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Novartis builds on neuroscience pipeline and xRNA platform capabilities with acquisition of DTx Pharma
Novartis has acquired DTx Pharma, a San-Diego based, preclinical stage biotechnology company focused on leveraging its proprietary FALCON platform to develop siRNA therapies for neuroscience indications. DTx’s lead program, DTx-1252 targets the root cause of CMT1A - the overexpression of PMP22, a protein that causes the myelin sheath that supports and insulates nerves in the peripheral nervous system to function abnormally.
Source: World Pharma News - July 19, 2023 Category: Pharmaceuticals Tags: Featured Novartis Business and Industry Source Type: news

Cancers, Vol. 13, Pages 5943: MEOX2 Transcription Factor Is Involved in Survival and Adhesion of Glioma Stem-Like Cells
In this study, we unraveled, for the first time, MEOX2 contribution to cell viability and proliferation through AKT/ERK pathway and its potential involvement in phenotype and adhesion properties of GSC.
Source: Cancers - November 25, 2021 Category: Cancer & Oncology Authors: Ga ëlle Tachon Konstantin Masliantsev Pierre Rivet Amandine Desette Serge Milin Elise Gueret Michel Wager Lucie Karayan-Tapon Pierre-Olivier Guichet Tags: Article Source Type: research

GSE173837 RNA-seq and small RNA-seq in fission yeast CPF mutants that enable small-RNA-mediated epigenetic gene silencing
In this study, we have combined chemical mutagenesis with whole-genome sequencing in a sensitized S. pombe reporter strain to obtain a more comprehensive list of putative suppressors of small-RNA-mediated epigenetic gene silencing. This revealed more than 20 novel silencing-enabling mutations in genes that are associated with RNA processing, regulation of transcription, or post-translational protein modification. Focusing on factors involved in pre-mRNA cleavage and polyadenylation, we for example show that single amino acid substitutions in Yth1, which is responsible for polyadenylation signal recognition, lead to nearly ...
Source: GEO: Gene Expression Omnibus - June 7, 2021 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Non-coding RNA profiling by high throughput sequencing Schizosaccharomyces pombe Source Type: research

Cancers, Vol. 12, Pages 174: The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2
kutan Acquisition of cell migration capacity is an early and essential process in cancer development. The aim of this study was to identify microRNA gene expression networks that induced high migration capacity. Using colon cancer HCT116 cells subcloned by transwell-based migrated cell selection, microRNA array analysis was performed to examine the microRNA expression profile. Promoter activity and microRNA targets were assessed with luciferase reporters. Cell migration capacity was assessed by either the transwell or scratch assay. In isolated subpopulations with high migration capacity, the expression levels of the m...
Source: Cancers - January 9, 2020 Category: Cancer & Oncology Authors: Kensei Nishida Yuki Kuwano Kazuhito Rokutan Tags: Article Source Type: research

PDZ Binding Kinase (PBK) - a Novel Gene Driving Genomic Evolution in Multiple Myeloma
As in all cancers, genomic instability leads to ongoing acquisition of new genetic changes in multiple myeloma (MM). This adaptability underlies the development of drug resistance and progression in MM. This genomic instability is driven by cellular processes, mainly related with DNA repair and perturbed by functional changes in limited number of genes. Since kinases play a critical role in the regulation of biological processes, including DNA damage/repair signaling and are relatively easy to screen for inhibitors, we investigated for novel genes involved in the acquisition of new genomic changes in MM. Using a large geno...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kumar, S., Buon, L., Talluri, S., Shi, J., Avet-Loiseau, H., Samur, M. K., Shammas, M. A., Munshi, N. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

High-degree and broad-spectrum resistance mediated by a combination of NIb siRNA and miRNA suppresses replication of necrotic and common strains of potato virus Y
In this study, we designed specific siRNAs and miRNAs to target two regions of the PVYO replicase gene (NIb). Eight plant expression vectors containing one or two sRNAs were constructed. Luciferase activity assays showed that the designed sRNAs successfully cleaved theNIb gene of PVYO and PVYN, and the vector carrying a combined siRNA- and miRNA-based short hairpin RNA (shRNA) demonstrated the strongest inhibitory effect. These effects were confirmed through the acquisition of PVYO and PVYN resistance in transgenic sRNA-expressingNicotiana tabacum plants. This phenomenon could be related to a plant defense mechanism in whi...
Source: Archives of Virology - August 10, 2018 Category: Virology Source Type: research

HIF-1 α coordinates epigenetic activation of SIAH1 in hepatocytes in response to nutritional stress
We report that in response to nutritional stress, SIAH1 expression was up-regulated in the liver in mice and in cultured hepatocytes. In the meantime, HIF-1α started to occupy the SIAH1 promoter. Depletion of HIF-1α with siRNA or inhibition of HIF-1α with chetomin abrogated the induction of SIAH1 expression. HIF-1α knockdown or inhibition paralleled epigenetic alterations surrounding the SIAH1 promoter characterized by the loss of acetylated histone H3 and trimethylated H3K4 as well as the acquisition of dimethylated H3K9. Further analyses revealed that HIF-1α interacted with and recruited the histone demethylase KDM3...
Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - September 1, 2017 Category: Genetics & Stem Cells Source Type: research

GSE100589 Gene expression profiling of SAS cell line transfected with siRNA targeting CYLD
Contributors : Satoru Shinriki ; Hirofumi JonoSeries Type : Expression profiling by arrayOrganism : Homo sapiensOral squamous cell carcinoma (OSCC) has a very poor prognosis due to its highly invasive nature, and 5-year survival rate has not changed apparently for the past 30 years. Although cylindromatosis (CYLD) is thought as a potent tumor suppressor, its biological and clinical significances in OSCC are largely unknown. The aim of this study was to clarify roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed that CYLD expression was significantly reduced at invasive lesions in OSCC tissues where...
Source: GEO: Gene Expression Omnibus - June 29, 2017 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

Focal adhesion kinase signaling determines the fate of lung epithelial cells in response to TGF-{beta}
In this report, we explore the role of focal adhesion kinase (FAK) signaling in determining the fate of lung epithelial cells in response to transforming growth factor-β1 (TGF-β1). Rat type II alveolar epithelial cells (RLE-6TN) were treated with or without TGF-β1, and the expressions of mesenchymal markers, phenotype, and function were analyzed. Pharmacological protein kinase inhibitors were utilized to screen for SMAD-dependent and -independent pathways. SMAD and FAK signaling was analyzed using siRNA knockdown, inhibitors, and expression of a mutant construct of FAK. Apoptosis was measured using cleaved c...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Ding, Q., Subramanian, I., Luckhardt, T. R., Che, P., Waghray, M., Zhao, X.-K., Bone, N., Kurundkar, A. R., Hecker, L., Hu, M., Zhou, Y., Horowitz, J. C., Vittal, R., Thannickal, V. J. Tags: RESEARCH ARTICLE Source Type: research

Induced neural stem cells modulate microglia activation states via CXCL12/CXCR4 signaling
In this study, we aimed to characterize the immunomodulatory effects of iNSCs on the activation states of microglia and to elucidate the mechanisms underlying these effects. Using a mouse model of closed head injury (CHI), we observed that iNSC grafts decreased the levels of ED1+/Iba1+ and TNF-α+/Iba1+ microglia but increased the levels of IGF1+/Iba1+ microglia in the injured cortex. Subsequently, using a Transwell co-culture system, we discovered that iNSCs could modulate LPS-pretreated microglia phenotypes in vitro via CXCL12/CXCR4 signaling, which we demonstrated through the administration of the CXCR4 antagonist AMD31...
Source: Brain, Behavior, and Immunity - December 7, 2016 Category: Neurology Source Type: research

DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia
Idiopathic CD4 lymphopenia (ICL) is a rare heterogeneous immunological syndrome of unclear etiology. ICL predisposes patients to severe opportunistic infections and frequently leads to poor vaccination effectiveness. Chronic immune activation, expansion of memory T cells, and impaired T-cell receptor (TCR) signaling have been reported in ICL, but the mechanistic and causative links remain unclear. We show that late-differentiated T cells in 20 patients with ICL displayed defective TCR responses and aging markers similar to those found in T cells from elderly subjects. Intrinsic T-cell defects were caused by increased expre...
Source: Blood - April 16, 2015 Category: Hematology Authors: Bignon, A., Regent, A., Klipfel, L., Desnoyer, A., de la Grange, P., Martinez, V., Lortholary, O., Dalloul, A., Mouthon, L., Balabanian, K. Tags: Immunobiology Source Type: research

Rab14 Regulates Maturation of Macrophage Phagosomes Containing the Fungal Pathogen Candida albicans and Outcome of the Host-Pathogen Interaction Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Avoidance of innate immune defense is an important mechanism contributing to the pathogenicity of microorganisms. The fungal pathogen Candida albicans undergoes morphogenetic switching from the yeast to the filamentous hyphal form following phagocytosis by macrophages, facilitating its escape from the phagosome, which can result in host cell lysis. We show that the intracellular host trafficking GTPase Rab14 plays an important role in protecting macrophages from lysis mediated by C. albicans hyphae. Live-cell imaging of macrophages expressing green fluorescent protein (GFP)-tagged Rab14 or dominant negative Rab14, or with ...
Source: Infection and Immunity - March 17, 2015 Category: Infectious Diseases Authors: Okai, B., Lyall, N., Gow, N. A. R., Bain, J. M., Erwig, L.-P. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Alnylam closes $175M purchase of Merck subsidiary
Alnylam Pharmaceuticals has closed its $175 million acquisition of Sirna Therapeutics Inc., a subsidiary of Merck & Co., it said Thursday. In January, Cambridge-based Alnylam (Nasdaq: ALNY), which develops therapies based on RNA interference, entered into a stock and cash deal to buy Merck’s rights and interest of Sirna. The price was far less than the $1.1 billion Merck paid for Sirna in 2006 for the San Francisco-based biotech, which is also focused on RNAi drugs. It was a move some considered…
Source: bizjournals.com Health Care:Hospitals headlines - March 6, 2014 Category: Hospital Management Authors: Patricia Resende Source Type: research

The EMT Phenotype Confers Resistance to CTLs
In this study, we investigated the functional consequences of this mode of epithelial cell plasticity on targeted cell lysis by cytotoxic T lymphocytes (CTL). Acquisition of the EMT phenotype in various derivatives of MCF-7 human breast cancer cells was associated with dramatic morphologic changes and actin cytoskeleton remodeling, with CD24−/CD44+/ALDH+ stem cell populations present exhibiting a higher degree of EMT relative to parental cells. Strikingly, acquisition of this phenotype also associated with an inhibition of CTL-mediated tumor cell lysis. Resistant cells exhibited attenuation in the formation of an immunol...
Source: Cancer Research - April 15, 2013 Category: Cancer & Oncology Authors: Akalay, I., Jan&jnodot;i, B., Hasmim, M., Noman, M. Z., Andre, F., De Cremoux, P., Bertheau, P., Badoual, C., Vielh, P., Larsen, A. K., Sabbah, M., Tan, T. Z., Keira, J. H., Ying Hung, N. T., Thiery, J. P., Mami–Chouaib, F., Chouaib, S. Tags: Priority Reports Source Type: research