@article{1228, abstract = {Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.}, author = {Sauerzopf, Ulrich and Sacco, Roberto and Novarino, Gaia and Niello, Marco and Weidenauer, Ana and Praschak Rieder, Nicole and Sitte, Harald and Willeit, Matthaeus}, journal = {European Journal of Neuroscience}, number = {1}, pages = {45 -- 57}, publisher = {Wiley-Blackwell}, title = {{Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence}}, doi = {10.1111/ejn.13418}, volume = {45}, year = {2017}, } @article{123, abstract = {The Leidenfrost effect occurs when an object near a hot surface vaporizes rapidly enough to lift itself up and hover. Although well understood for liquids and stiff sublimable solids, nothing is known about the effect with materials whose stiffness lies between these extremes. Here we introduce a new phenomenon that occurs with vaporizable soft solids - the elastic Leidenfrost effect. By dropping hydrogel spheres onto hot surfaces we find that, rather than hovering, they energetically bounce several times their diameter for minutes at a time. With high-speed video during a single impact, we uncover high-frequency microscopic gap dynamics at the sphere/substrate interface. We show how these otherwise-hidden agitations constitute work cycles that harvest mechanical energy from the vapour and sustain the bouncing. Our findings suggest a new strategy for injecting mechanical energy into a widely used class of soft materials, with potential relevance to fields such as active matter, soft robotics and microfluidics.}, author = {Waitukaitis, Scott R and Zuiderwijk, Antal and Souslov, Anton and Coulais, Corentin and Van Hecke, Martin}, journal = {Nature Physics}, number = {11}, pages = {1095 -- 1099}, publisher = {Nature Publishing Group}, title = {{Coupling the Leidenfrost effect and elastic deformations to power sustained bouncing}}, doi = {10.1038/nphys4194}, volume = {13}, year = {2017}, } @inproceedings{12571, abstract = {We consider the problems of maintaining approximate maximum matching and minimum vertex cover in a dynamic graph. Starting with the seminal work of Onak and Rubinfeld [STOC 2010], this problem has received significant attention in recent years. Very recently, extending the framework of Baswana, Gupta and Sen [FOCS 2011], Solomon [FOCS 2016] gave a randomized 2-approximation dynamic algorithm for this problem that has amortized update time of O(1) with high probability. We consider the natural open question of derandomizing this result. We present a new deterministic fully dynamic algorithm that maintains a O(1)-approximate minimum vertex cover and maximum fractional matching, with an amortized update time of O(1). Previously, the best deterministic algorithm for this problem was due to Bhattacharya, Henzinger and Italiano [SODA 2015]; it had an approximation ratio of (2+ϵ) and an amortized update time of O(logn/ϵ2). Our result can be generalized to give a fully dynamic O(f3)-approximation algorithm with O(f2) amortized update time for the hypergraph vertex cover and fractional matching problems, where every hyperedge has at most f vertices.}, author = {Bhattacharya, Sayan and Chakrabarty, Deeparnab and Henzinger, Monika H}, booktitle = {19th International Conference on Integer Programming and Combinatorial Optimization}, isbn = {9783319592497}, issn = {0302-9743}, location = {Waterloo, ON, Canada}, pages = {86--98}, publisher = {Springer Nature}, title = {{Deterministic fully dynamic approximate vertex cover and fractional matching in O(1) amortized update time}}, doi = {10.1007/978-3-319-59250-3_8}, volume = {10328}, year = {2017}, } @article{12608, abstract = {The spatio-temporal distribution of air temperature over mountain glaciers can demonstrate complex patterns, yet it is often represented simplistically using linear vertical temperature gradients (VTGs) extrapolated from off-glacier locations. We analyse a network of centreline and lateral air temperature observations at Tsanteleina Glacier, Italy, during summer 2015. On average, VTGs are steep (<−0.0065 °C m−1), but they are shallow under warm ambient conditions when the correlation between air temperature and elevation becomes weaker. Published along-flowline temperature distribution methods explain centreline observations well, including warming on the lower glacier tongue, but cannot estimate lateral temperature variability. Application of temperature distribution methods improves simulation of melt rates (RMSE) in an energy-balance model by up to 36% compared to the environmental lapse rate extrapolated from an off-glacier station. However, results suggest that model parameters are not easily transferable to glaciers with a small fetch without recalibration. Such methods have potential to improve estimates of temperature across a glacier, but their parameter transferability should be further linked to the glacier and atmospheric characteristics. Furthermore, ‘cold spots’, which can be >2°C cooler than expected for their elevation, whose occurrence is not predicted by the temperature distribution models, are identified at one-quarter of the measurement sites.}, author = {SHAW, THOMAS E. and BROCK, BEN W. and AYALA, ÁLVARO and RUTTER, NICK and Pellicciotti, Francesca}, issn = {1727-5652}, journal = {Journal of Glaciology}, keywords = {Earth-Surface Processes}, number = {242}, pages = {973--988}, publisher = {Cambridge University Press}, title = {{Centreline and cross-glacier air temperature variability on an Alpine glacier: Assessing temperature distribution methods and their influence on melt model calculations}}, doi = {10.1017/jog.2017.65}, volume = {63}, year = {2017}, } @article{12609, abstract = {Previous estimates of melt and surface sublimation on glaciers of the subtropical semiarid Andes (29–34°S) have been obtained at few specific locations, but it is not clear how ablation components vary across the entire extent of a glacier in this dry environment. Here, we simulate the distributed energy and mass balance of Juncal Norte Glacier (33°S) during a 2-month summer period. Forcing fields of near-surface air temperature and wind speed are generated using two methods accounting for the main physical processes that shape their spatial variations. Simulated meteorological variables and ablation agree well with observations on the glacier tongue and reveal complex patterns of energy and mass fluxes. Ablation decreases from 70 mm w.e. d−1 at the low-albedo glacier terminus (~3000 m), where almost 100% of total ablation corresponds to melt, to <5 mm w.e. d−1 at wind-exposed, strong-radiated sites above 5500 m, where surface sublimation represents >75% of total ablation. Our simulations provide the first glacier-scale estimates of ablation components on a glacier in the study region and better reproduce the observed and expected spatial variations of melt and surface sublimation, in comparison with more simple assumptions, such as linear gradients and uniform wind speeds.}, author = {AYALA, A. and Pellicciotti, Francesca and PELEG, N. and BURLANDO, P.}, issn = {1727-5652}, journal = {Journal of Glaciology}, keywords = {Earth-Surface Processes}, number = {241}, pages = {803--822}, publisher = {Cambridge University Press}, title = {{Melt and surface sublimation across a glacier in a dry environment: distributed energy-balance modelling of Juncal Norte Glacier, Chile}}, doi = {10.1017/jog.2017.46}, volume = {63}, year = {2017}, } @article{12610, abstract = {The hydrological systems of heavily-downwasted debris-covered glaciers differ from those of clean-ice glaciers due to the hummocky surface and debris mantle of such glaciers, leading to a relatively limited understanding of drainage pathways. Supraglacial ponds represent sinks within the discontinuous supraglacial drainage system, and occasionally drain englacially. To assess pond dynamics, we made pond water level measurements on Lirung Glacier, Nepal, during May and October of 2013 and 2014. Simultaneously, aerial, satellite, and terrestrial orthoimages and digital elevation models were obtained, providing snapshots of the ponds and their surroundings. We performed a DEM-based analysis of the glacier's closed surface catchments to identify surface drainage pathways and englacial drainage points, and compared this to field observations of surface and near-surface water flow. The total ponded area was higher in the pre-monsoon than post-monsoon, with individual ponds filling and draining seasonally associated with the surface exposure of englacial conduit segments. We recorded four pond drainage events, all of which occurred gradually (duration of weeks), observed diurnal fluctuations indicative of varying water supply and outflow discharge, and we documented instances of interaction between distant ponds. The DEM drainage analysis identified numerous sinks >3 m in depth across the glacier surface, few of which exhibited ponds (23%), while the field survey highlighted instances of surface water only explicable via englacial routes. Taken together, our observations provide evidence for widespread supraglacial-englacial connectivity of meltwater drainage paths. Results suggest that successive englacial conduit collapse events, themselves likely driven by supraglacial pond drainage, cause the glacier surface drainage system to evolve into a configuration following relict englacial conduit systems. Within this system, ponds form in depressions of reduced drainage efficiency and link the supraglacial and englacial drainage networks.}, author = {Miles, Evan S. and Steiner, Jakob and Willis, Ian and Buri, Pascal and Immerzeel, Walter W. and Chesnokova, Anna and Pellicciotti, Francesca}, issn = {2296-6463}, journal = {Frontiers in Earth Science}, keywords = {General Earth and Planetary Sciences}, publisher = {Frontiers Media}, title = {{Pond dynamics and supraglacial-englacial connectivity on debris-covered Lirung Glacier, Nepal}}, doi = {10.3389/feart.2017.00069}, volume = {5}, year = {2017}, } @article{12611, abstract = {We investigate the energy balance and ablation regimes of glaciers in high-elevation, dry environments using glaciometeorological data collected on six glaciers in the semiarid Andes of North-Central Chile (29–34°S, 3127–5324 m). We use a point-scale physically based energy balance (EB) model and an enhanced Temperature-Index (ETI) model that calculates melt rates only as a function of air temperature and net shortwave radiation. At all sites, the largest energy inputs are net shortwave and incoming longwave radiation, which are controlled by surface albedo and elevation, respectively. Turbulent fluxes cancel each other out at the lower sites, but as elevation increases, cold, dry and wind-exposed conditions increase the magnitude of negative latent heat fluxes, associated with large surface sublimation rates. In midsummer (January), ablation rates vary from 67.9 mm w.e. d−1 at the lowest site (∼100% corresponding to melt), to 2.3 mm w.e. d−1 at the highest site (>85% corresponding to surface sublimation). At low-elevation, low-albedo, melt-dominated sites, the ETI model correctly reproduces melt using a large range of possible parameters, but both the performance and parameter transferability decrease with elevation for two main reasons: (i) the air temperature threshold approach for melt onset does not capture the diurnal variability of melt in cold and strong irradiated environments and (ii) energy losses decrease the correlation between melt and net shortwave radiation. We summarize our results by means of an elevation profile of ablation components that can be used as reference in future studies of glacier ablation in the semiarid Andes.}, author = {Ayala, A. and Pellicciotti, Francesca and MacDonell, S. and McPhee, J. and Burlando, P.}, issn = {0043-1397}, journal = {Water Resources Research}, keywords = {Water Science and Technology}, number = {7}, pages = {5601--5625}, publisher = {American Geophysical Union}, title = {{Patterns of glacier ablation across North-Central Chile: Identifying the limits of empirical melt models under sublimation-favorable conditions}}, doi = {10.1002/2016wr020126}, volume = {53}, year = {2017}, } @article{12612, abstract = {Supraglacial ponds play a key role in absorbing atmospheric energy and directing it to the ice of debris-covered glaciers, but the spatial and temporal distribution of these features is not well documented. We analyse 172 Landsat TM/ETM+ scenes for the period 1999–2013 to identify thawed supraglacial ponds for the debris-covered tongues of five glaciers in the Langtang Valley of Nepal. We apply an advanced atmospheric correction routine (Landcor/6S) and use band ratio and image morphological techniques to identify ponds and validate our results with 2.5 m Cartosat-1 observations. We then characterize the spatial, seasonal and interannual patterns of ponds. We find high variability in pond incidence between glaciers (May–October means of 0.08–1.69% of debris area), with ponds most frequent in zones of low surface gradient and velocity. The ponds show pronounced seasonality, appearing in the pre-monsoon as snow melts, peaking at the monsoon onset at 2% of debris-covered area, then declining in the post-monsoon as ponds drain or freeze. Ponds are highly recurrent and persistent, with 40.5% of pond locations occurring for multiple years. Rather than a trend in pond cover over the study period, we find high interannual variability for each glacier after controlling for seasonality.}, author = {MILES, EVAN S. and WILLIS, IAN C. and ARNOLD, NEIL S. and STEINER, JAKOB and Pellicciotti, Francesca}, issn = {1727-5652}, journal = {Journal of Glaciology}, keywords = {Earth-Surface Processes}, number = {237}, pages = {88--105}, publisher = {Cambridge University Press}, title = {{Spatial, seasonal and interannual variability of supraglacial ponds in the Langtang Valley of Nepal, 1999–2013}}, doi = {10.1017/jog.2016.120}, volume = {63}, year = {2017}, } @inproceedings{12905, author = {Schlögl, Alois and Kiss, Janos}, booktitle = {AHPC17 – Austrian HPC Meeting 2017}, location = {Grundlsee, Austria}, pages = {28}, publisher = {FSP Scientific Computing}, title = {{Scientific Computing at IST Austria}}, year = {2017}, } @article{1294, abstract = {We study controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize the expected mean-payoff performance and stability (also known as variability in the literature). We argue that the basic notion of expressing the stability using the statistical variance of the mean payoff is sometimes insufficient, and propose an alternative definition. We show that a strategy ensuring both the expected mean payoff and the variance below given bounds requires randomization and memory, under both the above definitions. We then show that the problem of finding such a strategy can be expressed as a set of constraints.}, author = {Brázdil, Tomáš and Chatterjee, Krishnendu and Forejt, Vojtěch and Kučera, Antonín}, journal = {Journal of Computer and System Sciences}, pages = {144 -- 170}, publisher = {Elsevier}, title = {{Trading performance for stability in Markov decision processes}}, doi = {10.1016/j.jcss.2016.09.009}, volume = {84}, year = {2017}, } @inproceedings{13160, abstract = {Transforming deterministic ω -automata into deterministic parity automata is traditionally done using variants of appearance records. We present a more efficient variant of this approach, tailored to Rabin automata, and several optimizations applicable to all appearance records. We compare the methods experimentally and find out that our method produces smaller automata than previous approaches. Moreover, the experiments demonstrate the potential of our method for LTL synthesis, using LTL-to-Rabin translators. It leads to significantly smaller parity automata when compared to state-of-the-art approaches on complex formulae.}, author = {Kretinsky, Jan and Meggendorfer, Tobias and Waldmann, Clara and Weininger, Maximilian}, booktitle = {Tools and Algorithms for the Construction and Analysis of Systems}, isbn = {9783662545768}, issn = {1611-3349}, location = {Uppsala, Sweden}, pages = {443--460}, publisher = {Springer}, title = {{Index appearance record for transforming Rabin automata into parity automata}}, doi = {10.1007/978-3-662-54577-5_26}, volume = {10205}, year = {2017}, } @article{19810, abstract = {Engineering and enhancing the breaking of inversion symmetry in solids—that is, allowing electrons to differentiate between ‘up’ and ‘down’—is a key goal in condensed-matter physics and materials science because it can be used to stabilize states that are of fundamental interest and also have potential practical applications. Examples include improved ferroelectrics for memory devices and materials that host Majorana zero modes for quantum computing1,2. Although inversion symmetry is naturally broken in several crystalline environments, such as at surfaces and interfaces, maximizing the influence of this effect on the electronic states of interest remains a challenge. Here we present a mechanism for realizing a much larger coupling of inversion-symmetry breaking to itinerant surface electrons than is typically achieved. The key element is a pronounced asymmetry of surface hopping energies—that is, a kinetic-energy-coupled inversion-symmetry breaking, the energy scale of which is a substantial fraction of the bandwidth. Using spin- and angle-resolved photoemission spectroscopy, we demonstrate that such a strong inversion-symmetry breaking, when combined with spin–orbit interactions, can mediate Rashba-like3,4 spin splittings that are much larger than would typically be expected. The energy scale of the inversion-symmetry breaking that we achieve is so large that the spin splitting in the CoO2- and RhO2-derived surface states of delafossite oxides becomes controlled by the full atomic spin–orbit coupling of the 3d and 4d transition metals, resulting in some of the largest known Rashba-like3,4 spin splittings. The core structural building blocks that facilitate the bandwidth-scaled inversion-symmetry breaking are common to numerous materials. Our findings therefore provide opportunities for creating spin-textured states and suggest routes to interfacial control of inversion-symmetry breaking in designer heterostructures of oxides and other material classes.}, author = {Sunko, Veronika and Rosner, H. and Kushwaha, P. and Khim, S. and Mazzola, F. and Bawden, L. and Clark, O. J. and Riley, J. M. and Kasinathan, D. and Haverkort, M. W. and Kim, T. K. and Hoesch, M. and Fujii, J. and Vobornik, I. and Mackenzie, A. P. and King, P. D. C.}, issn = {1476-4687}, journal = {Nature}, number = {7673}, pages = {492--496}, publisher = {Springer Nature}, title = {{Maximal Rashba-like spin splitting via kinetic-energy-coupled inversion-symmetry breaking}}, doi = {10.1038/nature23898}, volume = {549}, year = {2017}, } @article{19811, abstract = {We report on a combined study of the de Haas-van Alphen effect and angle-resolved photoemission spectroscopy on single crystals of the metallic delafossite rounded off by ab initio band structure calculations. A high-sensitivity torque magnetometry setup with superconducting quantum interference device readout and synchrotron-based photoemission with a light spot size of enabled high-resolution data to be obtained from samples as small as . The Fermi surface shape is nearly cylindrical with a rounded hexagonal cross section enclosing a Luttinger volume of 1.00(1) electrons per formula unit.}, author = {Arnold, F. and Naumann, M. and Khim, S. and Rosner, H. and Sunko, Veronika and Mazzola, F. and King, P. D. C. and Mackenzie, A. P. and Hassinger, E.}, issn = {2469-9969}, journal = {Physical Review B}, number = {7}, publisher = {American Physical Society}, title = {{Quasi-two-dimensional Fermi surface topography of the delafossite PdRhO2}}, doi = {10.1103/physrevb.96.075163}, volume = {96}, year = {2017}, } @article{19815, abstract = {We report growth of single crystals of the nonmagnetic metallic delafossite PdRhO2, comparing the results from three different methods. Complete crystallographic data were obtained from single crystal X-ray diffraction, and electronic structure calculations were made using the refined structural parameters. Focused-ion beam microstructuring was used to prepare a sample for measurements of the in- and out-of-plane electrical resistivity, and the large observed anisotropy is qualitatively consistent with the cylindrical Fermi surface predicted by the calculations.}, author = {Kushwaha, P. and Borrmann, H. and Khim, S. and Rosner, H. and Moll, P. J. W. and Sokolov, D. A. and Sunko, Veronika and Grin, Yu. and Mackenzie, A. P.}, issn = {1528-7505}, journal = {Crystal Growth & Design}, number = {8}, pages = {4144--4150}, publisher = {American Chemical Society}, title = {{Single crystal growth, structure, and electronic properties of metallic delafossite PdRhO2}}, doi = {10.1021/acs.cgd.7b00418}, volume = {17}, year = {2017}, } @article{19474, abstract = {The complex behaviors underlying reward seeking and consumption are integral to organism survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is poorly understood. The central nucleus of the amygdala (CeA) has been implicated in feeding and reward, but the neurons and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we defined the neuronal mechanisms by which CeA neurons promote food consumption. Using in vivo activity manipulations and Ca2+ imaging in mice, we found that GABAergic serotonin receptor 2a (Htr2a)-expressing CeA neurons modulate food consumption, promote positive reinforcement and are active in vivo during eating. We demonstrated electrophysiologically, anatomically and behaviorally that intra-CeA and long-range circuit mechanisms underlie these behaviors. Finally, we showed that CeAHtr2a neurons receive inputs from feeding-relevant brain regions. Our results illustrate how defined CeA neural circuits positively regulate food consumption.}, author = {Douglass, Amelia May Barnett and Kucukdereli, Hakan and Ponserre, Marion and Markovic, Milica and Gründemann, Jan and Strobel, Cornelia and Alcala Morales, Pilar L and Conzelmann, Karl-Klaus and Lüthi, Andreas and Klein, Rüdiger}, issn = {1546-1726}, journal = {Nature Neuroscience}, number = {10}, pages = {1384--1394}, publisher = {Springer Nature}, title = {{Central amygdala circuits modulate food consumption through a positive-valence mechanism}}, doi = {10.1038/nn.4623}, volume = {20}, year = {2017}, } @article{15154, abstract = {Biofilm formation is critical for the infection cycle of Vibrio cholerae. Vibrio exopolysaccharides (VPS) and the matrix proteins RbmA, Bap1 and RbmC are required for the development of biofilm architecture. We demonstrate that RbmA binds VPS directly and uses a binary structural switch within its first fibronectin type III (FnIII-1) domain to control RbmA structural dynamics and the formation of VPS-dependent higher-order structures. The structural switch in FnIII-1 regulates interactions in trans with the FnIII-2 domain, leading to open (monomeric) or closed (dimeric) interfaces. The ability of RbmA to switch between open and closed states is important for V. cholerae biofilm formation, as RbmA variants with switches that are locked in either of the two states lead to biofilms with altered architecture and structural integrity.}, author = {Fong, Jiunn CN and Rogers, Andrew and Michael, Alicia Kathleen and Parsley, Nicole C and Cornell, William-Cole and Lin, Yu-Cheng and Singh, Praveen K and Hartmann, Raimo and Drescher, Knut and Vinogradov, Evgeny and Dietrich, Lars EP and Partch, Carrie L and Yildiz, Fitnat H}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications}, title = {{Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms}}, doi = {10.7554/elife.26163}, volume = {6}, year = {2017}, } @article{15155, abstract = {The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping. Both cis and trans isomers interact with transcriptional regulators, suggesting that isomerization could serve a role in assembling regulatory complexes in vivo. Toward this end, we show that locking the switch into the trans isomer leads to shortened circadian periods. Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination.}, author = {Gustafson, Chelsea L. and Parsley, Nicole C. and Asimgil, Hande and Lee, Hsiau-Wei and Ahlbach, Christopher and Michael, Alicia Kathleen and Xu, Haiyan and Williams, Owen L. and Davis, Tara L. and Liu, Andrew C. and Partch, Carrie L.}, issn = {1097-2765}, journal = {Molecular Cell}, keywords = {Cell Biology, Molecular Biology}, number = {4}, pages = {447--457.e7}, publisher = {Elsevier}, title = {{A slow conformational switch in the BMAL1 transactivation domain modulates circadian rhythms}}, doi = {10.1016/j.molcel.2017.04.011}, volume = {66}, year = {2017}, } @article{15156, abstract = {Circadian clocks are ubiquitous timing systems that induce rhythms of biological activities in synchrony with night and day. In cyanobacteria, timing is generated by a posttranslational clock consisting of KaiA, KaiB, and KaiC proteins and a set of output signaling proteins, SasA and CikA, which transduce this rhythm to control gene expression. Here, we describe crystal and nuclear magnetic resonance structures of KaiB-KaiC,KaiA-KaiB-KaiC, and CikA-KaiB complexes. They reveal how the metamorphic properties of KaiB, a protein that adopts two distinct folds, and the post–adenosine triphosphate hydrolysis state of KaiC create a hub around which nighttime signaling events revolve, including inactivation of KaiA and reciprocal regulation of the mutually antagonistic signaling proteins, SasA and CikA.}, author = {Tseng, Roger and Goularte, Nicolette F. and Chavan, Archana and Luu, Jansen and Cohen, Susan E. and Chang, Yong-Gang and Heisler, Joel and Li, Sheng and Michael, Alicia Kathleen and Tripathi, Sarvind and Golden, Susan S. and LiWang, Andy and Partch, Carrie L.}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {6330}, pages = {1174--1180}, publisher = {American Association for the Advancement of Science}, title = {{Structural basis of the day-night transition in a bacterial circadian clock}}, doi = {10.1126/science.aag2516}, volume = {355}, year = {2017}, } @article{15157, abstract = {The basic helix–loop–helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ∼24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here we show that CRY1 binds directly to the PAS domain core of CLOCK:BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.}, author = {Michael, Alicia Kathleen and Fribourgh, Jennifer L. and Chelliah, Yogarany and Sandate, Colby R. and Hura, Greg L. and Schneidman-Duhovny, Dina and Tripathi, Sarvind M. and Takahashi, Joseph S. and Partch, Carrie L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {7}, pages = {1560--1565}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1}}, doi = {10.1073/pnas.1615310114}, volume = {114}, year = {2017}, } @article{15158, abstract = {Cryptochromes are evolutionarily related to the light‐dependent DNA repair enzyme photolyase, serving as major regulators of circadian rhythms in insects and vertebrate animals. There are two types of cryptochromes in the animal kingdom: Drosophila‐like CRYs that act as nonvisual photopigments linking circadian rhythms to the environmental light/dark cycle, and vertebrate‐like CRYs that do not appear to sense light directly, but control the generation of circadian rhythms by acting as transcriptional repressors. Some animals have both types of CRYs, while others possess only one. Cryptochromes have two domains, the photolyase homology region (PHR) and an extended, intrinsically disordered C‐terminus. While all animal CRYs share a high degree of sequence and structural homology in their PHR domains, the C‐termini are divergent in both length and sequence identity. Recently, cryptochrome function has been shown to extend beyond its pivotal role in circadian clocks, participating in regulation of the DNA damage response, cancer progression and glucocorticoid signaling, as well as being implicated as possible magnetoreceptors. In this review, we provide a historical perspective on the discovery of animal cryptochromes, examine similarities and differences of the two types of animal cryptochromes and explore some of the divergent roles for this class of proteins.}, author = {Michael, Alicia Kathleen and Fribourgh, Jennifer L. and Van Gelder, Russell N. and Partch, Carrie L.}, issn = {1751-1097}, journal = {Photochemistry and Photobiology}, keywords = {Physical and Theoretical Chemistry, General Medicine, Biochemistry}, number = {1}, pages = {128--140}, publisher = {Wiley}, title = {{Animal cryptochromes: Divergent roles in light perception, circadian timekeeping and beyond}}, doi = {10.1111/php.12677}, volume = {93}, year = {2017}, }