Search results for "RNA interference"
showing 10 items of 202 documents
Established cotton stainer gut bacterial mutualists evade regulation by host antimicrobial peptides
2019
Symbioses with microorganisms are ubiquitous in nature and confer important ecological traits to animal hosts but also require control mechanisms to ensure homeostasis of the symbiotic interactions. In addition to protecting hosts against pathogens, animal immune systems recognize, respond to, and regulate mutualists. The gut bacterial symbionts of the cotton stainer bug, Dysdercus fasciatus, elicit an immune response characterized by the upregulation of c-type lysozyme and the antimicrobial peptide pyrrhocoricin in bugs with their native gut microbiota compared to that in dysbiotic insects. In this study, we investigated the impact of the elicited antimicrobial immune response on the estab…
Engineering Bacteria to Form a Biofilm and Induce Clumping in Caenorhabditis elegans
2014
Bacteria are needed for a vast range of biotechnological processes, which they carry out either as pure cultures or in association with other bacteria and/or fungi. The potential of bacteria as biofactories is hampered, though, by their limited mobility in solid or semisolid media such as agricultural or domestic waste. This work represents an attempt toward overcoming this limitation by associating bacterial biotechnological properties with the transport ability of the nematode Caenorhabditis elegans. We report here biofilm formation on C. elegans by engineered Escherichia coli expressing a Xhenorhabdus nematophila adhesion operon and induction of nematode social feeding behavior (clumping…
The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells
2014
The TH9 subset of helper T cells was initially shown to contribute to the induction of autoimmune and allergic diseases, but subsequent evidence has suggested that these cells also exert antitumor activities. However, the molecular events that account for their effector properties are elusive. Here we found that the transcription factor IRF1 enhanced the effector function of TH9 cells and dictated their anticancer properties. Under TH9-skewing conditions, interleukin 1β (IL-1β) induced phosphorylation of the transcription factor STAT1 and subsequent expression of IRF1, which bound to the promoters of Il9 and Il21 and enhanced secretion of the cytokines IL-9 and IL-21 from TH9 cells. Further…
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes
2015
Item does not contain fulltext Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequen…
Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery
2016
(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a gl…
Gadd45α modulates aversive learning through post‐transcriptional regulation of memory‐related mRNA s
2018
Abstract Learning is essential for survival and is controlled by complex molecular mechanisms including regulation of newly synthesized mRNAs that are required to modify synaptic functions. Despite the well‐known role of RNA‐binding proteins (RBPs) in mRNA functionality, their detailed regulation during memory consolidation is poorly understood. This study focuses on the brain function of the RBP Gadd45α (growth arrest and DNA damage‐inducible protein 45 alpha, encoded by the Gadd45a gene). Here, we find that hippocampal memory and long‐term potentiation are strongly impaired in Gadd45a‐deficient mice, a phenotype accompanied by reduced levels of memory‐related mRNAs. The majority of the Ga…
Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits.
2007
Parkinson's disease (PD) is a progressive movement disorder caused by the selective and massive loss of dopaminergic neurons (DA) in the substantia nigra pars compacta (SNc). DJ-1 loss-of-function mutations are involved in inherited early-onset PD forms and result in dysfunction of the oxidative stress response. In mice models, DJ-1 loss provokes sensitivity to oxidative insults but does not produce neurodegeneration. Similar results have been found when analyzing Drosophila mutants for the DJ-1 orthologous genes, DJ-1alpha and DJ-1beta. Here, we report the analysis of two new mutations for the Drosophila DJ-1 genes. Both ubiquitous induction of DJ-1alpha knockdown by RNAi and loss of funct…
Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma
2006
Overexpression of T-cadherin (T-cad) transcripts occurs in approximately 50% of human hepatocellular carcinomas (HCCs). To elucidate T-cad functions in HCC, we examined T-cad protein expression in normal and tumoral human livers and hepatoma cell lines and investigated its influence on invasive potential of HCC using RNA interference silencing of T-cad expression in Mahlavu cells. Whereas T-cad expression was restricted to endothelial cells (EC) from large blood vessels in normal livers, it was up-regulated in sinusoidal EC from 8/15 invasive HCCs. Importantly, in three of them (38%) T-cad was detected in tumor cells within regions in which E-cadherin expression was absent. Among six hepato…
Inhibiting proliferation in KB cancer cells by RNA interference-mediated knockdown of nicotinamide N-methyltransferase expression.
2011
The enzyme Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide and other pyridines, playing a pivotal role in the biotransformation and detoxification of many drugs and xenobiotic compounds. Several tumours have been associated with abnormal NNMT expression, however its role in tumour development remains largely unknown. In this study we investigated expression levels of Nicotinamide N-methyltransferase in a cancer cell line and we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation. Cancer cells were examined for NNMT expression by semiquantitative RT-PCR and Western blot analysis. A HPLC-based catalytic assay was performed to asses…
Gata4 Blocks Somatic Cell Reprogramming By Directly Repressing Nanog
2012
Abstract Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by ectopic expression of the four factors Oct4, Klf4, Sox2, and Myc. Here, we investigated the role of Gata4 in the reprogramming process and present evidence for a negative role of this family of transcription factors in the induction of pluripotency. Coexpression of Gata4 with Oct4, Klf4, and Sox2 with or without Myc in mouse embryonic fibroblasts greatly impaired reprogramming and endogenous Nanog expression. The lack of Nanog upregulation was associated with a blockade in the transition from the initiation phase of reprogramming to the full pluripotent state characteristic of iPS cells. Addition of Nanog …