bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-functional dielectric elastomer artificial muscles for soft and smart machines
Authors: Anderson Iain A. , Gisby Todd A. , McKay Thomas G. , O’Brien Benjamin M. , Calius Emilio P.
Published: August 2012

Dielectric elastomer (DE) actuators are popularly referred to as artificial muscles because their impressive actuation strain and speed, low density, compliant nature, and silent operation capture many of the desirable physical properties of muscle. Unlike conventional robots and machines, whose mechanisms and drive systems rapidly become very complex as the number of degrees of freedom increases, groups of DE artificial muscles have the potential to generate rich motions combining many translational and rotational degrees of freedom. These artificial muscle systems can mimic the agonist-antagonist approach found in nature, so that active expansion of one artificial muscle is taken up by passive contraction in the other. They can also vary their stiffness. In addition, they have the ability to produce electricity from movement. But departing from the high stiffness paradigm of electromagnetic motors and gearboxes leads to new control challenges, and for soft machines to be truly dexterous like their biological analogues, they need precise control. Humans control their limbs using sensory feedback from strain sensitive cells embedded in muscle. In DE actuators, deformation is inextricably linked to changes in electrical parameters that include capacitance and resistance, so the state of strain can be inferred by sensing these changes, enabling the closed loop control that is critical for a soft machine. But the increased information processing required for a soft machine can impose a substantial burden on a central controller. The natural solution is to distribute control within the mechanism itself. The octopus arm is an example of a soft actuator with a virtually infinite number of degrees of freedom (DOF). The arm utilizes neural ganglia to process sensory data at the local “arm” level and perform complex tasks. Recent advances in soft electronics such as the piezoresistive dielectric elastomer switch (DES) have the potential to be fully integrated with actuators and sensors. With the DE switch, we can produce logic gates, oscillators, and a memory element, the building blocks for a soft computer, thus bringing us closer to emulating smart living structures like the octopus arm. The goal of future research is to develop fully soft machines that exploit smart actuation networks to gain capabilities formerly reserved to nature, and open new vistas in mechanical engineering.
Topological field theory of dynamical systems
Authors: Ovchinnikov Igor V.
Published: August 2012

Here, it is shown that the path-integral representation of any stochastic or deterministic continuous-time dynamical model is a cohomological or Witten-type topological field theory, i.e., a model with global topological supersymmetry (Q-symmetry). As many other supersymmetries, Q-symmetry must be perturbatively stable due to what is generically known as non-renormalization theorems. As a result, all (equilibrium) dynamical models are divided into three major categories: Markovian models with unbroken Q-symmetry, chaotic models with Q-symmetry spontaneously broken on the mean-field level by, e.g., fractal invariant sets (e.g., strange attractors), and intermittent or self-organized critical (SOC) models with Q-symmetry dynamically broken by the condensation of instanton-antiinstanton configurations (earthquakes, avalanches, etc.) SOC is a full-dimensional phase separating chaos and Markovian dynamics. In the deterministic limit, however, antiinstantons disappear and SOC collapses into the “edge of chaos.” Goldstone theorem stands behind spatio-temporal self-similarity of Q-broken phases known under such names as algebraic statistics of avalanches, 1/f noise, sensitivity to initial conditions, etc. Other fundamental differences of Q-broken phases is that they can be effectively viewed as quantum dynamics and that they must also have time-reversal symmetry spontaneously broken. Q-symmetry breaking in non-equilibrium situations (quenches, Barkhausen effect, etc.) is also briefly discussed.
Dynamic polarizabilities of Zn and Cd and dispersion coefficients involving group 12 atoms
Authors: Qiao L. W. , Li P. , Tang K. T.
Published: August 2012

The refractive index data for Zn and Cd measured by Goebel and Hohm are analyzed with a three-term Maxwell-Sellmeier expression which incorporates the experimental oscillator strengths of the first two dipole transitions. These expressions are extended to imaginary frequencies for the determination of the upper and lower bounds of the dynamic polarizabilities α(iω), from which the van der Waals coefficients of two-body interactions and the non-additive three-body interactions are generated. The determined C6 values for Zn2 (359±8 a.u.) and Cd2 (686±10 a.u.) are much larger than those originally estimated by Goebel and Hohm. This is because their one-term approximation of α(ω), which fits the measurements very well in the normal frequency range, greatly underestimates α(iω) when the frequency is extended into the imaginary domain. On the other hand, the present results of heteronuclear interactions verify once again that Tang's one-term approximation of α(iω) leads to accurate combining rules. The two- and three-body interaction coefficients between group 12 atoms (Zn, Cd, Hg) and the alkali, alkaline-earth, rare-gas atoms, and some molecules are estimated with these combining rules.
An assessment of comparative methods for approaching electrode polarization in dielectric permittivity measurements
Authors: Ishai P. Ben , Sobol Z. , Nickels J. D. , Agapov A. L. , Sokolov A. P.
Published: August 2012

We examine the validity of three common methods for analysis and correction of the electrode polarization (EP) effect in dielectric spectroscopy measurements of conductive liquid samples. The methods considered are (i) algorithmic treatment by modeling the EP behavior at constant phase angle, (ii) varying the size of the electrode gap, and (iii) polypyrrole (PPyPss) layered electrodes. The latter is a relatively recent innovation suggested to be an efficient solution. We demonstrate that PPyPss coated electrodes do not diminish the effect of EP, and even add relaxation processes of its own. Our conclusion is that these polymer coated electrodes are not suitable for the correction of electrode polarization.
Phase behavior of colloids and proteins in aqueous suspensions: Theory and computer simulations
Authors: Valadez-Pérez Néstor E. , Benavides Ana L. , Schöll-Paschinger Elisabeth , Castañeda-Priego Ramón
Published: August 2012

The fluid phase behavior of colloidal suspensions with short-range attractive interactions is studied by means of Monte Carlo computer simulations and two theoretical approximations, namely, the discrete perturbation theory and the so-called self-consistent Ornstein-Zernike approximation. The suspensions are modeled as hard-core attractive Yukawa (HCAY) and Asakura-Oosawa (AO) fluids. A detailed comparison of the liquid-vapor phase diagrams obtained through different routes is presented. We confirm Noro-Frenkel's extended law of scaling according to which the properties of a short-ranged fluid at a given temperature and density are independent of the detailed form of the interaction, but just depend on the value of the second virial coefficient. By mapping the HCAY and AO fluids onto an equivalent square-well fluid of appropriate range at the critical point we show that the critical temperature as a function of the effective range is independent of the interaction potential, i.e., all curves fall in a master curve. Our findings are corroborated with recent experimental data for lysozyme proteins.
Efficient excitation of a monopole optical transducer for near-field recording
Authors: Peng Chubing
Published: August 2012

An optical near-field transducer composed of a rectangular patch and a protruded peg has been numerically studied for heat-assisted magnetic recording. This transducer strongly interacts with a planar solid immersion focusing field and efficiently couples optical energy into a recording medium in a region determined by the peg cross-section. The transducer is excited through the electric field predominantly normal to its edges. The optimal size of the rectangular patch is found to be a half-wave optical antenna in height and between half-wave and full-wave in width.
New application of temperature-dependent modelling of high temperature superconductors: Quench propagation and pulse magnetization
Authors: Zhang Min , Matsuda Koichi , Coombs T. A.
Published: August 2012

We present temperature-dependent modeling of high-temperature superconductors (HTS) to understand HTS electromagnetic phenomena where temperature fluctuation plays a nontrivial role. Thermal physics is introduced into the well-developed H-formulation model, and the effect of temperature-dependent parameters is considered. Based on the model, we perform extensive studies on two important HTS applications: quench propagation and pulse magnetization. A micrometer-scale quench model of HTS coil is developed, which can be used to estimate minimum quench energy and normal zone propagation velocity inside the coil. In addition, we study the influence of inhomogeneity of HTS bulk during pulse magnetization. We demonstrate how the inhomogeneous distribution of critical current inside the bulk results in varying degrees of heat dissipation and uniformity of final trapped field. The temperature-dependent model is proven to be a powerful tool to study the thermally coupled electromagnetic phenomena of HTS.
Magnetic tri-axial grain alignment in misfit-layered bismuth-based cobaltites
Authors: Horii Shigeru , Okamoto Natsuki , Aoki Keisuke , Haruta Masakazu , Shimoyama Jun-ichi , Kishio Kohji
Published: August 2012

The tri-axial grain alignment of thermoelectric Bi-based cobaltites with a misfit-layered structure by a modulated rotation magnetic field (MRF) of 10 tesla (T) was demonstrated. To maximize the degrees of tri-axial grain alignment in [(Bi2−xPbx)(AE2−yREy)O4]pCoO2 powder samples aligned under the MRF of 10 T, the following three crystallochemical approaches are important: doping of Pb into the Bi site, appropriate choice of an alkali earth (AE) ion, and doping of the appropriate rare earth (RE) ion into an AE site. Namely, simultaneous introduction of the relaxation effect of the misfit structure, creation of a domain structure with shear-type discontinuity, and single-ion magnetic anisotropy, which are induced by doping of Pb, Sr, and RE (Pr and Nd), respectively, into the Bi-based cobaltite achieved high degrees of tri-axial grain alignment below 4°. The present study provides a crystallochemical strategy for the fabrication of grain-aligned ceramics of misfit-layered Bi-based cobaltites with high thermoelectric performance by the magneto-scientific technique using MRF.
Optimizing the photovoltage of polymer/zinc oxide hybrid solar cells by calcium doping
Authors: Wang Mingqing , Sun Jon-Paul , Suei Sandy , Hill Ian G.
Published: August 2012

The voltage produced by an excitonic solar cell, such as an organic or a hybrid organic/inorganic solar cell is limited by the difference in potential energy between the state occupied by the electron in the acceptor (conduction band minimum (CBM)/lowest unoccupied molecular orbital) and that occupied by the hole in the donor (valence band maximum/highest occupied molecular orbital). Calcium doping of sol-gel ZnO has been used to change the electron affinity of the ZnO acceptor in ZnO/poly(3-hexyl thiophene) hybrid solar cells. The band gap of the mixed oxide system increases with Ca fraction, with most of this attributable to movement of the conduction band minimum toward the vacuum, as determined by UV-vis spectroscopy and Kelvin probe. In planar bilayer cells using Zn0.9Ca0.1O as the acceptor, the open circuit voltage can be increased by 0.24 V, and the efficiency doubled compared to devices using pure ZnO.
Device convolution effects on the collective scattering signal of the E × B mode from Hall thruster experiments: 2D dispersion relation
Authors: Cavalier J. , Lemoine N. , Bonhomme G. , Tsikata S. , Honoré C. , Grésillon D.
Published: August 2012

The effect of the collective light scattering diagnostic transfer function is considered in the context of the dispersion relation of the unstable E×B mode previously reported. This transfer function is found to have a contribution to the measured frequencies and mode amplitudes which is more or less significant depending on the measurement wavenumbers and angles. After deconvolution, the experimental data are found to be possibly compatible with the idea that the mode frequency in the jet frame (after subtraction of the Doppler effect due to the plasma motion along the thruster axis) is independent of the orientation of the wave vector in the plane orthogonal to the local magnetic field.
Field emission from diamond-coated multiwalled carbon nanotube “teepee” structures
Authors: Zou Y. , May P. W. , Vieira S. M. C. , Fox N. A.
Published: August 2012

Dense arrays of vertically aligned multiwalled carbon nanotubes (MWCNTs) have been seeded with a nanodiamond suspension in methanol using electrospray deposition. This treatment caused the tips of groups of 20–40 MWCNTs to stick together forming structures resembling “teepees.” Subsequent short chemical vapour deposition experiments using standard diamond-growing conditions allowed the nanodiamond seeds to grow into a thin continuous film, locking the teepee structures into this shape. Field emission tests show that these diamond-coated carbon nanotubes (CNTs) teepees retain the low threshold voltage of the uncoated CNTs but with greatly improved emission stability and lifetime.
Production traits and hatching of a Barred Rock 1 pure line, its feather sexable strains and their crosses
Authors: Durmus Ismail , Goger Huseyin , Demirtas Sahnur , Yurtogullari Sermin
Published: August 2012

The study was carried out to identify some production traits of the pure Barred Rock 1 (BR1) line and rapid × slow feathering line crosses derived from the BR1 pure line, in addition to F1 crosses of all these dam lines with Rhode Island Red 1 sire line. The BR1 line previously used a brown layer dam line for barred/non-barred day-old chick auto-sexing and synthetic slow and rapid wing feathering lines. Parent lines showed significant differences in sexual maturity and egg production (P < 0.01) and early embryonic mortality (P < 0.05). However, there was no significant difference in weight at sexual maturity, average egg weight, hatchability of fertile eggs, hatchability of total eggs set, and middle and late embryonic mortalities. A significant difference was found among F1 crosses with respect to weight at sexual maturity (P < 0.05), but no significant difference (P > 0.05) could be determined for age at sexual maturity and egg production. Overall, rapid feathering hens had better production traits than slow feathering hens. The dual crossbred parent lines exhibited almost the same level of egg production traits compared with the pure line.
GlyPh: a low-cost platform for phenotyping plant growth and water use
Authors: Pereyra-Irujo Gustavo A. , Gasco Emmanuel D. , Peirone Laura S. , Aguirrezábal Luis A. N.
Published: August 2012

Breeding drought-tolerant crop varieties with higher water use efficiency could help maintain food supply to a growing population and save valuable water resources. Fast and accurate phenotyping is currently a bottleneck in the process towards attaining this goal, as available plant phenotyping platforms have an excessive cost for many research institutes or breeding companies. Here we describe a simple and low-cost, automatic platform for high-throughput measurement of plant water use and growth and present its utilisation to assess the drought tolerance of two soybean genotypes. The platform allows the evaluation of up to 120 plants growing in individual pots. A cart moving in only one direction carries the measuring and watering devices. Watering and measurement routines allow the simulation of multiple water regimes for each plant individually and indicate the timing of measurement of soil water content and image capture for growth estimation. Water use, growth and water use efficiency were measured in two experiments with different water scenarios. Differences in water use efficiency between genotypes were detected only in some treatments, emphasising the importance of phenotyping platforms to evaluate a genotype’s phenotype under a broad range of conditions in order to capture valuable differences, minimising the chance of artefacts and increasing precision of measurements.
Early drought stress detection in cereals: simplex volume maximisation for hyperspectral image analysis
Authors: Römer Christoph , Wahabzada Mirwaes , Ballvora Agim , Pinto Francisco , Rossini Micol , Panigada Cinzia , Behmann Jan , Léon Jens , Thurau Christian , Bauckhage Christian , Kersting Kristian , Rascher Uwe , Plümer Lutz
Published: August 2012

Early water stress recognition is of great relevance in precision plant breeding and production. Hyperspectral imaging sensors can be a valuable tool for early stress detection with high spatio-temporal resolution. They gather large, high dimensional data cubes posing a significant challenge to data analysis. Classical supervised learning algorithms often fail in applied plant sciences due to their need of labelled datasets, which are difficult to obtain. Therefore, new approaches for unsupervised learning of relevant patterns are needed. We apply for the first time a recent matrix factorisation technique, simplex volume maximisation (SiVM), to hyperspectral data. It is an unsupervised classification approach, optimised for fast computation of massive datasets. It allows calculation of how similar each spectrum is to observed typical spectra. This provides the means to express how likely it is that one plant is suffering from stress. The method was tested for drought stress, applied to potted barley plants in a controlled rain-out shelter experiment and to agricultural corn plots subjected to a two factorial field setup altering water and nutrient availability. Both experiments were conducted on the canopy level. SiVM was significantly better than using a combination of established vegetation indices. In the corn plots, SiVM clearly separated the different treatments, even though the effects on leaf and canopy traits were subtle.
The effects of season and devil facial tumour disease on the reproductive physiology of the male Tasmanian devil (Sarcophilus harrisii)
Authors: Keeley T. , McGreevy P. D. , O'Brien J. K.
Published: August 2012

Devil facial tumour disease (DFTD) is the cause of the rapid decline of wild Tasmanian devils. Female devils are seasonal breeders with births peaking during autumn (i.e. March) but the degree of reproductive seasonality in male devils is unknown. The objective of this study was to examine the potential effects of season and DFTD on reproductive function in male devils (n = 55). Testicular (1.90 ± 0.23 g) and epididymal (0.90 ± 0.06 g) weights were maximal during autumn and spring (P < 0.05), whereas prostate (3.71 ± 0.74 g) and Cowper’s gland (0.68 ± 0.22; 0.52 ± 0.21 g) weights peaked during autumn (P < 0.001). The motility of spermatozoa from the cauda epididymides extracted post-mortem was similar (P > 0.05) across season and disease state (31.5 ± 13.1% total motility). Testicular and epididymal weights were no different between animals displaying late or early-stage DTFD signs or disease-free animals (P > 0.1). The accessory sex glands were larger in late-stage DFTD animals than in animals with early-stage disease signs or which were disease-free (P < 0.01) but effects of season on this result can’t be excluded. Serum testosterone concentrations peaked during summer (0.25 ± 0.18 ng mL–1) but values were not different from the preceding and subsequent seasons (P > 0.05), nor influenced by disease stage (P > 0.1). Seasonal and DFTD-related changes in serum cortisol concentrations were not evident (P > 0.1). Male devil reproduction does not appear to be restricted by season nor inhibited by DFTD.
Computational design of genomic transcriptional networks with adaptation to varying environments
Authors: Carrera Javier , Elena Santiago F. , Jaramillo Alfonso
Published: August 2012

Transcriptional profiling has been widely used as a tool for unveiling the coregulations of genes in response to genetic and environmental perturbations. These coregulations have been used, in a few instances, to infer global transcriptional regulatory models. Here, using the large amount of transcriptomic information available for the bacterium
Escherichia coli
, we seek to understand the design principles determining the regulation of its transcriptome. Combining transcriptomic and signaling data, we develop an evolutionary computational procedure that allows obtaining alternative genomic transcriptional regulatory network (GTRN) that still maintains its adaptability to dynamic environments. We apply our methodology to an
E. coli
GTRN and show that it could be rewired to simpler transcriptional regulatory structures. These rewired GTRNs still maintain the global physiological response to fluctuating environments. Rewired GTRNs contain 73% fewer regulated operons. Genes with similar functions and coordinated patterns of expression across environments are clustered into longer regulated operons. These synthetic GTRNs are more sensitive and show a more robust response to challenging environments. This result illustrates that the natural configuration of
E. coli
GTRN does not necessarily result from selection for robustness to environmental perturbations, but that evolutionary contingencies may have been important as well. We also discuss the limitations of our methodology in the context of the demand theory. Our procedure will be useful as a novel way to analyze global transcription regulation networks and in synthetic biology for the de novo design of genomes.
Pyranopterin conformation defines the function of molybdenum and tungsten enzymes
Authors: Rothery Richard A. , Stein Benjamin , Solomonson Matthew , Kirk Martin L. , Weiner Joel H.
Published: August 2012

We have analyzed the conformations of 319 pyranopterins in 102 protein structures of mononuclear molybdenum and tungsten enzymes. These span a continuum between geometries anticipated for quinonoid dihydro, tetrahydro, and dihydro oxidation states. We demonstrate that pyranopterin conformation is correlated with the protein folds defining the three major mononuclear molybdenum and tungsten enzyme families, and that binding-site micro-tuning controls pyranopterin oxidation state. Enzymes belonging to the bacterial dimethyl sulfoxide reductase (DMSOR) family contain a metal-bis-pyranopterin cofactor, the two pyranopterins of which have distinct conformations, with one similar to the predicted tetrahydro form, and the other similar to the predicted dihydro form. Enzymes containing a single pyranopterin belong to either the xanthine dehydrogenase (XDH) or sulfite oxidase (SUOX) families, and these have pyranopterin conformations similar to those predicted for tetrahydro and dihydro forms, respectively. This work provides keen insight into the roles of pyranopterin conformation and oxidation state in catalysis, redox potential modulation of the metal site, and catalytic function.
Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin
Authors: Bonnet Nicolas , Conway Simon J. , Ferrari Serge L.
Published: August 2012

Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult

Postn
−/−

and

Postn
+/+

mice to intermittent PTH. Compared with

Postn
+/+

,

Postn
−/−

mice had a lower bone mass, cortical bone volume, and strength response to PTH. PTH-stimulated bone-forming indices were all significantly lower in

Postn
−/−

mice, particularly at the periosteum. Furthermore, in vivo stimulation of Wnt-β-catenin signaling by PTH, as evaluated in TOPGAL reporter mice, was inhibited in the absence of periostin (

TOPGAL;Postn
−/−

mice). PTH stimulated periostin and inhibited
MEF2C
and sclerostin (Sost) expression in bone and osteoblasts in vitro. Recombinant periostin also suppressed Sost expression, which was mediated through the integrin αVβ3 receptor, whereas periostin-blocking antibody prevented inhibition of
MEF2C
and
Sost
by PTH. In turn, administration of a Sost-blocking antiboby partially restored the PTH-mediated increase in bone mass in

Postn
−/−

mice. In addition, primary osteoblasts from

Postn
−/−

mice showed a lower proliferation, mineralization, and migration, both spontaneously and in response to PTH. Osteoblastic gene expression levels confirmed a defect of

Postn
−/−

osteoblast differentiation with and without PTH, as well as an increased osteoblast apoptosis in the absence of periostin. These data elucidate the complex role of periostin on bone anabolism, through the regulation of Sost, Wnt-β-catenin signaling, and osteoblast differentiation.
Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome
Authors: Hurley Paula J. , Marchionni Luigi , Simons Brian W. , Ross Ashley E. , Peskoe Sarah B. , Miller Rebecca M. , Erho Nicholas , Vergara Ismael A. , Ghadessi Mercedeh , Huang Zhenhua , Gurel Bora , Park Ben Ho , Davicioni Elai , Jenkins Robert B. , Platz Elizabeth A. , Berman David M. , Schaeffer Edward M.
Published: August 2012

Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene,
Sparcl1
, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.
Modeling early bactericidal activity in murine tuberculosis provides insights into the activity of isoniazid and pyrazinamide
Authors: Grosset Jacques , Almeida Deepak , Converse Paul J. , Tyagi Sandeep , Li Si-Yang , Ammerman Nicole C. , Pym Alexander S. , Wallengren Kristina , Hafner Richard , Lalloo Umesh , Swindells Susan , Bishai William R.
Published: August 2012

Standard tuberculosis (TB) treatment includes an initial regimen containing drugs that are both rapidly bactericidal (isoniazid) and sterilizing (rifampin and pyrazinamide), and ethambutol to help prevent the emergence of drug resistance. Antagonism between isoniazid and pyrazinamide has been demonstrated in a TB treatment mouse model. Because isoniazid’s bactericidal activity is greatest during the initial two treatment days, we hypothesized that removing isoniazid after the second day would increase the effectiveness of the standard regimen. To test this hypothesis, we developed a mouse model to measure the early bactericidal activity (EBA) of drug regimens designed to analyze the essentiality of both isoniazid and pyrazinamide during the first 14 d of therapy. Our results clearly indicate that discontinuation of isoniazid after the second day of treatment increases the EBA of standard therapy in the mouse model, whereas omitting pyrazinamide during the first 14 d was detrimental. Substitution of moxifloxacin for isoniazid on day 3 did not increase the EBA compared with only removing isoniazid after day 2. Our data show that a mouse model can be used to analyze the EBA of TB drugs, and our findings support pursuing clinical trials to evaluate the possible benefit of removing isoniazid after the first 2 treatment days.
Endonuclease VIII-like 1 (NEIL1) promotes short-term spatial memory retention and protects from ischemic stroke-induced brain dysfunction and death in mice
Authors: Canugovi Chandrika , Yoon Jeong Seon , Feldman Neil H. , Croteau Deborah L. , Mattson Mark P. , Bohr Vilhelm A.
Published: August 2012

Recent findings suggest that neurons can efficiently repair oxidatively damaged DNA, and that both DNA damage and repair are enhanced by activation of excitatory glutamate receptors. However, in pathological conditions such as ischemic stroke, excessive DNA damage can trigger the death of neurons. Oxidative DNA damage is mainly repaired by base excision repair (BER), a process initiated by DNA glycosylases that recognize and remove damaged DNA bases. Endonuclease VIII-like 1 (NEIL1) is a DNA glycosylase that recognizes a broad range of oxidative lesions. Here, we show that mice lacking NEIL1 exhibit impaired memory retention in a water maze test, but no abnormalities in tests of motor performance, anxiety, or fear conditioning. NEIL1 deficiency results in increased brain damage and a defective functional outcome in a focal ischemia/reperfusion model of stroke. The incision capacity on a 5-hydroxyuracil–containing bubble substrate was lower in the ipsilateral side of ischemic brains and in the mitochondrial lysates of unstressed old NEIL1-deficient mice. These results indicate that NEIL1 plays an important role in learning and memory and in protection of neurons against ischemic injury.
Regulating synthetic gene networks in 3D materials
Authors: Deans Tara L. , Singh Anirudha , Gibson Matthew , Elisseeff Jennifer H.
Published: August 2012

Combining synthetic biology and materials science will enable more advanced studies of cellular regulatory processes, in addition to facilitating therapeutic applications of engineered gene networks. One approach is to couple genetic inducers into biomaterials, thereby generating 3D microenvironments that are capable of controlling intrinsic and extrinsic cellular events. Here, we have engineered biomaterials to present the genetic inducer, IPTG, with different modes of activating genetic circuits in vitro and in vivo. Gene circuits were activated in materials with IPTG embedded within the scaffold walls or chemically linked to the matrix. In addition, systemic applications of IPTG were used to induce genetic circuits in cells encapsulated into materials and implanted in vivo. The flexibility of modifying biomaterials with genetic inducers allows for patterned placement of these inducers that can be used to generate distinct patterns of gene expression. Together, these genetically interactive materials can be used to characterize genetic circuits in environments that more closely mimic cells’ natural 3D settings, to better explore complex cell–matrix and cell–cell interactions, and to facilitate therapeutic applications of synthetic biology.
Pathogenic bacterium
Helicobacter pylori
alters the expression profile of p53 protein isoforms and p53 response to cellular stresses
Authors: Wei Jinxiong , Noto Jennifer , Zaika Elena , Romero-Gallo Judith , Correa Pelayo , El-Rifai Wael , Peek Richard M. , Zaika Alexander
Published: August 2012

The p53 protein plays a central role in the prevention of tumorigenesis. Cellular stresses, such as DNA damage and aberrant oncogene activation, trigger induction of p53 that halts cellular proliferation and allows cells to be repaired. If cellular damage is beyond the capability of the repair mechanisms, p53 induces apoptosis or cell cycle arrest, preventing damaged cells from becoming cancerous. However, emerging evidence suggests that the function of p53 needs to be considered as isoform-specific. Here, we report that the expression profile of p53 can be shifted toward inhibitory p53 isoforms by the pathogenic bacterium
Helicobacter pylori
, which is known for its strong association with gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. We found that interaction of
H. pylori
with gastric epithelial cells, mediated via the
cag
pathogenicity island, induces N-terminally truncated ∆133p53 and ∆160p53 isoforms in human cells. Induction of an orthologous p53 isoform, ∆153p53, was also found in
H. pylori
-infected Mongolian gerbils. The p53 isoforms inhibit p53 and p73 activities, induce NF-κB, and increase survival of infected cells. Expression of ∆133p53, in response to
H. pylori
infection, is regulated by phosphorylation of c-Jun and activation of activator protein-1–dependent transcription. Together, these results provide unique insights into the regulation of p53 protein and may contribute to the understanding of tumorigenesis associated with
H. pylori
.
Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis
Authors: Castellano Joseph M. , Deane Rashid , Gottesdiener Andrew J. , Verghese Philip B. , Stewart Floy R. , West Tim , Paoletti Andrew C. , Kasper Tristan R. , DeMattos Ronald B. , Zlokovic Berislav V. , Holtzman David M.
Published: August 2012

The apolipoprotein E (
APOE
)
-
ε4 allele is the strongest genetic risk factor for late-onset, sporadic Alzheimer's disease, likely increasing risk by altering amyloid-β (Aβ) accumulation. We recently demonstrated that the low-density lipoprotein receptor (LDLR) is a major apoE receptor in the brain that strongly regulates amyloid plaque deposition. In the current study, we sought to understand the mechanism by which LDLR regulates Aβ accumulation by altering Aβ clearance from brain interstitial fluid. We hypothesized that increasing LDLR levels enhances blood–brain barrier-mediated Aβ clearance, thus leading to reduced Aβ accumulation. Using the brain Aβ efflux index method, we found that blood–brain barrier-mediated clearance of exogenously administered Aβ is enhanced with LDLR overexpression. We next developed a method to directly assess the elimination of centrally derived, endogenous Aβ into the plasma of mice using an anti-Aβ antibody that prevents degradation of plasma Aβ, allowing its rate of appearance from the brain to be measured. Using this plasma Aβ accumulation technique, we found that LDLR overexpression enhances brain-to-blood Aβ transport. Together, our results suggest a unique mechanism by which LDLR regulates brain-to-blood Aβ clearance, which may serve as a useful therapeutic avenue in targeting Aβ clearance from the brain.
Persistent cannabis users show neuropsychological decline from childhood to midlife
Authors: Meier Madeline H. , Caspi Avshalom , Ambler Antony , Harrington HonaLee , Houts Renate , Keefe Richard S. E. , McDonald Kay , Ward Aimee , Poulton Richie , Moffitt Terrie E.
Published: August 2012

Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health. Concomitantly, adolescents are initiating cannabis use at younger ages, and more adolescents are using cannabis on a daily basis. The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users. Participants were members of the Dunedin Study, a prospective study of a birth cohort of 1,037 individuals followed from birth (1972/1973) to age 38 y. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. Neuropsychological testing was conducted at age 13 y, before initiation of cannabis use, and again at age 38 y, after a pattern of persistent cannabis use had developed. Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, even after controlling for years of education. Informants also reported noticing more cognitive problems for persistent cannabis users. Impairment was concentrated among adolescent-onset cannabis users, with more persistent use associated with greater decline. Further, cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users. Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents.
Molecular basis for coupling the plasma membrane to the actin cytoskeleton during clathrin-mediated endocytosis
Authors: Skruzny Michal , Brach Thorsten , Ciuffa Rodolfo , Rybina Sofia , Wachsmuth Malte , Kaksonen Marko
Published: August 2012

Dynamic actin filaments are a crucial component of clathrin-mediated endocytosis when endocytic proteins cannot supply enough energy for vesicle budding. Actin cytoskeleton is thought to provide force for membrane invagination or vesicle scission, but how this force is transmitted to the plasma membrane is not understood. Here we describe the molecular mechanism of plasma membrane–actin cytoskeleton coupling mediated by cooperative action of epsin Ent1 and the HIP1R homolog Sla2 in yeast
Saccharomyces cerevisiae
. Sla2 anchors Ent1 to a stable endocytic coat by an unforeseen interaction between Sla2’s ANTH and Ent1’s ENTH lipid-binding domains. The ANTH and ENTH domains bind each other in a ligand-dependent manner to provide critical anchoring of both proteins to the membrane. The C-terminal parts of Ent1 and Sla2 bind redundantly to actin filaments via a previously unknown phospho-regulated actin-binding domain in Ent1 and the THATCH domain in Sla2. By the synergistic binding to the membrane and redundant interaction with actin, Ent1 and Sla2 form an essential molecular linker that transmits the force generated by the actin cytoskeleton to the plasma membrane, leading to membrane invagination and vesicle budding.
Serum Response Factor (SRF)-cofilin-actin signaling axis modulates mitochondrial dynamics
Authors: Beck Henning , Flynn Kevin , Lindenberg Katrin S. , Schwarz Heinz , Bradke Frank , Di Giovanni Simone , Knöll Bernd
Published: August 2012

Aberrant mitochondrial function, morphology, and transport are main features of neurodegenerative diseases. To date, mitochondrial transport within neurons is thought to rely mainly on microtubules, whereas actin might mediate short-range movements and mitochondrial anchoring. Here, we analyzed the impact of actin on neuronal mitochondrial size and localization. F-actin enhanced mitochondrial size and mitochondrial number in neurites and growth cones. In contrast, raising G-actin resulted in mitochondrial fragmentation and decreased mitochondrial abundance. Cellular F-actin/G-actin levels also regulate serum response factor (SRF)-mediated gene regulation, suggesting a possible link between SRF and mitochondrial dynamics. Indeed, SRF-deficient neurons display neurodegenerative hallmarks of mitochondria, including disrupted morphology, fragmentation, and impaired mitochondrial motility, as well as ATP energy metabolism. Conversely, constitutively active SRF-VP16 induced formation of mitochondrial networks and rescued huntingtin (HTT)-impaired mitochondrial dynamics. Finally, SRF and actin dynamics are connected via the actin severing protein cofilin and its slingshot phosphatase to modulate neuronal mitochondrial dynamics. In summary, our data suggest that the SRF-cofilin-actin signaling axis modulates neuronal mitochondrial function.
An insect-specific P450 oxidative decarbonylase for cuticular hydrocarbon biosynthesis
Authors: Qiu Yue , Tittiger Claus , Wicker-Thomas Claude , Le Goff Gaëlle , Young Sharon , Wajnberg Eric , Fricaux Thierry , Taquet Nathalie , Blomquist Gary J. , Feyereisen René
Published: August 2012

Insects use hydrocarbons as cuticular waterproofing agents and as contact pheromones. Although their biosynthesis from fatty acyl precursors is well established, the last step of hydrocarbon biosynthesis from long-chain fatty aldehydes has remained mysterious. We show here that insects use a P450 enzyme of the CYP4G family to oxidatively produce hydrocarbons from aldehydes. Oenocyte-directed RNAi knock-down of
Drosophila
CYP4G1 or NADPH-cytochrome P450 reductase results in flies deficient in cuticular hydrocarbons, highly susceptible to desiccation, and with reduced viability upon adult emergence. The heterologously expressed enzyme converts C
18
-trideuterated octadecanal to C
17
-trideuterated heptadecane, showing that the insect enzyme is an oxidative decarbonylase that catalyzes the cleavage of long-chain aldehydes to hydrocarbons with the release of carbon dioxide. This process is unlike cyanobacteria that use a nonheme diiron decarbonylase to make alkanes from aldehydes with the release of formate. The unique and highly conserved insect CYP4G enzymes are a key evolutionary innovation that allowed their colonization of land.
Structure and dynamics of protein waters revealed by radiolysis and mass spectrometry
Authors: Gupta Sayan , D’Mello Rhijuta , Chance Mark R.
Published: August 2012

Water is critical for the structure, stability, and functions of macromolecules. Diffraction and NMR studies have revealed structure and dynamics of bound waters at atomic resolution. However, localizing the sites and measuring the dynamics of bound waters, particularly on timescales relevant to catalysis and macromolecular assembly, is quite challenging. Here we demonstrate two techniques: first, temperature-dependent radiolytic hydroxyl radical labeling with a mass spectrometry (MS)-based readout to identify sites of bulk and bound water interactions with surface and internal residue side chains, and second, H
2
18
O radiolytic exchange coupled MS to measure the millisecond dynamics of bound water interactions with various internal residue side chains. Through an application of the methods to cytochrome
c
and ubiquitin, we identify sites of water binding and measure the millisecond dynamics of bound waters in protein crevices. As these MS-based techniques are very sensitive and not protein size limited, they promise to provide unique insights into protein–water interactions and water dynamics for both small and large proteins and their complexes.
Targeting collagen strands by photo-triggered triple-helix hybridization
Authors: Li Yang , Foss Catherine A. , Summerfield Daniel D. , Doyle Jefferson J. , Torok Collin M. , Dietz Harry C. , Pomper Martin G. , Yu S. Michael
Published: August 2012

Collagen remodeling is an integral part of tissue development, maintenance, and regeneration, but excessive remodeling is associated with various pathologic conditions. The ability to target collagens undergoing remodeling could lead to new diagnostics and therapeutics as well as applications in regenerative medicine; however, such collagens are often degraded and denatured, making them difficult to target with conventional approaches. Here, we present caged collagen mimetic peptides (CMPs) that can be photo-triggered to fold into triple helix and bind to collagens denatured by heat or by matrix metalloproteinase (MMP) digestion. Peptide-binding assays indicate that the binding is primarily driven by stereo-selective triple-helical hybridization between monomeric CMPs of high triple-helical propensity and denatured collagen strands. Photo-triggered hybridization allows specific staining of collagen chains in protein gels as well as photo-patterning of collagen and gelatin substrates. In vivo experiments demonstrate that systemically delivered CMPs can bind to collagens in bones, as well as prominently in articular cartilages and tumors characterized by high MMP activity. We further show that CMP-based probes can detect abnormal bone growth activity in a mouse model of Marfan syndrome. This is an entirely new way to target the microenvironment of abnormal tissues and could lead to new opportunities for management of numerous pathologic conditions associated with collagen remodeling and high MMP activity.
Photoperiodic regulation of the C-repeat binding factor (CBF) cold acclimation pathway and freezing tolerance inArabidopsis thaliana
Authors: Lee Chin-Mei , Thomashow Michael F.
Published: August 2012

The CBF (C-repeat binding factor) pathway has a major role in plant cold acclimation, the process whereby certain plants increase in freezing tolerance in response to low nonfreezing temperatures. InArabidopsis thaliana,the pathway is characterized by rapid cold induction ofCBF1,CBF2, andCBF3, which encode transcriptional activators, followed by induction of CBF-targeted genes that impart freezing tolerance. At warm temperatures,CBFtranscript levels are low, but oscillate due to circadian regulation with peak expression occurring at 8 h after dawn (zeitgeber time 8; ZT8). Here, we establish that the CBF pathway is also regulated by photoperiod at warm temperatures. At ZT8,CBFtranscript levels in short-day (SD; 8-h photoperiod) plants were three- to fivefold higher than in long-day plants (LD; 16-h photoperiod). Moreover, the freezing tolerance of SD plants was greater than that of LD plants. Genetic analysis indicated that phytochrome B (PHYB) and two phytochrome-interacting factors, PIF4 and PIF7, act to down-regulate the CBF pathway and freezing tolerance under LD conditions. Down-regulation of the CBF pathway in LD plants correlated with higherPIF4andPIF7transcript levels and greater stability of the PIF4 and PIF7 proteins under LD conditions. Our results indicate that during the warm LD growing season, the CBF pathway is actively repressed by PHYB, PIF4, and PIF7, thus mitigating allocation of energy and nutrient resources toward unneeded frost protection. This repression is relieved by shortening day length resulting in up-regulation of the CBF pathway and increased freezing tolerance in preparation for coming cold temperatures.
Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the
F
0
-ATPase
Authors: Mukherjee Shayantani , Warshel Arieh
Published: August 2012

The molecular origin of the action of the
F
0
proton gradient-driven rotor presents a major puzzle despite significant structural advances. Although important conceptual models have provided guidelines of how such systems should work, it has been challenging to generate a structure-based molecular model using physical principles that will consistently lead to the unidirectional proton-driven rotational motion during ATP synthesis. This work uses a coarse-grained (CG) model to simulate the energetics of the
F
0
-ATPase system in the combined space defined by the rotational coordinate and the proton transport (PTR) from the periplasmic side (P) to the cytoplasmic side (N). The model establishes the molecular origin of the rotation, showing that this effect is due to asymmetry in the energetics of the proton path rather than only the asymmetry of the interaction of the Asp on the c-ring helices and Arg on the subunit-a. The simulation provides a clear conceptual background for further exploration of the electrostatic basis of proton-driven mechanochemical systems.