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https://www.readbyqxmd.com/read/29932056/epigenetics-with-special-reference-to-the-human-x-chromosome-inactivation-and-the-enigma-of-drosophila-dna-methylation
#1
Deepti Deobagkar
Epigenetics confers adaptability and survival advantage to an organism. Most epigenetic processes demonstrate memory and heritability. DNA methylation is an epigenetic process that adds imprints which can be inherited during cell division and across generations. DNA methylation adds an additional level of information to the basic DNA sequence and can influence chromatin organization and the function of the DNA sequence. In bacteria, it works as a defence strategy and preserves genome integrity. DNA methylation in eukaryotes has been implicated in a large number of cellular regulatory processes and is implied in development, differentiation, life style diseases and cancer...
June 2018: Journal of Genetics
https://www.readbyqxmd.com/read/29912942/a-conserved-role-for-syntaxin-1-in-pre-and-post-commissural-midline-axonal-guidance-in-fly-chick-and-mouse
#2
Oriol Ros, Pablo José Barrecheguren, Tiziana Cotrufo, Martina Schaettin, Cristina Roselló-Busquets, Alba Vílchez-Acosta, Marc Hernaiz-Llorens, Ramón Martínez-Marmol, Fausto Ulloa, Esther T Stoeckli, Sofia J Araújo, Eduardo Soriano
Axonal growth and guidance rely on correct growth cone responses to guidance cues. Unlike the signaling cascades that link axonal growth to cytoskeletal dynamics, little is known about the crosstalk mechanisms between guidance and membrane dynamics and turnover. Recent studies indicate that whereas axonal attraction requires exocytosis, chemorepulsion relies on endocytosis. Indeed, our own studies have shown that Netrin-1/Deleted in Colorectal Cancer (DCC) signaling triggers exocytosis through the SNARE Syntaxin-1 (STX1)...
June 18, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29901093/efficacy-of-lentivirus%C3%A2-mediated-drosophila-melanogaster-deoxyribonucleoside-kinase-combined-with-e-%C3%A2-5%C3%A2-2%C3%A2-bromovinyl-%C3%A2-2-%C3%A2-deoxyuridine-or-1%C3%A2-%C3%AE-%C3%A2-d%C3%A2-arabinofuranosylthymine-therapy-in-human-keloid-fibroblasts
#3
Yiqun Sun, Haiyang Jiang, Ming Gu, Xinyu Zheng
Keloid scarring is a type of fibroproliferative disease with a high recurrence rate. However, no effective treatment is currently available. Combined therapy with recombinant lentivirus‑mediated Drosophila melanogaster deoxyribonucleoside kinase (Dm‑dNK) and prodrug has been widely studied and used for cancer treatment. Due to the similarities between keloid scars and tumors, the aim of the present study was to investigate the efficacy of a Dm‑dNK/nucleoside analog system for the treatment of keloid scars...
May 30, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29882348/non-mammalian-hosts-and-photobiomodulation-do-all-life-forms-respond-to-light
#4
Michael R Hamblin, Ying-Ying Huang, Vladimir Heiskanen
Photobiomodulation (PBM), also known as low-level laser (light) therapy, was discovered over 50 years ago, but only recently has it been making progress towards wide acceptance. PBM originally used red and near-infrared (NIR) lasers, but now other wavelengths and non-coherent light emitting diodes (LEDs) are being explored. The almost complete lack of side-effects makes the conduction of controlled clinical trials relatively easy. Laboratory research has mainly concentrated on mammalian cells (normal or cancer) in culture, and small rodents (mice and rats) as models of different diseases...
June 8, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29871910/lgl-reduces-endosomal-vesicle-acidification-and-notch-signaling-by-promoting-the-interaction-between-vap33-and-the-v-atpase-complex
#5
Marta Portela, Liu Yang, Sayantanee Paul, Xia Li, Alexey Veraksa, Linda M Parsons, Helena E Richardson
Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue than in wild-type tissue because of increased acidification of endosomal vesicles, which promotes the proteolytic processing and activation of Notch by γ-secretase. We showed that the increased Notch signaling and tissue growth defects of lgl mutant tissue depended on endosomal vesicle acidification mediated by the vacuolar adenosine triphosphatase (V-ATPase)...
June 5, 2018: Science Signaling
https://www.readbyqxmd.com/read/29863430/fruit-flies-provide-new-insights-in-low-radiation-background-biology-at-the-infn-underground-gran-sasso-national-laboratory-lngs
#6
Patrizia Morciano, Francesca Cipressa, Antonella Porrazzo, Giuseppe Esposito, Maria Antonella Tabocchini, Giovanni Cenci
Deep underground laboratories (DULs) were originally created to host particle, astroparticle or nuclear physics experiments requiring a low-background environment with vastly reduced levels of cosmic-ray particle interference. More recently, the range of science projects requiring an underground experiment site has greatly expanded, thus leading to the recognition of DULs as truly multidisciplinary science sites that host important studies in several fields, including geology, geophysics, climate and environmental sciences, technology/instrumentation development and biology...
June 4, 2018: Radiation Research
https://www.readbyqxmd.com/read/29861494/-src-cooperates-with-oncogenic-ras-in-tumourigenesis-via-the-jnk-and-pi3k-pathways-in-drosophila-epithelial-tissue
#7
Carole L C Poon, Anthony M Brumby, Helena E Richardson
The Ras oncogene (Rat Sarcoma oncogene, a small GTPase) is a key driver of human cancer, however alone it is insufficient to produce malignancy, due to the induction of cell cycle arrest or senescence. In a Drosophila melanogaster genetic screen for genes that cooperate with oncogenic Ras (bearing the RasV12 mutation, or RasACT ), we identified the Drosophila Src (Sarcoma virus oncogene) family non-receptor tyrosine protein kinase genes, Src42A and Src64B , as promoting increased hyperplasia in a whole epithelial tissue context in the Drosophila eye...
May 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29844320/tumour-associated-missense-mutations-in-the-dmi-2-atpase-alters-nucleosome-remodelling-properties-in-a-mutation-specific-manner
#8
Kristina Kovač, Anja Sauer, Igor Mačinković, Stephan Awe, Florian Finkernagel, Helen Hoffmeister, Andreas Fuchs, Rolf Müller, Christina Rathke, Gernot Längst, Alexander Brehm
ATP-dependent chromatin remodellers are mutated in more than 20% of human cancers. The consequences of these mutations on enzyme function are poorly understood. Here, we characterise the effects of CHD4 mutations identified in endometrial carcinoma on the remodelling properties of dMi-2, the highly conserved Drosophila homologue of CHD4. Mutations from different patients have surprisingly diverse defects on nucleosome binding, ATPase activity and nucleosome remodelling. Unexpectedly, we identify both mutations that decrease and increase the enzyme activity...
May 29, 2018: Nature Communications
https://www.readbyqxmd.com/read/29844126/the-tumor-suppressor-cic-directly-regulates-mapk-pathway-genes-via-histone-deacetylation
#9
Simon Weissmann, Paul A Cloos, Simone Sidoli, Ole N Jensen, Steven Pollard, Kristian Helin
Oligodendrogliomas (ODG) are brain tumors accounting for approximately 10% of all central nervous system cancers. CIC is a transcription factor that is mutated in most patients with ODG; these mutations are believed to be a key oncogenic event in such cancers. Analysis of the Drosophila melanogaster orthologue of CIC, Capicua, indicates that CIC loss phenocopies activation of the EGFR/RAS/MAPK pathway, and studies in mammalian cells have demonstrated a role for CIC in repressing the transcription of the PEA3 subfamily of ETS transcription factors...
May 29, 2018: Cancer Research
https://www.readbyqxmd.com/read/29844121/-restraining-network-response-to-targeted-cancer-therapies-improves-efficacy-and-reduces-cellular-resistance
#10
Tirtha K Das, Jessica Esernio, Ross Cagan
A key tool of cancer therapy has been targeted inhibition of oncogene addicted pathways. However, efficacy has been limited by progressive emergence of resistance as transformed cells adapt. Here we use Drosophila to dissect response to targeted therapies. Treatment with a range of kinase inhibitors led to hyperactivation of overall cellular networks, resulting in emergent resistance and expression of stem cell markers including Sox2. Genetic and drug screens revealed that inhibitors of histone deacetylases, proteasome, and Hsp90 family of proteins restrained this network hyperactivation...
May 29, 2018: Cancer Research
https://www.readbyqxmd.com/read/29800619/regulation-and-function-of-p53-a-perspective-from-drosophila-studies
#11
REVIEW
María Clara Ingaramo, Juan A Sánchez, Andrés Dekanty
Tp53 is a central regulator of cellular responses to stress and one of the most frequently mutated genes in human cancers. P53 is activated by a myriad of stress signals and drives specific cellular responses depending on stress nature, cell type and cellular context. Additionally to its classical functions in regulating cell cycle arrest, apoptosis and senescence, newly described non-canonical functions of p53 are increasingly coming under the spotlight as important functions not only for its role as a tumour suppressor but also for its non-cancer associated activities...
May 22, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/29769200/long-chain-n-3-fatty-acids-attenuate-oncogenic-kras-driven-proliferation-by-altering-plasma-membrane-nanoscale-proteolipid-composition
#12
Natividad R Fuentes, Mohamed Mlih, Rola Barhoumi, Yang-Yi Fan, Paul Hardin, Trevor J Steele, Spencer Behmer, Ian A Prior, Jason Karpac, Robert S Chapkin
Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that Ras nanocluster proteolipid composition could represent a novel target for future chemoprevention interventions. There is evidence that consumption of fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) may reduce colon cancer risk in humans, yet the mechanism underlying this effect is unknown...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764959/a-targeted-rnai-screen-reveals-drosophila-female-sterile-genes-that-control-the-size-of-germline-stem-cell-niche-during-development
#13
Yueh Cho, Chun-Ming Lai, Kun-Yang Lin, Hwei-Jan Hsu
Adult stem cells maintain tissue homeostasis. This unique capability largely depends on the stem cell niche, a specialized microenvironment, which preserves stem cell identity through physical contacts and secreted factors. In many cancers, latent tumor cell niches are thought to house stem cells and aid tumor initiation. However, in developing tissue and cancer it is unclear how the niche is established. The well-characterized germline stem cells (GSCs) and niches in the Drosophila melanogaster ovary provide an excellent model to address this fundamental issue...
May 15, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29764901/the-histone-demethylase-kdm5-is-essential-for-larval-growth-in-drosophila
#14
Coralie Drelon, Helen M Belalcazar, Julie Secombe
Regulated gene expression is necessary for developmental and homeostatic processes. The KDM5 family of transcriptional regulators are histone H3 lysine 4 demethylases that can function through both demethylase-dependent and independent mechanisms. While loss and overexpression of KDM5 proteins are linked to intellectual disability and cancer, respectively, their normal developmental functions remain less characterized. Drosophila melanogaster provides an ideal system to investigate KDM5 function, as it encodes a single ortholog in contrast to the four paralogs found in mammalian cells...
May 15, 2018: Genetics
https://www.readbyqxmd.com/read/29763934/inactivation-of-usp14-perturbs-ubiquitin-homeostasis-and-delays-the-cell-cycle-in-mouse-embryonic-fibroblasts-and-in-fruit-fly-drosophila
#15
Jung Hoon Lee, Seoyoung Park, Yejin Yun, Won Hoon Choi, Min-Ji Kang, Min Jae Lee
BACKGROUND/AIMS: The 26S proteasome is the key proteolytic complex for recognition and degradation of polyubiquitinated target substrates in eukaryotes. Among numerous proteasome-associated proteins, a deubiquitinating enzyme (DUB) USP14 has been identified as an endogenous inhibitor of the proteasome. Here, we explored the complex regulatory functions of USP14 that involve ubiquitin (Ub) homeostasis and substrate degradation in flies and mammals. METHODS: USP14-null primary and immortalized mouse embryonic fibroblasts (MEFs) and USP14 knocked-down Drosophila were analyzed in this study...
May 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29756514/ilex-paraguariensis-extends-lifespan-and-increases-an-ability-to-resist-environmental-stresses-in-drosophila
#16
Prakshit Niraula, Saurav Ghimire, Hanna Lee, Man Su Kim
Aging is a complex process resulting in: i) a decline in body functions and capacity to withstand environmental stress and ii) an increased susceptibility to diseases including, but not limited to, cardiovascular disorders, diabetes, cancer and dementia. Among a number of herbal products used to alleviate symptoms associated with aging is Ilex paraguariensis (IP). This product has been reported to have anticancer, anti-inflammatory and antioxidant activities. However, its effect on an organisms' longevity has not been thoroughly studied to date...
May 14, 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29749524/multifaceted-regulation-and-functions-of-yap-taz-in-tumors-review
#17
Huirong Liu, Suya Du, Tiantian Lei, Hailian Wang, Xia He, Rongsheng Tong, Yi Wang
The Hippo pathway, initially identified through screenings for mutant tumor suppressors in Drosophila, is an evolutionarily conserved signaling pathway that controls organ size by regulating cell proliferation and apoptosis. Abnormal regulation of the Hippo pathway may lead to cancer in mammals. As the major downstream effectors of the Hippo pathway, unphosphorylated Yes-associated protein (YAP) and its homolog transcriptional co-activator TAZ (also called WWTR1) (hereafter called YAP/TAZ) are translocated into the nucleus...
May 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29745898/somatic-clones-heterozygous-for-recessive-disease-alleles-of-bmpr1a-exhibit-unexpected-phenotypes-in-drosophila
#18
Takuya Akiyama, Sırma D User, Matthew C Gibson
The majority of mutations studied in animal models are designated as recessive based on the absence of visible phenotypes in germline heterozygotes. Accordingly, genetic studies primarily rely on homozygous loss-of-function to determine gene requirements, and a conceptually-related 'two-hit model' remains the central paradigm in cancer genetics. Here we investigate pathogenesis due to somatic mutation in epithelial tissues, a process that predominantly generates heterozygous cell clones. To study somatic mutation in Drosophila , we generated inducible alleles that mimic human Juvenile polyposis-associated BMPR1A mutations...
May 10, 2018: ELife
https://www.readbyqxmd.com/read/29742423/cdk5-inhibition-resolves-pka-camp-independent-activation-of-creb1-signaling-in-glioma-stem-cells
#19
Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Hithardhi Duggireddy, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel J Brat
Cancer stem cells promote neoplastic growth, in part by deregulating asymmetric cell division and enhancing self-renewal. To uncover mechanisms and potential therapeutic targets in glioma stem cell (GSC) self-renewal, we performed a genetic suppressor screen for kinases to reverse the tumor phenotype of our Drosophila brain tumor model and identified dCdk5 as a critical regulator. CDK5, the human ortholog of dCdk5 (79% identity), is aberrantly activated in GBMs and tightly aligned with both chromosome 7 gains and stem cell markers affecting tumor-propagation...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29730580/toll-like-receptors-in-immunity-and-inflammatory-diseases-past-present-and-future
#20
REVIEW
Kumar Vijay
The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells...
May 3, 2018: International Immunopharmacology
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