bluuebunny/crossref_metadata_2025 huggingface dataset:
Quizalofop interactions when mixed with clomazone and pendimethalin in acetyl coenzyme A carboxylase–inhibiting herbicide-resistant rice
Authors: Osterholt Matthew J. , Webster Eric P. , Blouin David C. , McKnight Benjamin M.
Published: July 2019

A study was conducted in 2017 and 2018 at the H. Rouse Caffey Rice Research Station near Crowley, LA, to evaluate quizalofop at 120 g ai ha−1 applied independently or in a mixture with clomazone, pendimethalin, clomazone plus pendimethalin, or a prepackaged mixture of clomazone plus pendimethalin when PVLO1 rice reached the two- to three-leaf stage. A second application of quizalofop at 120 g ha−1 was applied 21 d after the initial application. At 7 days after treatment (DAT), antagonism of quizalofop occurred when mixed with clomazone at 334 g ai ha−1, clomazone at 334 g ai ha−1 plus pendimethalin at 810 g ai ha−1, or a prepackaged mixture of clomazone plus pendimethalin at 334 plus 810 g ai ha−1, respectively, when applied to barnyardgrass. At 7 DAT, a neutral interaction occurred with a mixture of quizalofop plus pendimethalin at 810 g ha−1. These data indicate the antagonism of quizalofop was overcome at 14, 28, and 42 DAT with a neutral interaction for barnyardgrass control, 94% to 98%, with all herbicide mixtures evaluated. A neutral interaction occurred for CL-111, CLXL-745, and red rice control when treated with all the herbicide mixtures evaluated across all evaluation dates. Rice yield decreased when not treated with the initial quizalofop application.
The Decadal Variability of the Global Monsoon Links to the North Atlantic Climate Since 1851
Authors: Han Tao , Yu Kefu , Yan Hong , Yan Hongqiang , Tao Shichen , Zhang Huiling , Wang Shaopeng , Chen Tegu
Published: July 2019

To date, the decadal variability of the Global Monsoon (GM) has been mainly studied using instrumental data collected over the last 50 years, and further discussion has been hampered by the limited data length. Here, we present a coral δ18O record from the northern South China Sea, where the hydrology is related to the seasonal Intertropical Convergence Zone (ITCZ) migration, and we use this record to reconstruct the decadal migration of the ITCZ since 1851 A.D. Combining our record with a synthesis of monsoon records reveals an anti‐phase inter‐hemispheric variability of the GM over the last 150 years, indicating that the decadal‐scale hydrologic variability in the tropics is modulated by the meridional migration of the ITCZ. The plausible relationship observed between the decadal variability of the GM and the Atlantic Multidecadal Oscillation suggests that the decadal variability of tropical hydrological changes is likely linked to the climate perturbations in the North Atlantic.
Source Model for the Tsunami Inside Palu Bay Following the 2018 Palu Earthquake, Indonesia
Authors: Gusman Aditya Riadi , Supendi Pepen , Nugraha Andri Dian , Power William , Latief Hamzah , Sunendar Haris , Widiyantoro Sri , Daryono  , Wiyono Samsul Hadi , Hakim Aradea , Muhari Abdul , Wang Xiaoming , Burbidge David , Palgunadi Kadek , Hamling Ian , Daryono Mudrik Rahmawan
Published: July 2019

On 28 September 2018, a strike‐slip earthquake occurred in Palu, Indonesia, and was followed by a series of tsunami waves that devastated the coast of Palu Bay. The tsunami was recorded at the Pantoloan tide gauge station with a peak amplitude of ~2 m above the water level and struck at high tide. We use the Pantoloan tsunami waveform and synthetic aperture rada displacement data in a joint inversion to estimate the vertical displacement around the narrow bay. Our inversion result suggests that the middle of the bay was uplifted up to 0.8 m, while the other parts of the bay subsided by up to 1 m. However, this seafloor displacement model alone cannot fully explain the observed tsunami inundation. The observed tsunami inundation heights and extents could be reproduced by a tsunami inundation simulation with a source model that combined the estimated vertical displacement with multiple subaerial‐submarine landslides.
Magnetic Reconnection in a Quasi‐Parallel Shock: Two‐Dimensional Local Particle‐in‐Cell Simulation
Authors: Bessho N. , Chen L.‐J. , Wang S. , Hesse M. , Wilson L. B.
Published: July 2019

Magnetic reconnection in a quasi‐parallel bow shock is investigated with two‐dimensional local particle‐in‐cell simulations. In the shock transition and downstream regions, large amplitude magnetic fluctuations exist, and abundant current sheets form. In some current sheets, reconnection occurs, and ion‐scale and electron‐scale magnetic islands are generated. In electron‐scale island regions, only electron outflow jets are observed, producing a quadrupolar out‐of‐plane magnetic field pattern, while in ion‐scale islands, both ions and electrons are involved and energized in reconnection. Normalized reconnection rates are obtained to be between around 0.1 to 0.2, and particle acceleration signatures are seen in distribution functions.
Global Variability of Optical Backscattering by Non‐algal particles From a Biogeochemical‐Argo Data Set
Authors: Bellacicco M. , Cornec M. , Organelli E. , Brewin R. J. W. , Neukermans G. , Volpe G. , Barbieux M. , Poteau A. , Schmechtig C. , D'Ortenzio F. , Marullo S. , Claustre H. , Pitarch J.
Published: July 2019

Understanding spatial and temporal dynamics of non‐algal particles in open ocean is of the utmost importance to improve estimations of carbon export and sequestration. These particles covary with phytoplankton abundance but also accumulate independently of algal dynamics. The latter likely represents an important fraction of organic carbon, but it is largely overlooked. A possible way to study these particles is via their optical backscattering properties (bbp) and relationship with chlorophyll‐a (Chl). To this aim, we estimate the fraction of bbp associated with the non‐algal particle portion (
) that does not covary with Chl by using a global Biogeochemical‐Argo data set. We quantify the spatial, temporal, and vertical variability of
. In the northern productive areas,
is a small fraction of bbp and shows a clear seasonal cycle. In the Southern Ocean, bkbp is a major fraction of total bbp. In oligotrophic areas,
has a smooth annual cycle.
Atmospheric carbon monoxide oxidation is a widespread mechanism supporting microbial survival
Authors: Cordero Paul R F , Bayly Katherine , Man Leung Pok , Huang Cheng , Islam Zahra F , Schittenhelm Ralf B , King Gary M , Greening Chris
Published: July 2019

Carbon monoxide (CO) is a ubiquitous atmospheric trace gas produced by natural and anthropogenic sources. Some aerobic bacteria can oxidize atmospheric CO and, collectively, they account for the net loss of ~250 teragrams of CO from the atmosphere each year. However, the physiological role, genetic basis, and ecological distribution of this process remain incompletely resolved. In this work, we addressed these knowledge gaps through culture-based and culture-independent work. We confirmed through shotgun proteomic and transcriptional analysis that the genetically tractable aerobic soil actinobacterium Mycobacterium smegmatis upregulates expression of a form I molydenum–copper carbon monoxide dehydrogenase by 50-fold when exhausted for organic carbon substrates. Whole-cell biochemical assays in wild-type and mutant backgrounds confirmed that this organism aerobically respires CO, including at sub-atmospheric concentrations, using the enzyme. Contrary to current paradigms on CO oxidation, the enzyme did not support chemolithoautotrophic growth and was dispensable for CO detoxification. However, it significantly enhanced long-term survival, suggesting that atmospheric CO serves a supplemental energy source during organic carbon starvation. Phylogenetic analysis indicated that atmospheric CO oxidation is widespread and an ancestral trait of CO dehydrogenases. Homologous enzymes are encoded by 685 sequenced species of bacteria and archaea, including from seven dominant soil phyla, and we confirmed genes encoding this enzyme are abundant and expressed in terrestrial and marine environments. On this basis, we propose a new survival-centric model for the evolution of aerobic CO oxidation and conclude that, like atmospheric H2, atmospheric CO is a major energy source supporting persistence of aerobic heterotrophic bacteria in deprived or changeable environments.
Comparative characterization of human induced pluripotent stem cells (hiPSC) derived from patients with schizophrenia and autism
Authors: Grunwald Lena-Marie , Stock Ricarda , Haag Kathrina , Buckenmaier Sandra , Eberle Mark-Christian , Wildgruber Dirk , Storchak Helena , Kriebel Martin , Weißgraeber Stephanie , Mathew Lisha , Singh Yasmin , Loos Maarten , Li Ka Wan , Kraushaar Udo , Fallgatter Andreas J. , Volkmer Hansjürgen
Published: July 2019

Human induced pluripotent stem cells (hiPSC) provide an attractive tool to study disease mechanisms of neurodevelopmental disorders such as schizophrenia. A pertinent problem is the development of hiPSC-based assays to discriminate schizophrenia (SZ) from autism spectrum disorder (ASD) models. Healthy control individuals as well as patients with SZ and ASD were examined by a panel of diagnostic tests. Subsequently, skin biopsies were taken for the generation, differentiation, and testing of hiPSC-derived neurons from all individuals. SZ and ASD neurons share a reduced capacity for cortical differentiation as shown by quantitative analysis of the synaptic marker PSD95 and neurite outgrowth. By contrast, pattern analysis of calcium signals turned out to discriminate among healthy control, schizophrenia, and autism samples. Schizophrenia neurons displayed decreased peak frequency accompanied by increased peak areas, while autism neurons showed a slight decrease in peak amplitudes. For further analysis of the schizophrenia phenotype, transcriptome analyses revealed a clear discrimination among schizophrenia, autism, and healthy controls based on differentially expressed genes. However, considerable differences were still evident among schizophrenia patients under inspection. For one individual with schizophrenia, expression analysis revealed deregulation of genes associated with the major histocompatibility complex class II (MHC class II) presentation pathway. Interestingly, antipsychotic treatment of healthy control neurons also increased MHC class II expression. In conclusion, transcriptome analysis combined with pattern analysis of calcium signals appeared as a tool to discriminate between SZ and ASD phenotypes in vitro.
Nano-bio interactions: a neutrophil-centric view
Authors: Keshavan Sandeep , Calligari Paolo , Stella Lorenzo , Fusco Laura , Delogu Lucia Gemma , Fadeel Bengt
Published: July 2019

Neutrophils are key components of the innate arm of the immune system and represent the frontline of host defense against intruding pathogens. However, neutrophils can also cause damage to the host. Nanomaterials are being developed for a multitude of different purposes and these minute materials may find their way into the body through deliberate or inadvertent exposure; understanding nanomaterial interactions with the immune system is therefore of critical importance. However, whereas numerous studies have focused on macrophages, less attention is devoted to nanomaterial interactions with neutrophils, the most abundant leukocytes in the blood. We discuss the impact of engineered nanomaterials on neutrophils and how neutrophils, in turn, may digest certain carbon-based materials such as carbon nanotubes and graphene oxide. We also discuss the role of the corona of proteins adsorbed onto the surface of nanomaterials and whether nanomaterials are sensed as pathogens by cells of the immune system.
CircRNA_101505 sensitizes hepatocellular carcinoma cells to cisplatin by sponging miR-103 and promotes oxidored-nitro domain-containing protein 1 expression
Authors: Luo Yanwei , Fu Yunfeng , Huang Rong , Gao Meng , Liu Fengxia , Gui Rong , Nie Xinmin
Published: July 2019

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and a leading cause of cancer-related deaths worldwide. Emerging studies have shown that circular RNAs (circRNAs) are differentially expressed in HCC and play an important role in HCC pathogenesis and metastasis. However, the mechanism of circRNA in the chemoresistance of HCC remains unclear. In this study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We identified a novel circRNA circRNA_101505 that was decreased in cisplatin-resistant HCC tissues and cell lines, and associated with a poor survival outcome. Gain-of-function investigations showed that overexpression of circRNA_101505 suppressed cancer cell growth in vivo and in vitro, and enhanced cisplatin toxicity in HCC cells. Mechanistic studies found that circRNA_101505 could sensitize HCC cells to cisplatin by sponging miR-103, and thereby promoting oxidored-nitro domain-containing protein 1 (NOR1) expression. In conclusion, the significant inhibitory effects indicate circRNA_101505 to be a potential therapeutic target for HCC treatment. Our findings provide significant evidence to further elucidate the therapeutic use of circRNA in HCC.
Disturbance modifies payoffs in the explore-exploit trade-off
Authors: O’Farrell Shay , Sanchirico James N. , Spiegel Orr , Depalle Maxime , Haynie Alan C. , Murawski Steven A. , Perruso Larry , Strelcheck Andrew
Published: July 2019

Decision-making agents face a fundamental trade-off between exploring new opportunities with risky outcomes versus exploiting familiar options with more certain but potentially suboptimal outcomes. Although mediation of this trade-off is essential to adaptive behavior and has for decades been assumed to modulate performance, the empirical consequences of human exploratory strategies are unknown beyond laboratory or theoretical settings. Leveraging 540,000 vessel position records from 2494 commercial fishing trips along with corresponding revenues, here we find that during undisturbed conditions, there was no relationship between exploration and performance, contrary to theoretical predictions. However, during a major disturbance event which closed the most-utilized fishing grounds, explorers benefited significantly from less-impacted revenues and were also more likely to continue fishing. We conclude that in stochastic natural systems characterized by non-stationary rewards, the role of exploration in buffering against disturbance may be greater than previously thought in humans.
Microstructural control suppresses thermal activation of electron transport at room temperature in polymer transistors
Authors: Luzio Alessandro , Nübling Fritz , Martin Jaime , Fazzi Daniele , Selter Philipp , Gann Eliot , McNeill Christopher R. , Brinkmann Martin , Hansen Michael Ryan , Stingelin Natalie , Sommer Michael , Caironi Mario
Published: July 2019

Recent demonstrations of inverted thermal activation of charge mobility in polymer field-effect transistors have excited the interest in transport regimes not limited by thermal barriers. However, rationalization of the limiting factors to access such regimes is still lacking. An improved understanding in this area is critical for development of new materials, establishing processing guidelines, and broadening of the range of applications. Here we show that precise processing of a diketopyrrolopyrrole-tetrafluorobenzene-based electron transporting copolymer results in single crystal-like and voltage-independent mobility with vanishing activation energy above 280 K. Key factors are uniaxial chain alignment and thermal annealing at temperatures within the melting endotherm of films. Experimental and computational evidences converge toward a picture of electrons being delocalized within crystalline domains of increased size. Residual energy barriers introduced by disordered regions are bypassed in the direction of molecular alignment by a more efficient interconnection of the ordered domains following the annealing process.
Error-correcting dynamics in visual working memory
Authors: Panichello Matthew F. , DePasquale Brian , Pillow Jonathan W. , Buschman Timothy J.
Published: July 2019

Working memory is critical to cognition, decoupling behavior from the immediate world. Yet, it is imperfect; internal noise introduces errors into memory representations. Such errors have been shown to accumulate over time and increase with the number of items simultaneously held in working memory. Here, we show that discrete attractor dynamics mitigate the impact of noise on working memory. These dynamics pull memories towards a few stable representations in mnemonic space, inducing a bias in memory representations but reducing the effect of random diffusion. Model-based and model-free analyses of human and monkey behavior show that discrete attractor dynamics account for the distribution, bias, and precision of working memory reports. Furthermore, attractor dynamics are adaptive. They increase in strength as noise increases with memory load and experiments in humans show these dynamics adapt to the statistics of the environment, such that memories drift towards contextually-predicted values. Together, our results suggest attractor dynamics mitigate errors in working memory by counteracting noise and integrating contextual information into memories.
Realizing nearly-free-electron like conduction band in a molecular film through mediating intermolecular van der Waals interactions
Authors: Cui Xingxia , Han Ding , Guo Hongli , Zhou Linwei , Qiao Jingsi , Liu Qing , Cui Zhihao , Li Yafei , Lin Chungwei , Cao Limin , Ji Wei , Petek Hrvoje , Feng Min
Published: July 2019

Collective molecular physical properties can be enhanced from their intrinsic characteristics by templating at material interfaces. Here we report how a black phosphorous (BP) substrate concatenates a nearly-free-electron (NFE) like conduction band of a C60 monolayer. Scanning tunneling microscopy reveals the C60 lowest unoccupied molecular orbital (LUMO) band is strongly delocalized in two-dimensions, which is unprecedented for a molecular semiconductor. Experiment and theory show van der Waals forces between C60 and BP reduce the inter-C60 distance and cause mutual orientation, thereby optimizing the π-π wave function overlap and forming the NFE-like band. Electronic structure and carrier mobility calculations predict that the NFE band of C60 acquires an effective mass of 0.53–0.70 me (me is the mass of free electrons), and has carrier mobility of ~200 to 440 cm2V−1s−1. The substrate-mediated intermolecular van der Waals interactions provide a route to enhance charge delocalization in fullerenes and other organic semiconductors.
Hotspot motion caused the Hawaiian-Emperor Bend and LLSVPs are not fixed
Authors: Bono Richard K. , Tarduno John A. , Bunge Hans-Peter
Published: July 2019

Controversy surrounds the fixity of both hotspots and large low shear velocity provinces (LLSVPs). Paleomagnetism, plate-circuit analyses, sediment facies, geodynamic modeling, and geochemistry suggest motion of the Hawaiian plume in Earth’s mantle during formation of the Emperor seamounts. Herein, we report new paleomagnetic data from the Hawaiian chain (Midway Atoll) that indicate the Hawaiian plume arrived at its current latitude by 28 Ma. A dramatic decrease in distance between Hawaiian-Emperor and Louisville chain seamounts between 63 and 52 Ma confirms a high rate of southward Hawaiian hotspot drift (~47 mm yr−1), and excludes true polar wander as a relevant factor. These findings further indicate that the Hawaiian-Emperor chain bend morphology was caused by hotspot motion, not plate motion. Rapid plume motion was likely produced by ridge-plume interaction and deeper influence of the Pacific LLSVP. When compared to plate circuit predictions, the Midway data suggest ~13 mm yr−1 of African LLSVP motion since the Oligocene. LLSVP upwellings are not fixed, but also wander as they attract plumes and are shaped by deep mantle convection.
Mitofusins regulate lipid metabolism to mediate the development of lung fibrosis
Authors: Chung Kuei-Pin , Hsu Chia-Lang , Fan Li-Chao , Huang Ziling , Bhatia Divya , Chen Yi-Jung , Hisata Shu , Cho Soo Jung , Nakahira Kiichi , Imamura Mitsuru , Choi Mary E. , Yu Chong-Jen , Cloonan Suzanne M. , Choi Augustine M. K.
Published: July 2019

Accumulating evidence illustrates a fundamental role for mitochondria in lung alveolar type 2 epithelial cell (AEC2) dysfunction in the pathogenesis of idiopathic pulmonary fibrosis. However, the role of mitochondrial fusion in AEC2 function and lung fibrosis development remains unknown. Here we report that the absence of the mitochondrial fusion proteins mitofusin1 (MFN1) and mitofusin2 (MFN2) in murine AEC2 cells leads to morbidity and mortality associated with spontaneous lung fibrosis. We uncover a crucial role for MFN1 and MFN2 in the production of surfactant lipids with MFN1 and MFN2 regulating the synthesis of phospholipids and cholesterol in AEC2 cells. Loss of MFN1, MFN2 or inhibiting lipid synthesis via fatty acid synthase deficiency in AEC2 cells exacerbates bleomycin-induced lung fibrosis. We propose a tenet that mitochondrial fusion and lipid metabolism are tightly linked to regulate AEC2 cell injury and subsequent fibrotic remodeling in the lung.
The MTR4 helicase recruits nuclear adaptors of the human RNA exosome using distinct arch-interacting motifs
Authors: Lingaraju Mahesh , Johnsen Dennis , Schlundt Andreas , Langer Lukas M. , Basquin Jérôme , Sattler Michael , Heick Jensen Torben , Falk Sebastian , Conti Elena
Published: July 2019

The nuclear exosome and its essential co-factor, the RNA helicase MTR4, play crucial roles in several RNA degradation pathways. Besides unwinding RNA substrates for exosome-mediated degradation, MTR4 associates with RNA-binding proteins that function as adaptors in different RNA processing and decay pathways. Here, we identify and characterize the interactions of human MTR4 with a ribosome processing adaptor, NVL, and with ZCCHC8, an adaptor involved in the decay of small nuclear RNAs. We show that the unstructured regions of NVL and ZCCHC8 contain short linear motifs that bind the MTR4 arch domain in a mutually exclusive manner. These short sequences diverged from the arch-interacting motif (AIM) of yeast rRNA processing factors. Our results suggest that nuclear exosome adaptors have evolved canonical and non-canonical AIM sequences to target human MTR4 and demonstrate the versatility and specificity with which the MTR4 arch domain can recruit a repertoire of different RNA-binding proteins.
Meiosis I progression in spermatogenesis requires a type of testis-specific 20S core proteasome
Authors: Zhang Qianting , Ji Shu-Yan , Busayavalasa Kiran , Shao Jingchen , Yu Chao
Published: July 2019

Spermatogenesis is tightly regulated by ubiquitination and proteasomal degradation, especially during spermiogenesis, in which histones are replaced by protamine. However, the functions of proteasomal activity in meiosis I and II remain elusive. Here, we show that PSMA8-associated proteasomes are essential for the degradation of meiotic proteins and the progression of meiosis I during spermatogenesis. PSMA8 is expressed in spermatocytes from the pachytene stage, and assembles a type of testis-specific core proteasome. Deletion of PSMA8 decreases the abundance of proteasome in testes. Meiotic proteins that are normally degraded at late prophase I, such as RAD51 and RPA1, remain stable in PSMA8-deleted spermatocytes. Moreover, PSMA8-null spermatocytes exhibit delayed M-phase entry and are finally arrested at this stage, resulting in male infertility. However, PSMA8 is neither expressed nor required for female meiotic progression. Thus, meiosis I progression in spermatogenesis, particularly entry into and exit from M-phase, requires the proteasomal activity of PSMA8-associated proteasomes.
Long-term and persistent vocal plasticity in adult bats
Authors: Genzel Daria , Desai Janki , Paras Elana , Yartsev Michael M.
Published: July 2019

Bats exhibit a diverse and complex vocabulary of social communication calls some of which are believed to be learned during development. This ability to produce learned, species-specific vocalizations – a rare trait in the animal kingdom – requires a high-degree of vocal plasticity. Bats live extremely long lives in highly complex and dynamic social environments, which suggests that they might also retain a high degree of vocal plasticity in adulthood, much as humans do. Here, we report persistent vocal plasticity in adult bats (Rousettus aegyptiacus) following exposure to broad-band, acoustic perturbation. Our results show that adult bats can not only modify distinct parameters of their vocalizations, but that these changes persist even after noise cessation – in some cases lasting several weeks or months. Combined, these findings underscore the potential importance of bats as a model organism for studies of vocal plasticity, including in adulthood.
High performance III-V photoelectrodes for solar water splitting via synergistically tailored structure and stoichiometry
Authors: Lim Haneol , Young James L. , Geisz John F. , Friedman Daniel J. , Deutsch Todd G. , Yoon Jongseung
Published: July 2019

Catalytic interface of semiconductor photoelectrodes is critical for high-performance photoelectrochemical solar water splitting because of its multiple roles in light absorption, electrocatalysis, and corrosion protection. Nevertheless, simultaneously optimizing each of these processes represents a materials conundrum owing to conflicting requirements of materials attributes at the electrode surface. Here we show an approach that can circumvent these challenges by collaboratively exploiting corrosion-resistant surface stoichiometry and structurally-tailored reactive interface. Nanoporous, density-graded surface of ‘black’ gallium indium phosphide (GaInP2), when combined with ammonium-sulfide-based surface passivation, effectively reduces reflection and surface recombination of photogenerated carriers for high efficiency photocatalysis in the hydrogen evolution half-reaction, but also augments electrochemical durability with lifetime over 124 h via strongly suppressed kinetics of corrosion. Such synergistic control of stoichiometry and structure at the reactive interface provides a practical pathway to concurrently enhance efficiency and durability of semiconductor photoelectrodes without solely relying on the development of new protective materials.
Time-resolved NMR monitoring of tRNA maturation
Authors: Barraud Pierre , Gato Alexandre , Heiss Matthias , Catala Marjorie , Kellner Stefanie , Tisné Carine
Published: July 2019

Although the biological importance of post-transcriptional RNA modifications in gene expression is widely appreciated, methods to directly detect their introduction during RNA biosynthesis are rare and do not easily provide information on the temporal nature of events. Here, we introduce the application of NMR spectroscopy to observe the maturation of tRNAs in cell extracts. By following the maturation of yeast tRNAPhe with time-resolved NMR measurements, we show that modifications are introduced in a defined sequential order, and that the chronology is controlled by cross-talk between modification events. In particular, we show that a strong hierarchy controls the introduction of the T54, Ψ55 and m1A58 modifications in the T-arm, and we demonstrate that the modification circuits identified in yeast extract with NMR also impact the tRNA modification process in living cells. The NMR-based methodology presented here could be adapted to investigate different aspects of tRNA maturation and RNA modifications in general.
Activity-controlled annealing of colloidal monolayers
Authors: Ramananarivo Sophie , Ducrot Etienne , Palacci Jeremie
Published: July 2019

Molecular motors are essential to the living, generating fluctuations that boost transport and assist assembly. Active colloids, that consume energy to move, hold similar potential for man-made materials controlled by forces generated from within. Yet, their use as a powerhouse in materials science lacks. Here we show a massive acceleration of the annealing of a monolayer of passive beads by moderate addition of self-propelled microparticles. We rationalize our observations with a model of collisions that drive active fluctuations and activate the annealing. The experiment is quantitatively compared with Brownian dynamic simulations that further unveil a dynamical transition in the mechanism of annealing. Active dopants travel uniformly in the system or co-localize at the grain boundaries as a result of the persistence of their motion. Our findings uncover the potential of internal activity to control materials and lay the groundwork for the rise of materials science beyond equilibrium.
Correlating dynamic strain and photoluminescence of solid-state defects with stroboscopic x-ray diffraction microscopy
Authors: Whiteley S. J. , Heremans F. J. , Wolfowicz G. , Awschalom D. D. , Holt M. V.
Published: July 2019

Control of local lattice perturbations near optically-active defects in semiconductors is a key step to harnessing the potential of solid-state qubits for quantum information science and nanoscale sensing. We report the development of a stroboscopic scanning X-ray diffraction microscopy approach for real-space imaging of dynamic strain used in correlation with microscopic photoluminescence measurements. We demonstrate this technique in 4H-SiC, which hosts long-lifetime room temperature vacancy spin defects. Using nano-focused X-ray photon pulses synchronized to a surface acoustic wave launcher, we achieve an effective time resolution of ~100 ps at a 25 nm spatial resolution to map micro-radian dynamic lattice curvatures. The acoustically induced lattice distortions near an engineered scattering structure are correlated with enhanced photoluminescence responses of optically-active SiC quantum defects driven by local piezoelectric effects. These results demonstrate a unique route for directly imaging local strain in nanomechanical structures and quantifying dynamic structure-function relationships in materials under realistic operating conditions.
Development of bifunctional organocatalysts and application to asymmetric total synthesis of naucleofficine I and II
Authors: Yuan Yong-Hai , Han Xue , Zhu Fu-Ping , Tian Jin-Miao , Zhang Fu-Min , Zhang Xiao-Ming , Tu Yong-Qiang , Wang Shao-Hua , Guo Xiang
Published: July 2019

The proline-type organocatalysts has been efficiently employed to catalyze a wide range of asymmetric transformations; however, there are still many synthetically useful and challenging transformations that remain unachievable in an asymmetric fashion. Herein, a chiral bifunctional organocatalyst with a spirocyclic pyrrolidine backbone-derived containing fluoro-alkyl and aryl sulfonamide functionalities, are designed, prepared, and examined in the asymmetric Mannich/acylation/Wittig reaction sequence of 3,4-dihydro-β-carboline with acetaldehyde, acyl halides, and Wittig reagents. As a result, the spirocyclic pyrrolidine trifluoromethanesulfonamide catalyst can facilitate this versatile sequence as demonstrated by 18 examples displaying excellent enantioselectivity (up to 94% ee), as well as moderate to good yields (up to 54% over 3 steps). As a practical application, the asymmetric total synthesis of naucleofficine I (1a) and II (1b) in ten steps have been accomplished.
Author Correction: Reprogramming of regulatory network using expression uncovers sex-specific gene regulation in Drosophila
Authors: Wang Yijie , Cho Dong-Yeon , Lee Hangnoh , Fear Justin , Oliver Brian , Przytycka Teresa M.
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper
Genome of the Komodo dragon reveals adaptations in the cardiovascular and chemosensory systems of monitor lizards
Authors: Lind Abigail L. , Lai Yvonne Y. Y. , Mostovoy Yulia , Holloway Alisha K. , Iannucci Alessio , Mak Angel C. Y. , Fondi Marco , Orlandini Valerio , Eckalbar Walter L. , Milan Massimo , Rovatsos Michail , Kichigin Ilya G. , Makunin Alex I. , Johnson Pokorná Martina , Altmanová Marie , Trifonov Vladimir A. , Schijlen Elio , Kratochvíl Lukáš , Fani Renato , Velenský Petr , Rehák Ivan , Patarnello Tomaso , Jessop Tim S. , Hicks James W. , Ryder Oliver A. , Mendelson Joseph R. , Ciofi Claudio , Kwok Pui-Yan , Pollard Katherine S. , Bruneau Benoit G.
Published: July 2019

Monitor lizards are unique among ectothermic reptiles in that they have high aerobic capacity and distinctive cardiovascular physiology resembling that of endothermic mammals. Here, we sequence the genome of the Komodo dragon Varanus komodoensis, the largest extant monitor lizard, and generate a high-resolution de novo chromosome-assigned genome assembly for V. komodoensis using a hybrid approach of long-range sequencing and single-molecule optical mapping. Comparing the genome of V. komodoensis with those of related species, we find evidence of positive selection in pathways related to energy metabolism, cardiovascular homoeostasis, and haemostasis. We also show species-specific expansions of a chemoreceptor gene family related to pheromone and kairomone sensing in V. komodoensis and other lizard lineages. Together, these evolutionary signatures of adaptation reveal the genetic underpinnings of the unique Komodo dragon sensory and cardiovascular systems, and suggest that selective pressure altered haemostasis genes to help Komodo dragons evade the anticoagulant effects of their own saliva. The Komodo dragon genome is an important resource for understanding the biology of monitor lizards and reptiles worldwide.
Easy-to-use clinical tool for survival estimation in Ewing sarcoma at diagnosis and after surgery
Authors: Bosma S. E. , Lancia C. , Rueten-Budde A. J. , Ranft A. , Gelderblom H. , Fiocco M. , van de Sande M. A. J. , Dijkstra P. D. S. , Dirksen U.
Published: July 2019

Accurate survival estimations in Ewing sarcoma are necessary to develop risk- and response adaptive treatment strategies allowing for early decision-making. We aim to develop an easy-to-use survival estimation tool from diagnosis and surgery. A retrospective study of 1314 Ewing sarcoma patients was performed. Associations between prognostic variables at diagnosis/surgery and overall survival (OS), were investigated using Kaplan-Meier and multivariate Cox models. Predictive accuracy was evaluated by cross-validation and Harrell C-statistics. Median follow-up was 7.9 years (95%CI 7.6–8.3). Independent prognostic factors at diagnosis were age, volume, primary tumor localization and disease extent. 5 risk categories (A-E) were identified with 5-year OS of 88% (86–94), 69% (64–74), 57% (50–64), 51% (42–60) and 28% (22–34) respectively. Harrell C-statistic was 0.70. Independent prognostic factors from surgery were age, volume, disease extent and histological response. In categories A-B, 5y OS increased to 92% (87–97) and 79% (71–87) respectively for 100% necrosis and decreased to 76% (67–85) and 62% (55–69) respectively for <100% necrosis. In categories C-E, 5y OS increased to 65% (55–75), 65% (52–78) and 52% (38–66) respectively for ≥90% necrosis and decreased to 38% (22–54), 11% (0–26) and 7% (0–19) respectively for <90% necrosis. We present an easy-to-use survival estimation tool from diagnosis in Ewing sarcoma based on age, volume, primary tumor localization and disease extent. Histological response is a strong additional prognostic factor for OS.
Drought-induced soil microbial amino acid and polysaccharide change and their implications for C-N cycles in a climate change world
Authors: Kakumanu Madhavi L. , Ma Li , Williams Mark A.
Published: July 2019

High microbial carbon (MBC) demand, a proxy for energy demand (cost), during soil microbial response to stressors such as drought are a major gap in understanding global biogeochemical cycling of carbon (C) and nitrogen (N). The dynamics of two dominant microbial pools (amino acids; AA and exopolymeric substances; EPS) in soils exposed to drying and C and N amendment to mimic both low and high nutrient soil habitats were examined. It was hypothesized that dynamics of EPS and AA (osmolytes) would be greater when soil drying was preceded by a pulse of bioavailable C and N. Drying reduced AA content, even as overall soil MBC increased (~35%). The increase in absolute amounts and mol% of certain AA (eg: Taurine, glutamine, tyrosine, phenylalanine) in the driest treatment (−10 MPa) were similar in both soils regardless of amendment suggesting a common mechanism underlying the energy intensive acclimation across soils. MBC and EPS, both increased ~1.5X and ~3X due to drying and especially drying associated with amendment. Overall major pools of C and N based microbial metabolites are dynamic to drying (drought), and thus have implications for earth’s biogeochemical fluxes of C and N, perhaps costing 4–7% of forest fixed photosynthetic C input during a single drying (drought) period.
In vivo evaluation of the effect of lithium on peripheral circadian clocks by real-time monitoring of clock gene expression in near-freely moving mice
Authors: Sawai Yuka , Okamoto Takezo , Muranaka Yugo , Nakamura Rino , Matsumura Ritsuko , Node Koichi , Akashi Makoto
Published: July 2019

Lithium has been used as a mood stabilizer to treat human bipolar disorders for over half a century. Several studies have suggested the possibility that the efficacy of lithium treatment results in part from the amelioration of circadian dysfunction. However, the effect of lithium on clock gene expression has not yet been investigated in vivo because continuous measurement of gene expression in organs with high time resolution over a period of several days is difficult. To resolve this issue, we attached a small photo multiplier tube (PMT) tightly to the body surface of transgenic mice carrying a reporter gene such that the photon input window faced target organs such as the liver and kidney and succeeded in long-term continuous measurement of circadian gene expression in semi-freely moving mice over periods of several weeks. Using this simple method, we clearly showed that lithium causes circadian period elongation in peripheral clock gene expression rhythms in vivo. Further development of our detection system to maturity will aid a wide range of research fields in medicine and biology.
Prognostic Performance of Kidney Volume Measurement for Polycystic Kidney Disease: A Comparative Study of Ellipsoid vs. Manual Segmentation
Authors: Shi Beili , Akbari Pedram , Pourafkari Marina , Iliuta Ioan-Andrei , Guiard Elsa , Quist Crystal F. , Song Xuewen , Hillier David , Khalili Korosh , Pei York
Published: July 2019

Total kidney volume (TKV) is a validated prognostic biomarker for risk assessment in autosomal dominant polycystic kidney disease (ADPKD). TKV by manual segmentation (MS) is the “gold standard” but is time-consuming and requires expertise. The purpose of this study was to compare TKV-based prognostic performance by ellipsoid (EL) vs. MS in a large cohort of patients. Cross-sectional study of 308 patients seen at a tertiary referral center; all had a standardized MRI with typical imaging of ADPKD. An experienced radiologist blinded to patient clinical results performed all TKV measurements by EL and MS. We assessed the agreement of TKV measurements by intraclass correlation(ICC) and Bland-Altman plot and also how the disagreement of the two methods impact the prognostic performance of the Mayo Clinic Imaging Classification (MCIC). We found a high ICC of TKV measurements (0.991, p < 0.001) between EL vs. MS; however, 5.5% of the cases displayed disagreement of TKV measurements >20%. We also found a high degree of agreement of the individual MCIC risk classes (i.e. 1A to 1E) with a Cohen’s weighted-kappa of 0.89; but 42 cases (13.6%) were misclassified by EL with no misclassification spanning more than one risk class. The sensitivity and specificity of EL in distinguishing low-risk (1A-B) from high-risk (1C-E) MCIC prognostic grouping were 96.6% and 96.1%, respectively. Overall, we found an excellent agreement of TKV-based risk assessment between EL and MS. However, caution is warranted for patients with MCIC 1B and 1C, as misclassification can have therapeutic consequence.
Probing conformational changes of monomeric transthyretin with second derivative fluorescence
Authors: Jazaj Denisa , Ghadami Seyyed Abolghasem , Bemporad Francesco , Chiti Fabrizio
Published: July 2019

We have studied the intrinsic fluorescence spectra of a monomeric variant of human transthyretin (M-TTR), a protein involved in the transport of the thyroid hormone and retinol and associated with various forms of amyloidosis, extending our analysis to the second order derivative of the spectra. This procedure allowed to identify three peaks readily assigned to Trp41, as the three peaks were also visible in a mutant lacking the other tryptophan (Trp79) and had similar FRET efficiency values with an acceptor molecule positioned at position 10. The wavelength values of the three peaks and their susceptibility to acrylamide quenching revealed that the three corresponding conformers experience different solvent-exposure, polarity of the environment and flexibility. We could monitor the three peaks individually in urea-unfolding and pH-unfolding curves. This revealed changes in the distribution of the corresponding conformers, indicating conformational changes and alterations of the dynamics of the microenvironment that surrounds the associated tryptophan residue in such transitions, but also native-like conformers of such residues in unfolded states. We also found that the amyloidogenic state adopted by M-TTR at mildly low pH has a structural and dynamical microenvironment surrounding Trp41 indistinguishable from that of the fully folded and soluble state at neutral pH.
Regulation of Cardiac Mast Cell Maturation and Function by the Neurokinin-1 Receptor in the Fibrotic Heart
Authors: Widiapradja Alexander , Manteufel Edward J. , Dehlin Heather M. , Pena James , Goldspink Paul H. , Sharma Amit , Kolb Lauren L. , Imig John D. , Janicki Joseph S. , Lu Bao , Levick Scott P.
Published: July 2019

Cardiac fibrosis is an underlying cause of diastolic dysfunction, contributing to heart failure. Substance P (SP) activation of the neurokinin-1 receptor (NK-1R) contributes to cardiac fibrosis in hypertension. However, based on in vitro experiments, this does not appear to be via direct activation of cardiac fibroblasts. While numerous cells could mediate the fibrotic effects of SP, herein, we investigate mast cells (MC) as a mechanism mediating the fibrotic actions of SP, since MCs are known to play a role in cardiac fibrosis and respond to SP. Spontaneously hypertensive rats (SHR) were treated with the NK-1R antagonist L732138 (5 mg/kg/d) from 8 to 12 weeks of age. L732138 prevented increased MC maturation of resident immature MCs. NK-1R blockade also prevented increased cardiac MC maturation in angiotensin II-infused mice. MC-deficient mice were used to test the importance of MC NK-1Rs to MC activation. MC-deficient mice administered angiotensin II did not develop fibrosis; MC-deficient mice reconstituted with MCs did develop fibrosis. MC-deficient mice reconstituted with MCs lacking the NK-1R also developed fibrosis, indicating that NK-1Rs are not required for MC activation in this setting. In conclusion, the NK-1R causes MC maturation, however, other stimuli are required to activate MCs to cause fibrosis.
Golden Mutagenesis: An efficient multi-site-saturation mutagenesis approach by Golden Gate cloning with automated primer design
Authors: Püllmann Pascal , Ulpinnis Chris , Marillonnet Sylvestre , Gruetzner Ramona , Neumann Steffen , Weissenborn Martin J.
Published: July 2019

Site-directed methods for the generation of genetic diversity are essential tools in the field of directed enzyme evolution. The Golden Gate cloning technique has been proven to be an efficient tool for a variety of cloning setups. The utilization of restriction enzymes which cut outside of their recognition domain allows the assembly of multiple gene fragments obtained by PCR amplification without altering the open reading frame of the reconstituted gene. We have developed a protocol, termed Golden Mutagenesis that allows the rapid, straightforward, reliable and inexpensive construction of mutagenesis libraries. One to five amino acid positions within a coding sequence could be altered simultaneously using a protocol which can be performed within one day. To facilitate the implementation of this technique, a software library and web application for automated primer design and for the graphical evaluation of the randomization success based on the sequencing results was developed. This allows facile primer design and application of Golden Mutagenesis also for laboratories, which are not specialized in molecular biology.
Automated detection and classification of early AMD biomarkers using deep learning
Authors: Saha Sajib , Nassisi Marco , Wang Mo , Lindenberg Sophiana , kanagasingam Yogi , Sadda Srinivas , Hu Zhihong Jewel
Published: July 2019

Age-related macular degeneration (AMD) affects millions of people and is a leading cause of blindness throughout the world. Ideally, affected individuals would be identified at an early stage before late sequelae such as outer retinal atrophy or exudative neovascular membranes develop, which could produce irreversible visual loss. Early identification could allow patients to be staged and appropriate monitoring intervals to be established. Accurate staging of earlier AMD stages could also facilitate the development of new preventative therapeutics. However, accurate and precise staging of AMD, particularly using newer optical coherence tomography (OCT)-based biomarkers may be time-intensive and requires expert training which may not feasible in many circumstances, particularly in screening settings. In this work we develop deep learning method for automated detection and classification of early AMD OCT biomarker. Deep convolution neural networks (CNN) were explicitly trained for performing automated detection and classification of hyperreflective foci, hyporeflective foci within the drusen, and subretinal drusenoid deposits from OCT B-scans. Numerous experiments were conducted to evaluate the performance of several state-of-the-art CNNs and different transfer learning protocols on an image dataset containing approximately 20000 OCT B-scans from 153 patients. An overall accuracy of 87% for identifying the presence of early AMD biomarkers was achieved.
High concentration and yield production of mannose from açaí (Euterpe oleracea Mart.) seeds via mannanase-catalyzed hydrolysis
Authors: Monteiro Alvaro Ferreira , Miguez Ingrid Santos , Silva João Pedro R. Barros , Silva Ayla Sant’Ana da
Published: July 2019

The açaí seed corresponds to approximately 85% of the fruit’s weight and represents ~1.1 million metric tons of residue yearly accumulated in the Amazon region, resulting in an acute environmental and urban problem. To extract the highest value from this residue, this study aimed to evaluate its chemical composition to determine the appropriate applications and to develop conversion methods. First, mannan was confirmed as the major component of mature seeds, corresponding to 80% of the seed’s total carbohydrates and about 50% of its dry weight. To convert this high mannan content into mannose, a sequential process of dilute-acid and enzymatic hydrolysis was evaluated. Among different dilute-H2SO4hydrolysis conditions, 3%-acid for 60-min at 121 °C resulted in a 30% mannan hydrolysis yield and 41.7 g/L of mannose. Because ~70% mannan remained in the seed, a mannanase-catalyzed hydrolysis was sequentially performed with 2–20% seed concentration, reaching 146.3 g/L of mannose and a 96.8% yield with 20% solids. As far as we know, this is the highest reported concentration of mannose produced from a residue. Thus, this work provides fundamental data for achieving high concentrations and yields of mannose from açaí seeds, which could add commercial value to the seeds and improve the whole açaí productive chain.