Principles of assembly reveal a periodic table of protein complexes.

Structural insights into protein complexes have had a broad impact on our understanding of biological function and evolution. In this work, we sought a comprehensive understanding of the general principles underlying quaternary structure organization in protein complexes. We first examined the fundamental steps by which protein complexes can assemble, using experimental and structure-based characterization of assembly pathways. Most assembly transitions can be classified into three basic types, which can then be used to exhaustively enumerate a large set of possible quaternary structure topologies. These topologies, which include the vast majority of observed protein complex structures, enable a natural organization of protein complexes into a periodic table. On the basis of this table, we can accurately predict the expected frequencies of quaternary structure topologies, including those not yet observed. These results have important implications for quaternary structure prediction, modeling, and engineering.This work was supported by the Royal Society (S.E.A. and C.V.R.), the Human Frontier Science Program (J.A.M.), the Medical Research Council grant G1000819 (H.H. and C.V.R.) and the Lister Institute for Preventative Medicine (S.A.T.).This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aaa224

Association between Pseudonocardia symbionts and Atta leaf-cutting ants suggested by improved isolation methods

Fungus-growing ants associate with multiple symbiotic microbes, including Actinobacteria for production of antibiotics.The best studied of these bacteria are within the genus Pseudonocardia, which in most fungus-growing ants are conspicuouslyvisible on the external cuticle of workers. However, given that fungus-growing ants in the genus Atta do not carry visibleActinobacteria on their cuticle, it is unclear if this genus engages in the symbiosis with Pseudonocardia. Here we explore whetherimproving culturing techniques can allow for successful isolation of Pseudonocardia from Atta cephalotes leaf-cutting ants. Weobtained Pseudonocardia from 9 of 11 isolation method/colony component combinations from all 5 colonies intensively sampled.The most efficient technique was bead-beating workers in phosphate buffer solution, then plating the suspension on carboxymethylcellulosemedium. Placing these strains in a fungus-growing ant-associated Pseudonocardia phylogeny revealed that while somestrains grouped with clades of Pseudonocardia associated with other genera of fungus-growing ants, a large portion of the isolatesfell into two novel phylogenetic clades previously not identified from this ant-microbe symbiosis. Our findings suggest thatPseudonocardia may be associated with Atta fungus-growing ants, potentially internalized, and that localizing the symbiont andexploring its role is necessary to shed further light on the association. [Int Microbiol 2013; 16(1):17-25

Anode Catalysts in Anion‐Exchange‐Membrane Electrolysis without Supporting Electrolyte: Conductivity, Dynamics, and Ionomer Degradation

Anion-exchange-membrane water electrolyzers (AEMWEs) in principle operate without soluble electrolyte using earth-abundant catalysts and cell materials and thus lower the cost of green H2 . Current systems lack competitive performance and the durability needed for commercialization. One critical issue is a poor understanding of catalyst-specific degradation processes in the electrolyzer. While non-platinum-group-metal (non-PGM) oxygen-evolution catalysts show excellent performance and durability in strongly alkaline electrolyte, this has not transferred directly to pure-water AEMWEs. Here, AEMWEs with five non-PGM anode catalysts are built and the catalysts' structural stability and interactions with the alkaline ionomer are characterized during electrolyzer operation and post-mortem. The results show catalyst electrical conductivity is one key to obtaining high-performing systems and that many non-PGM catalysts restructure during operation. Dynamic Fe sites correlate with enhanced degradation rates, as does the addition of soluble Fe impurities. In contrast, electronically conductive Co3 O4 nanoparticles (without Fe in the crystal structure) yield AEMWEs from simple, standard preparation methods, with performance and stability comparable to IrO2 . These results reveal the fundamental dynamic catalytic processes resulting in AEMWE device failure under relevant conditions, demonstrate a viable non-PGM catalyst for AEMWE operation, and illustrate underlying design rules for engineering anode catalyst/ionomer layers with higher performance and durability

Permafrost Landscape History Shapes Fluvial Chemistry, Ecosystem Carbon Balance, and Potential Trajectories of Future Change

Intensifying permafrost thaw alters carbon cycling by mobilizing large amounts of terrestrial substrate into aquatic ecosystems. Yet, few studies have measured aquatic carbon fluxes and constrained drivers of ecosystem carbon balance across heterogeneous Arctic landscapes. Here, we characterized hydrochemical and landscape controls on fluvial carbon cycling, quantified fluvial carbon fluxes, and estimated fluvial contributions to ecosystem carbon balance across 33 watersheds in four ecoregions in the continuous permafrost zone of the western Canadian Arctic: unglaciated uplands, ice-rich moraine, and organic-rich lowlands and till plains. Major ions, stable isotopes, and carbon speciation and fluxes revealed patterns in carbon cycling across ecoregions defined by terrain relief and accumulation of organics. In previously unglaciated mountainous watersheds, bicarbonate dominated carbon export (70% of total) due to chemical weathering of bedrock. In lowland watersheds, where soil organic carbon stores were largest, lateral transport of dissolved organic carbon (50%) and efflux of biotic CO2 (25%) dominated. In watersheds affected by thaw-induced mass wasting, erosion of ice-rich tills enhanced chemical weathering and increased particulate carbon fluxes by two orders of magnitude. From an ecosystem carbon balance perspective, fluvial carbon export in watersheds not affected by thaw-induced wasting was, on average, equivalent to 6%–16% of estimated net ecosystem exchange (NEE). In watersheds affected by thaw-induced wasting, fluvial carbon export approached 60% of NEE. Because future intensification of thermokarst activity will amplify fluvial carbon export, determining the fate of carbon across diverse northern landscapes is a priority for constraining trajectories of permafrost region ecosystem carbon balance

Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects

Clonal hematopoiesis of indeterminate potential (CHIP) increases rapidly in prevalence beyond age 60 and has been associated with increased risk for malignancy, heart disease and ischemic stroke. CHIP is driven by somatic mutations in hematopoietic stem and progenitor cells (HSPCs). Because mutations in HSPCs often drive leukemia, we hypothesized that HSPC fitness substantially contributes to transformation from CHIP to leukemia. HSPC fitness is defined as the proliferative advantage over cells carrying no or only neutral mutations. If mutations in different genes lead to distinct fitness advantages, this could enable patient stratification. We quantified the fitness effects of mutations over 12 years in older age using longitudinal sequencing and developed a filtering method that considers individual mutational context alongside mutation co-occurrence to quantify the growth potential of variants within individuals. We found that gene-specific fitness differences can outweigh inter-individual variation and, therefore, could form the basis for personalized clinical management

Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain

A key aspect of nearly all single-cell sequencing experiments is dissociation of intact tissues into single-cell suspensions. While many protocols have been optimized for optimal cell yield, they have often overlooked the effects that dissociation can have on ex vivo gene expression. Here, we demonstrate that use of enzymatic dissociation on brain tissue induces an aberrant ex vivo gene expression signature, most prominently in microglia, which is prevalent in published literature and can substantially confound downstream analyses. To address this issue, we present a rigorously validated protocol that preserves both in vivo transcriptional profiles and cell-type diversity and yield across tissue types and species. We also identify a similar signature in postmortem human brain single-nucleus RNA-sequencing datasets, and show that this signature is induced in freshly isolated human tissue by exposure to elevated temperatures ex vivo. Together, our results provide a methodological solution for preventing artifactual gene expression changes during fresh tissue digestion and a reference for future deeper analysis of the potential confounding states present in postmortem human samples

CMB-S4 Science Book, First Edition

This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales