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Bisphosphates IV

Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
December 2018: Redox Report: Communications in Free Radical Research
Ding Li, Tuong Thi Mai Luong, Wen-Jia Dan, Yanliang Ren, Hoang Xuan Nien, An-Ling Zhang, Jin-Ming Gao
Several recently identified antifungal compounds share the backbone structure of acetophenones. The aim of the present study was to develop new isobutyrophenone analogs as new antifungal agents. A series of new 2,4-dihydroxy-5-methyl isobutyrophenone derivatives were prepared and characterized by1 H,13 C NMR and MS spectroscopic data. These products were evaluated for in vitro antifungal activities against seven plant fungal pathogens by the mycelial growth inhibitory rate assay. Compounds 3, 4a, 5a, 5b, 5e, 5f and 5g showed a broad-spectrum high antifungal activity...
January 15, 2018: Bioorganic & Medicinal Chemistry
Thomas Effertz, Lars Becker, Anthony W Peng, Anthony J Ricci
Membrane proteins, such as ion channels, interact dynamically with their lipid environment. Phosphoinositol-4,5-bisphosphate (PIP2 ) can directly or indirectly modify ion-channel properties. In auditory sensory hair cells of rats (Sprague Dawley) of either sex, PIP2 localizes within stereocilia, near stereocilia tips. Modulating the amount of free PIP2 in inner hair-cell stereocilia resulted in the following: (1) the loss of a fast component of mechanoelectric-transduction current adaptation, (2) an increase in the number of channels open at the hair bundle's resting position, (3) a reduction of single-channel conductance, (4) a change in ion selectivity, and (5) a reduction in calcium pore blocking effects...
November 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Qingfeng Chen, Ji She, Weizhong Zeng, Jiangtao Guo, Haoxing Xu, Xiao-Chen Bai, Youxing Jiang
Transient receptor potential mucolipin 1 (TRPML1) is a cation channel located within endosomal and lysosomal membranes. Ubiquitously expressed in mammalian cells, its loss-of-function mutations are the direct cause of type IV mucolipidosis, an autosomal recessive lysosomal storage disease. Here we present the single-particle electron cryo-microscopy structure of the mouse TRPML1 channel embedded in nanodiscs. Combined with mutagenesis analysis, the TRPML1 structure reveals that phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2 ) binds to the N terminus of the channel-distal from the pore-and the helix-turn-helix extension between segments S2 and S3 probably couples ligand binding to pore opening...
October 19, 2017: Nature
Marscha Hirschi, Mark A Herzik, Jinhong Wie, Yang Suo, William F Borschel, Dejian Ren, Gabriel C Lander, Seok-Yong Lee
The modulation of ion channel activity by lipids is increasingly recognized as a fundamental component of cellular signalling. The transient receptor potential mucolipin (TRPML) channel family belongs to the TRP superfamily and is composed of three members: TRPML1-TRPML3. TRPMLs are the major Ca2+ -permeable channels on late endosomes and lysosomes (LEL). They regulate the release of Ca2+ from organelles, which is important for various physiological processes, including organelle trafficking and fusion. Loss-of-function mutations in the MCOLN1 gene, which encodes TRPML1, cause the neurodegenerative lysosomal storage disorder mucolipidosis type IV, and a gain-of-function mutation (Ala419Pro) in TRPML3 gives rise to the varitint-waddler (Va) mouse phenotype...
October 19, 2017: Nature
Stephanie Zimmermann, Lennart Pfannkuch, Munir A Al-Zeer, Sina Bartfeld, Manuel Koch, Jianping Liu, Cindy Rechner, Meike Soerensen, Olga Sokolova, Alla Zamyatina, Paul Kosma, André P Mäurer, Frithjof Glowinski, Klaus-Peter Pleissner, Monika Schmid, Volker Brinkmann, Alexander Karlas, Michael Naumann, Marion Rother, Nikolaus Machuy, Thomas F Meyer
Activation of transcription factor NF-κB is a hallmark of infection with the gastric pathogen Helicobacter pylori, associated with inflammation and carcinogenesis. Genome-wide RNAi screening revealed numerous host factors involved in H. pylori-, but not IL-1β- and TNF-α-dependent NF-κB regulation. Pathway analysis including CRISPR/Cas9-knockout and recombinant protein technology, immunofluorescence microscopy, immunoblotting, mass spectrometry, and mutant H. pylori strains identified the H. pylori metabolite D-glycero-β-D-manno-heptose 1,7-bisphosphate (βHBP) as a cagPAI type IV secretion system (T4SS)-dependent effector of NF-κB activation in infected cells...
September 5, 2017: Cell Reports
Saskia C Stein, Eugenia Faber, Simon H Bats, Tatiana Murillo, Yvonne Speidel, Nina Coombs, Christine Josenhans
Highly virulent Helicobacter pylori cause proinflammatory signaling inducing the transcriptional activation and secretion of cytokines such as IL-8 in epithelial cells. Responsible in part for this signaling is the cag pathogenicity island (cagPAI) that codetermines the risk for pathological sequelae of an H. pylori infection such as gastric cancer. The Cag type IV secretion system (CagT4SS), encoded on the cagPAI, can translocate various molecules into cells, the effector protein CagA, peptidoglycan metabolites and DNA...
July 2017: PLoS Pathogens
Yan Yan, Ting-Hai Xu, Karsten Melcher, H Eric Xu
γ-Secretase is an intramembrane aspartyl protease that cleaves the C99 fragment of amyloid precursor protein to generate extracellular Aβ peptides. These peptides can oligomerize and aggregate to form amyloid plaques, processes that are widely believed to be causal for Alzheimer's disease. In spite of this critical function, it remains unknown how γ-secretase recognizes C99 and its other substrates, including Notch. In this study we determined E22-K55 as the minimal C99 fragment that was sufficient and required for initial cleavage...
October 2017: Acta Pharmacologica Sinica
Jennifer M Baker, Carli J Riester, Blair M Skinner, Austin W Newell, Wesley D Swingley, Michael T Madigan, Deborah O Jung, Marie Asao, Min Chen, Patrick C Loughlin, Hao Pan, Yuankui Lin, Yaqiong Li, Jacob Shaw, Mindy Prado, Chris Sherman, Joseph Kuo-Hsiang Tang, Robert E Blankenship, Tingting Zhao, Jeffrey W Touchman, W Matthew Sattley
Rhodoferax antarcticus is an Antarctic purple nonsulfur bacterium and the only characterized anoxygenic phototroph that grows best below 20 °C. We present here a high-quality draft genome of Rfx. antarcticus strain ANT.BR(T), isolated from an Antarctic microbial mat. The circular chromosome (3.8 Mbp) of Rfx. antarcticus has a 59.1% guanine + cytosine (GC) content and contains 4036 open reading frames. In addition, the bacterium contains a sizable plasmid (198.6 kbp, 48.4% GC with 226 open reading frames) that comprises about 5% of the total genetic content...
February 21, 2017: Microorganisms
Andrea Mafficini, Eliana Amato, Ivana Cataldo, Borislav C Rusev, Luca Bertoncello, Vincenzo Corbo, Michele Simbolo, Claudio Luchini, Matteo Fassan, Cinzia Cantù, Roberto Salvia, Giovanni Marchegiani, Giampaolo Tortora, Rita T Lawlor, Claudio Bassi, Aldo Scarpa
OBJECTIVE: To identify molecular prognostic factors and potentially actionable mutations in ampulla of Vater cancer (AVC). BACKGROUND: The largely variable outcomes of AVCs make clinical decisions difficult regarding the need of postsurgical therapy, which is based on morphological and immunohistochemical classification that do not adequately consider the varying degrees of heterogeneity present in many AVCs. No approved targeted therapies for AVC exist, but some show promising results requiring better molecular characterization to identify potential responders...
January 2018: Annals of Surgery
Jingga Inlora, Vineela Chukkapalli, Sukhmani Bedi, Akira Ono
UNLABELLED: The subcellular sites of HIV-1 assembly, determined by the localization of the structural protein Gag, vary in a cell-type-dependent manner. In T cells and transformed cell lines used as model systems, HIV-1 assembles at the plasma membrane (PM). The binding and localization of HIV-1 Gag to the PM are mediated by the interaction between the matrix (MA) domain, specifically the highly basic region, and a PM-specific acidic phospholipid, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]...
October 1, 2016: Journal of Virology
Denise A Yardley, Patrick J Ward, Brooke R Daniel, Janice F Eakle, Ruth E Lamar, Cassie M Lane, John D Hainsworth
BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype with poor prognosis, and treatment options are limited to chemotherapy. Because the epidermal growth factor receptor (EGFR) is overexpressed in up to 70% of these tumors, this phase II trial was designed to evaluate the efficacy and safety of panitumumab in combination with gemcitabine and carboplatin as first- or second-line treatment for metastatic TNBC. PATIENTS AND METHODS: Adult women with metastatic TNBC with a maximum of 1 previous chemotherapy regimen were eligible...
October 2016: Clinical Breast Cancer
Liubov A Dadinova, Eleonora V Shtykova, Petr V Konarev, Elena V Rodina, Natalia E Snalina, Natalia N Vorobyeva, Svetlana A Kurilova, Tatyana I Nazarova, Cy M Jeffries, Dmitri I Svergun
The structural analyses of four metabolic enzymes that maintain and regulate the stationary growth phase of Escherichia coli have been performed primarily drawing on the results obtained from solution small angle X-ray scattering (SAXS) and other structural techniques. The proteins are (i) class I fructose-1,6-bisphosphate aldolase (FbaB); (ii) inorganic pyrophosphatase (PPase); (iii) 5-keto-4-deoxyuronate isomerase (KduI); and (iv) glutamate decarboxylase (GadA). The enzyme FbaB, that until now had an unknown structure, is predicted to fold into a TIM-barrel motif that form globular protomers which SAXS experiments show associate into decameric assemblies...
2016: PloS One
Benjamin A Neely, Christopher E Wilkins, Laura A Marlow, Dariya Malyarenko, Yunee Kim, Alexandr Ignatchenko, Heather Sasinowska, Maciek Sasinowski, Julius O Nyalwidhe, Thomas Kislinger, John A Copland, Richard R Drake
Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC). This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of VHL that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC...
2016: PloS One
Yunpeng Wang, Tao Sun, Xingyan Gao, Mengliang Shi, Lina Wu, Lei Chen, Weiwen Zhang
3-hydroxypropionic acid (3-HP) is an important platform chemical with a wide range of applications. So far large-scale production of 3-HP has been mainly through petroleum-based chemical processes, whose sustainability and environmental issues have attracted widespread attention. With the ability to fix CO2 directly, cyanobacteria have been engineered as an autotrophic microbial cell factory to produce fuels and chemicals. In this study, we constructed the biosynthetic pathway of 3-HP in cyanobacterium Synechocystis sp...
March 2016: Metabolic Engineering
Mayra Denisse Ramírez-Quijas, Everardo López-Romero, Mayra Cuéllar-Cruz
In order for Candida species to adhere and colonize human host cells they must express cell wall proteins (CWP) and adapt to reactive oxygen species (ROS) generated by phagocytic cells of the human host during the respiratory burst. However, how these pathogens change the expression of CWP in response to oxidative stress (OSR) is not known. Here, fifteen moonlight-like CWP were identified that expressed differentially in four species of Candida after they were exposed to H2O2 or menadione (O2(-)). These proteins included: (i) glycolytic enzymes, such as glyceraldehyde-3-phosphate dehydrogenase (Gapdh), fructose-bisphosphate aldolase (Fba1), phosphoglycerate mutase (Gpm1), phosphoglycerate kinase (Pgk), pyruvate kinase (Pk) and enolase (Eno1); (ii) the heat shock proteins Ssb1 and Ssa2; (iii) OSR proteins such as peroxyredoxin (Tsa1), the stress protein Ddr48 (Ddr48) and glutathione reductase (Glr1); (iv) other metabolic enzymes such as ketol-acid reductoisomerase (Ilv5) and pyruvate decarboxylase (Pdc1); and (v) other proteins such as elongation factor 1-beta (Efb1) and the 14-3-3 protein homolog...
October 2015: Microbial Pathogenesis
S Andrea Moreno, Mayerly Nava
Trypanosoma evansi, which causes surra, is descended from Trypanosoma brucei brucei, which causes nagana. Although both parasites are presumed to be metabolically similar, insufficient knowledge of T. evansi precludes a full comparison. Herein, we provide the first report on the subcellular localisation of the glycolytic enzymes in T. evansi, which is a alike to that of the bloodstream form (BSF) of T. b. brucei: (i) fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hexokinase, phosphofructokinase, glucose-6-phosphate isomerase, phosphoglycerate kinase, triosephosphate isomerase (glycolytic enzymes) and glycerol-3-phosphate dehydrogenase (a glycolysis-auxiliary enzyme) in glycosomes, (ii) enolase, phosphoglycerate mutase, pyruvate kinase (glycolytic enzymes) and a GAPDH isoenzyme in the cytosol, (iii) malate dehydrogenase in cytosol and (iv) glucose-6-phosphate dehydrogenase in both glycosomes and the cytosol...
June 2015: Memórias do Instituto Oswaldo Cruz
Liliang Guo, Zhenghong Sui, Shu Zhang, Yuanyuan Ren, Yuan Liu
Diatoms form an enormous group of photoautotrophic micro-eukaryotes and play a crucial role in marine ecology. In this study, we evaluated typical genes to determine whether they were effective at different levels of diatom clustering analysis to assess the potential of these regions for barcoding taxa. Our test genes included nuclear rRNA genes (the nuclear small-subunit rRNA gene and the 5.8S rRNA gene+ITS-2), a mitochondrial gene (cytochrome c-oxidase subunit 1, COI), a chloroplast gene [ribulose-1,5-biphosphate carboxylase/oxygenase large subunit (rbcL)] and the universal plastid amplicon (UPA)...
April 2015: International Journal of Systematic and Evolutionary Microbiology
Jingga Inlora, David R Collins, Marc E Trubin, Ji Yeon J Chung, Akira Ono
UNLABELLED: The matrix (MA) domain of HIV-1 mediates proper Gag localization and membrane binding via interaction with a plasma-membrane (PM)-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. HIV-1 MA also interacts with RNA, which prevents Gag from binding to membranes containing phosphatidylserine, a prevalent cellular acidic phospholipid. These results suggest that the MA-bound RNA promotes PM-specific localization of HIV-1 Gag by blocking nonspecific interactions with cellular membranes that do not contain PI(4,5)P2...
December 9, 2014: MBio
Qiuyan Wang, Xiaohui Sun, Xiaobin Li, Xiang Dong, Peng Li, Li Zhao
Obstructive sleep apnea can induce chronic intermittent hypoxia (CIH) during sleep and is associated with obesity and diabetes. Resveratrol (RSV), a polyphenolic phytoalexin, can regulate glucose metabolism, thereby reducing insulin resistance. The present study aimed to assess whether RSV attenuates CIH-induced insulin resistance in rats and the underlying mechanisms. A total of 40 rats were randomly assigned into five groups: i) Control; ii) subjected to CIH only; iii) subjected to CIH and treated with 3 mg/kg/day of RSV; iv) subjected to CIH and treated with 30 mg/kg/day of RSV; v) subjected to CIH and treated with 60 mg/kg/day of RSV...
January 2015: Molecular Medicine Reports
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