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

Hardware-Software Co-Design of BIKE with HLS-Generated Accelerators

In order to mitigate the security threat of quantum computers, NIST is undertaking a process to standardize post-quantum cryptosystems, aiming to assess their security and speed up their adoption in production scenarios. Several hardware and software implementations have been proposed for each candidate, while only a few target heterogeneous platforms featuring CPUs and FPGAs. This work presents a HW/SW co-design of BIKE for embedded platforms featuring both CPUs and small FPGAs and employs high-level synthesis (HLS) to timely deliver the hardware accelerators. In contrast to state-of-the-art solutions targeting performance-optimized HLS accelerators, the proposed solution targets the small FPGAs implemented in the heterogeneous platforms for embedded systems. Compared to the software- only execution of BIKE, the experimental results collected on the systems-on-chip of the entire Xilinx Zynq-7000 family highlight a performance speedup ranging from 1.37x, on Z-7010, to 2.78x, on Z-7020

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

Effects of environmental, living space and climate variability on the utilization of impregnated bed nets in west Cameroon: A community based survey for policy implementation

Background: Despite the fact that Long Lasting Impregnated Mosquito Net (LLIN) represents one of the most effective tools in fighting malaria, its use remains limited. Our study aimed at determining how environmental, household characteristics and climate affect bed net use. Methodology: A cross sectional descriptive and analytic study was carried out from January to April 2014 in Mifi health district. Data collected were collected in households during a face to face interview with standard household questionnaires, entered and analyzed using Epi Info software version 3.5.3. Graphics and tables were obtained using MS Excel and Word. Results: Of the 317 participants interviewed, average age was 33.23 years (SD = 10.80) and female sex predominant (85.2%). Most participants had attended secondary education 53.6% (n= 170), married marital status was most represented (58.1%; n= 185).75.4% (n=239) of households had at least 1 LLIN and average district coverage estimated to 1 LLIN for 3.3 persons. 78% of occupants in households with at least one LLIN had slept under the night before the survey. The presence of a ceiling in a house reduced net usage by 2.5% (p = 0.67) compared to house lacking ceiling. Standing waters around the compound increased net utilization rate to 16.6% (p = 0.03), whereas the presence of a covered well decreased the rate by 1.4% (p = 0.86). The dry season was identified as the period during which 86.8% (n= 239) of respondents sleep less under a net. Heat (57.60% n = 138/239), increased choking (2.5%), reduction in vector breeding sites (39.90%; n = 95) were cited as main reasons. Conclusion: Although classified as zone of continuous transmission, our findings indicate that bed net usage by our study population depends on environmental, household characteristics and climate. There is therefore an urgent need to develop strategic communication and sensitization campaigns coupled to environmental management to help scale up and optimize malaria burden reductio

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

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

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

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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

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 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