Recently emerging two-dimensional (2D) superconductors in atomically thin layers and at heterogeneous interfaces are attracting growing interest in condensed matter physics. Here, we report that an ion-gated zirconium nitride chloride surface, exhibiting a dome-shaped phase diagram with a maximum critical temperature of 14.8 kelvin, behaves as a superconductor persisting to the 2D limit. The superconducting thickness estimated from the upper critical fields is ≅ 1.8 nanometers, which is thinner than one unit-cell. The majority of the vortex phase diagram down to 2 kelvin is occupied by a metallic state with a finite resistance, owing to the quantum creep of vortices caused by extremely weak pinning and disorder. Our findings highlight the potential of electric-field–induced superconductivity, establishing a new platform for accessing quantum phases in clean 2D superconductors. Authors: Yu Saito, Yuichi Kasahara, Jianting Ye, Yoshihiro Iwasa, Tsutomu Nojima

In a Dirac semimetal, each Dirac node is resolved into two Weyl nodes with opposite “handedness” or chirality. The two chiral populations do not mix. However, in parallel electric and magnetic fields (E||B), charge is predicted to flow between the Weyl nodes, leading to negative magnetoresistance. This “axial” current is the chiral (Adler-Bell-Jackiw) anomaly investigated in quantum field theory. We report the observation of a large, negative longitudinal magnetoresistance in the Dirac semimetal Na3Bi. The negative magnetoresistance is acutely sensitive to deviations of the direction of B from E and is incompatible with conventional transport. By rotating E (as well as B), we show that it is consistent with the prediction of the chiral anomaly. Authors: Jun Xiong, Satya K. Kushwaha, Tian Liang, Jason W. Krizan, Max Hirschberger, Wudi Wang, R. J. Cava, N. P. Ong

We combined the high-energy resolution of conventional spin resonance (here ~10 nano–electron volts) with scanning tunneling microscopy to measure electron paramagnetic resonance of individual iron (Fe) atoms placed on a magnesium oxide film. We drove the spin resonance with an oscillating electric field (20 to 30 gigahertz) between tip and sample. The readout of the Fe atom’s quantum state was performed by spin-polarized detection of the atomic-scale tunneling magnetoresistance. We determine an energy relaxation time of T1 ≈ 100 microseconds and a phase-coherence time of T2 ≈ 210 nanoseconds. The spin resonance signals of different Fe atoms differ by much more than their resonance linewidth; in a traditional ensemble measurement, this difference would appear as inhomogeneous broadening. Authors: Susanne Baumann, William Paul, Taeyoung Choi, Christopher P. Lutz, Arzhang Ardavan, Andreas J. Heinrich

The ground state of quantum systems is characterized by zero-point motion. This motion, in the form of vacuum fluctuations, is generally considered to be an elusive phenomenon that manifests itself only indirectly. Here, we report direct detection of the vacuum fluctuations of electromagnetic radiation in free space. The ground-state electric-field variance is inversely proportional to the four-dimensional space-time volume, which we sampled electro-optically with tightly focused laser pulses lasting a few femtoseconds. Subcycle temporal readout and nonlinear coupling far from resonance provide signals from purely virtual photons without amplification. Our findings enable an extreme time-domain approach to quantum physics, with nondestructive access to the quantum state of light. Operating at multiterahertz frequencies, such techniques might also allow time-resolved studies of intrinsic fluctuations of elementary excitations in condensed matter. Authors: C. Riek, D. V. Seletskiy, A. S. Moskalenko, J. F. Schmidt, P. Krauspe, S. Eckart, S. Eggert, G. Burkard, A. Leitenstorfer

Internal stellar magnetic fields are inaccessible to direct observations, and little is known about their amplitude, geometry, and evolution. We demonstrate that strong magnetic fields in the cores of red giant stars can be identified with asteroseismology. The fields can manifest themselves via depressed dipole stellar oscillation modes, arising from a magnetic greenhouse effect that scatters and traps oscillation-mode energy within the core of the star. The Kepler satellite has observed a few dozen red giants with depressed dipole modes, which we interpret as stars with strongly magnetized cores. We find that field strengths larger than ~105 gauss may produce the observed depression, and in one case we infer a minimum core field strength of ≈107 gauss. Authors: Jim Fuller, Matteo Cantiello, Dennis Stello, Rafael A. Garcia, Lars Bildsten

Tissue patterns are dynamically maintained. Continuous formation of plant tissues during postembryonic growth requires asymmetric divisions and the specification of cell lineages. We show that the BIRDs and SCARECROW regulate lineage identity, positional signals, patterning, and formative divisions throughout Arabidopsis root growth. These transcription factors are postembryonic determinants of the ground tissue stem cells and their lineage. Upon further activation by the positional signal SHORT-ROOT (a mobile transcription factor), they direct asymmetric cell divisions and patterning of cell types. The BIRDs and SCARECROW with SHORT-ROOT organize tissue patterns at all formative steps during growth, ensuring developmental plasticity. Authors: Miguel A. Moreno-Risueno, Rosangela Sozzani, Galip Gürkan Yardımcı, Jalean J. Petricka, Teva Vernoux, Ikram Blilou, Jose Alonso, Cara M. Winter, Uwe Ohler, Ben Scheres, Philip N. Benfey

Alzheimer’s disease (AD) manifests with memory loss and spatial disorientation. AD pathology starts in the entorhinal cortex, making it likely that local neural correlates of spatial navigation, particularly grid cells, are impaired. Grid-cell–like representations in humans can be measured using functional magnetic resonance imaging. We found that young adults at genetic risk for AD (APOE-ε4 carriers) exhibit reduced grid-cell–like representations and altered navigational behavior in a virtual arena. Both changes were associated with impaired spatial memory performance. Reduced grid-cell–like representations were also related to increased hippocampal activity, potentially reflecting compensatory mechanisms that prevent overt spatial memory impairment in APOE-ε4 carriers. Our results provide evidence of behaviorally relevant entorhinal dysfunction in humans at genetic risk for AD, decades before potential disease onset. Authors: Lukas Kunz, Tobias Navarro Schröder, Hweeling Lee, Christian Montag, Bernd Lachmann, Rayna Sariyska, Martin Reuter, Rüdiger Stirnberg, Tony Stöcker, Paul Christian Messing-Floeter, Juergen Fell, Christian F. Doeller, Nikolai Axmacher

Methanogenic and methanotrophic archaea play important roles in the global flux of methane. Culture-independent approaches are providing deeper insight into the diversity and evolution of methane-metabolizing microorganisms, but, until now, no compelling evidence has existed for methane metabolism in archaea outside the phylum Euryarchaeota. We performed metagenomic sequencing of a deep aquifer, recovering two near-complete genomes belonging to the archaeal phylum Bathyarchaeota (formerly known as the Miscellaneous Crenarchaeotal Group). These genomes contain divergent homologs of the genes necessary for methane metabolism, including those that encode the methyl–coenzyme M reductase (MCR) complex. Additional non-euryarchaeotal MCR-encoding genes identified in a range of environments suggest that unrecognized archaeal lineages may also contribute to global methane cycling. These findings indicate that methane metabolism arose before the last common ancestor of the Euryarchaeota and Bathyarchaeota. Authors: Paul N. Evans, Donovan H. Parks, Grayson L. Chadwick, Steven J. Robbins, Victoria J. Orphan, Suzanne D. Golding, Gene W. Tyson

Pollen grains undergo dramatic changes in cellular water potential as they deliver the male germ line to female gametes, and it has been proposed that mechanosensitive ion channels may sense the resulting mechanical stress. Here, we identify and characterize MscS-like 8 (MSL8), a pollen-specific, membrane tension–gated ion channel required for pollen to survive the hypoosmotic shock of rehydration and for full male fertility. MSL8 negatively regulates pollen germination but is required for cellular integrity during germination and tube growth. MSL8 thus senses and responds to changes in membrane tension associated with pollen hydration and germination. These data further suggest that homologs of bacterial MscS have been repurposed in eukaryotes to function as mechanosensors in multiple developmental and environmental contexts. Authors: Eric S. Hamilton, Gregory S. Jensen, Grigory Maksaev, Andrew Katims, Ashley M. Sherp, Elizabeth S. Haswell

Calcineurin inhibitors, such as cyclosporine A and FK506, are used as immunosuppressant drugs, but their adverse effects on male reproductive function remain unclear. The testis expresses somatic calcineurin and a sperm-specific isoform that contains a catalytic subunit (PPP3CC) and a regulatory subunit (PPP3R2). We demonstrate herein that male mice lacking Ppp3cc or Ppp3r2 genes (knockout mice) are infertile, with reduced sperm motility owing to an inflexible midpiece. Treatment of mice with cyclosporine A or FK506 creates phenocopies of the sperm motility and morphological defects. These defects appear within 4 to 5 days of treatment, which indicates that sperm-specific calcineurin confers midpiece flexibility during epididymal transit. Male mouse fertility recovered a week after we discontinued treatment. Because human spermatozoa contain PPP3CC and PPP3R2 as a form of calcineurin, inhibition of this sperm-specific calcineurin may lead to the development of a reversible male contraceptive that would target spermatozoa in the epididymis. Authors: Haruhiko Miyata, Yuhkoh Satouh, Daisuke Mashiko, Masanaga Muto, Kaori Nozawa, Kogiku Shiba, Yoshitaka Fujihara, Ayako Isotani, Kazuo Inaba, Masahito Ikawa

The hemoprotein myoglobin is a model system for the study of protein dynamics. We used time-resolved serial femtosecond crystallography at an x-ray free-electron laser to resolve the ultrafast structural changes in the carbonmonoxy myoglobin complex upon photolysis of the Fe-CO bond. Structural changes appear throughout the protein within 500 femtoseconds, with the C, F, and H helices moving away from the heme cofactor and the E and A helices moving toward it. These collective movements are predicted by hybrid quantum mechanics/molecular mechanics simulations. Together with the observed oscillations of residues contacting the heme, our calculations support the prediction that an immediate collective response of the protein occurs upon ligand dissociation, as a result of heme vibrational modes coupling to global modes of the protein. Authors: Thomas R. M. Barends, Lutz Foucar, Albert Ardevol, Karol Nass, Andrew Aquila, Sabine Botha, R. Bruce Doak, Konstantin Falahati, Elisabeth Hartmann, Mario Hilpert, Marcel Heinz, Matthias C. Hoffmann, Jürgen Köfinger, Jason E. Koglin, Gabriela Kovacsova, Mengning Liang, Despina Milathianaki, Henrik T. Lemke, Jochen Reinstein, Christopher M. Roome, Robert L. Shoeman, Garth J. Williams, Irene Burghardt, Gerhard Hummer, Sébastien Boutet, Ilme Schlichting

Energy production by chloroplasts and mitochondria causes constant oxidative damage. A functioning photosynthetic cell requires quality-control mechanisms to turn over and degrade chloroplasts damaged by reactive oxygen species (ROS). Here, we generated a conditionally lethal Arabidopsis mutant that accumulated excess protoporphyrin IX in the chloroplast and produced singlet oxygen. Damaged chloroplasts were subsequently ubiquitinated and selectively degraded. A genetic screen identified the plant U-box 4 (PUB4) E3 ubiquitin ligase as being necessary for this process. pub4-6 mutants had defects in stress adaptation and longevity. Thus, we have identified a signal that leads to the targeted removal of ROS-overproducing chloroplasts. Authors: Jesse D. Woodson, Matthew S. Joens, Andrew B. Sinson, Jonathan Gilkerson, Patrice A. Salomé, Detlef Weigel, James A. Fitzpatrick, Joanne Chory

Autoantibodies target the RNA binding protein Ro60 in systemic lupus erythematosus (SLE) and Sjögren’s syndrome. However, it is unclear whether Ro60 and its associated RNAs contribute to disease pathogenesis. We catalogued the Ro60-associated RNAs in human cell lines and found that among other RNAs, Ro60 bound an RNA motif derived from endogenous Alu retroelements. Alu transcripts were induced by type I interferon and stimulated proinflammatory cytokine secretion by human peripheral blood cells. Ro60 deletion resulted in enhanced expression of Alu RNAs and interferon-regulated genes. Anti-Ro60–positive SLE immune complexes contained Alu RNAs, and Alu transcripts were up-regulated in SLE whole blood samples relative to controls. These findings establish a link among the lupus autoantigen Ro60, Alu retroelements, and type I interferon. Authors: T. Hung, G. A. Pratt, B. Sundararaman, M. J. Townsend, C. Chaivorapol, T. Bhangale, R. R. Graham, W. Ortmann, L. A. Criswell, G. W. Yeo, T. W. Behrens

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This issue of Science includes the program of the 2016 AAAS Annual Meeting. The theme of the AAAS Annual Meeting in Washington, DC, 11 to 15 February 2016, is Global Science Engagement.A PDF of the program as it appears in this issue is available here; for more information on the meeting (including registration forms and information on accommodations), please visit www.aaas.org/meetings/.

Author: Carol Lynn Curchoe

Background: Despite ongoing reductions in the cost of sequencing technologies, whole genome SNP genotype imputation is often used as an alternative for obtaining abundant SNP genotypes for genome wide association studies. Several existing genotype imputation methods can be efficient for this purpose, while achieving various levels of imputation accuracy. Recent empirical results have shown that the two-step imputation may improve accuracy by imputing the low density genotyped study animals to a medium density array first and then to the target density. We are interested in building a series of staircase arrays that lead the low density array to the high density array or even the whole genome, such that genotype imputation along these staircases can achieve the highest accuracy. Results: For genotype imputation from a lower density to a higher density, we first show how to select untyped SNPs to construct a medium density array. Subsequently, we determine for each selected SNP those untyped SNPs to be imputed in the add-one two-step imputation, and lastly how the clusters of imputed genotype are pieced together as the final imputation result. We design extensive empirical experiments using several hundred sequenced and genotyped animals to demonstrate that our novel two-step piecemeal imputation always achieves an improvement compared to the one-step imputation by the state-of-the-art methods Beagle and FImpute. Using the two-step piecemeal imputation, we present some preliminary success on whole genome SNP genotype imputation for genotyped animals via a series of staircase arrays. Conclusions: From a low SNP density to the whole genome, intermediate pseudo-arrays can be computationally constructed by selecting the most informative SNPs for untyped SNP genotype imputation. Such pseudo-array staircases are able to impute more accurately than the classic one-step imputation.

Background: The RCSB Protein Data Bank (PDB) provides public access to experimentally determined 3D-structures of biological macromolecules (proteins, peptides and nucleic acids). While various tools are available to explore the PDB, options to access the global structural diversity of the entire PDB and to perceive relationships between PDB structures remain very limited. Methods: A 136-dimensional atom pair 3D-fingerprint for proteins (3DP) counting categorized atom pairs at increasing through-space distances was designed to represent the molecular shape of PDB-entries. Nearest neighbor searches examples were reported exemplifying the ability of 3DP-similarity to identify closely related biomolecules from small peptides to enzyme and large multiprotein complexes such as virus particles. The principle component analysis was used to obtain the visualization of PDB in 3DP-space. Results: The 3DP property space groups proteins and protein assemblies according to their 3D-shape similarity, yet shows exquisite ability to distinguish between closely related structures. An interactive website called PDB-Explorer is presented featuring a color-coded interactive map of PDB in 3DP-space. Each pixel of the map contains one or more PDB-entries which are directly visualized as ribbon diagrams when the pixel is selected. The PDB-Explorer website allows performing 3DP-nearest neighbor searches of any PDB-entry or of any structure uploaded as protein-type PDB file. All functionalities on the website are implemented in JavaScript in a platform-independent manner and draw data from a server that is updated daily with the latest PDB additions, ensuring complete and up-to-date coverage. The essentially instantaneous 3DP-similarity search with the PDB-Explorer provides results comparable to those of much slower 3D-alignment algorithms, and automatically clusters proteins from the same superfamilies in tight groups. Conclusion: A chemical space classification of PDB based on molecular shape was obtained using a new atom-pair 3D-fingerprint for proteins and implemented in a web-based database exploration tool comprising an interactive color-coded map of the PDB chemical space and a nearest neighbor search tool. The PDB-Explorer website is freely available at www.cheminfo.org/pdbexplorer and represents an unprecedented opportunity to interactively visualize and explore the structural diversity of the PDB.ᅟGraphical abstractᅟMaps of PDB in 3DP-space color-coded by heavy atom count and shape.

Background: The entire collection of genetic information resides within the chromosomes, which themselves reside within almost every cell nucleus of eukaryotic organisms. Each individual chromosome is found to have its own preferred three-dimensional (3D) structure independent of the other chromosomes. The structure of each chromosome plays vital roles in controlling certain genome operations, including gene interaction and gene regulation. As a result, knowing the structure of chromosomes assists in the understanding of how the genome functions. Fortunately, the 3D structure of chromosomes proves possible to construct through computational methods via contact data recorded from the chromosome. We developed a unique computational approach based on optimization procedures known as adaptation, simulated annealing, and genetic algorithm to construct 3D models of human chromosomes, using chromosomal contact data. Results: Our models were evaluated using a percentage-based scoring function. Analysis of the scores of the final 3D models demonstrated their effective construction from our computational approach. Specifically, the models resulting from our approach yielded an average score of 80.41 %, with a high of 91 %, across models for all chromosomes of a normal human B-cell. Comparisons made with other methods affirmed the effectiveness of our strategy. Particularly, juxtaposition with models generated through the publicly available method Markov chain Monte Carlo 5C (MCMC5C) illustrated the outperformance of our approach, as seen through a higher average score for all chromosomes. Our methodology was further validated using two consistency checking techniques known as convergence testing and robustness checking, which both proved successful. Conclusions: The pursuit of constructing accurate 3D chromosomal structures is fueled by the benefits revealed by the findings as well as any possible future areas of study that arise. This motivation has led to the development of our computational methodology. The implementation of our approach proved effective in constructing 3D chromosome models and proved consistent with, and more effective than, some other methods thereby achieving our goal of creating a tool to help advance certain research efforts. The source code, test data, test results, and documentation of our method, Gen3D, are available at our sourceforge site at: http://sourceforge.net/projects/gen3d/.