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https://www.readbyqxmd.com/read/28448599/simulation-of-the-dynamics-of-primary-immunodeficiencies-in-cd4-t-cells
#1
Gabriel N Teku, Mauno Vihinen
Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes...
2017: PloS One
https://www.readbyqxmd.com/read/28445980/the-pp4r1-sub-unit-of-protein-phosphatase-pp4-is-essential-for-inhibition-of-nf-%C3%AE%C2%BAb-by-merkel-polyomavirus-small-tumour-antigen
#2
Hussein Abdul-Sada, Marietta Müller, Rajni Mehta, Rachel Toth, J Simon C Arthur, Adrian Whitehouse, Andrew Macdonald
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418896/nfkb-is-essential-for-activin-induced-colorectal-cancer-migration-via-upregulation-of-pi3k-mdm2-pathway
#3
Arundhati Jana, Nancy L Krett, Grace Guzman, Ahmer Khalid, Ozkan Ozden, Jonas J Staudacher, Jessica Bauer, Seung Hyun Baik, Timothy Carroll, Cemal Yazici, Barbara Jung
Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402272/ginkgolic-acids-inhibit-migration-in-breast-cancer-cells-by-inhibition-of-nemo-sumoylation-and-nf-%C3%AE%C2%BAb-activity
#4
Sami Hamdoun, Thomas Efferth
Ginkgolic acids (GA), a group of alkyl phenols found in crude extracts of Ginkgo biloba leaves, are known to have anticancer activity, but their mode of action is not well understood. Our aim in this study was to investigate the anti-migratory activity of seven GA against breast cancer cells and to determine the molecular mechanism behind this activity. All seven GA and their mixture inhibited wound healing in MCF-7 and MDA-MB 231 breast cancer cells. None of the compounds nor the mixture showed cytotoxicity towards the two cell lines, if tested by the resazurin assay...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398225/a-low-cost-environmental-monitoring-system-how-to-prevent-systematic-errors-in-the-design-phase-through-the-combined-use-of-additive-manufacturing-and-thermographic-techniques
#5
Francesco Salamone, Ludovico Danza, Italo Meroni, Maria Cristina Pollastro
nEMoS (nano Environmental Monitoring System) is a 3D-printed device built following the Do-It-Yourself (DIY) approach. It can be connected to the web and it can be used to assess indoor environmental quality (IEQ). It is built using some low-cost sensors connected to an Arduino microcontroller board. The device is assembled in a small-sized case and both thermohygrometric sensors used to measure the air temperature and relative humidity, and the globe thermometer used to measure the radiant temperature, can be subject to thermal effects due to overheating of some nearby components...
April 11, 2017: Sensors
https://www.readbyqxmd.com/read/28392573/inducible-rubicon-facilitates-viral-replication-by-antagonizing-interferon-production
#6
Yushun Wan, Wei Cao, Tao Han, Sheng Ren, Jian Feng, TieLong Chen, Jun Wang, Ruth Broering, Mengji Lu, Ying Zhu
The RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon) protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner, but little is known regarding the role of Rubicon during viral infection. Here, we performed functional studies of the identified target in interferon (IFN) signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN. The Rubicon protein levels were elevated in peripheral blood mononuclear cells, sera and liver tissues from patients with hepatitis B virus (HBV) infection relative to those in healthy individuals...
April 10, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28366702/finding-nemo-nerve-sparing-midurethral-obstruction-a-pathophysiologically-accurate-model-of-rodent-partial-bladder-outlet-obstruction
#7
Martin Sidler, Karen Aitken, Janet Jiang, Dominika Bijos, Jaques Belik, Darius J Bägli
OBJECTIVE: To develop and evaluate a novel technique modeling partial bladder outlet obstruction (pBOO) using a Nerve-sparing Mid-urethral Obstruction (NeMO) approach. MATERIALS AND METHODS: Female unoperated rats were compared to rats after NeMO, NeMO-sham, proximal urethral obstruction (PU), or PU-sham. Residual volume, bladder capacity, voiding volume, and bladder mass were recorded; contractile characteristics of isolated bladder strips were also analyzed. Additionally, we quantitated nerve fibers at the bladder neck as well as extracellular matrix in the bladder wall...
March 30, 2017: Urology
https://www.readbyqxmd.com/read/28355270/the-nf-%C3%AE%C2%BAb-dependent-and-independent-transcriptome-and-chromatin-landscapes-of-human-coronavirus-229e-infected-cells
#8
Michael Poppe, Sascha Wittig, Liane Jurida, Marek Bartkuhn, Jochen Wilhelm, Helmut Müller, Knut Beuerlein, Nadja Karl, Sabin Bhuju, John Ziebuhr, M Lienhard Schmitz, Michael Kracht
Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKβ, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28332561/inertial-bioluminescence-rhythms-at-the-capo-passero-km3net-italia-site-central-mediterranean-sea
#9
J Aguzzi, E Fanelli, T Ciuffardi, A Schirone, J Craig
In the deep sea, the sense of time is dependent on geophysical fluctuations, such as internal tides and atmospheric-related inertial currents, rather than day-night rhythms. Deep-sea neutrino telescopes instrumented with light detecting Photo-Multiplier Tubes (PMT) can be used to describe the synchronization of bioluminescent activity of abyssopelagic organisms with hydrodynamic cycles. PMT readings at 8 different depths (from 3069 to 3349 m) of the NEMO Phase 2 prototype, deployed offshore Capo Passero (Sicily) at the KM3NeT-Italia site, were used to characterize rhythmic bioluminescence patterns in June 2013, in response to water mass movements...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317324/big-in-the-benthos-future-change-of-seafloor-community-biomass-in-a-global-body-size-resolved-model
#10
Andrew Yool, Adrian P Martin, Thomas R Anderson, Brian J Bett, Daniel O B Jones, Henry A Ruhl
Deep-water benthic communities in the ocean are almost wholly dependent on near-surface pelagic ecosystems for their supply of energy and material resources. Primary production in sunlit surface waters is channelled through complex food webs that extensively recycle organic material, but lose a fraction as particulate organic carbon (POC) that sinks into the ocean interior. This exported production is further rarefied by microbial breakdown in the abyssal ocean, but a residual ultimately drives diverse assemblages of seafloor heterotrophs...
March 19, 2017: Global Change Biology
https://www.readbyqxmd.com/read/28287961/expression-invariant-age-estimation-using-structured-learning
#11
Zhongyu Lou, Fares Alnajar, Jose Alvarez, Ninghang Hu, Theo Gevers
In this paper, we investigate and exploit the influence of facial expressions on automatic age estimation. Different from existing approaches, our method jointly learns the age and expression by introducing a new graphical model with a latent layer between the age/expression labels and the features. This layer aims to learn the relationship between the age and expression and captures the face changes which induce the aging and expression appearance, and thus obtaining expression-invariant age estimation. Conducted on three age-expression datasets (FACES [8], Lifespan [20] and NEMO [7]), our experiments illustrate the improvement in performance when the age is jointly learnt with expression in comparison to expression-independent age estimation...
March 8, 2017: IEEE Transactions on Pattern Analysis and Machine Intelligence
https://www.readbyqxmd.com/read/28284557/binimetinib-versus-dacarbazine-in-patients-with-advanced-nras-mutant-melanoma-nemo-a-multicentre-open-label-randomised-phase-3-trial
#12
Reinhard Dummer, Dirk Schadendorf, Paolo A Ascierto, Ana Arance, Caroline Dutriaux, Anna Maria Di Giacomo, Piotr Rutkowski, Michele Del Vecchio, Ralf Gutzmer, Mario Mandala, Luc Thomas, Lev Demidov, Claus Garbe, David Hogg, Gabriella Liszkay, Paola Queirolo, Ernesto Wasserman, James Ford, Marine Weill, L Andres Sirulnik, Valentine Jehl, Viviana Bozón, Georgina V Long, Keith Flaherty
BACKGROUND: There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma. METHODS: NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m(2) intravenously every 3 weeks...
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28250121/porcine-deltacoronavirus-nsp5-antagonizes-type-i-interferon-signaling-by-cleaving-stat2
#13
Xinyu Zhu, Dang Wang, Junwei Zhou, Ting Pan, Jiyao Chen, Yuting Yang, Mengting Lv, Xu Ye, Guiqing Peng, Liurong Fang, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The first outbreak of PDCoV was announced from the United States in 2014, followed by reports in Asia. The nonstructural protein nsp5 is a 3C-like protease of coronavirus and our previous study showed that PDCoV nsp5 inhibits type I interferon (IFN) production. In this study, we found that PDCoV nsp5 significantly inhibited IFN-stimulated response element (ISRE) promoter activity and transcription of IFN-stimulated genes (ISGs), suggesting that PDCoV nsp5 also suppresses IFN signaling...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28249776/lack-of-interaction-between-between-nemo-and-sharpin-impairs-linear-ubiquitination-and-nf-%C3%AE%C2%BAb-activation-and-leads-to-incontinentia-pigmenti
#14
E Bal, E Laplantine, Y Hamel, V Dubosclard, B Boisson, A Pesacatore, C Picard, S Hadj-Rabia, G Royer, J Steffann, J P Bonnefont, V M Ursini, P Vabres, A Munnich, J L Casanova, C Bodemer, R Weil, F Agou, A Smahi
BACKGROUND: Incontinentia pigmenti (IP; MIM308300) is a severe, male-lethal, X-linked, dominant genodermatosis resulting from loss-of-function mutations in the IKBKG gene encoding NF-κB essential modulator (NEMO, the regulatory subunit of the IKK complex). In 80% of cases of IP, the deletion of exons 4 to 10 leads to the absence of NEMO and total inhibition of NF-κB signaling. Here, we described a new IKBKG mutation responsible for IP resulting in an inactive truncated form of NEMO...
February 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28244869/yod1-traf6-association-balances-p62-dependent-il-1-signaling-to-nf-%C3%AE%C2%BAb
#15
Gisela Schimmack, Kenji Schorpp, Kerstin Kutzner, Torben Gehring, Jara Kerstin Brenke, Kamyar Hadian, Daniel Krappmann
The ubiquitin ligase TRAF6 is a key regulator of canonical IκB kinase (IKK)/NF-κB signaling in response to interleukin-1 (IL-1) stimulation. Here, we identified the deubiquitinating enzyme YOD1 (OTUD2) as a novel interactor of TRAF6 in human cells. YOD1 binds to the C-terminal TRAF homology domain of TRAF6 that also serves as the interaction surface for the adaptor p62/Sequestosome-1, which is required for IL-1 signaling to NF-κB. We show that YOD1 competes with p62 for TRAF6 association and abolishes the sequestration of TRAF6 to cytosolic p62 aggregates by a non-catalytic mechanism...
February 28, 2017: ELife
https://www.readbyqxmd.com/read/28221979/influence-of-transportation-conditions-and-postharvest-disinfection-treatments-on-microbiological-quality-of-fresh-market-tomatoes-cv-nemo-netta-in-a-south-african-supply-chain
#16
M S Sibomana, L W Ziena, S Schmidt, T S Workneh
Postharvest microbial spoilage due to suboptimal transportation and packaging conditions is a key concern for the South African tomato industry. This study investigated the influence of washing with tap water or aqueous disinfectant solutions (chlorinated and anolyte water) on the microbiological quality of tomatoes during storage after transportation in nonrefrigerated trucks along two supply routes when packaged in crates and boxes. Route 1 was 1,093 km from field to storage site, while route 2 was 1,057 km...
February 2017: Journal of Food Protection
https://www.readbyqxmd.com/read/28202068/the-dna-damage-response-promotes-polyomavirus-jc-infection-by-nucleus-to-cytoplasm-nf-kappab-activation
#17
Martyn K White, Anna Bellizzi, Gabriele Ibba, Valeria Pietropaolo, Anna T Palamara, Hassen S Wollebo
BACKGROUND: Infection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28192730/inducible-turnover-of-optineurin-regulates-t-cell-activation
#18
Angela Montecalvo, Simon C Watkins, Jordan Orange, Lawrence P Kane
Optineurin (Optn) is an adaptor protein with homology to NF-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase (IKK) complex. Dysregulation of Optn has been linked to neurodegenerative, autoimmune and bone diseases. Optn shares a high degree of homology with NEMO, but is not part of the same high-molecular weight complex containing IKKα and IKKβ. Despite its homology with NEMO and the fact that it has been the subject of extensive study in several cell types, there are no published studies addressing the role of Optn during T cell activation...
May 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#19
Seung-Ju Cho, Bok-Sik Cha, Ok-Seon Kwon, Jisun Lim, Dong-Myung Shin, Dong Wook Han, Tohru Ishitani, Eek-Hoon Jho, Albert J Fornace, Hyuk-Jin Cha
Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), enhancing its interaction with β-catenin...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28181378/sacral-nerve-stimulation-can-alleviate-symptoms-of-bowel-dysfunction-after-colorectal-resections
#20
Diane Mege, Guillaume Meurette, Veronique Vitton, Anne-Marie Leroi, Valerie Bridoux, Philippe Zerbib, Igor Sielezneff
BACKGROUND: Poor functional results, such as faecal incontinence (FI), low anterior resection syndrome (LARS) or high stool frequency can occur after colorectal resections; including proctocolectomy with ileal pouch-anal anastomosis (IPAA), rectal resection and left hemicolectomy. Management of these patients is an issue, and some case-reports have demonstrated the effectiveness of sacral nerve stimulation (SNS) in such situations. OUR AIM: was to analyse the effectiveness of SNS on poor functional results and on the quality of life, after different colorectal resections...
February 9, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
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