Germanium nanospheres for ultraresolution picotensiometry of kinesin motors
Kinesin motors are essential for the transport of cellular cargo along microtubules. How the motors step, detach, and cooperate with each other is still unclear. To dissect the molecular motion of kinesin-1, we developed germanium nanospheres as ultraresolution optical trapping probes. We found that single motors took 4-nanometer center-of-mass steps. Furthermore, kinesin-1 never detached from microtubules under hindering load conditions. Instead, it slipped on microtubules in microsecond-long, 8-nanometer steps and remained in this slip state before detaching or reengaging in directed motion. Unexpectedly, reengagement an...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Sudhakar, S., Abdosamadi, M. K., Jachowski, T. J., Bugiel, M., Jannasch, A., Schäffer, E. Tags: Biochemistry, Materials Science, Online Only r-articles Source Type: news
Cellular transcriptomics reveals evolutionary identities of songbird vocal circuits
Birds display advanced behaviors, including vocal learning and problem-solving, yet lack a layered neocortex, a structure associated with complex behavior in mammals. To determine whether these behavioral similarities result from shared or distinct neural circuits, we used single-cell RNA sequencing to characterize the neuronal repertoire of the songbird song motor pathway. Glutamatergic vocal neurons had considerable transcriptional similarity to neocortical projection neurons; however, they displayed regulatory gene expression patterns more closely related to neurons in the ventral pallium. Moreover, while -aminobutyric ...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Colquitt, B. M., Merullo, D. P., Konopka, G., Roberts, T. F., Brainard, M. S. Tags: Evolution, Neuroscience, Online Only r-articles Source Type: news
Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape
In this study, we generated four neutralizing nanobodies that target the receptor binding domain of the SARS-CoV-2 spike protein. We used x-ray crystallography and cryo–electron microscopy to define two distinct binding epitopes. On the basis of these structures, we engineered multivalent nanobodies with more than 100 times the neutralizing activity of monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor binding competition, whereas other monovalent and biparatopic nanobodies triggered aberrant activation of the spike ...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Koenig, P.-A., Das, H., Liu, H., Kümmerer, B. M., Gohr, F. N., Jenster, L.-M., Schiffelers, L. D. J., Tesfamariam, Y. M., Uchima, M., Wuerth, J. D., Gatterdam, K., Ruetalo, N., Christensen, M. H., Fandrey, C. I., Normann, S., Tödtmann, J. Tags: Biochemistry, Microbiology, Online Only r-articles Source Type: news
Response to Comment on "Structural evidence for a dynamic metallocofactor during N2 reduction by Mo-nitrogenase"
Peters et al. comment on our report of the dynamic structure of the nitrogenase metallocofactor during N2 reduction. Their claim that their independent structural refinement and consideration of biochemical data contradict our finding is incorrect and is strongly refuted by our biochemical and structural data that collectively and conclusively point to the binding of dinitrogen species to the nitrogenase cofactor. (Source: ScienceNOW)
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Kang, W., Lee, C. C., Jasniewski, A. J., Ribbe, M. W., Hu, Y. Tags: Biochemistry t-comment Source Type: news
Comment on "Structural evidence for a dynamic metallocofactor during N2 reduction by Mo-nitrogenase"
Kang et al. (Reports, 19 June 2020, p. 1381) report a structure of the nitrogenase MoFe protein that is interpreted to indicate binding of N2 or an N2-derived species to the active-site FeMo cofactor. Independent refinement of the structure and consideration of biochemical evidence do not support this claim. (Source: ScienceNOW)
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Peters, J. W., Einsle, O., Dean, D. R., DeBeer, S., Hoffman, B. M., Holland, P. L., Seefeldt, L. C. Tags: Biochemistry t-comment Source Type: news
Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment
The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of ...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Trujillo, C. A., Rice, E. S., Schaefer, N. K., Chaim, I. A., Wheeler, E. C., Madrigal, A. A., Buchanan, J., Preissl, S., Wang, A., Negraes, P. D., Szeto, R. A., Herai, R. H., Huseynov, A., Ferraz, M. S. A., Borges, F. S., Kihara, A. H., Byrne, A., Marin, Tags: Evolution, Genetics, Online Only r-articles Source Type: news
Communicating clocks shape circadian homeostasis
Circadian clocks temporally coordinate physiology and align it with geophysical time, which enables diverse life-forms to anticipate daily environmental cycles. In complex organisms, clock function originates from the molecular oscillator within each cell and builds upward anatomically into an organism-wide system. Recent advances have transformed our understanding of how clocks are connected to achieve coherence across tissues. Circadian misalignment, often imposed in modern society, disrupts coordination among clocks and has been linked to diseases ranging from metabolic syndrome to cancer. Thus, uncovering the physiolog...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Koronowski, K. B., Sassone-Corsi, P. Tags: Cell Biology, Engineering, Medicine, Diseases, Online Only review Source Type: news
Immunological characteristics govern the transition of COVID-19 to endemicity
We are currently faced with the question of how the severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may change in the years ahead. Our analysis of immunological and epidemiological data on endemic human coronaviruses (HCoVs) shows that infection-blocking immunity wanes rapidly but that disease-reducing immunity is long-lived. Our model, incorporating these components of immunity, recapitulates both the current severity of SARS-CoV-2 infection and the benign nature of HCoVs, suggesting that once the endemic phase is reached and primary exposure is in childhood, SARS-CoV-2 may be no mo...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Lavine, J. S., Bjornstad, O. N., Antia, R. Tags: Epidemiology, Immunology reports Source Type: news
Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice
Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles with four to eight distinct RBDs). Mice immunized with RBD nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic RBD nanoparticles elicited antibodies with superior cross-reactive recognition of heterol...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Cohen, A. A., Gnanapragasam, P. N. P., Lee, Y. E., Hoffman, P. R., Ou, S., Kakutani, L. M., Keeffe, J. R., Wu, H.-J., Howarth, M., West, A. P., Barnes, C. O., Nussenzweig, M. C., Bjorkman, P. J. Tags: Immunology, Virology reports Source Type: news
Seismic crustal imaging using fin whale songs
Fin whale calls are among the strongest animal vocalizations that are detectable over great distances in the oceans. We analyze fin whale songs recorded at ocean-bottom seismometers in the northeast Pacific Ocean and show that in addition to the waterborne signal, the song recordings also contain signals reflected and refracted from crustal interfaces beneath the stations. With these data, we constrain the thickness and seismic velocity of the oceanic sediment and basaltic basement and the P-wave velocity of the gabbroic lower crust beneath and around the ocean bottom seismic stations. The abundant and globally available f...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Kuna, V. M., Nabelek, J. L. Tags: Geochemistry, Geophysics reports Source Type: news
Orogenic quiescence in Earths middle age
Mountain belts modulate denudation flux and hydrologic processes and are thus fundamental to nutrient cycling on Earth’s surface. We used europium anomalies in detrital zircons to track mountain-building processes over Earth’s history. We show that the average thickness of active continental crust varied on billion-year time scales, with the thickest crust formed in the Archean and Phanerozoic. By contrast, the Proterozoic witnessed continuously decreasing crustal thickness, leaving the continents devoid of high mountains until the end of the eon. We link this gradually diminished orogenesis to the long-lived N...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Tang, M., Chu, X., Hao, J., Shen, B. Tags: Geochemistry, Geophysics reports Source Type: news
Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease
Mapping the gene-regulatory networks dysregulated in human disease would allow the design of network-correcting therapies that treat the core disease mechanism. However, small molecules are traditionally screened for their effects on one to several outputs at most, biasing discovery and limiting the likelihood of true disease-modifying drug candidates. Here, we developed a machine-learning approach to identify small molecules that broadly correct gene networks dysregulated in a human induced pluripotent stem cell (iPSC) disease model of a common form of heart disease involving the aortic valve (AV). Gene network correction...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Theodoris, C. V., Zhou, P., Liu, L., Zhang, Y., Nishino, T., Huang, Y., Kostina, A., Ranade, S. S., Gifford, C. A., Uspenskiy, V., Malashicheva, A., Ding, S., Srivastava, D. Tags: Genetics, Medicine, Diseases, Online Only r-articles Source Type: news
Enhanced atomic ordering leads to high thermoelectric performance in AgSbTe2
High thermoelectric performance is generally achieved through either electronic structure modulations or phonon scattering enhancements, which often counteract each other. A leap in performance requires innovative strategies that simultaneously optimize electronic and phonon transports. We demonstrate high thermoelectric performance with a near room-temperature figure of merit, ZT ~ 1.5, and a maximum ZT ~ 2.6 at 573 kelvin, by optimizing atomic disorder in cadmium-doped polycrystalline silver antimony telluride (AgSbTe2). Cadmium doping in AgSbTe2 enhances cationic ordering, which simultaneously improves electronic proper...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Roychowdhury, S., Ghosh, T., Arora, R., Samanta, M., Xie, L., Singh, N. K., Soni, A., He, J., Waghmare, U. V., Biswas, K. Tags: Chemistry, Materials Science reports Source Type: news
Two-dimensional superconductivity and anisotropic transport at KTaO3 (111) interfaces
The distinctive electronic structure found at interfaces between materials can allow unconventional quantum states to emerge. Here we report on the discovery of superconductivity in electron gases formed at interfaces between (111)-oriented KTaO3 and insulating overlayers of either EuO or LaAlO3. The superconducting transition temperature, as high as 2.2 kelvin, is about one order of magnitude higher than that of the LaAlO3/SrTiO3 system. Notably, similar electron gases at KTaO3 (001) interfaces remain normal down to 25 millikelvin. The critical field and current-voltage measurements indicate that the superconductivity is ...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Liu, C., Yan, X., Jin, D., Ma, Y., Hsiao, H.-W., Lin, Y., Bretz-Sullivan, T. M., Zhou, X., Pearson, J., Fisher, B., Jiang, J. S., Han, W., Zuo, J.-M., Wen, J., Fong, D. D., Sun, J., Zhou, H., Bhattacharya, A. Tags: Physics reports Source Type: news
A massive stellar bulge in a regularly rotating galaxy 1.2 billion years after the Big Bang
Cosmological models predict that galaxies forming in the early Universe experience a chaotic phase of gas accretion and star formation, followed by gas ejection due to feedback processes. Galaxy bulges may assemble later via mergers or internal evolution. Here we present submillimeter observations (with spatial resolution of 700 parsecs) of ALESS 073.1, a starburst galaxy at redshift when the Universe was 1.2 billion years old. This galaxy’s cold gas forms a regularly rotating disk with negligible noncircular motions. The galaxy rotation curve requires the presence of a central bulge in addition to a star-forming dis...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Lelli, F., Di Teodoro, E. M., Fraternali, F., Man, A. W. S., Zhang, Z.-Y., De Breuck, C., Davis, T. A., Maiolino, R. Tags: Astronomy reports Source Type: news
Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK
The United Kingdom’s COVID-19 epidemic during early 2020 was one of world’s largest and was unusually well represented by virus genomic sampling. We determined the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses combined with epidemiological and travel data, we quantified the size, spatiotemporal origins, and persistence of genetically distinct UK transmission lineages. Rapid flu...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: du Plessis, L., McCrone, J. T., Zarebski, A. E., Hill, V., Ruis, C., Gutierrez, B., Raghwani, J., Ashworth, J., Colquhoun, R., Connor, T. R., Faria, N. R., Jackson, B., Loman, N. J., OToole, A., Nicholls, S. M., Parag, K. V., Scher, E., Vasylyeva, T. I., Tags: Epidemiology, Evolution r-articles Source Type: news
Catalytic asymmetric and stereodivergent oligonucleotide synthesis
We report the catalytic stereocontrolled synthesis of dinucleotides. We have demonstrated, for the first time to our knowledge, that chiral phosphoric acid (CPA) catalysts control the formation of stereogenic phosphorous centers during phosphoramidite transfer. Unprecedented levels of diastereodivergence have also been demonstrated, enabling access to either phosphite diastereomer. Two different CPA scaffolds have proven to be essential for achieving stereodivergence: peptide-embedded phosphothreonine-derived CPAs, which reinforce and amplify the inherent substrate preference, and C2-symmetric BINOL-derived CPAs, which com...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Featherston, A. L., Kwon, Y., Pompeo, M. M., Engl, O. D., Leahy, D. K., Miller, S. J. Tags: Chemistry r-articles Source Type: news
The role of officer race and gender in police-civilian interactions in Chicago
Diversification is a widely proposed policing reform, but its impact is difficult to assess. We used records of millions of daily patrol assignments, determined through fixed rules and preassigned rotations that mitigate self-selection, to compare the average behavior of officers of different demographic profiles working in comparable conditions. Relative to white officers, Black and Hispanic officers make far fewer stops and arrests, and they use force less often, especially against Black civilians. These effects are largest in majority-Black areas of Chicago and stem from reduced focus on enforcing low-level offenses, wi...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Ba, B. A., Knox, D., Mummolo, J., Rivera, R. Tags: Sociology r-articles Source Type: news
Regulating multiple body clocks
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Alderton, G. Tags: Cell Biology, Engineering, Medicine, Diseases twis Source Type: news
A marine biodiversity plan for China and beyond
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Zhou, W., Wang, M., Huang, M., Wei, F. Tags: letters Source Type: news