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Updated: 8 years 17 weeks ago

[Editors' Choice] Does this taste fatty to you?

Thu, 08/27/2015 - 23:00
Author: Laura Schuhmacher
Categories: Journal Articles

[Editors' Choice] A cadherin gene enters MVP territory

Thu, 08/27/2015 - 23:00
Author: Paula A. Kiberstis
Categories: Journal Articles

[Editors' Choice] Deciphering function from single-cell data

Thu, 08/27/2015 - 23:00
Author: L. Bryan Ray
Categories: Journal Articles

[Review] Colloidal matter: Packing, geometry, and entropy

Thu, 08/27/2015 - 23:00
Colloidal particles with well-controlled shapes and interactions are an ideal experimental system for exploring how matter organizes itself. Like atoms and molecules, these particles form bulk phases such as liquids and crystals. But they are more than just crude analogs of atoms; they are a form of matter in their own right, with complex and interesting collective behavior not seen at the atomic scale. Their behavior is affected by geometrical or topological constraints, such as curved surfaces or the shapes of the particles. Because the interactions between the particles are often short-ranged, we can understand the effects of these constraints using geometrical concepts such as packing. The geometrical viewpoint gives us a window into how entropy affects not only the structure of matter, but also the dynamics of how it forms. Author: Vinothan N. Manoharan
Categories: Journal Articles

[Research Article] Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics

Thu, 08/27/2015 - 23:00
Super-resolution fluorescence microscopy is distinct among nanoscale imaging tools in its ability to image protein dynamics in living cells. Structured illumination microscopy (SIM) stands out in this regard because of its high speed and low illumination intensities, but typically offers only a twofold resolution gain. We extended the resolution of live-cell SIM through two approaches: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for approximately 20 to 40 frames. We applied these approaches to image dynamics near the plasma membrane of spatially resolved assemblies of clathrin and caveolin, Rab5a in early endosomes, and α-actinin, often in relationship to cortical actin. In addition, we examined mitochondria, actin, and the Golgi apparatus dynamics in three dimensions. Authors: Dong Li, Lin Shao, Bi-Chang Chen, Xi Zhang, Mingshu Zhang, Brian Moses, Daniel E. Milkie, Jordan R. Beach, John A. Hammer, Mithun Pasham, Tomas Kirchhausen, Michelle A. Baird, Michael W. Davidson, Pingyong Xu, Eric Betzig
Categories: Journal Articles

[Research Article] Estimating the reproducibility of psychological science

Thu, 08/27/2015 - 23:00
Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams. Author:
Categories: Journal Articles

[Report] Scalable T2 resistivity in a small single-component Fermi surface

Thu, 08/27/2015 - 23:00
Scattering among electrons generates a distinct contribution to electrical resistivity that follows a quadratic temperature (T) dependence. In strongly correlated electron systems, the prefactor A of this T2 resistivity scales with the magnitude of the electronic specific heat, γ. Here we show that one can change the magnitude of A by four orders of magnitude in metallic strontium titanate (SrTiO3) by tuning the concentration of the carriers and, consequently, the Fermi energy. The T2 behavior persists in the single-band dilute limit despite the absence of two known mechanisms for T2 behavior: distinct electron reservoirs and Umklapp processes. The results highlight the absence of a microscopic theory for momentum decay through electron-electron scattering in various Fermi liquids. Authors: Xiao Lin, Benoît Fauqué, Kamran Behnia
Categories: Journal Articles

[Report] Observation of chiral currents at the magnetic domain boundary of a topological insulator

Thu, 08/27/2015 - 23:00
A magnetic domain boundary on the surface of a three-dimensional topological insulator is predicted to host a chiral edge state, but direct demonstration is challenging. We used a scanning superconducting quantum interference device to show that current in a magnetized topological insulator heterostructure (EuS/Bi2Se3) flows at the edge when the Fermi level is gate-tuned to the surface band gap. We further induced micrometer-scale magnetic structures on the heterostructure and detected a chiral edge current at the magnetic domain boundary. The chirality of the current was determined by magnetization of the surrounding domain, and its magnitude by the local chemical potential rather than the applied current. Such magnetic structures provide a platform for detecting topological magnetoelectric effects and may enable progress in quantum information processing and spintronics. Authors: Y. H. Wang, J. R. Kirtley, F. Katmis, P. Jarillo-Herrero, J. S. Moodera, K. A. Moler
Categories: Journal Articles

[Report] Quantum squeezing of motion in a mechanical resonator

Thu, 08/27/2015 - 23:00
According to quantum mechanics, a harmonic oscillator can never be completely at rest. Even in the ground state, its position will always have fluctuations, called the zero-point motion. Although the zero-point fluctuations are unavoidable, they can be manipulated. Using microwave frequency radiation pressure, we have manipulated the thermal fluctuations of a micrometer-scale mechanical resonator to produce a stationary quadrature-squeezed state with a minimum variance of 0.80 times that of the ground state. We also performed phase-sensitive, back-action evading measurements of a thermal state squeezed to 1.09 times the zero-point level. Our results are relevant to the quantum engineering of states of matter at large length scales, the study of decoherence of large quantum systems, and for the realization of ultrasensitive sensing of force and motion. Authors: E. E. Wollman, C. U. Lei, A. J. Weinstein, J. Suh, A. Kronwald, F. Marquardt, A. A. Clerk, K. C. Schwab
Categories: Journal Articles

[Report] Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator

Thu, 08/27/2015 - 23:00
Amorphous nanoparticles (a-NPs) have physicochemical properties distinctly different from those of the corresponding bulk crystals; for example, their solubility is much higher. However, many materials have a high propensity to crystallize and are difficult to formulate in an amorphous structure without stabilizers. We fabricated a microfluidic nebulator that can produce amorphous NPs from a wide range of materials, even including pure table salt (NaCl). By using supersonic air flow, the nebulator produces drops that are so small that they dry before crystal nuclei can form. The small size of the resulting spray-dried a-NPs limits the probability of crystal nucleation in any given particle during storage. The kinetic stability of the a-NPs—on the order of months—is advantageous for hydrophobic drug molecules. Authors: Esther Amstad, Manesh Gopinadhan, Christian Holtze, Chinedum O. Osuji, Michael P. Brenner, Frans Spaepen, David A. Weitz
Categories: Journal Articles

[Report] Iron-catalyzed intermolecular [2+2] cycloadditions of unactivated alkenes

Thu, 08/27/2015 - 23:00
Cycloadditions, such as the [4+2] Diels-Alder reaction to form six-membered rings, are among the most powerful and widely used methods in synthetic chemistry. The analogous [2+2] alkene cycloaddition to synthesize cyclobutanes is kinetically accessible by photochemical methods, but the substrate scope and functional group tolerance are limited. Here, we report iron-catalyzed intermolecular [2+2] cycloaddition of unactivated alkenes and cross cycloaddition of alkenes and dienes as regio- and stereoselective routes to cyclobutanes. Through rational ligand design, development of this base metal–catalyzed method expands the chemical space accessible from abundant hydrocarbon feedstocks. Authors: Jordan M. Hoyt, Valerie A. Schmidt, Aaron M. Tondreau, Paul J. Chirik
Categories: Journal Articles

[Report] Irrationality in mate choice revealed by túngara frogs

Thu, 08/27/2015 - 23:00
Mate choice models derive from traditional microeconomic decision theory and assume that individuals maximize their Darwinian fitness by making economically rational decisions. Rational choices exhibit regularity, whereby the relative strength of preferences between options remains stable when additional options are presented. We tested female frogs with three simulated males who differed in relative call attractiveness and call rate. In binary choice tests, females’ preferences favored stimulus caller B over caller A; however, with the addition of an inferior “decoy” C, females reversed their preferences and chose A over B. These results show that the relative valuation of mates is not independent of inferior alternatives in the choice set and therefore cannot be explained with the rational choice models currently used in sexual selection theory. Authors: Amanda M. Lea, Michael J. Ryan
Categories: Journal Articles

[Report] Age-related mortality explains life history strategies of tropical and temperate songbirds

Thu, 08/27/2015 - 23:00
Life history theory attempts to explain why species differ in offspring number and quality, growth rate, and parental effort. I show that unappreciated interactions of these traits in response to age-related mortality risk challenge traditional perspectives and explain life history evolution in songbirds. Counter to a long-standing paradigm, tropical songbirds grow at similar overall rates to temperate species but grow wings relatively faster. These growth tactics are favored by predation risk, both in and after leaving the nest, and are facilitated by greater provisioning of individual offspring by parents. Increased provisioning of individual offspring depends on partitioning effort among fewer young because of constraints on effort from adult and nest mortality. These growth and provisioning responses to mortality risk finally explain the conundrum of small clutch sizes of tropical birds. Author: Thomas E. Martin
Categories: Journal Articles

[Report] Global assessment of arbuscular mycorrhizal fungus diversity reveals very low endemism

Thu, 08/27/2015 - 23:00
The global biogeography of microorganisms remains largely unknown, in contrast to the well-studied diversity patterns of macroorganisms. We used arbuscular mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to determine the global distribution of these plant symbionts. We found that AM fungal communities reflected local environmental conditions and the spatial distance between sites. However, despite AM fungi apparently possessing limited dispersal ability, we found 93% of taxa on multiple continents and 34% on all six continents surveyed. This contrasts with the high spatial turnover of other fungal taxa and with the endemism displayed by plants at the global scale. We suggest that the biogeography of AM fungi is driven by unexpectedly efficient dispersal, probably via both abiotic and biotic vectors, including humans. Authors: J. Davison, M. Moora, M. Öpik, A. Adholeya, L. Ainsaar, A. Bâ, S. Burla, A. G. Diedhiou, I. Hiiesalu, T. Jairus, N. C. Johnson, A. Kane, K. Koorem, M. Kochar, C. Ndiaye, M. Pärtel, Ü. Reier, Ü. Saks, R. Singh, M. Vasar, M. Zobel
Categories: Journal Articles

[Report] Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord

Thu, 08/27/2015 - 23:00
Glycerophospholipids, the structural components of cell membranes, have not been considered to be spatial cues for intercellular signaling because of their ubiquitous distribution. We identified lyso-phosphatidyl-β-d-glucoside (LysoPtdGlc), a hydrophilic glycerophospholipid, and demonstrated its role in modality-specific repulsive guidance of spinal cord sensory axons. LysoPtdGlc is locally synthesized and released by radial glia in a patterned spatial distribution to regulate the targeting of nociceptive but not proprioceptive central axon projections. Library screening identified the G protein–coupled receptor GPR55 as a high-affinity receptor for LysoPtdGlc, and GPR55 deletion or LysoPtdGlc loss of function in vivo caused the misallocation of nociceptive axons into proprioceptive zones. These findings show that LysoPtdGlc/GPR55 is a lipid-based signaling system in glia-neuron communication for neural development. Authors: Adam T. Guy, Yasuko Nagatsuka, Noriko Ooashi, Mariko Inoue, Asuka Nakata, Peter Greimel, Asuka Inoue, Takuji Nabetani, Akiho Murayama, Kunihiro Ohta, Yukishige Ito, Junken Aoki, Yoshio Hirabayashi, Hiroyuki Kamiguchi
Categories: Journal Articles

[Report] Base triplet stepping by the Rad51/RecA family of recombinases

Thu, 08/27/2015 - 23:00
DNA strand exchange plays a central role in genetic recombination across all kingdoms of life, but the physical basis for these reactions remains poorly defined. Using single-molecule imaging, we found that bacterial RecA and eukaryotic Rad51 and Dmc1 all stabilize strand exchange intermediates in precise three-nucleotide steps. Each step coincides with an energetic signature (0.3 kBT) that is conserved from bacteria to humans. Triplet recognition is strictly dependent on correct Watson-Crick pairing. Rad51, RecA, and Dmc1 can all step over mismatches, but only Dmc1 can stabilize mismatched triplets. This finding provides insight into why eukaryotes have evolved a meiosis-specific recombinase. We propose that canonical Watson-Crick base triplets serve as the fundamental unit of pairing interactions during DNA recombination. Authors: Ja Yil Lee, Tsuyoshi Terakawa, Zhi Qi, Justin B. Steinfeld, Sy Redding, YoungHo Kwon, William A. Gaines, Weixing Zhao, Patrick Sung, Eric C. Greene
Categories: Journal Articles

[Report] Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy

Thu, 08/27/2015 - 23:00
Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell–derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling. Authors: John T. Hinson, Anant Chopra, Navid Nafissi, William J. Polacheck, Craig C. Benson, Sandra Swist, Joshua Gorham, Luhan Yang, Sebastian Schafer, Calvin C. Sheng, Alireza Haghighi, Jason Homsy, Norbert Hubner, George Church, Stuart A. Cook, Wolfgang A. Linke, Christopher S. Chen, J. G. Seidman, Christine E. Seidman
Categories: Journal Articles

[Report] Emergent genetic oscillations in a synthetic microbial consortium

Thu, 08/27/2015 - 23:00
A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an “activator” strain and a “repressor” strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types. Authors: Ye Chen, Jae Kyoung Kim, Andrew J. Hirning, Krešimir Josić, Matthew R. Bennett
Categories: Journal Articles

[Report] The microbiota regulates type 2 immunity through RORγt+ T cells

Thu, 08/27/2015 - 23:00
Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (TH17) cells and regulatory T cells (Tregs) in the intestine. Here, we report that microbiota-induced Tregs express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to TH17 cells. In the absence of RORγt+ Tregs, TH2-driven defense against helminths is more efficient, whereas TH2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt+ Tregs and TH17 cells and acts as a key factor in balancing immune responses at mucosal surfaces. Authors: Caspar Ohnmacht, Joo-Hong Park, Sascha Cording, James B. Wing, Koji Atarashi, Yuuki Obata, Valérie Gaboriau-Routhiau, Rute Marques, Sophie Dulauroy, Maria Fedoseeva, Meinrad Busslinger, Nadine Cerf-Bensussan, Ivo G. Boneca, David Voehringer, Koji Hase, Kenya Honda, Shimon Sakaguchi, Gérard Eberl
Categories: Journal Articles

[Report] Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells

Thu, 08/27/2015 - 23:00
T regulatory cells that express the transcription factor Foxp3 (Foxp3+ Tregs) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct Treg population in the mouse colon, which constrains immuno-inflammatory responses. This induction—which we find to map to a broad, but specific, array of individual bacterial species—requires the transcription factor Rorγ, paradoxically, in that Rorγ is thought to antagonize FoxP3 and to promote T helper 17 (TH17) cell differentiation. Rorγ’s transcriptional footprint differs in colonic Tregs and TH17 cells and controls important effector molecules. Rorγ, and the Tregs that express it, contribute substantially to regulating colonic TH1/TH17 inflammation. Thus, the marked context-specificity of Rorγ results in very different outcomes even in closely related cell types. Authors: Esen Sefik, Naama Geva-Zatorsky, Sungwhan Oh, Liza Konnikova, David Zemmour, Abigail Manson McGuire, Dalia Burzyn, Adriana Ortiz-Lopez, Mercedes Lobera, Jianfei Yang, Shomir Ghosh, Ashlee Earl, Scott B. Snapper, Ray Jupp, Dennis Kasper, Diane Mathis, Christophe Benoist
Categories: Journal Articles