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https://www.readbyqxmd.com/read/29791256/nlrp6-induces-pyroptosis-by-activation-of-caspase-1-in-gingival-fibroblasts
#1
W Liu, J Liu, W Wang, Y Wang, X Ouyang
NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, has been reported to participate in inflammasome formation. Activation of inflammasome triggers a caspase-1-dependent programming cell death called pyroptosis. However, whether NLRP6 induces pyroptosis has not been investigated. In this study, we showed that NLRP6 overexpression activated caspase-1 and gasdermin-D and then induced pyroptosis of human gingival fibroblasts, resulting in release of proinflammatory mediators interleukin (IL)-1β and IL-18...
May 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29790920/elucidating-the-role-of-the-maternal-embryonic-leucine-zipper-kinase-melk-in-adrenocortical-carcinoma
#2
Katja Kiseljak-Vassiliades, Yu Zhang, Adwitiya Kar, Raud Razzaghi, Mei Xu, Katherine Gowan, Christopher D Raeburn, Maria Albuja-Cruz, Kenneth L Jones, Hilary Somerset, Lauren Fishbein, Stephen Leong, Margaret E Wierman
Adrenocortical carcinoma (ACC) is an aggressive cancer with a five-year survival less than 35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified Maternal Embryonic Leucine Zipper Kinase (MELK) as 4.1-fold overexpressed in ACC compared to normal adrenal samples. High MELK expression in human tumors correlated with shorter survival and with increased expression of genes involved in cell division and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells...
May 21, 2018: Endocrinology
https://www.readbyqxmd.com/read/29790624/effects-of-rearing-system-on-meat-quality-fatty-acid-and-amino-acid-profiles-of-hu-lambs
#3
Jianmin Chai, Qiyu Diao, Jiangchao Zhao, Haichao Wang, Kaidong Deng, Minli Qi, Mingfei Nie, Naifeng Zhang
To determine the effects of early rearing system on meat quality traits, fatty acid and amino acid profiles of meat, 48 Hu lambs were selected and randomly divided into four treatments: control lambs were ewe-reared from birth to 60 days of age (ER), while treatment lambs were segregated from their dams at 10, 20 and 30 days of age, then artificially reared with milk replacer until 60 days of age (EW10, EW20 and EW30, respectively). All lambs had no access to the milk replacer or their dams from 61 to 90 days...
May 23, 2018: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/29790585/the-intracellular-nucleotide-binding-leucine-rich-repeat-receptor-slnrc4a-enhances-immune-signaling-elicited-by-extracellular-perception
#4
Meirav Leibman-Markus, Lorena Pizarro, Silvia Schuster, Z J Daniel Lin, Ofir Gershony, Maya Bar, Gitta Coaker, Adi Avni
Plant recognition and defense against pathogens employs a two-tiered perception system. Surface localized pattern recognition receptors (PRRs) act to recognize microbial features, while intracellular nucleotide binding leucine-rich repeat receptors (NLRs) directly or indirectly recognize pathogen effectors inside host cells. Employing the tomato PRR LeEIX2/EIX model system, we explored the molecular mechanism of signaling pathways. We identified an NLR that can associate with LeEIX2, termed SlNRC4a (NB-LRR Required for HR-associated Cell death-4)...
May 23, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29789389/lrrk2-is-a-negative-regulator-of-mycobacterium-tuberculosis-phagosome-maturation-in-macrophages
#5
Anetta Härtlova, Susanne Herbst, Julien Peltier, Angela Rodgers, Orsolya Bilkei-Gorzo, Antony Fearns, Brian D Dill, Heyne Lee, Rowan Flynn, Sally A Cowley, Paul Davies, Patrick A Lewis, Ian G Ganley, Jennifer Martinez, Dario R Alessi, Alastair D Reith, Matthias Trost, Maximiliano G Gutierrez
Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, chronic inflammation and mycobacterial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29788408/effects-of-4-hydroxy-2-3-3-4-5-pentachlorobiphenyl-4-oh-cb107-on-liver-transcriptome-in-rats-implication-in-the-disruption-of-circadian-rhythm-and-fatty-acid-metabolism
#6
Mari Ochiai, Midori Iida, Tetsuro Agusa, Kohki Takaguchi, Satoshi Fujiic, Kei Nomiyama, Hisato Iwata
Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical...
May 21, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29788256/distinct-hla-associations-of-lgi1-and-caspr2-antibody-diseases
#7
Sophie Binks, James Varley, Wanseon Lee, Mateusz Makuch, Katherine Elliott, Jeffrey M Gelfand, Saiju Jacob, M Isabel Leite, Paul Maddison, Mian Chen, Michael D Geschwind, Eleanor Grant, Arjune Sen, Patrick Waters, Mark McCormack, Gianpiero L Cavalleri, Martin Barnardo, Julian C Knight, Sarosh R Irani
The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies...
May 18, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29787835/the-expression-of-the-genes-involved-in-leucine-catabolism-of-pseudomonas-aeruginosa-is-controlled-by-the-transcriptional-regulator-liur-and-by-the-cbrab-crc-system
#8
Alma Laura Díaz-Pérez, Cinthia Núñez, Victor Meza Carmen, Jesús Campos-García
Pseudomonas aeruginosa metabolizes leucine through the leucine/isovalerate utilization pathway, whose enzymes are encoded in the liuRABCDE gene cluster (liu). In this study, we investigated the role of the LiuR protein in the liu cluster regulation. Our results indicated that liu expression is regulated at the transcriptional level by LiuR. Mobility shift assays using purified recombinant His-tagged LiuR showed that it was able to bind at the promoter region of liuR, in a dose-dependent manner. Results revealed that expression of the liu operon is subjected to carbon catabolite repression control (CCR); protein LiuD was strongly expressed in the presence of leucine, but it was repressed in the presence of glucose or succinate...
May 19, 2018: Research in Microbiology
https://www.readbyqxmd.com/read/29786747/microrna-137-dysregulation-predisposes-to-osteoporotic-fracture-by-impeding-alp-activity-and-expression-via-suppression-of-leucine-rich-repeat-containing-g-protein-coupled-receptor-4-expression
#9
Xiangjun Liu, Xiaohui Xu
Osteoporosis is defined as a loss of bone mass and deterioration of its architecture resulting in bone weakness, which becomes prone to fracture. The objective of this study was to investigate the molecular mechanism by which miR-137 can reduce the risk of fracture in patients with osteoporosis. An online miRNA database and a luciferase reporter assay system were used to confirm that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) was the target of miR-137. Real-time PCR and western blot analysis were used to study miR-137 mRNA, the expression of LGR4 mRNA and protein among different groups or cells transfected with a scrambled miRNA control, miR-137 mimic, LGR4 siRNA and miR-137 inhibitor...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786048/cardiac-hypertrophy-is-positively-regulated-by-microrna-24-in-ratsmicrorna-24
#10
Juan Gao, Min Zhu, Rui-Feng Liu, Jian-Shu Zhang, Ming Xu
Background: MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Methods: Twelve Sprague-Dawley rats with a body weight of 50 ± 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group...
June 5, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29785669/characterization-of-an-aryl-alcohol-oxidase-from-the-plant-saprophytic-basidiomycete-coprinopsis-cinerea-with-broad-substrate-specificity-against-aromatic-alcohols
#11
Yoshiaki Tamaru, Kiwamu Umezawa, Makoto Yoshida
OBJECTIVES: The aim of the study was to obtain information about the enzymatic properties of aryl-alcohol oxidase from the plant saprophytic basidiomycete Coprinopsis cinerea (rCcAAO), which is classified into the auxiliary activities family 3 subfamily 2 (AA3_2). RESULTS: The gene encoding AAO from the plant saprophytic basidiomycete Coprinopsis cinerea (CcAAO) was cloned, and the recombinant CcAAO (rCcAAO) was heterologously expressed in the methylotrophic yeast Pichia pastoris...
May 22, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29785123/leucine-rich-alpha-2-glycoprotein-1-is-up-regulated-in-colorectal-cancer-and-is-a-tumor-promoter
#12
Qian Zhang, Rui Huang, Qingchao Tang, Yang Yu, Quanlong Huang, Yinggang Chen, Guiyu Wang, Xishan Wang
Background: Leucine-rich α-2-glycoprotein-1 (LRG1) is differentially expressed in many kinds of diseases including cancer, however, it has not been thoroughly studied yet. Purpose: The objective of this study was to detect the expression and potential mechanism of LRG1 in colorectal cancer (CRC). In our study, we examined LRG1 levels in CRC tissue and plasma with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29784826/deletion-of-lrrtm1-and-lrrtm2-in-adult-mice-impairs-basal-ampa-receptor-transmission-and-ltp-in-hippocampal-ca1-pyramidal-neurons
#13
Mehdi Bhouri, Wade Morishita, Paul Temkin, Debanjan Goswami, Hiroshi Kawabe, Nils Brose, Thomas C Südhof, Ann Marie Craig, Tabrez J Siddiqui, Robert Malenka
Leucine-rich repeat transmembrane (LRRTM) proteins are synaptic cell adhesion molecules that influence synapse formation and function. They are genetically associated with neuropsychiatric disorders, and via their synaptic actions likely regulate the establishment and function of neural circuits in the mammalian brain. Here, we take advantage of the generation of a LRRTM1 and LRRTM2 double conditional knockout mouse ( LRRTM1,2 cKO) to examine the role of LRRTM1,2 at mature excitatory synapses in hippocampal CA1 pyramidal neurons...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784813/coordination-of-the-leucine-sensing-rag-gtpase-cycle-by-leucyl-trna-synthetase-in-the-mtorc1-signaling-pathway
#14
Minji Lee, Jong Hyun Kim, Ina Yoon, Chulho Lee, Mohammad Fallahi Sichani, Jong Soon Kang, Jeonghyun Kang, Min Guo, Kang Young Lee, Gyoonhee Han, Sunghoon Kim, Jung Min Han
A protein synthesis enzyme, leucyl-tRNA synthetase (LRS), serves as a leucine sensor for the mechanistic target of rapamycin complex 1 (mTORC1), which is a central effector for protein synthesis, metabolism, autophagy, and cell growth. However, its significance in mTORC1 signaling and cancer growth and its functional relationship with other suggested leucine signal mediators are not well-understood. Here we show the kinetics of the Rag GTPase cycle during leucine signaling and that LRS serves as an initiating "ON" switch via GTP hydrolysis of RagD that drives the entire Rag GTPase cycle, whereas Sestrin2 functions as an "OFF" switch by controlling GTP hydrolysis of RagB in the Rag GTPase-mTORC1 axis...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29783958/sanguinarine-triggers-intrinsic-apoptosis-to-suppress-colorectal-cancer-growth-through-disassociation-between-strap-and-melk
#15
Xianling Gong, Zhihong Chen, Qinrui Han, Chunhui Chen, Linlin Jing, Yawei Liu, Liang Zhao, Xueqing Yao, Xuegang Sun
BACKGROUND: Previous studies showed sanguinarine induced apoptosis in CRC cells but did not define the underlying mechanisms. The purpose of this work was to determine the in vivo and in vitro effects of sanguinarine on CRC tumors and to elucidate the mechanism in regulating the intrinsic apoptosis. METHODS: Cell viability of CRC cell lines treated with sanguinarine was measured by MTT assay. Apoptotic cells stained with Annexin V and 7-AAD were detected by flow cytometry...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29783655/gdf11-modulates-ca-2-dependent-smad2-3-signaling-to-prevent-cardiomyocyte-hypertrophy
#16
Javier Duran, Mayarling Francisca Troncoso, Daniel Lagos, Sebastian Ramos, Gabriel Marin, Manuel Estrada
Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β family, has been shown to act as a negative regulator in cardiac hypertrophy. Ca2+ signaling modulates cardiomyocyte growth; however, the role of Ca2+ -dependent mechanisms in mediating the effects of GDF11 remains elusive. Here, we found that GDF11 induced intracellular Ca2+ increases in neonatal rat cardiomyocytes and that this response was blocked by chelating the intracellular Ca2+ with BAPTA-AM or by pretreatment with inhibitors of the inositol 1,4,5-trisphosphate (IP₃) pathway...
May 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783624/growth-responses-of-preterm-pigs-fed-formulas-with-different-protein-levels-and-supplemented-with-leucine-or-%C3%AE-hydroxyl-%C3%AE-methylbutyrate
#17
Randal K Buddington, Scott C Howard, Harold W Lee, Karyl K Buddington
Growth after preterm birth is an important determinant of long-term outcomes. Yet, many preterm infants suffer ex utero growth retardation. We evaluated effects of leucine and the metabolite, β-hydroxy β-methylbutyrate (HMB) on growth of preterm pigs, a previously-validated translational model for preterm infants. After 48 h of parenteral nutrition preterm pigs were fed for 6 to 7 days isocaloric formulas with different levels of protein (50 or 100 g/L) with leucine (10 g/L, 76 mM) or HMB (at 1.1 g/L, 4 mM) added to stimulate protein synthesis or with alanine (6...
May 18, 2018: Nutrients
https://www.readbyqxmd.com/read/29781573/overexpression-of-ostf1l-a-rice-hd-zip-transcription-factor-promotes-lignin-biosynthesis-and-stomatal-closure-that-improves-drought-tolerance
#18
Seung Woon Bang, Dong-Keun Lee, Harin Jung, Pil Joong Chung, Youn Shic Kim, Yang Do Choi, Joo-Won Suh, Ju-Kon Kim
Drought stress seriously impacts on plant development and productivity. Improvement of drought tolerance without yield penalty is a great challenge in crop biotechnology. Here, we report that the rice (Oryza sativa) homeodomain-leucine zipper transcription factor gene, OsTF1L (Oryza sativa transcription factor 1-like), is a key regulator of drought tolerance mechanisms. Overexpression of the OsTF1L in rice significantly increased drought tolerance at the vegetative stages of growth and promoted both effective photosynthesis and a reduction in the water loss rate under drought conditions...
May 21, 2018: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29779709/a-mutation-in-transcription-factor-mafb-causes-focal-segmental-glomerulosclerosis-with-duane-retraction-syndrome
#19
Yoshinori Sato, Hiroyasu Tsukaguchi, Hiroyuki Morita, Koichiro Higasa, Mai Thi Nhu Tran, Michito Hamada, Toshiaki Usui, Naoki Morito, Shoichiro Horita, Takao Hayashi, Junko Takagi, Izumi Yamaguchi, Huan Thanh Nguyen, Masayo Harada, Kiyoko Inui, Yuichi Maruta, Yoshihiko Inoue, Fumihiko Koiwa, Hiroshi Sato, Fumihiko Matsuda, Shinya Ayabe, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Ashio Yoshimura
Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease in children and adults. Genetic factors significantly contribute to early-onset FSGS, but the etiologies of most adult cases remain unknown. Genetic studies of monogenic syndromic FSGS exhibiting extra-renal manifestations have uncovered an unexpected biological role for genes in the development of both podocytes and other cellular lineages. To help define these roles, we studied two unrelated families with FSGS associated with Duane Retraction Syndrome, characterized by impaired horizontal eye movement due to cranial nerve malformation...
May 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29779472/effect-of-body-weight-on-metabolic-hormones-and-fatty-acid-metabolism-in-follicular-fluid-of-women-undergoing-in-vitro-fertilization-a-pilot-study
#20
Laurice Bou Nemer, Haolin Shi, Bruce Richard Carr, Ruth Ann Word, Orhan Bukulmez
INTRODUCTION: Obesity is an epidemic affecting more than one-third of adults in the United States. Obese women experience decreased fertility, explained in part by oocyte quality. Since follicular fluid (FF) provides an important microenvironment for oocyte growth, we sought to evaluate the effect of increased body weight on FF levels of 11 metabolic hormones and fatty acid metabolism. METHODS: The FF was collected from 25 women (10 normal weight, 10 overweight, and 5 obese) with diminished ovarian reserve undergoing in vitro fertilization (IVF) following a minimal stimulation protocol...
January 1, 2018: Reproductive Sciences
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