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https://www.readbyqxmd.com/read/29775608/regulation-of-the-gyr-operon-of-mycobacterium-tuberculosis-by-overlapping-promoters-dna-topology-and-reiterative-transcription
#1
Rajiv Kumar Jha, Priyanka Tare, Valakunja Nagaraja
DNA gyrase introduces negative supercoils into DNA to maintain topological homeostasis. The genes encoding gyrase, gyrB and gyrA, form a dicistronic operon in Mycobacterium tuberculosis (Mtb) and other actinobacteria. Earlier work indicated that DNA relaxation stimulates the expression of the gyr genes, a phenomenon termed relaxation-stimulated transcription (RST). The present study addresses the underlying mechanism of gyr operon regulation. The operon is regulated by overlapping and divergently oriented promoters located upstream of gyrB...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29774023/ferritin-h-deficiency-in-myeloid-compartments-dysregulates-host-energy-metabolism-and-increases-susceptibility-to-mycobacterium-tuberculosis-infection
#2
Vineel P Reddy, Krishna C Chinta, Vikram Saini, Joel N Glasgow, Travis D Hull, Amie Traylor, Fernanda Rey-Stolle, Miguel P Soares, Rajhmun Madansein, Md Aejazur Rahman, Coral Barbas, Kievershen Nargan, Threnesan Naidoo, Pratistadevi K Ramdial, James F George, Anupam Agarwal, Adrie J C Steyn
Iron is an essential factor for the growth and virulence of Mycobacterium tuberculosis ( Mtb) . However, little is known about the mechanisms by which the host controls iron availability during infection. Since ferritin heavy chain (FtH) is a major intracellular source of reserve iron in the host, we hypothesized that the lack of FtH would cause dysregulated iron homeostasis to exacerbate TB disease. Therefore, we used knockout mice lacking FtH in myeloid-derived cell populations to study Mtb disease progression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773644/bhlhe40-is-an-essential-repressor-of-il-10-during-mycobacterium-tuberculosis-infection
#3
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/29770076/the-use-of-technology-to-improve-health-care-to-saskatchewan-s-first-nations-communities
#4
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/29769016/whole-genome-sequencing-data-of-1110-mycobacterium-tuberculosis-isolates-identifies-insertions-and-deletions-associated-with-drug-resistance
#5
Xi Zeng, Jamie Sui-Lam Kwok, Kevin Yi Yang, Kenneth Siu-Sing Leung, Mai Shi, Zhiyuan Yang, Wing-Cheong Yam, Stephen Kwok-Wing Tsui
BACKGROUND: Drug resistance in Mycobacterium tuberculosis (MTB) is one of the major challenges in tuberculosis (TB) treatment. However, known mutations cannot explain all of the cases of resistance and little research has focused on the relationship between insertions / deletions (indels) and drug resistance. RESULTS: Here, we retrieved whole genome sequencing data of 743 drug-resistant MTB strains and 367 pan-susceptible strains from TB patients from the public domain to identify novel genomic markers of drug resistance...
May 16, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29768561/the-role-of-the-xpert-mtb-rif-assay-among-adolescents-suspected-of-pulmonary-tuberculosis-in-rio-de-janeiro-brazil
#6
Thania Luiza de Andrade Sieiro, Rafaela Baroni Aurílio, Elizabeth Cristina C Soares, Silvia S Chiang, Clemax Couto Sant Anna
INTRODUCTION: The teste rápido molecular para tuberculose (TRM-TB) was introduced in 2014 in Brazil for tuberculosis screening. However, its role in adolescents in Brazil has not been studied. METHODS: A descriptive study of adolescents with suspected tuberculosis using National Laboratory software. RESULTS: Of 852 (15.4%) suspected cases, 131 were positive by TRM-TB and 2% were resistant to rifampicin. Among TRM-TB-positive cases, 105 (91...
March 2018: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29762680/tuberculosis-and-the-art-of-macrophage-manipulation
#7
S Upadhyay, E Mittal, J A Philips
Macrophages are first-line responders against microbes. The success of Mycobacterium tuberculosis (Mtb) rests upon its ability to convert these antimicrobial cells into a permissive cellular niche. This is a remarkable accomplishment, as the antimicrobial arsenal of macrophages is extensive. Normally bacteria are delivered to an acidic, degradative lysosome through one of several trafficking pathways, including LC3-associated phagocytosis (LAP) and autophagy. Once phagocytozed, the bacilli are subjected to reactive oxygen and nitrogen species, and they induce the expression of proinflammatory cytokines, which serve to augment host responses...
June 1, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29761826/computational-discovery-of-potent-drugs-to-improve-the-treatment-of-pyrazinamide-resistant-mycobacterium-tuberculosis-mutants
#8
Manaswini Jagadeb, Surya N Rath, Avinash Sonawane
Emergence of multi-drug resistance tuberculosis has become a serious health problem globally. Accumulation of mutations in the drug target led to the development of multi-drug resistant mycobacterial strains that have made most of the conventional drugs ineffective. Hence, there is desperate need for the development of new therapeutic strategies. Here, we focused on the analysis of mutations in Mycobacterium tuberculosis (Mtb) PncA (pyrazinamidase) that is responsible for resistance against first-line anti-tuberculosis pyrazinamide (PZA) drug...
May 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29760437/cd82-hypomethylation-is-essential-for-tuberculosis-pathogenesis-via-regulation-of-runx1-rab5-22
#9
Hyun-Jung Koh, Ye-Ram Kim, Jae-Sung Kim, Jin-Seung Yun, Sojin Kim, Sun Young Kim, Kiseok Jang, Chul-Su Yang
The tumor suppressor gene CD82/KAI1 is a member of the tetraspanin superfamily and organizes various membrane-based processes. Mycobacterium tuberculosis (MTB) persists in host macrophages by interfering with phagolysosome biogenesis and inflammatory responses, but the role of CD82 in controlling the intracellular survival of pathogenic mycobacteria within macrophages remains poorly understood. In this study, we demonstrated that the virulent MTB strain H37Rv (MTB Rv) induced CD82 promoter hypomethylation, resulting in CD82 expression...
May 14, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29755479/lysophosphatidylcholine-promotes-phagosome-maturation-and-regulates-inflammatory-mediator-production-through-the-protein-kinase-a-phosphatidylinositol-3-kinase-p38-mitogen-activated-protein-kinase-signaling-pathway-during-mycobacterium-tuberculosis-infection
#10
Hyo-Ji Lee, Hyun-Jeong Ko, Dong-Kun Song, Yu-Jin Jung
Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754051/label-free-nano-biosensing-on-the-road-to-tuberculosis-detection
#11
REVIEW
Behrouz Golichenari, Kelly Velonia, Rahim Nosrati, Alireza Nezami, Aref Farokhi-Fard, Khalil Abnous, Javad Behravan, Aristidis M Tsatsakis
Tuberculosis, an ailment caused by the bacterium Mycobacterium tuberculosis (Mtb) complex, is one of the catastrophic transmittable diseases that affect human. Reports published by WHO indicate that in 2017 about 6.3 million people progressed to TB and 53 million TB patients died from 2000 to 2016. Therefore, early diagnosis of the disease is of great importance for global health care programs. Common diagnostics like the traditional PPD test and antibody-assisted assays suffer the lack of sensitivity, long processing time and cumbersome post-test proceedings...
August 15, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29753941/an-integrated-computational-approach-of-molecular-dynamics-simulations-receptor-binding-studies-and-pharmacophore-mapping-analysis-in-search-of-potent-inhibitors-against-tuberculosis
#12
Shivangi Agarwal, Ekta Verma, Vivek Kumar, Namrita Lall, Samaresh Sau, Arun K Iyer, Sushil K Kashaw
Tuberculosis is an infectious chronic disease caused by obligate pathogen Mycobacterium tuberculosis that affects millions of people worldwide. Although many first and second line drugs are available for its treatment, but their irrational use has adversely lead to the emerging cases of multiple drug resistant and extensively drug-resistant tuberculosis. Therefore, there is an intense need to develop novel potent analogues for its treatment. This has prompted us to develop potent analogues against TB. The Mycobacterium tuberculosis genome provides us with number of validated targets to combat against TB...
May 3, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29752576/in-silico-docking-and-molecular-dynamics-simulation-of-3-dehydroquinate-synthase-dhqs-from-mycobacterium-tuberculosis
#13
Mustafa Alhaji Isa, Rita Singh Majumdhar, Shazia Haider
The shikimate pathway is as an attractive target because it is present in bacteria, algae, fungi, and plants but does not occur in mammals. In Mycobacterium tuberculosis (MTB), the shikimate pathway is integral to the biosynthesis of naphthoquinones, menaquinones, and mycobactin. In these study, novel inhibitors of 3-dehydroquinate synthase (DHQS), an enzyme that catalyzes the second step of the shikimate pathway in MTB, were determined. 12,165 compounds were selected from two public databases through virtual screening and molecular docking analysis using PyRx 8...
May 11, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29752410/identification-and-structural-characterization-of-a-histidinol-phosphate-phosphatase-from-mycobacterium-tuberculosis
#14
Bhavya Jha, Deepak Kumar, Arun Sharma, Abhisek Dwivedy, Ramandeep Singh, Bichitra Kumar Biswal
The absence of a histidine biosynthesis pathway in humans, coupled with histidine essentiality for survival of the important human pathogen Mycobacterium tuberculosis ( Mtb ), underscores the importance of the bacterial enzymes of this pathway as major anti-tuberculosis drug targets. However, the identity of the mycobacterial enzyme that functions as the histidinol phosphate phosphatase (HolPase) of this pathway remains to be established. Here, we demonstrate that the enzyme encoded by the Rv3137 gene, belonging to the inositol monophosphatase (IMPase) family, functions as the Mtb HolPase and specifically dephosphorylates histidinol phosphate...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29752320/rediagnosis-of-lung-cancer-as-nut-midline-carcinoma-based-on-clues-from-tumor-genomic-profiling
#15
Alexander S Baras, Jarushka Naidoo, Christine L Hann, Peter B Illei, Charles W Reninger, Josh Lauring
Tumor DNA sequencing can identify rare driver genomic alterations that suggest targets for cancer therapy, even when these drivers cannot be suspected on clinical grounds. In some cases, genomic alterations identified in the tumor can lead to a change in diagnosis with implications for prognosis and therapy. This report describes a case in which evaluation of tumor sequencing results by a molecular tumor board (MTB) led to rediagnosis of a non-small cell lung cancer as highly aggressive NUT midline carcinoma, with implications for targeted therapy using an investigational bromodomain and extraterminal (BET) inhibitor...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29752301/mitochondrial-cyclophilin-d-regulates-t-cell-metabolic-responses-and-disease-tolerance-to-tuberculosis
#16
Fanny Tzelepis, Julianna Blagih, Nargis Khan, Joshua Gillard, Laura Mendonca, Dominic G Roy, Eric H Ma, Philippe Joubert, Russell G Jones, Maziar Divangahi
Mycobacterium tuberculosis ( Mtb ) is one of the most ancient human pathogens, yet the exact mechanism(s) of host defense against Mtb remains unclear. Although one-third of the world's population is chronically infected with Mtb , only 5 to 10% develop active disease. This indicates that, in addition to resistance mechanisms that control bacterial burden, the host has also evolved strategies to tolerate the presence of Mtb to limit disease severity. We identify mitochondrial cyclophilin D (CypD) as a critical checkpoint of T cell metabolism that controls the expansion of activated T cells...
May 11, 2018: Science Immunology
https://www.readbyqxmd.com/read/29752010/comparison-of-genexpert-mtb-rif-assay-and-led-fm-microscopy-for-the-diagnosis-of-extra-pulmonary-tuberculosis-in-khyber-pakhtunkhwa-pakistan
#17
Anwar Sheed Khan, Sajid Ali, Muhammad Tahir Khan, Sajjad Ahmed, Yasir Khattak, Abduljabbar, Muhammad Irfan, Wasim Sajjad
GeneXpert is one of the recent technological instruments used to diagnose tuberculosis in a short span of time. In this study, the performance of GeneXpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis (EPTB) was compared with light-emitting diode Fluorescent Microscopy (LED-FM) in Khyber Pakhtunkhwa, Pakistan. A total of 737 EPTB samples were collected from tuberculosis (TB) suspected patients. Out of these samples, male to female ratio was 53% (n=390) to 47% (n=347) respectively. The sensitivity and specificity was 73% and 100% for GeneXpert, while 40% and 100% for LED-FM microscopy...
April 27, 2018: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/29751798/clinic-flow-for-sti-hiv-and-tb-patients-in-an-urban-infectious-disease-clinic-offering-point-of-care-testing-services-in-durban-south-africa
#18
Katrina J Stime, Nigel Garrett, Yukteshwar Sookrajh, Jienchi Dorward, Ntuthu Dlamini, Ayo Olowolagba, Monisha Sharma, Ruanne V Barnabas, Paul K Drain
BACKGROUND: Many clinics in Southern Africa have long waiting times. The implementation of point-of-care (POC) tests to accelerate diagnosis and improve clinical management in resource-limited settings may improve or worsen clinic flow and waiting times. The objective of this study was to describe clinic flow with special emphasis on the impact of POC testing at a large urban public healthcare clinic in Durban, South Africa. METHODS: We used time and motion methods to directly observe patients and practitioners...
May 11, 2018: BMC Health Services Research
https://www.readbyqxmd.com/read/29748525/an-adaption-broadcast-radius-based-code-dissemination-scheme-for-low-energy-wireless-sensor-networks
#19
Shidi Yu, Xiao Liu, Anfeng Liu, Naixue Xiong, Zhiping Cai, Tian Wang
Due to the Software Defined Network (SDN) technology, Wireless Sensor Networks (WSNs) are getting wider application prospects for sensor nodes that can get new functions after updating program codes. The issue of disseminating program codes to every node in the network with minimum delay and energy consumption have been formulated and investigated in the literature. The minimum-transmission broadcast (MTB) problem, which aims to reduce broadcast redundancy, has been well studied in WSNs where the broadcast radius is assumed to be fixed in the whole network...
May 10, 2018: Sensors
https://www.readbyqxmd.com/read/29746130/expanding-benzoxazole-based-inosine-5-monophosphate-dehydrogenase-impdh-inhibitor-structure-activity-as-potential-anti-tuberculosis-agents
#20
Shibin Chacko, Helena I M Boshoff, Vinayak Singh, Davide M Ferraris, Deviprasad R Gollapalli, Minjia Zhang, Ann P Lawson, Michael J Pepi, Andrzej Joachimiak, Menico Rizzi, Valerie Mizrahi, Gregory D Cuny, Lizbeth Hedstrom
New drugs and molecular targets are urgently needed to address the emergence and spread of drug-resistant tuberculosis. Mycobacterium tuberculosis (Mtb) inosine 5'-monophosphate dehydrogenase 2 (MtbIMPDH2) is a promising yet controversial potential target. Inhibition of MtbIMPDH2 blocks the biosynthesis of guanine nucleotides, but high concentrations of guanine can potentially rescue the bacteria. Herein we describe an expansion of the structure-activity relationship (SAR) for the benzoxazole series of MtbIMPDH2 inhibitors and demonstrate that minimum inhibitory concentrations (MIC) of ≤ 1 μM can be achieved...
May 10, 2018: Journal of Medicinal Chemistry
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