bluuebunny/crossref_metadata_2025 huggingface dataset:
The interaction between AMPKβ2 and the PP1-targeting subunit R6 is dynamically regulated by intracellular glycogen content
Authors: Oligschlaeger Yvonne , Miglianico Marie , Dahlmans Vivian , Rubio-Villena Carla , Chanda Dipanjan , Garcia-Gimeno Maria Adelaida , Coumans Will A. , Liu Yilin , Voncken J. Willem , Luiken Joost J.F.P. , Glatz Jan F.C. , Sanz Pascual , Neumann Dietbert
Published: February 2016

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing kinase. We previously showed that glucose deprivation induces autophosphorylation of AMPKβ at Thr-148, which prevents the binding of AMPK to glycogen. Furthermore, in MIN6 cells, AMPKβ1 binds to R6 (PPP1R3D), a glycogen-targeting subunit of protein phosphatase type 1 (PP1), thereby regulating the glucose-induced inactivation of AMPK. In the present study, we further investigated the interaction of R6 with AMPKβ and the possible dependency on Thr-148 phosphorylation status. Yeast two-hybrid (Y2H) analyses and co-immunoprecipitation (IP) of the overexpressed proteins in human embryonic kidney (HEK) 293T) cells revealed that both AMPKβ1 and AMPK-β2 wild-type (WT) isoforms bind to R6. The AMPKβ–R6 interaction was stronger with the muscle-specific AMPKβ2-WT and required association with the substrate-binding motif of R6. When HEK293T cells or C2C12 myotubes were cultured in high-glucose medium, AMPKβ2-WT and R6 weakly interacted. In contrast, glycogen depletion significantly enhanced this protein interaction. Mutation of AMPKβ2 Thr-148 prevented the interaction with R6 irrespective of the intracellular glycogen content. Treatment with the AMPK activator oligomycin enhanced the AMPKβ2–R6 interaction in conjunction with increased Thr-148 phosphorylation in cells grown in low-glucose medium. These data are in accordance with R6 binding directly to AMPKβ2 when both proteins detach from the diminishing glycogen particle, which is simultaneous with increased AMPKβ2 Thr-148 autophosphorylation. Such a model points to a possible control of AMPK by PP1-R6 upon glycogen depletion in muscle.
Coagulansin-A has beneficial effects on the development of bovine embryos in vitro via HSP70 induction
Authors: Khan Imran , Lee Kyeong-Lim , Fakruzzaman Md. , Song Seok-Hwan , Ihsan-ul-Haq  , Mirza Bushra , Yan Chang Guo , Kong Il-Keun
Published: February 2016

Coagulansin-A (withanolide) is the steroidal lactone obtained from Withania coagulans which belong to Solanaceae family. The present study investigated the effects of coagulansin-A on bovine oocyte maturation and embryo development in vitro. All these oocytes were aspirated from the ovaries obtained from Korean Hanwoo cows at a local abattoir. To determine whether coagulansin-A has beneficial effects on bovine oocyte maturation in vitro, 355 oocytes per group (control and treated) in seven replicates were subjected with different concentrations (1, 2.5, 5, 7.5 and 10 μM) of coagulansin-A. The coagulansin-A was added in the in vitro maturation (IVM) media followed by in vitro fertilization (IVF) and then in vitro culture (IVC). Only treatment with 5 μM coagulansin-A remarkably (P<0.05) improved embryos development (Day 8 blastocyst) having 27.30 and 40.01% for control and coagulansin-A treated groups respectively. Treatment with 5 μM coagulansin-A significantly induced activation of heat shock protein 70 (HSP70) (P<0.05). Immunofluorescence analysis revealed that 5 μM coagulansin-A treatment also significantly inhibited oxidative stress and inflammation during bovine embryo development in vitro by decreasing 8-oxoguanosine (8-OxoG) (P<0.05) and nuclear factor-κB (NF-κB) (P<0.05). The expressions of HSP70 and NF-κB were also conformed through real-time PCR (RT-PCR). Additionally, the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay confirmed that coagulansin-A treatment significantly improved the embryo quality and reduced bovine embryo DNA damage (P<0.05). The present study provides new information regarding the mechanisms by which coagulansin-A promotes bovine embryo development in vitro.
Mapping time-course mitochondrial adaptations in the kidney in experimental diabetes
Authors: Coughlan Melinda T. , Nguyen Tuong-Vi , Penfold Sally A. , Higgins Gavin C. , Thallas-Bonke Vicki , Tan Sih Min , Van Bergen Nicole J. , Sourris Karly C. , Harcourt Brooke E. , Thorburn David R. , Trounce Ian A. , Cooper Mark E. , Forbes Josephine M.
Published: February 2016

Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homoeostasis. In diabetic kidney disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics have not been previously documented. In the present study, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological changes. Specifically, in early diabetes (4 weeks), a decrease in ATP content and mitochondrial fragmentation within proximal tubule epithelial cells (PTECs) of diabetic kidneys were clearly apparent, but no changes in urinary albumin excretion or glomerular morphology were evident at this time. By 8 weeks of diabetes, there was increased capacity for mitochondrial permeability transition (mPT) by pore opening, which persisted over time and correlated with mitochondrial hydrogen peroxide (H2O2) generation and glomerular damage. Late in diabetes, by week 16, tubular damage was evident with increased urinary kidney injury molecule-1 (KIM-1) excretion, where an increase in the Complex I-linked oxygen consumption rate (OCR), in the context of a decrease in kidney ATP, indicated mitochondrial uncoupling. Taken together, these data show that changes in mitochondrial bioenergetics and dynamics may precede the development of the renal lesion in diabetes, and this supports the hypothesis that mitochondrial dysfunction is a primary cause of DKD.
Passive wireless tags for tongue controlled assistive technology interfaces
Authors: Rakibet Osman O. , Horne Robert J. , Kelly Stephen W. , Batchelor John C.
Published: February 2016

Tongue control with low profile, passive mouth tags is demonstrated as a human–device interface by communicating values of tongue‐tag separation over a wireless link. Confusion matrices are provided to demonstrate user accuracy in targeting by tongue position. Accuracy is found to increase dramatically after short training sequences with errors falling close to 1% in magnitude with zero missed targets. The rate at which users are able to learn accurate targeting with high accuracy indicates that this is an intuitive device to operate. The significance of the work is that innovative very unobtrusive, wireless tags can be used to provide intuitive human–computer interfaces based on low cost and disposable mouth mounted technology. With the development of an appropriate reading system, control of assistive devices such as computer mice or wheelchairs could be possible for tetraplegics and others who retain fine motor control capability of their tongues. The tags contain no battery and are intended to fit directly on the hard palate, detecting tongue position in the mouth with no need for tongue piercings.
Approximated MILP model for AC transmission expansion planning: global solutions versus local solutions
Authors: Akbari Tohid , Tavakoli Bina Mohammad
Published: February 2016

This study presents a novel linear approximated methodology for AC‐transmission expansion planning (AC‐TEP). The AC‐TEP can provide more precise picture of active and reactive power flow, along with the voltage profile of buses compared with DC‐transmission expansion planning. While the AC‐TEP is inherently a mixed‐integer non‐linear programming problem, this can be transformed into a mixed‐integer linear programming framework by the proposed model which is based upon the binary expansion theory. The global optimality of the solution for the approximated model can be guaranteed by existing algorithms. The presented mathematical model has been successfully applied to several power systems and the results are compared with the exact AC‐TEP model. Simulation results are promising and show that the proposed method is effective, reliable and accurate.
Individual utility‐based path suggestions in transit trip planners
Authors: Nuzzolo Agostino , Comi Antonio
Published: February 2016

The opportunities offered by telematics development and the features required by travellers moving on more complex multimodal transit networks push to investigate new methods for generating path advice in transit trip planners. First, the study focuses on characteristics and limits of the methods used by current trip planners for path generation and then analyses the new methods applied by a new generation of trip planners (most at the prototypical developing stage). These methods use a group or, better, an individual traveller utility function, which allows personal preferences to be pointed out. As the individual utility functions in the transport modelling literature has been largely neglected, the second part of the study reports the state‐of‐the‐art and some theoretical considerations on individual path utility function modelling, and recalls the approaches developed for including individual utility in new trip planners. Further, the results of individual utility function estimations, using surveys relative to the city of Rome, are presented and some aspects of the utility function calibration, including the info provider learning process of traveller preferences, are explored. The analyses show a significant improvement in using individual functions for path advice and a substantial influence of network complexity on the learning process.
Investigation into the characteristics of proton exchange membrane fuel cell‐based power system
Authors: Alrewq Mohmmad , Albarbar Alhussein
Published: February 2016

Fuel cells (FCs) use hydrogen as their prime fuel source, which promotes them as one of the attractive options for clean energy generators. Though they have been around for some time, their characteristics are not yet fully understood. This study offers a thorough investigation into the characteristics of proton exchange membrane (PEM) type of FCs based power system. This study first presents a concise explanation of the working principles of the PEM electrolyser and FCs supported by novel modelling using MATLAB. The simulation results are then validated by a series of experiments carried out on operational 500 mW FC followed by detailed performance parameters of such type of FCs. Parameters affect the efficiencies of each part of the system are investigated and the total system's efficiency is then calculated. The efficiency of the electrolyser and PEM FC was found to be 85 and 60%, respectively. Polarisation curve has been used in order to evaluate FC's performance. From the polarisation curve, it is noted the efficiency of the FC increases with increasing pressure and temperature. The activation losses are reduced when the temperature increased. Moreover, the mass transfer is enhanced toward reducing the PEMFC's resistance.
Automatic method for vertebral morphometry measurements
Authors: Franchini Roberto , Conversano Francesco , Pisani Paola , Casciaro Ernesto , Peccarisi Marco , Quarta Eugenio , Grimaldi Antonella , Muratore Maurizio , Casciaro Sergio
Published: February 2016

Aim of this study was to perform a detailed clinical validation of a novel fully automatic method for vertebral morphometry. About 80 spine lateral radiographs were evaluated both automatically, by the proposed algorithm, and manually, by an experienced radiologist. The following metrics were used for algorithm performance assessment: sensitivity and specificity in vertebra detection; errors in the localisation of characteristic points of vertebral border; errors in the measurement of six diagnostic parameters; level of agreement and correlation between manual and automatic morphometric measurements; overall accuracy of automatic diagnoses with respect to manual ones. Obtained results showed a very good performance in vertebra detection (sensitivity = 89.1% and specificity = 100.0%). Average errors in the localisation of vertebral characteristic points were always smaller than 3 mm (range 0.85–2.79 mm), causing relative errors in diagnostic parameter values ranging from −5.01 to +6.10%. Bland–Altman analysis documented a mean error in automatic measurements of diagnostic ratios of 0.01 ± 0.18 (bias ± 2 SDs), while Pearson's correlation coefficient resulted r = 0.71 (p < 0.001). Finally, an optimal diagnostic coincidence (92.8%) was found between automatic and manual diagnoses. Therefore, the adopted method has a potential for an effective employment in clinical routine for reliable diagnosis of vertebral fractures.
The microlocal spectrum condition, initial value formulations, and background independence
Authors: Stottmeister Alexander , Thiemann Thomas
Published: February 2016

We analyze implications of the microlocal spectrum/Hadamard condition for states in a (linear) quantum field theory on a globally hyperbolic spacetime M in the context of a (distributional) initial value formulation. More specifically, we work in 3+1-split M ≅ ℝ × Σ and give a bound, independent of the spacetime metric, on the wave front sets of the initial data for a quasi-free Hadamard state in a quantum field theory defined by a normally hyperbolic differential operator P acting in a vector bundle E→πM. This aims at a possible way to apply the concept of Hadamard states within approaches to quantum field theory/gravity relying on a Hamiltonian formulation, potentially without a (classical) background metric g.
On the rogue wave propagation in ion pair superthermal plasma
Authors: Abdelwahed H. G. , El-Shewy E. K. , Zahran M. A. , Elwakil S. A.
Published: February 2016

Effects of superthermal electron on the features of nonlinear acoustic waves in unmagnetized collisionless ion pair plasma with superthermal electrons have been examined. The system equations are reduced in the form of the nonlinear Schrodinger equation. The rogue wave characteristics dependences on the ionic density ratio (ν = n–0/n+0), ionic mass ratio (Q = m+/m−), and superthermality index (κ) are investigated. It is worth mentioning that the results present in this work could be applicable in the Earth's ionosphere plasmas.
Two interacting particles on the half-line
Authors: Kerner Joachim , Mühlenbruch Tobias
Published: February 2016

In the case of general compact quantum graphs, many-particle models with singular two-particle interactions were introduced by Bolte and Kerner [J. Phys. A: Math. Theor. 46, 045206 (2013); 46, 045207 (2013)] in order to provide a paradigm for further studies on many-particle quantum chaos. In this note, we discuss various aspects of such singular interactions in a two-particle system restricted to the half-line ℝ+. Among others, we give a description of the spectrum of the two-particle Hamiltonian and obtain upper bounds on the number of eigenstates below the essential spectrum. We also specify conditions under which there is exactly one such eigenstate. As a final result, it is shown that the ground state is unique and decays exponentially as x2+y2→∞.
Effects of confinement for single-well potentials
Authors: Gannot Oran
Published: February 2016

We study bound states generated by a unique potential minimum in the situation where the system is strongly confined to a bounded region containing the minimum (by imposing Dirichlet boundary conditions). In this case, the eigenvalues of the confined system differ from those of the unconfined system by an exponentially small quantity in the semiclassical limit. An asymptotic expansion for this shift is established. The formulas are evaluated explicitly for the harmonic oscillator and an application to the Coulomb potential at a fixed angular momentum is given.
Self-diffusion in the non-Newtonian regime of shearing liquid crystal model systems based on the Gay-Berne potential
Authors: Sarman Sten , Wang Yong-Lei , Laaksonen Aatto
Published: February 2016

The self-diffusion coefficients of nematic phases of various model systems consisting of regular convex calamitic and discotic ellipsoids and non-convex bodies such as bent-core molecules and soft ellipsoid strings have been obtained as functions of the shear rate in a shear flow. Then the self-diffusion coefficient is a second rank tensor with three different diagonal components and two off-diagonal components. These coefficients were found to be determined by a combination of two mechanisms, which previously have been found to govern the self-diffusion of shearing isotropic liquids, namely, (i) shear alignment enhancing the diffusion in the direction parallel to the streamlines and hindering the diffusion in the perpendicular directions and (ii) the distortion of the shell structure in the liquid whereby a molecule more readily can escape from a surrounding shell of nearest neighbors, so that the mobility increases in every direction. Thus, the diffusion parallel to the streamlines always increases with the shear rate since these mechanisms cooperate in this direction. In the perpendicular directions, these mechanisms counteract each other so that the behaviour becomes less regular. In the case of the nematic phases of the calamitic and discotic ellipsoids and of the bent core molecules, mechanism (ii) prevails so that the diffusion coefficients increase. However, the diffusion coefficients of the soft ellipsoid strings decrease in the direction of the velocity gradient because the broadsides of these molecules are oriented perpendicularly to this direction due the shear alignment (i). The cross coupling coefficient relating a gradient of tracer particles in the direction of the velocity gradient and their flow in the direction of the streamlines is negative and rather large, whereas the other coupling coefficient relating a gradient in the direction of the streamlines and a flow in the direction of the velocity gradient is very small.
Critical analysis of fragment-orbital DFT schemes for the calculation of electronic coupling values
Authors: Schober Christoph , Reuter Karsten , Oberhofer Harald
Published: February 2016

We present a critical analysis of the popular fragment-orbital density-functional theory (FO-DFT) scheme for the calculation of electronic coupling values. We discuss the characteristics of different possible formulations or “flavors” of the scheme which differ by the number of electrons in the calculation of the fragments and the construction of the Hamiltonian. In addition to two previously described variants based on neutral fragments, we present a third version taking a different route to the approximate diabatic state by explicitly considering charged fragments. In applying these FO-DFT flavors to the two molecular test sets HAB7 (electron transfer) and HAB11 (hole transfer), we find that our new scheme gives improved electronic couplings for HAB7 (−6.2% decrease in mean relative signed error) and greatly improved electronic couplings for HAB11 (−15.3% decrease in mean relative signed error). A systematic investigation of the influence of exact exchange on the electronic coupling values shows that the use of hybrid functionals in FO-DFT calculations improves the electronic couplings, giving values close to or even better than more sophisticated constrained DFT calculations. Comparing the accuracy and computational cost of each variant, we devise simple rules to choose the best possible flavor depending on the task. For accuracy, our new scheme with charged-fragment calculations performs best, while numerically more efficient at reasonable accuracy is the variant with neutral fragments.
Optical properties of single crystalline SrMoO3 thin films
Authors: Radetinac Aldin , Zimmermann Jörg , Hoyer Karoline , Zhang Hongbin , Komissinskiy Philipp , Alff Lambert
Published: February 2016

The optical properties of pulsed laser deposited highly crystalline SrMoO3 thin films were investigated. Due to their low resistivity below 30 μΩ cm, thin films of SrMoO3 are candidates for transparent conductor applications. The transparency of SrMoO3 extends into the ultraviolet range to about 300 nm. In this range, SrMoO3 has a higher transparency at similar sheet resistance as compared to alternative oxide or metallic materials. Density functional theory shows that electron-electron correlation effects are small in SrMoO3 as compared to other low-resistivity transition metal oxides and predicts the optical properties in good agreement with experiment.
Stability phenomena far beyond the Nusselt flow – Revealed by experimental asymptotics
Authors: Schörner Mario , Reck Daniel , Aksel Nuri
Published: February 2016

The present article contributes detailed experimental results on the linear stability of gravity-driven viscous films flowing down periodically corrugated inclines. We asymptotically left the well-known Nusselt flow by gradually increasing the topography’s amplitude. Systematic variations of the channel’s inclination and the fluid’s viscosity followed. That way, we revealed non-trivial stability charts and phenomena far beyond the limits of the Nusselt regime. For the sake of understanding these phenomena, we thoroughly measured the steady-state free surfaces and velocity fields of the respective flows. This comprehensive approach provided us with the exceptional opportunity to unveil that the complex shape, which stability charts of film flows over strongly corrugated inclines exhibit, can be attributed to the simultaneous presence of stabilizing as well as destabilizing effects provoked by the topography. We proved that the stabilization of the flow due to an increased film thickness and the destabilization of the flow due to resonant standing waves are competing effects. Which one dominates in this competition depends on the amplitude and inclination of the substrate and on the viscosity of the fluid.
Time-dependent wave packet averaged vibrational frequencies from femtosecond stimulated Raman spectra
Authors: Wu Yue-Chao , Zhao Bin , Lee Soo-Y.
Published: February 2016

Femtosecond stimulated Raman spectroscopy (FSRS) on the Stokes side arises from a third order polarization, P(3)(t), which is given by an overlap of a first order wave packet, Ψ2(1)(pu,t), prepared by a narrow band (ps) Raman pump pulse, Epu(t), on the upper electronic e2 potential energy surface (PES), with a second order wave packet, Ψ1(2)(pr∗,pu,t), that is prepared on the lower electronic e1 PES by a broadband (fs) probe pulse, Epr(t), acting on the first-order wave packet. In off-resonant FSRS, Ψ2(1)(pu,t) resembles the zeroth order wave packet Ψ1(0)(t) on the lower PES spatially, but with a force on Ψ2(1)(pu,t) along the coordinates of the reporter modes due to displacements in the equilibrium position, so that Ψ1(2)(pr∗,pu,t) will oscillate along those coordinates thus giving rise to similar oscillations in P(3)(t) with the frequencies of the reporter modes. So, by recovering P(3)(t) from the FSRS spectrum, we are able to deduce information on the time-dependent quantum-mechanical wave packet averaged frequencies, ω̄j(t), of the reporter modes j along the trajectory of Ψ1(0)(t). The observable FSRS Raman gain is related to the imaginary part of P(3)(ω). The imaginary and real parts of P(3)(ω) are related by the Kramers-Kronig relation. Hence, from the FSRS Raman gain, we can obtain the complex P(3)(ω), whose Fourier transform then gives us the complex P(3)(t) to analyze for ω̄j(t). We apply the theory, first, to a two-dimensional model system with one conformational mode of low frequency and one reporter vibrational mode of higher frequency with good results, and then we apply it to the time-resolved FSRS spectra of the cis-trans isomerization of retinal in rhodopsin [P. Kukura et al., Science 310, 1006 (2005)]. We obtain the vibrational frequency up-shift time constants for the C12-H wagging mode at 216 fs and for the C10-H wagging mode at 161 fs which are larger than for the C11-H wagging mode at 127 fs, i.e., the C11-H wagging mode arrives at its final frequency while the C12-H and C10-H wagging modes are still up-shifting to their final values, agreeing with the findings of Yan et al. [Biochemistry 43, 10867 (2004)].
An integrated temperature-compensated flexible shear-stress sensor microarray with concentrated leading-wire
Authors: Tang Jian , Liu Wu , Zhang Weiping , Sun Yongming , Chen Honghai
Published: February 2016

Flexible shear stress sensor is quite important for characterizing curved surface flows. In this work, a novel integrated shear stress sensor microarray is designed with twenty parallel channels, which share the concentrated leading-wire to transmit the ground signal. Electrical pads in rows are easily connected to the circuits with two separate Wheatstone bridges and constant-temperature-difference mode operation is provided for the hot-wires. Temperature crosstalk between adjacent hot-wires is prevented well and the effectiveness of the temperature compensated circuits is verified. Relatively large output response is obtained as the shear stress varies and the sensitivity of the sensors is measured about 0.086 V2/Pa1/3 with nonlinearity lower than 1%, revealing high performance characteristic of the sensors.
Temperature dependence of mid-infrared intersubband absorption in AlGaN/GaN multiple quantum wells
Authors: Kotani Teruhisa , Arita Munetaka , Hoshino Katsuyuki , Arakawa Yasuhiko
Published: February 2016

The temperature dependence of the mid-infrared intersubband (ISB) absorption in non-polar (m-plane) and polar (c-plane) AlGaN/GaN quantum wells (QWs) is studied. The ISB absorption shifts to higher energy as the temperature is reduced from 300 K to below 10 K. Both m-plane and c-plane QWs show a small energy shift (1.6–2.6 meV) compared to AlGaAs/GaAs (3.5–5.2 meV) and AlSb/InAs (6.2 and 12 meV) QWs. Theoretical calculations considering the temperature induced material constant changes show good agreement with the experimental results. These results suggest that ISB transition energies in AlGaN/GaN QWs are more stable against temperature change mainly because of the heavy effective masses and small nonparabolicities.
Spin-dependent tunneling time in periodic diluted-magnetic-semiconductor/nonmagnetic-barrier superlattices
Authors: Yang Ping-Fan , Guo Yong
Published: February 2016

We investigate the tunneling time (dwell time) in periodic diluted-magnetic-semiconductor/nonmagnetic-barrier (DMS/NB) superlattices subjected to an external magnetic field. It is found that spin-dependent resonant bands form in the spectra of dwell time, which can be effectively manipulated by not only the external magnetic field but also the geometric parameters of the system. Moreover, an intuitive semiclassical delay is defined to illustrate the behavior of the dwell time, and the former one is shown to be the result of “smoothing out” the latter one. We also find that the dwell time in diluted-magnetic-semiconductor/semiconductor superlattices behaves surprisingly different from the DMS/NB case, especially for spin-down electrons.
Communication: Librational dynamics in water, sI and sII clathrate hydrates, and ice Ih: Molecular-dynamics insights
Authors: Burnham Christian J. , English Niall J.
Published: February 2016

Equilibrium molecular-dynamics simulations have been performed for liquid water, and on metastable sI and sII polymorphs of empty hydrate lattices, in addition to ice Ih, in order to study the dynamical properties of librational motion (rotation oscillation) depicted by protons in water molecules. In particular, hydrate lattices were found to display prominent “bifurcated” features, or peaks, at circa 70 and 80-95 meV (or ∼560 and 640-760 cm−1, respectively), also displayed by ice, in essentially quantitative agreement with experimental neutron-scattering data. However, observed differences in dispersion between these librational modes between these two structures (both hydrate polymorphs vis-à-vis ice), owing primarily to density effects, have been decomposed into contributions arising from angular-velocity dynamics about axes in the local molecular frame of water molecules, with in-plane “wagging” and “twisting” rationalising one mode at ∼70 meV, and out-of-plane motion for the higher-frequency band. This was confirmed explicitly by a type of de facto normal-mode analysis, in which only immediate layers of water molecules about the one under consideration were allowed to move. In contrast, liquid water displayed no marked preference for such local in- or out-of-plane modes characterising librational motion, owing to the marked absence of rigid, pentamers or hexamers therein.
How drought-induced forest die-off alters microclimate and increases fuel loadings and fire potentials
Authors: Ruthrof Katinka X. , Fontaine Joseph B. , Matusick George , Breshears David D. , Law Darin J. , Powell Sarah , Hardy Giles
Published: February 2016

Forest die-offs associated with drought and heat have recently occurred across the globe, raising concern that associated changes in fuels and microclimate could link initial die-off disturbance to subsequent fire disturbance. Despite widespread concern, little empirical data exist. Following forest die-off in the Northern Jarrah Forest, south-western Australia, we quantified fuel dynamics and associated microclimate for die-off and control plots. Sixteen months post die-off, die-off plots had significantly increased 1-h fuels (11.8 vs 9.8 tonnes ha–1) but not larger fuel classes (10-h and 100-h fuels). Owing to stem mortality, die-off plots had significantly greater standing dead wood mass (100 vs 10 tonnes ha–1), visible sky (hemispherical images analysis: 31 vs 23%) and potential near-ground solar radiation input (measured as Direct Site Factor: 0.52 vs 0.34). Supplemental mid-summer microclimate measurements (temperature, relative humidity and wind speed) were combined with long-term climatic data and fuel load estimates to parameterise fire behaviour models. Fire spread rates were predicted to be 30% greater in die-off plots with relatively equal contributions from fuels and microclimate, highlighting need for operational consideration by fire managers. Our results underscore potential for drought-induced tree die-off to interact with subsequent fire under climate change.
Chimera proteins with affinity for membranes and microtubule tips polarize in the membrane of fission yeast cells
Authors: Recouvreux Pierre , Sokolowski Thomas R. , Grammoustianou Aristea , ten Wolde Pieter Rein , Dogterom Marileen
Published: February 2016

Significance

Cells have to spatially organize their interior to fulfill important functions. In fission yeast, this includes the concentration of polarity factors at cell ends. The molecular network that is responsible for organizing polarity factors consists of a large number of components, including proteins that travel at the ends of microtubules. In an attempt to reduce the complexity of this network, we engineered an artificial chimera protein that interacts both with microtubule ends and the membrane. As predicted by numerical simulations, this simple molecule is able to concentrate at cell ends, but the established polarity is less robust than for natural polarity factors. This finding may lead to a better understanding of the molecular mechanisms that lead to natural polarity patterns.
Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel
Authors: Degani-Katzav Nurit , Gortler Revital , Gorodetzki Lilach , Paas Yoav
Published: February 2016

Significance

Cys-loop receptors (CLRs) are transmembrane ion channels activated by neurotransmitters to mediate chemoelectric excitation or inhibition throughout the nervous system. Hence, CLRs play a key role in our day-to-day life, from coordination of motions to cognition. Impairment of CLRs’ activity leads to various pathophysiological conditions. The CLR studied here is a glutamate-gated chloride-selective receptor (GluClR). GluClRs are unique to invertebrates, yet they are pharmacologically important because they serve as targets for ivermectin, an anthelmintic drug used to treat humans suffering from filarial diseases. This study provides better understanding of the subunit arrangement and stoichiometry of Glu-binding sites in GluClRs.
Conditional cooperation and confusion in public-goods experiments
Authors: Burton-Chellew Maxwell N. , El Mouden Claire , West Stuart A.
Published: February 2016

Significance

The finding that people vary in how they play economic games has led to the conclusion that people vary in their preference for fairness. Consequently, people have been divided into fair cooperators that make sacrifices for the good of the group and selfish free-riders that exploit the cooperation of others. This conclusion has been used to challenge evolutionary theory and economic theory and to guide social policy. We show that variation in behavior in the public-goods game is better explained by variation in understanding and that misunderstanding leads to cooperation.
Stimulus-induced visual cortical networks are recapitulated by spontaneous local and interareal synchronization
Authors: Lewis Christopher M. , Bosman Conrado A. , Womelsdorf Thilo , Fries Pascal
Published: February 2016

Significance

The greatest proportion of brain activity is endogenously generated. The brain’s endogenous activity is highly structured and affects sensory coding, behavior, and perception. The observation of structured endogenous activity across spatial scales suggests that it plays a role in the maintenance and formation of brain networks. The correlation of spontaneous functional MRI signals has demonstrated the existence of multiple intrinsic networks, previously observed during controlled cognitive paradigms. The prevalence and reliability of intrinsic networks have generated intense interest in the functional relevance and electrophysiological basis of interareal correlations. Using multisite recordings from areas V1 and V4 of awake monkeys, we show that endogenously generated activity, both during stimulation and passive fixation, exhibits a similar pattern of local and interareal rhythmic synchronization.
Synthetic gene network restoring endogenous pituitary–thyroid feedback control in experimental Graves’ disease
Authors: Saxena Pratik , Charpin-El Hamri Ghislaine , Folcher Marc , Zulewski Henryk , Fussenegger Martin
Published: February 2016

Significance

Graves’ disease is caused by autoantibodies that activate the thyroid-stimulating hormone (TSH) receptor and trigger a chronic increase in thyroid hormone levels. Current treatment options remain unchanged for decades and include antithyroid drugs as well as radioiodine treatment and thyroidectomy, which result in the destruction of the thyroid gland and require lifelong prescription of thyroid hormones. We designed a closed-loop gene circuit that enables engineered cells to monitor increased thyroid hormone levels and drive the expression of a validated TSH receptor antagonist that competes with TSH as well as TSH receptor autoantibodies, thereby overcoming the pathophysiological activation of the thyroid gland. Hyperthyroid animals implanted with these designer cells had thyroid hormone levels corrected by restoring the feedback control system of the hypothalamus–pituitary–thyroid axis.
SutA is a bacterial transcription factor expressed during slow growth inPseudomonas aeruginosa
Authors: Babin Brett M. , Bergkessel Megan , Sweredoski Michael J. , Moradian Annie , Hess Sonja , Newman Dianne K. , Tirrell David A.
Published: February 2016

Significance

Pathogens that are dormant or growing slowly play important roles in chronic infections, but studying how cells adapt to these conditions is difficult experimentally. This work demonstrates that time-selective analysis of cellular protein synthesis, using bioorthogonal noncanonical amino acid tagging (BONCAT), can provide the sensitivity needed to identify important factors in slow-growth physiology. We identified inPseudomonas aeruginosa, a previously uncharacterized transcriptional regulator that is expressed preferentially under slow-growth conditions, binds RNA polymerase, and has widespread effects on gene expression. This factor is one of several proteins of unknown function identified in our proteomic analysis, and our results suggest that further characterization of fundamental cellular processes under these conditions will shed light on important and understudied realms of biology.
Nuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant
Drosophila
Authors: Afschar Sonita , Toivonen Janne M. , Hoffmann Julia Marianne , Tain Luke Stephen , Wieser Daniela , Finlayson Andrew John , Driege Yasmine , Alic Nazif , Emran Sahar , Stinn Julia , Froehlich Jenny , Piper Matthew D. , Partridge Linda
Published: February 2016

Significance

Lifespan of animals can be extended by genetic and environmental interventions, which often also induce resistance to toxins. This association has given rise to the Green Theory of Aging, which suggests that the ability to remove toxins is limiting for lifespan. To test this idea, we genetically increased resistance to toxins in
Drosophila
, but found no consequent increase in lifespan. Furthermore, we could block the xenobiotic resistance of genetically long-lived flies without reducing their lifespan. It will be important to understand whether the xenobiotic resistance of long-lived mice is also a correlated, rather than a causal, trait, and to understand the functional significance of the common increase in xenobiotic resistance in long-lived animals.
The decadal state of the terrestrial carbon cycle: Global retrievals of terrestrial carbon allocation, pools, and residence times
Authors: Bloom A. Anthony , Exbrayat Jean-François , van der Velde Ivar R. , Feng Liang , Williams Mathew
Published: February 2016

Significance

Quantitative knowledge of terrestrial carbon pathways and processes is fundamental for understanding the biosphere’s response to a changing climate. Carbon allocation, stocks, and residence times together define the dynamic state of the terrestrial carbon cycle. These quantities are difficult to measure and remain poorly quantified on a global scale. Here, we retrieve global 1° × 1° carbon state and process variables by combining a carbon balance model with satellite observations of biomass and leaf area (where and when available) and global soil carbon data. Our results reveal emergent continental-scale patterns and relationships between carbon states and processes. We find that conventional land cover types cannot capture continental-scale variations of retrieved carbon variables; this mismatch has strong implications for terrestrial carbon cycle predictions.
LDL receptor-related protein-1 regulates NFκB and microRNA-155 in macrophages to control the inflammatory response
Authors: Mantuano Elisabetta , Brifault Coralie , Lam Michael S. , Azmoon Pardis , Gilder Andrew S. , Gonias Steven L.
Published: February 2016

Significance

We have identified the transmembrane receptor, LDL receptor-related protein-1 (LRP1), as a regulator of innate immunity and inflammatory responses in macrophages.
LRP1
gene deletion in myeloid cells is proinflammatory in mice, as is
LRP1
gene deletion in cultured macrophages. In LRP1-expressing macrophages, different LRP1 ligands have opposing effects on LRP1 activity, promoting or attenuating inflammatory mediator expression. NFκB is rapidly regulated by LRP1 ligands and responsible for the initial effects of LRP1 on macrophage gene expression. Regulation of microRNA-155 (miR-155) expression is a key downstream event, which may sustain or inhibit the macrophage inflammatory response. LRP1, NFκB, and miR-155 are thus members of a previously unidentified system, with the potential to control inflammation in a macrophage microenvironment-dependent manner.
Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies
Authors: Jackson Nicholas J. , Isen Joshua D. , Khoddam Rubin , Irons Daniel , Tuvblad Catherine , Iacono William G. , McGue Matt , Raine Adrian , Baker Laura A.
Published: February 2016

Significance

Marijuana is the most commonly used recreational drug in the United States. Some studies suggest that marijuana use in adolescence is linked to declines in intellectual functioning. Because of the infeasibility of studying this phenomenon experimentally, it is unclear whether the association can be causally attributed to marijuana use itself or is instead the result of confounding factors. We approach this issue quasiexperimentally using longitudinal samples of adolescent twins. Among twin pairs discordant for marijuana use, we assessed intelligence quotient (IQ) score changes while adjusting for the effects of genetic influences and other factors shared by members of the same twin pair. Results suggest that familial confounds underlie the association between adolescent marijuana use and declining IQ scores.
Marine mixotrophy increases trophic transfer efficiency, mean organism size, and vertical carbon flux
Authors: Ward Ben A. , Follows Michael J.
Published: February 2016

Significance

Marine plankton commonly combine the autotrophic use of light and inorganic resources with the heterotrophic ingestion of prey. These mixotrophs blur the strict boundary between producers and consumers and allow energy and biomass to enter the food web across multiple trophic levels. Incorporating this flexibility into a global simulation of the surface ocean food web reveals that mixotrophy enhances the transfer of biomass to larger organisms at higher trophic levels, which in turn increases the efficiency of oceanic carbon storage through the production of larger, faster-sinking, and carbon-enriched organic detritus.
Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes
Authors: Grigoryev Sergei A. , Bascom Gavin , Buckwalter Jenna M. , Schubert Michael B. , Woodcock Christopher L. , Schlick Tamar
Published: February 2016

Significance

Though the two-start zigzag geometry of a nucleosome chain is dominant in chromatin fibers in vitro, it remains unknown whether it is preserved in living cells. Our combined nucleosome interaction capture technique and mesoscale modeling reveal that the zigzag motif is persistent in interphase and metaphase chromatin. For metaphase chromosomes, we observe a striking increase in occurrence of long-range internucleosome interactions, inconsistent with hierarchical coiling or a liquid melt. Instead, the data point to a new mechanism for higher-order folding, via hierarchical looping, similar to rope flaking used in mountaineering. This mechanism brings together distant DNA elements in a manner that can be controlled by linker histones and histone modifications. Implications for genomic accessibility and epigenetic functions naturally arise.
Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers
Authors: Mehine Miika , Kaasinen Eevi , Heinonen Hanna-Riikka , Mäkinen Netta , Kämpjärvi Kati , Sarvilinna Nanna , Aavikko Mervi , Vähärautio Anna , Pasanen Annukka , Bützow Ralf , Heikinheimo Oskari , Sjöberg Jari , Pitkänen Esa , Vahteristo Pia , Aaltonen Lauri A.
Published: February 2016

Significance

The clinical and scientific community widely regards uterine leiomyomas as a single entity, although evidence of genetic heterogeneity exists. The aim of this study was to explore transcriptional differences between leiomyomas harboring different genetic alterations, including high mobility group AT-hook 2 rearrangements, mediator complex subunit 12 mutations, biallelic inactivation of fumarate hydratase, and collagen, type IV, alpha 5-collagen, type IV, alpha 6 deletions. The evidence presented herein strongly suggests that specific driver mutations are the major determinants of expression changes in leiomyomas. Here we highlight subtype-specific expression differences in key driver pathways and emphasize the utility of stratification in leiomyoma research. Finally, we offer a set of candidate biomarkers that will facilitate the molecular classification of leiomyomas.
Folding and assembly of the large molecular machine Hsp90 studied in single-molecule experiments
Authors: Jahn Markus , Buchner Johannes , Hugel Thorsten , Rief Matthias
Published: February 2016

Significance

Understanding protein folding is, as yet, an unsolved question in the life sciences that has relevance for many diseases. While the folding of simple and small protein domains is well studied, for large proteins, the abundance of pathways and intermediate states makes them difficult to characterize using standard protein folding experiments. With single-molecule optical tweezers experiments, we can overcome these limitations. We observe in real time the folding of a dimeric, three-domain protein from the fully unfolded chain to the biologically active, quaternary structure. The likelihood of the folding process being hindered by misfolded intermediates increases with chain length. These misfolded states can slow down folding significantly and may lead to aggregation in vivo.
C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation
Authors: Harris Samantha P. , Belknap Betty , Van Sciver Robert E. , White Howard D. , Galkin Vitold E.
Published: February 2016

Significance

Cardiac myosin binding protein C (cMyBP-C) is a regulatory protein that modulates the strength and speed of heart contractions. cMyBP-C is required for normal heart function, and mutations in the gene encoding cMyBP-C are the most common cause of hypertrophic cardiomyopathy, a disease affecting an estimated 1 in 500 people. Here we used an integrated structure–function approach to determine how C0 and C1, the first two domains of cMyBP-C, interact with muscle thin filaments (composed of F-actin and regulatory proteins) to influence their ability to interact with myosin, the force-generating protein of muscle. Results reveal that C0 and C1 both bind to actin at multiple, distinct sites and that C0 and C1 exert different effects on heart muscle contraction.
Decision-related perturbations of decision-irrelevant eye movements
Authors: Joo Sung Jun , Katz Leor N. , Huk Alexander C.
Published: February 2016

Significance

Studies using limb movements to probe cognitive states have suggested an interactive model of cognition and motor action. Despite ample evidence showing that the neural activity in oculomotor brain circuits is correlated with the formation of decisions about where to move the eyes, it is not known whether there are interactions between such decision-related activity and decision-irrelevant oculomotor processing. By probing the oculomotor system with a decision-irrelevant saccadic eye movement during decision formation, we found that saccade metrics are affected by the strength and direction of motion evidence. Our results suggest that decision signals continuously flow into the oculomotor system during decision making, and further extend the interactive model of cognition and action into the oculomotor system.
Protonation-dependent conformational dynamics of the multidrug transporter EmrE
Authors: Dastvan Reza , Fischer Axel W. , Mishra Smriti , Meiler Jens , Mchaourab Hassane S.
Published: February 2016

Significance

Small multidrug resistance (SMR) transporters play an important role in the protection of prokaryotes from cytotoxic molecules. They exploit the proton electrochemical gradient to drive the transport of these molecules out of the cell against their concentration gradient. This work investigated how binding of protons power the conformational changes that enable substrate binding and subsequent alternating access of the
Escherichia coli
SMR transporter EmrE. The results show that protonation induces large-scale reconfiguration of the structure, including helical rotation and tilt and repacking of loops. A highly conserved charged residue primarily accounts for proton sensing, but other acidic residues control local structures. Our findings stimulate a structural model of transport, offering a novel perspective on proton-coupled multidrug transport.