ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

1

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Rapid approach to complex boronic acids (2019)

Neochoritis, C. G., Shaabani, S., Ahmadianmoghaddam, M., Zarganes-Tzitzikas, T., Gao, L., Novotna, M., Mitrikova, T., Romero, A. R., Irianti, M. I., Xu, R., Olechno, J., Ellson, R., Helan, V., Kossenjans, M., Groves, M. R., Dömling, A.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing–enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Hippocampal theta phases organize the reactivation of large-scale electrophysiological representations during goal-directed navigation (2019)

Kunz, L., Wang, L., Lachner-Piza, D., Zhang, H., Brandt, A., Dümpelmann, M., Reinacher, P. C., Coenen, V. A., Chen, D., Wang, W.-X., Zhou, W., Liang, S., Grewe, P., Bien, C. G., Bierbrauer, A., Navarro Schröder, T., Schulze-Bonhage, A., Axmacher, N.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Humans are adept in simultaneously following multiple goals, but the neural mechanisms for maintaining specific goals and distinguishing them from other goals are incompletely understood. For short time scales, working memory studies suggest that multiple mental contents are maintained by theta-coupled reactivation, but evidence for similar mechanisms during complex behaviors such as goal-directed navigation is scarce. We examined intracranial electroencephalography recordings of epilepsy patients performing an object-location memory task in a virtual environment. We report that large-scale electrophysiological representations of objects that cue for specific goal locations are dynamically reactivated during goal-directed navigation. Reactivation of different cue representations occurred at stimulus-specific hippocampal theta phases. Locking to more distinct theta phases predicted better memory performance, identifying hippocampal theta phase coding as a mechanism for separating competing goals. Our findings suggest shared neural mechanisms between working memory and goal-directed navigation and provide new insights into the functions of the hippocampal theta rhythm.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Voter information campaigns and political accountability: Cumulative findings from a preregistered meta-analysis of coordinated trials (2019)

Dunning, T., Grossman, G., Humphreys, M., Hyde, S. D., McIntosh, C., Nellis, G., Adida, C. L., Arias, E., Bicalho, C., Boas, T. C., Buntaine, M. T., Chauchard, S., Chowdhury, A., Gottlieb, J., Hidalgo, F. D., Holmlund, M., Jablonski, R., Kramon, E., Larre

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Voters may be unable to hold politicians to account if they lack basic information about their representatives’ performance. Civil society groups and international donors therefore advocate using voter information campaigns to improve democratic accountability. Yet, are these campaigns effective? Limited replication, measurement heterogeneity, and publication biases may undermine the reliability of published research. We implemented a new approach to cumulative learning, coordinating the design of seven randomized controlled trials to be fielded in six countries by independent research teams. Uncommon for multisite trials in the social sciences, we jointly preregistered a meta-analysis of results in advance of seeing the data. We find no evidence overall that typical, nonpartisan voter information campaigns shape voter behavior, although exploratory and subgroup analyses suggest conditions under which informational campaigns could be more effective. Such null estimated effects are too seldom published, yet they can be critical for scientific progress and cumulative, policy-relevant learning.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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An ultrafast system for signaling mechanical pain in human skin (2019)

Nagi, S. S., Marshall, A. G., Makdani, A., Jarocka, E., Liljencrantz, J., Ridderström, M., Shaikh, S., ONeill, F., Saade, D., Donkervoort, S., Foley, A. R., Minde, J., Trulsson, M., Cole, J., Bönnemann, C. G., Chesler, A. T., Bushnell, M. C., McGlone,

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated ("fast" pain) or unmyelinated ("slow" pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Osteoblastic lysosome plays a central role in mineralization (2019)

Iwayama, T., Okada, T., Ueda, T., Tomita, K., Matsumoto, S., Takedachi, M., Wakisaka, S., Noda, T., Ogura, T., Okano, T., Fratzl, P., Ogura, T., Murakami, S.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Mineralization is the most fundamental process in vertebrates. It is predominantly mediated by osteoblasts, which secrete mineral precursors, most likely through matrix vesicles (MVs). These vesicular structures are calcium and phosphate rich and contain organic material such as acidic proteins. However, it remains largely unknown how intracellular MVs are transported and secreted. Here, we use scanning electron-assisted dielectric microscopy and super-resolution microscopy for assessing live osteoblasts in mineralizing conditions at a nanolevel resolution. We found that the calcium-containing vesicles were multivesicular bodies containing MVs. They were transported via lysosome and secreted by exocytosis. Thus, we present proof that the lysosome transports amorphous calcium phosphate within mineralizing osteoblasts.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Global restoration opportunities in tropical rainforest landscapes (2019)

Brancalion, P. H. S., Niamir, A., Broadbent, E., Crouzeilles, R., Barros, F. S. M., Almeyda Zambrano, A. M., Baccini, A., Aronson, J., Goetz, S., Reid, J. L., Strassburg, B. B. N., Wilson, S., Chazdon, R. L.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Over 140 Mha of restoration commitments have been pledged across the global tropics, yet guidance is needed to identify those landscapes where implementation is likely to provide the greatest potential benefits and cost-effective outcomes. By overlaying seven recent, peer-reviewed spatial datasets as proxies for socioenvironmental benefits and feasibility of restoration, we identified restoration opportunities (areas with higher potential return of benefits and feasibility) in lowland tropical rainforest landscapes. We found restoration opportunities throughout the tropics. Areas scoring in the top 10% (i.e., restoration hotspots) are located largely within conservation hotspots (88%) and in countries committed to the Bonn Challenge (73%), a global effort to restore 350 Mha by 2030. However, restoration hotspots represented only a small portion (19.1%) of the Key Biodiversity Area network. Concentrating restoration investments in landscapes with high benefits and feasibility would maximize the potential to mitigate anthropogenic impacts and improve human well-being.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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7

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Role of indentation depth and contact area on human perception of softness for haptic interfaces (2019)

Dhong, C., Miller, R., Root, N. B., Gupta, S., Kayser, L. V., Carpenter, C. W., Loh, K. J., Ramachandran, V. S., Lipomi, D. J.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉In engineering, the "softness" of an object, as measured by an indenter, manifests as two measurable parameters: (i) indentation depth and (ii) contact area. For humans, softness is not well defined, although it is believed that perception depends on the same two parameters. Decoupling their relative contributions, however, has not been straightforward because most bulk—"off-the-shelf"—materials exhibit the same ratio between the indentation depth and contact area. Here, we decoupled indentation depth and contact area by fabricating elastomeric slabs with precise thicknesses and microstructured surfaces. Human subject experiments using two-alternative forced-choice and magnitude estimation tests showed that the indentation depth and contact area contributed independently to perceived softness. We found an explicit relationship between the perceived softness of an object and its geometric properties. Using this approach, it is possible to design objects for human interaction with a desired level of perceived softness.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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8

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Binding energy of solvated electrons and retrieval of true UV photoelectron spectra of liquids (2019)

Nishitani, J., Yamamoto, Y.-i., West, C. W., Karashima, S., Suzuki, T.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉The electronic energy and dynamics of solvated electrons, the simplest yet elusive chemical species, is of interest in chemistry, physics, and biology. Here, we present the electron binding energy distributions of solvated electrons in liquid water, methanol, and ethanol accurately measured using extreme ultraviolet (EUV) photoelectron spectroscopy of liquids with a single-order high harmonic. The distributions are Gaussian in all cases. Using the EUV and UV photoelectron spectra of solvated electrons, we succeeded in retrieving sharp electron kinetic energy distributions from the spectra broadened and energy shifted by inelastic scattering in liquids, overcoming an obstacle in ultrafast UV photoelectron spectroscopy of liquids. The method is demonstrated for the benchmark systems of charge transfer to solvent reaction and ultrafast internal conversion of hydrated electron from the first excited state.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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9

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Magnetization switching using topological surface states (2019)

Li, P., Kally, J., Zhang, S. S.- L., Pillsbury, T., Ding, J., Csaba, G., Ding, J., Jiang, J. S., Liu, Y., Sinclair, R., Bi, C., DeMann, A., Rimal, G., Zhang, W., Field, S. B., Tang, J., Wang, W., Heinonen, O. G., Novosad, V., Hoffmann, A., Samarth, N., Wu

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Topological surface states (TSSs) in a topological insulator are expected to be able to produce a spin-orbit torque that can switch a neighboring ferromagnet. This effect may be absent if the ferromagnet is conductive because it can completely suppress the TSSs, but it should be present if the ferromagnet is insulating. This study reports TSS-induced switching in a bilayer consisting of a topological insulator Bi〈sub〉2〈/sub〉Se〈sub〉3〈/sub〉 and an insulating ferromagnet BaFe〈sub〉12〈/sub〉O〈sub〉19〈/sub〉. A charge current in Bi〈sub〉2〈/sub〉Se〈sub〉3〈/sub〉 can switch the magnetization in BaFe〈sub〉12〈/sub〉O〈sub〉19〈/sub〉 up and down. When the magnetization is switched by a field, a current in Bi〈sub〉2〈/sub〉Se〈sub〉3〈/sub〉 can reduce the switching field by ~4000 Oe. The switching efficiency at 3 K is 300 times higher than at room temperature; it is ~30 times higher than in Pt/BaFe〈sub〉12〈/sub〉O〈sub〉19〈/sub〉. These strong effects originate from the presence of more pronounced TSSs at low temperatures due to enhanced surface conductivity and reduced bulk conductivity.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Carbon speciation in organic fossils using 2D to 3D x-ray Raman multispectral imaging (2019)

Georgiou, R., Gueriau, P., Sahle, C. J., Bernard, S., Mirone, A., Garrouste, R., Bergmann, U., Rueff, J.-P., Bertrand, L.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉The in situ two-dimensional (2D) and 3D imaging of the chemical speciation of organic fossils is an unsolved problem in paleontology and cultural heritage. Here, we use x-ray Raman scattering (XRS)–based imaging at the carbon K-edge to form 2D and 3D images of the carbon chemistry in two exceptionally preserved specimens, a fossil plant dating back from the Carboniferous and an ancient insect entrapped in 53-million-year-old amber. The 2D XRS imaging of the plant fossil reveals a homogeneous chemical composition with micrometric "pockets" of preservation, likely inherited from its geological history. The 3D XRS imaging of the insect cuticle displays an exceptionally well preserved remaining chemical signature typical of polysaccharides such as chitin around a largely hollowed-out inclusion. Our results open up new perspectives for in situ chemical speciation imaging of fossilized organic materials, with the potential to enhance our understanding of organic specimens and their paleobiology.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Repair of tooth enamel by a biomimetic mineralization frontier ensuring epitaxial growth (2019)

Shao, C., Jin, B., Mu, Z., Lu, H., Zhao, Y., Wu, Z., Yan, L., Zhang, Z., Zhou, Y., Pan, H., Liu, Z., Tang, R.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉The regeneration of tooth enamel, the hardest biological tissue, remains a considerable challenge because its complicated and well-aligned apatite structure has not been duplicated artificially. We herein reveal that a rationally designed material composed of calcium phosphate ion clusters can be used to produce a precursor layer to induce the epitaxial crystal growth of enamel apatite, which mimics the biomineralization crystalline-amorphous frontier of hard tissue development in nature. After repair, the damaged enamel can be recovered completely because its hierarchical structure and mechanical properties are identical to those of natural enamel. The suggested phase transformation–based epitaxial growth follows a promising strategy for enamel regeneration and, more generally, for biomimetic reproduction of materials with complicated structure.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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12

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Non-Abelian band topology in noninteracting metals (2019)

Wu, Q., Soluyanov, A. A., Bzdusek, T.

American Association for the Advancement of Science (AAAS)

In: Science First Release

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Publikationsdatum: 2019

Beschreibung: 〈sec〉〈st〉Electron energy bands of crystalline solids generically exhibit degeneracies called band-structure nodes. Here, we introduce non-Abelian topological charges that characterize line nodes inside the momentum space of〈/st〉〈p〉〈b〉-symmetric crystalline metals with weak spin-orbit coupling. We show that these are quaternion charges, similar to those describing disclinations in biaxial nematics. Starting from two-band considerations, we develop the complete many-band description of nodes in the presence of 〈/b〉 〈b〉and mirror symmetries, which allows us to investigate the topological stability of nodal chains in metals. The non-Abelian charges put strict constraints on the possible nodal line configurations. Our analysis goes beyond the standard approach to band topology, and implies the existence of 1D topological phases not present in existing classifications.〈/b〉〈/p〉〈/sec〉

Print ISSN: 0036-8075

Digitale ISSN: 1095-9203

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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An interacting topological phase (2019)

Stajic, J.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

Digitale ISSN: 1095-9203

Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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CRISPR propels a smart hydrogel (2019)

Han, D., Li, J., Tan, W.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

Digitale ISSN: 1095-9203

Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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NAD depletion as pathogen response (2019)

Hines, P. J.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Geography of loss (2019)

Weiland, M.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Reducing tropical deforestation (2019)

Seymour, F., Harris, N. L.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Warning signs (2019)

Servick, K.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Italian ministry aids animal rights groups (2019)

Abbott, A.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Pathways to prevention (2019)

Miller, G.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Sharing data (2019)

Greenbaum, D., Gerstein, M.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Manifold destiny (2019)

Mao, S.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Ebb and flow of parasite populations (2019)

Ash, C.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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The slow earthquake spectrum in the Japan Trench illuminated by the S-net seafloor observatories (2019)

Nishikawa, T., Matsuzawa, T., Ohta, K., Uchida, N., Nishimura, T., Ide, S.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Beschreibung: 〈p〉Investigating slow earthquake activity in subduction zones provides insight into the slip behavior of megathrusts, which can provide important clues about the rupture extent of future great earthquakes. Using the S-net ocean-bottom seismograph network along the Japan Trench, we mapped a detailed distribution of tectonic tremors, which coincided with very-low-frequency earthquakes and a slow slip event. Compiling these and other related observations, including repeating earthquakes and earthquake swarms, we found that the slow earthquake distribution is complementary to the Tohoku-Oki earthquake rupture. We used our observations to divide the megathrust in the Japan Trench into three along-strike segments characterized by different slip behaviors. We found that the rupture of the Tohoku-Oki earthquake, which nucleated in the central segment, was terminated by the two adjacent segments.〈/p〉

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Programmable CRISPR-responsive smart materials (2019)

English, M. A., Soenksen, L. R., Gayet, R. V., de Puig, H., Angenent-Mari, N. M., Mao, A. S., Nguyen, P. Q., Collins, J. J.

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉Stimuli-responsive materials activated by biological signals play an increasingly important role in biotechnology applications. We exploit the programmability of CRISPR-associated nucleases to actuate hydrogels containing DNA as a structural element or as an anchor for pendant groups. After activation by guide RNA–defined inputs, Cas12a cleaves DNA in the gels, thereby converting biological information into changes in material properties. We report four applications: (i) branched poly(ethylene glycol) hydrogels releasing DNA-anchored compounds, (ii) degradable polyacrylamide-DNA hydrogels encapsulating nanoparticles and live cells, (iii) conductive carbon-black–DNA hydrogels acting as degradable electrical fuses, and (iv) a polyacrylamide-DNA hydrogel operating as a fluidic valve with an electrical readout for remote signaling. These materials allow for a range of in vitro applications in tissue engineering, bioelectronics, and diagnostics.〈/p〉

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Keeping RNA processing contained (2019)

Vinson, V.

American Association for the Advancement of Science (AAAS)

In: Science

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Major subpopulations of Plasmodium falciparum in sub-Saharan Africa (2019)

Amambua-Ngwa, A., Amenga-Etego, L., Kamau, E., Amato, R., Ghansah, A., Golassa, L., Randrianarivelojosia, M., Ishengoma, D., Apinjoh, T., Maïga-Ascofare, O., Andagalu, B., Yavo, W., Bouyou-Akotet, M., Kolapo, O., Mane, K., Worwui, A., Jeffries, D., Simp

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉Understanding genomic variation and population structure of 〈i〉Plasmodium falciparum〈/i〉 across Africa is necessary to sustain progress toward malaria elimination. Genome clustering of 2263 〈i〉P. falciparum〈/i〉 isolates from 24 malaria-endemic settings in 15 African countries identified major western, central, and eastern ancestries, plus a highly divergent Ethiopian population. Ancestry aligned to these regional blocs, overlapping with both the parasite’s origin and with historical human migration. The parasite populations are interbred and shared genomic haplotypes, especially across drug resistance loci, which showed the strongest recent identity-by-descent between populations. A recent signature of selection on chromosome 12 with candidate resistance loci against artemisinin derivatives was evident in Ghana and Malawi. Such selection and the emerging substructure may affect treatment-based intervention strategies against 〈i〉P. falciparum〈/i〉 malaria.〈/p〉

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A roadmap for malaria research (2019)

Winzeler, E. A.

American Association for the Advancement of Science (AAAS)

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The 200-year effort to see the embryo (2019)

Wallingford, J. B.

American Association for the Advancement of Science (AAAS)

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Maleness-on-the-Y (MoY) orchestrates male sex determination in major agricultural fruit fly pests (2019)

Meccariello, A., Salvemini, M., Primo, P., Hall, B., Koskinioti, P., Dalikova, M., Gravina, A., Gucciardino, M. A., Forlenza, F., Gregoriou, M.-E., Ippolito, D., Monti, S. M., Petrella, V., Perrotta, M. M., Schmeing, S., Ruggiero, A., Scolari, F., Giordan

American Association for the Advancement of Science (AAAS)

In: Science First Release

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Beschreibung: 〈p〉In insects, rapidly evolving primary sex-determining signals are transduced by a conserved regulatory module controlling sexual differentiation. In the agricultural pest 〈i〉Ceratitis capitata〈/i〉 (Mediterranean fruit fly, Medfly) we identified a Y-linked gene, 〈i〉Maleness-on the-Y〈/i〉 (〈i〉MoY〈/i〉), encoding a small protein that is necessary and sufficient for male development. Silencing or disruption of 〈i〉MoY〈/i〉 in XY embryos causes feminization whereas overexpression of 〈i〉MoY〈/i〉 in XX embryos induces masculinization. Crosses between transformed XY females and XX males give rise to males and females, indicating that a Y chromosome can be transmitted by XY females. 〈i〉MoY〈/i〉 is Y-linked and functionally conserved in other species of the Tephritidae family, highlighting its potential to serve as a tool for developing more effective control strategies against these major agricultural insect pests.〈/p〉

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Safe and effective gene delivery (2019)

Maroso, M.

American Association for the Advancement of Science (AAAS)

In: Science

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CRISPR comes to the silver screen (2019)

Winkleman, T.

American Association for the Advancement of Science (AAAS)

In: Science

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Financial crisis looms at Brazilian science agency (2019)

Mega, E. R.

American Association for the Advancement of Science (AAAS)

In: Science

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Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation (2019)

Kim, T. H., Tsang, B., Vernon, R. M., Sonenberg, N., Kay, L. E., Forman-Kay, J. D.

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉Membraneless organelles involved in RNA processing are biomolecular condensates assembled by phase separation. Despite the important role of intrinsically disordered protein regions (IDRs), the specific interactions underlying IDR phase separation and its functional consequences remain elusive. To address these questions, we used minimal condensates formed from the C-terminal disordered regions of two interacting translational regulators, FMRP and CAPRIN1. Nuclear magnetic resonance spectroscopy of FMRP-CAPRIN1 condensates revealed interactions involving arginine-rich and aromatic-rich regions. We found that different FMRP serine/threonine and CAPRIN1 tyrosine phosphorylation patterns control phase separation propensity with RNA, including subcompartmentalization, and tune deadenylation and translation rates in vitro. The resulting evidence for residue-specific interactions underlying co–phase separation, phosphorylation-modulated condensate architecture, and enzymatic activity within condensates has implications for how the integration of signaling pathways controls RNA processing and translation.〈/p〉

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NAD+ cleavage activity by animal and plant TIR domains in cell death pathways (2019)

Horsefield, S., Burdett, H., Zhang, X., Manik, M. K., Shi, Y., Chen, J., Qi, T., Gilley, J., Lai, J.-S., Rank, M. X., Casey, L. W., Gu, W., Ericsson, D. J., Foley, G., Hughes, R. O., Bosanac, T., von Itzstein, M., Rathjen, J. P., Nanson, J. D., Boden, M.,

American Association for the Advancement of Science (AAAS)

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Beschreibung: 〈p〉SARM1 (sterile alpha and TIR motif containing 1) is responsible for depletion of nicotinamide adenine dinucleotide in its oxidized form (NAD〈sup〉+〈/sup〉) during Wallerian degeneration associated with neuropathies. Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors recognize pathogen effector proteins and trigger localized cell death to restrict pathogen infection. Both processes depend on closely related Toll/interleukin-1 receptor (TIR) domains in these proteins, which, as we show, feature self-association–dependent NAD〈sup〉+〈/sup〉 cleavage activity associated with cell death signaling. We further show that SARM1 SAM (sterile alpha motif) domains form an octamer essential for axon degeneration that contributes to TIR domain enzymatic activity. The crystal structures of ribose and NADP〈sup〉+〈/sup〉 (the oxidized form of nicotinamide adenine dinucleotide phosphate) complexes of SARM1 and plant NLR RUN1 TIR domains, respectively, reveal a conserved substrate binding site. NAD〈sup〉+〈/sup〉 cleavage by TIR domains is therefore a conserved feature of animal and plant cell death signaling pathways.〈/p〉

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Genomic analysis informs malaria evolution (2019)

Sibley, C. H.

American Association for the Advancement of Science (AAAS)

In: Science

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News at a glance (2019)

American Association for the Advancement of Science (AAAS)

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Images from the surface of asteroid Ryugu show rocks similar to carbonaceous chondrite meteorites (2019)

Jaumann, R., Schmitz, N., Ho, T.- M., Schröder, S. E., Otto, K. A., Stephan, K., Elgner, S., Krohn, K., Preusker, F., Scholten, F., Biele, J., Ulamec, S., Krause, C., Sugita, S., Matz, K.- D., Roatsch, T., Parekh, R., Mottola, S., Grott, M., Michel, P.,

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉The near-Earth asteroid (162173) Ryugu is a 900-m-diameter dark object expected to contain primordial material from the solar nebula. The Mobile Asteroid Surface Scout (MASCOT) landed on Ryugu’s surface on 3 October 2018. We present images from the MASCOT camera (MASCam) taken during the descent and while on the surface. The surface is covered by decimeter- to meter-sized rocks, with no deposits of fine-grained material. Rocks appear either bright, with smooth faces and sharp edges, or dark, with a cauliflower-like, crumbly surface. Close-up images of a rock of the latter type reveal a dark matrix with small, bright, spectrally different inclusions, implying that it did not experience extensive aqueous alteration. The inclusions appear similar to those in carbonaceous chondrite meteorites.〈/p〉

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Comment on "Legacy nitrogen may prevent achievement of water quality goals in the Gulf of Mexico" (2019)

Ballard, T. C., Michalak, A. M., McIsaac, G. F., Rabalais, N. N., Turner, R. E.

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉Van Meter 〈i〉et al〈/i〉. (Reports, 27 April 2018, p. 427) warn that achieving nitrogen reduction goals in the Gulf of Mexico will take decades as a result of legacy nitrogen effects. We discuss limitations of the modeling approach and demonstrate that legacy effects ranging from a few years to decades are equally consistent with observations. The presented time scales for system recovery are therefore highly uncertain.〈/p〉

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No inflation of threatened species (2019)

Purvis, A., Butchart, S. H. M., Brondizio, E. S., Settele, J., Diaz, S.

American Association for the Advancement of Science (AAAS)

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Spastin uses its network (2019)

Vinson, V.

American Association for the Advancement of Science (AAAS)

In: Science

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The Malaria Cell Atlas: Single parasite transcriptomes across the complete Plasmodium life cycle (2019)

Howick, V. M., Russell, A. J. C., Andrews, T., Heaton, H., Reid, A. J., Natarajan, K., Butungi, H., Metcalf, T., Verzier, L. H., Rayner, J. C., Berriman, M., Herren, J. K., Billker, O., Hemberg, M., Talman, A. M., Lawniczak, M. K. N.

American Association for the Advancement of Science (AAAS)

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Beschreibung: 〈p〉Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. We profiled the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire 〈i〉Plasmodium berghei〈/i〉 life cycle. We then used our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a eukaryotic parasite and an open-access reference dataset for the study of malaria parasites.〈/p〉

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The case for strategic and managed climate retreat (2019)

Siders, A. R., Hino, M., Mach, K. J.

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In: Science

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Mapping the malaria parasite (2019)

Ash, C.

American Association for the Advancement of Science (AAAS)

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The global soil community and its influence on biogeochemistry (2019)

Crowther, T. W., van den Hoogen, J., Wan, J., Mayes, M. A., Keiser, A. D., Mo, L., Averill, C., Maynard, D. S.

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Beschreibung: 〈p〉Soil organisms represent the most biologically diverse community on land and govern the turnover of the largest organic matter pool in the terrestrial biosphere. The highly complex nature of these communities at local scales has traditionally obscured efforts to identify unifying patterns in global soil biodiversity and biogeochemistry. As a result, environmental covariates have generally been used as a proxy to represent the variation in soil community activity in global biogeochemical models. Yet over the past decade, broad-scale studies have begun to see past this local heterogeneity to identify unifying patterns in the biomass, diversity, and composition of certain soil groups across the globe. These unifying patterns provide new insights into the fundamental distribution and dynamics of organic matter on land.〈/p〉

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Robust memories through neuron networks (2019)

Stern, P.

American Association for the Advancement of Science (AAAS)

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Joining the laser welding club (2019)

Grocholski, B.

American Association for the Advancement of Science (AAAS)

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Ultrafast laser welding of ceramics (2019)

Penilla, E. H., Devia-Cruz, L. F., Wieg, A. T., Martinez-Torres, P., Cuando-Espitia, N., Sellappan, P., Kodera, Y., Aguilar, G., Garay, J. E.

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Beschreibung: 〈p〉Welding of ceramics is a key missing component in modern manufacturing. Current methods cannot join ceramics in proximity to temperature-sensitive materials like polymers and electronic components. We introduce an ultrafast pulsed laser welding approach that relies on focusing light on interfaces to ensure an optical interaction volume in ceramics to stimulate nonlinear absorption processes, causing localized melting rather than ablation. The key is the interplay between linear and nonlinear optical properties and laser energy–material coupling. The welded ceramic assemblies hold high vacuum and have shear strengths comparable to metal-to-ceramic diffusion bonds. Laser welding can make ceramics integral components in devices for harsh environments as well as in optoelectronic and/or electronic packages needing visible-radio frequency transparency.〈/p〉

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Landing on the surface of Ryugu (2019)

Smith, K. T.

American Association for the Advancement of Science (AAAS)

In: Science

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Salmon-smeared notebooks reveal fisheries past bounty (2019)

Ogden, L. E.

American Association for the Advancement of Science (AAAS)

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Linking development to metabolism (2019)

Mao, S.

American Association for the Advancement of Science (AAAS)

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Suicide--turning the tide (2019)

Nordentoft, M., Erlangsen, A.

American Association for the Advancement of Science (AAAS)

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Think local when protecting forests (2019)

Fahrenkamp-Uppenbrink, J.

American Association for the Advancement of Science (AAAS)

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Observation of a symmetry-protected topological phase of interacting bosons with Rydberg atoms (2019)

de Leseleuc, S., Lienhard, V., Scholl, P., Barredo, D., Weber, S., Lang, N., Büchler, H. P., Lahaye, T., Browaeys, A.

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉The concept of topological phases is a powerful framework for characterizing ground states of quantum many-body systems that goes beyond the paradigm of symmetry breaking. Topological phases can appear in condensed-matter systems naturally, whereas the implementation and study of such quantum many-body ground states in artificial matter require careful engineering. Here, we report the experimental realization of a symmetry-protected topological phase of interacting bosons in a one-dimensional lattice and demonstrate a robust ground state degeneracy attributed to protected zero-energy edge states. The experimental setup is based on atoms trapped in an array of optical tweezers and excited into Rydberg levels, which gives rise to hard-core bosons with an effective hopping generated by dipolar exchange interaction.〈/p〉

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A CRISPR set of materials (2019)

Lavine, M. S.

American Association for the Advancement of Science (AAAS)

In: Science

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Response to Comment on "Legacy nitrogen may prevent achievement of water quality goals in the Gulf of Mexico" (2019)

Van Meter, K. J., Van Cappellen, P., Basu, N. B.

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉Ballard 〈i〉et al〈/i〉. argue that our prediction of a 30-year or longer recovery time for Gulf of Mexico water quality is highly uncertain, and that much shorter time lags are equally likely. We demonstrate that their argument, based on the use of a two-component regression model, does not sufficiently consider fundamental watershed processes or multiple lines of evidence suggesting the existence of decadal-scale lags.〈/p〉

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Paths out of darkness (2019)

Couzin-Frankel, J.

American Association for the Advancement of Science (AAAS)

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Canadian cannabis research hits licensing logjam (2019)

Wadman, M.

American Association for the Advancement of Science (AAAS)

In: Science

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Super-old mantle plumes (2019)

Grocholski, B.

American Association for the Advancement of Science (AAAS)

In: Science

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TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death (2019)

Wan, L., Essuman, K., Anderson, R. G., Sasaki, Y., Monteiro, F., Chung, E.-H., Osborne Nishimura, E., DiAntonio, A., Milbrandt, J., Dangl, J. L., Nishimura, M. T.

American Association for the Advancement of Science (AAAS)

In: Science

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Beschreibung: 〈p〉Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors activate cell death and confer disease resistance by unknown mechanisms. We demonstrate that plant Toll/interleukin-1 receptor (TIR) domains of NLRs are enzymes capable of degrading nicotinamide adenine dinucleotide in its oxidized form (NAD〈sup〉+〈/sup〉). Both cell death induction and NAD〈sup〉+〈/sup〉 cleavage activity of plant TIR domains require known self-association interfaces and a putative catalytic glutamic acid that is conserved in both bacterial TIR NAD〈sup〉+〈/sup〉-cleaving enzymes (NADases) and the mammalian SARM1 (sterile alpha and TIR motif containing 1) NADase. We identify a variant of cyclic adenosine diphosphate ribose as a biomarker of TIR enzymatic activity. TIR enzymatic activity is induced by pathogen recognition and functions upstream of the genes 〈i〉enhanced disease susceptibility 1〈/i〉 (〈i〉EDS1〈/i〉) and 〈i〉N requirement gene 1〈/i〉 (〈i〉NRG1〈/i〉), which encode regulators required for TIR immune function. Thus, plant TIR-NLR receptors require NADase function to transduce recognition of pathogens into a cell death response.〈/p〉

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A gut check (2019)

Lavine, M. S.

American Association for the Advancement of Science (AAAS)

In: Science

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Microbes' role in soil decomposition (2019)

Sugden, A. M.

American Association for the Advancement of Science (AAAS)

In: Science

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New Products (2019)

American Association for the Advancement of Science (AAAS)

In: Science

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Persistence of neuronal representations through time and damage in the hippocampus (2019)

Gonzalez, W. G., Zhang, H., Harutyunyan, A., Lois, C.

American Association for the Advancement of Science (AAAS)

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Beschreibung: 〈p〉How do neurons encode long-term memories? Bilateral imaging of neuronal activity in the mouse hippocampus reveals that, from one day to the next, ~40% of neurons change their responsiveness to cues, but thereafter only 1% of cells change per day. Despite these changes, neuronal responses are resilient to a lack of exposure to a previously completed task or to hippocampus lesions. Unlike individual neurons, the responses of which change after a few days, groups of neurons with inter- and intrahemispheric synchronous activity show stable responses for several weeks. The likelihood that a neuron maintains its responsiveness across days is proportional to the number of neurons with which its activity is synchronous. Information stored in individual neurons is relatively labile, but it can be reliably stored in networks of synchronously active neurons.〈/p〉

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A tale of two trenches (2019)

Houston, H.

American Association for the Advancement of Science (AAAS)

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Seeing the embryo (2019)

Alderton, G.

American Association for the Advancement of Science (AAAS)

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Codemakers find algorithms immune to quantum hacks (2019)

Cho, A.

American Association for the Advancement of Science (AAAS)

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Calvin F. Quate (1923-2019) (2019)

Rugar, D., Giessibl, F.

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Arctic researchers prepare to go with the floes (2019)

Kintisch, E.

American Association for the Advancement of Science (AAAS)

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Microbial metabolites control the thymic development of mucosal-associated invariant T cells (2019)

Legoux, F., Bellet, D., Daviaud, C., El Morr, Y., Darbois, A., Niort, K., Procopio, E., Salou, M., Gilet, J., Ryffel, B., Balvay, A., Foussier, A., Sarkis, M., El Marjou, A., Schmidt, F., Rabot, S., Lantz, O.

American Association for the Advancement of Science (AAAS)

In: Science First Release

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Beschreibung: 〈p〉How the microbiota modulate immune functions remains poorly understood. Mucosal-associated invariant T (MAIT) cells are implicated in mucosal homeostasis and absent in germ-free mice. Here, we show that commensal bacteria govern murine MAIT intrathymic development, as MAIT cells did not recirculate to the thymus. MAIT development required 〈i〉RibD〈/i〉 expression in bacteria, indicating that production of the MAIT antigen 5-(2-oxopropylideneamino)-6-〈scp〉d〈/scp〉-ribitylaminouracil (5-OP-RU) was necessary. 5-OP-RU rapidly traveled from mucosal surfaces to the thymus, where it was captured by the major histocompatibility complex class Ib molecule MR1. This led to increased numbers of the earliest MAIT precursors and the expansion of more mature receptor–related orphan receptor t–positive MAIT cells. Thus, a microbiota-derived metabolite controls development of mucosally targeted T cells, in a process blurring the distinction between exogenous and self-antigens.〈/p〉

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N6-methyladenosine RNA modification-mediated cellular metabolism rewiring inhibits viral replication (2019)

Liu, Y., You, Y., Lu, Z., Yang, J., Li, P., Liu, L., Xu, H., Niu, Y., Cao, X.

American Association for the Advancement of Science (AAAS)

In: Science First Release

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Beschreibung: 〈p〉Host cell metabolism can be modulated by viral infection, affecting viral survival or clearance. The cellular metabolism rewiring mediated by 〈i〉N〈/i〉〈sup〉6〈/sup〉-methyladenosine (m〈sup〉6〈/sup〉A) modification in virus-host interaction remains largely unknown. Here we report that in response to viral infection, host cells impair the enzymatic activity of RNA m〈sup〉6〈/sup〉A demethylase ALKBH5. This increases the m〈sup〉6〈/sup〉A methylation on α-ketoglutarate dehydrogenase (OGDH) mRNA to reduce its mRNA stability and protein expression. Reduced OGDH decreases the production of metabolite itaconate that is required for viral replication. With reduced OGDH and itaconate production in vivo, ALKBH5-deficient mice display an innate immune response-independent resistance to viral challenge. Our findings reveal that m〈sup〉6〈/sup〉A RNA modification-mediated down-regulation of OGDH-Itaconate pathway reprograms cellular metabolism to inhibit viral replication, proposing potential targets for controlling viral infection.〈/p〉

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Phase-change heterostructure enables ultralow noise and drift for memory operation (2019)

Ding, K., Wang, J., Zhou, Y., Tian, H., Lu, L., Mazzarello, R., Jia, C., Zhang, W., Rao, F., Ma, E.

American Association for the Advancement of Science (AAAS)

In: Science First Release

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Beschreibung: 〈p〉Artificial intelligence and other data-intensive applications have escalated the demand for data storage and processing. New computing devices, e.g., phase-change random access memory (PCRAM) based neuro-inspired devices, are promising options for breaking the von Neumann barrier by unifying storage with computing in memory cells. However, current PCRAM devices have considerable noise and drift in electrical resistance that erodes the precision and consistency of these devices. We designed a phase-change heterostructure (PCH) consisting of alternately stacked phase-change and confinement nanolayers to suppress the noise and drift, allowing reliable iterative RESET and cumulative SET operations for high-performance neuro-inspired computing. Our PCH architecture is amenable to industrial production as an intrinsic materials solution, without complex manufacturing procedure nor much increased fabrication cost.〈/p〉

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Choosing male or female (2019)

Purnell, B. A.

American Association for the Advancement of Science (AAAS)

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Innovations in an ATPase/ATP synthase (2019)

Funk, M. A.

American Association for the Advancement of Science (AAAS)

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Certification for gene-edited forests (2019)

Strauss, S. H., Boerjan, W., Chiang, V., Costanza, A., Coleman, H., Davis, J. M., Lu, M.-Z., Mansfield, S. D., Merkle, S., Myburg, A., Nilsson, O., Pilate, G., Powell, W., Seguin, A., Valenzuela, S.

American Association for the Advancement of Science (AAAS)

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A reverse route into metastasis (2019)

Ferrarelli, L. K.

American Association for the Advancement of Science (AAAS)

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Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase (2019)

Zhou, L., Sazanov, L. A.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Beschreibung: 〈p〉V (vacuolar)/A (archaeal)-type adenosine triphosphatases (ATPases), found in archaea and eubacteria, couple ATP hydrolysis or synthesis to proton translocation across the plasma membrane using the rotary-catalysis mechanism. They belong to the V-type ATPase family, which differs from the mitochondrial/chloroplast F-type ATP synthases in overall architecture. We solved cryo–electron microscopy structures of the intact 〈i〉Thermus thermophilus〈/i〉 V/A-ATPase, reconstituted into lipid nanodiscs, in three rotational states and two substates. These structures indicate substantial flexibility between V〈sub〉1〈/sub〉 and V〈sub〉o〈/sub〉 in a working enzyme, which results from mechanical competition between central shaft rotation and resistance from the peripheral stalks. We also describe details of adenosine diphosphate inhibition release, V〈sub〉1〈/sub〉-V〈sub〉o〈/sub〉 torque transmission, and proton translocation, which are relevant for the entire V-type ATPase family.〈/p〉

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Familial roots of an opioid epidemic (2019)

Wible, B.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

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Venezuela's upheaval threatens Yanomami (2019)

Mondolfi, A. E. P., Grillet, M. E., Tami, A., Oliveira-Miranda, M. A., Noguera, L. D., Hotez, P., Oletta, J. F.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

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Probing an evolutionary riddle (2019)

Culotta, E.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

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Stand out as a speaker (2019)

His, M.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

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Slow earthquake segmentation (2019)

Grocholski, B.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

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Exploring genetic interaction manifolds constructed from rich single-cell phenotypes (2019)

Norman, T. M., Horlbeck, M. A., Replogle, J. M., Ge, A. Y., Xu, A., Jost, M., Gilbert, L. A., Weissman, J. S.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Beschreibung: 〈p〉How cellular and organismal complexity emerges from combinatorial expression of genes is a central question in biology. High-content phenotyping approaches such as Perturb-seq (single-cell RNA-sequencing pooled CRISPR screens) present an opportunity for exploring such genetic interactions (GIs) at scale. Here, we present an analytical framework for interpreting high-dimensional landscapes of cell states (manifolds) constructed from transcriptional phenotypes. We applied this approach to Perturb-seq profiling of strong GIs mined from a growth-based, gain-of-function GI map. Exploration of this manifold enabled ordering of regulatory pathways, principled classification of GIs (e.g., identifying suppressors), and mechanistic elucidation of synergistic interactions, including an unexpected synergy between 〈i〉CBL〈/i〉 and 〈i〉CNN1〈/i〉 driving erythroid differentiation. Finally, we applied recommender system machine learning to predict interactions, facilitating exploration of vastly larger GI manifolds.〈/p〉

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

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Reading an anguished brain (2019)

Underwood, E.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

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Numerical operations in living cells by programmable RNA devices (2019)

Endo, K., Hayashi, K., Saito, H.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Integrated bioengineering systems can make executable decisions according to the cell state. To sense the state, multiple biomarkers are detected and processed via logic gates with synthetic biological devices. However, numerical operations have not been achieved. Here, we show a design principle for messenger RNA (mRNA) devices that recapitulates intracellular information by multivariate calculations in single living cells. On the basis of this principle and the collected profiles of multiple microRNA activities, we demonstrate that rationally programmed mRNA sets classify living human cells and track their change during differentiation. Our mRNA devices automatically perform multivariate calculation and function as a decision-maker in response to dynamic intracellular changes in living cells.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Water scaling of ecosystem carbon cycle feedback to climate warming (2019)

Quan, Q., Tian, D., Luo, Y., Zhang, F., Crowther, T. W., Zhu, K., Chen, H. Y. H., Zhou, Q., Niu, S.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉It has been well established by field experiments that warming stimulates either net ecosystem carbon uptake or release, leading to negative or positive carbon cycle–climate change feedback, respectively. This variation in carbon-climate feedback has been partially attributed to water availability. However, it remains unclear under what conditions water availability enhances or weakens carbon-climate feedback or even changes its direction. Combining a field experiment with a global synthesis, we show that warming stimulates net carbon uptake (negative feedback) under wet conditions, but depresses it (positive feedback) under very dry conditions. This switch in carbon-climate feedback direction arises mainly from scaling effects of warming-induced decreases in soil water content on net ecosystem productivity. This water scaling of warming effects offers generalizable mechanisms not only to help explain varying magnitudes and directions of observed carbon-climate feedback but also to improve model prediction of ecosystem carbon dynamics in response to climate change.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Cranial endocast of a stem platyrrhine primate and ancestral brain conditions in anthropoids (2019)

Ni, X., Flynn, J. J., Wyss, A. R., Zhang, C.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Understanding of ancestral conditions for anthropoids has been hampered by the paucity of well-preserved early fossils. Here, we provide an unprecedented view of the cerebral morphology of the 20-million-year-old 〈i〉Chilecebus carrascoensis〈/i〉, the best-preserved early diverging platyrrhine known, obtained via high-resolution CT scanning and 3D digital reconstruction. These analyses are crucial for reconstructing ancestral brain conditions in platyrrhines and anthropoids given the early diverging position of 〈i〉Chilecebus.〈/i〉 Although small, the brain of 〈i〉Chilecebus〈/i〉 is not lissencephalic and presents at least seven pairs of sulci on its endocast. Comparisons of 〈i〉Chilecebus〈/i〉 and other basal anthropoids indicate that the major brain subdivisions of these early anthropoids exhibit no consistent scaling pattern relative to the overall brain size. Many gross cerebral features appear to have transformed in a mosaic fashion and probably have originated in platyrrhine and catarrhine anthropoids independently, involving multiple, independent instances of size increase, as well as some secondary decreases.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Data-driven phenotype discovery of FMR1 premutation carriers in a population-based sample (2019)

Movaghar, A., Page, D., Brilliant, M., Baker, M. W., Greenberg, J., Hong, J., DaWalt, L. S., Saha, K., Kuusisto, F., Stewart, R., Berry-Kravis, E., Mailick, M. R.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉The impact of the 〈i〉FMR1〈/i〉 premutation on human health is the subject of considerable controversy. A fundamental unanswered question is whether carrying the premutation allele is directly correlated with clinical phenotypes. A challenging problem in past genotype-phenotype studies of the 〈i〉FMR1〈/i〉 premutation is ascertainment bias, which could lead to invalid research conclusions and negatively affect clinical practice. Here, we created the first population-based 〈i〉FMR1〈/i〉-informed biobank to find the pattern of health characteristics in premutation carriers. Our extensive phenotyping shows that premutation carriers experience a clinical profile that is significantly different from controls and is evident throughout adulthood. Comprehensive understanding of the clinical risk associated with this genetic variant is critical for premutation carriers, their families, and clinicians and has important implications for public health.〈/p〉

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Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Weakening Atlantic Nino-Pacific connection under greenhouse warming (2019)

Jia, F., Cai, W., Wu, L., Gan, B., Wang, G., Kucharski, F., Chang, P., Keenlyside, N.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Sea surface temperature variability in the equatorial eastern Atlantic, which is referred to as an Atlantic Niño (Niña) at its warm (cold) phase and peaks in boreal summer, dominates the interannual variability in the equatorial Atlantic. By strengthening of the Walker circulation, an Atlantic Niño favors a Pacific La Niña, which matures in boreal winter, providing a precursory memory for El Niño–Southern Oscillation (ENSO) predictability. How this Atlantic impact responds to greenhouse warming is unclear. Here, we show that greenhouse warming leads to a weakened influence from the Atlantic Niño/Niña on the Pacific ENSO. In response to anomalous equatorial Atlantic heating, ascending over the equatorial Atlantic is weaker due to an increased tropospheric stability in the mean climate, resulting in a weaker impact on the Pacific Ocean. Thus, as greenhouse warming continues, Pacific ENSO is projected to be less affected by the Atlantic Niño/Niña and more challenging to predict.〈/p〉

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Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Quantitative prediction of erythrocyte sickling for the development of advanced sickle cell therapies (2019)

Lu, L., Li, Z., Li, H., Li, X., Vekilov, P. G., Karniadakis, G. E.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Sickle cell disease is induced by a mutation that converts normal adult hemoglobin to sickle hemoglobin (HbS) and engenders intracellular polymerization of deoxy-HbS and erythrocyte sickling. Development of anti-sickling therapies requires quantitative understanding of HbS polymerization kinetics under organ-specific conditions, which are difficult to assess with existing experimental techniques. Thus, we developed a kinetic model based on the classical nucleation theory to examine the effectiveness of potential anti-sickling drug candidates. We validated this model by comparing its predictability against prior in vivo and in vitro experimental results. We used the model to quantify the efficacy of sickling inhibitors and obtain results consistent with recent screening assays. Global sensitivity analysis on the kinetic parameters in the model revealed that the solubility, nucleation rate prefactor, and oxygen affinity are quantities that dictate HbS polymerization. This finding provides quantitative guidelines for the discovery of intracellular processes to be targeted by sickling inhibitors.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Paramo islands through the Pleistocene (2019)

Sugden, A. M.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2019

Print ISSN: 0036-8075

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Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Off-on switching of enzyme activity by near-infrared light-induced photothermal phase transition of nanohybrids (2019)

Zhang, S., Wang, C., Chang, H., Zhang, Q., Cheng, Y.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉The off-on manipulation of enzyme activity is a challenging task. We report a new strategy for reversible off-on control of enzyme activity by near-infrared light. Enzymes acting on macromolecular substrates are embedded with an ultrasmall platinum nanoparticle and decorated with thermoresponsive copolymers, which exhibit upper critical solution temperature (UCST) behavior. The polymer-enzyme nanohybrids form microscale aggregates in solution below the UCST to prevent macromolecular substrates from approaching the enzymes and thus inhibit the enzyme activity, and they disassemble above the UCST to reactivate the enzyme. Upon near-infrared irradiation, platinum nanoparticles inside the enzymes generate heat through a photothermal effect to cause phase transition of the copolymers. Therefore, we can reversibly switch off and on the activities of three enzymes acting on polysaccharide, protein, and plasmid. The enzyme activities are increased by up to 61-fold after laser irradiation. This study provides a facile and efficient method for off-on control of enzyme activity.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Discriminative T cell recognition of cross-reactive islet-antigens is associated with HLA-DQ8 transdimer-mediated autoimmune diabetes (2019)

Chow, I.-T., Gates, T. J., Papadopoulos, G. K., Moustakas, A. K., Kolawole, E. M., Notturno, R. J., McGinty, J. W., Torres-Chinn, N., James, E. A., Greenbaum, C., Nepom, G. T., Evavold, B. D., Kwok, W. W.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Human leukocyte antigen (HLA)–DQ8 transdimer (HLA-DQA1*0501/DQB1*0302) confers exceptionally high risk in autoimmune diabetes. However, little is known about HLA-DQ8 transdimer–restricted CD4 T cell recognition, an event crucial for triggering HLA-DQ8 transdimer–specific anti-islet immunity. Here, we report a high degree of epitope overlap and T cell promiscuity between susceptible HLA-DQ8 and HLA-DQ8 transdimer. Despite preservation of putative residues for T cell receptor (TCR) contact, stronger disease-associated responses to cross-reactive, immunodominant islet epitopes are elicited by HLA-DQ8 transdimer. Mutagenesis at the α chain of HLA-DQ8 transdimer in complex with the disease-relevant GAD65〈sub〉250–266〈/sub〉 peptide and in silico analysis reveal the DQ α52 residue located within the N-terminal edge of the peptide-binding cleft for the enhanced T cell reactivity, altering avidity and biophysical affinity between TCR and HLA-peptide complexes. Accordingly, a structurally promiscuous but nondegenerate TCR-HLA-peptide interface is pivotal for HLA-DQ8 transdimer–mediated autoimmune diabetes.〈/p〉

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Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Parallel processing of polarization and intensity information in fiddler crab vision (2019)

Smithers, S. P., Roberts, N. W., How, M. J.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Many crustaceans are sensitive to the polarization of light and use this information for object-based visually guided behaviors. For these tasks, it is unknown whether polarization and intensity information are integrated into a single-contrast channel, whereby polarization directly contributes to perceived intensity, or whether they are processed separately and in parallel. Using a novel type of visual display that allowed polarization and intensity properties of visual stimuli to be adjusted independently and simultaneously, we conducted behavioral experiments with fiddler crabs to test which of these two models of visual processing occurs. We found that, for a loom detection task, fiddler crabs process polarization and intensity information independently and in parallel. The crab’s response depended on whichever contrast was the most salient. By contributing independent measures of visual contrast, polarization and intensity provide a greater range of detectable contrast information for the receiver, increasing the chance of detecting a potential threat.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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A prokaryotic-eukaryotic hybrid viral vector for delivery of large cargos of genes and proteins into human cells (2019)

Zhu, J., Tao, P., Mahalingam, M., Sha, J., Kilgore, P., Chopra, A. K., Rao, V.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Development of safe and efficient nanoscale vehicles that can deliver large molecular cargos into human cells could transform future human therapies and personalized medicine. Here, we design a hybrid viral vector composed of a prokaryotic virus (bacteriophage T4) and a eukaryotic virus [adeno-associated virus (AAV)]. The small 25-nm AAV is attached to the large 120 nm x 86 nm T4 head through avidin-biotin cross-bridges using the phage decoration proteins Soc and Hoc. AAV "piggy-backed" on T4 capsid, by virtue of its natural ability to enter human cells acted as an efficient "driver," delivering the largest payloads of foreign DNA (up to 170 kb) and protein (up to 1025 molecules) reported to date, and elicited robust immune responses in mice against flu and plague pathogens and conferred complete protection against lethal pneumonic plague challenge. The T4-AAV represents a unique platform for assembly of natural building blocks into potential therapeutics against genetic and infectious diseases.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Viruses mobilize plant immunity to deter nonvector insect herbivores (2019)

Zhao, P., Yao, X., Cai, C., Li, R., Du, J., Sun, Y., Wang, M., Zou, Z., Wang, Q., Kliebenstein, D. J., Liu, S.-S., Fang, R.-X., Ye, J.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉A parasite-infected host may promote performance of associated insect vectors; but possible parasite effects on nonvector insects have been largely unexplored. Here, we show that 〈i〉Begomovirus〈/i〉, the largest genus of plant viruses and transmitted exclusively by whitefly, reprogram plant immunity to promote the fitness of the vector and suppress performance of nonvector insects (i.e., cotton bollworm and aphid). Infected plants accumulated begomoviral βC1 proteins in the phloem where they were bound to the plant transcription factor WRKY20. This viral hijacking of WRKY20 spatiotemporally redeployed plant chemical immunity within the leaf and had the asymmetrical benefiting effects on the begomoviruses and its whitefly vectors while negatively affecting two nonvector competitors. This type of interaction between a parasite and two types of herbivores, i.e., vectors and nonvectors, occurs widely in various natural and agricultural ecosystems; thus, our results have broad implications for the ecological significance of parasite-vector-host tripartite interactions.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019)

Elyahu, Y., Hekselman, I., Eizenberg-Magar, I., Berner, O., Strominger, I., Schiller, M., Mittal, K., Nemirovsky, A., Eremenko, E., Vital, A., Simonovsky, E., Chalifa-Caspi, V., Friedman, N., Yeger-Lotem, E., Monsonego, A.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Age-associated changes in CD4 T-cell functionality have been linked to chronic inflammation and decreased immunity. However, a detailed characterization of CD4 T cell phenotypes that could explain these dysregulated functional properties is lacking. We used single-cell RNA sequencing and multidimensional protein analyses to profile thousands of CD4 T cells obtained from young and old mice. We found that the landscape of CD4 T cell subsets differs markedly between young and old mice, such that three cell subsets—exhausted, cytotoxic, and activated regulatory T cells (aT〈sub〉regs〈/sub〉)—appear rarely in young mice but gradually accumulate with age. Most unexpected were the extreme pro- and anti-inflammatory phenotypes of cytotoxic CD4 T cells and aT〈sub〉regs〈/sub〉, respectively. These findings provide a comprehensive view of the dynamic reorganization of the CD4 T cell milieu with age and illuminate dominant subsets associated with chronic inflammation and immunity decline, suggesting new therapeutic avenues for age-related diseases.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Accurate high-throughput screening based on digital protein synthesis in a massively parallel femtoliter droplet array (2019)

Zhang, Y., Minagawa, Y., Kizoe, H., Miyazaki, K., Iino, R., Ueno, H., Tabata, K. V., Shimane, Y., Noji, H.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉We report a general strategy based on digital counting principle that enables an efficient acquisition of enzyme mutants with desired activities from just a few clones within a day. We prepared a high-density femtoliter droplet array, consisting of 1 million uniform droplets per 1 cm〈sup〉2〈/sup〉 to carry out high-throughput protein synthesis and screening. Single DNA molecules were randomly distributed into each droplet following a Poisson process to initiate the protein synthesis with coupled cell-free transcription and translation reactions and then recovered by a microcapillary. The protein yield in each droplet was proportional to the number of DNA molecules, meaning that droplets with apparent intensities higher than the Poisson distribution–predicted maximum can be readily identified as the exact hits exhibiting the desired increased activity. We improved the activity of an alkaline phosphatase up to near 20-fold by using less than 10 nl of reagents.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Life on the thermodynamic edge: Respiratory growth of an acetotrophic methanogen (2019)

Prakash, D., Chauhan, S. S., Ferry, J. G.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Although two-thirds of the nearly 1 billion metric tons of methane produced annually in Earth’s biosphere derives from acetate, the in situ process has escaped rigorous understanding. The unresolved question concerns the mechanism by which the exceptionally marginal amount of available energy supports acetotrophic growth of methanogenic archaea in the environment. Here, we show that 〈i〉Methanosarcina acetivorans〈/i〉 conserves energy by Fe(III)-dependent respiratory metabolism of acetate, augmenting production of the greenhouse gas methane. An extensively revised, ecologically relevant, biochemical pathway for acetotrophic growth is presented, in which the conservation of respiratory energy is maximized by electron bifurcation, a previously unknown mechanism of biological energy coupling. The results transform the ecological and biochemical understanding of methanogenesis and the role of iron in the mineralization of organic matter in anaerobic environments.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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North American April tornado occurrences linked to global sea surface temperature anomalies (2019)

Chu, J.- E., Timmermann, A., Lee, J.- Y.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2019

Beschreibung: 〈p〉Annual tornado occurrences over North America display large interannual variability and a statistical linkage to sea surface temperature (SST) anomalies. However, the underlying physical mechanisms for this connection and its modulation in a rapidly varying seasonal environment still remain elusive. Using tornado data over the United States from 1954 to 2016 in combination with SST-forced atmospheric general circulation models, we show a robust dynamical linkage between global SST conditions in April, the emergence of the Pacific-North American teleconnection pattern (PNA), and the year-to-year tornado activity in the Southern Great Plains (SGP) region of the United States. Contrasting previous studies, we find that only in April SST-driven atmospheric circulation anomalies can effectively control the northward moisture-laden flow from the Gulf of Mexico, boosting low-level moisture flux convergence over the SGP. These strong large-scale connections are absent in other months because of the strong seasonality of the PNA and background moisture conditions.〈/p〉

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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