• Anisotropic attosecond charge carrier dynamics and layer decoupling in quasi-2D layered SnS2

      Eads, Calley N.; Bandak, Dmytro; Neupane, Mahesh R.; Nordlund, Dennis; Monti, Oliver L. A.; Univ Arizona, Dept Chem & Biochem; Univ Arizona, Dept Phys (NATURE PUBLISHING GROUP, 2017-11-08)
      Strong quantum confinement effects lead to striking new physics in two-dimensional materials such as graphene or transition metal dichalcogenides. While spectroscopic fingerprints of such quantum confinement have been demonstrated widely, the consequences for carrier dynamics are at present less clear, particularly on ultrafast timescales. This is important for tailoring, probing, and understanding spin and electron dynamics in layered and two-dimensional materials even in cases where the desired bandgap engineering has been achieved. Here we show by means of core-hole clock spectroscopy that SnS2 exhibits spin-dependent attosecond charge delocalization times (tau(deloc)) for carriers confined within a layer, tau(deloc) < 400 as, whereas interlayer charge delocalization is dynamically quenched in excess of a factor of 10, tau(deloc) > 2.7 fs. These layer decoupling dynamics are a direct consequence of strongly anisotropic screening established within attoseconds, and demonstrate that important two-dimensional characteristics are also present in bulk crystals of van der Waals-layered materials, at least on ultrafast timescales.
    • A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4

      Galletta, Brian J.; Fagerstrom, Carey J.; Schoborg, Todd A.; McLamarrah, Tiffany A.; Ryniawec, John M.; Buster, Daniel W.; Slep, Kevin C.; Rogers, Gregory C.; Rusan, Nasser M.; Univ Arizona, Ctr Canc, Dept Cellular & Mol Med (NATURE PUBLISHING GROUP, 2016-08-25)
      The centrosome is the major microtubule-organizing centre of many cells, best known for its role in mitotic spindle organization. How the proteins of the centrosome are accurately assembled to carry out its many functions remains poorly understood. The non-membranebound nature of the centrosome dictates that protein-protein interactions drive its assembly and functions. To investigate this massive macromolecular organelle, we generated a `domain-level' centrosome interactome using direct protein-protein interaction data from a focused yeast two-hybrid screen. We then used biochemistry, cell biology and the model organism Drosophila to provide insight into the protein organization and kinase regulatory machinery required for centrosome assembly. Finally, we identified a novel role for Plk4, the master regulator of centriole duplication. We show that Plk4 phosphorylates Cep135 to properly position the essential centriole component Asterless. This interaction landscape affords a critical framework for research of normal and aberrant centrosomes.
    • Direct effects dominate responses to climate perturbations in grassland plant communities

      Chu, Chengjin; Kleinhesselink, Andrew R.; Havstad, Kris M.; McClaran, Mitchel P.; Peters, Debra P.; Vermeire, Lance T.; Wei, Haiyan; Adler, Peter B.; Univ Arizona, Sch Nat Resources & Environm (NATURE PUBLISHING GROUP, 2016-06-08)
      Theory predicts that strong indirect effects of environmental change will impact communities when niche differences between competitors are small and variation in the direct effects experienced by competitors is large, but empirical tests are lacking. Here we estimate negative frequency dependence, a proxy for niche differences, and quantify the direct and indirect effects of climate change on each species. Consistent with theory, in four of five communities indirect effects are strongest for species showing weak negative frequency dependence. Indirect effects are also stronger in communities where there is greater variation in direct effects. Overall responses to climate perturbations are driven primarily by direct effects, suggesting that single species models may be adequate for forecasting the impacts of climate change in these communities.
    • DNA transposon activity is associated with increased mutation rates in genes of rice and other grasses

      Wicker, Thomas; Yu, Yeisoo; Haberer, Georg; Mayer, Klaus F. X.; Marri, Pradeep Reddy; Rounsley, Steve; Chen, Mingsheng; Zuccolo, Andrea; Panaud, Olivier; Wing, Rod A.; et al. (NATURE PUBLISHING GROUP, 2016-09-07)
      DNA (class 2) transposons are mobile genetic elements which move within their 'host' genome through excising and re-inserting elsewhere. Although the rice genome contains tens of thousands of such elements, their actual role in evolution is still unclear. Analysing over 650 transposon polymorphisms in the rice species Oryza sativa and Oryza glaberrima, we find that DNA repair following transposon excisions is associated with an increased number of mutations in the sequences neighbouring the transposon. Indeed, the 3,000 bp flanking the excised transposons can contain over 10 times more mutations than the genome-wide average. Since DNA transposons preferably insert near genes, this is correlated with increases in mutation rates in coding sequences and regulatory regions. Most importantly, we find this phenomenon also in maize, wheat and barley. Thus, these findings suggest that DNA transposon activity is a major evolutionary force in grasses which provide the basis of most food consumed by humankind.
    • Endocytosis regulates TDP-43 toxicity and turnover

      Liu, Guangbo; Coyne, Alyssa N.; Pei, Fen; Vaughan, Spencer; Chaung, Matthew; Zarnescu, Daniela C.; Buchan, J. Ross; Univ Arizona, Dept Mol & Cellular Biol (NATURE PUBLISHING GROUP, 2017-12-12)
      Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease. ALS-affected motor neurons exhibit aberrant localization of a nuclear RNA binding protein, TDP-43, into cytoplasmic aggregates, which contributes to pathology via unclear mechanisms. Here, we demonstrate that TDP-43 turnover and toxicity depend in part upon the endocytosis pathway. TDP-43 inhibits endocytosis, and co-localizes strongly with endocytic proteins, including in ALS patient tissue. Impairing endocytosis increases TDP-43 toxicity, aggregation, and protein levels, whereas enhancing endocytosis reverses these phenotypes. Locomotor dysfunction in a TDP-43 ALS fly model is also exacerbated and suppressed by impairment and enhancement of endocytic function, respectively. Thus, endocytosis dysfunction may be an underlying cause of ALS pathology.
    • Endocytosis regulates TDP-43 toxicity and turnover

      Liu, Guangbo; Coyne, Alyssa N.; Pei, Fen; Vaughan, Spencer; Chaung, Matthew; Zarnescu, Daniela C.; Buchan, J. Ross; Univ Arizona, Dept Mol & Cellular Biol (Springer Nature, 2017)
      Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease. ALS-affected motor neurons exhibit aberrant localization of a nuclear RNA binding protein, TDP-43, into cytoplasmic aggregates, which contributes to pathology via unclear mechanisms. Here, we demonstrate that TDP-43 turnover and toxicity depend in part upon the endocytosis pathway. TDP-43 inhibits endocytosis, and co-localizes strongly with endocytic proteins, including in ALS patient tissue. Impairing endocytosis increases TDP-43 toxicity, aggregation, and protein levels, whereas enhancing endocytosis reverses these phenotypes. Locomotor dysfunction in a TDP-43 ALS fly model is also exacerbated and suppressed by impairment and enhancement of endocytic function, respectively. Thus, endocytosis dysfunction may be an underlying cause of ALS pathology.
    • Evolutionary interplay between sister cytochrome P450 genes shapes plasticity in plant metabolism

      Liu, Zhenhua; Tavares, Raquel; Forsythe, Evan S.; André, François; Lugan, Raphaël; Jonasson, Gabriella; Boutet-Mercey, Stéphanie; Tohge, Takayuki; Beilstein, Mark A.; Werck-Reichhart, Danièle; et al. (NATURE PUBLISHING GROUP, 2016-10-07)
      Expansion of the cytochrome P450 gene family is often proposed to have a critical role in the evolution of metabolic complexity, in particular in microorganisms, insects and plants. However, the molecular mechanisms underlying the evolution of this complexity are poorly understood. Here we describe the evolutionary history of a plant P450 retrogene, which emerged and underwent fixation in the common ancestor of Brassicales, before undergoing tandem duplication in the ancestor of Brassicaceae. Duplication leads first to gain of dual functions in one of the copies. Both sister genes are retained through subsequent speciation but eventually return to a single copy in two of three diverging lineages. In the lineage in which both copies are maintained, the ancestral functions are split between paralogs and a novel function arises in the copy under relaxed selection. Our work illustrates how retrotransposition and gene duplication can favour the emergence of novel metabolic functions.
    • Exit from quiescence displays a memory of cell growth and division

      Wang, Xia; Fujimaki, Kotaro; Mitchell, Geoffrey C.; Kwon, Jungeun Sarah; Della Croce, Kimiko; Langsdorf, Chris; Zhang, Hao Helen; Yao, Guang; Univ Arizona, Dept Mol & Cellular Biol; Univ Arizona, Dept Math; et al. (NATURE PUBLISHING GROUP, 2017-08-22)
      Reactivating quiescent cells to proliferate is critical to tissue repair and homoeostasis. Quiescence exit is highly noisy even for genetically identical cells under the same environmental conditions. Deregulation of quiescence exit is associated with many diseases, but cellular mechanisms underlying the noisy process of exiting quiescence are poorly understood. Here we show that the heterogeneity of quiescence exit reflects a memory of preceding cell growth at quiescence induction and immediate division history before quiescence entry, and that such a memory is reflected in cell size at a coarse scale. The deterministic memory effects of preceding cell cycle, coupled with the stochastic dynamics of an Rb-E2F bistable switch, jointly and quantitatively explain quiescence-exit heterogeneity. As such, quiescence can be defined as a distinct state outside of the cell cycle while displaying a sequential cell order reflecting preceding cell growth and division variations.
    • Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease

      Hartiala, Jaana A.; Wilson Tang, W. H.; Wang, Zeneng; Crow, Amanda L.; Stewart, Alexandre F. R.; Roberts, Robert; McPherson, Ruth; Erdmann, Jeanette; Willenborg, Christina; Hazen, Stanley L.; et al. (NATURE PUBLISHING GROUP, 2016-01-29)
      Metabolites derived from dietary choline and L-carnitine, such as trimethylamine N-oxide and betaine, have recently been identified as novel risk factors for atherosclerosis in mice and humans. We sought to identify genetic factors associated with plasma betaine levels and determine their effect on risk of coronary artery disease (CAD). A two-stage genome-wide association study (GWAS) identified two significantly associated loci on chromosomes 2q34 and 5q14.1. The lead variant on 2q24 (rs715) localizes to carbamoyl-phosphate synthase 1 (CPS1), which encodes a mitochondrial enzyme that catalyses the first committed reaction and rate-limiting step in the urea cycle. Rs715 is also significantly associated with decreased levels of urea cycle metabolites and increased plasma glycine levels. Notably, rs715 yield a strikingly significant and protective association with decreased risk of CAD in only women. These results suggest that glycine metabolism and/or the urea cycle represent potentially novel sex-specific mechanisms for the development of atherosclerosis.
    • The giant protein titin regulates the length of the striated muscle thick filament

      Tonino, Paola; Kiss, Balazs; Strom, Josh; Methawasin, Mei; Smith, John E.; Kolb, Justin; Labeit, Siegfried; Granzier, Henk; Univ Arizona, Dept Cellular & Mol Med; Univ Arizona, Sarver Mol Cardiovasc Res Program (NATURE PUBLISHING GROUP, 2017-10-19)
      The contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised of the molecular motor myosin. The thick filament is of a precisely controlled length, defining thereby the force level that muscles generate and how this force varies with muscle length. It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists. Here we show that in a mouse model in which we deleted two of titin's C-zone super-repeats, thick filament length is reduced in cardiac and skeletal muscles. In addition, functional studies reveal reduced force generation and a dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length depends on titin and is critical for maintaining muscle health.
    • The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity

      Hanschen, Erik R.; Marriage, Tara N.; Ferris, Patrick J.; Hamaji, Takashi; Toyoda, Atsushi; Fujiyama, Asao; Neme, Rafik; Noguchi, Hideki; Minakuchi, Yohei; Suzuki, Masahiro; et al. (NATURE PUBLISHING GROUP, 2016-04-22)
      The transition to multicellularity has occurred numerous times in all domains of life, yet its initial steps are poorly understood. The volvocine green algae are a tractable system for understanding the genetic basis of multicellularity including the initial formation of cooperative cell groups. Here we report the genome sequence of the undifferentiated colonial alga, Gonium pectorale, where group formation evolved by co-option of the retinoblastoma cell cycle regulatory pathway. Significantly, expression of the Gonium retinoblastoma cell cycle regulator in unicellular Chlamydomonas causes it to become colonial. The presence of these changes in undifferentiated Gonium indicates extensive group-level adaptation during the initial step in the evolution of multicellularity. These results emphasize an early and formative step in the evolution of multicellularity, the evolution of cell cycle regulation, one that may shed light on the evolutionary history of other multicellular innovations and evolutionary transitions.
    • Imaging low-mass planets within the habitable zone of α Centauri

      Wagner, K.; Boehle, A.; Pathak, P.; Kasper, M.; Arsenault, R.; Jakob, G.; Käufl, U.; Leveratto, S.; Maire, A.-L.; Pantin, E.; et al. (Nature Research, 2021-02-10)
      Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we present a ground-based mid-infrared observing approach that enables imaging low-mass temperate exoplanets around nearby stars, and in particular within the closest stellar system, α Centauri. Based on 75–80% of the best quality images from 100 h of cumulative observations, we demonstrate sensitivity to warm sub-Neptune-sized planets throughout much of the habitable zone of α Centauri A. This is an order of magnitude more sensitive than state-of-the-art exoplanet imaging mass detection limits. We also discuss a possible exoplanet or exozodiacal disk detection around α Centauri A. However, an instrumental artifact of unknown origin cannot be ruled out. These results demonstrate the feasibility of imaging rocky habitable-zone exoplanets with current and upcoming telescopes. © 2021, The Author(s).
    • Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

      Zillikens, M. Carola; Demissie, Serkalem; Hsu, Yi-Hsiang; Yerges-Armstrong, Laura M.; Chou, Wen-Chi; Stolk, Lisette; Livshits, Gregory; Broer, Linda; Johnson, Toby; Koller, Daniel L.; et al. (NATURE PUBLISHING GROUP, 2017-07-19)
      Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
    • A microfluidics-based in vitro model of the gastrointestinal human–microbe interface

      Shah, Pranjul; Fritz, Joëlle V.; Glaab, Enrico; Desai, Mahesh S.; Greenhalgh, Kacy; Frachet, Audrey; Niegowska, Magdalena; Estes, Matthew; Jäger, Christian; Seguin-Devaux, Carole; et al. (NATURE PUBLISHING GROUP, 2016-05-11)
      Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human-microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface. We demonstrate the ability of HuMiX to recapitulate in vivo transcriptional, metabolic and immunological responses in human intestinal epithelial cells following their co-culture with the commensal Lactobacillus rhamnosus GG (LGG) grown under anaerobic conditions. In addition, we show that the co-culture of human epithelial cells with the obligate anaerobe Bacteroides caccae and LGG results in a transcriptional response, which is distinct from that of a co-culture solely comprising LGG. HuMiX facilitates investigations of host-microbe molecular interactions and provides insights into a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease.
    • Normal and inverted regimes of charge transfer controlled by density of states at polymer electrodes

      Rudolph, M.; Ratcliff, E. L.; Univ Arizona, Dept Mat Sci & Engn (NATURE PUBLISHING GROUP, 2017-10-19)
      Conductive polymer electrodes have exceptional promise for next-generation bioelectronics and energy conversion devices due to inherent mechanical flexibility, printability, biocompatibility, and low cost. Conductive polymers uniquely exhibit hybrid electronic-ionic transport properties that enable novel electrochemical device architectures, an advantage over inorganic counterparts. Yet critical structure-property relationships to control the potential-dependent rates of charge transfer at polymer/electrolyte interfaces remain poorly understood. Herein, we evaluate the kinetics of charge transfer between electrodeposited poly-(3-hexylthiophene) films and a model redox-active molecule, ferrocenedimethanol. We show that the kinetics directly follow the potential-dependent occupancy of electronic states in the polymer. The rate increases then decreases with potential *(both normal and inverted kinetic regimes), a phenomenon distinct from inorganic semiconductors. This insight can be invoked to design polymer electrodes with kinetic selectivity toward redox active species and help guide synthetic approaches for the design of alternative device architectures and approaches.
    • Optical analogues of the Newton–Schrödinger equation and boson star evolution

      Roger, Thomas; Maitland, Calum; Wilson, Kali; Westerberg, Niclas; Vocke, David; Wright, Ewan M.; Faccio, Daniele; Univ Arizona, Coll Opt Sci (NATURE PUBLISHING GROUP, 2016-11-14)
      Many gravitational phenomena that lie at the core of our understanding of the Universe have not yet been directly observed. An example in this sense is the boson star that has been proposed as an alternative to some compact objects currently interpreted as being black holes. In the weak field limit, these stars are governed by the Newton-Schrodinger equation. Here we present an optical system that, under appropriate conditions, identically reproduces such equation in two dimensions. A rotating boson star is experimentally and numerically modelled by an optical beam propagating through a medium with a positive thermal nonlinearity and is shown to oscillate in time while also stable up to relatively high densities. For higher densities, instabilities lead to an apparent breakup of the star, yet coherence across the whole structure is maintained. These results show that optical analogues can be used to shed new light on inaccessible gravitational objects.
    • Pressure-induced commensurate stacking of graphene on boron nitride

      Yankowitz, Matthew; Watanabe, K.; Taniguchi, T.; San-Jose, Pablo; LeRoy, Brian J.; Univ Arizona, Dept Phys (NATURE PUBLISHING GROUP, 2016-10-20)
      Combining atomically-thin van der Waals materials into heterostructures provides a powerful path towards the creation of designer electronic devices. The interaction strength between neighbouring layers, most easily controlled through their interlayer separation, can have significant influence on the electronic properties of these composite materials. Here, we demonstrate unprecedented control over interlayer interactions by locally modifying the interlayer separation between graphene and boron nitride, which we achieve by applying pressure with a scanning tunnelling microscopy tip. For the special case of aligned or nearly-aligned graphene on boron nitride, the graphene lattice can stretch and compress locally to compensate for the slight lattice mismatch between the two materials. We find that modifying the interlayer separation directly tunes the lattice strain and induces commensurate stacking underneath the tip. Our results motivate future studies tailoring the electronic properties of van der Waals heterostructures by controlling the interlayer separation of the entire device using hydrostatic pressure.
    • Rapid 14C excursion at 3372-3371 BCE not observed at two different locations

      Timothy Jull, A. J.; Panyushkina, Irina P.; Molnár, Mihály; Varga, Tamás; Wacker, Lukas; Brehm, Nicolas; Laszló, Elemér; Baisan, Chris; Salzer, Matthew W.; Tegel, Willy; et al. (Nature Research, 2021-01-29)
    • Rapid visualization of grain boundaries in monolayer MoS2 by multiphoton microscopy

      Karvonen, Lasse; Saynatjoki, Antti; Huttunen, Mikko J.; Autere, Anton; Amirsolaimani, Babak; Li, Shisheng; Norwood, Robert A.; Peyghambarian, Nasser; Lipsanen, Harri; Eda, Goki; et al. (NATURE PUBLISHING GROUP, 2017-06-05)
      Grain boundaries have a major effect on the physical properties of two-dimensional layered materials. Therefore, it is important to develop simple, fast and sensitive characterization methods to visualize grain boundaries. Conventional Raman and photoluminescence methods have been used for detecting grain boundaries; however, these techniques are better suited for detection of grain boundaries with a large crystal axis rotation between neighbouring grains. Here we show rapid visualization of grain boundaries in chemical vapour deposited monolayer MoS2 samples with multiphoton microscopy. In contrast to Raman and photoluminescence imaging, third-harmonic generation microscopy provides excellent sensitivity and high speed for grain boundary visualization regardless of the degree of crystal axis rotation. We find that the contrast associated with grain boundaries in the third-harmonic imaging is considerably enhanced by the solvents commonly used in the transfer process of two-dimensional materials. Our results demonstrate that multiphoton imaging can be used for fast and sensitive characterization of two-dimensional materials.
    • Recent enhanced high-summer North Atlantic Jet variability emerges from three-century context

      Trouet, V.; Babst, F.; Meko, M.; Univ Arizona, Lab Tree Ring Res (NATURE PUBLISHING GROUP, 2018-01-12)
      A recent increase in mid-latitude extreme weather events has been linked to Northern Hemisphere polar jet stream anomalies. To put recent trends in a historical perspective, long-term records of jet stream variability are needed. Here we combine two tree-ring records from the British Isles and the northeastern Mediterranean to reconstruct variability in the latitudinal position of the high-summer North Atlantic Jet (NAJ) back to 1725 CE. We find that northward NAJ anomalies have resulted in heatwaves and droughts in northwestern Europe and southward anomalies have promoted wildfires in southeastern Europe. We further find an unprecedented increase in NAJ variance since the 1960s, which co-occurs with enhanced late twentieth century variance in the Central and North Pacific Basin. Our results suggest increased late twentieth century interannual meridional jet stream variability and support more sinuous jet stream patterns and quasi-resonant amplification as potential dynamic pathways for Arctic warming to influence mid-latitude weather.