Notes

Searching for oncogene-driven remodelling of the intestinal tract base mobile or portable area of interest.
Phosphatidic acid (PA) is the simplest phospholipid and is involved in the regulation of various cellular events. Recently, we developed a new PA sensor, the N-terminal region of α-synuclein (α-Syn-N). However, whether α-Syn-N can sense physiologically produced, endogenous PA remains unclear. We first established an inactive PA sensor (α-Syn-N-KQ) as a negative control by replacing all eleven lysine residues with glutamine residues. Using confocal microscopy, we next verified that α-Syn-N, but not α-Syn-N-KQ, detected PA in macrophagic phagosomes in which PA is known to be enriched, further indicating that α-Syn-N can be used as a reliable PA sensor in cells. Finally, because PA generated during neuronal differentiation is critical for neurite outgrowth, we investigated the subcellular distribution of PA using α-Syn-N. We found that α-Syn-N, but not α-Syn-N-KQ, accumulated at the peripheral regions (close to the plasma membrane) of neuronal growth cones. Experiments using a phospholipase D (PLD) inhibitor strongly suggested that PA in the peripheral regions of the growth cone was primarily produced by PLD. Our findings provide a reliable sensor of endogenous PA and novel insights into the distribution of PA during neuronal differentiation.Our recent study revealed an important role of the neuroplastin (NPTN)β downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTNβ is a serial activation of the key molecules we identified tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF). The question of how dissemination is controlled by SPDEF under the activated NPTNβ has not been answered. Here, we show that the NPTNβ-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTNβ pathway in lung cancer cells. In vitro, the induced EMT is linked to the acquisition of active cellular motility but not growth, and this is correlated with highly disseminative tumor progression in vivo. The publicly available data also show the poor survival of SLC22A18AS-overexpressing lung cancer patients. Taken together, these data highlight a crucial role of SLC22A18AS in lung cancer dissemination, which provides novel input of this molecule to the signal cascade of NPTNβ. Our findings contribute to a better understanding of NPTNβ-mediated lung cancer metastasis.Cardiomyopathy caused by A-type lamins gene (LMNA) mutations (LMNA cardiomyopathy) is associated with dysfunction of the heart, often leading to heart failure. LMNA cardiomyopathy is highly penetrant with bad prognosis with no specific therapy available. Searching for alternative ways to halt the progression of LMNA cardiomyopathy, we studied the role of calcium homeostasis in the evolution of this disease. We showed that sarcolipin, an inhibitor of the sarco/endoplasmic reticulum (SR) Ca2+ ATPase (SERCA) was abnormally elevated in the ventricular cardiomyocytes of mutated mice compared with wild type mice, leading to an alteration of calcium handling. This occurs early in the progression of the disease, when the left ventricular function was not altered. We further demonstrated that down regulation of sarcolipin using adeno-associated virus (AAV) 9-mediated RNA interference delays cardiac dysfunction in mouse model of LMNA cardiomyopathy. These results showed a novel role for sarcolipin on calcium homeostasis in heart and open perspectives for future therapeutic interventions to LMNA cardiomyopathy.[This corrects the article DOI 10.1016/j.bbrep.2019.100712.].The aim of this study was to generate an antibody specific to Ki-67 acetylated at lysine 3180, whose existence was reported in an acetylome study (Scholz, C., B.T. Weinert, S.A. Wagner, P. Beli, Y. Miyake, J. Qi, L.J. Jensen, W. Streicher, A.R. McCarthy, N.J. Westwood, S. Lain, J. Cox, P. Matthias, M. Mann, J.E. Bradner, and C. Choudhary. 2015). Rabbits were immunized with a synthetic acetylated peptide corresponding to acetylated lysine 3180 of Ki-67 and the residues flanking it. The obtained antibody, referred to as Ab3180 in this study, was affinity purified with the antigen peptide and characterized. Immunoblot analysis of cell extracts using Ab3180 revealed that this antibody unexpectedly recognized a set of acetylated proteins unrelated to Ki-67. Ab3180-recognizable proteins were immunoprecipitated from cell extracts in a stringent condition and identified by mass-spec analysis as subunits of BAF (mammalian SWI/SNF) chromatin remodeling complexes. The unique specificity of Ab3180 will allow this antibody to be a useful tool for analyzing the acetylation of BAF complexes and its significance to the formation/function of BAF complexes.Background Breast cancer is the most common invasive cancer and the leading cause of cancer death in women. The function of over a thousand genes is reported as affected by genetic modifications in breast cancer. Objectives To study the gene expression of Epithelial Membrane 2 (EMP2) and β1-Integrin genes in patients with breast cancer. Subjects and methods This study was carried out by cooperation between the Biochemistry Division Department of Chemistry, Faculty of Science and Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University. This study included 120 subjects divided into 2 groups Group I Included 60 women with breast cancer undergoing modified radical mastectomy. Tissue specimens were taken from the cancerous breast tissue and from the marginal healthy breast tissues. Group II Included 60 age and sex-matched apparently healthy women served as a control group. All patients participants were subjected to full history taking, general clinical examination, abdominal ultrasound, CT-scan for abdomen, mammography, fine needle biopsy, histopathological examination, immunostaining of tissues, metastatic work up (chest x-ray and bone scan) and laboratory investigations including Complete blood count (patients and controls), serum carbohydrate antigen 15-3 (patients and controls), detection of EMP2 and β1-Integrin genes expression in the tissue samples by formation of cDNA by reverse transcription PCR after RNA extraction and real-time PCR using SYBR Green technique. Results Compared to healthy tissues, the breast cancer tissues had significant higher EMP2 and β1-Integringene expression levels. Azacitidine Also, there was a significant increase in CA15-3 in patients group as compared with the control group. It was found that EMP2 and β1-Integrin expression in malignant tissue samples correlates with advanced and metastatic disease. Conclusion The gene expression of EMP2 and β1-Integrin are important markers for the severity of breast cancer and they are good indicators of its prognosis.
Read More: https://www.selleckchem.com/products/Azacitidine(Vidaza).html