Clonal Selection and Population Dynamics of Vγ2/Vδ2 T Cells in Macaca Fascicularis

HIV infection increases the susceptibility to new M. tuberculosis (Mtb) infections, the risk of reactivating latent infections and the risk of rapid TB progression. γδ T cells, in particular the Vγ2Jγ1.2 subset, are thought to be part of the innate immune response to both HIV and Mtb. Importantly, both HIV and Mtb perturb gd T cells homeostasis, causing a profound and highly specific depletion of the Vγ2Jγ1.2 subset

pH-Dependent Capping Interactions Induce Large-Scale Structural Transitions in i-Motifs

We study here a DNA oligonucleotide having the ability to form two different i-motif structures whose relative stability depends on pH and temperature. The major species at neutral pH is stabilized by two C:C+ base pairs capped by two minor groove G:C:G:C tetrads. The high pH and thermal stability of this structure are mainly due to the favorable effect of the minor groove tetrads on their adjacent positively charged C:C+ base pairs. At pH 5, we observe a more elongated i-motif structure consisting of four C:C+ base pairs capped by two G:T:G:T tetrads. Molecular dynamics calculations show that the conformational transition between the two structures is driven by the protonation state of key cytosines. In spite of large conformational differences, the transition between the acidic and neutral structures can occur without unfolding of the i-motif. These results represent the first case of a conformational switch between two different i-motif structures and illustrate the dramatic pH-dependent plasticity of this fascinating DNA motif

Antibacterial activity of alkaloids from Sida acuta

Sida acuta is a shrub indigenous to pantropical regions. The plant is widely used for its various pharmacological properties. Among compounds of pharmacological interest occurring in the plant, are indoloquinoline alkaloids. The aim of the present study was to investigate the antimicrobial activity ofalkaloids of S. acuta from Burkina Faso. The alkaloids had a good antimicrobial activity against the test microorganisms. In the agar-well diffusion assay, highest inhibition zone diameters were recorded with Gram-positive bacteria. The broth microdilution assay gave minimal inhibitory concentration values ranging from 16 to 400 ìg/ml and minimal bactericidal concentration values ranging from 80 to up to 400 ìg/ml. The gas chromatography-mass spectrometry analysis of the same alkaloids led to the identification of cryptolepine and quindoline as the major components

Asymmetric base-pair opening drives helicase unwinding dynamics

The opening of a Watson-Crick double helix is required for crucial cellular processes, including replication, repair, and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here, we uncover a systematic stepwise process driven by the asymmetric flipping-out probability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases toward substrates that bear highly dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easily unwound from one side than the other, in a quantifiable and predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix

Abusive use of antibiotics in poultry farming in Cameroon and the public health implications

The types and methods of use of antibiotics in poultry farms in Cameroon, residual levels and potential microbial resistance were determined. A questionnaire-based survey identified the different antibiotics used and high-performance liquid chromatography (HPLC) was used to determine residual levels of antibiotics. Pathogens were isolated, identified by use of commercial API kits and minimum inhibition concentration (MIC) was determined. Oxytetracyclin, tylocip and TCN (oxytetracycline, chloramphenicol and neomycin) were the most frequently used antibiotics. Antibiotics screened by HPLC were chloramphenicol, tetracycline and vancomycin. All of them except vancomycin were detected, and the concentration of these antibiotics was higher than the maximum residual limits (MRL) set by regulatory authorities. No residues of various antibiotics were found in egg albumen or yolk. The concentration of tetracycline was significantly higher in liver (150 ± 30 µg/g) than in other tissues. Foodborne pathogens, including Salmonella spp., Staphylococcus spp., Listeria spp., Clostridium spp. and Escherichia spp., were identified. Most of the pathogens were resistant to these various antibiotics tested. These findings imply the need for better management of antibiotic use to control sources of food contamination and reduce health risks associated with the presence of residues and the development of resistant pathogens by further legislation and enforcement of regulations on food hygiene and use of antibiotics

HIV replication leads to skewed maturation of CD8-positive T-cell responses in infected children

HIV-1 infection causes a severe T-cell impairment with alteration of immune response. However, in children the natural decline of lymphocytes and CD4 cells in early life makes it more difficult to monitor immunocompetence and progression of HIV-infection. Aim of this study was to characterize the CD8 response in non-vertically HIV-infected children exposed persistently to viremia and in HIV-infected children controlling efficiently viremia by ART, by analysing the effect of persistent viremia on CD4 and CD8 T-cells count, HIV-specific immune-response and naive/memory pattern of CD8 T-cell. Whereas, no differences of CD4 count between viremic patients and viral controllers were observed (1046.9 +/- 472.1 cells/microl vs 1101.3 +/- 415.4 cells/microl; p > 0.05), CD8 count was higher in the viremic patients (1080.6 +/- 652.1 cells/microl vs 747.5 +/- 389.9 cells/microl, p < 0.05). In viremic patients, HIV-specific CD8 T-cells correlated with viral load. However, in this group a loss of HIV-specific CD8 response was associated with a 7 fold decrease of naïve and increase of pre-effector CD8 T-cells (62.8% +/- 10.21% vs 10.37% +/- 7.91%, p < 0.03). Persistent exposure to viremia alters HIV-specific CD8 response possibly through a persistent immune activation process leading to exhaustion of naive CD8 T-cells and skewed maturation of memory subset. Therefore, memory CD8 T-cells might lose the ability to respond correctly and efficiently to HIV-antigen exposure

Evaluation of treatment response, drug resistance and HIV-1 variability among adolescents on first- And second-line antiretroviral therapy: A study protocol for a prospective observational study in the centre region of Cameroon (EDCTP READY-study)

BackgroundSub-Saharan Africa (SSA) alone has nine out of every 10 children living with HIV globally and monitoring in this setting remains suboptimal, even as these children grow older. With scalability of antiretroviral therapy (ART), several HIV-infected children are growing towards adolescence (over 2.1 million), with the potentials to reach adulthood. However, despite an overall reduction in HIV-related mortality, there are increasing deaths among adolescents living with HIV (ADLHIV), with limited evidence for improved policy-making. Of note, strategies for adolescent transition from pediatrics to adult-healthcare are critical to ensure successful treatment response and longer life expectancy. Interestingly, with uptakes in prevention of mother-to-child transmission, challenges in ART programs, and high viremia among children in SSA, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance (HIVDR) emergence, especially after years of paediatric ART exposure. Therefore, monitoring ART response in adolescents and evaluating HIVDR patterns might limit disease progression and guide on subsequent ART options for SSA ADLHIV.ObjectivesAmong Cameroonian ADLHIV receiving ART, we shall evaluate the rate of immunovirologic failure, acquired HIVDR-associated mutations, HIV-1 subtype distribution, genetic variability in circulating (plasma) versus archived (cellular) viral strains, and HIVDR early warning indicators (EWIs) at different time-points.MethodsA prospective and observational study will be conducted among 250 ADLHIV (10-19years old) receiving ART in the centre region of Cameroon, and followed-up at 6 and 12months after enrollment. Following consecutive sampling at enrolment, plasma viral load and CD4/CD8 count will be measured, and genotypic resistance testing (GRT) will be performed both in plasma and in buffy coat for participants experiencing virological failure (two consecutive viremia &gt;=1000 copies/ml). Plasma viral load and CD4/CD8 will be monitored for all participants at 6 and 12months after enrolment. HIVDR-EWIs will be monitored and survival analysis performed during the 12months follow-up. Primary outcomes are rates of virological failure, acquired-HIVDR, and mortality.DiscussionOur findings will provide evidence-based recommendations to ensure successful transition from paediatrics to adult ART regimens and highlight further needs of active ART combinations, for reduced morbidity and mortality in populations of ADLHIV within SSA

Charge Ordering and Ferroelectricity in Half-doped Manganites

By means of density-functional simulations for half-doped manganites, such as pseudocubic Pr0.5Ca0.5MnO3 and bilayer PrCa2Mn2O7, we discuss the occurrence of ferroelectricity and we explore its crucial relation to the crystal structure and to peculiar charge/spin/orbital ordering effects. In pseudocubic Pr0.5Ca0.5MnO3, ferroelectricity is induced in the Zener polaron type structure, where Mn ions are dimerized. In marked contrast, in bilayer PrCa2Mn2O7, it is the displacements of apical oxygens bonded to either Mn3+ or Mn4+ ions that play a key role in the rising of ferroelectricity. Importantly, local dipoles due to apical oxygens are also intimately linked to charge and orbital ordering patterns in MnO2 planes, which in turn contribute to polarization. Finally, an important outcome of our work consists in proposing Born effective charges as a valid mean to quantify charge disproportionation effects, in terms of anisotropy and size of electronic clouds around Mn ions.Comment: 5 pages, 2 figures, submitted for publicatio