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https://www.readbyqxmd.com/read/28523286/synthetic-lethality-screens-using-rnai-in-combination-with-crispr-based-knockout-in-drosophila-cells
#1
Benjamin E Housden, Hilary E Nicholson, Norbert Perrimon
A synthetic lethal interaction is a type of genetic interaction where the disruption of either of two genes individually has little effect but their combined disruption is lethal. Knowledge of synthetic lethal interactions can allow for elucidation of network structure and identification of candidate drug targets for human diseases such as cancer. In Drosophila, combinatorial gene disruption has been achieved previously by combining multiple RNAi reagents. Here we describe a protocol for high-throughput combinatorial gene disruption by combining CRISPR and RNAi...
February 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28520736/the-bantam-microrna-acts-through-numb-to-exert-cell-growth-control-and-feedback-regulation-of-notch-in-tumor-forming-stem-cells-in-the-drosophila-brain
#2
Yen-Chi Wu, Kyu-Sun Lee, Yan Song, Stephan Gehrke, Bingwei Lu
Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb...
May 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28510116/obscure-functions-the-location-function-relationship-of-obscurins
#3
REVIEW
Heather R Manring, Olivia A Carter, Maegen A Ackermann
The obscurin family of polypeptides is essential for normal striated muscle function and contributes to the pathogenesis of fatal diseases, including cardiomyopathies and cancers. The single mammalian obscurin gene, OBSCN, gives rise to giant (∼800 kDa) and smaller (∼40-500 kDa) proteins that are composed of tandem adhesion and signaling motifs. Mammalian obscurin proteins are expressed in a variety of cell types, including striated muscles, and localize to distinct subcellular compartments where they contribute to diverse cellular processes...
March 29, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28509532/nanodiamonds-mediate-oral-delivery-of-proteins-for-stem-cell-activation-and-intestinal-remodeling-in-drosophila
#4
Xingjie Hu, Xiaojiao Li, Min Yin, Ping Li, Ping Huang, Lihua Wang, Yiguo Jiang, Hui Wang, Nan Chen, Chunhai Fan, Haiyun Song
Introduction of exogenous biomacromolecules into living systems is of great interest in genome editing, cancer immunotherapy, and stem cell reprogramming. Whereas current strategies generally depend on nucleic acids transfection, direct delivery of functional proteins that provides enhanced specificity, increased safety, and fast and temporal regulation is highly desirable. Nevertheless, intracellular delivery of intact and bioactive proteins, especially in vivo, remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based protein delivery system in cultured cells and in Drosophila that showed high adsorption, high efficiency, and effective cytosolic release of fully functional proteins...
May 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28508872/actin-stress-fiber-organization-promotes-cell-stiffening-and-proliferation-of-pre-invasive-breast-cancer-cells
#5
Sandra Tavares, André Filipe Vieira, Anna Verena Taubenberger, Margarida Araújo, Nuno Pimpao Martins, Catarina Brás-Pereira, António Polónia, Maik Herbig, Clara Barreto, Oliver Otto, Joana Cardoso, José B Pereira-Leal, Jochen Guck, Joana Paredes, Florence Janody
Studies of the role of actin in tumour progression have highlighted its key contribution in cell softening associated with cell invasion. Here, using a human breast cell line with conditional Src induction, we demonstrate that cells undergo a stiffening state prior to acquiring malignant features. This state is characterized by the transient accumulation of stress fibres and upregulation of Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src activation and progression towards a fully transformed state...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28508063/the-long-noncoding-rna-sprightly-acts-as-an-intranuclear-organizing-hub-for-pre-mrna-molecules
#6
Bongyong Lee, Anupama Sahoo, John Marchica, Erwin Holzhauser, Xiaoli Chen, Jian-Liang Li, Tatsuya Seki, Subramaniam Shyamala Govindarajan, Fatu Badiane Markey, Mona Batish, Sonali J Lokhande, Shaojie Zhang, Animesh Ray, Ranjan J Perera
Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence cancerous condition are poorly understood. The aberrant expression of SPRIGHTLY lncRNA, encoded within the drosophila gene homolog Sprouty-4 intron, is correlated with a variety of cancers, including human melanomas. We demonstrate by SHAPE-seq and dChIRP that SPRIGHTLY RNA secondary structure has a core pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre-mRNAs: SOX5, SMYD3, SND1, MEOX2, DCTN6, and RASAL2, all of which have cancer-related functions...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28495673/parallel-imaging-of-drosophila-embryos-for-quantitative-analysis-of-genetic-perturbations-of-the-ras-pathway
#7
Yogesh Goyal, Thomas J Levario, Henry H Mattingly, Susan Holmes, Stanislav Y Shvartsman, Hang Lu
The Ras pathway patterns the poles of the Drosophila embryo by downregulating the levels and activity of a DNA-binding transcriptional repressor Capicua (Cic). We demonstrate that the spatiotemporal pattern of Cic during this signaling event can be harnessed for functional studies of the Ras-pathway mutations from human diseases. Our approach relies on a new microfluidic device that enables parallel imaging of Cic dynamics in dozens of live embryos. We found that although the pattern of Cic in early embryos is complex, it can be accurately approximated by a product of one spatial profile and one time-dependent amplitude...
May 11, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28483915/rab2-promotes-autophagic-and-endocytic-lysosomal-degradation
#8
Péter Lőrincz, Sarolta Tóth, Péter Benkő, Zsolt Lakatos, Attila Boda, Gábor Glatz, Martina Zobel, Sara Bisi, Krisztina Hegedűs, Szabolcs Takáts, Giorgio Scita, Gábor Juhász
Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes in yeast and metazoan cells, acting together with its effector, the tethering complex HOPS. Here we show that another small GTPase, Rab2, is also required for autophagosome and endosome maturation and proper lysosome function in Drosophila melanogaster We demonstrate that Rab2 binds to HOPS, and that its active, GTP-locked form associates with autolysosomes. Importantly, expression of active Rab2 promotes autolysosomal fusions unlike that of GTP-locked Rab7, suggesting that its amount is normally rate limiting...
May 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28476910/the-immune-phenotype-of-three-drosophila-leukemia-models
#9
Badrul Arefin, Martin Kunc, Robert Krautz, Ulrich Theopold
Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruitfly Drosophila melanogaster has an innate immune system including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia we established three models by driving expression of a dominant-active version of the Ras oncogene (Ras(V12) ) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes...
May 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28471262/mtv-sings-jubilation-for-telomere-biology-in-drosophila
#10
Lin Cheng, Ming Cui, Yikang S Rong
Telomere protects the ends of linear chromosomes. Telomere dysfunction fuels genome instability that can lead to diseases such as cancer. For over 30 years, Drosophila has fascinated the field as the only major model organism that does not rely on the conserved telomerase enzyme for end protection. Instead of short DNA repeats at chromosome ends, Drosophila has domesticated retrotransposons. In addition, telomere protection can be entirely sequence-independent under normal laboratory conditions, again dissimilar to what has been established for telomerase-maintained systems...
May 4, 2017: Fly
https://www.readbyqxmd.com/read/28459369/grainyhead-like-2-in-development-and-cancer
#11
Lijun Ma, Hongli Yan, Hui Zhao, Jianmin Sun
Grainyhead-like 2 is a human homolog of Drosophila grainyhead. It inhibits epithelial-to-mesenchymal transition that is necessary for cell migration, and it is involved in neural tube closure, epithelial morphogenesis, and barrier formation during embryogenesis by regulation of the expression of cell junction proteins such as E-cadherin and vimentin. Cancer shares many common characters with development such as epithelial-to-mesenchymal transition. In addition to its important role in development, grainyhead-like 2 is implicated in carcinogenesis as well...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28458991/steroid-hormones-and-the-physiological-regulation-of-tissue-resident-stem-cells-lessons-from-the-drosophila-ovary
#12
Elizabeth T Ables, Daniela Drummond-Barbosa
PURPOSE OF REVIEW: Stem cells respond to local paracrine signals; more recently, however, systemic hormones have also emerged as key regulators of stem cells. This review explores the role of steroid hormones in stem cells, using the Drosophila germline stem cell as a centerpiece for discussion. RECENT FINDINGS: Stem cells sense and respond directly and indirectly to steroid hormones, which regulate diverse sets of target genes via interactions with nuclear hormone receptors...
March 2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28455414/hdac-inhibitors-disrupt-programmed-resistance-to-apoptosis-during-drosophila-development
#13
Yunsik Kang, Khailee Marischuk, Gina D Castelvecchi, Arash Bashirullah
We have previously shown that the ability to respond to apoptotic triggers is regulated during Drosophila development, effectively dividing the fly life cycle into stages that are either sensitive or resistant to apoptosis. Here, we show that the developmentally programmed resistance to apoptosis involves transcriptional repression of critical pro-apoptotic genes by histone deacetylases (HDACs). Administration of HDAC inhibitors (HDACi), like Trichostatin A (TSA) or Suberoylanilide Hydroxamic Acid (SAHA), increases expression of pro-apoptotic genes and is sufficient to sensitize otherwise resistant stages...
April 28, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28422722/the-clinical-value-regulatory-mechanisms-and-gene-network-of-the-cancer-testis-gene-stk31-in-pancreatic-cancer
#14
Kai Zhang, Zipeng Lu, Yi Zhu, Lei Tian, Jingjing Zhang, Chunhua Xi, Wentao Gao, Kuirong Jiang, Yi Miao
We aimed to identify STK31 as a cancer-testis (CT) gene and to explore its potential clinical value, regulatory mechanisms, and gene network in pancreatic cancer (PC). Gene expression data were generated from normal organ samples and pancreatic cancer samples from three public databases. STK31 expression patterns in normal and PC tissues were identified, and we explored its regulatory mechanisms. Gene ontology (GO) and pathway analyses of STK31-related genes were performed and an STK31 protein-protein interaction (PPI) network was constructed...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420161/myc-cell-competition-and-cell-death-in-cancer-the-inseparable-triad
#15
REVIEW
Simone Di Giacomo, Manuela Sollazzo, Simona Paglia, Daniela Grifoni
Deregulation of MYC family proteins in cancer is associated with a global reprogramming of gene expression, ultimately promoting glycolytic pathways, cell growth, and proliferation. It is well known that MYC upregulation triggers cell-autonomous apoptosis in normal tissues, while frankly malignant cells develop resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell-autonomous apoptotic death through an evolutionarily conserved mechanism known as "cell competition"...
April 17, 2017: Genes
https://www.readbyqxmd.com/read/28404605/proteomics-analysis-identifies-orthologs-of-human-chitinase-like-proteins-as-inducers-of-tube-morphogenesis-defects-in-drosophila
#16
Sandra G Zimmerman, Gennifer E Merrihew, Michael J MacCoss, Celeste A Berg
Elevated levels of human chitinase-like proteins (CLPs) are associated with numerous chronic inflammatory diseases and several cancers, often correlating with poor prognosis. Nevertheless, there is scant knowledge of their function. The CLPs normally mediate immune responses and wound healing, and when upregulated, they can promote disease progression by remodeling tissue, activating signaling cascades, stimulating proliferation and migration, and by regulating adhesion. We identified Imaginal disc growth factors (Idgfs), orthologs of human CLPs CHI3L1, CHI3L2, and OVGP1, in a proteomics analysis designed to discover factors that regulate tube morphogenesis in a Drosophila melanogaster model of tube formation...
April 12, 2017: Genetics
https://www.readbyqxmd.com/read/28401354/novel-triazole-linked-2-phenyl-benzoxazole-derivatives-induce-apoptosis-by-inhibiting-mir-2-mir-13-and-mir-14-function-in-drosophila-melanogaster
#17
Tanmoy Mondal, A V S Lavanya, Akash Mallick, Tulshiram L Dadmala, Ravindra M Kumbhare, Utpal Bhadra, Manika Pal Bhadra
Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis...
June 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28398229/controlling-the-master-chromatin-dynamics-at-the-myc-promoter-integrate-developmental-signaling
#18
REVIEW
Olga Zaytseva, Leonie M Quinn
The transcription factor and cell growth regulator MYC is potently oncogenic and estimated to contribute to most cancers. Decades of attempts to therapeutically target MYC directly have not resulted in feasible clinical applications, and efforts have moved toward indirectly targeting MYC expression, function and/or activity to treat MYC-driven cancer. A multitude of developmental and growth signaling pathways converge on the MYC promoter to modulate transcription through their downstream effectors. Critically, even small increases in MYC abundance (<2 fold) are sufficient to drive overproliferation; however, the details of how oncogenic/growth signaling networks regulate MYC at the level of transcription remain nebulous even during normal development...
April 11, 2017: Genes
https://www.readbyqxmd.com/read/28396508/adipocyte-metabolic-pathways-regulated-by-diet-control-the-female-germline-stem-cell-lineage-in-drosophila
#19
Shinya Matsuoka, Alissa Armstrong, Leesa L Sampson, Kaitlin M Laws, Daniela Drummond-Barbosa
Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. Drosophila melanogaster has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage...
April 10, 2017: Genetics
https://www.readbyqxmd.com/read/28389882/hormetic-efficacy-of-rutin-to-promote-longevity-in-drosophila-melanogaster
#20
Debarati Chattopadhyay, Atith Chitnis, Aishwarya Talekar, Prajakta Mulay, Manyata Makkar, Joel James, Kavitha Thirumurugan
Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals...
June 2017: Biogerontology
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