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https://www.readbyqxmd.com/read/29166595/positive-and-negative-regulation-of-the-master-metabolic-regulator-mtorc1-by-two-families-of-legionella-pneumophila-effectors
#1
Justin A De Leon, Jiazhang Qiu, Christopher J Nicolai, Jessica L Counihan, Kevin C Barry, Li Xu, Rosalie E Lawrence, Brian M Castellano, Roberto Zoncu, Daniel K Nomura, Zhao-Qing Luo, Russell E Vance
All pathogens must acquire nutrients from their hosts. The intracellular bacterial pathogen Legionella pneumophila, the etiological agent of Legionnaires' disease, requires host amino acids for growth within cells. The mechanistic target of rapamycin complex 1 (mTORC1) is an evolutionarily conserved master regulator of host amino acid metabolism. Here, we identify two families of translocated L. pneumophila effector proteins that exhibit opposing effects on mTORC1 activity. The Legionella glucosyltransferase (Lgt) effector family activates mTORC1, through inhibition of host translation, whereas the SidE/SdeABC (SidE) effector family acts as mTORC1 inhibitors...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166558/understanding-the-cellular-uptake-of-ph-responsive-zwitterionic-gold-nanoparticles-a-computer-simulation-study
#2
Xuebo Quan, Daohui Zhao, Libo Li, Jian Zhou
Surface functionalization of nanoparticles (NPs) with stealth polymers (e.g., hydrophilic and zwitterionic polymers) has become a common strategy to resist non-specific protein adsorption recently. Understanding the role of surface decoration on NP-biomembrane interactions is of great significance to promote the application of NPs in biomedical fields. Herein, using coarse-grained molecular dynamics (CGMD) simulations, we investigate the interactions between stealth polymer-coated gold nanoparticles (AuNPs) and lipid membranes...
November 22, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29165686/optimal-timing-for-blastomere-biopsy-of-8-cell-embryos-for-preimplantation-genetic-diagnosis
#3
Y Kalma, L Bar-El, S Asaf-Tisser, M Malcov, A Reches, J Hasson, H Amir, F Azem, D Ben-Yosef
STUDY QUESTION: What is the optimal timing for blastomere biopsy during the 8-cell stage, at which embryos will have the best implantation potential? SUMMARY ANSWER: Fast-cleaving embryos that are biopsied during the last quarter (Q4) of the 8-cell stage and are less affected by the biopsy procedure, and their implantation potential is better than that of embryos biopsied earlier during the 8-cell stage (Q1-Q3). WHAT IS KNOWN ALREADY: Blastomer biopsy from cleavage-stage embryos is usually performed on the morning of Day 3 when the embryos are at the 6- to 8-cell stage and is still the preferred biopsy method for preimplantation genetic diagnosis (PGD) for monogentic disorders or chromosomal translocations...
November 20, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29165589/ns3-helicase-from-dengue-virus-specifically-recognizes-viral-rna-sequence-to-ensure-optimal-replication
#4
Crystall M D Swarbrick, Chandrakala Basavannacharya, Kitti W K Chan, Shu-Ann Chan, Daljit Singh, Na Wei, Wint Wint Phoo, Dahai Luo, Julien Lescar, Subhash G Vasudevan
The protein-RNA interactions within the flavivirus replication complex (RC) are not fully understood. Our structure of dengue virus NS3 adenosine triphosphatase (ATPase)/helicase bound to the conserved 5' genomic RNA 5'-AGUUGUUAGUCU-3' reveals that D290 and R538 make specific interactions with G2 and G5 bases respectively. We show that single-stranded 12-mer RNA stimulates ATPase activity of NS3, however the presence of G2 and G5 leads to significantly higher activation. D290 is adjacent to the DEXH motif found in SF2 helicases like NS3 and interacts with R387, forming a molecular switch that activates the ATPase site upon RNA binding...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165402/quercetin-mitigates-inflammatory-responses-induced-by-vascular-endothelial-growth-factor-in-mouse-retinal-photoreceptor-cells-through-suppression-of-nuclear-factor-kappa-b
#5
Minsup Lee, Seohyeon Yun, Hyesook Lee, Jaewook Yang
Retinal vascular endothelial growth factor (VEGF) increased by neovascularization is well known as a pathogenic factor in ocular neovascular diseases. However, it is still unclear how retinal neurons are damaged by VEGF. The aims of this study are to demonstrate the inflammatory protein expression regulated by VEGF using mouse photoreceptor-derived cells and the protective effect of quercetin against VEGF-induced inflammatory response. Expression and phosphorylation of protein and expression of mRNA were detected by immunoblot and reverse transcriptase polymerase chain reaction...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165030/in-mammalian-skeletal-muscle-phosphorylation-of-tomm22-by-protein-kinase-csnk2-ck2-controls-mitophagy
#6
Bojana Kravic, Angelika B Harbauer, Vanina Romanello, Luca Simeone, F-Nora Vögtle, Tobias Kaiser, Marion Straubinger, Danyil Huraskin, Martin Böttcher, Cristina Cerqua, Eva Denise Martin, Daniel Poveda-Huertes, Andreas Buttgereit, Adam J Rabalski, Dieter Heuss, Rüdiger Rudolf, Oliver Friedrich, David Litchfield, Michael Marber, Leonardo Salviati, Dimitrios Mougiakakos, Winfried Neuhuber, Marco Sandri, Chris Meisinger, Said Hashemolhosseini
In yeast, Tom22 the central component of the TOMM (translocase of outer mitochondrial membrane) receptor complex is responsible for the recognition and translocation of synthesized mitochondrial precursor proteins, and its protein kinase CK2-dependent phosphorylation is mandatory for TOMM complex biogenesis and proper mitochondrial protein import. In mammals, the biological function of protein kinase CSNK2/CK2 remains vastly elusive and it is unknown whether CSNK2-dependent phosphorylation of TOMM protein subunits has a similar role as that in yeast...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29164633/capillarisin-blocks-prostate-specific-antigen-expression-on-activation-of-androgen-receptor-in-prostate-carcinoma-cells
#7
Ke-Hung Tsui, Ying-Ling Chang, Tsui-Hsia Feng, Chen-Pang Hou, Yu-Hsiang Lin, Pei-Shan Yang, Bing-Wei Lee, Horng-Heng Juang
BACKGROUND: Capillarisin (Cap), an active ingredient of Artemisia capillaris extracts, has known for its anti-inflammatory, antioxidant, and anticancer properties. Functions of Cap in prostate cancer are not clear. We investigate effects of Cap on downregulation of prostate specific antigen (PSA) via modulation of androgen receptor (AR) in prostate carcinoma cells. METHODS: Cell proliferation was measured by water-soluble tetrazolium-1 (WST-1) cell proliferation assays...
November 22, 2017: Prostate
https://www.readbyqxmd.com/read/29164305/nuclear-transport-of-the-human-aryl-hydrocarbon-receptor-and-subsequent-gene-induction-relies-on-its-residue-histidine-291
#8
A Tkachenko, M Bermudez, S Irmer-Stooff, D Genkinger, F Henkler-Stephani, G Wolber, A Luch
The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor involved in the metabolism of physiological substances and xenobiotics, representing an interesting target in both toxicology and pharmacology. In this study, we investigated the ligand-dependent conjunction of nuclear import of the human AHR in living cells and target gene induction. Our findings strengthen the theory that the AHR triggers a precisely defined and rapid reaction upon binding to endogenous ligands, while the xenobiotic β-naphthoflavone only induces rather unspecific and slow effects...
November 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29164068/comparative-pan-genome-analysis-of-piscirickettsia-salmonis-reveals-genomic-divergences-within-genogroups
#9
Guillermo Nourdin-Galindo, Patricio Sánchez, Cristian F Molina, Daniela A Espinoza-Rojas, Cristian Oliver, Pamela Ruiz, Luis Vargas-Chacoff, Juan G Cárcamo, Jaime E Figueroa, Marcos Mancilla, Vinicius Maracaja-Coutinho, Alejandro J Yañez
Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis, functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29163600/plastome-rearrangements-in-the-adenocalymma-neojobertia-clade-bignonieae-bignoniaceae-and-its-phylogenetic-implications
#10
Luiz H M Fonseca, Lúcia G Lohmann
The chloroplast is one of the most important organelles of plants. This organelle has a circular DNA with approximately 130 genes. The use of plastid genomic data in phylogenetic and evolutionary studies became possible with high-throughput sequencing methods, which allowed us to rapidly obtain complete genomes at a reasonable cost. Here, we use high-throughput sequencing to study the "Adenocalymma-Neojobertia" clade (Bignonieae, Bignoniaceae). More specifically, we use Hi-Seq Illumina technology to sequence 10 complete plastid genomes...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29163349/kainic-acid-induced-post-status-epilepticus-models-of-temporal-lobe-epilepsy-with-diverging-seizure-phenotype-and-neuropathology
#11
Daniele Bertoglio, Halima Amhaoul, Annemie Van Eetveldt, Ruben Houbrechts, Sebastiaan Van De Vijver, Idrish Ali, Stefanie Dedeurwaerdere
The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29163222/an-update-on-sec61-channel-functions-mechanisms-and-related-diseases
#12
REVIEW
Sven Lang, Stefan Pfeffer, Po-Hsien Lee, Adolfo Cavalié, Volkhard Helms, Friedrich Förster, Richard Zimmermann
The membrane of the endoplasmic reticulum (ER) of nucleated human cells harbors the protein translocon, which facilitates membrane integration or translocation of almost every newly synthesized polypeptide targeted to organelles of the endo- and exocytotic pathway. The translocon comprises the polypeptide-conducting Sec61 channel and several additional proteins and complexes that are permanently or transiently associated with the heterotrimeric Sec61 complex. This ensemble of proteins facilitates ER targeting of precursor polypeptides, modification of precursor polypeptides in transit through the Sec61 complex, and Sec61 channel gating, i...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29163156/role-of-translocator-18-kda-ligands-in-the-activation-of-leukotriene-b4-activated-g-protein-coupled-receptor-and-toll-like-receptor-4-pathways-in-neutrophils
#13
Léonard de Vinci Kanda Kupa, Carine C Drewes, Eric D Barioni, Camila L Neves, Sandra Coccuzzo Sampaio, Sandra H P Farsky
TSPO (Translocator 18 KDa; tryptophan-rich sensory protein oxygen sensor) is a constitutive outer mitochondrial membrane protein overexpressed in inflammatory cells during local or systemic processes. Despite its expression is characterized, role of TSPO in inflammation remains elusive. For this study, we investigated the role of TSPO ligands on neutrophil functions elicited by two different inflammatory pathways. Peritoneal neutrophils were isolated from male Balb-C mice, treated with TSPO ligand diazepam, Ro5-4864 or PK11195 (1,100 or 1000 nM; 2 h) and further stimulated with lipopolysaccharide from Escherichia coli (LPS), a binding for Toll-Like Receptor-4 (TLR4), or leukotriene B4 (LTB4), a G-protein coupled receptor (GPCR) ligand...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163038/electroacupuncture-suppresses-the-nf-%C3%AE%C2%BAb-signaling-pathway-by-upregulating-cylindromatosis-to-alleviate-inflammatory-injury-in-cerebral-ischemia-reperfusion-rats
#14
Jin Jiang, Yong Luo, Wenyi Qin, Hongmei Ma, Qiongli Li, Jian Zhan, Ying Zhang
Electroacupuncture (EA) may reduce inflammatory injury by inhibiting nuclear factor-kappa B (NF-κB) signaling pathway activation after ischemic stroke. Thus, we explored temporal and spatial expression of cylindromatosis (CYLD), a negative feedback inhibitor of the NF-κB signaling pathway, to learn whether CYLD is essential for EA and reduction of inflammatory injury after focal cerebral ischemia/reperfusion. A middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in male Sprague-Dawley (SD) rats and CYLD gene interference was used to investigate a potential role of neuroprotection...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29162902/shear-stress-regulates-trpv4-channel-clustering-and-translocation-from-adherens-junctions-to-the-basal-membrane
#15
Sara Baratchi, Markus Knoerzer, Khashayar Khoshmanesh, Arnan Mitchell, Peter McIntyre
Localized Ca(2+) influx via TRPV4 on the surface of endothelial cells greatly influences endothelial adaptation to blood flow, but how mechanical stress from blood flow controls TRPV4 integration into this physiological function is not fully understood. Here, we studied the spatial organization of TRPV4 and its relationship to the adherens junction component β-catenin using single- and dual-color direct stochastic optical reconstruction microscopy (dSTORM). In non-stimulated endothelial cells, TRPV4 is clustered in small protein islands, as is β-catenin...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162829/single-molecule-visualization-of-conformational-changes-and-substrate-transport-in-the-vitamin-b12-abc-importer-btucd-f
#16
Joris M H Goudsmits, Dirk Jan Slotboom, Antoine M van Oijen
ATP-binding cassette (ABC) transporters form the largest class of active membrane transport proteins. Binding and hydrolysis of ATP by their highly conserved nucleotide-binding domains drive conformational changes of the complex that mediate transport of substrate across the membrane. The vitamin B12 importer BtuCD-F in Escherichia coli is an extensively studied model system. The periplasmic soluble binding protein BtuF binds the ligand; the transmembrane and ATPase domains BtuCD mediate translocation. Here we report the direct observation at the single-molecule level of ATP, vitamin B12 and BtuF-induced events in the transporter complex embedded in liposomes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162747/therapeutic-effect-of-a-novel-wnt-pathway-inhibitor-on-cardiac-regeneration-after-myocardial-infarction
#17
Chunyu Zeng, Dezhong Yang, Wenbin Fu, Liangpeng Li, Xuewei Xia, Qiao Liao, Rongchuan Yue, Hongmei Chen, Xiongwen Chen, Songzhu An, Wei Eric Wang
After myocardial infarction (MI), the heart is difficult to repair because of great loss of cardiomyoctyes and lack of cardiac regeneration. Novel drug candidates that aim at reducing pathological remodeling and stimulating cardiac regeneration are highly desirable. In this study, we identified if and how a novel porcupine inhibitor CGX1321 influenced MI and cardiac regeneration. Permanent ligation of left anterior descending (LAD) coronary artery was performed in mice to induce MI injury. Cardiac function was measured by echocardiography, infarct size was examined by TTC staining...
November 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29162741/nuclear-hyaluronidase-2-drives-alternative-splicing-of-cd44-pre-mrna-to-determine-profibrotic-or-antifibrotic-cell-phenotype
#18
Adam C Midgley, Sebastian Oltean, Vincent Hascall, Emma L Woods, Robert Steadman, Aled O Phillips, Soma Meran
The cell surface protein CD44 is involved in diverse physiological processes, and its aberrant function is linked to various pathologies such as cancer, immune dysregulation, and fibrosis. The diversity of CD44 biological activity is partly conferred by the generation of distinct CD44 isoforms through alternative splicing. We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing. Standard CD44 is associated with fibrotic disease, and its production is promoted through serine-arginine-rich (SR) protein-mediated exon exclusion...
November 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/29161615/more-than-a-tad-spatiotemporal-control-of-caulobacter-pili
#19
REVIEW
Johann Mignolet, Gaël Panis, Patrick H Viollier
The Type IV pilus (T4P) is a powerful and sophisticated bacterial nanomachine involved in numerous cellular processes, including adhesion, DNA uptake and motility. Aside from the well-described subtype T4aP of the Gram-negative genera, including Myxococcus, Pseudomonas and Neisseria, the Tad (tight adherence) pilus secretion system re-shuffles homologous parts from other secretion systems along with uncharacterized components into a new type of protein translocation apparatus. A representative of the Tad apparatus, the Caulobacter crescentus pilus assembly (Cpa) machine is built exclusively at the newborn cell pole once per cell cycle...
November 18, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29160935/oh-the-places-they-ll-go-a-survey-of-phytopathogen-effectors-and-their-host-targets
#20
Madiha Khan, Derek Seto, Rajagopal Subramaniam, Darrell Desveaux
Phytopathogens translocate effector proteins into plant cells where they sabotage the host cellular machinery to promote infection. An individual pathogen can translocate numerous distinct effectors during the infection process to target an array of host macromolecules (proteins, metabolites, DNA, etc…) and manipulate them using a variety of enzymatic activities. In this review, we have surveyed the literature for effector targets and curated them to convey the range of functions carried out by phytopathogenic proteins inside host cells...
November 21, 2017: Plant Journal: for Cell and Molecular Biology
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