Structural basis for the recognition of Sonic Hedgehog by human Patched1
We report the structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 and 3.6 angstroms, respectively, as determined by cryo–electron microscopy. Ptch1 comprises two interacting extracellular domains, ECD1 and ECD2, and 12 transmembrane segments (TMs), with TMs 2 to 6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2 and the other in the membrane-facing cavity of the SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dep...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Gong, X., Qian, H., Cao, P., Zhao, X., Zhou, Q., Lei, J., Yan, N. Tags: Biochemistry r-articles Source Type: news
Dissipative Kerr solitons in optical microresonators
The development of compact, chip-scale optical frequency comb sources (microcombs) based on parametric frequency conversion in microresonators has seen applications in terabit optical coherent communications, atomic clocks, ultrafast distance measurements, dual-comb spectroscopy, and the calibration of astophysical spectrometers and have enabled the creation of photonic-chip integrated frequency synthesizers. Underlying these recent advances has been the observation of temporal dissipative Kerr solitons in microresonators, which represent self-enforcing, stationary, and localized solutions of a damped, driven, and detuned ...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Kippenberg, T. J., Gaeta, A. L., Lipson, M., Gorodetsky, M. L. Tags: Physics, Applied, Physics review Source Type: news
Mapping the dark space of chemical reactions with extended nanomole synthesis and MALDI-TOF MS
Understanding the practical limitations of chemical reactions is critically important for efficiently planning the synthesis of compounds in pharmaceutical, agrochemical, and specialty chemical research and development. However, literature reports of the scope of new reactions are often cursory and biased toward successful results, severely limiting the ability to predict reaction outcomes for untested substrates. We herein illustrate strategies for carrying out large-scale surveys of chemical reactivity by using a material-sparing nanomole-scale automated synthesis platform with greatly expanded synthetic scope combined w...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Lin, S., Dikler, S., Blincoe, W. D., Ferguson, R. D., Sheridan, R. P., Peng, Z., Conway, D. V., Zawatzky, K., Wang, H., Cernak, T., Davies, I. W., DiRocco, D. A., Sheng, H., Welch, C. J., Dreher, S. D. Tags: Chemistry r-articles Source Type: news
Response to Comment on "Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment"
Wolf and Ziska suggest that soil and species attributes can explain an unexpected 20-year reversal of C3-C4 grass responses to elevated CO2. This is consistent with our original interpretation; however, we disagree with the assertion that such explanations somehow render our results irrelevant for questioning a long-standing paradigm of plant response to CO2 based on C3-C4 differences in photosynthetic pathway. (Source: ScienceNOW)
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Reich, P. B., Hobbie, S. E., Lee, T. D., Pastore, M. A. Tags: Botany t-comment Source Type: news
Comment on "Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment"
Reich et al. (Reports, 20 April 2018, p. 317) assert that the responses of C3 and C4 grass biomass to elevated CO2 "challenge the current C3-C4 [elevated CO2] paradigm," but these responses can be explained by the natural history of the experimental plants and soils without challenging this paradigm. (Source: ScienceNOW)
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Wolf, J., Ziska, L. Tags: Botany t-comment Source Type: news
Apoptosis propagates through the cytoplasm as trigger waves
Apoptosis is an evolutionarily conserved form of programmed cell death critical for development and tissue homeostasis in animals. The apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves. We tested this possibility in cell-free Xenopus laevis egg extracts and observed apoptotic trigger waves with speeds of ~30 micrometers per minute. Fractionation and inhibitor studies implicated multiple feedback loops in generating the waves. Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers per minut...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Cheng, X., Ferrell, J. E. Tags: Cell Biology reports Source Type: news
A liquid phase of synapsin and lipid vesicles
Neurotransmitter-containing synaptic vesicles (SVs) form tight clusters at synapses. These clusters act as a reservoir from which SVs are drawn for exocytosis during sustained activity. Several components associated with SVs that are likely to help form such clusters have been reported, including synapsin. Here we found that synapsin can form a distinct liquid phase in an aqueous environment. Other scaffolding proteins could coassemble into this condensate but were not necessary for its formation. Importantly, the synapsin phase could capture small lipid vesicles. The synapsin phase rapidly disassembled upon phosphorylatio...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Milovanovic, D., Wu, Y., Bian, X., De Camilli, P. Tags: Cell Biology, Neuroscience reports Source Type: news
Lacteal junction zippering protects against diet-induced obesity
Excess dietary lipid uptake causes obesity, a major global health problem. Enterocyte-absorbed lipids are packaged into chylomicrons, which enter the bloodstream through intestinal lymphatic vessels called lacteals. Here, we show that preventing lacteal chylomicron uptake by inducible endothelial genetic deletion of Neuropilin1 (Nrp1) and Vascular endothelial growth factor receptor 1 (Vegfr1; also known as Flt1) renders mice resistant to diet-induced obesity. Absence of NRP1 and FLT1 receptors increased VEGF-A bioavailability and signaling through VEGFR2, inducing lacteal junction zippering and chylomicron malabsorption. R...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Zhang, F., Zarkada, G., Han, J., Li, J., Dubrac, A., Ola, R., Genet, G., Boye, K., Michon, P., Künzel, S. E., Camporez, J. P., Singh, A. K., Fong, G.-H., Simons, M., Tso, P., Fernandez-Hernando, C., Shulman, G. I., Sessa, W. C., Eichmann, A. Tags: Cell Biology, Medicine, Diseases reports Source Type: news
Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors
Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor compos...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Young, M. D., Mitchell, T. J., Vieira Braga, F. A., Tran, M. G. B., Stewart, B. J., Ferdinand, J. R., Collord, G., Botting, R. A., Popescu, D.-M., Loudon, K. W., Vento-Tormo, R., Stephenson, E., Cagan, A., Farndon, S. J., Del Castillo Velasco-Herrera, M., Tags: Development, Medicine, Diseases reports Source Type: news
Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals
Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species’ blood plasma. This co...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Meyer, W. K., Jamison, J., Richter, R., Woods, S. E., Partha, R., Kowalczyk, A., Kronk, C., Chikina, M., Bonde, R. K., Crocker, D. E., Gaspard, J., Lanyon, J. M., Marsillach, J., Furlong, C. E., Clark, N. L. Tags: Evolution reports Source Type: news
Opioid prescribing decreases after learning of a patients fatal overdose
Most opioid prescription deaths occur among people with common conditions for which prescribing risks outweigh benefits. General psychological insights offer an explanation: People may judge risk to be low without available personal experiences, may be less careful than expected when not observed, and may falter without an injunction from authority. To test these hypotheses, we conducted a randomized trial of 861 clinicians prescribing to 170 persons who subsequently suffered fatal overdoses. Clinicians in the intervention group received notification of their patients’ deaths and a safe prescribing injunction from th...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Doctor, J. N., Nguyen, A., Lev, R., Lucas, J., Knight, T., Zhao, H., Menchine, M. Tags: Medicine, Diseases reports Source Type: news
Global extent of rivers and streams
The turbulent surfaces of rivers and streams are natural hotspots of biogeochemical exchange with the atmosphere. At the global scale, the total river-atmosphere flux of trace gasses such as carbon dioxide depends on the proportion of Earth’s surface that is covered by the fluvial network, yet the total surface area of rivers and streams is poorly constrained. We used a global database of planform river hydromorphology and a statistical approach to show that global river and stream surface area at mean annual discharge is 773,000 ± 79,000 square kilometers (0.58 ± 0.06%) of Earth’s nonglaciated la...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Allen, G. H., Pavelsky, T. M. Tags: Evolution reports Source Type: news
Unusual high thermal conductivity in boron arsenide bulk crystals
We report experimental evidence that departs from these long-held criteria. We measured a local room-temperature thermal conductivity exceeding 1000 watts per meter-kelvin and an average bulk value reaching 900 watts per meter-kelvin in bulk boron arsenide (BAs) crystals, where boron and arsenic are light and heavy elements, respectively. The high values are consistent with a proposal for phonon-band engineering and can only be explained by higher-order phonon processes. These findings yield insight into the physics of heat conduction in solids and show BAs to be the only known semiconductor with ultrahigh thermal conducti...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Tian, F., Song, B., Chen, X., Ravichandran, N. K., Lv, Y., Chen, K., Sullivan, S., Kim, J., Zhou, Y., Liu, T.-H., Goni, M., Ding, Z., Sun, J., Udalamatta Gamage, G. A. G., Sun, H., Ziyaee, H., Huyan, S., Deng, L., Zhou, J., Schmidt, A. J., Chen, S., Chu, Tags: Physics reports Source Type: news
High thermal conductivity in cubic boron arsenide crystals
We report the experimental discovery of high thermal conductivity at room temperature in cubic boron arsenide (BAs) grown through a modified chemical vapor transport technique. The thermal conductivity of BAs, 1000 ± 90 watts per meter per kelvin meter-kelvin, is higher than that of silicon carbide by a factor of 3 and is surpassed only by diamond and the basal-plane value of graphite. This work shows that BAs represents a class of ultrahigh–thermal conductivity materials predicted by a recent theory, and that it may constitute a useful thermal management material for high–power density electronic device...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Li, S., Zheng, Q., Lv, Y., Liu, X., Wang, X., Huang, P. Y., Cahill, D. G., Lv, B. Tags: Physics, Applied, Materials Science reports Source Type: news
Experimental observation of high thermal conductivity in boron arsenide
Improving the thermal management of small-scale devices requires developing materials with high thermal conductivities. The semiconductor boron arsenide (BAs) is an attractive target because of ab initio calculation indicating that single crystals have an ultrahigh thermal conductivity. We synthesized BAs single crystals without detectable defects and measured a room-temperature thermal conductivity of 1300 watts per meter-kelvin. Our spectroscopy study, in conjunction with atomistic theory, reveals that the distinctive band structure of BAs allows for very long phonon mean free paths and strong high-order anharmonicity th...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Kang, J. S., Li, M., Wu, H., Nguyen, H., Hu, Y. Tags: Physics, Applied, Materials Science reports Source Type: news
The role of electron-electron interactions in two-dimensional Dirac fermions
The role of electron-electron interactions in two-dimensional Dirac fermion systems remains enigmatic. Using a combination of nonperturbative numerical and analytical techniques that incorporate both the contact and long-range parts of the Coulomb interaction, we identify the two previously discussed regimes: a Gross-Neveu transition to a strongly correlated Mott insulator and a semimetallic state with a logarithmically diverging Fermi velocity accurately described by the random phase approximation. We predict that experimental realizations of Dirac fermions span this crossover and that this determines whether the Fermi ve...
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Tang, H.-K., Leaw, J. N., Rodrigues, J. N. B., Herbut, I. F., Sengupta, P., Assaad, F. F., Adam, S. Tags: Physics r-articles Source Type: news
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Jones, K. R., Venter, O., Fuller, R. A., Allan, J. R., Maxwell, S. L., Negret, P. J., Watson, J. E. M. Tags: letters Source Type: news
Protected land: Many factors shape success
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Gavin, M. C., McCarter, J., Berkes, F., Sterling, E. J., Turner, N. J. Tags: letters Source Type: news
Building an evidence base for stakeholder engagement
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Lavery, J. V. Tags: Science and Policy, Sociology p-forum Source Type: news
The future of humans as model organisms
Source: ScienceNOW - August 9, 2018 Category: Science Authors: FitzGerald, G., Botstein, D., Califf, R., Collins, R., Peters, K., Van Bruggen, N., Rader, D. Tags: perspective Source Type: news
Tighter lymphatic junctions prevent obesity
Source: ScienceNOW - August 9, 2018 Category: Science Authors: McDonald, D. M. Tags: Cell Biology, Medicine, Diseases perspective Source Type: news
Ultrahigh thermal conductivity confirmed in boron arsenide
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Dames, C. Tags: Physics, Applied, Materials Science perspective Source Type: news
Phase changes in neurotransmission
Source: ScienceNOW - August 9, 2018 Category: Science Authors: Boczek, E. E., Alberti, S. Tags: Cell Biology, Neuroscience perspective Source Type: news