Sulfated Polysaccharide, Curdlan Sulfate, Efficiently Prevents Entry/Fusion and Restricts Antibody-Dependent Enhancement of Dengue Virus Infection In Vitro: A Possible Candidate for Clinical Application

10.1371/journal.pntd.0002188PLoS Neglected Tropical Diseases74

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

Effect of non-uniform basic temperature gradient on the onset of Marangoni convection in a fluid with suspended particles

The effect of a non-uniform basic temperature gradient on the onset of convection driven by surface tension in a horizontal layer of a Boussinesq fluid with suspended particles confined between an upper free, constant heat flux boundary and a lower rigid isothermal boundary is considered. The microrotation is assumed to vanish at the boundaries. A linear stability analysis is performed. The Rayleigh-Ritz technique is used to obtain the eigenvalues. The influence of various parameters on the onset of convection has been analyzed. Six different non-uniform basic state temperature profiles are considered and their comparative influence on onset is discussed. It is observed that the fluid layer with suspended particles heated from below is more stable compared to the classical fluid layer without suspended particles. The problem has possible applications in microgravity situations

Effects of Electric Field, Couple Stress and Permeability of Poorly conducting Polluted Fluid Through Composite Materials

Session 7: Nanocomposites & Multi-Functional Composites / Smart Materials (2

Observations on some abnormal foliage in the sandal trees of hangal forest range of Mysore State

This article does not have an abstract

Genetic Diversity and Streptomycin Sensitivity in <i>Xanthomonas axonopodis</i> pv. <i>punicae</i> Causing Oily Spot Disease in Pomegranates

Xanthomonas axonopodis pv. punicae (Xap) causes bacterial blight disease in pomegranates, often leading to 60–80% economic loss. In absence of a suitable Xap-resistant variety, the near-monoculture of the susceptible variety, Bhagwa, has aggravated the problem further. In recent times, Xap has spread to different geographical regions, indicating the wide adaptability of the pathogen. Moreover, lower sensitivity of Xap towards streptocycline containing streptomycin sulphate and tetracycline sulphate (9:1) under field conditions is frequently reported. Therefore, the current study was undertaken to assess the genetic variability of Xap isolates using SSR markers, their in vitro sensitivity towards streptomycin was evaluated, and the probable molecular basis of acquired resistance was studied. Two highly diverse isolates showed extreme differences in their pathogenicity, indicating the highly evolving nature of the pathogen. Moreover, all the isolates showed less than 50% growth inhibition on media containing 1500 µg/mL streptomycin, indicating a lower level of antibiotic sensitivity. On the molecular level, 90% of the isolates showed the presence of strA-strB genes involved in streptomycin metabolism. Additionally, G to A transitions were observed in the rpsL gene in some of the isolates. The molecular data suggest that horizontal gene transfer (strAB) and/or spontaneous gene mutation (in rpsL) could be responsible for the observed lower sensitivity of Xap towards streptomycin

Genetic Diversity and Streptomycin Sensitivity in Xanthomonas axonopodis pv. punicae Causing Oily Spot Disease in Pomegranates

Xanthomonas axonopodis pv. punicae (Xap) causes bacterial blight disease in pomegranates, often leading to 60&ndash;80% economic loss. In absence of a suitable Xap-resistant variety, the near-monoculture of the susceptible variety, Bhagwa, has aggravated the problem further. In recent times, Xap has spread to different geographical regions, indicating the wide adaptability of the pathogen. Moreover, lower sensitivity of Xap towards streptocycline containing streptomycin sulphate and tetracycline sulphate (9:1) under field conditions is frequently reported. Therefore, the current study was undertaken to assess the genetic variability of Xap isolates using SSR markers, their in vitro sensitivity towards streptomycin was evaluated, and the probable molecular basis of acquired resistance was studied. Two highly diverse isolates showed extreme differences in their pathogenicity, indicating the highly evolving nature of the pathogen. Moreover, all the isolates showed less than 50% growth inhibition on media containing 1500 &micro;g/mL streptomycin, indicating a lower level of antibiotic sensitivity. On the molecular level, 90% of the isolates showed the presence of strA-strB genes involved in streptomycin metabolism. Additionally, G to A transitions were observed in the rpsL gene in some of the isolates. The molecular data suggest that horizontal gene transfer (strAB) and/or spontaneous gene mutation (in rpsL) could be responsible for the observed lower sensitivity of Xap towards streptomycin