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https://www.readbyqxmd.com/read/28087809/trim13-potentiates-tlr2-mediated-nf-%C3%AE%C2%BAb-activation-via-k29-linked-polyubiquitination-of-traf6
#1
Bin Huang, Suk-Hwan Baek
Ubiquitination is a versatile post-translational modification involved in NF-κB activation of TLR signaling. Here, we demonstrated that Trim13, an E3 ubiquitin ligase, is up-regulated in macrophages upon stimulation with TLR2 ligand. Knock-down of Trim13 attenuated TLR2-mediated production of cytokines/chemokines and formation of foam cells, as well as activation of NF-κB. Trim13 interacts with TRAF6 and potentiates NF-κB activity via ubiquitination of TRAF6. Overexpression of inactive mutant (C10/13A) or RING deletion mutant of Trim13 did not potentiate ubiquitination of TRAF6 or activation of NF-κB...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087765/synapsin-ii-regulation-of-gabaergic-synaptic-transmission-is-dependent-on-interneuron-subtype
#2
Pedro Feliciano, Heidi Matos, Rodrigo Andrade, Maria Bykhovskaia
: Synapsins are epilepsy susceptibility genes that encode phosphoproteins reversibly associated with synaptic vesicles. Synapsin II (SynII) gene deletion produces a deficit in inhibitory synaptic transmission, and this defect is thought to cause epileptic activity. We systematically investigated how SynII affects synchronous and asynchronous release components of inhibitory transmission in the CA1 region of the mouse hippocampus. We found that the asynchronous GABAergic release component is diminished in SynII deleted (SynII(-)) slices...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28087729/phosphatase-and-tensin-homolog-deleted-on-chromosome-10-pten-and-ph-domain-and-leucine-rich-repeat-phosphatase-cross-talk-phlpp-in-cancer-cells-and-in-transforming-growth-factor-%C3%AE-activated-stem-cells
#3
Aram Ghalali, Zhi-Wei Ye, Johan Högberg, Ulla Stenius
No abstract text is available yet for this article.
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087726/benefit-of-mineralocorticoid-receptor-antagonism-in-aki-role-of-vascular-smooth-muscle-rac1
#4
Jonatan Barrera-Chimal, Gwennan André-Grégoire, Aurelie Nguyen Dinh Cat, Sebastian M Lechner, Jérôme Cau, Sonia Prince, Peter Kolkhof, Gervaise Loirand, Vincent Sauzeau, Thierry Hauet, Frédéric Jaisser
AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury...
January 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#5
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087711/ctcf-mediated-topological-boundaries-during-development-foster-appropriate-gene-regulation
#6
Varun Narendra, Milica Bulajić, Job Dekker, Esteban O Mazzoni, Danny Reinberg
The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087698/inhibition-of-trpml1-by-lysosomal-adenosine-involved-in-severe-combined-immunodeficiency-diseases
#7
Xi Zoë Zhong, Yuanjie Zou, Xue Sun, Gaofeng Dong, Qi Cao, Aditya Pandey, Jan K Rainey, Xiaojuan Zhu, Xian-Ping Dong
Impaired adenosine homeostasis has been associated with numerous human diseases. Lysosomes are referred to as the cellular recycling centers which generate adenosine by breaking down nucleic acids or ATP. Recent studies have suggested that lysosomal adenosine overload causes lysosome defects which phenocopy patients with mutations in TRPML1, a lysosomal Ca2+ channel, suggesting that lysosomal adenosine overload may impair TRPML1 and then lead to subsequent lysosomal dysfunction. In this study, we demonstrate that lysosomal adenosine is elevated by deleting adenosine deaminase (ADA), an enzyme responsible for adenosine degradation...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087685/bst-2-restricts-iav-release-and-is-countered-by-the-viral-m2-protein
#8
Siqi Hu, Lijuan Yin, Shan Mei, Jian Li, Fengwen Xu, Hong Sun, Xiaoman Liu, Shan Cen, Chen Liang, Ailing Li, Fei Guo
BST-2 (tetherin, CD317, HM1.24) is induced by interferon and restricts virus release by tethering the enveloped viruses to the cell surface. The effect of BST-2 on influenza A virus (IAV) infection has been inconclusive. In this study, we report that BST-2 diminishes the production of IAV virus-like particles, that are generated by viral NA and HA proteins, to a much greater degree than inhibits the production of wild type IAV particles. This relatively weaker inhibition of IAV is associated with reduction of BST-2 levels, which is caused by the M2 protein that interacts with BST-2 and leads to downregulation of cell surface BST-2 via the proteasomal pathway...
January 13, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28087672/elimination-of-sucrose-transport-and-hydrolysis-in-saccharomyces-cerevisiae-a-platform-strain-for-engineering-sucrose-metabolism
#9
Wesley Leoricy Marques, Robert Mans, Eko Roy Marella, Rosa Lorizolla Cordeiro, Marcel van den Broek, Jean-Marc G Daran, Jack T Pronk, Andreas K Gombert, Antonius J A van Maris
Many relevant options to improve efficacy and kinetics of sucrose metabolism in Saccharomyces cerevisiae and, thereby, the economics of sucrose-based processes, remain to be investigated. An essential first step is to identify all native sucrose-hydrolysing enzymes and sucrose transporters in this yeast, including those that can be activated by suppressor mutations in sucrose-negative strains. A strain in which all known sucrose-transporter genes (MAL11, MAL21, MAL31, MPH2, MPH3) were deleted did not grow on sucrose after 2 months of incubation...
January 12, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28087643/tumor-brca1-reversion-mutation-arising-during-neoadjuvant-platinum-based-chemotherapy-in-triple-negative-breast-cancer-is-associated-with-therapy-resistance
#10
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth A Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
BACKGROUND: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy. METHODS: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80)...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087621/the-hook-region-of-voltage-gated-ca2-channel-%C3%AE-subunits-senses-and-transmits-pip2-signals-to-the-gate
#11
Cheon-Gyu Park, Yongsoo Park, Byung-Chang Suh
The β subunit of voltage-gated Ca(2+) (CaV) channels plays an important role in regulating gating of the α1 pore-forming subunit and its regulation by phosphatidylinositol 4,5-bisphosphate (PIP2). Subcellular localization of the CaV β subunit is critical for this effect; N-terminal-dependent membrane targeting of the β subunit slows inactivation and decreases PIP2 sensitivity. Here, we provide evidence that the HOOK region of the β subunit plays an important role in the regulation of CaV biophysics. Based on amino acid composition, we broadly divide the HOOK region into three domains: S (polyserine), A (polyacidic), and B (polybasic)...
January 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28087536/the-regulator-of-type-iv-pili-synthesis-pilr-from-lysobacter-controls-antifungal-antibiotic-production-via-a-c-di-gmp-pathway
#12
Yuan Chen, Jing Xia, Zhenhe Su, Gaoge Xu, Mark Gomelsky, Guoliang Qian, Fengquan Liu
Lysobacter enzymogenes is a ubiquitous soil gammaproteobacterium that produces a broad-spectrum antifungal antibiotic, known as Heat-Stable Antifungal Factor (HSAF). To increase HSAF production for the use against fungal crop diseases, it is important to understand how HSAF synthesis is regulated. To gain insights into transcriptional regulation of the HSAF synthesis gene cluster, we generated a library of deletion mutants in the genes predicted to encode response regulators of the two-component signaling systems in L...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28087391/clonal-cytogenetic-abnormalities-are-predictor-in-developing-non-hodgkin-lymphomas
#13
Ying Wang, Yi Xiao, Xiangyu Meng, Heng Zhang, Qinlu Li, Fankai Meng, Lifang Huang, Chunrui Li, Jianfeng Zhou
Pathological analysis is the cornerstone for diagnosing malignant lymphoma. Status of cytogenetic abnormalities is frequently left unexamined if no evidence of malignancy is found in pathological analysis. In this study, we presented 3 cases in which clonal cytogenetic abnormalities were detected but morphological alterations of the same tissue did not support malignant non Hodgkin lymphoma at the first lymph node biopsy. Case 1 is a 55-year-old female with lymphadenopathy neoplastic process confirmed by flow cytometry and polymerase chain reaction (PCR)...
January 10, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28087245/the-severe-clinical-phenotype-for-a-heterozygous-fabry-female-patient-correlates-to-the-methylation-of-non-mutated-allele-associated-with-chromosome-10q26-deletion-syndrome
#14
Mohammad Arif Hossain, Hiroko Yanagisawa, Takashi Miyajima, Chen Wu, Ayumi Takamura, Keiko Akiyama, Rina Itagaki, Kaoru Eto, Takeo Iwamoto, Takayuki Yokoi, Kenji Kurosawa, Hironao Numabe, Yoshikatsu Eto
Heterozygous Fabry females usually have an attenuated form of Fabry disease, causing them to be symptomatic; however, in rare cases, they can present with a severe phenotype. In this study, we report on a 37-year-old woman with acroparesthesia, a dysmorphic face, left ventricular hypertrophy, and intellectual disability. Her father had Fabry disease and died due to chronic renal and congestive cardiac failure. Her paternal uncle had chronic renal failure and intellectual disability, and her paternal aunt was affected with congestive cardiac failure...
January 7, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28087155/population-genetic-data-of-38-insertion-deletion-markers-in-six-populations-of-the-northern-fringe-of-the-iberian-peninsula
#15
Sergio Cardoso, Rubén Sevillano, David Gamarra, Ana Santurtún, Begoña Martínez-Jarreta, Marian M de Pancorbo
Insertion-deletions have been reported very useful markers for forensic purposes. To further deepen in this matter, 38 non-coding bi-allelic autosomal indels were analyzed in 575 individuals representing six populations from the northern fringe of the Iberian Peninsula. Autochthonous populations from the Basque Country, northern Navarre, the Pas Valley in Cantabria and Aragon were analyzed, together with non-autochthonous populations from the Basque Country and northern Navarre. At the intra-population level, all loci analyzed were in Hardy-Weinberg equilibrium except for marker rs33917182 in autochthonous Basques...
January 3, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28087047/rational-design-of-low-immunogenic-anti-cd25-recombinant-immunotoxin-for-t-cell-malignancies-by-elimination-of-t-cell-epitopes-in-pe38
#16
Ronit Mazor, Gilad Kaplan, Dong Park, Youjin Jang, Fred Lee, Robert Kreitman, Ira Pastan
LMB-2, is a potent recombinant immunotoxin (RIT) that is composed of scFv antibody that targets CD25 (Tac) and a toxin fragment (PE38). It is used to treat T cell leukemias and lymphomas. To make LMB-2 less immunogenic, we introduced a large deletion in domain II and six point mutations in domain III that were previously shown to reduce T cell activation in other RITs. We found that unlike other RITs, deletion of domain II from LMB-2 severely compromised its activity. Rather than deletion, we identified T cell epitopes in domain II and used alanine substitutions to identify point mutations that diminished those epitopes...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28087006/new-insights-into-the-pathogenesis-and-treatment-of-heavy-chain-deposition-disease
#17
Jonathan J Hogan, Glen S Markowitz
Heavy chain deposition disease is defined by the presence of tissue deposits of truncated monoclonal Ig heavy chains, usually associated with an underlying plasma cell clone. In this issue of Kidney International, Bridoux et al. described the clinical, histologic, and molecular characterization of 15 patients with heavy chain deposition disease, which is the largest case series to date. Notable findings included the frequent presence of C3 deposits and hypocomplementemia, the uniform finding of truncated heavy chains with the deletion in the heavy chain constant region 1, and the common occurrence of an abnormal serum-free κ:λ ratio, despite the absence of light-chain tissue deposition...
February 2017: Kidney International
https://www.readbyqxmd.com/read/28086908/hiv-integration-sites-in-latently-infected-cell-lines-evidence-of-ongoing-replication
#18
Jori Symons, Abha Chopra, Eva Malantinkova, Ward De Spiegelaere, Shay Leary, Don Cooper, Chike O Abana, Ajantha Rhodes, Simin D Rezaei, Linos Vandekerckhove, Simon Mallal, Sharon R Lewin, Paul U Cameron
BACKGROUND: Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. RESULTS: We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines...
January 13, 2017: Retrovirology
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#19
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28086794/characterization-of-the-sdw1-semi-dwarf-gene-in-barley
#20
Yanhao Xu, Qiaojun Jia, Gaofeng Zhou, Xiao-Qi Zhang, Tefera Angessa, Sue Broughton, George Yan, Wenying Zhang, Chengdao Li
BACKGROUND: The dwarfing gene sdw1 has been widely used throughout the world to develop commercial barley varieties. There are at least four different alleles at the sdw1 locus. RESULTS: Mutations in the gibberellin 20-oxidase gene (HvGA20ox2) resulted in multiple alleles at the sdw1 locus. The sdw1.d allele from Diamant is due to a 7-bp deletion in exon 1, while the sdw1.c allele from Abed Denso has 1-bp deletion and a 4-bp insertion in the 5' untranslated region...
January 13, 2017: BMC Plant Biology
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