Ligand-induced stabilization of the aptamer terminal helix in the add adenine riboswitch

Riboswitches are structured mRNA elements that modulate gene expression. They undergo conformational changes triggered by highly specific interactions with sensed metabolites. Among the structural rearrangements engaged by riboswitches, the forming and melting of the aptamer terminal helix, the so called P1 stem, is essential for genetic control. The structural mechanisms by which this conformational change is modulated upon ligand binding mostly remain to be elucidated. Here, we used pulling molecular dynamics simulations to study the thermodynamics of the P1 stem in the add adenine riboswitch. The P1 ligand-dependent stabilization was quantified in terms of free energy and compared with thermodynamic data. This comparison suggests a model for the aptamer folding in which direct P1-ligand interactions play a minor role on the conformational switch when compared with those related to the ligand-induced aptamer preorganization

Prevalence of HIV, HBV and Chlamydia infections in Cameroonian University context: case of the University of Dschang, in the Western Region

Introduction: In sub-Saharan Africa HIV infection remains largely epidemic, whereas HBV infection is highly endemic (>8%). In Cameroon, HIV prevalence is 4.3%. Concerning HBV and chlamydia infections, their prevalence are both ≥10%. Young adults, including university students, are the population groups mostly affected. Epidemiological data on these infections, among university students could be helpful to implement specific prevention strategies. Methods: A descriptive study was performed in May 2013 among 624 students from the University of Dschang, Cameroon. Participants were screened for HIV, HBV and Chlamydia infections. Data was collected by a standard questionnaire and analyzed by Epi Info. Results: Average age of participants was 23.3 years (σ = 3.2) with female predominance (58.7%). Prevalence of HIV, HBV and Chlamydia infection was 1.1% (7/624), 2.8% (5/176) and 2.0% (2/100) respectively. 83.2% of participants were sexually active. Concerning sexual risk behaviors, participants reported having multi partners (14.8%), using condom occasionally (58.6%) or never (5.0%). 100%, 62.6% and 52.2% reported to be aware on HIV, HBV and Chlamydia infections respectively. In addition, only 5.5% and 21.3% of the participants were aware of their HBV and Chlamydia status respectively, versus 64.4% for HIV. The excessive cost of HBV and Chlamydia tests has been identified as the major barrier to testing (87.6%). Conclusion: Among college Cameroonian students the prevalence of HIV, HBV and Chlamydia infections seems to be relatively low if compared to general population. However, having multiple sexual partners in addition to non-systematic use of condoms during sexual intercourse represents risk behaviors among students. Awareness campaigns and screening facilitation on HBV and chlamydia infections need to be strengthened

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

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

Delivering HIV treatment & care in resource limited settings - Therapeutic mobile units

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Whole genome methylation profiles as independent markers of survival in stage IIIc melanoma patients

Background: The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.Methods: Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.Results: Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a " favorable" methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a " favorable" vs. " unfavorable" methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a " favorable" methylation profile was 41.2% as compared to 0% for patients with an " unfavorable" methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for " unfavorable" methylation profile; 95% Confidence Interval: 1.02-5.70; P = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.Conclusions: A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients. © 2012 Sigalotti et al.; licensee BioMed Central Ltd

HIV and HBV infection in Cameroonian university context: Case of the University of Dschang

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Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma.

Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas

Assessment of attitudes and practices of rural women towards malaria in Western Region, Cameroon: Strategic implications for prevention programs

M. Sanou Sobze1, J. Fokam2, J.-F. Onohiol1,∗, G.B. Djeunang Dongho1, P.M. Nkamedjie Pete1, A. Tenoh Guedoung1, G. Temgue1, V. Colizzi3, G. Russo4 1 Faculty of Sciences; University of Dschang, Dschang, Cameroon 2 Chantal Biya International Reference Centre (CIRCB) for research on HIV/AIDS prevention and management, Yaounde, Cameroon 3 University of Rome "Tor Vergata", Rome, Italy 4 Sapienza University of Rome, Rome, Ital

Evaluation of the nutritional status of infants from mothers tested positive to HIV/AIDS in the health district of Dschang, Cameroon

INTRODUCTION: Poor infant feeding practices are common in Africa, resulting in physical and intellectual developmental impairments. Good feeding practices are crucial, especially in the first year of growth. HIV/AIDS has worsened the clinical and nutritional status of both mothers and their children, exacerbating high rates of malnutrition. The aim of this study was to assess by participative approach, the nutritional status of infants from mothers tested positive to HIV in the health district of Dschang. METHODS: This is a cross sectional study with a period of recruitment of 2 years (2010-2012). Data Collection was done by the aim of a personal slip followed by training to strengthen the nutritional and hygienic capacity of targeted parents. Height and weight of infants were measured and body mass index (BMI) calculated. RESULTS: Significant difference (p ≤ 0.05) was noticed in height-for-age z-score (HAZ) of girls aged between 1 to 2 years compared to 1-year old girls as well as to boys of all ages, defining them as stunted. Furthermore, the weight-for-age z-score (WAZ) results indicate that both girls and boys of all age are in moderate state of malnutrition. The results of BMI thinness classified according to gender and age groups, indicates that most infants (68/130, 52.3%) showed grade 2 thinness predominantly in 2-years old both boys and girls. However, no participants fall within the normal category for age and sex, as well as overweight and obesity categories. CONCLUSION: Undernutrition exists among infants from mothers tested positive to HIV residing in Dschang, as most of the infants are underweight, and malnourished