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https://www.readbyqxmd.com/read/27933579/oligomerization-and-chaperone-like-activity-of-drosophila-melanogaster-small-heat-shock-protein-dmhsp27-and-three-arginine-mutants-in-the-alpha-crystallin-domain
#1
Mohamed Taha Moutaoufik, Geneviève Morrow, Halim Maaroufi, Céline Férard, Stéphanie Finet, Robert M Tanguay
The small Hsp DmHsp27 from Drosophila melanogaster is one of the few small heat shock proteins (sHsps) found within the nucleus. We report that its dimerization is independent of disulfide bond formation and seems to rely on salt bridges. Unlike metazoan sHsps, DmHsp27 forms two populations of oligomers not in equilibrium. Mutations at highly conserved arginine residues in mammalian sHsps have been reported to be associated with protein conformational defects and intracellular aggregation. Independent mutation of three highly conserved arginines (R122, R131, and R135) to glycine in DmHsp27 results in only one population of higher molecular weight form...
December 8, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27933109/functional-characterization-of-rare-foxp2-variants-in-neurodevelopmental-disorder
#2
Sara B Estruch, Sarah A Graham, Swathi M Chinnappa, Pelagia Deriziotis, Simon E Fisher
BACKGROUND: Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. METHODS: We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins...
2016: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/27933035/life-without-dutpase
#3
Csaba Kerepesi, Judit E Szabó, Veronika Papp-Kádár, Orsolya Dobay, Dóra Szabó, Vince Grolmusz, Beáta G Vértessy
Fine-tuned regulation of the cellular nucleotide pools is indispensable for faithful replication of Deoxyribonucleic Acid (DNA). The genetic information is also safeguarded by DNA damage recognition and repair processes. Uracil is one of the most frequently occurring erroneous bases in DNA; it can arise from cytosine deamination or thymine-replacing incorporation. Two enzyme activities are primarily involved in keeping DNA uracil-free: dUTPase (dUTP pyrophosphatase) activity that prevent thymine-replacing incorporation and uracil-DNA glycosylase activity that excise uracil from DNA and initiate uracil-excision repair...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932745/-association-of-deep-venous-thrombosis-with-d-dimer-values-in-patients-with-hemorrhagic-stroke
#4
Atsushi Arai, Junji Koyama, Taichiro Imahori, Ryoji Shiomi, Hirofumi Iwahashi, Kazuhiro Tanaka, Eiji Kohmura
Pulmonary embolism(PE)in the early phase of stroke worsens the prognosis. It is necessary to detect deep venous thrombosis(DVT)to avoid PE. We conducted the D-dimer screening in order to detect DVT at an earlier stage. We retrospectively analyzed the clinical data of patients with hemorrhagic stroke who were admitted to the local stroke center, and investigated the complication rates of DVT, PE, D-dimer values, and risk factors of DVT. From October 2012 to August 2014, 261 patients were included. DVT was detected in 46 patients(17...
December 2016: No Shinkei Geka. Neurological Surgery
https://www.readbyqxmd.com/read/27932568/targeting-hif2-in-clear-cell-renal-cell-carcinoma
#5
Hyejin Cho, William G Kaelin
Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1...
December 8, 2016: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/27932494/loss-of-a-doublecortin-dcx-domain-protein-causes-structural-defects-in-a-tubulin-based-organelle-of-toxoplasma-gondii-and-impairs-host-cell-invasion
#6
Eiji Nagayasu, Yu-Chen Hwang, Jun Liu, John M Murray, Ke Hu
The ∼6000 species in phylum Apicomplexa are single-celled obligate intracellular parasites. Their defining characteristic is the "apical complex", membranous and cytoskeletal elements at the apical end of the cell that participate in host-cell invasion. The apical complex of Toxoplasma gondii and some other apicomplexans includes a cone-shaped assembly, the "conoid", which (in T. gondii) comprises 14 spirally arranged fibers that are non-tubular polymers of tubulin. The tubulin dimers of the conoid fibers make canonical microtubules elsewhere in the same cell, suggesting that non-tubulin protein dictates their special arrangement in the conoid fibers...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27932461/structural-characterization-and-ligand-inhibitor-identification-provide-functional-insights-into-the-mycobacterium-tuberculosis-cytochrome-p450-cyp126a1
#7
Jude T Chenge, Duyet Van Le, Shalini Swami, Kirsty J McLean, Madeline E Kavanagh, Anthony G Coyne, Stephen E J Rigby, Myles R Cheesman, Hazel M Girvan, Colin W Levy, Bernd Rupp, Jens P von Kries, Chris Abell, David Leys, Andrew W Munro
The Mycobacterium tuberculosis (Mtb) H37Rv genome encodes 20 cytochromes P450, including P450s crucial to infection and bacterial viability. Many Mtb P450s remain uncharacterized, suggesting their further analysis may provide new insights into Mtb metabolic processes and new targets for drug discovery. CYP126A1 is representative of a P450 family widely distributed in mycobacteria and other bacteria. Here we explore the biochemical and structural properties of CYP126A1, including its interactions with new chemical ligands...
December 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27932457/structural-basis-for-the-dimerization-of-nab2-generated-by-rna-binding-provides-insight-into-its-contribution-to-both-poly-a-tail-length-determination-and-transcript-compaction-in-saccharomyces-cerevisiae
#8
Shintaro Aibara, James M B Gordon, Anja S Riesterer, Stephen H McLaughlin, Murray Stewart
In Saccharomyces cerevisiae generation of export-competent mRNPs terminates the nuclear phase of the gene expression pathway and facilitates transport to the cytoplasm for translation. Nab2 functions in this process to control both mRNP compaction that facilitates movement through nuclear pore complexes and the length of transcript poly(A) tails. Nab2 has a modular structure that includes seven CCCH Zn fingers that bind to A-rich RNAs and fingers 5-7 are critical for these functions. Here, we demonstrate, using both biophysical and structural methods, that binding A11G RNA induces dimerization of Zn fingers 5-7 mediated by the novel spatial arrangement of the fingers promoting each RNA chain binding two protein chains...
December 8, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27932354/longitudinal-impact-of-smoking-and-smoking-cessation-on-inflammatory-markers-of-cardiovascular-disease-risk
#9
Cecile C King, Megan E Piper, Adam D Gepner, Michael C Fiore, Timothy B Baker, James H Stein
OBJECTIVE: To evaluate longitudinal changes in 6 inflammatory markers that predict cardiovascular disease events among smokers making a quit attempt and to characterize their cross-sectional associations between smoking and smoking heaviness. APPROACH AND RESULTS: In a longitudinal cohort study of contemporary smokers (n=1652), we evaluated (1) independent associations of smoking heaviness markers (exhaled carbon monoxide, cigarettes/d, pack-years) with inflammatory markers (C-reactive protein, D-dimer, fibrinogen, urinary F2 isoprostane:creatinine [F2:Cr] ratio, white blood cell [WBC] count, myeloperoxidase) and (2) the effects of smoking cessation and continued smoking on these inflammatory markers after 1 year, among the 888 smokers who made an aided quit attempt as part of a randomized comparative effectiveness trial or standard care...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27932064/bax-and-bak-pores-are-we-closing-the-circle
#10
REVIEW
Katia Cosentino, Ana J García-Sáez
Bax and its homolog Bak are key regulators of the mitochondrial pathway of apoptosis. On cell stress Bax and Bak accumulate at distinct foci on the mitochondrial surface where they undergo a conformational change, oligomerize, and mediate cytochrome c release, leading to cell death. The molecular mechanisms of Bax and Bak assembly and mitochondrial permeabilization have remained a longstanding question in the field. Recent structural and biophysical studies at several length scales have shed light on key aspects of Bax and Bak function that have shifted how we think this process occurs...
December 5, 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27930994/testosterone-and-its-dimers-alter-trna-morphology
#11
P Chanphai, D Agudelo, A R Vesper, G Bérubé, H A Tajmir-Riahi
The morphology of tRNA was studied upon conjugation with testosterone and its aliphatic and aromatic dimers, using multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling. Structural analysis showed that testosterone binds tRNA through A62, A64, C60, C61, C63, G51, U50 and U59 bases. The binding affinity was testosterone dimer-aromatic>testosterone dimer-aliphatic>testosterone. The steroid loading efficacy was 35-45%. Transmission electron microscopy showed major changes in tRNA morphology upon testosterone interaction with an increase in the diameter of the tRNA aggregate, indicating encapsulation of testosterone by tRNA...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27929426/serum-soluble-fms-like-tyrosine-kinase-1-sflt-1-predicts-the-severity-of-acute-pancreatitis
#12
Paulina Dumnicka, Mateusz Sporek, Małgorzata Mazur-Laskowska, Piotr Ceranowicz, Marek Kuźniewski, Ryszard Drożdż, Tadeusz Ambroży, Rafał Olszanecki, Beata Kuśnierz-Cabala
Organ failure is the most important determinant of the severity of acute pancreatitis (AP). Soluble fms-like tyrosine kinase 1 (sFlt-1) is positively associated with organ failure in sepsis. Our aim was to evaluate the diagnostic utility of automated sFlt-1 measurements for early prediction of AP severity. Adult patients (66) with AP were recruited, including 46 with mild (MAP), 15 with moderately-severe (MSAP) and 5 with severe AP (SAP). Serum and urine samples were collected twice. Serum sFlt-1 was measured with automated electrochemiluminescence immunoassay...
December 6, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27929200/obesity-insulin-resistance-rather-than-liver-fat-increases-coagulation-factor-activities-and-expression-in-humans
#13
Susanna Lallukka, Panu K Luukkonen, You Zhou, Elina M Petäjä, Marja Leivonen, Anne Juuti, Antti Hakkarainen, Marju Orho-Melander, Nina Lundbom, Vesa M Olkkonen, Riitta Lassila, Hannele Yki-Järvinen
Increased liver fat may be caused by insulin resistance and adipose tissue inflammation or by the common I148M variant in PNPLA3 at rs738409, which lacks both of these features. We hypothesised that obesity/insulin resistance rather than liver fat increases circulating coagulation factor activities. We measured plasma prothrombin time (PT, Owren method), activated partial thromboplastin time (APTT), activities of several coagulation factors, VWF:RCo and fibrinogen, and D-dimer concentration in 92 subjects divided into groups based on insulin sensitivity [insulin-resistant ('IR') versus insulin-sensitive ('IS')] and PNPLA3 genotype (PNPLA3(148MM/MI) vs PNPLA3(148II))...
December 8, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27929170/cyclometalated-ir-iii-complexes-containing-quinoline-benzimidazole-based-n-n-ancillary-ligands-structural-and-luminescence-modulation-by-varying-the-substituent-groups-or-the-protonation-deprotonation-state-of-imidazole-units
#14
Dan-Ping Gong, Tai-Bao Gao, Deng-Ke Cao, Michael D Ward
Cyclometalated Ir(iii) complexes [Ir(dfppy)2(qbiH)](PF6) (1), [Ir(dfppy)2(qbim)](PF6)·H2O (2), [Ir(dfppy)2(qbio)](PF6) (3) and [Ir(dfppy)2(qbi)] (4) have been designed and prepared, in which the N^N ligands qbiH, qbim and qbio incorporate different substituent groups R on their imidazole units (H atom, CH3 group and n-C8H17 group, respectively) in order to explore the influence of the substituent groups R and the protonation/deprotonation state of imidazole units in these Ir(iii) complexes on their structures and luminescence behaviors...
December 8, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27929165/occurrence-of-photoinduced-charge-separation-by-the-modulation-of-the-electronic-coupling-between-pyrene-dimers-and-chemically-converted-graphenes
#15
Tomokazu Umeyama, Jinseok Baek, Junya Mihara, Nikolai V Tkachenko, Hiroshi Imahori
The photoexcitation of the pyrene dimer on graphene resulted in the final formation of a charge-separated state following an exciplex formation, while that of the pyrene monomer on graphene generated the corresponding exciplex solely due to the difference in the electronic coupling between the pyrene and the graphene.
December 8, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27929160/do-primary-carriers-of-both-positive-charge-and-unpaired-electron-spin-exist-in-irradiated-propylene-carbonate
#16
V I Borovkov
In disagreement with the common concept of primary radiation-induced events in liquid carbonates, an analysis of the fluorescence response of irradiated luminophore solutions in propylene carbonate to magnetic fields reveals the presence of radical cations formed from the solvent. On the basis of their magnetic resonance characteristics, the radical cations are proposed to be ionised dimeric complexes with the spin density delocalised over two antiparallel carbonyl groups. The finding suggests that the basic models underlying the application of radiolysis to study the mechanisms of the oxidative decomposition of carbonates should be reexamined...
December 8, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27929153/local-environment-inside-a-novel-aromatic-micelle-investigated-by-steady-state-and-femtosecond-fluorescence-spectroscopy-of-an-encapsulated-solvatochromic-probe
#17
Matthew M Sartin, Kei Kondo, Michito Yoshizawa, Satoshi Takeuchi, Tahei Tahara
The local environment within a recently developed anthracene-shelled micelle (ASM), which is a micelle-like nanocapsule composed of anthracene-embedded amphiphiles, was investigated by steady-state and time-resolved spectroscopy of an encapsulated solvatochromic fluorescent probe molecule, coumarin 153 (C153). The absorption maximum of encapsulated C153 (452 nm) is more red-shifted than that of free C153 in water, indicating a highly polar environment inside the micelle. Despite this, the fluorescence Stokes shift of encapsulated C153 (∼3700 cm(-1)) is substantially smaller than that of free C153 in water...
December 8, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27929144/intermolecular-interactions-in-the-tmem16a-dimer-controlling-channel-activity
#18
Paolo Scudieri, Ilaria Musante, Ambra Gianotti, Oscar Moran, Luis J V Galietta
TMEM16A and TMEM16B are plasma membrane proteins with Ca(2+)-dependent Cl(-) channel function. By replacing the carboxy-terminus of TMEM16A with the equivalent region of TMEM16B, we obtained channels with potentiation of channel activity. Progressive shortening of the chimeric region restricted the "activating domain" to a short sequence close to the last transmembrane domain and led to TMEM16A channels with high activity at very low intracellular Ca(2+) concentrations. To elucidate the molecular mechanism underlying this effect, we carried out experiments based on double chimeras, Forster resonance energy transfer, and intermolecular cross-linking...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928941/molecular-dynamics-analysis-of-the-structural-and-dynamic-properties-of-the-functionally-enhanced-hepta-variant-of-mouse-5-aminolevulinate-synthase
#19
Insung Na, Shelly DeForte, Bosko M Stojanovski, Gloria C Ferreira, Vladimir N Uversky
Heme biosynthesis, a complex, multistage, and tightly controlled process, starts with 5-aminolevulinate (ALA) production, which, in metazoa and certain bacteria, is a reaction catalyzed by 5-aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. Functional aberrations in ALAS are associated with several human diseases. ALAS can adopt open and closed conformations, with segmental rearrangements of a C-terminal, 16-amino acid loop and an α-helix regulating accessibility to the ALAS active site...
December 8, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27928502/improving-cardiovascular-outcomes-among-aboriginal-australians-lessons-from-research-for-primary-care
#20
Sandra C Thompson, Emma Haynes, John A Woods, Dawn C Bessarab, Lynette A Dimer, Marianne M Wood, Frank M Sanfilippo, Sandra J Hamilton, Judith M Katzenellenbogen
BACKGROUND: The Aboriginal people of Australia have much poorer health and social indicators and a substantial life expectancy gap compared to other Australians, with premature cardiovascular disease a major contributor to poorer health. This article draws on research undertaken to examine cardiovascular disparities and focuses on ways in which primary care practitioners can contribute to reducing cardiovascular disparities and improving Aboriginal health. METHODS: The overall research utilised mixed methods and included data analysis, interviews and group processes which included Aboriginal people, service providers and policymakers...
2016: SAGE Open Medicine
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