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https://www.readbyqxmd.com/read/27926995/frozen-but-no-accident-why-the-20-standard-amino-acids-were-selected
#1
REVIEW
Andrew J Doig
The 20 standard amino acids encoded by the Genetic Code were adopted during the RNA World, around 4 billion years ago. This amino acid set could be regarded as a frozen accident, implying that other possible structures could equally well have been chosen to use in proteins. Amino acids were not primarily selected for their ability to support catalysis, since the RNA World already had highly effective cofactors to perform reactions, such as oxidation, reduction and transfer of small molecules. Rather, they were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926978/potential-blood-biomarkers-in-chronic-spontaneous-urticaria
#2
Pavel Kolkhir, Fiona Andre, Martin K Church, Marcus Maurer, Martin Metz
BACKGROUND: Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is defined as the recurrence of wheals, angioedema, or both for >6 weeks due to known or unknown causes. As of yet, disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease-related biomarkers. OBJECTIVE: To review available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroups allocation or response to treatment...
December 7, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27926928/an-interactome-centered-protein-discovery-approach-reveals-novel-components-involved-in-mitosome-function-and-homeostasis-in-giardia-lamblia
#3
Samuel Rout, Jon Paulin Zumthor, Elisabeth M Schraner, Carmen Faso, Adrian B Hehl
Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#4
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926838/high-resolution-mapping-of-a-repeat-protein-folding-free-energy-landscape
#5
Martin J Fossat, Thuy P Dao, Kelly Jenkins, Mariano Dellarole, Yinshan Yang, Scott A McCallum, Angel E Garcia, Doug Barrick, Christian Roumestand, Catherine A Royer
A complete description of the pathways and mechanisms of protein folding requires a detailed structural and energetic characterization of the conformational ensemble along the entire folding reaction coordinate. Simulations can provide this level of insight for small proteins. In contrast, with the exception of hydrogen exchange, which does not monitor folding directly, experimental studies of protein folding have not yielded such structural and energetic detail. NMR can provide residue specific atomic level structural information, but its implementation in protein folding studies using chemical or temperature perturbation is problematic...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926833/conformational-plasticity-in-the-transsynaptic-neurexin-cerebellin-glutamate-receptor-adhesion-complex
#6
Shouqiang Cheng, Alpay B Seven, Jing Wang, Georgios Skiniotis, Engin Özkan
Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain...
December 6, 2016: Structure
https://www.readbyqxmd.com/read/27926792/the-transcription-factor-pparalpha-is-overexpressed-and-is-associated-with-a-favourable-prognosis-in-idh-wildtype-primary-glioblastoma
#7
H R Haynes, P White, K M Hares, J Redondo, K C Kemp, W G B Singleton, C L Killick-Cole, J R Stevens, K Garadi, S Guglani, A Wilkins, K M Kurian
AIMS: PPARα agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPARα in large-scale glioblastoma data sets has not been examined. We aimed to investigate the expression of the transcription factor PPARα in primary glioblastoma, the relationship between PPARα expression and patients' clinicopathological features and other molecular markers associated with gliomagenesis...
December 7, 2016: Histopathology
https://www.readbyqxmd.com/read/27926790/molecular-surveillance-of-dengue-in-minas-gerais-provides-insights-on-dengue-virus-1-and-4-circulation-in-brazil
#8
Karina Rocha Dutra, Betânia Paiva Drumond, Izabela Maurício de Rezende, Maurício Lacerda Nogueira, Débora de Oliveira Lopes, Carlos Eduardo Calzavara Silva, Jaqueline Maria Siqueira Ferreira, Luciana Lara Dos Santos
Dengue, caused by any of the four types of Dengue virus (DENV) is the most important arbovirus in the world. In this study we performed a molecular surveillance of dengue during the greatest dengue outbreak that took place in Divinópolis, Minas Gerais state, Southeast Brazil, in 2013. Samples from 100 patients with clinical symptoms of dengue were studied and 26 were positive. The capsid/premembrane (CprM) and envelope gene sequences of some samples were amplified and sequenced. Molecular analyses demonstrated that two DENV-1 lineages, belonging to genotype V were introduced and co-circulated in Divinópolis...
November 5, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27926776/synuclein-%C3%AE-in-uterine-serous-carcinoma-impacts-survival-an-nrg-oncology-gynecologic-oncology-group-study
#9
Abigail D Winder, Kruti P Maniar, Jian-Jun Wei, Dachao Liu, Denise M Scholtens, John R Lurain, Julian C Schink, Barbara M Buttin, Virginia L Filiaci, Heather A Lankes, Nilsa C Ramirez, Kay Park, Meenakshi Singh, Richard W Lieberman, Robert S Mannel, Matthew A Powell, Floor J Backes, Cara A Mathews, Michael L Pearl, Angeles Alvarez Secord, David J Peace, David G Mutch, William T Creasman, J Julie Kim
BACKGROUND: Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023). METHODS: High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu...
December 7, 2016: Cancer
https://www.readbyqxmd.com/read/27926762/association-of-arterial-and-lymph-node-inflammation-with-distinct-inflammatory-pathways-in-human-immunodeficiency-virus-infection
#10
Ahmed Tawakol, Amorina Ishai, Danny Li, Richard A P Takx, Sophia Hur, Yannick Kaiser, Miguel Pampaloni, Adam Rupert, Denise Hsu, Irini Sereti, Rémi Fromentin, Nicolas Chomont, Peter Ganz, Steven G Deeks, Priscilla Y Hsue
Importance: Human immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals. Objective: To test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs). Design, Setting, and Participants: For this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center...
December 7, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#11
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#12
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926536/a-minimal-titration-model-of-the-mammalian-dynamical-heat-shock-response
#13
Aude Sivéry, Emmanuel Courtade, Quentin Thommen
Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities...
December 7, 2016: Physical Biology
https://www.readbyqxmd.com/read/27926490/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#14
Jiang He, Feiyu Tang, Liyu Liu, Lin Chen, Jiang Li, Danming Ou, Lu Zhang, Zhi Li, Deyun Feng, Wenzheng Li, Lun-Quan Sun
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926486/novel-epstein-barr-virus-like-particles-incorporating-gh-gl-ebna1-or-gb-lmp2-induce-high-neutralizing-antibody-titers-and-ebv-specific-t-cell-responses-in-immunized-mice
#15
Elizabeth M Perez, Joslyn Foley, Timelia Tison, Rute Silva, Javier Gordon Ogembo
Previous Epstein-Barr virus (EBV) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. In this study, we reasoned that incorporating gH/gL or gB, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (VLP) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral infection of both epithelial and B cell lines...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926483/the-metastasis-suppressor-cd82-kai1-inhibits-fibronectin-adhesion-induced-epithelial-to-mesenchymal-transition-in-prostate-cancer-cells-by-repressing-the-associated-integrin-signaling
#16
Jaeseob Lee, Hee-Jung Byun, Moon-Sung Lee, Young-June Jin, Dooil Jeoung, Young-Myeong Kim, Hansoo Lee
The transmembrane protein CD82/KAI1 suppresses the metastatic potential of various cancer cell types. Moreover, decrease or loss of CD82 expression is closely associated with malignancy and poor prognosis in many human cancers including prostate cancer. Despite intense scrutiny, the mechanisms underlying the metastasis-suppressing role of CD82 are still not fully understood. Here, we found that a fibronectin matrix induced mesenchymal phenotypes in human prostate cancer cells with no or low CD82 expression levels...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926480/calcium-dependent-binding-of-myc-to-calmodulin
#17
Philipp Raffeiner, Andrea Schraffl, Thomas Schwarz, Ruth Röck, Karin Ledolter, Markus Hartl, Robert Konrat, Eduard Stefan, Klaus Bister
The bHLH-LZ (basic region/helix-loop-helix/leucine zipper) oncoprotein Myc and the bHLH-LZ protein Max form a binary transcription factor complex controlling fundamental cellular processes. Deregulated Myc expression leads to neoplastic transformation and is a hallmark of most human cancers. The dynamics of Myc transcription factor activity are post-translationally coordinated by defined protein-protein interactions. Here, we present evidence for a second messenger controlled physical interaction between the Ca2+ sensor calmodulin (CaM) and all Myc variants (v-Myc, c-Myc, N-Myc, and L-Myc)...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926476/mitochondrial-cytochrome-c-oxidase-is-inhibited-by-atp-only-at-very-high-atp-adp-ratios
#18
Rabia Ramzan, Andreas K Schaper, Petra Weber, Annika Rhiel, Muhammad Saad Siddiq, Sebastian Vogt
In the past, divergent results have been reported based on different methods and conditions used for enzymatic activity measurements of cytochrome c oxidase (CytOx). Here, we analyze in detail and show comparable and reproducible polarographic activity measurements of ATP- dependent inhibition of CytOx kinetics in intact and non-intact rat heart mitochondria and mitoplasts. We found that this mechanism is always present in isolated rat heart mitochondria and mitoplasts; however, it is measurable only at high ATP/ADP ratios using optimal protein concentrations...
December 7, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27926473/growth-differentiation-factor-15-increases-following-oral-glucose-ingestion-effect-of-meal-composition-and-obesity
#19
Marie Helene Schernthaner-Reiter, Dominik Kasses, Christina Tugendsam, Michaela Riedl, Slobodan Peric, Gerhard Prager, Michael Krebs, Miriam Promintzer-Schifferl, Martin Clodi, Anton Luger, Greisa Vila
OBJECTIVE: Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. DESIGN: Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting...
December 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27925687/dna-base-excision-repair-proteins-ape-1-and-xrcc-1-are-overexpressed-in-oral-tongue-squamous-cell-carcinoma
#20
Thalita Santana, Melka Coêlho Sá, Edilmar de Moura Santos, Hébel Cavalcanti Galvão, Ricardo D Coletta, Roseana de Almeida Freitas
BACKGROUND: DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens. Modifications in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. This study aimed to assess the immunoexpression of DNA repair proteins APE-1 and XRCC-1 and its association with clinical, histological and survival parameters in oral tongue squamous cell carcinoma in order to investigate a possible role for those proteins in tumor behavior...
December 7, 2016: Journal of Oral Pathology & Medicine
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