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https://www.readbyqxmd.com/read/28814200/all-atom-molecular-dynamics-comparison-of-disease-associated-zinc-fingers
#1
Ryan C Godwin, William H Gmeiner, Freddie R Salsbury
An important regulatory domain of NEMO is a ubiquitin-binding zinc finger, with a tetrahedral CYS3HIS1 zinc-coordinating binding site. Two variations of NEMO's zinc finger are implicated in various disease states including ectodermal dysplasia and adult-onset glaucoma. To discern structural and dynamical differences between these disease states, we present results of 48-$\mu s$ of molecular dynamics simulations for three zinc finger systems each in two states, with and without zinc-bound and correspondingly appropriate cysteine thiol/thiolate configurations...
August 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28813403/quick-hits
#2
Leslie Nemo
No abstract text is available yet for this article.
August 15, 2017: Scientific American
https://www.readbyqxmd.com/read/28813374/change-of-heartbeat
#3
Leslie Nemo
No abstract text is available yet for this article.
August 15, 2017: Scientific American
https://www.readbyqxmd.com/read/28808806/brca1-mimetic-compound-nsc35446-hcl-inhibits-ikkb-expression-by-reducing-estrogen-receptor-%C3%AE-occupancy-in-the-ikkb-promoter-and-inhibits-nf-%C3%AE%C2%BAb-activity-in-antiestrogen-resistant-human-breast-cancer-cells
#4
Shyam Nathan, Yongxian Ma, York A Tomita, Eliseu De Oliveira, Milton L Brown, Eliot M Rosen
PURPOSE: We previously identified small molecules that fit into a BRCA1-binding pocket within estrogen receptor-alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity ("BRCA1-mimetics"), and overcome antiestrogen resistance. One such compound, the hydrochloride salt of NSC35446 ("NSC35446.HCl"), also inhibited the growth of antiestrogen-resistant LCC9 tumor xenografts. The purpose of this study was to investigate the down-stream effects of NSC35446.HCl and its mechanism of action...
August 14, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28803967/igdb-2-an-ig-fniii-protein-binds-the-ion-channel-lgc-34-and-controls-sensory-compartment-morphogenesis-in-c-elegans
#5
Wendy Wang, Elliot A Perens, Grigorios Oikonomou, Yun Lu, Shai Shaham
Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized compartment important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. We previously showed that DAF-6, a Patched-related protein, is required in glia of the C. elegans amphid sensory organ to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion. To further explore the machinery underlying compartment size control, we sought genes whose inactivation restores normal compartment size to daf-6 mutants...
August 10, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28799290/visualizing-correlated-motion-with-hdbscan-clustering
#6
Ryan L Melvin, Jiajie Xiao, Ryan C Godwin, Kenneth S Berenhaut, Freddie R Salsbury
Correlated motion analysis provides a method for understanding communication between and dynamic similarities of biopolymer residues and domains. The typical equal-time correlation matrices - frequently visualized with pseudo-colorings or heat maps - quickly convey large regions of highly correlated motion but hide more subtle similarities of motion. Here we propose a complementary method for visualizing correlations within proteins (or general biopolymers) that quickly conveys intuition about which residues have a similar dynamic behavior...
August 11, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28794079/unusual-father-to-daughter-transmission-of-incontinentia-pigmenti-due-to-mosaicism-in-ip-males
#7
Francesca Fusco, Matilde Immacolata Conte, Andrea Diociauti, Stefania Bigoni, Maria Francesca Branda, Alessandra Ferlini, Maya El Hachem, Matilde Valeria Ursini
Incontinentia pigmenti (IP; Online Mendelian Inheritance in Man catalog #308300) is an X-linked dominant ectodermal disorder caused by mutations of the inhibitor of κ polypeptide gene enchancer in B cells, kinase γ (IKBKG)/ nuclear factor κB, essential modulator (NEMO) gene. Hemizygous IKBKG/NEMO loss-of-function (LoF) mutations are lethal in males, thus patients are female, and the disease is always transmitted from an IP-affected mother to her daughter. We present 2 families with father-to-daughter transmission of IP and provide for the first time molecular evidence that the combination of somatic and germ-line mosaicism for IKBKG/NEMO loss of function mutations in IP males resulted in the transmission of the disease to a female child...
August 9, 2017: Pediatrics
https://www.readbyqxmd.com/read/28791733/incontinentia-pigmenti-in-a-male-xy-infant-with-long-term-follow-up-over-8-years
#8
Yasushi Matsuzaki, Akiko Rokunohe, Satoko Minakawa, Kazuo Nomura, Hajime Nakano, Etsuro Ito, Daisuke Sawamura
Incontinentia pigmenti (IP) is an X-linked genodermatosis affecting the skin and other sites, including the teeth, nails, hair, eyes and nervous system defects in female patients. Generally lethal in males, there are only a few known cases of males surviving this condition. Nuclear factor (NF)-κB essential modulator (NEMO), also known as inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG), constitutes an essential activator of NF-κB. Over 80% of female patients with IP carry a common deletion mutation involving exons 4-10 of the IKBKG/NEMO gene...
August 9, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28702714/immunodeficiency-in-two-female-patients-with-incontinentia-pigmenti-with-heterozygous-nemo-mutation-diagnosed-by-lps-unresponsiveness
#9
Hidenori Ohnishi, Yuka Kishimoto, Tomohide Taguchi, Norio Kawamoto, Mina Nakama, Tomoki Kawai, Manabu Nakayama, Osamu Ohara, Kenji Orii, Toshiyuki Fukao
PURPOSE: Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is caused by mutations in the NF-κB essential modulator (NEMO) or NF-κB inhibitor, alpha (IKBA) genes. A heterozygous NEMO mutation causes incontinentia pigmenti (IP) in females, while a hemizygous hypomorphic mutation of NEMO causes EDA-ID in males. In general, immunodeficiency is not shown in IP patients. Here, we investigated two female patients with IP and immunodeficiency. METHODS: The patients were initially suspected to have IRAK4 deficiency and Mendelian susceptibility to mycobacterial disease, respectively, because of recurrent pneumonia with delayed umbilical cord detachment or disseminated mycobacterial infectious disease...
July 12, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28679735/hematopoietic-stem-cell-transplantation-in-29-patients-hemizygous-for-hypomorphic-ikbkg-nemo-mutations
#10
Charline Miot, Kohsuke Imai, Chihaya Imai, Anthony J Mancini, Zeynep Yesim Kucuk, Tokomki Kawai, Ryuta Nishikomori, Etsuro Ito, Isabelle Pellier, Sophie Dupuis Girod, Jeremie Rosain, Shinya Sasaki, Shanmuganathan Chandrakasan, Jana Pachlopnik Schmid, Tsubasa Okano, Estelle Colin, Alberto Olaya-Vargas, Marco Yamazaki-Nakashimada, Waseem Qasim, Sara Espinosa Padilla, Andrea Jones, Alfons Krol, Nyree Cole, Stephen Jolles, Jack Bleesing, Thomas Vraetz, Andrew R Gennery, Mario Abinun, Tayfun Güngör, Beatriz Costa-Carvalho, Antonio Condino-Neto, Paul Veys, Steven M Holland, Gulbu Uzel, Despina Moshous, Benedicte Neven, Stéphane Blanche, Stephan Ehl, Rainer Döffinger, Smita Y Patel, Anne Puel, Jacinta Bustamante, Erwin W Gelfand, Jean-Laurent Casanova, Jordan S Orange, Capucine Picard
X-linked recessive ectodermal dysplasia (EDA) with immunodeficiency (XR-EDA-ID) is a rare primary immunodeficiency (PID) caused by hypomorphic mutations of the IKBKG gene encoding the NEMO protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and non-hematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests that it has been reserved for only the most severe cases...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28673044/ctenopharyngodon-idella-ikk%C3%AE-interacts-with-pkr-and-i%C3%AE%C2%BAb%C3%AE
#11
Haizhou Wang, Qun Xu, Xiaowen Xu, Yousheng Hu, Qunhao Hou, Youlin Zhu, Chengyu Hu
Inhibitor of nuclear factor kappa-B kinase β (IKKβ) is a subunit of the IKK complex. It can activate the NF-κB pathway through phosphorylating IκB in response to a wide range of stimuli. In the present study, an IKKβ gene from grass carp (Ctenopharyngodon idella; KT282114) was cloned and identified by homologous cloning and rapid-amplification of cDNA ends (RACE) technique. The complete CiIKKβ cDNA is 3428 bp in length, with the longest open reading frame (ORF) of 2337 bp encoding a polypeptide of 778 amino acids...
August 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28654673/double-hit-of-nemo-gene-in-preeclampsia
#12
Agata Sakowicz, Tadeusz Pietrucha, Magda Rybak-Krzyszkowska, Hubert Huras, Agnieszka Gach, Bartosz Sakowicz, Mateusz Banaszczyk, Mariusz Grzesiak, Lidia Biesiada
The precise etiology of preeclampsia is unknown. Family studies indicate that both genetic and environmental factors influence its development. One of these factors is NFkB, whose activation depends on NEMO (NFkB essential modulator. This is the first study to investigate the association between the existence of single nucleotide variant of the NEMO gene and the appearance of preeclampsia. A total of 151 women (72 preeclamptic women and 79 controls) and their children were examined. Sanger sequencing was performed to identify variants in the NEMO gene in the preeclamptic mothers...
2017: PloS One
https://www.readbyqxmd.com/read/28628231/gene-therapy-decreases-seizures-in-a-model-of-incontinentia-pigmenti
#13
Godwin K Dogbevia, Kathrin Töllner, Jakob Körbelin, Sonja Bröer, Dirk A Ridder, Hanna Grasshoff, Claudia Brandt, Jan Wenzel, Beate K Straub, Martin Trepel, Wolfgang Löscher, Markus Schwaninger
OBJECTIVE: Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. METHODS: In a mouse model of IP we administered a single intravenous dose of the AAV vector AAV-BR1-CAG-NEMO delivering the Nemo gene to the brain endothelium...
June 19, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28626608/c-kit-modifies-the-inflammatory-status-of-smooth-muscle-cells
#14
Lei Song, Laisel Martinez, Zachary M Zigmond, Diana R Hernandez, Roberta M Lassance-Soares, Guillermo Selman, Roberto I Vazquez-Padron
BACKGROUND: c-Kit is a receptor tyrosine kinase present in multiple cell types, including vascular smooth muscle cells (SMC). However, little is known about how c-Kit influences SMC biology and vascular pathogenesis. METHODS: High-throughput microarray assays and in silico pathway analysis were used to identify differentially expressed genes between primary c-Kit deficient (Kit(W/W-v)) and control (Kit(+/+)) SMC. Quantitative real-time RT-PCR and functional assays further confirmed the differences in gene expression and pro-inflammatory pathway regulation between both SMC populations...
2017: PeerJ
https://www.readbyqxmd.com/read/28623244/it-s-a-cod-finding-nemo-impacted-fishbone-in-the-emergency-department
#15
Aileen McCabe, Andrew Patton, Nigel Salter
A 23-year-old woman presented to the emergency department (ED) with a sensation of a 'fish bone' stuck in her throat after eating cod. On physical examination, while she reported an uncomfortable sensation in her throat, no airway compromise was evident. Clinical examination, including ear, nose and throat (ENT) and oropharyngeal assessment, was unremarkable. A linear opacity consistent with a fishbone was visualised on a soft tissue lateral neck X-ray anterior to the vertebral body of C4-6. One attempt to visualise the fishbone on direct laryngoscopy failed in the ED...
June 15, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28610600/the-cumulative-number-of-micro-haemorrhages-and-micro-thromboses-in-nailfold-videocapillaroscopy-is-a-good-indicator-of-disease-activity-in-systemic-sclerosis-a-validation-study-of-the-nemo-score
#16
Romina Andracco, Rosaria Irace, Eleonora Zaccara, Serena Vettori, Wanda Maglione, Antonella Riccardi, Francesca Pignataro, Roberta Ferrara, Domenico Sambataro, Gianluca Sambataro, Claudio Vitali, Gabriele Valentini, Nicoletta Del Papa
BACKGROUND: Some abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that the number of micro-haemorrhages and micro-thromboses (the so-called NEMO score) was the NVC feature more closely associated with DA. The present study was aimed at validating the NEMO score as a measure of DA in patients with SSc...
June 13, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28607106/ubash3a-mediates-risk-for-type-1-diabetes-through-inhibition-of-t-cell-receptor-induced-nf-%C3%AE%C2%BAb-signaling
#17
Yan Ge, Taylor K Paisie, Jeremy R B Newman, Lauren M McIntyre, Patrick Concannon
Although over 40 type 1 diabetes (T1D) risk loci have been mapped in humans, the causative genes and variants for T1D are largely unknown. Here, we investigated a candidate gene in the 21q22.3 risk locus-UBASH3A, which is primarily expressed in T cells where it is thought to play a largely redundant role. Genetic variants in UBASH3A have been shown to be associated with several autoimmune diseases in addition to T1D. However, the molecular mechanism underlying these genetic associations is unresolved. Our study reveals a previously unrecognized role of UBASH3A in human T cells: UBASH3A attenuates the NF-κB signal transduction upon T-cell receptor (TCR) stimulation by specifically suppressing the activation of the IκB kinase complex...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28572277/immunotherapies-in-neuromyelitis-optica-spectrum-disorder-efficacy-and-predictors-of-response
#18
MULTICENTER STUDY
Jan-Patrick Stellmann, Markus Krumbholz, Tim Friede, Anna Gahlen, Nadja Borisow, Katrin Fischer, Kerstin Hellwig, Florence Pache, Klemens Ruprecht, Joachim Havla, Tania Kümpfel, Orhan Aktas, Hans-Peter Hartung, Marius Ringelstein, Christian Geis, Christoph Kleinschnitz, Achim Berthele, Bernhard Hemmer, Klemens Angstwurm, Kim Lea Young, Simon Schuster, Martin Stangel, Florian Lauda, Hayrettin Tumani, Christoph Mayer, Lena Zeltner, Ulf Ziemann, Ralf Andreas Linker, Matthias Schwab, Martin Marziniak, Florian Then Bergh, Ulrich Hofstadt-van Oy, Oliver Neuhaus, Uwe Zettl, Jürgen Faiss, Brigitte Wildemann, Friedemann Paul, Sven Jarius, Corinna Trebst, Ingo Kleiter
OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes...
August 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28559054/continuous-monitoring-of-noise-levels-in-the-gulf-of-catania-ionian-sea-study-of-correlation-with-ship-traffic
#19
S Viola, R Grammauta, V Sciacca, G Bellia, L Beranzoli, G Buscaino, F Caruso, F Chierici, G Cuttone, A D'Amico, V De Luca, D Embriaco, P Favali, G Giovanetti, G Marinaro, S Mazzola, F Filiciotto, G Pavan, C Pellegrino, S Pulvirenti, F Simeone, F Speziale, G Riccobene
Acoustic noise levels were measured in the Gulf of Catania (Ionian Sea) from July 2012 to May 2013 by a low frequency (<1000Hz) hydrophone, installed on board the NEMO-SN1 multidisciplinary observatory. NEMO-SN1 is a cabled node of EMSO-ERIC, which was deployed at a water depth of 2100m, 25km off Catania. The study area is characterized by the proximity of mid-size harbors and shipping lanes. Measured noise levels were correlated with the passage of ships tracked with a dedicated AIS antenna. Noise power was measured in the frequency range between 10Hz and 1000Hz...
May 28, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28543390/the-effect-of-ebv-on-wif1-nlk-and-apc-gene-methylation-and-expression-in-gastric-carcinoma-and-nasopharyngeal-cancer
#20
Zhenzhen Zhao, Wen Liu, Jincheng Liu, Jiayi Wang, Bing Luo
Epstein-Barr virus (EBV) is an important DNA tumor virus that is associated with approximately 10% of gastric carcinomas and 99% of nasopharyngeal cancers (NPC). DNA methylation and microRNAs (miRNAs) are the most studied epigenetic mechanisms that can prompt disease susceptibility. This study aimed to detect the effect of EBV on Wnt inhibitory factor 1 (WIF1), Nemo-like kinase (NLK), and adenomatous polyposis coli (APC) gene methylation, and expression in gastric carcinoma and NPC. The WIF1, NLK, and APC gene mRNA expression levels were measured by real-time quantitative RT-PCR in four EBV-positive cell lines and four EBV-negative cell lines...
May 23, 2017: Journal of Medical Virology
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