The N-terminal intrinsically disordered domain of mgm101p is localized to the mitochondrial nucleoid.

The mitochondrial genome maintenance gene, MGM101, is essential for yeasts that depend on mitochondrial DNA replication. Previously, in Saccharomyces cerevisiae, it has been found that the carboxy-terminal two-thirds of Mgm101p has a functional core. Furthermore, there is a high level of amino acid sequence conservation in this region from widely diverse species. By contrast, the amino-terminal region, that is also essential for function, does not have recognizable conservation. Using a bioinformatic approach we find that the functional core from yeast and a corresponding region of Mgm101p from the coral Acropora millepora have an ordered structure, while the N-terminal domains of sequences from yeast and coral are predicted to be disordered. To examine whether ordered and disordered domains of Mgm101p have specific or general functions we made chimeric proteins from yeast and coral by swapping the two regions. We find, by an in vivo assay in S.cerevisiae, that the ordered domain of A.millepora can functionally replace the yeast core region but the disordered domain of the coral protein cannot substitute for its yeast counterpart. Mgm101p is found in the mitochondrial nucleoid along with enzymes and proteins involved in mtDNA replication. By attaching green fluorescent protein to the N-terminal disordered domain of yeast Mgm101p we find that GFP is still directed to the mitochondrial nucleoid where full-length Mgm101p-GFP is targeted

Building social capital through breastfeeding peer support: Insights from an evaluation of a voluntary breastfeeding peer support service in North-West England

Background: Peer support is reported to be a key method to help build social capital in communities. To date there are no studies that describe how this can be achieved through a breastfeeding peer support service. In this paper we present findings from an evaluation of a voluntary model of breastfeeding peer support in North-West England to describe how the service was operationalized and embedded into the community. This study was undertaken from May, 2012 to May, 2013. Methods: Interviews (group or individual) were held with 87 participants: 24 breastfeeding women, 13 peer supporters and 50 health and community professionals. The data contained within 23 monthly monitoring reports (January, 2011 to February 2013) compiled by the voluntary peer support service were also extracted and analysed. Results: Thematic analysis was undertaken using social capital concepts as a theoretical lens. Key findings were identified to resonate with ’bonding’, ‘bridging’ and ‘linking’ forms of social capital. These insights illuminate how the peer support service facilitates ‘bonds’ with its members, and within and between women who access the service; how the service ‘bridges’ with individuals from different interests and backgrounds, and how ‘links’ were forged with those in authority to gain access and reach to women and to promote a breastfeeding culture. Some of the tensions highlighted within the social capital literature were also identified. Conclusions: Horizontal and vertical relationships forged between the peer support service and community members enabled peer support to be embedded into care pathways, helped to promote positive attitudes to breastfeeding and to disseminate knowledge and maximise reach for breastfeeding support across the community. Further effort to engage with those of different ethnic backgrounds and to resolve tensions between peer supporters and health professionals is warranted

Characterizations of how species mediate ecosystem properties require more comprehensive functional effect descriptors

The importance of individual species in mediating ecosystem process and functioning is generally accepted, but categorical descriptors that summarize species-specific contributions to ecosystems tend to reference a limited number of biological traits and underestimate the importance of how organisms interact with their environment. Here, we show how three functionally contrasting sediment-dwelling marine invertebrates affect fluid and particle transport - important processes in mediating nutrient cycling - and use high-resolution reconstructions of burrow geometry to determine the extent and nature of biogenic modification. We find that individual functional effect descriptors fall short of being able to adequately characterize how species mediate the stocks and flows of important ecosystem properties and that, in contrary to common practice and understanding, they are not substitutable with one another because they emphasize different aspects of species activity and behavior. When information derived from these metrics is combined with knowledge of how species behave and modify their environment, however, detailed mechanistic information emerges that increases the likelihood that a species functional standing will be appropriately summarized. Our study provides evidence that more comprehensive functional effect descriptors are required if they are to be of value to those tasked with projecting how altered biodiversity will influence future ecosystems

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

The Hepatitis E Virus Polyproline Region Is Involved in Viral Adaptation

Genomes of hepatitis E virus (HEV), rubivirus and cutthroat virus (CTV) contain a region of high proline density and low amino acid (aa) complexity, named the polyproline region (PPR). In HEV genotypes 1, 3 and 4, it is the only region within the non-structural open reading frame (ORF1) with positive selection (4–10 codons with dN/dS>1). This region has the highest density of sites with homoplasy values >0.5. Genotypes 3 and 4 show ∼3-fold increase in homoplastic density (HD) in the PPR compared to any other region in ORF1, genotype 1 does not exhibit significant HD (p<0.0001). PPR sequence divergence was found to be 2-fold greater for HEV genotypes 3 and 4 than for genotype 1. The data suggest the PPR plays an important role in host-range adaptation. Although the PPR appears to be hypervariable and homoplastic, it retains as much phylogenetic signal as any other similar sized region in the ORF1, indicating that convergent evolution operates within the major HEV phylogenetic lineages. Analyses of sequence-based secondary structure and the tertiary structure identify PPR as an intrinsically disordered region (IDR), implicating its role in regulation of replication. The identified propensity for the disorder-to-order state transitions indicates the PPR is involved in protein-protein interactions. Furthermore, the PPR of all four HEV genotypes contains seven putative linear binding motifs for ligands involved in the regulation of a wide number of cellular signaling processes. Structure-based analysis of possible molecular functions of these motifs showed the PPR is prone to bind a wide variety of ligands. Collectively, these data suggest a role for the PPR in HEV adaptation. Particularly as an IDR, the PPR likely contributes to fine tuning of viral replication through protein-protein interactions and should be considered as a target for development of novel anti-viral drugs

Citizenship Norms in Eastern Europe

Research on Eastern Europe stresses the weakness of its civil society and the lack of political and social involvement, neglecting the question: What do people themselves think it means to be a good citizen? This study looks at citizens’ definitions of good citizenship in Poland, Slovenia, the Czech Republic and Hungary, using 2002 European Social Survey data. We investigate mean levels of civic mindedness in these countries and perform regression analyses to investigate whether factors traditionally associated with civic and political participation are also correlated with citizenship norms across Eastern Europe. We show that mean levels of civic mindedness differ significantly across the four Eastern European countries. We find some support for theories on civic and political participation when explaining norms of citizenship, but also demonstrate that individual-level characteristics are differently related to citizenship norms across the countries of our study. Hence, our findings show that Eastern Europe is not a monolithic and homogeneous bloc, underscoring the importance of taking the specificities of countries into account

Removal of Hepatitis B virus surface HBsAg and core HBcAg antigens using microbial fuel cells producing electricity from human urine

© 2019, The Author(s). Microbial electrochemical technology is emerging as an alternative way of treating waste and converting this directly to electricity. Intensive research on these systems is ongoing but it currently lacks the evaluation of possible environmental transmission of enteric viruses originating from the waste stream. In this study, for the first time we investigated this aspect by assessing the removal efficiency of hepatitis B core and surface antigens in cascades of continuous flow microbial fuel cells. The log-reduction (LR) of surface antigen (HBsAg) reached a maximum value of 1.86 ± 0.20 (98.6% reduction), which was similar to the open circuit control and degraded regardless of the recorded current. Core antigen (HBcAg) was much more resistant to treatment and the maximal LR was equal to 0.229 ± 0.028 (41.0% reduction). The highest LR rate observed for HBsAg was 4.66 ± 0.19 h−1 and for HBcAg 0.10 ± 0.01 h−1. Regression analysis revealed correlation between hydraulic retention time, power and redox potential on inactivation efficiency, also indicating electroactive behaviour of biofilm in open circuit control through the snorkel-effect. The results indicate that microbial electrochemical technologies may be successfully applied to reduce the risk of environmental transmission of hepatitis B virus but also open up the possibility of testing other viruses for wider implementation

Examining the strategy development process through the lens of complex adaptive systems theory

The development of strategy remains a debate for academics and a concern for practitioners. Published research has focused on producing models for strategy development and on studying how strategy is developed in organisations. The Operational Research literature has highlighted the importance of considering complexity within strategic decision making; but little has been done to link strategy development with complexity theories, despite organisations and organisational environments becoming increasingly more complex. We review the dominant streams of strategy development and complexity theories. Our theoretical investigation results in the first conceptual framework which links an established Strategic Operational Research model, the Strategy Development Process model, with complexity via Complex Adaptive Systems theory. We present preliminary findings from the use of this conceptual framework applied to a longitudinal, in-depth case study, to demonstrate the advantages of using this integrated conceptual model. Our research shows that the conceptual model proposed provides rich data and allows for a more holistic examination of the strategy development process. © 2012 Operational Research Society Ltd. All rights reserved

Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme

Biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. We explored a biomolecular recognition process that involves a major conformational change – protein folding. In particular, we explore the binding-induced folding of IA3, an intrinsically disordered protein that blocks the active site cleft of the yeast aspartic proteinase saccharopepsin (YPrA) by folding its own N-terminal residues into an amphipathic alpha helix. We developed a multi-scaled approach that explores the underlying mechanism by combining structure-based molecular dynamics simulations at the residue level with a stochastic path method at the atomic level. Both the free energy profile and the associated kinetic paths reveal a common scheme whereby IA3 binds to its target enzyme prior to folding itself into a helix. This theoretical result is consistent with recent time-resolved experiments. Furthermore, exploration of the detailed trajectories reveals the important roles of non-native interactions in the initial binding that occurs prior to IA3 folding. In contrast to the common view that non-native interactions contribute only to the roughness of landscapes and impede binding, the non-native interactions here facilitate binding by reducing significantly the entropic search space in the landscape. The information gained from multi-scaled simulations of the folding of this intrinsically disordered protein in the presence of its binding target may prove useful in the design of novel inhibitors of aspartic proteinases