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Modeling gene regulation

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https://www.readbyqxmd.com/read/29667742/genetic-association-and-expression-analyses-of-the-phosphatidylinositol-4-phosphate-5-kinase-pip5k1c-gene-in-alcohol-use-disorder-relevance-for-pain-signaling-and-alcohol-use
#1
Ji Soo Lee, Jill L Sorcher, Allison D Rosen, Ruslan Damadzic, Hui Sun, Melanie Schwandt, Markus Heilig, John Kelly, Kelsey L Mauro, Audrey Luo, Daniel Rosoff, Christine Muench, Jeesun Jung, Zachary A Kaminsky, Falk W Lohoff
BACKGROUND: The gene encoding Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) has been recently implicated in pain regulation. Interestingly, a recent cross-tissue and cross-phenotypic epigenetic analysis identified the same gene in alcohol use disorder (AUD). Given the high comorbidity between AUD and chronic pain, we hypothesized that genetic variation in PIP5K1C might contribute to susceptibility to AUD. METHODS: We conducted a case-control association study of genetic variants in PIP5K1C...
April 18, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29667529/emerging-therapeutic-targets-for-neurofibromatosis-type-1
#2
James A Walker, Meena Upadhyaya
Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited tumor predisposition syndrome with an incidence of one in 3000-4000 individuals with no currently effective therapies. The NF1 gene on chromosome 17 encodes neurofibromin, which functions as a negative regulator of RAS. NF1 is a chronic multi-system disorder affecting many different tissues. Due to cell-specific complexities of RAS signaling, therapeutic approaches for NF1 will likely have to focus on a particular tissue and manifestation of the disease...
April 18, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29667298/distinct-chromatin-structures-at-the-monoamine-oxidase-a-maoa-promoter-correlate-with-allele-specific-expression-in-sh-sy5y-cells
#3
M Manca, V Pessoa, P Myers, A Pickles, J Hill, H Sharp, C Murgatroyd, V J Bubb, J P Quinn
Monoamine oxidase-A (MAOA) metabolises monoamines and is implicated in the pathophysiology of psychiatric disorders. A polymorphic repetitive DNA domain, termed the uVNTR (upstream variable number tandem repeat), located at the promoter of the MAOA gene is a risk factor for many of these disorders. MAOA is on the X chromosome suggesting gender could play a role in regulation. We analysed MAOA regulation in the human female cell line, SH-SY5Y, which is polymorphic for the uVNTR. This heterozygosity allowed us to correlate allele specific gene expression with allele specific transcription factor binding and epigenetic marks for MAOA...
April 18, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29666780/identification-expression-analysis-and-molecular-modeling-of-iron-deficiency-specific-clone-3-ids3-like-gene-in-hexaploid-wheat
#4
Priyanka Mathpal, Upendra Kumar, Anuj Kumar, Sanjay Kumar, Sachin Malik, Naveen Kumar, H S Dhaliwal, Sundip Kumar
Graminaceous plants secrete hydroxylated phytosiderophores encoded by the genes iron-deficiency-specific clone 2 ( Ids2 ) and iron-deficiency-specific clone 3 ( Ids3 ). An effort was made to identify a putative ortholog of Hodeum vulgare Ids3 gene in hexaploid wheat. The protein structure of TaIDS3 was modeled using homology modeling and structural behavior of modeled structure was analyzed at 20 ns. The simulation trajectory using molecular dynamics simulation suggested the model to be stable with no large fluctuations in residues and local domain level RMSF values (< 2...
April 2018: 3 Biotech
https://www.readbyqxmd.com/read/29666766/mirnaome-expression-profiles-in-the-gonads-of-adult-melopsittacus-undulatus
#5
Lan Jiang, Qingqing Wang, Jue Yu, Vinita Gowda, Gabriel Johnson, Jianke Yang, Xianzhao Kan, Xiaojun Yang
The budgerigar ( Melopsittacus undulatus ) is one of the most widely studied parrot species, serving as an excellent animal model for behavior and neuroscience research. Until recently, it was unknown how sexual differences in the behavior, physiology, and development of organisms are regulated by differential gene expression. MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that can post-transcriptionally regulate gene expression and play a critical role in gonadal differentiation as well as early development of animals...
2018: PeerJ
https://www.readbyqxmd.com/read/29666621/the-role-of-aire-in-the-immunity-against-candida-albicans-in-a-model-of-human-macrophages
#6
Jose Antonio Tavares de Albuquerque, Pinaki Prosad Banerjee, Angela Castoldi, Royce Ma, Nuria Bengala Zurro, Leandro Hideki Ynoue, Christina Arslanian, Marina Uchoa Wall Barbosa-Carvalho, Joya Emilie de Menezes Correia-Deur, Fernanda Guimarães Weiler, Magnus Regios Dias-da-Silva, Marise Lazaretti-Castro, Luis Alberto Pedroza, Niels Olsen Saraiva Câmara, Emily Mace, Jordan Scott Orange, Antonio Condino-Neto
Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene ( AIRE ). Patients with AIRE mutations are susceptible to Candida albicans infection and present with autoimmune disorders. We previously demonstrated that cytoplasmic AIRE regulates the Syk-dependent Dectin-1 pathway. In this study, we further evaluated direct contact with fungal elements, synapse formation, and the response of macrophage-like THP-1 cells to C...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29666442/matrix-stiffness-controls-lymphatic-vessel-formation-through-regulation-of-a-gata2-dependent-transcriptional-program
#7
Maike Frye, Andrea Taddei, Cathrin Dierkes, Ines Martinez-Corral, Matthew Fielden, Henrik Ortsäter, Jan Kazenwadel, Dinis P Calado, Pia Ostergaard, Marjo Salminen, Liqun He, Natasha L Harvey, Friedemann Kiefer, Taija Mäkinen
Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels...
April 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29666409/exposure-to-phthalate-an-endocrine-disrupting-chemical-alters-the-first-trimester-placental-methylome-and-transcriptome-in-women
#8
N M Grindler, L Vanderlinden, R Karthikraj, K Kannan, S Teal, A J Polotsky, T L Powell, I V Yang, T Jansson
Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666403/intact-interleukin-10-receptor-signaling-protects-from-hippocampal-damage-elicited-by-experimental-neurotropic-virus-infection-of-sjl-mice
#9
Ann-Kathrin Uhde, Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Niko Hensel, Peter Claus, Michael Beckstette, René Teich, Stefan Floess, Wolfgang Baumgärtner, Klaus Jung, Jochen Huehn, Andreas Beineke
Theiler's murine encephalomyelitis virus (TMEV) infection represents an experimental mouse model to study hippocampal damage induced by neurotropic viruses. IL-10 is a pleiotropic cytokine with profound anti-inflammatory properties, which critically controls immune homeostasis. In order to analyze IL-10R signaling following virus-induced polioencephalitis, SJL mice were intracerebrally infected with TMEV. RNA-based next generation sequencing revealed an up-regulation of Il10, Il10rα and further genes involved in IL-10 downstream signaling, including Jak1, Socs3 and Stat3 in the brain upon infection...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666277/disparate-binding-kinetics-by-an-intrinsically-disordered-domain-enables-temporal-regulation-of-transcriptional-complex-formation
#10
Neil O Robertson, Ngaio C Smith, Athina Manakas, Mahiar Mahjoub, Gordon McDonald, Ann H Kwan, Jacqueline M Matthews
Intrinsically disordered regions are highly represented among mammalian transcription factors, where they often contribute to the formation of multiprotein complexes that regulate gene expression. An example of this occurs with LIM-homeodomain (LIM-HD) proteins in the developing spinal cord. The LIM-HD protein LHX3 and the LIM-HD cofactor LDB1 form a binary complex that gives rise to interneurons, whereas in adjacent cell populations, LHX3 and LDB1 form a rearranged ternary complex with the LIM-HD protein ISL1, resulting in motor neurons...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666220/synergistic-anti-proliferative-effect-of-mtor-inhibitor-rad001-plus-gemcitabine-on-cholangiocarcinoma-by-decreasing-choline-kinase-activity
#11
Gigin Lin, Kun-Ju Lin, Frank Wang, Tse-Ching Chen, Tzu-Chen Yen, Ta-Sen Yeh
Although gemcitabine plus cisplatin is the gold standard chemotherapy regimen for advanced cholangiocarcinoma, the response rate has been disappointing. This study aims to investigate a novel therapeutic regimen (gemcitabine plus rad001, an mTOR inhibitor) for cholangiocarcinoma. Gemcitabine, oxaliplatin, cetuximab, and rad001 in various combinations were first evaluated in vitro using six cholangiocarcinoma cell lines. In vivo therapeutic efficacies of gemcitabine, rad001 alone and combination were further evaluated using a xenograft mouse model and a chemically induced orthotopic cholangiocarcinoma rat model...
April 12, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29666172/genetic-editing-of-colonic-organoids-provides-a-molecularly-distinct-and-orthotopic-preclinical-model-of-serrated-carcinogenesis
#12
Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein...
April 17, 2018: Gut
https://www.readbyqxmd.com/read/29666166/type-i-interferons-in-tuberculosis-foe-and-occasionally-friend
#13
REVIEW
Lúcia Moreira-Teixeira, Katrin Mayer-Barber, Alan Sher, Anne O'Garra
Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis...
April 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29666150/epigenetics-and-epitranscriptomics-in-temporal-patterning-of-cortical-neural-progenitor-competence
#14
REVIEW
Ki-Jun Yoon, Caroline Vissers, Guo-Li Ming, Hongjun Song
During embryonic brain development, neural progenitor/stem cells (NPCs) sequentially give rise to different subtypes of neurons and glia via a highly orchestrated process. To accomplish the ordered generation of distinct progenies, NPCs go through multistep transitions of their developmental competence. The molecular mechanisms driving precise temporal coordination of these transitions remains enigmatic. Epigenetic regulation, including changes in chromatin structures, DNA methylation, and histone modifications, has been extensively investigated in the context of cortical neurogenesis...
April 17, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29666142/tumor-xenograft-modeling-identifies-tcf4-itf2-loss-associated-with-breast-cancer-chemoresistance
#15
Gorka Ruiz de Garibay, Francesca Mateo, Agostina Stradella, Rafael Valdés-Mas, Luis Palomero, Jordi Serra-Musach, Diana A Puente, Ander Díaz-Navarro, Gardenia Vargas-Parra, Eva Tornero, Idoia Morilla, Lourdes Farré, María Martinez-Iniesta, Carmen Herranz, Emmet McCormack, August Vidal, Anna Petit, Teresa Soler, Conxi Lázaro, Xose S Puente, Alberto Villanueva, Miguel Angel Pujana
Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patient-derived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify loss of transcription factor 4 (TCF4) associated with this process. A triple-negative BRCA1 -mutated PDX was used to study the genetics of chemoresistance...
April 13, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29666124/generation-of-a-double-binary-transgenic-zebrafish-model-to-study-myeloid-gene-regulation-in-response-to-oncogene-activation-in-melanocytes
#16
Amy Kenyon, Daria Gavriouchkina, Jernej Zorman, Vanessa Chong-Morrison, Giorgio Napolitani, Vincenzo Cerundolo, Tatjana Sauka-Spengler
A complex network of inflammatory genes is closely linked to somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. Here, we describe the development of a double binary zebrafish model that enables regulatory programming of the myeloid cells as they respond to oncogene-activated melanocytes to be explored, focussing on the initial phase when cells become the precursors of cancer...
April 6, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29665845/deletion-of-hp1%C3%AE-in-cardiac-myocytes-affects-h4k20me3-levels-but-does-not-impact-cardiac-growth
#17
Kyohei Oyama, Danny El-Nachef, Chen Fang, Hidemi Kajimoto, Jeremy P Brown, Prim B Singh, W Robb MacLellan
BACKGROUND: Heterochromatin, which is formed when tri-methyl lysine 9 of histone H3 (H3K9me3) is bound by heterochromatin 1 proteins (HP1s), plays an important role in differentiation and senescence by silencing cell cycle genes. Cardiac myocytes (CMs) accumulate heterochromatin during differentiation and demethylation of H3K9me3 inhibits cell cycle gene silencing and cell cycle exit in CMs; however, it is unclear if this process is mediated by HP1s. In this study, we created a conditional CM-specific HP1 gamma (HP1γ) knockout (KO) mouse model and tested whether HP1γ is required for cell cycle gene silencing and cardiac growth...
April 17, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29665657/recent-advances-in-the-diagnosis-and-management-of-primary-myelofibrosis
#18
Katsuto Takenaka, Kazuya Shimoda, Koichi Akashi
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) in which dysregulation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways is the major pathogenic mechanism. Most patients with PMF carry a driver mutation in the JAK2, MPL (myeloproliferative leukemia), or CALR (calreticulin) genes. Mutations in epigenetic regulators and RNA splicing genes may also occur, and play critical roles in PMF disease progression. Based on revised World Health Organization diagnostic criteria for MPNs, both screening for driver mutations and bone marrow biopsy are required for a specific diagnosis...
April 20, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29665565/evaluation-of-nkx3-1-and-c-myc-expression-in-canine-prostatic-cancer
#19
Carlos Eduardo Fonseca-Alves, Priscila Emiko Kobayashi, Renée Laufer-Amorim
NKX3.1/C-MYC cross-regulation has been reported in the normal human prostate, and loss of NKX3.1 and gain of C-MYC seem to be important events in prostate cancer development and progression. The dog can be an interesting model for human prostatic disease, and yet only one previous research study has shown deregulation of NKX3.1 and MYC in the canine prostate. To address the expression of NKX3.1 and C-MYC in different canine prostatic lesions, this study verified the gene and protein expression of NKX3.1 and C-MYC in normal canine prostatic tissues...
April 10, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29665429/autophagy-in-mammalian-neurodevelopment-and-implications-for-childhood-neurological-disorders
#20
REVIEW
Derek Marsh, Joanna M Dragich
Here we explore the neurodevelopmental aspects of macroautophagy (henceforth known as autophagy), the process by which cells remove and remodel their structure in a regulated and spatially restricted manner. Autophagy is a catabolic pathway in which cytosolic substances, such as protein complexes, lipids, and organelles, are engulfed by an autophagic vesicle. Degradation occurs once an autophagosome fuses with a lysosome, allowing the macromolecular cargo sequestered within the autophagic vesicle to be recycled...
April 14, 2018: Neuroscience Letters
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