Leishmania aethiopica field isolates bearing an endosymbiontic dsRNA virus induce pro-inflammatory cytokine response

Infection with Leishmania parasites causes mainly cutaneous lesions at the site of the sand fly bite. Inflammatory metastatic forms have been reported with Leishmania species such as L. braziliensis, guyanensis and aethiopica. Little is known about the factors underlying such exacerbated clinical presentations. Leishmania RNA virus (LRV) is mainly found within South American Leishmania braziliensis and guyanensis. In a mouse model of L. guyanensis infection, its presence is responsible for an hyper-inflammatory response driven by the recognition of the viral dsRNA genome by the host Toll-like Receptor 3 leading to an exacerbation of the disease. In one instance, LRV was reported outside of South America, namely in the L. major ASKH strain from Turkmenistan, suggesting that LRV appeared before the divergence of Leishmania subgenera. LRV presence inside Leishmania parasites could be one of the factors implicated in disease severity, providing rationale for LRV screening in L. aethiopica.A new LRV member was identified in four L. aethiopica strains (LRV-Lae). Three LRV-Lae genomes were sequenced and compared to L. guyanensis LRV1 and L. major LRV2. LRV-Lae more closely resembled LRV2. Despite their similar genomic organization, a notable difference was observed in the region where the capsid protein and viral polymerase open reading frames overlap, with a unique -1 situation in LRV-Lae. In vitro infection of murine macrophages showed that LRV-Lae induced a TLR3-dependent inflammatory response as previously observed for LRV1.In this study, we report the presence of an immunogenic dsRNA virus in L. aethiopica human isolates. This is the first observation of LRV in Africa, and together with the unique description of LRV2 in Turkmenistan, it confirmed that LRV was present before the divergence of the L. (Leishmania) and (Viannia) subgenera. The potential implication of LRV-Lae on disease severity due to L. aethiopica infections is discussed

Efficacious, effective, and embedded interventions: Implementation research in infectious disease control

Background: Research in infectious disease control is heavily skewed towards high end technology; development of new drugs, vaccines and clinical interventions. Oft ignored, is the evidence to inform the best strategies that ensure the embedding of interventions into health systems and amongst populations. In this paper we undertake an analysis of the challenge in the development of research for the sustainable implementation of disease control interventions. Results: We highlight the fundamental differences between the research paradigms associated with the development of technologies and interventions for disease control on the one hand and the research paradigms required for enhancing the sustainable uptake of those very same interventions within the communities on the other. We provide a definition for implementation research in an attempt to underscore its critical role and explore the multidisciplinary science needed to address the challenges in disease control. Conclusion: The greatest value for money in health research lies in the sustainable and effective implementation of already proven, efficacious solutions. The development of implementation research that can help provide some solutions on how this can be achieved is sorely needed

Cholest-5-en-3β-yl N-phenyl­carbamate

In the title compound, C34H51NO2, the dihedral angle between the planes of the phenyl ring and the carbonyl group is 9.30 (2)°. No significant inter­molecular inter­actions are observed in the crystal structure. The C5H11 fragment is disordered over two positions with site occupancies of 0.611 (6) and 0.389 (6)

3-(2-Amino-5-nitro­anilino)-5,5-dimethyl­cyclo­hex-2-en-1-one 0.25-hydrate

The asymmetric unit of the title compound, C14H17N3O3·0.25H2O, comprises two independent organic mol­ecules and a water mol­ecule lying on a crystallographic twofold rotation axis with 50% site occupancy. In both independent mol­ecules, the cyclo­hexene rings adopt envelope conformations but superposition of the two molecules shows that the flap atoms point in opposite directions. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds inter­connect adjacent mol­ecules into a three-dimensional network. Weak inter­molecular π–π aromatic stacking inter­actions [centroid–centroid distances = 3.4985 (9) and 3.6630 (9) Å] are also observed

2,3-Dimethyl-6-nitro­quinoxaline

The asymmetric unit of the title quinoxaline compound, C10H9N3O2, contains two crystallographically independent mol­ecules (A and B). The quinoxaline ring systems are essentially planar, with maximum deviations of 0.006 (1) and 0.017 (1) Å, respectively, for mol­ecules A and B. In mol­ecule A, the dihedral angle formed between the quinoxaline ring system and nitro group is 10.94 (3)° [6.31 (13)° for mol­ecule B]. In the crystal, mol­ecules are linked into chains propagating along [001]: one forms zigzag chains linked by C—H⋯O hydrogen bonds, whilst the other forms ladder-like chains by way of C—H⋯N and C—H⋯O hydrogen bonds. The packing is further consolidated by weak π–π inter­actions [range of centroid–centroid distances = 3.5895 (7)–3.6324 (7) Å]

Redetermination of ethyl (3a-cis)-3a,8b-dihydr­oxy-2-methyl-4-oxo-3a,8b-dihydro-4H-indeno[1,2-b]furan-3-carboxyl­ate monohydrate

The crystal structure of the title compound, C15H14O6·H2O, has been redetermined from single-crystal X-ray data. The structure was originally determined by Peet et al. [J. Heterocycl. Chem. (1995), 32, 33–41] but the atomic coordinates were not reported or deposited in the Cambridge Structural Database. The ethyl substituent is disordered over two sites with refined occupancies of 0.815 (6) and 0.185 (6). The indeno group is almost planar [maximum deviation 0.0922 (14) Å] and makes an angle of 68.81 (4)° with the furan ring. The fused ring molecules are assembled in pairs by intermolecular O—H⋯O hydrogen bonds. The resulting dimers are also hydrogen bonded to the water molecules, forming double-stranded chains running along the a axis

9-(3,4-Dimeth­oxy­phen­yl)-3,4,5,6,7,9-hexa­hydroxanthene-1,8(2H)-dione

In the title compound, C21H22O5, the mean planes of the pyran and dimeth­oxy­phenyl rings are nearly perpendicular to one another, with the dihedral angle between them being 88.21 (8)°. The pyran ring adopts a boat conformation whereas the two fused cyclo­hexane rings adopt envelope conformations. In the crystal, mol­ecules are linked into a three-dimensional network by inter­molecular C—H⋯O hydrogen bonds

SYNTHESIS, CHARACTERIZATIONAND ANTIMICROBIALACTIVITYOF FRIEDELIN [2, 3-d] SElENADIAZOlE

ABSTRACT The new 1, 2, 3, selenadiazole derivative (3) was prepared from friedelin (1) via the co"esponding semicarbazone (2) using Lalezari cyclization. The compounds were prepared, separated and characterized on the basis of microanalysis and spectral studies. The isolated friedelin and its selenadiazole were screened in vitro for their antimicrobial activities against various pathogenic bacterial were found to be highly active against al/ the selected pathogens. Compound 3 showed an inhibition zone of 14 mm and 12 mm respectively against highly resistant S. albus and C. albicans. A general mechanistic scheme for these reactions is also suggested based on current and previous results

Behavior of Gypseous Soil Treated by Arabic Gum Biopolymer Under Cycles of Wetting and Drying

Gypseous soil is classified as problematic soil since the main source that makes it problematic soil is the dissolving of gypsum in water. Treatment by biopolymers offers an environmentally friendly and sustainable way of soil enhancement that has recently been adopted by geotechnical engineers. However, it is vulnerable to periodical environmental impacts, particularly changes in moisture content. The main objective of this study is to find out the effect of wetting and drying cycles on the shear strength behavior of gypseous soil treated by Arabic gum biopolymer. Gypseous soil specimens of 40% gypsum content treated with 2% biopolymer Arabic gum were prepared for this investigation. The soil specimen was exposed to several cycles of wetting and drying (1, 5, 10, and 15 cycles). For each number of cycles, the shear strength parameters were evaluated for soil specimens. The results showed that the angle of internal friction (ɸ) increased until the fifth cycle, from 40o to 44o, and then approximately returned to its original value at 15 cycles. Similarly, cohesion increased by 67% at the 5th cycle and decreased to 58% at the 15th, respectively. Whereas the value of unconfined compressive strength (qu) decreased with the cycles increasing, reaching 54% after the 5th cycle and 68% at cycle 15th. It can be concluded to some extent that Arabic gum reduces changes and deformations in treated soil samples for a limited number of wetting and drying cycles and preserves its shear strength