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https://www.readbyqxmd.com/read/29777693/cleavage-of-molybdopterin-synthase-moad-moae-linear-fusion-by-jamm-mpn-domain-containing-metalloprotease-dr0402-from-deinococcus-radiodurans
#1
Yoon-Mo Yang, Young-Bin Won, Chang-Jun Ji, Jung-Hoon Kim, Su-Hyun Ryu, Youn-Ha Ok, Jin-Won Lee
Molybdenum cofactor (Moco), molybdopterin (MPT) complexed with molybdenum, is an essential cofactor required for the catalytic center of diverse enzymes in all domains of life. Since Moco cannot be taken up as a nutrient unlike many other cofactors, Moco requires de novo biosynthesis. During the synthesis of MPT, the sulfur atom on the C-terminus of MoaD is transferred to cyclic pyranopterin monophosphate (cPMP) which is bound in the substrate pocket of MoaE. MoaD is a ubiquitin-like (Ubl) protein and has a C-terminal di-Gly motif which is a common feature of Ubl proteins...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777407/modelling-the-delay-between-pharmacokinetics-and-eeg-effects-of-morphine-in-rats-binding-kinetic-versus-effect-compartment-models
#2
Wilhelmus E A de Witte, Vivi Rottschäfer, Meindert Danhof, Piet H van der Graaf, Lambertus A Peletier, Elizabeth C M de Lange
Drug-target binding kinetics (as determined by association and dissociation rate constants, k on and k off ) can be an important determinant of the kinetics of drug action. However, the effect compartment model is used most frequently instead of a target binding model to describe hysteresis. Here we investigate when the drug-target binding model should be used in lieu of the effect compartment model. The utility of the effect compartment (EC), the target binding kinetics (TB) and the combined effect compartment-target binding kinetics (EC-TB) model were tested on either plasma (ECPL , TBPL and EC-TBPL ) or brain extracellular fluid (ECF) (ECECF , TBECF and EC-TBECF ) morphine concentrations and EEG amplitude in rats...
May 18, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29777023/xanthates-metabolism-by-flavoprotein-containing-monooxygenases-fmo-and-antimycobacterial-activity
#3
Stanislav Yanev, Tsveta Stoyanova, Violeta Valcheva, Paul R Ortiz De Montellano
Ethionamide (ETH) plays a central role in the treatment of tuberculosis in patients resistant to the first-line drugs. The ETH, thioamide, and thiourea class of antituberculosis agents are pro-drugs that are oxidatively converted to their active S-oxides by the flavin monooxygenase EtaA of M. tuberculosis, thus initiating the chain of reactions that result in inhibition of mycolic acid biosynthesis and cell lysis. As part of a search for new lead candidates, we report here that several xanthates are oxidized by purified EtaA to S-oxide metabolites (perxanthates) that are implicated in the antimycobacterial activity of these compounds...
May 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29776430/recurrent-bilateral-mycobacterium-bovis-necrotizing-epididymitis-a-case-report
#4
Simon Grandjean-Lapierre, Simon-Djamel Thiberville, Mustapha Fellag, Christophe Eghazarian, Feriel Bouzid, Christina Gavril, Michel Drancourt
BACKGROUND: Mycobacterium bovis causing tuberculosis in animals is responsible for zoonotic tuberculosis in patients. Veterinary control measures and milk pasteurization has led to a significant decrease in human cases of M. bovis infections in developed countries. CASE PRESENTATION: We diagnosed recurrent M. bovis epididymitis in a 63-year old Caucasian man without any signs of pulmonary or disseminated disease. Relevant epidemiological expositions included camel milk drinking during prolonged travels in Niger, prior to initial clinical manifestations...
May 18, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29774850/mycobacterium-bovis-infection-of-red-fox-france
#5
Lorraine Michelet, Krystel De Cruz, Sylvie Hénault, Jennifer Tambosco, Céline Richomme, Édouard Réveillaud, Hélène Gares, Jean-Louis Moyen, María Laura Boschiroli
Mycobacterium bovis infection in wild red foxes was found in southern France, where livestock and other wildlife species are infected. Foxes frequently interact with cattle but have been underestimated as a reservoir of M. bovis. Our results suggest a possible role of the red fox in the epidemiology of bovine tuberculosis.
June 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29773644/bhlhe40-is-an-essential-repressor-of-il-10-during-mycobacterium-tuberculosis-infection
#6
Jeremy P Huynh, Chih-Chung Lin, Jacqueline M Kimmey, Nicholas N Jarjour, Elizabeth A Schwarzkopf, Tara R Bradstreet, Irina Shchukina, Oleg Shpynov, Casey T Weaver, Reshma Taneja, Maxim N Artyomov, Brian T Edelson, Christina L Stallings
The cytokine IL-10 antagonizes pathways that control Mycobacterium tuberculosis ( Mtb ) infection. Nevertheless, the impact of IL-10 during Mtb infection has been difficult to decipher because loss-of-function studies in animal models have yielded only mild phenotypes. We have discovered that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) is required to repress Il10 expression during Mtb infection. Loss of Bhlhe40 in mice results in higher Il10 expression, higher bacterial burden, and early susceptibility similar to that observed in mice lacking IFN-γ...
May 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29773279/-non-tuberculous-mycobacterial-cervical-adenitis-in-children-2-cases
#7
N Sigg, S Bailleul, J-M Turmel, G Legrand, S Kettani, L Martin
BACKGROUND: Cervical lymphadenitis is the most common manifestation of infection with nontuberculous mycobacteria (NTM) in immunocompetent children. Nevertheless, it is poorly known by dermatologists. Its incidence, which is currently increasing since the cessation of BCG vaccination in 2007, raises several issues regarding its pathophysiology, diagnosis and management. PATIENTS AND METHODS: We report two cases of NTM adenitis: one in a 2-year-old girl vaccinated with BCG and one in an unvaccinated 22-month-old boy, in whom a misleading presentation led to delayed diagnosis...
May 14, 2018: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29771143/cell-envelope-lipids-in-the-pathophysiology-of-mycobacterium-tuberculosis
#8
Parul Singh, Nagender Rao Rameshwaram, Sudip Ghosh, Sangita Mukhopadhyay
Mycobacterium tuberculosis is an intracellular bacterium that persists and replicates inside macrophages. The bacterium possesses an unusual lipid-rich cell envelope that provides a hydrophobic impermeable barrier against many environmental stressors and allows it to survive extremely hostile intracellular surroundings. Since the lipid-rich envelope is crucial for M. tuberculosis virulence, the components of the cell wall lipid biogenesis pathways constitute an attractive target for the development of vaccines and antimycobacterial chemotherapeutics...
May 17, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29770694/detection-of-pcr-amplified-tuberculosis-dna-fragments-with-polyelectrolyte-modified-field-effect-sensors
#9
Thomas Stefan Bronder, Max Philipp Jessing, Arshak Poghossian, Michael Keusgen, Michael J Schöning
Field-effect-based electrolyte-insulator-semiconductor (EIS) sensors were modified with a bilayer of positively charged weak polyelectrolyte (poly(allylamine hydrochloride) (PAH)) and probe single-stranded deoxyribonucleic acid (ssDNA) and are used for the detection of target complementary deoxyribonucleic acid (cDNA) in different test solutions. The sensing mechanism is based on the detection of the intrinsic molecular charge of target cDNA molecules after the hybridization event between cDNA and immobilized probe ssDNA...
May 17, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29770360/biomarkers-associated-with-death-after-initiating-treatment-for-tuberculosis-and-hiv-in-patients-with-very-low-cd-4-cells
#10
Fred R Sattler, Daniel Chelliah, Xingye Wu, Alejandro Sanchez, Michelle A Kendall, Evelyn Hogg, David Lagat, Umesh Lalloo, Valdilea Veloso, Diane V Havlir, Alan Landay
Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death. Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3 ...
2018: Pathogens & Immunity
https://www.readbyqxmd.com/read/29770076/the-use-of-technology-to-improve-health-care-to-saskatchewan-s-first-nations-communities
#11
I Khan, N Ndubuka, K Stewart, V McKinney, I Mendez
Background: Saskatchewan is a province of over one million people and over 13% are Indigenous peoples, many of whom live on reserve lands. Despite continued efforts, access to health care remains a significant challenge for these Indigenous people, especially those in the North. Objective: To address this challenge, Saskatchewan's health care providers have been incorporating the use of technology for various health services. This paper describes various ways technology has been used in First Nations communities in Saskatchewan...
June 1, 2017: Canada Communicable Disease Report, Relevé des Maladies Transmissibles Au Canada
https://www.readbyqxmd.com/read/29769379/activation-of-bacterial-histidine-kinases-insights-into-the-kinetics-of-the-cis-autophosphorylation-mechanism
#12
Gaurav D Sankhe, Narendra M Dixit, Deepak K Saini
Two-component signaling systems (TCSs) are central to bacterial adaptation. However, the mechanisms underlying the reactions involving TCS proteins and their reaction rates are largely undetermined. Here, we employed a combined experimental and theoretical approach to elucidate the kinetics of autophosphorylation of three histidine kinases (HKs) of Mycobacterium tuberculosis , viz. , MtrB, PrrB, and PhoR, all known to play a role in regulating its virulence. Using wild-type and mutant proteins, we performed dimerization assays, thermophoretic-affinity measurements, and competition-based phosphorylation assays to establish that for HK, MtrB autophosphorylation occurs in cis , similar to what has been proposed for the PhoR and PrrB HKs...
June 27, 2018: MSphere
https://www.readbyqxmd.com/read/29769160/cross-border-outbreak-of-extensively-drug-resistant-tuberculosis-linked-to-a-university-in-romania
#13
O Popovici, Ph Monk, D Chemtob, D Chiotan, P J Freidlin, R Groenheit, M Haanperä, D Homorodean, M Mansjö, E Robinson, E Rorman, G Smith, H Soini, M J Van Der Werf
Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases...
May 2018: Epidemiology and Infection
https://www.readbyqxmd.com/read/29769017/a-cross-sectional-investigation-of-the-health-needs-of-asylum-seekers-in-a-refugee-clinic-in-germany
#14
Laura F Goodman, Guy W Jensen, Joseph M Galante, Diana L Farmer, Stephanie Taché
BACKGROUND: Over one million asylum seekers were registered in Germany in 2016, most from Syria and Afghanistan. The Refugee Convention guarantees access to healthcare, however delivery mechanisms remain heterogeneous. There is an urgent need for more data describing the health conditions of asylum seekers to guide best practices for healthcare delivery. In this study, we describe the state of health of asylum seekers presenting to a multi-specialty primary care refugee clinic. METHODS: Demographic and medical diagnosis data were extracted from the electronic medical records of patients seen at the ambulatory refugee clinic in Dresden, Germany between 15 September 2015 and 31 December 2016...
May 16, 2018: BMC Family Practice
https://www.readbyqxmd.com/read/29768381/tuberculous-pleurisy-mimicking-mycoplasma-pneumoniae-infection-in-a-previously-healthy-young-adult-a-case-report
#15
Daizo Yaguchi, Motoshi Ichikawa, Masato Shizu, Noriko Inoue, Daisuke Kobayashi, Naoyuki Imai, Masao Ito
RATONALE: Sometimes, pleural effusion accompanying an acute Mycoplasma pneumoniae infection or tuberculous pleurisy has similar analysis results. We report a case of tuberculous pleurisy which was initially diagnosed as acute M pneumoniae infection, which is of special interest because anti-Mycoplasma antibody results were positive, which served as a red herring. PATIENT CONCERNS: A 20-year-old woman visited the outpatient emergency romm of our hospital for chief complaints of high fever, dry cough, and pleuralgia persiting for 2 days...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29767993/multi-metallic-microparticles-increase-the-potency-of-rifampicin-against-intracellular-mycobacterium-tuberculosis
#16
Timothy Ellis, Michele Chiappi, Andres Garcia-Trenco, Maryam Al-Ejji, Srijata Sarkar, Theoni K Georgiou, Milo Sebastian Peter Shaffer, Teresa D Tetley, Stephan Schwander, Mary P Ryan, Alexandra E Porter
Mycobacterium tuberculosis (M.tb) has the extraordinary ability to adapt to the administration of antibiotics through the development of resistance mechanisms. By rapidly exporting drugs from within the cytosol, these pathogenic bacteria diminish antibiotic potency and drive the presentation of drug tolerant tuberculosis (TB). The membrane integrity of M.tb is pivotal in retaining these drug-resistant traits. Silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) are established antimicrobial agents that effectively compromise membrane stability, giving rise to increased bacterial permeability to antibiotics...
May 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29766819/synthesis-in-silico-molecular-docking-and-pharmacokinetic-studies-in-vitro-antimycobacterial-and-antimicrobial-studies-of-new-imidozolones-clubbed-with-thiazolidinedione
#17
Imran H Khan, Navin B Patel, Vatsal M Patel
BACKGROUND: A series of (E)-5-(4-((Z)-4-substitutedbenzylidene/2-thienylmethylene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl) benzylidene)thiazolidine-2,4-dione were synthesized and evaluated for antimycobacterial and antimicrobial activity. All these ligands were docked against protein (InhA) Enoyl-ACP reductase of the type II fatty acid syntase (FAS-II) system, (PDB ID: 4COD). OBJECTIVE: In this report we have designed and synthesized azole scaffolds with good antitubercular activities as there is a real need to develop new candidates with less toxicity and more efficient toward pathogen...
May 15, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29766527/exploring-workplace-tb-interventions-with-foreign-born-latino-workers
#18
Donald E Eggerth, Brenna M Keller, Michael A Flynn
BACKGROUND: Persons born outside the United States are more likely to be diagnosed with tuberculosis disease (TB) than native-born individuals. Foreign-born Latinos at risk of TB may be difficult to reach with public health interventions due to cultural and institutional barriers. Workplaces employing large concentrations of foreign-born Latinos may be useful locations for TB interventions targeting this high-risk population. METHOD: This study used a two-phase approach to investigate the feasibility of workplace TB interventions...
May 15, 2018: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/29765644/identification-of-potent-chromone-embedded-1-2-3-triazoles-as-novel-anti-tubercular-agents
#19
Viswanadh Nalla, Aslam Shaikh, Sanket Bapat, Renu Vyas, M Karthikeyan, P Yogeeswari, D Sriram, M Muthukrishnan
A series of 20 novel chromone embedded [1,2,3]-triazoles derivatives were synthesized via an easy and convenient synthetic procedure starting from 2-hydroxy acetophenone. The in vitro anti-mycobacterial evaluation studies carried out in this work reveal that seven compounds exhibit significant inhibition against Mycobacterium tuberculosis H37Rv strain with MIC in the range of 1.56-12.5 µg ml-1 . Noticeably, compound 6s was the most potent compound in vitro with a MIC value of 1.56 µg ml-1 . Molecular docking and chemoinformatics studies revealed that compound 6s displayed drug-like properties against the enoyl-acyl carrier protein reductase of M...
April 2018: Royal Society Open Science
https://www.readbyqxmd.com/read/29765372/is-iqg-607-a-potential-metallodrug-or-metallopro-drug-with-a-defined-molecular-target-in-mycobacterium-tuberculosis
#20
REVIEW
Bruno L Abbadi, Valnês da Silva Rodrigues-Junior, Adilio da Silva Dadda, Kenia Pissinate, Anne D Villela, Maria M Campos, Luiz G de França Lopes, Cristiano V Bizarro, Pablo Machado, Eduardo H S Sousa, Luiz A Basso
The emergence of strains of Mycobacterium tuberculosis resistant to isoniazid (INH) has underscored the need for the development of new anti-tuberculosis agents. INH is activated by the mycobacterial katG -encoded catalase-peroxidase, forming an acylpyridine fragment that is covalently attached to the C4 of NADH. This isonicotinyl-NAD adduct inhibits the activity of 2- trans -enoyl-ACP(CoA) reductase (InhA), which plays a role in mycolic acid biosynthesis. A metal-based INH analog, Na3 [FeII (CN)5 (INH)]·4H2 O, IQG-607, was designed to have an electronic redistribution on INH moiety that would lead to an intramolecular electron transfer to bypass KatG activation...
2018: Frontiers in Microbiology
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