174 research outputs found

    Carbon Trading with Blockchain

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    Blockchain has the potential to accelerate the deployment of emissions trading systems (ETS) worldwide and improve upon the efficiency of existing systems. In this paper, we present a model for a permissioned blockchain implementation based on the successful European Union (EU) ETS and discuss its potential advantages over existing technology. We propose an ETS model that is both backwards compatible and future-proof, characterised by interconnectedness, transparency, tamper-resistance and high liquidity. Further, we identify key challenges to implementation of a blockchain ETS, as well as areas of future work required to enable a fully-decentralised blockchain ETS

    Key Amino Acid Residues of Ankyrin-Sensitive Phosphatidylethanolamine/Phosphatidylcholine-Lipid Binding Site of βI-Spectrin

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    It was shown previously that an ankyrin-sensitive, phosphatidylethanolamine/phosphatidylcholine (PE/PC) binding site maps to the N-terminal part of the ankyrin-binding domain of β-spectrin (ankBDn). Here we have identified the amino acid residues within this domain which are responsible for recognizing monolayers and bilayers composed of PE/PC mixtures. In vitro binding studies revealed that a quadruple mutant with substituted hydrophobic residues W1771, L1775, M1778 and W1779 not only failed to effectively bind PE/PC, but its residual PE/PC-binding activity was insensitive to inhibition with ankyrin. Structure prediction and analysis, supported by in vitro experiments, suggests that “opening” of the coiled-coil structure underlies the mechanism of this interaction. Experiments on red blood cells and HeLa cells supported the conclusions derived from the model and in vitro lipid-protein interaction results, and showed the potential physiological role of this binding. We postulate that direct interactions between spectrin ankBDn and PE-rich domains play an important role in stabilizing the structure of the spectrin-based membrane skeleton

    Genome-Wide Analysis of Effectors of Peroxisome Biogenesis

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    Peroxisomes are intracellular organelles that house a number of diverse metabolic processes, notably those required for β-oxidation of fatty acids. Peroxisomes biogenesis can be induced by the presence of peroxisome proliferators, including fatty acids, which activate complex cellular programs that underlie the induction process. Here, we used multi-parameter quantitative phenotype analyses of an arrayed mutant collection of yeast cells induced to proliferate peroxisomes, to establish a comprehensive inventory of genes required for peroxisome induction and function. The assays employed include growth in the presence of fatty acids, and confocal imaging and flow cytometry through the induction process. In addition to the classical phenotypes associated with loss of peroxisomal functions, these studies identified 169 genes required for robust signaling, transcription, normal peroxisomal development and morphologies, and transmission of peroxisomes to daughter cells. These gene products are localized throughout the cell, and many have indirect connections to peroxisome function. By integration with extant data sets, we present a total of 211 genes linked to peroxisome biogenesis and highlight the complex networks through which information flows during peroxisome biogenesis and function

    Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases

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    Current antibiotics tend to be broad spectrum, leading to indiscriminate killing of commensal bacteria and accelerated evolution of drug resistance. Here, we use CRISPR-Cas technology to create antimicrobials whose spectrum of activity is chosen by design. RNA-guided nucleases (RGNs) targeting specific DNA sequences are delivered efficiently to microbial populations using bacteriophage or bacteria carrying plasmids transmissible by conjugation. The DNA targets of RGNs can be undesirable genes or polymorphisms, including antibiotic resistance and virulence determinants in carbapenem-resistant Enterobacteriaceae and enterohemorrhagic Escherichia coli. Delivery of RGNs significantly improves survival in a Galleria mellonella infection model. We also show that RGNs enable modulation of complex bacterial populations by selective knockdown of targeted strains based on genetic signatures. RGNs constitute a class of highly discriminatory, customizable antimicrobials that enact selective pressure at the DNA level to reduce the prevalence of undesired genes, minimize off-target effects and enable programmable remodeling of microbiota.National Institutes of Health (U.S.) (New Innovator Award 1DP2OD008435)National Centers for Systems Biology (U.S.) (Grant 1P50GM098792)United States. Defense Threat Reduction Agency (HDTRA1-14-1-0007)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (W911NF13D0001)National Institute of General Medical Sciences (U.S.) (Interdepartmental Biotechnology Training Program 5T32 GM008334)Fonds de la recherche en sante du Quebec (Master's Training Award

    Metatranscriptomics reveal differences in in situ energy and nitrogen metabolism among hydrothermal vent snail symbionts

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    Despite the ubiquity of chemoautotrophic symbioses at hydrothermal vents, our understanding of the influence of environmental chemistry on symbiont metabolism is limited. Transcriptomic analyses are useful for linking physiological poise to environmental conditions, but recovering samples from the deep sea is challenging, as the long recovery times can change expression profiles before preservation. Here, we present a novel, in situ RNA sampling and preservation device, which we used to compare the symbiont metatranscriptomes associated with Alviniconcha, a genus of vent snail, in which specific host–symbiont combinations are predictably distributed across a regional geochemical gradient. Metatranscriptomes of these symbionts reveal key differences in energy and nitrogen metabolism relating to both environmental chemistry (that is, the relative expression of genes) and symbiont phylogeny (that is, the specific pathways employed). Unexpectedly, dramatic differences in expression of transposases and flagellar genes suggest that different symbiont types may also have distinct life histories. These data further our understanding of these symbionts' metabolic capabilities and their expression in situ, and suggest an important role for symbionts in mediating their hosts' interaction with regional-scale differences in geochemistry

    Nuclear Mitochondrial DNA Activates Replication in Saccharomyces cerevisiae

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    The nuclear genome of eukaryotes is colonized by DNA fragments of mitochondrial origin, called NUMTs. These insertions have been associated with a variety of germ-line diseases in humans. The significance of this uptake of potentially dangerous sequences into the nuclear genome is unclear. Here we provide functional evidence that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae. We show that NUMTs are rich in key autonomously replicating sequence (ARS) consensus motifs, whose mutation results in the reduction or loss of DNA replication activity. Furthermore, 2D-gel analysis of the mrc1 mutant exposed to hydroxyurea shows that several NUMTs function as late chromosomal origins. We also show that NUMTs located close to or within ARS provide key sequence elements for replication. Thus NUMTs can act as independent origins, when inserted in an appropriate genomic context or affect the efficiency of pre-existing origins. These findings show that migratory mitochondrial DNAs can impact on the replication of the nuclear region they are inserted in

    Effectiveness of an implementation strategy for a breastfeeding guideline in Primary Care: cluster randomised trial

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    <p>Abstract</p> <p>Background</p> <p>The protection and promotion of breastfeeding is considered a priority in Europe where only 22% of infants less than 6 months old are exclusively breastfed. In Spain this percentage reaches 24.8% but in our city it falls to 18.26%. Various studies emphasise that the improvement of these results should be based upon the training of health professionals. Following the recommendations of a breastfeeding guide can modify the practice of health professionals and improve results with respect to exclusively or predominatly breastfed children at 6 months of age.</p> <p>Method/Design</p> <p>This study involves a community based cluster randomized trial in primary healthcare centres in Leganés (Madrid, Spain). The project aims to determine whether the use of an implementation strategy (including training session, information distribution, opinion leader) of a breastfeeding guideline in primary care is more effective than usual diffusion.</p> <p>The number of patients required will be 240 (120 in each arm). It will be included all the mothers of infants born during the study period (6 months) who come to the health centre on the first visit of the child care programme and who give their consent to participate. The main outcome variable is the exclusive o predominant breastfeeding at 6 moths of age..</p> <p>Main effectiveness will be analyzed by comparing the percentage of infants with exclusive or predominant breastfeeding at 6 months between the intervention group and the control group. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis.</p> <p>Discussion</p> <p>Strategies need to be found which facilitate the giving of effective advice on breastfeeding by professionals and which provide support to women during the breastfeeding period. By applying the guide's recommendations, clinical variability can be reduced and the care received by patients can be improved.</p> <p>Trial registration</p> <p>The trial was registered with ClinicalTrials.gov, number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01474096">NCT01474096</a></p
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