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Artigos de revistas sobre o tema "Complexe GATOR1"

Autor: Grafiati

Publicado: 28 de setembro de 2024

Última modificação: 31 de julho de 2025

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1

Bettedi, Lucia, Yingbiao Zhang, Shu Yang, and Mary A. Lilly. "Unveiling GATOR2 Function: Novel Insights from Drosophila Research." Cells 13, no. 21 (2024): 1795. http://dx.doi.org/10.3390/cells13211795.

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The multiprotein Target of Rapamycin (TOR) Complex 1 (TORC1) is a serine/threonine kinase that stimulates anabolic metabolism and suppresses catabolism. Deregulation of TORC1 is implicated in various human pathologies, including cancer, epilepsy, and neurodegenerative disorders. The Gap Activity Towards Rags (GATOR) complex contains two subcomplexes: GATOR1, which inhibits TORC1 activity; and GATOR2, which counteracts GATOR1s function. Structural and biochemical studies have elucidated how GATOR1 regulates TORC1 activity by acting as a GTPase activating protein for Rag GTPase. However, while c

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Kurrle, Nina, Frank Schnütgen, Juliana Heidler, et al. "Exploring the Function of Sestrin/Gator As Novel Regulators of Hematopoiesis." Blood 128, no. 22 (2016): 1484. http://dx.doi.org/10.1182/blood.v128.22.1484.1484.

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Abstract The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that responds to multiple environmental cues such as reactive oxygen species (ROS) and thereby regulates many fundamental biological processes including cell growth and autophagy. mTOR is found in two distinct multiprotein complexes, mTORC1 and mTORC2, of which mTORC1 has been established to play an important role in the regulation of hematopoiesis. For example, mTORC1 inhibition, combined with activation of canonical Wnt-signaling, was shown to increase long term repopulating (LT)-HSC self-renewal, whereas

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Haidurov, Alexander, and Andrei V. Budanov. "Locked in Structure: Sestrin and GATOR—A Billion-Year Marriage." Cells 13, no. 18 (2024): 1587. http://dx.doi.org/10.3390/cells13181587.

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Sestrins are a conserved family of stress-responsive proteins that play a crucial role in cellular metabolism, stress response, and ageing. Vertebrates have three Sestrin genes (SESN1, SESN2, and SESN3), while invertebrates encode only one. Initially identified as antioxidant proteins that regulate cell viability, Sestrins are now recognised as crucial inhibitors of the mechanistic target of rapamycin complex 1 kinase (mTORC1), a central regulator of anabolism, cell growth, and autophagy. Sestrins suppress mTORC1 through an inhibitory interaction with the GATOR2 protein complex, which, in conc

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Solanki, Sumeet, Jun-Hee Lee, and Yatrik Shah. "AMINO ACID SENSING PATHWAYS IN INFLAMMATORY BOWEL DISEASE." Inflammatory Bowel Diseases 28, Supplement_1 (2022): S23—S24. http://dx.doi.org/10.1093/ibd/izac015.036.

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Abstract IBD is a chronic inflammatory disease of the gastrointestinal tract affecting millions of people worldwide. The last few decades have seen rapid increase of IBD cases in the US contributing to exorbitant health-care costs and morbidity rates. IBD comprises of two major subtypes: ulcerative colitis and Crohn’s disease. Although the etiology of IBD is not completely understood, a complex interaction of environmental, genetic, immune, and gut microbial factors contributes to its pathogenesis. These factors ultimately converge to disrupt intestinal epithelial cell homeostasis, compromisin

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Padi, Sathish K. R., Neha Singh, Jeremiah J. Bearss, et al. "Phosphorylation of DEPDC5, a component of the GATOR1 complex, releases inhibition of mTORC1 and promotes tumor growth." Proceedings of the National Academy of Sciences 116, no. 41 (2019): 20505–10. http://dx.doi.org/10.1073/pnas.1904774116.

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The Pim and AKT serine/threonine protein kinases are implicated as drivers of cancer. Their regulation of tumor growth is closely tied to the ability of these enzymes to mainly stimulate protein synthesis by activating mTORC1 (mammalian target of rapamycin complex 1) signaling, although the exact mechanism is not completely understood. mTORC1 activity is normally suppressed by amino acid starvation through a cascade of multiple regulatory protein complexes, e.g., GATOR1, GATOR2, and KICSTOR, that reduce the activity of Rag GTPases. Bioinformatic analysis revealed that DEPDC5 (DEP domain contai

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Wei, Youheng, Brad Reveal, Weili Cai, and Mary A. Lilly. "The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster." G3 Genes|Genomes|Genetics 6, no. 12 (2016): 3859–67. http://dx.doi.org/10.1534/g3.116.035337.

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Abstract TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here, we characterize null mutants of the GATOR1 components nprl2, nprl3, and iml1 in Drosophila melanogaster. We demonstrate that all three mutants have inappropriately hig

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Muller, Maéline, Jasmine Bélanger, Imane Hadj-Aissa, Conghao Zhang, Chantelle F. Sephton, and Paul A. Dutchak. "GATOR1 Mutations Impair PI3 Kinase-Dependent Growth Factor Signaling Regulation of mTORC1." International Journal of Molecular Sciences 25, no. 4 (2024): 2068. http://dx.doi.org/10.3390/ijms25042068.

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GATOR1 (GAP Activity TOward Rag 1) is an evolutionarily conserved GTPase-activating protein complex that controls the activity of mTORC1 (mammalian Target Of Rapamycin Complex 1) in response to amino acid availability in cells. Genetic mutations in the GATOR1 subunits, NPRL2 (nitrogen permease regulator-like 2), NPRL3 (nitrogen permease regulator-like 3), and DEPDC5 (DEP domain containing 5), have been associated with epilepsy in humans; however, the specific effects of these mutations on GATOR1 function and mTORC1 regulation are not well understood. Herein, we report that epilepsy-linked muta

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Gu, Xin, Jose M. Orozco, Robert A. Saxton, et al. "SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway." Science 358, no. 6364 (2017): 813–18. http://dx.doi.org/10.1126/science.aao3265.

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mTOR complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple environmental cues. Nutrients signal via the Rag guanosine triphosphatases (GTPases) to promote the localization of mTORC1 to the lysosomal surface, its site of activation. We identified SAMTOR, a previously uncharacterized protein, which inhibits mTORC1 signaling by interacting with GATOR1, the GTPase activating protein (GAP) for RagA/B. We found that the methyl donor S-adenosylmethionine (SAM) disrupts the SAMTOR-GATOR1 complex by binding directly to SAMTOR with a dissociation constant of approximately 7 μM.

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Smieszek, S. P. "0018 Whole Genome Sequencing Study Identifies Novel Variants Associated with Intrinsic Circadian Period in Humans." Sleep 43, Supplement_1 (2020): A7—A8. http://dx.doi.org/10.1093/sleep/zsaa056.017.

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Abstract Introduction Non-24 is a circadian rhythm disorder in which the master body clock runs either slightly earlier or, more commonly in the disorder, longer than 24 hours. Methods We conducted the first whole genome sequencing study of a non-24 population of 174 individuals that we identified as being totally blind with Non-24 Disorder. We have directly tested the association between SNPs and circadian period length (tau) (n=69). Linear regression corrected for PCs and covariates identified a strong signal in HCN1, Brain Cyclic Nucleotide-Gated Channel 1, HCN1. Results HCN1 channel is res

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Shen, Kuang, Rick K. Huang, Edward J. Brignole, et al. "Architecture of the human GATOR1 and GATOR1–Rag GTPases complexes." Nature 556, no. 7699 (2018): 64–69. http://dx.doi.org/10.1038/nature26158.

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Jang, Ki Beom, Agus Suryawan, Marta L. Fiorotto, and Teresa A. Davis. "PSII-18 Prematurity alters nutrient signaling and protein synthesis in skeletal muscle of neonatal piglets." Journal of Animal Science 102, Supplement_3 (2024): 694–95. http://dx.doi.org/10.1093/jas/skae234.783.

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Abstract Extrauterine growth restriction is common in infants born preterm, and negatively affects lean mass accretion and health. Prematurity has been shown to inhibit the feeding-induced stimulation of protein synthesis in skeletal muscle. We hypothesized that nutrient signaling, activation of the mechanistic target of rapamycin complex 1 (mTORC1), and protein synthesis in the muscle are limited in preterm infants which negatively impacts muscle growth. The objective of this study was to examine how prematurity influences the mechanisms involved in insulin- and amino acid-induced signaling a

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Loissell-Baltazar, Yahir A., and Svetlana Dokudovskaya. "SEA and GATOR 10 Years Later." Cells 10, no. 10 (2021): 2689. http://dx.doi.org/10.3390/cells10102689.

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The SEA complex was described for the first time in yeast Saccharomyces cerevisiae ten years ago, and its human homologue GATOR complex two years later. During the past decade, many advances on the SEA/GATOR biology in different organisms have been made that allowed its role as an essential upstream regulator of the mTORC1 pathway to be defined. In this review, we describe these advances in relation to the identification of multiple functions of the SEA/GATOR complex in nutrient response and beyond and highlight the consequence of GATOR mutations in cancer and neurodegenerative diseases.

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Xu, Dandan, Kevin L. Shimkus, Holly A. Lacko, Lydia Kutzler, Leonard S. Jefferson, and Scot R. Kimball. "Evidence for a role for Sestrin1 in mediating leucine-induced activation of mTORC1 in skeletal muscle." American Journal of Physiology-Endocrinology and Metabolism 316, no. 5 (2019): E817—E828. http://dx.doi.org/10.1152/ajpendo.00522.2018.

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Previous studies established that leucine stimulates protein synthesis in skeletal muscle to the same extent as a complete mixture of amino acids, and the effect occurs through activation of the mechanistic target of rapamycin in complex 1 (mTORC1). Recent studies using cells in culture showed that the Sestrins bind leucine and are required for leucine-dependent activation of mTORC1. However, the role they play in mediating leucine-dependent activation of the kinase in vivo has been questioned because the dissociation constant of Sestrin2 for leucine is well below circulating and intramuscular

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Kovačević, Maša, Nikola Vojvodić, and Ivana Novaković. "GATOR1 gene variants in focal epilepsy." Medicinski podmladak 75, no. 3 (2024): 21–27. http://dx.doi.org/10.5937/mp75-45140.

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Significant genetic contributions to focal epilepsy have only recently been recognized, despite the well-established hereditary nature of other epilepsy syndromes. In 2013, the significant role of the DEPDC5 gene in a rare familial focal epilepsy syndrome was described, followed by the discovery of variants in NPRL2 and NPRL3 genes in patients with similar clinical features three years later. The genes listed above code the three subunits that comprise the GTPase-activating protein (GAP) activity towards Rags 1 (GATOR1) complex, a negative regulator of the mechanistic target of rapamycin (mTOR

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Kowalsky, Allison Ho, Sim Namkoong, Eric Mettetal, et al. "The GATOR2–mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr kinase activation." Journal of Biological Chemistry 295, no. 7 (2020): 1769–80. http://dx.doi.org/10.1074/jbc.ra119.010857.

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Sestrins represent a family of stress-inducible proteins that prevent the progression of many age- and obesity-associated disorders. Endogenous Sestrins maintain insulin-dependent AKT Ser/Thr kinase (AKT) activation during high-fat diet–induced obesity, and overexpressed Sestrins activate AKT in various cell types, including liver and skeletal muscle cells. Although Sestrin-mediated AKT activation improves metabolic parameters, the mechanistic details underlying such improvement remain elusive. Here, we investigated how Sestrin2, the Sestrin homolog highly expressed in liver, induces strong AK

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Van ’t Hof, Femke, and Eva Brilstra. "Focale epilepsie en de GATOR1 complex genen." Epilepsie, periodiek voor professionals 19, no. 2 (2021): 11–13. http://dx.doi.org/10.54160/epilepsie.11027.

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Een monogene oorzaak bij focale epilepsie is minder zeldzaam dan vroeger werd gedacht. De meest voorkomende groep erfelijke, focale epilepsieën worden veroorzaakt door varianten in de GATOR1 complex genen (DEPDC5, NPRL2 en NPRL3), ook wel de ‘GATORopathieën’ genoemd. Er is steeds meer bekend over de verschillende ziekte-uitingen van deze aandoeningen, en zelfs over de consequenties voor behandeling. Dit maakt genetische diagnostiek belangrijk.

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Nada, Shigeyuki, and Masato Okada. "Genetic dissection of Ragulator structure and function in amino acid-dependent regulation of mTORC1." Journal of Biochemistry 168, no. 6 (2020): 621–32. http://dx.doi.org/10.1093/jb/mvaa076.

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Abstract Ragulator is a heteropentameric protein complex consisting of two roadblock heterodimers wrapped by the membrane anchor p18/Lamtor1. The Ragulator complex functions as a lysosomal membrane scaffold for Rag GTPases to recruit and activate mechanistic target of rapamycin complex 1 (mTORC1). However, the roles of Ragulator structure in the regulation of mTORC1 function remain elusive. In this study, we disrupted Ragulator structure by directly anchoring RagC to lysosomes and monitored the effect on amino acid-dependent mTORC1 activation. Expression of lysosome-anchored RagC in p18-defici

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Laufenberg, Lacee J., Kristen T. Crowell, and Charles H. Lang. "Alcohol Acutely Antagonizes Refeeding-Induced Alterations in the Rag GTPase-Ragulator Complex in Skeletal Muscle." Nutrients 13, no. 4 (2021): 1236. http://dx.doi.org/10.3390/nu13041236.

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The Ragulator protein complex is critical for directing the Rag GTPase proteins and mTORC1 to the lysosome membrane mediating amino acid-stimulated protein synthesis. As there is a lack of evidence on alcohol’s effect on the Rag-Ragulator complex as a possible mechanism for the development of alcoholic skeletal muscle wasting, the aim of our study was to examine alterations in various protein–protein complexes in the Rag-Ragulator pathway produced acutely by feeding and how these are altered by alcohol under in vivo conditions. Mice (C57Bl/6; adult males) were fasted, and then provided rodent

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Meng, Jin, and Shawn M. Ferguson. "GATOR1-dependent recruitment of FLCN–FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids." Journal of Cell Biology 217, no. 8 (2018): 2765–76. http://dx.doi.org/10.1083/jcb.201712177.

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Folliculin (FLCN) is a tumor suppressor that coordinates cellular responses to changes in amino acid availability via regulation of the Rag guanosine triphosphatases. FLCN is recruited to lysosomes during amino acid starvation, where it interacts with RagA/B as a heterodimeric complex with FLCN-interacting proteins (FNIPs). The FLCN–FNIP heterodimer also has GTPase-activating protein (GAP) activity toward RagC/D. These properties raised two important questions. First, how is amino acid availability sensed to regulate lysosomal abundance of FLCN? Second, what is the relationship between FLCN ly

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Hesketh, Geoffrey G., Fotini Papazotos, Judy Pawling, et al. "The GATOR–Rag GTPase pathway inhibits mTORC1 activation by lysosome-derived amino acids." Science 370, no. 6514 (2020): 351–56. http://dx.doi.org/10.1126/science.aaz0863.

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The mechanistic target of rapamycin complex 1 (mTORC1) couples nutrient sufficiency to cell growth. mTORC1 is activated by exogenously acquired amino acids sensed through the GATOR–Rag guanosine triphosphatase (GTPase) pathway, or by amino acids derived through lysosomal degradation of protein by a poorly defined mechanism. Here, we revealed that amino acids derived from the degradation of protein (acquired through oncogenic Ras-driven macropinocytosis) activate mTORC1 by a Rag GTPase–independent mechanism. mTORC1 stimulation through this pathway required the HOPS complex and was negatively re

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Krenn, Martin, Matias Wagner, Christoph Hotzy, et al. "Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes." Journal of Medical Genetics 57, no. 9 (2020): 624–33. http://dx.doi.org/10.1136/jmedgenet-2019-106658.

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BackgroundThe genetic architecture of non-acquired focal epilepsies (NAFEs) becomes increasingly unravelled using genome-wide sequencing datasets. However, it remains to be determined how this emerging knowledge can be translated into a diagnostic setting. To bridge this gap, we assessed the diagnostic outcomes of exome sequencing (ES) in NAFE.Methods112 deeply phenotyped patients with NAFE were included in the study. Diagnostic ES was performed, followed by a screen to detect variants of uncertain significance (VUSs) in 15 well-established focal epilepsy genes. Explorative gene prioritisation

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Suryawan, Agus, Marko Rudar, Marta L. Fiorotto та Teresa A. Davis. "Differential regulation of mTORC1 activation by leucine and β-hydroxy-β-methylbutyrate in skeletal muscle of neonatal pigs". Journal of Applied Physiology 128, № 2 (2020): 286–95. http://dx.doi.org/10.1152/japplphysiol.00332.2019.

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Leucine (Leu) and its metabolite β-hydroxy-β-methylbutyrate (HMB) stimulate mechanistic target of rapamycin (mTOR) complex 1 (mTORC1)-dependent protein synthesis in the skeletal muscle of neonatal pigs. This study aimed to determine whether HMB and Leu utilize common nutrient-sensing mechanisms to activate mTORC1. In study 1, neonatal pigs were fed one of five diets for 24 h: low protein (LP), high protein (HP), or LP supplemented with 4 (LP+HMB4), 40 (LP+HMB40), or 80 (LP+HMB80) μmol HMB·kg body wt−1·day−1. In study 2, neonatal pigs were fed for 24 h: LP, LP supplemented with Leu (LP+Leu), or

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Suryawan, Agus, and Teresa A. Davis. "Amino Acid- and Insulin-Induced Activation of mTORC1 in Neonatal Piglet Skeletal Muscle Involves Sestrin2-GATOR2, Rag A/C-mTOR, and RHEB-mTOR Complex Formation." Journal of Nutrition 148, no. 6 (2018): 825–33. http://dx.doi.org/10.1093/jn/nxy044.

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Abstract Background Feeding stimulates protein synthesis in skeletal muscle of neonates and this response is regulated through activation of mechanistic target of rapamycin complex 1 (mTORC1). The identity of signaling components that regulate mTORC1 activation in neonatal muscle has not been fully elucidated. Objective We investigated the independent effects of the rise in amino acids (AAs) and insulin after a meal on the abundance and activation of potential regulators of mTORC1 in muscle and whether the responses are modified by development. Methods Overnight-fasted 6- and 26-d-old pigs wer

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Figlia, Gianluca, Sandra Müller, Anna M. Hagenston, et al. "Brain-enriched RagB isoforms regulate the dynamics of mTORC1 activity through GATOR1 inhibition." Nature Cell Biology 24, no. 9 (2022): 1407–21. http://dx.doi.org/10.1038/s41556-022-00977-x.

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AbstractMechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to appropriately regulate cellular anabolism and catabolism. During nutrient restriction, different organs in an animal do not respond equally, with vital organs being relatively spared. This raises the possibility that mTORC1 is differentially regulated in different cell types, yet little is known about this mechanistically. The Rag GTPases, RagA or RagB bound to RagC or RagD, tether mTORC1 in a nutrient-dependent manner to lysosomes where mTORC1 becomes activated. Although the RagA and B paralogues were a

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Davis, Teresa A., Samer El-Kadi, Agus Suryawan, and Marta Fiorotto. "356 Meal feeding compared with continuous feeding enhances insulin and amino acid signaling to translation initiation in skeletal muscle of pigs." Journal of Animal Science 97, Supplement_3 (2019): 127–28. http://dx.doi.org/10.1093/jas/skz258.261.

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Abstract Objectives: Meal feeding enhances skeletal muscle protein synthesis and lean growth more than continuous feeding in piglets. This enhanced muscle protein synthesis with meal feeding is associated with increased activation of mTORC1-dependent translation initiation. The mechanism underlying this response is unknown. We aimed to identify insulin and amino acid signaling components involved in the enhanced lean growth that results from meal feeding vs. continuous feeding in term-born pigs. Methods: Newborn piglets were fed for 21 d an equal amount of sow milk replacer (12.8 g protein and

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Cheng, Yang, Jiadong Cai, Yuanyuan Fu, Congjing Feng, Yue Hao, and Youheng Wei. "Royal jelly attenuates metabolic defects in a Drosophila mutant with elevated TORC1 activity." Biology Open 9, no. 11 (2020): bio054999. http://dx.doi.org/10.1242/bio.054999.

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ABSTRACTTarget of rapamycin complex 1 (TORC1) is a master regulator of cell metabolism, and its dysregulation has been linked to an array of pathologies, including cancer and age-related diseases. Nprl3, a component of GTPase-activating protein towards Rags complex 1 (GATOR1), inhibits TORC1 activity under nutrient scarcity status. The nprl3 mutant exhibits some metabolic defects due to hyper TORC1 activity in Drosophila. Royal jelly (RJ) is a honeybee-secreted product and plays an essential role in caste differentiation that requires TORC1 activity. RJ is also used as a health-benefit food fo

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Sharma, Vijendra, Rapita Sood, Danning Lou, et al. "4E-BP2–dependent translation in parvalbumin neurons controls epileptic seizure threshold." Proceedings of the National Academy of Sciences 118, no. 15 (2021): e2025522118. http://dx.doi.org/10.1073/pnas.2025522118.

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The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals to regulate critical cellular processes such as mRNA translation, lipid biogenesis, and autophagy. Germline and somatic mutations in mTOR and genes upstream of mTORC1, such as PTEN, TSC1/2, AKT3, PIK3CA, and components of GATOR1 and KICSTOR complexes, are associated with various epileptic disorders. Increased mTORC1 activity is linked to the pathophysiology of epilepsy in both humans and animal models, and mTORC1 inhibition suppresses epileptogenesis in humans with tuberous sclerosis and animal models

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Snow, Jonathan W., and Stuart H. Orkin. "Translational Isoforms of FOG1 Regulate GATA1-interacting Complexes." Journal of Biological Chemistry 284, no. 43 (2009): 29310–19. http://dx.doi.org/10.1074/jbc.m109.043497.

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Papadopoulos, Petros, Laura Gutiérrez, Jeroen Demmers, et al. "TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis." Molecular and Cellular Biology 35, no. 12 (2015): 2103–18. http://dx.doi.org/10.1128/mcb.01370-14.

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The ordered assembly of a functional preinitiation complex (PIC), composed of general transcription factors (GTFs), is a prerequisite for the transcription of protein-coding genes by RNA polymerase II. TFIID, comprised of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs), is the GTF that is thought to recognize the promoter sequences allowing site-specific PIC assembly. Transcriptional cofactors, such as SAGA, are also necessary for tightly regulated transcription initiation. The contribution of the two TAF10-containing complexes (TFIID, SAGA) to erythropoiesis remains elusiv

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Becchetti, Andrea, Laura Clara Grandi, Giulia Colombo, Simone Meneghini, and Alida Amadeo. "Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology." Brain Sciences 10, no. 12 (2020): 907. http://dx.doi.org/10.3390/brainsci10120907.

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Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na+-gated K+ channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic rec

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Platani, Melpomeni, Laura Trinkle-Mulcahy, Michael Porter, A. Arockia Jeyaprakash, and William C. Earnshaw. "Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes." Journal of Cell Biology 210, no. 1 (2015): 45–62. http://dx.doi.org/10.1083/jcb.201410001.

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Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localiz

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Drissen, Roy, Boris Guyot, Lin Zhang, et al. "Lineage-specific combinatorial action of enhancers regulates mouse erythroid Gata1 expression." Blood 115, no. 17 (2010): 3463–71. http://dx.doi.org/10.1182/blood-2009-07-232876.

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Abstract Precise spatiotemporal control of Gata1 expression is required in both early hematopoietic progenitors to determine erythroid/megakaryocyte versus granulocyte/monocyte lineage output and in the subsequent differentiation of erythroid cells and megakaryocytes. An enhancer element upstream of the mouse Gata1 IE (1st exon erythroid) promoter, mHS−3.5, can direct both erythroid and megakaryocytic expression. However, loss of this element ablates only megakaryocytes, implying that an additional element has erythroid specificity. Here, we identify a double DNaseI hypersensitive site, mHS−25

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Tauchmann, Samantha, Frederik Otzen Bagger, Thomas Bock, et al. "Dissecting GATA1 Protein Interactions in Normal and Malignant Human Erythroblasts." Blood 138, Supplement 1 (2021): 3293. http://dx.doi.org/10.1182/blood-2021-148351.

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Abstract Acute erythroid leukemia (AEL) is characterized by uncontrolled accumulation of transformed erythroblasts. Previous analysis of murine and human AEL revealed aberrant regulation of the master regulator GATA1, which controls terminal erythroid differentiation in multi-protein complexes acting as activators or repressors of gene expression. Although most malignant erythroblasts constitutively express abundant GATA1 protein, terminal erythroid differentiation is impaired. Notably, overexpression of GATA1 significantly induced partial or complete terminal erythroid differentiation of the

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Suryawan, Agus, Jane Naberhuis, Marko Rudar, Marta Fiorotto, and Teresa Davis. "Prematurity Negatively Alters Activation of the Amino Acid Signaling Pathway That Regulates Protein Synthesis in Muscle of a Preterm Piglet Model." Current Developments in Nutrition 6, Supplement_1 (2022): 472. http://dx.doi.org/10.1093/cdn/nzac058.011.

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Abstract Objectives Preterm birth is often associated with reduced postnatal lean mass gain. Recently we found that postnatal weight gain and postprandial skeletal muscle protein synthesis in prematurely born piglets were blunted compared to term born pigs. This anabolic resistance is associated with reduced activation of mTORC1, a central regulator of protein synthesis. To identify the responsible mechanisms, we evaluated key regulatory components involved in the amino acid (AA)-induced activation of mTORC1 in skeletal muscle in preterm compared to term pigs. Methods Piglets were delivered by

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Barbosa, R. C. C., C. B. Gitti, M. C. N. Castro, and F. Mendes-de-Almeida. "Aspectos clínicos e laboratoriais do complexo gengivite-estomatite em gatos domésticos." Arquivo Brasileiro de Medicina Veterinária e Zootecnia 70, no. 6 (2018): 1784–92. http://dx.doi.org/10.1590/1678-4162-10037.

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RESUMO Foram incluídos 76 gatos domésticos com diferentes graus (I a IV) de lesões em cavidade oral, os quais foram avaliados clinicamente e tiveram coletadas amostras de sangue e suabes da cavidade oral. A maioria dos gatos portadores de CGE eram machos, castrados, adultos, sem raça definida e com estilo de vida confinado. Os sinais clínicos observados e associados à gravidade da inflamação na cavidade oral foram halitose (98,7%); ptialismo (22,4%); hemorragia bucal (9,2%) e úlcera na parte superior dos lábios (2,6%); desconforto à manipulação da cavidade oral (44,7%) e perda dentária (55,3%)

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Hamlett, Isla, Julia Draper, John Strouboulis, Francisco Iborra, Catherine Porcher, and Paresh Vyas. "Characterization of megakaryocyte GATA1-interacting proteins: the corepressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation." Blood 112, no. 7 (2008): 2738–49. http://dx.doi.org/10.1182/blood-2008-03-146605.

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Abstract The transcription factor GATA1 coordinates timely activation and repression of megakaryocyte gene expression. Loss of GATA1 function results in excessive megakaryocyte proliferation and disordered terminal platelet maturation, leading to thrombocytopenia and leukemia in patients. The mechanisms by which GATA1 does this are unclear. We have used in vivo biotinylated GATA1 to isolate megakaryocyte GATA1-partner proteins. Here, several independent approaches show that GATA1 interacts with several proteins in the megakaryocyte cell line L8057 and in primary megakaryocytes. They include FO

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Tamura, Kotaro, Hidefumi Kitazawa, Satoshi Sugita, et al. "Tyrosine Is a Booster of Leucine-Induced Muscle Anabolic Response." Nutrients 16, no. 1 (2023): 84. http://dx.doi.org/10.3390/nu16010084.

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Leucine (Leu), an essential amino acid, is known to stimulate protein synthesis in the skeletal muscle via mTOR complex 1 (mTORC1) activation. However, the intrinsic contribution of other amino acids to Leu-mediated activation of mTORC1 signaling remains unexplored. This study aimed to identify amino acids that can promote mTORC1 activity in combination with Leu and to assess the effectiveness of these combinations in vitro and in vivo. We found that tyrosine (Tyr) enhanced Leu-induced phosphorylation of S6 kinase (S6K), an indicator of mTORC1 activity, although it exerted no such effect indiv

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Hernández, Aurora, Ana Villegas, Francisco Iborra, William G. Wood, and Eduardo Anguita. "Multiple Site Gfi1b Self-Regulation and GATA1/SCL Pentameric Complex: Shifting the Equilibrium towards Repression." Blood 112, no. 11 (2008): 4766. http://dx.doi.org/10.1182/blood.v112.11.4766.4766.

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Abstract Transcription factor Gfi1b is required for erythroid and megakaryocytic differentiation. Gfi1b is over-expressed in patients and cell lines of erythroid and megakaryocytic leukemias. This indicates that this gene must be tightly regulated to achieve normal erythropoiesis and megakaryopoiesis. The mechanism of it is largely unknown. We have searched for conserved noncoding sequences from multiple evolutionary diverse species (multispecies conserved sequences, MCSs) between Gfi1b neighboring genes and localized several elements containing multiple highly conserved erythroid specific tra

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Dumitru, ROMAN. "ACHIZIȚIA DE CONTROL – PROCEDEU PROBATORIU IMPORTANT LA CERCETAREA UNOR CATEGORII DE INFRACȚIUNI." STUDIA UNIVERSITATIS MOLDAVIAE Științe Sociale, no. 8(158) (2022): 46–49. https://doi.org/10.5281/zenodo.7277485.

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Achiziția de control se desfășoară, de regulă, la cercetarea infracțiunilor trafic de droguri, trafic de arme și de punere în circulație a banilor falși. Prin achiziția de control și prin percheziția bănuitului și/sau percheziția domiciliului acestuia se obțin mijlocele de probă materiale – corpuri delicte. Achiziția de control obligatoriu se realizeză în complex cu alte măsuri speciale de investigație: 1) investigaţia sub acoperire; 2) interceptarea şi înregistrarea comunicărilor dintre agentul sub acoperire şi participanții la fapta penală. Achiziția de control c

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Callejon, Francisco Balaguer. "Normative Function of Constitutional Decisions." Pravosudie / Justice 3, no. 1 (2021): 32–50. http://dx.doi.org/10.37399/2686-9241.2021.1.32-50.

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Introduction. This work analyses the normative function of constitutional judgments, their cha- racteristics and their limits. Theoretical Basis. Methods. The theoretical bases start from the work of Hans Kelsen in relation to the condition of “negative legislator” of the constitutional court, which already implies a dero- gatory capacity on the legal order and, therefore, a normative function, completed with the differ- entiation of Vezio Crisafulli between “disposition and norm” that allows opening the constitution- al jurisdiction to a consideration as “positive legislator”. Likewise, theor

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Timothy, A. Redl. "Accelerating Students Successfully through Developmental and College-Level Mathematics and Embracing Co-Requisite Models: An 8-week + 8-week Model." Journal of Education and Social Development 4, no. 2 (2020): 17–21. https://doi.org/10.5281/zenodo.4263590.

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We describe the framework, supports, successes, challenges, goals, and next steps for a Texas four-year public university’s accelerated and co-requisite 8-week + 8-week course model for developmental mathematics students. Through this model, these students can successfully complete both their developmental mathematics and subsequent college-level core mathematics course in the same 16-week semester. The university’s award-winning Supplemental Instruction (SI) Program, Center for Mathematics and Statistics Support tutoring lab, and the Gator Success Center all play a major role in s

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Shinhmar, Sonia, Judith Schaf, Katie Lloyd Jones, Olivier E. Pardo, Philip Beesley, and Robin S. B. Williams. "Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma." International Journal of Molecular Sciences 25, no. 12 (2024): 6586. http://dx.doi.org/10.3390/ijms25126586.

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Tanshinone IIA (T2A) is a bioactive compound that provides promise in the treatment of glioblastoma multiforme (GBM), with a range of molecular mechanisms including the inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy. Recently, T2A has been demonstrated to function through sestrin 2 (SESN) to inhibit mTORC1 activity, but its possible impact on autophagy through this pathway has not been investigated. Here, the model system Dictyostelium discoideum and GBM cell lines were employed to investigate the cellular role of T2A in regulating SESN to i

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Tauchmann, S., F. Otzen Bagger, T. Bock, et al. "P467: FUNCTIONAL CHARACTERIZATION OF ABERRANT GATA1 PROTEIN COMPLEXES IN NORMAL AND MALIGNANT HUMAN ERYTHROBLASTS." HemaSphere 6 (June 2022): 366–67. http://dx.doi.org/10.1097/01.hs9.0000844756.12257.0a.

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Ferreira, Guadalupe Sampaio, Amanda Leal de VASCONCELLOS, Guido Carlos Iselda Hermans MASSON, André Luiz Baptista GALVÃO, Elzylene LÉGA, and Mildre PINTO. "ABORDAGEM SOBRE COMPLEXO GENGIVITE-ESTOMATITE-FARINGITE EM GATO – RELATO DE CASO." Nucleus Animalium 4, no. 1 (2012): 13–18. http://dx.doi.org/10.3738/1982.2278.582.

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Xavier Júnior, Francisco Antônio Félix, Glayciane Bezerra Morais, Marrie Silva Dutra, et al. "Doença Renal Aguda em gatos: conquistas e desafios." Medicina Veterinária (UFRPE) 13, no. 3 (2019): 352. http://dx.doi.org/10.26605/medvet-v13n3-3308.

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A doença renal aguda (DRA) refere-se a uma síndrome clínica associada a alta morbidade e mortalidade, fazendo parte da síndrome de disfunção de múltiplos órgãos. Em medicina veterinária, estudos sobre a incidência de casos com DRA ainda são pouco elucidados, e a fisiopatologia da lesão renal aguda (LRA) é complexa, sendo caracterizada pela rápida diminuição da função excretora renal e consequente acúmulo de produtos do metabolismo de nitrogênio. Nesse contexto, o objetivo desse estudo foi apresentar a DRA com dados atuais sobre etiologia, patogenia, diagnóstico e tratamento.

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Sapin, Carolina Da Fonseca, Luísa Cerqueira Silva-Mariano, Aline Galiza Fialho-Xavier, et al. "PATOLOGIAS DO SISTEMA GENITAL FEMININO DE CÃES E GATOS." SCIENCE AND ANIMAL HEALTH 5, no. 1 (2017): 35. http://dx.doi.org/10.15210/sah.v5i1.9022.

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Considerando a sobrevivência de uma espécie, o sistema reprodutivo é um dos sistemas mais importantes. As gônadas indiferenciadas são formadas por células germinativas que quando estimuladas pelo fator de diferenciação testicular se diferenciam em testículos, ou quando não estimuladas, em ovários. Aqui serão abordadas lesões do desenvolvimento sexual e anomalias da formação e do desenvolvimento gonadal feminino. Dentre as patologias abordadas estão o complexo hiperplasia endometrial cística - piometra, metrite, neoplasmas ovarianos e uterinos.

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Nabavi Nouri, Maryam, Lama Alandijani, Kalene van Engelen, Soumitra Tole, Emilie Lalonde, and Tugce B. Balci. "From Alpha-Thalassemia Trait to NPRL3-Related Epilepsy: A Genomic Diagnostic Odyssey." Genes 15, no. 7 (2024): 836. http://dx.doi.org/10.3390/genes15070836.

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Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusu

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Papadopoulos, Petros, Laura Gutierrez, Jeroen Demmers, et al. "TAF10 Interacts with GATA1 Transcription Factor and Controls Mouse Erythropoiesis." Blood 124, no. 21 (2014): 2912. http://dx.doi.org/10.1182/blood.v124.21.2912.2912.

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Abstract The ordered assembly of a functional preinitiation complex (PIC), composed of general transcription factors (GTFs) is a prerequisite for the transcription of protein coding genes by RNA polymerase II. TFIID, comprised of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs), is the GTF that is thought to recognize the promoter sequences allowing site-specific PIC assembly. Transcriptional cofactors, such as SAGA (Spt-Ada-Gcn5-acetyltransferase), are also necessary to have tightly regulated transcription initiation. However, a new era on the role of the GTFs and specifica

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da Graça Costa, Marcia Maria, and Alzira Lobo de Arruda Campos. "A Estátua de Borba Gato." Veredas - Revista Interdisciplinar de Humanidades 2, no. 3 (2019): 34–54. http://dx.doi.org/10.56242/revistaveredas;2019;2;3;34-54.

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A estátua de Borba Gato é o eixo a partir do qual se estabelece uma reflexão sobre as relações entre a sociedade contemporânea e seus monumentos históricos. Em meio à tensão e ao caos urbano das grandes cidades, esses monumentos sobrevivem como lugares de memória. São sinais de reconhecimento e de pertencimento, elementos simbólicos do patrimônio memorial de uma comunidade. A memória social, e a consequente identidade que se apresenta na relação entre o bairro e a estátua, mostra-se difusa e complexa, entre a ideia da estátua como simples monumento, e a memória histórica ali representada. Memó

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Larsson, C. E., E. H. Delayte, A. C. Balda, et al. "Dermatite micobacteriana atípica em gato: relato de caso." Arquivo Brasileiro de Medicina Veterinária e Zootecnia 58, no. 6 (2006): 1092–98. http://dx.doi.org/10.1590/s0102-09352006000600018.

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Relata-se, pela primeira vez no Brasil, um caso de dermatite decorrente de infecção por micobactéria atípica do complexo Mycobacterium fortuitum-peregrinum, em espécie felina, sem raça definida, fêmea, com cinco anos de idade. Há oito meses, evoluía com lesões maculares equimóticas, nodulares, erosadas, ulceradas, acompanhadas de fístulas exsudativas, com intenso prurido e algia. Evidenciou-se a presença de micobactéria do complexo Mycobacterium fortuitum-peregrinum (grupo IV de Runyon ) identificada após evidenciação histopatológica, cultivo bacteriano e por testes bioquímicos. Após dois mese

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