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https://www.readbyqxmd.com/read/30311575/regulation-of-epithelial-cell-proliferation-differentiation-and-plasticity-by-grainyhead-like-2-during-oral-carcinogenesis
#1
Mo K Kang, Wei Chen, No-Hee Park
Grainyhead-Like 2 (GRHL2) was originally described as one of the three mammalian isoforms with sequence homology to Grainyhead (GRH) in Drosophila, which determines the cuticle formation in fruit flies. Earlier studies characterized GRHL2 as an epithelial-specific transcription factor that regulates epithelial morphogenesis and differentiation. Using a high-throughput proteomic approach, we discovered GRHL2 as a novel trans-regulator of the hTERT gene, which codes for the catalytic subunit of the human telomerase...
2018: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/30281408/mir-206-partially-rescues-myogenesis-deficiency-by-inhibiting-cugbp1-accumulation-in-the-cell-models-of-myotonic-dystrophy
#2
Wei Dong, Xuanying Chen, Menghong Wang, Zeqi Zheng, Xing Zhang, Qunlin Xiao, Xiaoping Peng
OBJECTIVES: In this study, we aim to determine how CUG-expansion and the abundance of Celf1 regulates normal myocyte differentiation and reveal the role ofmiR-206 in myotonic dystrohy and explore a possible gene therapy vector. METHODS:  we set up CUG-expansion and Celf1 overexpression C2C12 cell models to imitate the myocyte differentiation defects of DM1, then transfected AdvmiR-206 into cell models, tested the level of myogenic markers MyoD, MyoG, Mef2c, Celf1 by RT-PCRand Western Blotting, detected myotube formation by myosin heavy chain immunostaining...
October 3, 2018: Neurological Research
https://www.readbyqxmd.com/read/30266909/deubiquitinase-usp12-functions-noncatalytically-to-induce-autophagy-and-confer-neuroprotection-in-models-of-huntington-s-disease
#3
Rebecca Aron, Pasquale Pellegrini, Edward W Green, Daniel C Maddison, Kwadwo Opoku-Nsiah, Jinny S Wong, Aaron C Daub, Flaviano Giorgini, Steven Finkbeiner
Huntington's disease is a progressive neurodegenerative disorder caused by polyglutamine-expanded mutant huntingtin (mHTT). Here, we show that the deubiquitinase Usp12 rescues mHTT-mediated neurodegeneration in Huntington's disease rodent and patient-derived human neurons, and in Drosophila. The neuroprotective role of Usp12 may be specific amongst related deubiquitinases, as the closely related homolog Usp46 does not suppress mHTT-mediated toxicity. Mechanistically, we identify Usp12 as a potent inducer of neuronal autophagy...
September 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/30259360/functional-analysis-of-circular-rnas
#4
Shanmugapriya, Hisham Alkatib Huda, Soundararajan Vijayarathna, Chern Ein Oon, Yeng Chen, Jagat R Kanwar, Mei Li Ng, Sreenivasan Sasidharan
Circular RNAs characterize a class of widespread and diverse endogenous RNAs which are non-coding RNAs that are made by back-splicing events and have covalently closed loops with no polyadenylated tails. Various indications specify that circular RNAs (circRNAs) are plentiful in the human transcriptome. However, their participation in biological processes remains mostly undescribed. To date thousands of circRNAs have been revealed in organisms ranging from Drosophila melanogaster to Homo sapiens. Functional studies specify that these transcripts control expression of protein-coding linear transcripts and thus encompass a key component of gene expression regulation...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/30258723/g%C3%AE-q-and-phospholipase-c%C3%AE-signaling-regulate-nociceptor-sensitivity-in-drosophila-melanogaster-larvae
#5
Joshua A Herman, Adam B Willits, Andrew Bellemer
Drosophila melanogaster larvae detect noxious thermal and mechanical stimuli in their environment using polymodal nociceptor neurons whose dendrites tile the larval body wall. Activation of these nociceptors by potentially tissue-damaging stimuli elicits a stereotyped escape locomotion response. The cellular and molecular mechanisms that regulate nociceptor function are increasingly well understood, but gaps remain in our knowledge of the broad mechanisms that control nociceptor sensitivity. In this study, we use cell-specific knockdown and overexpression to show that nociceptor sensitivity to noxious thermal and mechanical stimuli is correlated with levels of Gαq and phospholipase Cβ signaling...
2018: PeerJ
https://www.readbyqxmd.com/read/30257938/modulation-of-the-hippo-pathway-and-organ-growth-by-rna-processing-proteins
#6
Jana Mach, Mardelle Atkins, Kathleen M Gajewski, Violaine Mottier-Pavie, Leticia Sansores-Garcia, Jun Xie, Robert Andrew Mills, Weronika Kowalczyk, Leen Van Huffel, Gordon B Mills, Georg Halder
The Hippo tumor-suppressor pathway regulates organ growth, cell proliferation, and stem cell biology. Defects in Hippo signaling and hyperactivation of its downstream effectors-Yorkie (Yki) in Drosophila and YAP/TAZ in mammals-result in progenitor cell expansion and overgrowth of multiple organs and contribute to cancer development. Deciphering the mechanisms that regulate the activity of the Hippo pathway is key to understanding its function and for therapeutic targeting. However, although the Hippo kinase cascade and several other upstream inputs have been identified, the mechanisms that regulate Yki/YAP/TAZ activity are still incompletely understood...
September 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30250066/enah-overexpression-is-correlated-with-poor-survival-and-aggressive-phenotype-in-gastric-cancer
#7
Di Chen, Li Xu, Xiaowei Li, Yi Chu, Mingzuo Jiang, Bing Xu, Min Zhao, Weijie Wang, Hua Wang, Huijie Kang, Kai Wang, Kaichun Wu, Jie Liang, Gui Ren
Enabled homolog (Enah), which is a member of the Ena/VASP family that also includes VASP (vasodilator-stimulated phosphoprotein) and Ena/VASP like, is a mammalian ortholog of Drosophila Enabled (Ena). An increasing number of studies demonstrated Enah overexpression is involved in human colorectal carcinomas, breast cancers and hepatocellular carcinoma. However, the significance of Enah expression in gastric cancer (GC) is poorly elucidated. Here, we demonstrate that Enah is upregulated in GC and associated with AJCC stage, depth of invasion and poor overall survival (OS)...
September 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/30249792/a-druggable-genome-screen-identifies-modifiers-of-%C3%AE-synuclein-levels-via-a-tiered-cross-species-validation-approach
#8
Maxime W C Rousseaux, Gabriel E Vázquez-Vélez, Ismael Al-Ramahi, Hyun-Hwan Jeong, Aleksandar Bajic, Jean-Pierre Revelli, Hui Ye, Emily T Phan, Jennifer M Deger, Alma M Perez, Ji-Yoen Kim, Laura A Lavery, Qikia Xu, Mamie Z Li, Hyojin Kang, Jean J Kim, Joshua M Shulman, Thomas F Westbrook, Stephen J Elledge, Zhandong Liu, Juan Botas, Huda Y Zoghbi
Accumulation of α-Synuclein (α-Syn) causes Parkinson's disease (PD) as well as other synucleopathies. α-Syn is the major component of Lewy bodies and Lewy neurites, the proteinaceous aggregates that are a hallmark of sporadic PD. In familial forms of PD, mutations or copy number variations in SNCA (the α-Syn gene) result in a net increase of its protein levels. Furthermore, common risk variants tied to PD are associated with small increases of wild-type α-Syn levels. These findings are further bolstered by animal studies which show that overexpression of α-Syn is sufficient to cause PD-like features...
September 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/30246928/regulation-of-notch-signaling-in-the-developing-drosophila-eye-by-a-t-box-containing-transcription-factor-dorsocross
#9
Maimuna Sali Paul, Debdeep Dutta, Ankita Singh, Mousumi Mutsuddi, Ashim Mukherjee
Owing to a multitude of functions, there is barely a tissue or a cellular process that is not being regulated by Notch signaling. To allow the Notch signal to be deployed in numerous contexts, many different mechanisms have evolved to regulate the level, duration and spatial distribution of Notch activity. To identify novel effectors of Notch signaling in Drosophila melanogaster, we analyzed the whole transcriptome of the wing and eye imaginal discs in which an activated form of Notch was overexpressed. Selected candidate genes from the transcriptome analysis were subjected to genetic interaction experiments with Notch pathway components...
September 24, 2018: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/30242104/disrupting-hedgehog-cardin-weintraub-sequence-and-positioning-changes-cellular-differentiation-and-compartmentalization-in-vivo
#10
Philipp Kastl, Dominique Manikowski, Georg Steffes, Sabine Schürmann, Shyam Bandari, Christian Klämbt, Kay Grobe
Metazoan Hedgehog (Hh) morphogens are essential regulators of growth and patterning at significant distances from their source, despite being produced as N-terminally palmitoylated and C-terminally cholesteroylated proteins, which firmly tethers them to the outer plasma membrane leaflet of producing cells and limits their spread. One mechanism to overcome this limitation is proteolytic processing of both lipidated terminal peptides, called shedding, but molecular target site requirements for effective Hh shedding remained undefined...
September 21, 2018: Development
https://www.readbyqxmd.com/read/30233643/the-lysine-demethylase-dkdm2-is-non-essential-for-viability-but-regulates-circadian-rhythms-in-drosophila
#11
Yani Zheng, Yongbo Xue, Xingjie Ren, Mengmeng Liu, Xiao Li, Yu Jia, Ye Niu, Jian-Quan Ni, Yong Zhang, Jun-Yuan Ji
Post-translational modification of histones, such as histone methylation controlled by specific methyltransferases and demethylases, play critical roles in modulating chromatin dynamics and transcription in eukaryotes. Misregulation of histone methylation can lead to aberrant gene expression, thereby contributing to abnormal development and diseases such as cancer. As such, the mammalian lysine-specific demethylase 2 (KDM2) homologs, KDM2A and KDM2B, are either oncogenic or tumor suppressive depending on specific pathological contexts...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/30232002/sugar-promotes-feeding-in-flies-via-the-serine-protease-homolog-scarface
#12
Naveen Prasad, Korneel Hens
A balanced diet of macronutrients is critical for animal health. A lack of specific elements can have profound effects on behavior, reproduction, and lifespan. Here, we used Drosophila to understand how the brain responds to carbohydrate deprivation. We found that serine protease homologs (SPHs) are enriched among genes that are transcriptionally regulated in flies deprived of carbohydrates. Stimulation of neurons expressing one of these SPHs, Scarface (Scaf), or overexpression of scaf positively regulates feeding on nutritious sugars, whereas inhibition of these neurons or knockdown of scaf reduces feeding...
September 18, 2018: Cell Reports
https://www.readbyqxmd.com/read/30228985/cinnamaldehyde-improves-lifespan-and-healthspan-in-drosophila-melanogaster-models-for-alzheimer-s-disease
#13
Hanh M Pham, Anna Xu, Samuel E Schriner, Evgueni A Sevrioukov, Mahtab Jafari
Cinnamon extract has been reported to have positive effects in fruit fly and mouse models for Alzheimer's disease (AD). However, cinnamon contains numerous potential active compounds that have not been individually evaluated. The main objective of this study was to evaluate the impact of cinnamaldehyde, a known putative active compound in cinnamon, on the lifespan and healthspan of Drosophila melanogaster models for Alzheimer's disease, which overexpress A β 42 and MAPT (Tau). We found that cinnamaldehyde significantly improved the lifespan of both AD and non-AD flies...
2018: BioMed Research International
https://www.readbyqxmd.com/read/30213867/a-drosophila-crispr-cas9-toolkit-for-conditionally-manipulating-gene-expression-in-the-prothoracic-gland-as-a-test-case-for-polytene-tissues
#14
Nhan Huynh, Jie Zeng, Wen Liu, Kirst King-Jones
Targeting gene function with spatial or temporal specificity is a key goal in molecular genetics. CRISPR-Cas9 has greatly facilitated this strategy, but some standard approaches are problematic. For instance, simple tissue-specific or global overexpression of Cas9 can cause significant lethality or developmental delays even in the absence of gRNAs. In particular, we found that Gal4-mediated expression of UAS-Cas9 in the Drosophila prothoracic gland (PG) was not a suitable strategy to disrupt gene expression, since Cas9 alone caused widespread lethality...
September 13, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/30209068/-xrp1-genetically-interacts-with-the-als-associated-fus-orthologue-caz-and-mediates-its-toxicity
#15
Moushami Mallik, Marica Catinozzi, Clemens B Hug, Li Zhang, Marina Wagner, Julia Bussmann, Jonas Bittern, Sina Mersmann, Christian Klämbt, Hannes C A Drexler, Martijn A Huynen, Juan M Vaquerizas, Erik Storkebaum
Cabeza ( caz ) is the single Drosophila melanogaster orthologue of the human FET proteins FUS, TAF15, and EWSR1, which have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we identified Xrp1 , a nuclear chromatin-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was strongly up-regulated in caz mutants, and Xrp1 heterozygosity rescued their motor defects and life span. Interestingly, selective neuronal Xrp1 knockdown was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied caz mutant phenotypes...
September 12, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30188612/the-kr%C3%A3-ppel-like-factor-dar1-restricts-the-proliferation-of-drosophila-intestinal-stem-cells
#16
Xiaochun Wu, Zhi Chen, Yuan Gao, Lei Wang, Xiaofan Sun, Yaping Jin, Wei Liu
The krüppel-like factors (KLFs) are a family of transcription factor proteins that regulate a wide range of biological processes. In an RNAi-based screening experiment, we identified dendritic arbor reduction 1 (Dar1), which is a KLF member in Drosophila, that inhibited the proliferation of intestinal stem cells (ISCs). We found suppression of Dar1-activated ISC proliferation; as a consequence, the ISCs and the young differentiated cells were increased. On the other hand, overexpression (OE) of Dar1 inhibited ISC division and blocked the formation of ISC lineages...
September 6, 2018: FEBS Journal
https://www.readbyqxmd.com/read/30185553/altered-er-mitochondria-contact-impacts-mitochondria-calcium-homeostasis-and-contributes-to-neurodegeneration-in-vivo-in-disease-models
#17
Kyu-Sun Lee, Sungun Huh, Seongsoo Lee, Zhihao Wu, Ae-Kyeong Kim, Ha-Young Kang, Bingwei Lu
Calcium (Ca2+ ) homeostasis is essential for neuronal function and survival. Altered Ca2+ homeostasis has been consistently observed in neurological diseases. How Ca2+ homeostasis is achieved in various cellular compartments of disease-relevant cell types is not well understood. Here we show in Drosophila Parkinson's disease (PD) models that Ca2+ transport from the endoplasmic reticulum (ER) to mitochondria through the ER-mitochondria contact site (ERMCS) critically regulates mitochondrial Ca2+ (mito-Ca2+ ) homeostasis in dopaminergic (DA) neurons, and that the PD-associated PINK1 protein modulates this process...
September 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30181804/-pumilio2-regulates-synaptic-plasticity-via-translational-repression-of-synaptic-receptors-in-mice
#18
Hongxin Dong, Mengyi Zhu, Liping Meng, Yan Ding, Ding Yang, Shanshan Zhang, Wenan Qiang, Daniel W Fisher, Eugene Yujun Xu
PUMILIO 2 (PUM2) is a member of Pumilio and FBF (PUF) family, an RNA binding protein family with phylogenetically conserved roles in germ cell development. The Drosophila Pumilio homolog is also required for dendrite morphogenesis and synaptic function via translational control of synaptic proteins, such as glutamate receptors, and recent mammalian studies demonstrated a similar role in neuronal culture with associated motor and memory abnormalities in vivo . Importantly, transgenic mice with PUM2 knockout show prominent epileptiform activity, and patients with intractable temporal lobe epilepsy and mice with pilocarpine-induced seizures have decreased neuronal PUM2, possibly leading to further seizure susceptibility...
August 14, 2018: Oncotarget
https://www.readbyqxmd.com/read/30181710/exploration-of-teratogenic-and-genotoxic-effects-of-fruit-ripening-retardant-alar-daminozide-on-model-organism-drosophila-melanogaster
#19
Sohini Singha Roy, Morium Begum, Sujay Ghosh
Alar (Daminozide) is a plant growth regulator which is widely used as a fruit preservative for apple and mango to prevent pre-harvest fruit drop, promote color development and to delay excessive ripening. The aim of the present work was to demonstrate the effect of Alar on several life history traits, adult morphology, Hsp70 protein expression and in vivo DNA damage in the brain of the model organism Drosophila melanogaster . We assessed the life history and morphological traits including fecundity, developmental time, pupation height, egg-to-adult viability and mean wing length, body length, arista length and sternopleural bristle number of the emerging flies...
May 2018: Interdisciplinary Toxicology
https://www.readbyqxmd.com/read/30177553/ttyh1-regulates-embryonic-neural-stem-cell-properties-by-enhancing-the-notch-signaling-pathway
#20
Juwan Kim, Dasol Han, Sung-Hyun Byun, Mookwang Kwon, Jae Youl Cho, Samuel J Pleasure, Keejung Yoon
Despite growing evidence linking Drosophila melanogaster tweety-homologue 1 (Ttyh1) to normal mammalian brain development and cell proliferation, its exact role has not yet been determined. Here, we show that Ttyh1 is required for the maintenance of neural stem cell (NSC) properties as assessed by neurosphere formation and in vivo analyses of cell localization after in utero electroporation. We find that enhanced Ttyh1-dependent stemness of NSCs is caused by enhanced γ-secretase activity resulting in increased levels of Notch intracellular domain (NICD) production and activation of Notch targets...
September 3, 2018: EMBO Reports
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