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https://www.readbyqxmd.com/read/28544588/the-in-vivo-th17-and-treg-immune-responses-to-aggregatibacter-actinomycetemcomitans
#1
Susan Mahabady, Natalia Tjokro, Shant Aharonian, Homayoun H Zadeh, Casey Chen, Hooman Allayee, Parish P Sedghizadeh
The periodontal pathogen Aggregatibacter actinomycetemcomitans is known to elicit systemic immune response in infected host, and occasionally causes non-oral infections. Detailed information on its immunopathological responses and the involvement of bacterial virulence factors remains to be elucidated. The aim of this study was to assess the systemic immune response to A. actinomycetemcomitans oral infection. We used an animal model that simulates systemic dissemination of the bacteria by injecting live wild type (WT) D7S-1 and double knockout mutant of leukotoxin and cytolethal distending toxin (ΔltxΔcdt) A...
May 22, 2017: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/28544477/hashimoto-thyroiditis-anti-thyroid-antibodies-and-systemic-lupus-erythematosus
#2
Rayana T Posselt, Vinícius N Coelho, Thelma L Skare
AIM: To study the prevalence of Hashimoto thyroiditis (HT), anti-thyroid autoantibodies (anti-thyroglobulin or TgAb and thyroperoxidase or TPOAb) in systemic lupus erythematosus (SLE) patients. To analyze if associated HT, TgAb and/or TPOAb influence clinical or serological profiles, disease activity and/or its cumulative damage. METHODS: Three hundred and one SLE patients and 141 controls were studied for thyroid stimulating hormone, thyroxin, TgAb and TPOAb by chemiluminescence and immunometric assays...
May 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28543567/tgr5-contributes-to-hepatic-cystogenesis-in-rodents-with-polycystic-liver-diseases-via-camp-g%C3%AE-s-signaling
#3
Tatyana V Masyuk, Anatoliy I Masyuk, Maria Lorenzo Pisarello, Brynn N Howard, Bing Q Huang, Pui-Yuen Lee, Xavier Fung, Eduard Sergienko, Robert J Ardesky, Thomas Dy Chung, Anthony B Pinkerton, Nicholas F LaRusso
Hepatic cystogenesis in Polycystic Liver Disease (PLD) is associated with increased levels of cAMP in cholangiocytes lining liver cysts. TGR5, a G protein-coupled bile acid receptor, is linked to cAMP and expressed in cholangiocytes. Therefore, we hypothesized that TGR5 might contribute to disease progression. We examined expression of TGR5 and Gα proteins in cultured cholangiocytes and in livers of animal models and humans with PLD. In vitro, we assessed cholangiocyte proliferation, cAMP levels, and cyst growth in response to: (i) TGR5 agonists [taurolithocholic acid (TLCA), oleanolic acid (OA) and two synthetic compounds]; (ii) a novel TGR5 antagonist (SBI-115); and (iii) a combination of SBI-115 and pasireotide, a somatostatin receptor (SSTR) analog...
May 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28542638/a-single-amino-acid-mutation-affects-elicitor-and-expansins-like-activities-of-cerato-platanin-a-non-catalytic-fungal-protein
#4
Simone Luti, Federica Martellini, Francesco Bemporad, Lorenzo Mazzoli, Paolo Paoli, Luigia Pazzagli
Cerato-platanin (CP) is a non-catalytic, cysteine-rich protein, the first member of the cerato-platanin family. It is a single-domain protein with a double Ψ/β barrel domain resembling the D1 domain of plant and bacterial expansins. Similarly to expansins, CP shows a cell wall-loosening activity on cellulose and can be defined as an expanisin-like protein, in spite of the missing D2 domain, normally present in plant expansins. The weakening activity shown on cellulose may facilitate the CP-host interaction, corroborating the role of CP in eliciting plant defence response...
2017: PloS One
https://www.readbyqxmd.com/read/28542158/identifying-pathogenicity-of-human-variants-via-paralog-based-yeast-complementation
#5
Fan Yang, Song Sun, Guihong Tan, Michael Costanzo, David E Hill, Marc Vidal, Brenda J Andrews, Charles Boone, Frederick P Roth
To better understand the health implications of personal genomes, we now face a largely unmet challenge to identify functional variants within disease-associated genes. Functional variants can be identified by trans-species complementation, e.g., by failure to rescue a yeast strain bearing a mutation in an orthologous human gene. Although orthologous complementation assays are powerful predictors of pathogenic variation, they are available for only a few percent of human disease genes. Here we systematically examine the question of whether complementation assays based on paralogy relationships can expand the number of human disease genes with functional variant detection assays...
May 25, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28539326/systematic-evaluation-of-protein-reduction-and-alkylation-reveals-massive-unspecific-side-effects-by-iodine-containing-reagents
#6
Torsten Müller, Dominic Winter
Reduction and alkylation of cysteine residues is part of virtually any proteomics workflow. Despite its frequent use, up to date no systematic investigation of the impact of different conditions on the outcome of proteomics studies has been performed. In this study, we compared common reduction reagents (dithiothreitol, tris-(2-carboxyethyl)-phosphine, and beta-mercaptoethanol) and alkylation reagents (iodoacetamide, iodoacetic acid, acrylamide, and chloroacetamide). Using in-gel digests as well as SAX fractionated in-solution digests of cytosolic fractions of HeLa cells, we evaluated 13 different reduction and alkylation conditions resulting in considerably varying identification rates...
May 24, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28538144/probing-the-potential-role-of-non-b-dna-structures-at-yeast-meiosis-specific-dna-double-strand-breaks
#7
Rucha Kshirsagar, Krishnendu Khan, Mamata V Joshi, Ramakrishna V Hosur, K Muniyappa
A plethora of evidence suggests that different types of DNA quadruplexes are widely present in the genome of all organisms. The existence of a growing number of proteins that selectively bind and/or process these structures underscores their biological relevance. Moreover, G-quadruplex DNA has been implicated in the alignment of four sister chromatids by forming parallel guanine quadruplexes during meiosis; however, the underlying mechanism is not well defined. Here we show that a G/C-rich motif associated with a meiosis-specific DNA double-strand break (DSB) in Saccharomyces cerevisiae folds into G-quadruplex, and the C-rich sequence complementary to the G-rich sequence forms an i-motif...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28535477/the-effect-of-crash-characteristics-on-cyclist-injuries-an-analysis-of-virginia-automobile-bicycle-crash-data
#8
Erin Robartes, T Donna Chen
This paper examines bicyclist, automobile driver, vehicle, environmental, and roadway characteristics that influence cyclist injury severity in order to determine which factors should be addressed to mitigate the worst bicyclist injuries. An ordered probit model is used to examine single bicycle-single vehicle crashes from Virginia police crash report data from 2010 to 2014. Five injury severity levels are considered: fatalities, severe injuries, minor or possible injuries, no apparent injuries, and no injury...
May 20, 2017: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/28533243/roles-of-ramr-and-tet-a-mutations-in-conferring-tigecycline-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-clinical-isolates
#9
Sheng-Kang Chiu, Li-Yueh Huang, Hsi Chen, Yu-Kuo Tsai, Ci-Hong Liou, Jung-Chung Lin, L Kristopher Siu, Feng-Yee Chang, Kuo-Ming Yeh
Tigecycline is regarded as a last-resort treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, but increasing numbers of tigecycline-resistant K. pneumoniae isolates have been reported. Tigecycline resistance mechanisms are underdetermined in CRKP. This study aimed to elucidate mechanisms underlying tigecycline resistance in 16 tigecycline- and carbapenem-resistant K. pneumoniae (TCRKP) isolates. Mutations in tigecycline resistance determinant genes (ramR, acrR, oqxR, tet(A), tet(L), tet(X), tet(M), rpsJ) were assessed by PCR amplicon sequencing, and mutations in ramR and tet(A) exhibited high prevalences individually (81%) and in combination (63%)...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533093/safety-and-immunogenicity-of-a-live-attenuated-influenza-h5-candidate-vaccine-strain-a-17-turkey-turkey-05-133-h5n2-and-its-priming-effects-for-potential-pre-pandemic-use-a-randomised-double-blind-placebo-controlled-trial
#10
Punnee Pitisuttithum, Kobporn Boonnak, Supat Chamnanchanunt, Pilaipan Puthavathana, Viravarn Luvira, Hatairat Lerdsamran, Jaranit Kaewkungwal, Saranath Lawpoolsri, Vipa Thanachartwet, Udomsak Silachamroon, Wanibtisam Masamae, Alexandra Schuetz, Ponthip Wirachwong, Sit Thirapakpoomanunt, Larisa Rudenko, Erin Sparrow, Martin Friede, Marie-Paule Kieny
BACKGROUND: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. METHODS: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts...
May 19, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28527830/crispr-cas9-mediated-precise-targeted-integration-in-vivo-using-a-double-cut-donor-with-short-homology-arms
#11
Xuan Yao, Xing Wang, Junlai Liu, Xinde Hu, Linyu Shi, Xiaowen Shen, Wenqin Ying, Xinyao Sun, Xin Wang, Pengyu Huang, Hui Yang
Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold) than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah(-/-) liver failure mice, offering an efficient approach for precisely targeted gene therapies...
May 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28526743/systematic-identification-of-functional-residues-of-artemisia-annua-amorpha-4-11-diene-synthase
#12
Xin Fang, Jian-Xu Li, Jin-Quan Huang, You-Li Xiao, Peng Zhang, Xiao-Ya Chen
Terpene synthases (TPSs) are responsible for the extremely diversified and complex structure of terpenoids. Amorpha-4,11-diene synthase (ADS) has a high (90%) fidelity in generating the sesquiterpene precursor for biosynthesis of artemisinin, an antimalarial drug, however, little is known about how active site residues of ADS involved in the carbocation rearrangement and cyclization reactions. Here, we identify seven residues that are key to most of the catalytic steps in ADS. By structural modeling and amino acid sequence alignments of ADS with two functionally relevant sesquiterpene synthases from Artemisia annua, we performed site-directed mutagenesis and found that a single substitution, T296V, impaired the ring closure activity almost completely, and tetra-substitutions (L374Y/L404V/L405I/G439S) led to an enzyme generating 80% monocyclic bisabolyl-type sesquiterpenes, whereas a double mutant (T399L/T447G) showed compromised activity in regioselective deprotonation to yield 34...
May 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28526561/mitochondrial-contact-site-and-cristae-organizing-system-a-central-player-in-membrane-shaping-and-crosstalk
#13
Florian Wollweber, Karina von der Malsburg, Martin van der Laan
Mitochondria are multifunctional metabolic factories and integrative signaling organelles of eukaryotic cells. The structural basis for their numerous functions is a complex and dynamic double-membrane architecture. The outer membrane connects mitochondria to the cytosol and other organelles. The inner membrane is composed of a boundary region and highly folded cristae membranes. The evolutionarily conserved mitochondrial contact site and cristae organizing system (MICOS) connects the two inner membrane domains via formation and stabilization of crista junction structures...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28525515/lidocaine-prevents-oxidative-stress-induced-endothelial-dysfunction-of-the-systemic-artery-in-rats-with-intermittent-periodontal-inflammation
#14
Takumi Saito, Yasuhiro Yamamoto, Guo-Gang Feng, Yoshiaki Kazaoka, Yoshihiro Fujiwara, Hiroyuki Kinoshita
BACKGROUND: Periodontal inflammation causes endothelial dysfunction of the systemic artery. However, it is unknown whether the use of local anesthetics during painful dental procedures alleviates periodontal inflammation and systemic endothelial function. This study was designed to examine whether the gingival or systemic injection of lidocaine prevents oxidative stress-induced endothelial dysfunction of the systemic artery in rats with intermittent periodontal inflammation caused by lipopolysaccharides (LPS)...
June 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28523480/2-methoxylated-fa-display-unusual-antibacterial-activity-towards-clinical-isolates-of-methicillin-resistant-staphylococcus-aureus-cimrsa-and-escherichia-coli
#15
Néstor M Carballeira, Nashbly Montano, Christian Morales, Joseph Mooney, Xiomara Torres, Dakeishla Díaz, David J Sanabria-Rios
The naturally occurring (6Z)-(±)-2-methoxy-6-hexadecenoic acid (1) and (6Z)-(±)-2-methoxy-6-octadecenoic acid (2) were synthesized in 7-8 steps with 38 and 13% overall yields, respectively, by using an acetylide coupling approach, which made it possible to obtain a 100% cis-stereochemistry for the double bonds. In a similar fashion, the acetylenic analogs (±)-2-methoxy-6-hexadecynoic acid (3) and (±)-2-methoxy-6-octadecynoic acid (4) were also synthesized in 6-7 steps with 48 and 16% overall yields, respectively...
May 18, 2017: Lipids
https://www.readbyqxmd.com/read/28522295/reversal-of-adipose-tissue-loss-by-probucol-in-mice-with-deficiency-of-both-scavenger-receptor-class-b-type-1-and-ldl-receptor-on-high-fat-diet
#16
Xin Guo, Jiawei Liao, Xiaomin Huang, Yuhui Wang, Wei Huang, George Liu
Scavenger receptor class B type 1(SR-B1) and low density lipoprotein receptor (LDLR) play vital roles in cholesterol homeostasis. Previous studies indicated a strong link between cholesterol and adipose tissue (AT). In this study, adult male SR-B1 and LDLR double knockout (DKO) mice were fed with high fat diet (HFD) for 3 months. Interestingly, we found severe loss of AT in DKO mice fed with HFD. To reverse the AT loss in DKO mice, 1% probucol was added in HFD. In DKO mice on HFD, plasma total cholesterol (TC) and free cholesterol (FC) levels were increased 6 and 15 folds respectively compared with wild type (WT) mice...
May 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28521880/pharmacokinetics-of-oral-hydrocortisone-results-and-implications-from-a-randomized-controlled-trial
#17
Jorien Werumeus Buning, Daan J Touw, Pauline Brummelman, Robin P F Dullaart, Gerrit van den Berg, Melanie M van der Klauw, Jasper Kamp, Bruce H R Wolffenbuttel, André P van Beek
CONTEXT AND OBJECTIVE: This study aimed at comparing pharmacokinetics of two different doses of hydrocortisone (HC) in patients with secondary adrenal insufficiency (SAI). DESIGN, SETTING AND PATIENTS: Forty-six patients with SAI participated in this randomized double-blind crossover study. INTERVENTION: Patients received two different doses of HC (0.2-0.3mg HC/kg body weight/day and 0.4-0.6mg HC/kg body weight/day). MAIN OUTCOME MEASURES: One- and two-compartment population models for plasma free cortisol, plasma total cortisol and salivary cortisol were parameterized...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28520687/3-nacl-adenosine-lidocaine-mg2-alm-bolus-and-4-hours-drip-infusion-reduces-noncompressible-hemorrhage-by-60-in-a-rat-model
#18
Hayley L Letson, Geoffrey P Dobson
BACKGROUND: Noncompressible torso hemorrhage is the leading cause of potentially survivable trauma in far-forward combat environments. Our aim was to examine the effect of small-volume 3% NaCl adenosine, lidocaine, and Mg (ALM) bolus and 0.9% NaCl/ALM "drip" on survivability and cardiac/gut/kidney function in a rat model of hepatic hemorrhage and shock. METHODS: Male Sprague-Dawley rats (428 ± 4 g) were anesthetized and randomly assigned to one of five groups (n = 16): (1) Sham, (2) No treatment, (3) Saline controls, (4) ALM therapy, and (5) Hextend...
June 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28520414/structural-and-magnetic-transitions-in-caco3v4o12-perovskite-at-extreme-conditions
#19
Sergey V Ovsyannikov, Elena Bykova, Anna Pakhomova, Denis P Kozlenko, Maxim Bykov, Sergey E Kichanov, Natalia V Morozova, Igor V Korobeinikov, Fabrice Wilhelm, Andrei Rogalev, Alexander A Tsirlin, Alexander V Kurnosov, Yury G Zainulin, Nadezda I Kadyrova, Alexander P Tyutyunnik, Leonid Dubrovinsky
We investigated the structural, vibrational, magnetic, and electronic properties of the recently synthesized CaCo3V4O12 double perovskite with the high-spin (HS) Co(2+) ions in a square-planar oxygen coordination at extreme conditions of high pressures and low temperatures. The single-crystal X-ray diffraction and Raman spectroscopy studies up to 60 GPa showed a conservation of its cubic crystal structure but indicated a crossover near 30 GPa. Above 30 GPa, we observed both an abnormally high "compressibility" of the Co-O bonds in the square-planar oxygen coordination and a huge anisotropic displacement of HS-Co(2+) ions in the direction perpendicular to the oxygen planes...
May 18, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28514723/genomic-profiling-of-pelvic-genital-type-leiomyosarcoma-in-a-woman-with-a-germline-chek2-c-1100delc-mutation-and-a-concomitant-diagnosis-of-metastatic-invasive-ductal-breast-carcinoma
#20
My Linh Thibodeau, Caralyn Reisle, Eric Zhao, Lee Ann Martin, Yazeed Alwelaie, Karen L Mungall, Carolyn Ch'ng, Ruth Thomas, Tony Ng, Stephen Yip, Howard Lim, Sophie Sun, Sean S Young, Aly Karsan, Yongjun Zhao, Andrew J Mungall, Richard A Moore, Daniel Renouf, Karen Gelmon, Yussanne P Ma, Malcolm Hayes, Janessa Laskin, Marco A Marra, Kasmintan A Schrader, Steven J M Jones
INTRODUCTION: We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumour suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximate 2-fold increase in breast cancer risk...
May 16, 2017: Cold Spring Harbor Molecular Case Studies
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