16 research outputs found
Contribution of the land sector to a 1.5 °C world
Acknowledgements The analysis in this study was guided by the valuable feedback and recommendations of expert consultations and interviews, and we extend our gratitude to all those individuals who contributed to our research and analysis: Jeff Atkins (Virginia Commonwealth University), Jonah Busch (Earth Innovation Institute), Peter Ellis (The Nature Conservancy), Jason Funk (Center for Carbon Removal), Trisha Gopalakrishna (The Nature Conservancy), Alan Kroeger (Climate Focus), Bernice Lee (Chatham House), Donna Lee (Climate and Land Use Alliance), Simon Lewis (University College London), Guy Lomax (The Nature Conservancy), Dann Mitchell (University of Bristol), Raoni Rajão (University of Minas Gerais), Joeri Rogelj (IIASA), Carl-Friedrich Schleussner (Climate Analytics), Paul West (University of Minnesota), Graham Wynne (Prince of Wales International Sustainability Unit), Ana Yang (Children’s Investment Fund Foundation) and Dan Zarin (Climate and Land Use Alliance). A special thank you to Esther Chak and Mary-Jo Valentino (Imaginary Office) for designing the figures in this study. This work was generously supported by the Children’s Investment Fund Foundation and the authors’ institutions and funding sources.Peer reviewedPostprin
Scaffold-mediated Nucleation of Protein Signaling Complexes: Elementary Principles
Proteins with multiple binding sites play important roles in cell signaling
systems by nucleating protein complexes in which, for example, enzymes and
substrates are co-localized. Proteins that specialize in this function are
called by a variety names, including adapter, linker and scaffold.
Scaffold-mediated nucleation of protein complexes can be either constitutive or
induced. Induced nucleation is commonly mediated by a docking site on a
scaffold that is activated by phosphorylation. Here, by considering minimalist
mathematical models, which recapitulate scaffold effects seen in more
mechanistically detailed models, we obtain analytical and numerical results
that provide insights into scaffold function. These results elucidate how
recruitment of a pair of ligands to a scaffold depends on the concentrations of
the ligands, on the binding constants for ligand-scaffold interactions, on
binding cooperativity, and on the milieu of the scaffold, as ligand recruitment
is affected by competitive ligands and decoy receptors. For the case of a
bivalent scaffold, we obtain an expression for the unique scaffold
concentration that maximally recruits a pair of monovalent ligands. Through
simulations, we demonstrate that a bivalent scaffold can nucleate distinct sets
of ligands to equivalent extents when the scaffold is present at different
concentrations. Thus, the function of a scaffold can potentially change
qualitatively with a change in copy number. We also demonstrate how a scaffold
can change the catalytic efficiency of an enzyme and the sensitivity of the
rate of reaction to substrate concentration. The results presented here should
be useful for understanding scaffold function and for engineering scaffolds to
have desired properties.Comment: 12 pages, 8 figure
Strategies for protein synthetic biology
Proteins are the most versatile among the various biological building blocks and a mature field of protein engineering has lead to many industrial and biomedical applications. But the strength of proteins—their versatility, dynamics and interactions—also complicates and hinders systems engineering. Therefore, the design of more sophisticated, multi-component protein systems appears to lag behind, in particular, when compared to the engineering of gene regulatory networks. Yet, synthetic biologists have started to tinker with the information flow through natural signaling networks or integrated protein switches. A successful strategy common to most of these experiments is their focus on modular interactions between protein domains or domains and peptide motifs. Such modular interaction swapping has rewired signaling in yeast, put mammalian cell morphology under the control of light, or increased the flux through a synthetic metabolic pathway. Based on this experience, we outline an engineering framework for the connection of reusable protein interaction devices into self-sufficient circuits. Such a framework should help to ‘refacture’ protein complexity into well-defined exchangeable devices for predictive engineering. We review the foundations and initial success stories of protein synthetic biology and discuss the challenges and promises on the way from protein- to protein systems design
Recommended from our members
The Drosophila melanogaster Genetic Reference Panel
A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype–phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype–phenotype mapping using the power of Drosophila genetics
Electronic structure and luminescence of various carcinogens
Self-consistent field calculations were used to determine the bond orders of various aromatic hydrocarbons, some of which were carcinogenic. The phosphorescent half-lives of these compounds were determined experimentally and regression analysis was used to test first, the linear correlation of the phosphorescent half-lives of these compounds versus their carcinogenic indices and then to test the linear correlation of highest bond orders and the phosphorescent half-lives of these compounds versus their carcinogenic indices. Regression analysis was also used to test various combinations of electronic parameters and the phosphorescent half-lives of the compounds studied versus their carcinogenic indices
Electronic structure and luminescence of various carcinogens
Self-consistent field calculations were used to determine the bond orders of various aromatic hydrocarbons, some of which were carcinogenic. The phosphorescent half-lives of these compounds were determined experimentally and regression analysis was used to test first, the linear correlation of the phosphorescent half-lives of these compounds versus their carcinogenic indices and then to test the linear correlation of highest bond orders and the phosphorescent half-lives of these compounds versus their carcinogenic indices. Regression analysis was also used to test various combinations of electronic parameters and the phosphorescent half-lives of the compounds studied versus their carcinogenic indices
Café Shapiro Anthology, Selected Poems and Short Stories from the 14th Annual Café Shapiro
http://deepblue.lib.umich.edu/bitstream/2027.42/116065/1/CafeShapiro_2011.pd