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https://www.readbyqxmd.com/read/28107502/rnai-based-functional-genomics-identifies-new-virulence-determinants-in-mucormycosis
#1
Trung Anh Trieu, María Isabel Navarro-Mendoza, Carlos Pérez-Arques, Marta Sanchis, Javier Capilla, Patricia Navarro-Rodriguez, Loida Lopez-Fernandez, Santiago Torres-Martínez, Victoriano Garre, Rosa María Ruiz-Vázquez, Francisco E Nicolás
Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28106737/a-novel-combination-rnai-toward-warburg-effect-by-replacement-with-mir-145-and-silencing-of-ptbp1-induces-apoptotic-cell-death-in-bladder-cancer-cells
#2
Tomoaki Takai, Yuki Yoshikawa, Teruo Inamoto, Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Haruka Shinohara, Minami Kumazaki, Takuya Tsujino, Kiyoshi Takahara, Yuko Ito, Yukihiro Akao, Haruhito Azuma
Bladder cancer is one of the most difficult malignancies to control. We explored the use of a novel RNA-interference method for a driver oncogene regulating cancer specific energy metabolism by the combination treatment with a small interfering RNA (siRNA) and a microRNA. After transfection of T24 and 253JB-V cells with miR-145 and/or siR-PTBP1, we examined the effects of cell growth and gene expression by performing the trypan blue dye exclusion test, Western blot, Hoechst 33342 staining, reverse transcription polymerase chain reaction (RT-PCR), and electron microscopy...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106473/overexpression-of-buffy-enhances-the-loss-of-parkin-and-suppresses-the-loss-of-pink1-phenotypes-in-drosophila
#3
P Githure M'Angale, Brian E Staveley
Mutations in parkin (PARK2) and Pink1 (PARK6) are responsible for autosomal recessive forms of early onset Parkinson's disease (PD). Attributed to the failure of neurons to clear dysfunctional mitochondria, loss of gene expression leads to loss of nigrostriatal neurons. The Pink1/parkin pathway plays a role in the quality control mechanism aimed at eliminating defective mitochondria, and the failure of this mechanism results in a reduced lifespan and impaired locomotor ability, among other phenotypes. Inhibition of parkin or Pink1 through the induction of stable RNAi transgene in the Ddc-Gal4-expressing neurons results in such phenotypes to model PD...
December 22, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28105147/fgfr3-silencing-by-sirna-inhibits-invasion-of-a549-cells
#4
Yuhua Li, Xiguang Liu, Hongjun Zhang, Tao Jiang, Wenjing Xiao, Shufen Zhao, Xiaoyun Yu, Fanjie Han
The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105136/arid1a-gene-silencing-reduces-the-sensitivity-of-ovarian-clear-cell-carcinoma-to-cisplatin
#5
Changshuai Lyu, Yinglan Zhang, Xingnan Zhou, Jinghe Lang
In ovarian clear cell carcinoma (OCCC), the mutation rate of the AT-rich interaction domain 1A (ARID1A) gene is 46-57%. However, the effects of ARID1A gene silencing by small interfering RNA (siRNA) on the sensitivity of OCCC to cisplatin have not been investigated. Thus, this study aimed to elucidate the association between ARID1A gene silencing and drug resistance in OCCC. Three pairs of ARID1A gene siRNA fragments (siRNA-1, siRNA-2 and siRNA-3) were designed and transiently transfected into ES2 OCCC cells using RNAi Max reagent...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28105110/wt1-shrna-delivery-using-transferrin-conjugated-peg-liposomes-in-an-in-vivo-model-of-melanoma
#6
Santiago Saavedra-Alonso, Pablo Zapata-Benavides, Ana Karina Chavez-Escamilla, Edgar Manilla-Muñoz, Diana Elisa Zamora-Avila, Moisés Armides Franco-Molina, Cristina Rodriguez-Padilla
The global incidence of melanoma is increasing. Mortality from melanoma is influenced primarily by metastasis in advanced stages of the disease. Current treatments are largely ineffective; thus, novel gene delivery approaches that target tumor-specific markers may be useful for the treatment of melanoma. Systemic administration of encapsulated RNA-interference plasmids targeted against tumor cells is a potential alternative therapy for cancer. Formulations of transferrin (Tf)-conjugated polyethylene glycol (PEG) liposomes loaded with short hairpin RNA (shRNA) against WT1 (Lip + RNAi + Tf), PEG liposomes loaded with shRNA against WT1 (Lip + RNAi), Tf-conjugated PEG liposomes loaded with pEGFP-N3 (Lip + GFP + Tf) and saline solution as negative control (untreated) were administered systemically to C57BL/6 mice implanted subcutaneously with a melanoma cell line...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104305/cp39-cp75-and-cp91-are-major-structural-components-of-the-dictyostelium-centrosome-s-core-structure
#7
Irene Meyer, Tatjana Peter, Petros Batsios, Oliver Kuhnert, Anne Krüger-Genge, Carl Camurça, Ralph Gräf
The acentriolar Dictyostelium centrosome is a nucleus-associated body consisting of a core structure with three plaque-like layers, which are surrounded by a microtubule-nucleating corona. The core duplicates once per cell cycle at the G2/M transition, whereby its central layer disappears and the two outer layers form the mitotic spindle poles. Through proteomic analysis of isolated centrosomes, we have identified CP39 and CP75, two essential components of the core structure. Both proteins can be assigned to the central core layer as their centrosomal presence is correlated to the disappearance and reappearance of the central core layer in the course of centrosome duplication...
January 12, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28103400/the-sufbc2-d-complex-is-required-for-the-biogenesis-of-all-major-classes-of-plastid-fe-s-proteins
#8
Xueyun Hu, Yukako Kato, Akihiro Sumida, Ayumi Tanaka, Ryouichi Tanaka
Iron-sulfur (Fe-S) proteins play crucial roles in plastids, participating in photosynthesis and other metabolic pathways. Fe-S clusters are thought to be assembled on a scaffold complex composed of SUFB, SUFC and SUFD proteins. However, several additional proteins provide putative scaffold functions in plastids, and, therefore, the contribution of SUFB, C and D proteins to overall Fe-S assembly still remains unclear. In order to gain insights regarding Fe-S cluster biosynthesis in plastids, we analyzed the complex composed of SUFB, C and D in Arabidopsis by blue-native polyacrylamide gel electrophoresis...
January 19, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28102736/dengue-and-zika-viruses-subvert-reticulophagy-by-ns2b3-mediated-cleavage-of-fam134b
#9
Nicholas J Lennemann, Carolyn B Coyne
The endoplasmic reticulum (ER) is exploited by a number of diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), utilize the ER as a source of membranes to establish their replication organelles and to facilitate their assembly and eventual maturation along the secretory pathway. In order to maintain normal homeostasis, host cells have evolved highly efficient processes to dynamically regulate the ER, such as through reticulophagy, a selective form of autophagy that leads to ER degradation...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28102363/smarca4-inactivating-mutations-increase-sensitivity-to-aurora-kinase-a-inhibitor-vx-680-in-non-small-cell-lung-cancers
#10
Vural Tagal, Shuguang Wei, Wei Zhang, Rolf A Brekken, Bruce A Posner, Michael Peyton, Luc Girard, TaeHyun Hwang, David A Wheeler, John D Minna, Michael A White, Adi F Gazdar, Michael G Roth
Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102206/g%C3%AE-13-negatively-controls-osteoclastogenesis-through-inhibition-of-the-akt-gsk3%C3%AE-nfatc1-signalling-pathway
#11
Mengrui Wu, Wei Chen, Yun Lu, Guochun Zhu, Liang Hao, Yi-Ping Li
Many positive signalling pathways of osteoclastogenesis have been characterized, but negative signalling pathways are less well studied. Here we show by microarray and RNAi that guanine nucleotide-binding protein subunit α13 (Gα13) is a negative regulator of osteoclastogenesis. Osteoclast-lineage-specific Gna13 conditional knockout mice have a severe osteoporosis phenotype. Gna13-deficiency triggers a drastic increase in both osteoclast number and activity (hyper-activation), mechanistically through decreased RhoA activity and enhanced Akt/GSK3β/NFATc1 signalling...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101904/functional-analysis-of-the-circadian-clock-gene-timeless-in-tribolium-castaneum
#12
Chengjun Li, Xiaopei Yun, Xiaojuan Yu, Bin Li
Circadian rhythms are endogenous oscillations with a period of about 24 h driven by a circadian clock. So far, the variable oscillators were designed in insects. To explore the circadian clock of Tribolium castaneum, we have cloned the clock gene timeless (Tctimeless). Its open reading frame is 3240 bp in length and consists of 10 exons. Tctimeless is highly expressed in the late pupal stage. Tissue-specific expression analysis in late adult stages revealed high expression of Tctimeless in the head, epidermis, fat body and accessory glands...
January 19, 2017: Insect Science
https://www.readbyqxmd.com/read/28100781/biogenesis-of-a-mitochondrial-outer-membrane-protein-in-trypanosoma-brucei-targeting-signal-and-dependence-on-an-unique-biogenesis-factor
#13
Julia Bruggisser, Sandro K Aumlser, Jan Mani, Andre Schneider
The mitochondrial outer membrane (OM) contains single and multiple membrane-spanning proteins which need to contain signals that ensure correct targeting and insertion into the OM. The biogenesis of such proteins has so far essentially only been studied in yeast and related organisms. Here we show that POMP10, an OM protein of the early diverging protozoan Trypanosoma brucei, is signal-anchored. Transgenic cells expressing variants of POMP10 fused to GFP demonstrate that the N-terminal membrane-spanning domain flanked by a few positively charged or neutral residues is both necessary and sufficient for mitochondrial targeting...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100297/transcriptional-analysis-of-mating-and-pre-infection-stages-of-the-anther-smut-microbotryum-lychnidis-dioicae
#14
Su San Toh, Zehua Chen, David J Schultz, Christina A Cuomo, Michael H Perlin
Microbotryum lychnidis-dioicae is an obligate biotrophic parasite of the wildflower species, Silene latifolia. This dikaryotic fungus, commonly known as an anther smut, requires that haploid, yeast-like sporidia of opposite mating types fuse and differentiate into dikaryotic hyphae that penetrate host tissue as part of the fungal lifecycle. Mating occurs under conditions of cool temperatures and limited nutrients. Further development requires host cues or chemical mimics, including a variety of lipids, e.g...
January 17, 2017: Microbiology
https://www.readbyqxmd.com/read/28100270/pro-inflammation-nf-%C3%AE%C2%BAb-signaling-triggers-a-positive-feedback-via-enhancing-cholesterol-accumulation-in-liver-cancer-cells
#15
Mingyan He, Wenhui Zhang, Yinying Dong, Lishun Wang, Tingting Fang, Wenqing Tang, Bei Lv, Guanglang Chen, Biwei Yang, Peixin Huang, Jinglin Xia
BACKGROUND: Hepatocellular carcinoma (HCC) develops in a complex microenvironment characterized by chronic inflammation. In recent years, cholesterol metabolic abnormalities have been implicated the importance in cancer cell physiology. This study was designed to investigate the relationship between inflammation and cholesterol accumulation in HCC cells. METHODS: Human HCC cells HepG2 and Huh7 were cultured and stimulated with lipopolysaccharide (LPS) for 24 h...
January 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28099851/a-molecular-and-cellular-context-dependent-role-for-ir76b-in-detection-of-amino-acid-taste
#16
Anindya Ganguly, Lisa Pang, Vi-Khoi Duong, Angelina Lee, Hanni Schoniger, Erika Varady, Anupama Dahanukar
Amino acid taste is expected to be a universal property among animals. Although sweet, bitter, salt, and water tastes have been well characterized in insects, the mechanisms underlying amino acid taste remain elusive. From a Drosophila RNAi screen, we identify an ionotropic receptor, Ir76b, as necessary for yeast preference. Using calcium imaging, we identify Ir76b(+) amino acid taste neurons in legs, overlapping partially with sweet neurons but not those that sense other tastants. Ir76b mutants have reduced responses to amino acids, which are rescued by transgenic expression of Ir76b and a mosquito ortholog AgIr76b...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099780/the-genetic-architecture-of-defense-as-resistance-to-and-tolerance-of-bacterial-infection-in-drosophila-melanogaster
#17
Virginia M Howick, Brian P Lazzaro
Defense against pathogenic infection can take two forms: resistance and tolerance. Resistance is the ability of the host to limit a pathogen burden, whereas tolerance is the ability to limit the negative consequences of infection at a given level of infection intensity. Evolutionarily, a tolerance strategy that is independent of resistance could allow the host to avoid mounting a costly immune response and, theoretically, to avoid a coevolutionary arms race between pathogen virulence and host resistance. Biomedically, understanding the mechanisms of tolerance and how they relate to resistance could potentially yield treatment strategies that focus on health improvement instead of pathogen elimination...
January 18, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28098854/lsd1-sustains-estrogen-driven-endometrial-carcinoma-cell-proliferation-through-the-pi3k-akt-pathway-via-di-demethylating-h3k9-of-cyclin%C3%A2-d1
#18
Chunqin Chen, Yanan Wang, Shiyu Wang, Yuan Liu, Jiawen Zhang, Yuyao Xu, Zhenbo Zhang, Wei Bao, Sufang Wu
A recent study reported that histone lysine specific demethylase 1 (LSD1, KDM1A) is overexpressed in endometrioid endometrial carcinoma (EEC) and associated with tumor progression as well as poor prognosis. However, the physiological function and mechanism of LSD1 in endometrial cancer (EC) remains largely unknown. In this study, we demonstrate that β-estradiol (E2) treatment increased LSD1 expression via the GPR30/PI3K/AKT pathway in endometrial cancer cells. Both siGPR30 and the PI3K inhibitor LY294002 block this effect...
January 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28094937/click-qms-identifies-piwil3-as-a-mechanistic-target-of-rna-interference-activator-enoxacin-in-cancer-cells
#19
Nathan Abell, Marvin Mercado, Tatiana Cañeque, Raphaël Rodriguez, Blerta Xhemalce
Enoxacin is a small molecule that stimulates RNA interference (RNAi) and acts as a growth inhibitor selectively in cancer but not in untransformed cells. Here, we used alkenox, a clickable enoxacin surrogate, coupled with quantitative Mass Spectrometry, to identify PIWIL3 as a mechanistic target of enoxacin. PIWIL3 is an Argonaut protein of the PIWI subfamily that is mainly expressed in the germline and that mediates RNAi through piRNAs. Our results suggest that cancer cells re-express PIWIL3 to repress RNAi through miRNAs and thus open a new opportunity for cancer specific targeting...
January 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28094036/centriole-remodeling-during-spermiogenesis-in-drosophila
#20
Atul Khire, Kyoung H Jo, Dong Kong, Tara Akhshi, Stephanie Blachon, Anthony R Cekic, Sarah Hynek, Andrew Ha, Jadranka Loncarek, Vito Mennella, Tomer Avidor-Reiss
The first cell of an animal (zygote) requires centrosomes that are assembled from paternally inherited centrioles and maternally inherited pericentriolar material (PCM) [1]. In some animals, sperm centrioles with typical ultrastructure are the origin of the first centrosomes in the zygote [2-4]. In other animals, however, sperm centrioles lose their proteins and are thought to be degenerated and non-functional during spermiogenesis [5, 6]. Here, we show that the two sperm centrioles (the giant centriole [GC] and the proximal centriole-like structure [PCL]) in Drosophila melanogaster are remodeled during spermiogenesis through protein enrichment and ultrastructure modification in parallel to previously described centrosomal reduction [7]...
December 5, 2016: Current Biology: CB
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