bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Hoogsteen dynamics on DNA recognition
Authors: Xu Yu , McSally James , Andricioaei Ioan , Al-Hashimi Hashim M.
Published: April 2018

In naked duplex DNA, G–C and A–T Watson-Crick base pairs exist in dynamic equilibrium with their Hoogsteen counterparts. Here, we used nuclear magnetic resonance (NMR) relaxation dispersion and molecular dynamics (MD) simulations to examine how Watson-Crick/Hoogsteen dynamics are modulated upon recognition of duplex DNA by the bisintercalator echinomycin and monointercalator actinomycin D. In both cases, DNA recognition results in the quenching of Hoogsteen dynamics at base pairs involved in intermolecular base-specific hydrogen bonds. In the case of echinomycin, the Hoogsteen population increased 10-fold for base pairs flanking the chromophore most likely due to intermolecular stacking interactions, whereas actinomycin D minimally affected Hoogsteen dynamics at other sites. Modulation of Hoogsteen dynamics at binding interfaces may be a general phenomenon with important implications for DNA–ligand and DNA–protein recognition.
Probing the strongly driven spin-boson model in a superconducting quantum circuit
Authors: Magazzù L. , Forn-Díaz P. , Belyansky R. , Orgiazzi J.-L. , Yurtalan M. A. , Otto M. R. , Lupascu A. , Wilson C. M. , Grifoni M.
Published: April 2018

Quantum two-level systems interacting with the surroundings are ubiquitous in nature. The interaction suppresses quantum coherence and forces the system towards a steady state. Such dissipative processes are captured by the paradigmatic spin-boson model, describing a two-state particle, the “spin”, interacting with an environment formed by harmonic oscillators. A fundamental question to date is to what extent intense coherent driving impacts a strongly dissipative system. Here we investigate experimentally and theoretically a superconducting qubit strongly coupled to an electromagnetic environment and subjected to a coherent drive. This setup realizes the driven Ohmic spin-boson model. We show that the drive reinforces environmental suppression of quantum coherence, and that a coherent-to-incoherent transition can be achieved by tuning the drive amplitude. An out-of-equilibrium detailed balance relation is demonstrated. These results advance fundamental understanding of open quantum systems and bear potential for the design of entangled light-matter states.
Ultrastable metallic glasses formed on cold substrates
Authors: Luo P. , Cao C. R. , Zhu F. , Lv Y. M. , Liu Y. H. , Wen P. , Bai H. Y. , Vaughan G. , di Michiel M. , Ruta B. , Wang W. H.
Published: April 2018

Vitrification from physical vapor deposition is known to be an efficient way for tuning the kinetic and thermodynamic stability of glasses and significantly improve their properties. There is a general consensus that preparing stable glasses requires the use of high substrate temperatures close to the glass transition one, Tg. Here, we challenge this empirical rule by showing the formation of Zr-based ultrastable metallic glasses (MGs) at room temperature, i.e., with a substrate temperature of only 0.43Tg. By carefully controlling the deposition rate, we can improve the stability of the obtained glasses to higher values. In contrast to conventional quenched glasses, the ultrastable MGs exhibit a large increase of Tg of ∼60 K, stronger resistance against crystallization, and more homogeneous structure with less order at longer distances. Our study circumvents the limitation of substrate temperature for developing ultrastable glasses, and provides deeper insight into glasses stability and their surface dynamics.
Directed evolution of broadly crossreactive chemokine-blocking antibodies efficacious in arthritis
Authors: Angelini Alessandro , Miyabe Yoshishige , Newsted Daniel , Kwan Byron H. , Miyabe Chie , Kelly Ryan L. , Jamy Misha N. , Luster Andrew D. , Wittrup K. Dane
Published: April 2018

Chemokine receptors typically have multiple ligands. Consequently, treatment with a blocking antibody against a single chemokine is expected to be insufficient for efficacy. Here we show single-chain antibodies can be engineered for broad crossreactivity toward multiple human and mouse proinflammatory ELR+CXC chemokines. The engineered molecules recognize functional epitopes of ELR+CXC chemokines and inhibit neutrophil activation ex vivo. Furthermore, an albumin fusion of the most crossreactive single-chain antibody prevents and reverses inflammation in the K/BxN mouse model of arthritis. Thus, we report an approach for the molecular evolution and selection of broadly crossreactive antibodies towards a family of structurally related, yet sequence-diverse protein targets, with general implications for the development of novel therapeutics.
Generation and characterization of ultrathin free-flowing liquid sheets
Authors: Koralek Jake D. , Kim Jongjin B. , Brůža Petr , Curry Chandra B. , Chen Zhijiang , Bechtel Hans A. , Cordones Amy A. , Sperling Philipp , Toleikis Sven , Kern Jan F. , Moeller Stefan P. , Glenzer Siegfried H. , DePonte Daniel P.
Published: April 2018

The physics and chemistry of liquid solutions play a central role in science, and our understanding of life on Earth. Unfortunately, key tools for interrogating aqueous systems, such as infrared and soft X-ray spectroscopy, cannot readily be applied because of strong absorption in water. Here we use gas-dynamic forces to generate free-flowing, sub-micron, liquid sheets which are two orders of magnitude thinner than anything previously reported. Optical, infrared, and X-ray spectroscopies are used to characterize the sheets, which are found to be tunable in thickness from over 1 μm  down to less than 20 nm, which corresponds to fewer than 100 water molecules thick. At this thickness, aqueous sheets can readily transmit photons across the spectrum, leading to potentially transformative applications in infrared, X-ray, electron spectroscopies and beyond. The ultrathin sheets are stable for days in vacuum, and we demonstrate their use at free-electron laser and synchrotron light sources.
Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation
Authors: Li Hui , Yao Qi , Mariscal Alberto Garcia , Wu Xudong , Hülse Justus , Pedersen Esben , Helin Kristian , Waisman Ari , Vinkel Caroline , Thomsen Simon Francis , Avgustinova Alexandra , Benitah Salvador Aznar , Lovato Paola , Norsgaard Hanne , Mortensen Mette Sidsel , Veng Lone , Rozell Björn , Brakebusch Cord
Published: April 2018

The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune cells, only the immune cell-derived IL-23 is believed to be disease relevant. Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is sufficient to cause a chronic skin inflammation with an IL-17 profile. Furthermore, we reveal a cell-autonomous nuclear function for the actin polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by regulating the degradation of the histone methyltransferases G9a and GLP, and H3K9 dimethylation of the IL-23 promoter. This mechanism mediates the induction of IL-23 by TNF, a known inducer of IL-23 in psoriasis. Finally, in keratinocytes of psoriatic lesions a decrease in H3K9 dimethylation correlates with increased IL-23 expression, suggesting relevance for disease. Taken together, our data describe a molecular pathway where epigenetic regulation of keratinocytes can contribute to chronic skin inflammation.
Publisher Correction: ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma
Authors: Han Shujun , Ren Yibo , He Wangxiao , Liu Huadong , Zhi Zhe , Zhu Xinliang , Yang Tielin , Rong Yu , Ma Bohan , Purwin Timothy J. , Ouyang Zhenlin , Li Caixia , Wang Xun , Wang Xueqiang , Yang Huizi , Zheng Yan , Aplin Andrew E. , Liu Jiankang , Shao Yongping
Published: April 2018

In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include the following: The National Basic Research Program (2015CB553602 to J.L.), the National Natural Science Foundation of China (31570777, 91649106, 31770917 to J.L.) and Tianjin Applied Basic and Frontier Tech Major Project (12JCZDJC34400 to J.L.) and Tianjin Higher Education Sci-Tech Development Project (20112D05 to J.L.).
Continuous-variable protocol for oblivious transfer in the noisy-storage model
Authors: Furrer Fabian , Gehring Tobias , Schaffner Christian , Pacher Christoph , Schnabel Roman , Wehner Stephanie
Published: April 2018

Cryptographic protocols are the backbone of our information society. This includes two-party protocols which offer protection against distrustful players. Such protocols can be built from a basic primitive called oblivious transfer. We present and experimentally demonstrate here a quantum protocol for oblivious transfer for optical continuous-variable systems, and prove its security in the noisy-storage model. This model allows us to establish security by sending more quantum signals than an attacker can reliably store during the protocol. The security proof is based on uncertainty relations which we derive for continuous-variable systems, that differ from the ones used in quantum key distribution. We experimentally demonstrate in a proof-of-principle experiment the proposed oblivious transfer protocol for various channel losses by using entangled two-mode squeezed states measured with balanced homodyne detection. Our work enables the implementation of arbitrary two-party quantum cryptographic protocols with continuous-variable communication systems.
Combining CO2 reduction with propane oxidative dehydrogenation over bimetallic catalysts
Authors: Gomez Elaine , Kattel Shyam , Yan Binhang , Yao Siyu , Liu Ping , Chen Jingguang G.
Published: April 2018

The inherent variability and insufficiencies in the co-production of propylene from steam crackers has raised concerns regarding the global propylene production gap and has directed industry to develop more on-purpose propylene technologies. The oxidative dehydrogenation of propane by CO2 (CO2-ODHP) can potentially fill this gap while consuming a greenhouse gas. Non-precious FeNi and precious NiPt catalysts supported on CeO2 have been identified as promising catalysts for CO2-ODHP and dry reforming, respectively, in flow reactor studies conducted at 823 K. In-situ X-ray absorption spectroscopy measurements revealed the oxidation states of metals under reaction conditions and density functional theory calculations were utilized to identify the most favorable reaction pathways over the two types of catalysts.
Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression
Authors: Feist Maren , Schwarzfischer Philipp , Heinrich Paul , Sun Xueni , Kemper Judith , von Bonin Frederike , Perez-Rubio Paula , Taruttis Franziska , Rehberg Thorsten , Dettmer Katja , Gronwald Wolfram , Reinders Jörg , Engelmann Julia C. , Dudek Jan , Klapper Wolfram , Trümper Lorenz , Spang Rainer , Oefner Peter J. , Kube Dieter
Published: April 2018

Knowledge of stromal factors that have a role in the transcriptional regulation of metabolic pathways aside from c-Myc is fundamental to improvements in lymphoma therapy. Using a MYC-inducible human B-cell line, we observed the cooperative activation of STAT3 and NF-κB by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYClow cells depends on glutaminolysis. By 13C- and 15N-tracing of glutamine metabolism and metabolite rescue experiments, we demonstrate that GOT2 provides aspartate and nucleotides to cells with activated or aberrant Jak/STAT and NF-κB signaling. A model of GOT2 transcriptional regulation is proposed, in which the cooperative phosphorylation of STAT3 and direct joint binding of STAT3 and p65/NF-κB to the proximal GOT2 promoter are important. Furthermore, high aberrant GOT2 expression is prognostic in diffuse large B-cell lymphoma underscoring the current findings and importance of stromal factors in lymphoma biology.
Synaptically silent sensory hair cells in zebrafish are recruited after damage
Authors: Zhang Qiuxiang , Li Suna , Wong Hiu-Tung C. , He Xinyi J. , Beirl Alisha , Petralia Ronald S. , Wang Ya-Xian , Kindt Katie S.
Published: April 2018

Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is challenging in many species. To overcome this challenge, we used optical indicators to investigate mechanotransduction among collections of hair cells in intact zebrafish. Our imaging reveals a previously undiscovered disconnect between hair-cell mechanosensation and synaptic transmission. We show that saturating mechanical stimuli able to open mechanically gated channels are unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells. Although synaptically silent, latent hair cells can be rapidly recruited after damage, demonstrating that they are synaptically competent. Therefore synaptically silent hair cells may be an important reserve that acts to maintain sensory function. Our results demonstrate a previously unidentified level of complexity in sculpting sensory transmission from the periphery.
Optical characterization of surface adlayers and their compositional demixing at the nanoscale
Authors: Xiang Limin , Wojcik Michal , Kenny Samuel J. , Yan Rui , Moon Seonah , Li Wan , Xu Ke
Published: April 2018

Under ambient conditions, the behavior of a solid surface is often dominated by a molecularly thin adsorbed layer (adlayer) of small molecules. Here we develop an optical approach to unveil the nanoscale structure and composition of small-molecule adlayers on glass surfaces through spectrally resolved super-resolution microscopy. By recording the images and emission spectra of millions of individual solvatochromic molecules that turn fluorescent in the adlayer phase, we obtain ~30 nm spatial resolution and achieve concurrent measurement of local polarity. This allows us to establish that the adlayer dimensionality gradually increases through a sequence of 0D (nanodroplets), 1D (nano-lines), and 2D (films) for liquids of increasing polarity. Moreover, we find that in adlayers, a solution of two miscible liquids spontaneously demixes into nanodroplets of different compositions that correlate strongly with droplet size and location. We thus reveal unexpectedly rich structural and compositional behaviors of surface adlayers at the nanoscale.
Disclosing the temperature of columnar jointing in lavas
Authors: Lamur Anthony , Lavallée Yan , Iddon Fiona E. , Hornby Adrian J. , Kendrick Jackie E. , von Aulock Felix W. , Wadsworth Fabian B.
Published: April 2018

Columnar joints form by cracking during cooling-induced contraction of lava, allowing hydrothermal fluid circulation. A lack of direct observations of their formation has led to ambiguity about the temperature window of jointing and its impact on fluid flow. Here we develop a novel thermo-mechanical experiment to disclose the temperature of columnar jointing in lavas. Using basalts from Eyjafjallajökull volcano (Iceland) we show that contraction during cooling induces stress build-up below the solidus temperature (980 °C), resulting in localised macroscopic failure between 890 and 840 °C. This temperature window for incipient columnar jointing is supported by modelling informed by mechanical testing and thermal expansivity measurements. We demonstrate that columnar jointing takes place well within the solid state of volcanic rocks, and is followed by a nonlinear increase in system permeability of <9 orders of magnitude during cooling. Columnar jointing may promote advective cooling in magmatic-hydrothermal environments and fluid loss during geothermal drilling and thermal stimulation.
Self-cleaning and surface chemical reactions during hafnium dioxide atomic layer deposition on indium arsenide
Authors: Timm Rainer , Head Ashley R. , Yngman Sofie , Knutsson Johan V. , Hjort Martin , McKibbin Sarah R. , Troian Andrea , Persson Olof , Urpelainen Samuli , Knudsen Jan , Schnadt Joachim , Mikkelsen Anders
Published: April 2018

Atomic layer deposition (ALD) enables the ultrathin high-quality oxide layers that are central to all modern metal-oxide-semiconductor circuits. Crucial to achieving superior device performance are the chemical reactions during the first deposition cycle, which could ultimately result in atomic-scale perfection of the semiconductor–oxide interface. Here, we directly observe the chemical reactions at the surface during the first cycle of hafnium dioxide deposition on indium arsenide under realistic synthesis conditions using photoelectron spectroscopy. We find that the widely used ligand exchange model of the ALD process for the removal of native oxide on the semiconductor and the simultaneous formation of the first hafnium dioxide layer must be significantly revised. Our study provides substantial evidence that the efficiency of the self-cleaning process and the quality of the resulting semiconductor–oxide interface can be controlled by the molecular adsorption process of the ALD precursors, rather than the subsequent oxide formation.
Understanding the adsorption process in ZIF-8 using high pressure crystallography and computational modelling
Authors: Hobday Claire L. , Woodall Christopher H. , Lennox Matthew J. , Frost Mungo , Kamenev Konstantin , Düren Tina , Morrison Carole A. , Moggach Stephen A.
Published: April 2018

Some porous crystalline solids change their structure upon guest inclusion. Unlocking the potential of these solids for a wide variety of applications requires full characterisation of the response to adsorption and the underlying framework–guest interactions. Here, we introduce an approach to understanding gas uptake in porous metal-organic frameworks (MOFs) by loading liquefied gases at GPa pressures inside the Zn-based framework ZIF-8. An integrated experimental and computational study using high-pressure crystallography, grand canonical Monte Carlo (GCMC) and periodic DFT simulations has revealed six symmetry-independent adsorption sites within the framework and a transition to a high-pressure phase. The cryogenic high-pressure loading method offers a different approach to obtaining atomistic detail on guest molecules. The GCMC simulations provide information on interaction energies of the adsorption sites allowing to classify the sites by energy. DFT calculations reveal the energy barrier of the transition to the high-pressure phase. This combination of techniques provides a holistic approach to understanding both structural and energetic changes upon adsorption in MOFs.
LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
Authors: Cobo-Vuilleumier Nadia , Lorenzo Petra I. , Rodríguez Noelia García , Herrera Gómez Irene de Gracia , Fuente-Martin Esther , López-Noriega Livia , Mellado-Gil José Manuel , Romero-Zerbo Silvana-Yanina , Baquié Mathurin , Lachaud Christian Claude , Stifter Katja , Perdomo German , Bugliani Marco , De Tata Vincenzo , Bosco Domenico , Parnaud Geraldine , Pozo David , Hmadcha Abdelkrim , Florido Javier P. , Toscano Miguel G. , de Haan Peter , Schoonjans Kristina , Sánchez Palazón Luis , Marchetti Piero , Schirmbeck Reinhold , Martín-Montalvo Alejandro , Meda Paolo , Soria Bernat , Bermúdez-Silva Francisco-Javier , St-Onge Luc , Gauthier Benoit R.
Published: April 2018

Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.
Decoding the influence of anticipatory states on visual perception in the presence of temporal distractors
Authors: van Ede Freek , Chekroud Sammi R. , Stokes Mark G. , Nobre Anna C.
Published: April 2018

Anticipatory states help prioritise relevant perceptual targets over competing distractor stimuli and amplify early brain responses to these targets. Here we combine electroencephalography recordings in humans with multivariate stimulus decoding to address whether anticipation also increases the amount of target identity information contained in these responses, and to ask how targets are prioritised over distractors when these compete in time. We show that anticipatory cues not only boost visual target representations, but also delay the interference on these target representations caused by temporally adjacent distractor stimuli—possibly marking a protective window reserved for high-fidelity target processing. Enhanced target decoding and distractor resistance are further predicted by the attenuation of posterior 8–14 Hz alpha oscillations. These findings thus reveal multiple mechanisms by which anticipatory states help prioritise targets from temporally competing distractors, and they highlight the potential of non-invasive multivariate electrophysiology to track cognitive influences on perception in temporally crowded contexts.
Deciphering the dark proteome of Chikungunya virus
Authors: Singh Ankur , Kumar Ankur , Yadav Rakhi , Uversky Vladimir N. , Giri Rajanish
Published: April 2018

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. The outbreak of CHIKV infection has been seen in many tropical and subtropical regions of the biosphere. Current reports evidenced that after outbreaks in 2005–06, the fitness of this virus propagating in Aedes albopictus enhanced due to the epistatic mutational changes in its envelope protein. In our study, we evaluated the prevalence of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) in CHIKV proteome. IDPs/IDPRs are known as members of a ‘Dark Proteome’ that defined as a set of polypeptide segments or whole protein without unique three-dimensional structure within the cellular milieu but with significant biological functions, such as cell cycle regulation, control of signaling pathways, and maintenance of viral proteomes. However, the intrinsically disordered aspects of CHIKV proteome and roles of IDPs/IDPRs in the pathogenic mechanism of this important virus have not been evaluated as of yet. There are no existing reports on the analysis of intrinsic disorder status of CHIKV. To fulfil this goal, we have analyzed the abundance and functionality of IDPs/IDPRs in CHIKV proteins, involved in the replication and maturation. It is likely that these IDPs/IDPRs can serve as novel targets for disorder based drug design.
Causal Pathways from Blood Pressure to Larger QRS Amplitudes: a Mendelian Randomization Study
Authors: Van Der Ende M. Yldau , Hendriks Tom , Van Veldhuisen Dirk J. , Snieder Harold , Verweij Niek , Van Der Harst Pim
Published: April 2018

Abnormal QRS duration and amplitudes on the electrocardiogram are indicative of cardiac pathology and are associated with adverse outcomes. The causal nature of these associations remains uncertain and could be due to QRS abnormalities being a symptom of cardiac damage rather than a factor on the causal pathway. By performing Mendelian randomization (MR) analyses using summary statistics of genome wide association study consortia with sample sizes between 20,687 and 339,224 individuals, we aimed to determine which cardiovascular risk factors causally lead to changes in QRS duration and amplitude (Sokolow-Lyon, Cornell and 12-leadsum products). Additionally, we aimed to determine whether QRS traits have a causal relationship with mortality and longevity. We performed inverse-variance weighted MR as main analyses and MR-Egger regression and weighted median estimation as sensitivity analyses. We found evidence for a causal relationship between higher blood pressure and larger QRS amplitudes (systolic blood pressure on Cornell: 55SNPs, causal effect estimate per 1 mmHg = 9.77 millimeters·milliseconds (SE = 1.38,P = 1.20 × 10−12) and diastolic blood pressure on Cornell: 57SNPs, causal effect estimate per 1 mmHg = 14.89 millimeters·milliseconds (SE = 1.82,P = 3.08 × 10−16), but not QRS duration. Genetically predicted QRS traits were not associated with longevity, suggesting a more prominent role of acquired factors in explaining the well-known link between QRS abnormalities and outcome.
Characterization and non-parametric modeling of the developing serum proteome during infancy and early childhood
Authors: Lietzén Niina , Cheng Lu , Moulder Robert , Siljander Heli , Laajala Essi , Härkönen Taina , Peet Aleksandr , Vehtari Aki , Tillmann Vallo , Knip Mikael , Lähdesmäki Harri , Lahesmaa Riitta
Published: April 2018

Children develop rapidly during the first years of life, and understanding the sources and associated levels of variation in the serum proteome is important when using serum proteins as markers for childhood diseases. The aim of this study was to establish a reference model for the evolution of a healthy serum proteome during early childhood. Label-free quantitative proteomics analyses were performed for 103 longitudinal serum samples collected from 15 children at birth and between the ages of 3–36 months. A flexible Gaussian process-based probabilistic modelling framework was developed to evaluate the effects of different variables, including age, living environment and individual variation, on the longitudinal expression profiles of 266 reliably identified and quantified serum proteins. Age was the most dominant factor influencing approximately half of the studied proteins, and the most prominent age-associated changes were observed already during the first year of life. High inter-individual variability was also observed for multiple proteins. These data provide important details on the maturing serum proteome during early life, and evaluate how patterns detected in cord blood are conserved in the first years of life. Additionally, our novel modelling approach provides a statistical framework to detect associations between covariates and non-linear time series data.
The local and global climate forcings induced inhomogeneity of Indian rainfall
Authors: Nair P. J. , Chakraborty A. , Varikoden H. , Francis P. A. , Kuttippurath J.
Published: April 2018

India is home for more than a billion people and its economy is largely based on agrarian society. Therefore, rainfall received not only decides its livelihood, but also influences its water security and economy. This situation warrants continuous surveillance and analysis of Indian rainfall. These kinds of studies would also help forecasters to better tune their models for accurate weather prediction. Here, we introduce a new method for estimating variability and trends in rainfall over different climate regions of India. The method based on multiple linear regression helps to assess contributions of different remote and local climate forcings to seasonal and regional inhomogeneity in rainfall. We show that the Indian Summer Monsoon Rainfall (ISMR) variability is governed by Eastern and Central Pacific El Niño Southern Oscillation, equatorial zonal winds, Atlantic zonal mode and surface temperatures of the Arabian Sea and Bay of Bengal, and the North East Monsoon Rainfall variability is controlled by the sea surface temperature of the North Atlantic and extratropial oceans. Also, our analyses reveal significant positive trends (0.43 mm/day/dec) in the North West for ISMR in the 1979–2017 period. This study cautions against the significant changes in Indian rainfall in a perspective of global climate change.
Lagged influence of Atlantic and Pacific climate patterns on European extreme precipitation
Authors: Tabari Hossein , Willems Patrick
Published: April 2018

The risk of European extreme precipitation and flooding as an economic and humanitarian disaster is modulated by large-scale atmospheric processes that operate over (multi-)decadal periods and transport huge quantities of moisture inland from the oceans. Yet the previous studies for better understanding of extreme precipitation variability and its skillful seasonal prediction are far from comprehensive. Here we show that the winter North Atlantic Oscillation (NAO) and, to a lesser extent, winter ENSO signal have a controlling influence not only concurrently on European extreme precipitation anomaly in winter, but in a delayed way on the extremes in the following seasons. In a similar pattern, there is a strong footprint of summer atmospheric circulations over the Mediterranean Sea on summer extreme precipitation and with 1-, 2- and 3-season lags on the following autumn, winter and spring extremes. The combined influences of the different atmospheric circulation patterns mark a significant step forward for an improved predictability of European extreme precipitation in the state-of-the-art seasonal prediction systems.
A cell surface display fluorescent biosensor for measuring MMP14 activity in real-time
Authors: Braun Alexander , Farber Matthew J. , Klase Zachary A. , Berget Peter B. , Myers Kenneth A.
Published: April 2018

Despite numerous recent advances in imaging technologies, one continuing challenge for cell biologists and microscopists is the visualization and measurement of endogenous proteins as they function within living cells. Achieving this goal will provide a tool that investigators can use to associate cellular outcomes with the behavior and activity of many well-studied target proteins. Here, we describe the development of a plasmid-based fluorescent biosensor engineered to measure the location and activity of matrix metalloprotease-14 (MMP14). The biosensor design uses fluorogen-activating protein technology coupled with a MMP14-selective protease sequence to generate a binary, “switch-on” fluorescence reporter capable of measuring MMP14 location, activity, and temporal dynamics. The MMP14-fluorogen activating protein biosensor approach is applicable to both short and long-term imaging modalities and contains an adaptable module that can be used to study many membrane-bound proteases. This MMP14 biosensor promises to serve as a tool for the advancement of a broad range of investigations targeting MMP14 activity during cell migration in health and disease.
Discovery of the World’s Smallest Terrestrial Pteridophyte
Authors: Patel Mitesh , Reddy Mandadi Narsimha
Published: April 2018

Ophioglossum L. commonly known as “adder’s tongue fern”, has been of great interest due to the highest number of chromosomes in any organism so far known in biological world. Here, a new species of adder’s tongue fern has been discovered and reported from Western Ghats of India. It is prominently distinct from the other known taxa in Ophioglossaceae family. Phylogenetic analysis of three chloroplast DNA (cpDNA) regions (trnL-F, rbcL and psbA-trnH) unambiguously designate this adder’s tongue fern as the distinct lineage and is sister to the clade containing O. parvifolium and O. nudicaule. Azolla caroliniana – an aquatic fern (average size, 0.5–1.5 cm), is the smallest fern on the earth. Our discovery discloses a new species of adder’s tongue fern and ranking it among the smallest terrestrial fern in the world, attaining an average size of only 1–1.2 cm.
Alternative SNP detection platforms, HRM and biosensors, for varietal identification in Vitis vinifera L. using F3H and LDOX genes
Authors: Gomes Sónia , Castro Cláudia , Barrias Sara , Pereira Leonor , Jorge Pedro , Fernandes José R. , Martins-Lopes Paula
Published: April 2018

The wine sector requires quick and reliable methods for Vitis vinifera L. varietal identification. The number of V. vinifera varieties is estimated in about 5,000 worldwide. Single Nucleotide Polymorphisms (SNPs) represent the most basic and abundant form of genetic sequence variation, being adequate for varietal discrimination. The aim of this work was to develop DNA-based assays suitable to detect SNP variation in V. vinifera, allowing varietal discrimination. Genotyping by sequencing allowed the detection of eleven SNPs on two genes of the anthocyanin pathway, the flavanone 3-hydroxylase (F3H, EC: 1.14.11.9), and the leucoanthocyanidin dioxygenase (LDOX, EC 1.14.11.19; synonym anthocyanidin synthase, ANS) in twenty V. vinifera varieties. Three High Resolution Melting (HRM) assays were designed based on the sequencing information, discriminating five of the 20 varieties: Alicante Bouschet, Donzelinho Tinto, Merlot, Moscatel Galego and Tinta Roriz. Sanger sequencing of the HRM assay products confirmed the HRM profiles. Three probes, with different lengths and sequences, were used as bio-recognition elements in an optical biosensor platform based on a long period grating (LPG) fiber optic sensor. The label free platform detected a difference of a single SNP using genomic DNA samples. The two different platforms were successfully applied for grapevine varietal identification.
Defective immuno- and thymoproteasome assembly causes severe immunodeficiency
Authors: Treise Irina , Huber Eva M. , Klein-Rodewald Tanja , Heinemeyer Wolfgang , Grassmann Simon A. , Basler Michael , Adler Thure , Rathkolb Birgit , Helming Laura , Andres Christian , Klaften Matthias , Landbrecht Christina , Wieland Thomas , Strom Tim M. , McCoy Kathy D. , Macpherson Andrew J. , Wolf Eckhard , Groettrup Marcus , Ollert Markus , Neff Frauke , Gailus-Durner Valerie , Fuchs Helmut , Hrabě de Angelis Martin , Groll Michael , Busch Dirk H.
Published: April 2018

By N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated the mutant mouse line TUB6 that is characterised by severe combined immunodeficiency (SCID) and systemic sterile autoinflammation in homozygotes, and a selective T cell defect in heterozygotes. The causative missense point mutation results in the single amino acid exchange G170W in multicatalytic endopeptidase complex subunit-1 (MECL-1), the β2i-subunit of the immuno- and thymoproteasome. Yeast mutagenesis and crystallographic data suggest that the severe TUB6-phenotype compared to the MECL-1 knockout mouse is caused by structural changes in the C-terminal appendage of β2i that prevent the biogenesis of immuno- and thymoproteasomes. Proteasomes are essential for cell survival, and defective proteasome assembly causes selective death of cells expressing the mutant MECL-1, leading to the severe immunological phenotype. In contrast to the immunosubunits β1i (LMP2) and β5i (LMP7), mutations in the gene encoding MECL-1 have not yet been assigned to human disorders. The TUB6 mutant mouse line exemplifies the involvement of MECL-1 in immunopathogenesis and provides the first mouse model for primary immuno- and thymoproteasome-associated immunodeficiency that may also be relevant in humans.
Scalability assessment of Group-IV mono-chalcogenide based tunnel FET
Authors: Brahma Madhuchhanda , Kabiraj Arnab , Saha Dipankar , Mahapatra Santanu
Published: April 2018

Selection of appropriate channel material is the key to design high performance tunnel field effect transistor (TFET), which promises to outperform the conventional metal oxide semiconductor field effect transistor (MOSFET) in ultra-low energy switching applications. Recently discovered atomically thin GeSe, a group IV mono-chalcogenide, can be a potential candidate owing to its direct electronic band gap and low carrier effective mass. In this work we employ ballistic quantum transport model to assess the intrinsic performance limit of monolayer GeSe-TFET. We first study the electronic band structure by regular and hybrid density functional theory and develop two band k · p hamiltonian for the material. We find that the complex band wraps itself within the conduction band and valence band edges and thus signifies efficient band to band tunneling mechanism. We then use the k · p hamiltonian to calculate self-consistent solution of the transport equations within the non-equilibrium Green’s function formalism and the Poisson’s equation based electrostatic potential. Keeping the OFF-current fixed at 10 pA/μm we investigate different static and dynamic performance metrics (ON current, energy and delay) under three different constant-field scaling rules: 40, 30 and 20 nm/V. Our study shows that monolayer GeSe-TFET is scalable till 8 nm while preserving ON/OFF current ratio higher than 104.
The effect of ageing and osteoarthritis on the mechanical properties of cartilage and bone in the human knee joint
Authors: Peters Abby E. , Akhtar Riaz , Comerford Eithne J. , Bates Karl T.
Published: April 2018

Osteoarthritis is traditionally associated with cartilage degeneration although is now widely accepted as a whole-joint disease affecting the entire osteochondral unit; however site-specific cartilage and bone material properties during healthy ageing and disease are absent limiting our understanding. Cadaveric specimens (n = 12; 31–88 years) with grades 0–4 osteoarthritis, were dissected and spatially correlated cartilage, subchondral and trabecular bone samples (n = 8 per cadaver) were harvested from femoral and tibial localities. Nanoindentation was utilised to obtain cartilage shear modulus (G′) and bone elastic modulus (E). Cartilage G′ is strongly correlated to age (p = 0.003) and osteoarthritis grade (p = 0.007). Subchondral bone E is moderately correlated to age (p = 0.072) and strongly correlated to osteoarthritis grade (p = 0.013). Trabecular bone E showed no correlation to age (p = 0.372) or osteoarthritis grade (p = 0.778). Changes to cartilage G′ was significantly correlated to changes in subchondral bone E (p = 0.007). Results showed preferential medial osteoarthritis development and moderate correlations between cartilage G′ and sample location (p = 0.083). Also demonstrated for the first time was significant correlations between site-matched cartilage and subchondral bone material property changes during progressive ageing and osteoarthritis, supporting the role of bone in disease initiation and progression. This clinically relevant data indicates a causative link with osteoarthritis and medial habitual loading.
High-resolution computed tomographic analysis of tooth replacement pattern of the basal neoceratopsian Liaoceratops yanzigouensis informs ceratopsian dental evolution
Authors: He Yiming , Makovicky Peter J , Xu Xing , You Hailu
Published: April 2018

The dental morphology and tooth replacement pattern of Liaoceratops yanzigouensis, the earliest known neoceratopsian, are important for our understanding of the evolution of the ceratopsian dental system. Here we describe the dental morphology and tooth replacement of Liaoceratops yanzigouensis based on high-resolution computed tomographic (CT) scan data of three specimens including the holotype, the first study for basal ceratopsian. The three-dimensional reconstructions reveal some important new information, including: three teeth in the premaxilla in one side, two more teeth in the dentary than in the maxilla, incipiently developed mesial grooves on some crowns, two generations of replacement teeth within some tooth families; and most functional teeth were under heavy resorption by the replacement process, but still remained functional. Comparisons of tooth pair positions from opposite sides in the four jaw quadrants of three specimens revealed a degree of bilateral symmetry in replacement pattern. Reconstruction of Zahnreihen yields an avergae z-spacing of 2.58 with simultaneous front-to-back tooth replacement. Our study presents the earliest evidence of derived neoceratopsian traits of the complex dental batteries in ceratopsids. Most significantly, our models reveal the tracts of partially resorbed functional teeth which appears to track the growth of the jaws, traits previously undocumented in Ceratopsia.
Spinal cord gray matter segmentation using deep dilated convolutions
Authors: Perone Christian S. , Calabrese Evan , Cohen-Adad Julien
Published: April 2018

Gray matter (GM) tissue changes have been associated with a wide range of neurological disorders and were recently found relevant as a biomarker for disability in amyotrophic lateral sclerosis. The ability to automatically segment the GM is, therefore, an important task for modern studies of the spinal cord. In this work, we devise a modern, simple and end-to-end fully-automated human spinal cord gray matter segmentation method using Deep Learning, that works both on in vivo and ex vivo MRI acquisitions. We evaluate our method against six independently developed methods on a GM segmentation challenge. We report state-of-the-art results in 8 out of 10 evaluation metrics as well as major network parameter reduction when compared to the traditional medical imaging architectures such as U-Nets.
Carboxythiazole is a key microbial nutrient currency and critical component of thiamin biosynthesis
Authors: Paerl Ryan W. , Bertrand Erin M. , Rowland Elden , Schatt Phillippe , Mehiri Mohamed , Niehaus Thomas D. , Hanson Andrew D. , Riemann Lasse , Bouget Francois-Yves
Published: April 2018

Almost all cells require thiamin, vitamin B1 (B1), which is synthesized via the coupling of thiazole and pyrimidine precursors. Here we demonstrate that 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole-2-carboxylic acid (cHET) is a useful in vivo B1 precursor for representatives of ubiquitous marine picoeukaryotic phytoplankton and Escherichia coli – drawing attention to cHET as a valuable exogenous micronutrient for microorganisms with ecological, industrial, and biomedical value. Comparative utilization experiments with the terrestrial plant Arabidopsis thaliana revealed that it can also use exogenous cHET, but notably, picoeukaryotic marine phytoplankton and E. coli were adapted to grow on low (picomolar) concentrations of exogenous cHET. Our results call for the modification of the conventional B1 biosynthesis model to incorporate cHET as a key precursor for B1 biosynthesis in two domains of life, and for consideration of cHET as a microbial micronutrient currency modulating marine primary productivity and community interactions in human gut-hosted microbiomes.
Effects of scavenger receptors-1 class A stimulation on macrophage morphology and highly modified advanced glycation end product-protein phagocytosis
Authors: Hamasaki Shinichi , Kobori Takuro , Yamazaki Yui , Kitaura Atsuhiro , Niwa Atsuko , Nishinaka Takashi , Nishibori Masahiro , Mori Shuji , Nakao Shinichi , Takahashi Hideo
Published: April 2018

Advanced glycation end-products (AGEs), which comprise non-enzymatically glycosylated proteins, lipids, and nucleic acid amino groups, play an important role in several diseases and aging processes including angiopathy, renal failure, diabetic complications, and neurodegenerative diseases. Among AGE-associated phenotypes, toxic AGEs, glyceraldehyde-derived AGE-2, and glycolaldehyde-derived AGE-3 are involved in the pathogenesis of diabetic complications. In addition, macrophages are reported to remove extracellular AGEs from tissues via scavenger receptors, leading to the progression of atherosclerosis. In the present study, we found that AGE-2 and AGE-3 enhanced their own endocytic uptake by RAW264.7 mouse macrophage-like cells in a concentration-dependent manner. Furthermore, we demonstrated, for the first time, the morphology of phagocytic macrophages and the endocytosis of AGE particles. The toxic AGEs induced the expression of a scavenger receptor, CD204/scavenger receptors-1 class A (SR-A). Notably, an antibody against CD204 significantly prevented toxic AGE uptake. Moreover, an SR-A antagonistic ligand, fucoidan, also attenuated the AGE-2- and AGE-3-evoked uptake in a concentration-dependent manner. These results indicated that SR-A stimulation, at least in part, plays a role in AGE uptake.
Charge mobility retrieval approach from apparent charge packet movements based on the negative differential resistance theory
Authors: Meng Jia , Zhang Yewen , Holé Stéphane , Zheng Feihu , An Zhenlian
Published: April 2018

Space charge migration characteristics play an important role in the evaluation of polymer insulation performance. However, an accurate description of charge carrier mobility in several typical insulating polymers such as polyethylene, polypropylene is currently not available. Recently, with the observation of a series of negative charge packet movements associated with the negative differential resistance characteristic of charge mobility in LDPE films, the extraction of charge mobility from the apparent charge packet movement has been attempted using appropriate methods. Based on the previous report of the successful derivation of charge mobility from experimental results using numerical methods, the present research improves the derivation accuracy and describes the details of the charge mobility derivation procedure. Back simulation results under several typical polarizing fields using the derived charge mobility are exhibited. The results indicate that both the NDR theory and the simulation models for the polyethylene materials are reasonable. A significant migration velocity difference between the charge carrier and the charge packet is observed. Back simulations of the charge packet under several typical polarizing fields using the obtained E-v curve show good agreement with the experimental results. The charge packet shapes during the migrations were also found to vary with the polarizing field.
Endogenous reference RNAs for microRNA quantitation in formalin-fixed, paraffin-embedded lymph node tissue
Authors: Inada Katsushige , Okoshi Yasushi , Cho-Isoda Yukiko , Ishiguro Shingo , Suzuki Hisashi , Oki Akinori , Tamaki Yoshio , Shimazui Toru , Saito Hitoaki , Hori Mitsuo , Iijima Tatsuo , Kojima Hiroshi
Published: April 2018

Lymph node metastasis is one of the most important factors for tumor dissemination. Quantifying microRNA (miRNA) expression using real-time PCR in formalin-fixed, paraffin-embedded (FFPE) lymph node can provide valuable information regarding the biological research for cancer metastasis. However, a universal endogenous reference gene has not been identified in FFPE lymph node. This study aimed to identify suitable endogenous reference genes for miRNA expression analysis in FFPE lymph node. FFPE lymph nodes were obtained from 41 metastatic cancer and from 16 non-cancerous tissues. We selected 10 miRNAs as endogenous reference gene candidates using the global mean method. The stability of candidate genes was assessed by the following four statistical tools: BestKeeper, geNorm, NormFinder, and the comparative ΔCt method. miR-103a was the most stable gene among candidate genes. However, the use of a single miR-103a was not recommended because its stability value exceeded the reference value. Thus, we combined stable genes and investigated the stability and the effect of gene normalization. The combination of miR-24, miR-103a, and let-7a was identified as one of the most stable sets of endogenous reference genes for normalization in FFPE lymph node. This study may provide a basis for miRNA expression analysis in FFPE lymph node tissue.