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https://www.readbyqxmd.com/read/28106929/conformational-analysis-of-an-antibacterial-cyclodepsipeptide-active-against-m-tuberculosis-by-a-combined-roe-and-rdc-analysis
#1
Maic Fredersdorf, Michael Kurz, Armin Bauer, Marc-Olivier Ebert, Carla Rigling, Laurie Lannes, Christina Thiele
Griselimycin (GM) and methylgriselimycin (MGM), naturally produced by microorganisms of the genus Streptomyces, are cyclic depsipeptides composed of ten amino acids. They exhibit antibacterial activity against mycobacterium species by inhibiting the sliding clamp of prokaryotic DNA polymerase III and are therefore considered as potential anti-tuberculosis drugs. The difference between both peptides is the presence of L -(R)-4-methylproline in MGM instead of L -proline in GM at position 8 of the amino acid sequence...
January 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28105911/integrating-gene-set-analysis-and-nonlinear-predictive-modeling-of-disease-phenotypes-using-a-bayesian-multitask-formulation
#2
Mehmet Gönen
BACKGROUND: Identifying molecular signatures of disease phenotypes is studied using two mainstream approaches: (i) Predictive modeling methods such as linear classification and regression algorithms are used to find signatures predictive of phenotypes from genomic data, which may not be robust due to limited sample size or highly correlated nature of genomic data. (ii) Gene set analysis methods are used to find gene sets on which phenotypes are linearly dependent by bringing prior biological knowledge into the analysis, which may not capture more complex nonlinear dependencies...
December 13, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28103313/mycobacterium-marinum-degrades-both-triacylglycerols-and-phospholipids-from-its-dictyostelium-host-to-synthesise-its-own-triacylglycerols-and-generate-lipid-inclusions
#3
Caroline Barisch, Thierry Soldati
During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28102172/dr-j%C3%A3-zef-aleksiewicz-activity-in-support-of-the-development-of-orthopedics-and-rehabilitation-in-iwonicz-zdr%C3%A3-j-1921-1957
#4
Sławomir Jandziś, Stanisław Zaborniak
Based on source materials in the possession of Józef Aleksiewicz family (typescripts, manuscripts, photographs, other documents) and articles published in professional medical journals and newspapers, the authors present the contribution of Dr. J. Aleksiewicz to the development of orthopedics and rehabilitation in Iwonicz-Zdrój. In May 1921, he was appointed Surgeon General of the Spa Commission in Iwonicz-Zdrój. After holding several scholarly trips abroad in 1925 to sanatoriums treating cases of osteo-articular tuberculosis, he commenced the construction of "Sanato", a modern sanatorium...
August 30, 2016: Ortopedia, Traumatologia, Rehabilitacja
https://www.readbyqxmd.com/read/28100788/genomic-infectious-disease-epidemiology-in-partially-sampled-and-ongoing-outbreaks
#5
Xavier Didelot, Christophe Fraser, Jennifer Gardy, Caroline Colijn
Genomic data is increasingly being used to understand infectious disease epidemiology. Isolates from a given outbreak are sequenced, and the patterns of shared variation are used to infer which isolates within the outbreak are most closely related to each other. Unfortunately, the phylogenetic trees typically used to represent this variation are not directly informative about who infected whom - a phylogenetic tree is not a transmission tree. However, a transmission tree can be inferred from a phylogeny while accounting for within-host genetic diversity by colouring the branches of a phylogeny according to which host those branches were in...
January 18, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28100438/high-dose-rifampicin-moxifloxacin-and-sq109-for-treating-tuberculosis-a-multi-arm-multi-stage-randomised-controlled-trial
#6
Martin J Boeree, Norbert Heinrich, Rob Aarnoutse, Andreas H Diacon, Rodney Dawson, Sunita Rehal, Gibson S Kibiki, Gavin Churchyard, Ian Sanne, Nyanda E Ntinginya, Lilian T Minja, Robert D Hunt, Salome Charalambous, Madeleine Hanekom, Hadija H Semvua, Stellah G Mpagama, Christina Manyama, Bariki Mtafya, Klaus Reither, Robert S Wallis, Amour Venter, Kim Narunsky, Anka Mekota, Sonja Henne, Angela Colbers, Georgette Plemper van Balen, Stephen H Gillespie, Patrick P J Phillips, Michael Hoelscher
BACKGROUND: Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. METHODS: We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15-20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15-20 mg/kg ethambutol)...
January 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#7
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28096490/comprehensive-essentiality-analysis-of-the-mycobacterium-tuberculosis-genome-via-saturating-transposon-mutagenesis
#8
Michael A DeJesus, Elias R Gerrick, Weizhen Xu, Sae Woong Park, Jarukit E Long, Cara C Boutte, Eric J Rubin, Dirk Schnappinger, Sabine Ehrt, Sarah M Fortune, Christopher M Sassetti, Thomas R Ioerger
: For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28093078/treatment-outcomes-for-multidrug-resistant-tuberculosis-under-dots-plus-a-systematic-review-and-meta-analysis-of-published-studies
#9
Kelemu Tilahun Kibret, Yonatan Moges, Peter Memiah, Sibhatu Biadgilign
BACKGROUND: Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide. Treatment success rates of multidrug-resistant tuberculosis (MDR-TB) is a key issue that cannot be ignored. There is a paucity of evidence that assessed studies on the treatment of MDR-TB, which focus on the effectiveness of the directly observed treatment, short-course (DOTS)-Plus program. Therefore, it is crucial to assess and summarize the overall treatment outcomes for MDR-TB patients enrolled in the DOTS-Plus program in recent years...
January 17, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28092959/mixed-vaccination-strategy-for-the-control-of-tuberculosis-a-case-study-in-china
#10
Siyu Liu, Yong Li, Yingjie Bi, Qingdao Huang
This study first presents a mathematical model of TB transmission considering BCG vaccination compartment to investigate the transmission dynamics nowadays. Based on data reported by the National Bureau of Statistics of China, the basic reproduction number is estimated approximately as R0=1.1892. To reach the new End TB goal raised by WHO in 2015, considering the health system in China, we design a mixed vaccination strategy. Theoretical analysis indicates that the infectious population asymptotically tends to zero with the new vaccination strategy which is the combination of constant vaccination and pulse vaccination...
June 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/28091336/who-are-the-patients-that-default-tuberculosis-treatment-space-matters
#11
C Nunes, R Duarte, A M Veiga, B Taylor
The goals of this article are: (i) to understand how individual characteristics affect the likelihood of patients defaulting their pulmonary tuberculosis (PTB) treatment regimens; (ii) to quantify the predictive capacity of these risk factors; and (iii) to quantify and map spatial variation in the risk of defaulting. We used logistic regression models and generalized additive models with a spatial component to determine the odds of default across continental Portugal. We focused on new PTB cases, diagnosed between 2000 and 2013, and included some individual information (sex, age, residence area, alcohol abuse, intravenous drug use, homelessness, HIV, imprisonment status)...
January 16, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28088237/association-between-diabetes-mellitus-and-multi-drug-resistant-tuberculosis-a-protocol-for-a-systematic-review-and-meta-analysis
#12
Balewgizie Sileshi Tegegne, Tesfa Dejenie Habtewold, Melkamu Merid Mengesha, Johannes G M Burgerhof
INTRODUCTION: Multi-drug-resistant tuberculosis (MDR-TB) has emerged as a challenge to global tuberculosis (TB) control and remains a major public health concern in many countries. Diabetes mellitus (DM) is an increasingly recognized comorbidity that can both accelerate TB disease and complicate its treatment. The aim of this study is to summarize available evidence on the association of DM and MDR-TB among TB patients and to provide a pooled estimate of risks. METHODS: All studies published in English before October 2016 will be searched using comprehensive search strings through PubMed, EMBASE, Web of Science, and WHO Global Health Library databases which have reported the association of DM and MDR-TB in adults with TB (age > =15)...
January 14, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28087948/regulation-of-immunity-to-tuberculosis
#13
Susanna Brighenti, Diane J Ordway
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087940/the-memory-immune-response-to-tuberculosis
#14
Joanna R Kirman, Marcela I Henao-Tamayo, Else Marie Agger
Immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses to Mycobacterium tuberculosis will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087924/clinical-testing-of-tuberculosis-vaccine-candidates
#15
Mark Hatherill, Dereck Tait, Helen McShane
It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087528/engineering-mycobacteria-for-the-production-of-self-assembling-biopolyesters-displaying-mycobacterial-antigens-for-use-as-tuberculosis-vaccine
#16
Jason W Lee, Natalie A Parlane, Bernd H A Rehm, Bryce M Buddle, Axel Heiser
: Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads produced in both E. coli and Lactococcus lactis displaying mycobacterial antigens were found to induce significant cell mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities which we hypothesized to have the potential to induce immunity...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28086846/stochastic-agent-based-modeling-of-tuberculosis-in-canadian-indigenous-communities
#17
Ashleigh R Tuite, Victor Gallant, Elaine Randell, Annie-Claude Bourgeois, Amy L Greer
BACKGROUND: In Canada, active tuberculosis (TB) disease rates remain disproportionately higher among the Indigenous population, especially among the Inuit in the north. We used mathematical modeling to evaluate how interventions might enhance existing TB control efforts in a region of Nunavut. METHODS: We developed a stochastic, agent-based model of TB transmission that captured the unique household and community structure. Evaluated interventions included: (i) rapid treatment of active cases; (ii) rapid contact tracing; (iii) expanded screening programs for latent TB infection (LTBI); and (iv) reduced household density...
January 13, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28078341/the-role-of-uv-radiation-and-vitamin-d-in-the-seasonality-and-outcomes-of-infectious-disease
#18
Abhimanyu, Anna K Coussens
The seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. One of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (UVR), and its subsequent control of vitamin D production. Here we show how UVR and vitamin D, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne infections...
January 12, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28077441/predicting-ifn-%C3%AE-responses-after-bcg-vaccination-in-humans-from-macaques-a-proof-of-concept-study-of-immunostimulation-immunodynamic-modelling-methods
#19
Sophie J Rhodes, Charlotte Sarfas, Gwenan M Knight, Andrew White, Ansar A Pathan, Helen McShane, Thomas G Evans, Helen Fletcher, Sally Sharpe, Richard G White
INTRODUCTION: Macaques play a central role in human tuberculosis(TB) vaccine development. Immune and challenge responses differ across macaque and human subpopulations. We determined which macaque subpopulations best predicted immune responses in different human subpopulations, using novel immunostimulation/immunodynamic modelling methods in a proof of concept study. METHODS: Data on IFN-γ secreting CD4+ T cells over time after recent BCG vaccination were available for 55 humans and 81 macaques...
January 11, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28075556/biosynthesis-of-the-methylthioxylose-capping-motif-of-lipoarabinomannan-in-mycobacterium-tuberculosis
#20
Shiva Kumar Angala, Michael R McNeil, Libin Shi, Maju Joe, Ha Pham, Sophie Zuberogoitia, Jerome Nigou, Claudia M Boot, Todd L Lowary, Martine Gilleron, Mary Jackson
Lipoarabinomannan (LAM) is a lipoglycan found in abundant quantities in the cell envelope of all mycobacteria. The non-reducing arabinan termini of LAM display species-specific structural micro-heterogeneity that impacts the biological activity of the entire molecule. Mycobacterium tuberculosis, for instance, produces mannoside caps made of one to three α(1→2)-Manp-linked residues that may be further substituted with an α(1→4)-linked methylthio-D-xylose (MTX) residue. While the biological functions and catalytic steps leading to the formation of the mannoside caps of M...
January 11, 2017: ACS Chemical Biology
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