DprE2 is a molecular target of the anti-tubercular nitroimidazole compounds pretomanid and delamanid

Abstract Mycobacterium tuberculosis is one of the global leading causes of death due to a single infectious agent. Pretomanid and delamanid are new antitubercular agents that have progressed through the drug discovery pipeline. These compounds are bicyclic nitroimidazoles that act as pro-drugs, requiring activation by a mycobacterial enzyme; however, the precise mechanisms of action of the active metabolite(s) are unclear. Here, we identify a molecular target of activated pretomanid and delamanid: the DprE2 subunit of decaprenylphosphoribose-2’-epimerase, an enzyme required for the synthesis of cell wall arabinogalactan. We also provide evidence for an NAD-adduct as the active metabolite of pretomanid. Our results highlight DprE2 as a potential antimycobacterial target and provide a foundation for future exploration into the active metabolites and clinical development of pretomanid and delamanid

Introducing standard protocol for enrichment of Artemia urmiana nauplii with Canola oil

This research was performed to introduce a standard protocol for enrichment of Artemia urmian with Canola oil. Artemia urmiana nauplii were enriched at three densities (50000, 100000 and 200000 nauplii L^-1) and three concentrations of Canola oil (0.1, 0.2 and 0.3 g L^-1). Their effects were evaluated on survival, total length and profile of fatty acids at 6, 9, 12, 15 and 18 hours after the onset of enrichment. Cysts of A.urmiana were hatched according to the standard method. A.urmiana nauplii were stocked at above densities in 7 L cylindrical containers. Canola oil emulsion was added at concentrations of 0.1, 0.2 and 0.3 g L^-1 at the beginning and 12 hours after the onset of enrichment. The results of analysis showed that enrichment of A.urmiana with 0.3 g L^ -1 Canola oil at 100000 nauplii L^-1 for 18 hours was considered as the best treatment. Artemia nauplii enriched in this treatment had significantly higher levels of (n-3) PUFA and survival and minimum total length comparing to other treatments. The treatment had significantly higher levels of (n-6) PUFA than all treatments except treatment with a density of 50,000 nauplii L^-1 with 0.1 g L^-1 Canola oil for 18 hours

A Numerical Study of the Frontal System between the Inflow and Outflow Waters in the Persian Gulf

In this study the dynamical characteristics of the salinity front between the Persian Gulf inflow and outflow were studied using the HYCOM numerical model. This model was integrated for 5 years from the beginning of 2011 to the end of 2015and the results of 2015 were discussed. The results of the model clearly showed seasonal variations in the salinity front in which the intrusion of the salinity front extends much farther into the Persian Gulf in summer. The salinity front appears to be prone to baroclinic instability with maximum intensity in spring and summer months (with a strong density stratification), forming cyclonic eddies (saline center) and anticyclones (sweeter center), that peaks in August. Results showed that some anti-cascade processes occur in mesoscale eddy activity, in agreement with the quasi-two-dimensional turbulence behavior. Spectral analysis of salinity time series in the front showed eddies with time scales ranging from a few hours to about 3 months. The result also showed that there was a reasonable relation between mixed layer depth and the formation of mesoscale eddies, so that mesoscale eddies disappeared when the thickness of mixed layer was increased in winter

Processing and characterization of nanostructured Grade 2 Ti processed by combination of warm isothermal ECAP and extrusion

In this study, combined multi pass equal channel angular pressing (ECAP), and subsequent warm extrusion at different temperatures are performed on commercial purity titanium. Mechanical and microstructural evolutions are then investigated. Since it was observed that the four passes ECAP processed sample showed the best strength and reasonable elongation, this sample was selected for studying the extrusion temperature effects on the structure and mechanical properties of Grade 2 titanium. Therefore, the 4th passes ECAP processed sample was extruded at different temperatures of 300 °C, 350 °C, 400 °C, 450 °C and 500 °C. The result revealed that the best mechanical properties were achieved from the specimen processed by four passes ECAP followed by warm extrusion at 300 °C. The strength, and hardness of this sample were considerably improved in comparison with that of the unprocessed sample. Also, its ultra-fine grained and nanograined microstructure were homogeneous, with a grain size ranged from 40 to 200 nm with an average grain size of about 123 nm. It was seen that the mechanical properties of some samples after applying this combined process (ECAP + warm extrusion) are comparable with those of Grade 5 titanium which is commonly used in medical applications but contains alloying elements that are toxic to human health

Nanomaterials by severe plastic deformation: review of historical developments and recent advances

International audienceSevere plastic deformation (SPD) is effective in producing bulk ultrafine-grained and nanostructured materials with large densities of lattice defects. This field, also known as NanoSPD, experienced a significant progress within the past two decades. Beside classic SPD methods such as high-pressure torsion, equal-channel angular pressing, accumulative roll-bonding, twist extrusion, and multi-directional forging, various continuous techniques were introduced to produce upscaled samples. Moreover, numerous alloys, glasses, semiconductors, ceramics, polymers, and their composites were processed. The SPD methods were used to synthesize new materials or to stabilize metastable phases with advanced mechanical and functional properties. High strength combined with high ductility, low/room-temperature superplasticity, creep resistance, hydrogen storage, photocatalytic hydrogen production, photocatalytic CO2 conversion, superconductivity, thermoelectric performance, radiation resistance, corrosion resistance, and biocompatibility are some highlighted properties of SPD-processed materials. This article reviews recent advances in the NanoSPD field and provides a brief history regarding its progress from the ancient times to modernity

Metabolic Engineering of Cofactor F420 Production in Mycobacterium smegmatis

Cofactor F420 is a unique electron carrier in a number of microorganisms including Archaea and Mycobacteria. It has been shown that F420 has a direct and important role in archaeal energy metabolism whereas the role of F420 in mycobacterial metabolism has only begun to be uncovered in the last few years. It has been suggested that cofactor F420 has a role in the pathogenesis of M. tuberculosis, the causative agent of tuberculosis. In the absence of a commercial source for F420, M. smegmatis has previously been used to provide this cofactor for studies of the F420-dependent proteins from mycobacterial species. Three proteins have been shown to be involved in the F420 biosynthesis in Mycobacteria and three other proteins have been demonstrated to be involved in F420 metabolism. Here we report the over-expression of all of these proteins in M. smegmatis and testing of their importance for F420 production. The results indicate that co–expression of the F420 biosynthetic proteins can give rise to a much higher F420 production level. This was achieved by designing and preparing a new T7 promoter–based co-expression shuttle vector. A combination of co–expression of the F420 biosynthetic proteins and fine-tuning of the culture media has enabled us to achieve F420 production levels of up to 10 times higher compared with the wild type M. smegmatis strain. The high levels of the F420 produced in this study provide a suitable source of this cofactor for studies of F420-dependent proteins from other microorganisms and for possible biotechnological applications

Evaluating the Anti-Leech Effects of Methanolic Extracts of Peganum harmala L. and Olea europaea L. on Limnatis nilotica. World's Vet

ABSTRACT Leeches had several complications such as pain, itching, inflammation, severe anemia, short-term bleeding, hypersensitivity, and anaphylactic reactions in their hosts. Harmal Peganum harmala L. is used as an analgesic and anti-inflammatory agent and it has antibacterial activity. Olive Olea europaea L. has antibacterial, anti-viral, hypoglycemic and the relaxation of blood vessels properties. Antioxidant properties of olive also had been reported. This study was carried out to detect the effects of methanolic extracts of P. harmala L. and O. europaea L. on L. nilotica immature form. In 2011, 55 immature leeches collected from the southern area of Ilam province were prepared. The methanolic extract of O. europaea L and P. harmala L. were compared with levamisole as the control drug. Distilled water was evaluated as the placebo group which investigated L. nilotica using anti-leech assay. Then extract and drugs were added and their effects were screened for 720 min and time to paralyze, kill and death of each leech was recorded. The results showed that olive methanolic extractions (600 and 300mg) could kill the leeches in an average time of 145±77.57 and171±33.28 min, respectively. An average death time for levamisole was found to be 15±7.49 min. The highest effectiveness was found for levamisole at dose 300 mg. Methanol extracts of the Harmal (300 and 600 μg/m) and springs water showed no anti-leech. In sum, olive plant could use for anti Limnatis nilotica expenditure