Self-organized enhancement of conductivity in biological ion channels

We discuss an example of self-organization in a biological system. It arises from long-range ion–ion interactions, and it leads us to propose a new kind of enhanced conduction in ion channels. The underlying mechanism involves charge fluctuations near the channel mouth, amplified by the mismatch between the relative permittivities of water and the protein of the channel walls. We use Brownian dynamics simulations to show that, as in conventional 'knock on' permeation, these interactions can strongly enhance the channel current; but unlike the conventional mechanism, the enhancement occurs without the instigating bath ion entering the channel. The transition between these two mechanisms is clearly demonstrated, emphasizing their distinction. A simple model accurately reproduces the observed phenomena. We point out that electrolyte plus protein of low relative permittivity are universal in living systems, so that long-range ion–ion correlations of the kind considered must be common

Spatial accessibility and social inclusion: The impact of Portugal's last health reform

Health policies seek to promote access to health care and should provide appropriate geographical accessibility to each demographical functional group. The dispersal demand of health‐careservices and the provision for such services atfixed locations contribute to the growth of inequality intheir access. Therefore, the optimal distribution of health facilities over the space/area can lead toaccessibility improvements and to the mitigation of the social exclusion of the groups considered mostvulnerable. Requiring for such, the use of planning practices joined with accessibility measures. However,the capacities of Geographic Information Systems in determining and evaluating spatial accessibility inhealth system planning have not yet been fully exploited. This paper focuses on health‐care services planningbased on accessibility measures grounded on the network analysis. The case study hinges on mainlandPortugal. Different scenarios were developed to measure and compare impact on the population'saccessibility. It distinguishes itself from other studies of accessibility measures by integrating network data ina spatial accessibility measure: the enhanced two‐stepfloating catchment area. The convenient location forhealth‐care facilities can increase the accessibility standards of the population and consequently reducethe economic and social costs incurred. Recently, the Portuguese government implemented a reform thataimed to improve, namely, the access and equity in meeting with the most urgent patients. It envisaged,in terms of equity, the allocation of 89 emergency network points that ensured more than 90% of thepopulation be within 30 min from any one point in the network. Consequently, several emergency serviceswere closed, namely, in rural areas. This reform highlighted the need to improve the quality of the emergencycare, accessibility to each care facility, and equity in their access. Hence, accessibility measures becomean efficient decision‐making tool, despite its absence in effective practice planning. According to anapplication of this type of measure, it was possible to verify which levels of accessibility were decreased,including the most disadvantaged people, with a larger time of dislocation of 12 min between 2001 and 2011

Stochastic dynamics of remote knock-on permeation in biological ion channels

Brownian dynamics simulations provide evidence for a remote knock-on mechanism facilitating the permeation of a biological ion channel by an ion that is initially trapped at the selectivity filter (SF). Unlike the case of conventional direct knock-on, the second ion that instigates permeation does not need to enter the channel. Nor does it necessarily take the place of the permeating ion at the SF, and it can even be of a different ionic species. The study is based on the simultaneous, self-consistent, solution of the coupled Poisson and Langevin equations for a simple generic model, taking account of all the charges present. The new permeation mechanism involves electrostatic amplification attributable to the permittivity mismatch between water and protein: the arrival of the instigating ion at the channel entrance reduces the exit barrier for the ion trapped at the SF, facilitating escape

Influence of Co layer thickness on the structural and magnetic properties of multilayers

International audienceThe correlated effects of the insertion of a Pt spacer between ferromagnetic and antiferromagnetic layers and of the variation of the Co layers thickness on the structural and magnetic properties of [ (Pt/Co tCo) 3 /Pt tPt /IrMn ] n multilayers have been studied. Samples with n = 1 and 7, t Co = 0.4 and 0.6 nm, t Pt = 0 and 0.4 nm have been investigated by tomographic atom probe and superconducting quantum interference device magnetometry. For spacer free samples (t Pt = 0), the structural investigation shows that when t Co = 0.4 nm, Mn and Ir atoms diffuse deeply in the (Pt/Co) multilayers. In contrast for t Co = 0.6 nm, the Mn and Ir diffusion is much reduced. Because Pt acts as a barrier against the Mn and Ir diffusion, this difference is less pronounced in samples with Pt insertion. The hysteresis loops shapes, the exchange bias fields and the saturation magnetization values were correlated with the structural properties of these samples and discussed, taking into account the susceptibility, exchange stiffness, and perpendicular magnetic anisotropy

Microbiome profiling by Illumina sequencing of combinatorial sequence-tagged PCR products

We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads al- lowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an ob- servation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bac- terial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.Comment: 28 pages, 13 figure

Hybrid approach for energy aware management of multi-cloud architecture integrating user machines

International audienceThe arrival and development of remotely accessible services via the cloud has transfigured computer technology. However, its impact on personal computing remains limited to cloud-based applications. Meanwhile, acceptance and usage of telephony and smartphones have exploded. Their sparse administration needs and general user friendliness allows all people, regardless of technology literacy, to access, install and use a large variety of applications.We propose in this paper a model and a platform to offer personal computing a simple and transparent usage similar to modern telephony. In this model, user machines are integrated within the classical cloud model, consequently expanding available resources and management targets. In particular, we defined and implemented a modular architecture including resource managers at different levels that take into account energy and QoS concerns. We also propose simulation tools to design and size the underlying infrastructure to cope with the explosion of usage. Functionalities of the resulting platform are validated and demonstrated through various utilization scenarios. The internal scheduler managing resource usage is experimentally evaluated and compared with classical method-ologies, showing a significant reduction of energy consumption with almost no QoS degradation

Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Rhizobium leguminosarum HupE is a highly-specific diffusion facilitator for nickel uptake

Bacteria require nickel transporters for the synthesis of Ni-containing metalloenzymes in natural, low nickel habitats. In this work we carry out functional and topological characterization of Rhizobium leguminosarum HupE, a nickel permease required for the provision of this element for [NiFe] hydrogenase synthesis. Expression studies in the Escherichia coli nikABCDE mutant strain HYD723 revealed that HupE is a medium-affinity permease (apparent Km 227 ! 21 nM; Vmax 49 ! 21 pmol Ni2+ min"1 mg"1 bacterial dry weight) that functions as an energy-independent diffusion facilitator for the uptake of Ni(II) ions. This Ni2+ transport is not inhibited by similar cations such as Mn2+, Zn2+, or Co2+, but is blocked by Cu2+. Analysis of site-directed HupE mutants allowed the identification of several residues (H36, D42, H43, F69, E90, H130, and E133) that are essential for HupE-mediated Ni uptake in E. coli cells. By using translational fusions to reporter genes we demonstrated the presence of five transmembrane domains with a periplasmic N-terminal domain and a C-terminal domain buried in the lipid bilayer. The periplasmic N-terminal domain contributes to stability and functionality of the protei