Poor Prognosis and Lapatinib Resistance

Despite the initial benefit from treating ERBB2-positive breast cancer with tyrosine kinase inhibitor lapatinib, resistance develops inevitably. Since the expression of protein tyrosine phosphatase receptor-type O (PTPRO), a member of the R3 subfamily of receptor protein tyrosine phosphatases (PTPs), is inversely correlated with the aggressiveness of multiple malignancies, we decided to explore the correlation between PTPRO and lapatinib resistance in ERBB2-positive breast cancer. Results of immunohistochemical (IHC) staining and the correlation analysis between the expression levels of PTPRO and the clinicopathological parameters indicate that PTPRO is downregulated in cancer tissues as compared with normal tissues and negatively associated with differentiation, tumor size, tumor depth, as well as the expression of ERBB2 and Ki67. Results from Kaplan–Meier analyses indicate that lower expression of PTPRO is correlated with shorter relapse-free survival for patients with ERBB2-positive breast cancer, and multivariable Cox regression analysis found that PTPRO can potentially serve as an independent prognostic indicator for ERBB2-positive breast cancer. Results from both human breast cancer cells with PTPRO knockdown or overexpression and mouse embryonic fibroblasts (MEFs) which derived from Ptpro ( +/+ ) and Ptpro ( −/− ) mice with then stably transfected plasmid FUGW-Erbb2 consistently demonstrated the essentiality of PTPRO in the lapatinib-mediated anticancer process. Our findings suggest that PTPRO is not only able to serve as an independent prognostic indicator, but upregulating PTPRO can also reverse the lapatinib resistance of ERBB2-positive breast cancer

Notch1 Inhibits Rosiglitazone-Induced Adipogenic Differentiation in Primary Thymic Stromal Cells

Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution. Herein, we cultured primary thymic stromal cells (TSCs), used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation, and investigated the differentially expressed genes during adipogenic differentiation by using RNA-sequencing analysis. Furthermore, the effects of Notch1 on rosiglitazone-induced adipogenic differentiation of TSCs as well as the underlying mechanisms were also investigated. As a result, we identified a total of 1737 differentially expressed genes, among which 965 genes were up-regulated and 772 genes were down-regulated in rosiglitazone-treated cells compared with control cells. Gene ontology (GO) enrichment analysis showed that the GO terms were enriched in metabolic process, intracellular, and protein binding. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that a number of pathways, including ubiquitin mediated proteolysis, PPAR signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway were predominantly over-represented. Meanwhile, overexpression of Notch1 suppressed and inhibition of Notch1 promoted rosiglitazone-induced adipogenic differentiation in TSCs, and the pro-adipogenic effects of the Notch inhibitor DAPT were associated with the activation of autophagy. Taken together, our results suggest that Notch1 is a key regulator in thymic adipogenesis and may serve as a potential target to hinder thymic adiposity in age-related thymic involution