On the ion coupling mechanism of the MATE transporter ClbM

Bacteria use a number of mechanisms to defend themselves from antimicrobial drugs. One important defense strategy is the ability to export drugs by multidrug transporters. One class of multidrug transporter, the so-called multidrug and toxic compound extrusion (MATE) transporters, extrude a variety of antibiotic compounds from the bacterial cytoplasm. These MATE transporters are driven by a Na+, H+, or combined Na+/H+ gradient, and act as antiporters to drive a conformational change in the transporter from the outward to the inward-facing conformation. In the inward-facing conformation, a chemical compound (drug) binds to the protein, resulting in a switch to the opposite conformation, thereby extruding the drug. Using molecular dynamics simulations, we now report the structural basis for Na+ and H+ binding in the dual ion coupled MATE transporter ClbM from Escherichia coli, which is connected to colibactin-induced genotoxicity, yielding novel insights into the ion/drug translocation mechanism of this bacterial transporter.</p

Implanted Pacemaker Regarding to Complete Atrioventricular Block : a Case Report

Scientific advisers: assis. prof. M.V. Pochinskaya, prof. M. I. Yabluchanski

Single mutations in the ε subunit from thermophilic Bacillus PS3 generate a high binding affinity site for ATP

The ε subunit from ATP synthases acts as an ATP sensor in the bacterial cell to prevent ATP hydrolysis and thus the waste of ATP under conditions of low ATP concentration. However, the ATP binding affinities from various bacterial organisms differ markedly, over several orders of magnitude. For example, the ATP synthases from thermophilic Bacillus PS3 and Escherichia coli exhibit affinities of 4 µM and 22 mM, respectively. The recently reported R103A/R115A double mutant of Bacillus PS3 ATP synthase demonstrated an increased binding affinity by two orders of magnitude with respect to the wild type. Here, we used atomic-resolution molecular dynamics simulations to determine the role of the R103A and R115A single mutations. These lead us to predict that both single mutations also cause an increased ATP binding affinity. Evolutionary analysis reveals R103 and R115 substitutions in the ε subunit from other bacillic organisms, leading us to predict they likely have a higher ATP binding affinity than previously expected

A QUASI-STATIC MODELLING APPROACH OF AIRBORNE POWER SYSTEMS

Abstract Modelling the whole power system of an airborne system requires very high computational capacity. This paper presents a possible approach to overcome this obstacle when considering new technology and topologies in airborne systems. Using Step-down and step-up voltage converters are described as fictive DC/DC transformers. This approach makes it possible to reduce the complexity of power system models of tentative systems to such extent that the resulting computational tool can be used for studies of the system performance during entire flight missions and/or for optimisation

Managing biological and genetic diversity in tropical agroforestry

Abstract The issues of biological and genetic diversity management in agroforestry are extremely complex. This paper focuses on genetic diversity management and its implications for sustainable agroforestry systems in the tropics, and presents an analysis of the role and importance of inter-and intra-specific diversity in agroforestry. Diversity within and between tree species in traditional agroforestry systems and modern agroforestry technologies in the tropics is assessed, with a view to understanding the functional elements within them and assessing the role and place of diversity. The assessment shows that although the practice of agroforestry has been a diversity management and conservation system, research in agroforestry over time has de-emphasized the diversity element; nevertheless farmers do value diversity and do manage agroforestry from that perspective. Based on a profiling of various traditional agroforestry systems and research-developed technologies, a strong case is made for increased speciesand genetic diversity, at both inter-and intra-specific levels. The review and analysis point to the need for increased awareness, training/education, partnerships and collaborative efforts in support of genetic diversity in agroforestry systems; of special importance is increased cross-disciplinary research. All the flowers of all the tomorrows are in the seeds of today -A Chinese prover

Effector and Central Memory Poly-Functional CD4+ and CD8+ T Cells are Boosted upon ZOSTAVAX® Vaccination

ZOSTAVAX® is a live attenuated varicella-zoster virus (VZV) vaccine that is licensed for the protection of individuals ≥ 50 years against shingles, and its most common complication, post-herpetic neuralgia. While IFN responses increase upon vaccination, the quality of the T cell response has not been elucidated. By using polychromatic flow cytometry, we characterized the breadth, magnitude, and quality of ex vivo CD4+ and CD8+ T cell responses induced 3 – 4 weeks after ZOSTAVAX vaccination of healthy adults. We show, for the first time that the highest frequencies of VZV-specific CD4+ T cells were poly-functional CD154+IFNγ+IL-2+TNFα+ cells, which were boosted upon vaccination. The CD4+ T cells were broadly reactive to several VZV proteins, with IE63 ranking the highest amongst them in the fold-rise of poly-functional cells, followed by IE62, gB, ORF9, and gE. We identified a novel poly-functional ORF9-specific CD8+ T cell population in 62% of the subjects, and these were boosted upon vaccination. Poly-functional CD4+ and CD8+ T cells produced significantly higher levels of IFNγ, IL-2, and TNFα compared to mono-functional cells. After vaccination, a boost in the expression of IFN by poly-functional IE63-and ORF9-specific CD4+ T cells, and IFNγ, IL-2, and TNFα by ORF9-specific poly-functional CD8+ T cells was observed. Responding poly-functional T cells exhibited both effector (CCR7−CD45RA−CD45RO+), and central (CCR7+CD45RA−CD45RO+) memory phenotypes, which expressed comparable levels of cytokines. Altogether, our studies demonstrate that a boost in memory poly-functional CD4+ T cells, and ORF9-specific CD8+ T cells may contribute towards ZOSTAVAX efficacy

Integrating Traditional Healers into the Health Care System:Challenges and Opportunities in Rural Northern Ghana

Traditional medicine is widespread in Ghana, with 80% of Ghanaians relying on its methods for primary health care. This paper argues that integrating traditional and biomedical health systems expands the reach and improves outcomes of community health care. Moving beyond literature, it stresses the importance of trust-relationships between healers and biomedical staff. Insights are based on qualitative research conducted in Ghana’s Northern Region (2013–2014). Five challenges to integration emerged out of the data: a lack of understanding of traditional medicine, discrimination, high turnover of biomedical staff, declining interest in healing as a profession, and equipment scarcity. Besides challenges, opportunities for integration exist, including the extensive infrastructure of traditional medicine, openness to collaboration, and grassroots initiatives. Contemplating challenges and opportunities this paper provides recommendations for integration, including: identify/select healers, promote best practices, institute appropriate forms of appreciation/recognition of healers, provide aid and equipment, use communication campaigns to promote integration and steer attitudinal change towards healers among biomedical staff. Most crucial, we argue successful implementation of these recommendations depends on a concerted investment in relationships between healers and biomedical staff