bluuebunny/crossref_metadata_2025 huggingface dataset:
Transpancreatic sphincterotomy has a higher cannulation success rate than needle-knife precut papillotomy – a meta-analysis
Authors: Pécsi Dániel , Farkas Nelli , Hegyi Péter , Balaskó Márta , Czimmer József , Garami András , Illés Anita , Mosztbacher Dóra , Pár Gabriella , Párniczky Andrea , Sarlós Patrícia , Szabó Imre , Szemes Kata , Szűcs Ákos , Vincze Áron
Published: June 2017

Background and aim While many studies have discussed the different cannulation techniques used in patients with difficult biliary access, no previous meta-analyses have compared transpancreatic sphincterotomy (TPS) to other advanced techniques. Therefore, we aimed to identify all studies comparing the efficacy and adverse event rates of TPS with needle-knife precut papillotomy (NKPP), the most commonly used technique, and to perform a meta-analysis.

Methods The Embase, PubMed, and Cochrane databases were searched for trials comparing the outcomes of TPS with NKPP up till December 2016. A meta-analysis focusing on outcome (cannulation success, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), post-procedural bleeding, and total adverse events) was performed. The population, intervention, comparison, outcome (PICO) format was used to compare these cannulation approaches. Five prospective and eight retrospective studies were included in our meta-analysis.

Results NKPP has a significantly lower success rate (odds ratio [OR] 0.50, P = 0.046; relative risk [RR] 0.92, P = 0.03) and a higher rate of bleeding complications (OR 2.24, P = 0.02; RR 2.18, P = 0.02) than TPS. However, no significant differences were found in PEP (OR 0.79, P = 0.24; RR 0.80, P = 0.19), perforation (risk difference [RD] 0.01, P = 0.23), or total complication rates (OR 1.22, P = 0.44; RR 1.17, P = 0.47).

Conclusion While TPS has a higher success rate in difficult biliary access and causes less bleeding than NKPP, there are no differences in PEP, perforation, or total complication rates between the two approaches. We conclude that TPS, in the hands of expert endoscopists, is a safe procedure, which should be used more widely in patients with difficult biliary access.
Molecular origin of aging of pure Se glass: Growth of inter-chain structural correlations, network compaction, and partial ordering
Authors: Dash S. , Chen P. , Boolchand P.
Published: June 2017

Glass transition width W of pure Se narrows from 7.1(3) °C to 1.5(2) °C and the non-reversing enthalpy of relaxation (ΔHnr) at Tg increases from 0.23(5) cal/g to 0.90(5) cal/g upon room temperature aging for 4 months in the dark as examined in modulated differential scanning colorimetry (MDSC) at low scan rates. In Raman scattering, such aging leads the A1 mode of Sen-chains (near 250 cm−1) to narrow by 26% and its scattering strength to decrease as the strength of modes of correlated chains (near 235 cm−1) and of Se8 rings (near 264 cm−1) systematically grows. These calorimetric and Raman scattering results are consistent with the “molecular” chains of Sen, predominant in the fresh glass, reconstructing with each other to compact and partially order the network. Consequences of the aging induced reconstruction of the long super-flexible and uncorrelated Sen-chains are also manifested upon alloying up to 4 mol. % of Ge as revealed by a qualitative narrowing (by 25%) of the Raman vibrational mode of the corner-sharing GeSe4 tetrahedra and a blue-shift of the said mode by nearly 1 cm−1 in 194 cm−1. But, at higher Ge content (x> 6%), as the length of Sen chain-segments across Ge cross-links decreases qualitatively (⟨n⟩ < 8), these aging induced chain-reconstruction effects are suppressed. The width of Tg increases beyond 15 °C in binary GexSe100−x glasses as x> 10% to acquire values observed earlier as alloying concentration approaches 20% and networks become spontaneously rigid.
Strongly aligned molecules inside helium droplets in the near-adiabatic regime
Authors: Shepperson Benjamin , Chatterley Adam S. , Søndergaard Anders A. , Christiansen Lars , Lemeshko Mikhail , Stapelfeldt Henrik
Published: June 2017

Iodine (I2) molecules embedded in He nanodroplets are aligned by a 160 ps long laser pulse. The highest degree of alignment, occurring at the peak of the pulse and quantified by ⟨cos2𝜃2D⟩, is measured as a function of the laser intensity. The results are well described by ⟨cos2𝜃2D⟩ calculated for a gas of isolated molecules each with an effective rotational constant of 0.6 times the gas-phase value and at a temperature of 0.4 K. Theoretical analysis using the angulon quasiparticle to describe rotating molecules in superfluid helium rationalizes why the alignment mechanism is similar to that of isolated molecules with an effective rotational constant. A major advantage of molecules in He droplets is that their 0.4 K temperature leads to stronger alignment than what can generally be achieved for gas phase molecules—here demonstrated by a direct comparison of the droplet results to measurements on a ∼1 K supersonic beam of isolated molecules. This point is further illustrated for a more complex system by measurements on 1,4-diiodobenzene and 1,4-dibromobenzene. For all three molecular species studied, the highest values of ⟨cos2𝜃2D⟩ achieved in He droplets exceed 0.96.
Low-energy photoelectron transmission through aerosol overlayers
Authors: Amanatidis Stavros , Yoder Bruce L. , Signorell Ruth
Published: June 2017

The transmission of low-energy (<1.8 eV) photoelectrons through the shell of core-shell aerosol particles is studied for liquid squalane, squalene, and di-ethyl-hexyl-sebacate shells. The photoelectrons are exclusively formed in the core of the particles by two-photon ionization. The total photoelectron yield recorded as a function of shell thicknesses (1–80 nm) shows a bi-exponential attenuation. For all substances, the damping parameter for shell thicknesses below 15 nm lies around 8 to 9 nm and is tentatively assigned to the electron attenuation length at electron kinetic energies of ≲1 eV. The significantly larger damping parameters for thick shells (>20 nm) are presumably a consequence of distorted core-shell structures. A first comparison of aerosol and traditional thin film overlayer methods is provided.
Comment on “The thermodynamical instability induced by pressure ionization in fluid helium” [Phys. Plasmas 23, 112709 (2016)]
Authors: Quan W. L.
Published: June 2017

In a recent paper, Li et al. [Phys. Plasmas 23, 112709 (2016)] reported the instability induced by pressure ionization in fluid helium based on minimization of Helmholtz free energy within chemical picture. Here, I argue that their calculations may have some bugs directly resulting in the so-called instability, because a problematic iterative strategy also produces a similar, but mathematically incorrect instability that can be removed by improving iterative strategy.
Transient growth of optimal perturbation in a decaying channel flow
Authors: Nayak Avinash , Das Debopam
Published: June 2017

Stability of an unsteady channel flow is investigated by incorporating the effect of the base flow change with time and comparing with the optimal growth of the normal mode analysis. The existing literature shows that the modal analysis can be done on the velocity profiles in a quasi-steady manner to study the stability characteristics of unsteady internal flows. But, in the current study, it is shown that the mode obtained from the optimal growth analysis provides higher growth and estimates the structures observed in experiments. Initially, the optimal mode is obtained using Farrell’s analysis, and its energy growth is compared with that of the most unstable eigenmode. Later, to incorporate the base flow change, the optimal mode for maximum growth is obtained by solving the problem with a variational approach. The results are compared to provide justification of Farrell’s analysis, which is quasi-steady, against the requirement of complete study considering the time dependent base flow.
Fragment size distribution statistics in dynamic fragmentation of laser shock-loaded tin
Authors: He Weihua , Xin Jianting , Zhao Yongqiang , Chu Genbai , Xi Tao , Shui Min , Lu Feng , Gu Yuqiu
Published: June 2017

This work investigates the geometric statistics method to characterize the size distribution of tin fragments produced in the laser shock-loaded dynamic fragmentation process. In the shock experiments, the ejection of the tin sample with etched V-shape groove in the free surface are collected by the soft recovery technique. Subsequently, the produced fragments are automatically detected with the fine post-shot analysis techniques including the X-ray micro-tomography and the improved watershed method. To characterize the size distributions of the fragments, a theoretical random geometric statistics model based on Poisson mixtures is derived for dynamic heterogeneous fragmentation problem, which reveals linear combinational exponential distribution. The experimental data related to fragment size distributions of the laser shock-loaded tin sample are examined with the proposed theoretical model, and its fitting performance is compared with that of other state-of-the-art fragment size distribution models. The comparison results prove that our proposed model can provide far more reasonable fitting result for the laser shock-loaded tin.
Structural entanglements in protein complexes
Authors: Zhao Yani , Chwastyk Mateusz , Cieplak Marek
Published: June 2017

We consider multi-chain protein native structures and propose a criterion that determines whether two chains in the system are entangled or not. The criterion is based on the behavior observed by pulling at both termini of each chain simultaneously in the two chains. We have identified about 900 entangled systems in the Protein Data Bank and provided a more detailed analysis for several of them. We argue that entanglement enhances the thermodynamic stability of the system but it may have other functions: burying the hydrophobic residues at the interface and increasing the DNA or RNA binding area. We also study the folding and stretching properties of the knotted dimeric proteins MJ0366, YibK, and bacteriophytochrome. These proteins have been studied theoretically in their monomeric versions so far. The dimers are seen to separate on stretching through the tensile mechanism and the characteristic unraveling force depends on the pulling direction.
Thermal transport dynamics in the quasi-single helicity state
Authors: McKinney I. J. , Terry P. W.
Published: June 2017

A dynamical model describing oscillations between multiple and single helicity configurations in the quasi-single helicity (QSH) state of the reversed field pinch [P. W. Terry and G. G. Whelan, Plasma Phys. Controlled Fusion 56, 094003 (2014)] is extended to include electron temperature profile dynamics. It is shown that QSH dynamics is linked to the electron temperature profile because the suppression of mode coupling between tearing modes proposed to underlie QSH also suppresses magnetic-fluctuation-induced thermal transport. Above the threshold of dominant-mode shear that marks the transition to QSH, the model produces temperature-gradient steepening in the strong shear region. Oscillations of the dominant and secondary mode amplitudes give rise to oscillations of the temperature gradient. The phasing and amplitude of temperature gradient oscillations relative to those of the dominant mode are in agreement with experiment. This provides further evidence that the model, while heuristic, captures key physical aspects of the QSH state.
Noncollinear antiferromagnetic Haldane magnon insulator
Authors: Owerre S. A.
Published: June 2017

In this paper, we present a comprehensive study of topological magnon bands and thermal Hall effect in non-collinear antiferromagnetic systems on the honeycomb lattice with an intrinsic Dzyaloshinskii-Moriya interaction. We theoretically show that the system possesses topological magnon bands with Chern number protected edge modes accompanied by a nonzero thermal magnon Hall effect. These features result from non-collinearity of the magnetic moments due to an applied out-of-plane magnetic field. Our results provide an experimental clue towards the realization of topological magnon transports in honeycomb antiferromagnetic compounds such as XPS3 (X = Mn,Fe) and α-Cu2V2O7.
Role of oxygen vacancies for resistive switching in noble metal sandwiched Pr0.67Ca0.33MnO3-δ
Authors: Kramer Thilo , Scherff Malte , Mierwaldt Daniel , Hoffmann Joerg , Jooss Christian
Published: June 2017

Non-volatile resistance change under electric stimulation in oxides is a promising path to next generation memory devices. However, the underlying mechanisms are still not fully understood. We report here on the study of switching in Pr0.67Ca0.33MnO3-δ (PCMO) films sandwiched by noble metal Pt electrodes, where electrode oxidation can be excluded. In order to develop an understanding of the switching induced oxygen migration, its initial concentration is modified by post-annealing of the deposited PCMO films. The oxygen distribution is obtained by manganese valence determination using spatially resolved electron energy loss spectroscopy in scanning transmission electron microscopy mode. We observe correlations between virgin state resistance, resistive switching properties, oxygen vacancy distribution, and stress/strain state of the PCMO films and propose a simplified interface resistance model based on the measured valence distribution. It assumes a linear correlation of oxygen vacancy concentration with conductivity and a metal to insulator transition above a critical vacancy concentration threshold. Our results suggest that resistance changes can take place at both interfaces of symmetric devices and only requires small changes in oxygen vacancy concentration.
A novel large thrust-weight ratio V-shaped linear ultrasonic motor with a flexible joint
Authors: Li Xiaoniu , Yao Zhiyuan , Yang Mojian
Published: June 2017

A novel large thrust-weight ratio V-shaped linear ultrasonic motor with a flexible joint is proposed in this paper. The motor is comprised of a V-shaped transducer, a slider, a clamp, and a base. The V-shaped transducer consists of two piezoelectric beams connected through a flexible joint to form an appropriate coupling angle. The V-shaped motor is operated in the coupled longitudinal-bending mode. Longitudinal and bending movements are transferred by the flexible joint between the two beams. Compared with the coupled longitudinal-bending mode of the single piezoelectric beam or the symmetrical and asymmetrical modes of the previous V-shaped transducer, the coupled longitudinal-bending mode of the V-shaped transducer with a flexible joint provides higher vibration efficiency and more convenient mode conformance adjustment. A finite element model of the V-shaped transducer is created to numerically study the influence of geometrical parameters and to determine the final geometrical parameters. In this paper, three prototypes were then fabricated and experimentally investigated. The modal test results match well with the finite element analysis. The motor mechanical output characteristics of three different coupling angles θ indicate that V-90 (θ = 90°) is the optimal angle. The mechanical output experiments conducted using the V-90 prototype (Size: 59.4 mm × 30.7 mm × 4 mm) demonstrate that the maximum unloaded speed is 1.2 m/s under a voltage of 350 Vpp, and the maximum output force is 15 N under a voltage of 300 Vpp. The proposed novel V-shaped linear ultrasonic motor has a compact size and a simple structure with a large thrust-weight ratio (0.75 N/g) and high speed.
Formation and interaction of multiple coherent phase space structures in plasma
Authors: Kakad Amar , Kakad Bharati , Omura Yoshiharu
Published: June 2017

The head-on collision of multiple counter-propagating coherent phase space structures associated with the ion acoustic solitary waves (IASWs) in plasmas composed of hot electrons and cold ions is studied here by using one-dimensional Particle-in-Cell simulation. The chains of counter-propagating IASWs are generated in the plasma by injecting the Gaussian perturbations in the equilibrium electron and ion densities. The head-on collisions of the counter-propagating electron and ion phase space structures associated with IASWs are allowed by considering the periodic boundary condition in the simulation. Our simulation shows that the phase space structures are less significantly affected by their collision with each other. They emerge out from each other by retaining their characteristics, so that they follow soliton type behavior. We also find that the electrons trapped within these IASW potentials are accelerated, while the ions are decelerated during the course of their collisions.
In vitro-assisted single-seed descent for breeding-cycle compression in subterranean clover (Trifolium subterraneum L.)
Authors: Pazos-Navarro Maria , Castello Marieclaire , Bennett Richard G. , Nichols Phillip , Croser Janine
Published: June 2017

Subterranean clover (Trifolium subterraneum L.) is widely grown for its forage and ability to fix atmospheric nitrogen. Development of new varieties is constrained by the slow turnover time of generations, with only one generation per year possible under field conditions. We present an in vitro-assisted single-seed descent (IVASSD) technique, which enabled turnover of 2.7–6.1 generations per year across a diverse range of 27 T. subterraneum cultivars encompassing subspecies subterraneum, yanninicum and brachycalycinum. The IVASSD protocol accelerated the generation cycle in two ways: (i) time to floral initiation was minimised by growth under controlled temperature and extended photoperiod; and (ii) the seed-filling period was truncated and embryo and seed-coat dormancy avoided by the in vitro germination of immature seed on B5 medium plus L6KK overlay (0.525 mg gibberellic acid and 1.5 mg indole-butyric acid L–1). For the first time, an IVASSD system was validated on a full-scale breeding population with the production of 175 F7 recombinant inbred lines from an F4 population in less than one year. All F7 plants obtained were morphologically normal and fertile.
Application of a livestock weight model to the 2009–2010 winter disaster in Mongolia
Authors: Tachiiri Kaoru , Komiyama Hiroshi , Morinaga Yuki , Shinoda Masato
Published: June 2017

Mongolia has historically experienced winter disasters (called dzud in Mongolian), which seriously damage the livestock sector. To reduce this damage, it is necessary to foresee the risk in advance. To do so, we applied a process-based livestock weight model based on the balance of energy intake and energy loss, each of which is calculated from environmental conditions. The spatial unit of the model is the province (aimag), and biomass amount derived from remote sensing and climatic data extracted from existing datasets were used as environmental conditions. We ran the model with parameters for sheep and validated the output using data of dzud in 2009–2010 and of the prior and subsequent years, comparing modelled sheep weight with spatial and temporal variation of observed sheep mortality. The model represented the basic feature of observed seasonal sheep weight change, and output smaller weights during 2009–2010, corresponding to the historic dzud of that period. A statistically significant (at 1% level) negative correlation was found between modelled weight and observed mortality. Determining the anomaly from the provincial average for 3 years further improved consistency. The model still has significant residuals, but is expected to contribute to dzud risk assessment by incorporating the effect of short-term, extreme climatic events (e.g. storms) and social factors.
Socioeconomic disadvantage, gestational immune activity, and neurodevelopment in early childhood
Authors: Gilman Stephen E. , Hornig Mady , Ghassabian Akhgar , Hahn Jill , Cherkerzian Sara , Albert Paul S. , Buka Stephen L. , Goldstein Jill M.
Published: June 2017

Significance

Children raised in economically disadvantaged households face increased risks of poor health in adulthood, suggesting early origins of socioeconomic inequalities in health. In fact, maternal immune activity in response to stressful conditions during pregnancy has been found to play a key role in fetal brain development. Here we show that socioeconomic disadvantage is associated with lower concentrations of the pro-inflammatory cytokine IL-8 during the third trimester of pregnancy and, in turn, with offspring’s neurologic abnormalities during the first year of life. These results suggest stress–immune mechanisms as one potential pathophysiologic pathway involved in the early origins of population health inequalities.
Carbohydrate microarrays and their use for the identification of molecular markers for plant cell wall composition
Authors: Wood Ian P. , Pearson Bruce M. , Garcia-Gutierrez Enriqueta , Havlickova Lenka , He Zhesi , Harper Andrea L. , Bancroft Ian , Waldron Keith W.
Published: June 2017

Significance

Plant cell wall (PCW) composition determines the nature and quality of many biologically derived products and, therefore, is a major target for genetic improvement. However, the identities and functions of many genes involved in PCW synthesis are still not known. Genome-wide association mapping studies (GWAS) are one of the few ways to identify these genes. However, collecting precise and quantitative PCW phenotype data at the scale required for GWAS is a significant challenge. Here, we demonstrate that high-density carbohydrate microarrays can be used as a PCW phenotyping strategy suitable for GWAS. Results presented in this study will aid in the understanding of PCW genetics and crop breeding for improved PCW composition.
Brain circuit–gene expression relationships and neuroplasticity of multisensory cortices in blind children
Authors: Ortiz-Terán Laura , Diez Ibai , Ortiz Tomás , Perez David L. , Aragón Jose Ignacio , Costumero Victor , Pascual-Leone Alvaro , El Fakhri Georges , Sepulcre Jorge
Published: June 2017

Significance

This cortical connectivity study shows that neuroplastic reorganization in blind children involves key multisensory integration regions. Using two complementary functional connectivity graph theory analyses, multimodal integration areas exhibited increased connectivity in blind children compared with matched controls; within-group analyses also demonstrated that functional connectivity changes increased with age. Evidence is provided that the spatial cortical expression of genes implicated in neuroplasticity underlies the reorganizational capabilities of the multimodal cortex.
Females manipulate behavior of caring males via prenatal maternal effects
Authors: Paquet Matthieu , Smiseth Per T.
Published: June 2017

Significance

In biparental species, sexual conflict arises as each parent attempts to minimize its personal effort. Most work has focused on how this conflict is resolved through symmetrical decisions between parents. We investigated whether females can influence male decisions by altering the offspring’s phenotype via the eggs. We manipulated the prenatal presence of the male, performed a cross-fostering experiment, and monitored the subsequent effects on offspring and parent performance. Offspring laid in presence of a male were smaller at hatching. In addition, males lost more weight when with larvae laid in presence of a male. Our results show that females can manipulate male behavior, suggesting that prenatal maternal effects can play an important role in the resolution of sexual conflict between parents.
Specific targeting of TGF-β family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease
Authors: Chen Justin L. , Walton Kelly L. , Hagg Adam , Colgan Timothy D. , Johnson Katharine , Qian Hongwei , Gregorevic Paul , Harrison Craig A.
Published: June 2017

Significance

Myostatin, via activation of the Smad2/3 pathway, has long been recognized as the body’s major negative regulator of skeletal muscle mass. In this study, however, we demonstrate that other TGF-β proteins, particularly activin A and activin B, act in concert with myostatin to repress muscle growth. Preventing activin and myostatin signaling in the tibialis anterior muscles of mice resulted in massive hypertrophy (>150%), which was dependent upon both the complete inhibition of the Smad2/3 pathway and activation of the parallel bone morphogenetic protein (BMP)/Smad1/5 axis. Using this approach in models of muscular dystrophy and cancer cachexia increased muscle mass or prevented muscle wasting, respectively, highlighting the potential therapeutic advantages of complete inhibition of Smad2/3 ligand activity in skeletal muscle.
Computationally optimized deimmunization libraries yield highly mutated enzymes with low immunogenicity and enhanced activity
Authors: Salvat Regina S. , Verma Deeptak , Parker Andrew S. , Kirsch Jack R. , Brooks Seth A. , Bailey-Kellogg Chris , Griswold Karl E.
Published: June 2017

Significance

Nature produces a variety of proteins that could be tapped for therapeutic applications. This paper focuses on the bacterial enzyme β-lactamase, a component of antibody-directed enzyme prodrug therapies designed to activate cytotoxic prodrugs selectively at sites of malignancy. Unfortunately, like many other nonhuman proteins, β-lactamase evokes an antidrug immune response that limits its clinical potential. This paper demonstrates that a multiobjective library-design method enables incorporation of mutations throughout the protein, modifying portions that trigger immune recognition while simultaneously preserving stability and catalytic activity. The libraries were inherently enriched in beneficial variants, and they produced numerous candidates that were both highly functional and immunologically stealthy. The method is general purpose and could enable functional deimmunization of other biotherapeutic agents.
Electron-shuttling antibiotics structure bacterial communities by modulating cellular levels of c-di-GMP
Authors: Okegbe Chinweike , Fields Blanche L. , Cole Stephanie J. , Beierschmitt Christopher , Morgan Chase J. , Price-Whelan Alexa , Stewart Richard C. , Lee Vincent T. , Dietrich Lars E. P.
Published: June 2017

Significance

In cells residing within communities, limitation for electron acceptors (e.g., oxygen) leads to redox imbalance and hampers metabolism.
Pseudomonas aeruginosa
bacteria in biofilms produce antibiotics called phenazines that facilitate redox balancing. When phenazines and oxygen are not sufficiently available,
P. aeruginosa
biofilms increase production of ECM, which increases surface area-to-volume ratio and access to oxygen. Here, we describe RmcA, a protein that regulates matrix production in response to phenazine exposure. RmcA contains four sensing domains and two domains that modulate levels of a small-molecule inducer of matrix secretion. These results provide molecular insight into mechanisms underpinning the adaptability of
P. aeruginosa
biofilms, which likely contributes to their persistence in diverse hosts and clinical settings.
Ca
2+
-induced movement of tropomyosin on native cardiac thin filaments revealed by cryoelectron microscopy
Authors: Risi Cristina , Eisner Jamie , Belknap Betty , Heeley David H. , White Howard D. , Schröder Gunnar F. , Galkin Vitold E.
Published: June 2017

Significance

Muscle contraction is required for critical physiological functions. It relies on the interaction of myosin motors with the thin filament (TF), which is regulated through a translocation of tropomyosin on the surface of F-actin by the troponin complex in response to Ca
2+
. The lack of high-resolution structure of the TF under relaxing (low-Ca
2+
) and activating (high-Ca
2+
) conditions impairs our understanding of the mechanism of cardiac muscle regulation. Here we report high-resolution structures of the native cardiac TF under relaxing and activating conditions. Our data lead to a model for cardiac TF regulation by Ca
2+
levels that is an important step in understanding how the components of cardiac muscle work in concert to maintain healthy heart functions.
Biomechanical coupling facilitates spinal neural tube closure in mouse embryos
Authors: Galea Gabriel L. , Cho Young-June , Galea Gauden , Molè Matteo A. , Rolo Ana , Savery Dawn , Moulding Dale , Culshaw Lucy H. , Nikolopoulou Evanthia , Greene Nicholas D. E. , Copp Andrew J.
Published: June 2017

Significance

Neurulation has been intensively studied in lower vertebrates, but marked species differences call into question the relevance of these models for human neural tube (NT) closure. Here, using mouse embryos, we demonstrate that mammalian neural fold apposition results from constriction of the open posterior NT, which is biomechanically coupled to the zippering point by an F-actin network. Using the
Zic2
mutant model, we show that genetic predisposition to spina bifida, which likely underlies most human cases, directly affects the biomechanics of closure. We also identify a NT closure point at the caudal end of the embryo. Many spina bifida cases correspond to this anatomic portion of the NT, suggesting that this closure point may be important in humans as well.
Selective oxidation of aliphatic C–H bonds in alkylphenols by a chemomimetic biocatalytic system
Authors: Du Lei , Dong Sheng , Zhang Xingwang , Jiang Chengying , Chen Jingfei , Yao Lishan , Wang Xiao , Wan Xiaobo , Liu Xi , Wang Xinquan , Huang Shaohua , Cui Qiu , Feng Yingang , Liu Shuang-Jiang , Li Shengying
Published: June 2017

Significance

Selective oxidation of aliphatic C–H bonds in alkylphenols is important for both structural derivatization and biological degradation of these fundamental chemicals. However, significant problems are persistently associated with the chemical methods for this oxofunctionalization. In this study, we developed a unique chemomimetic biocatalytic system that is capable of selectively oxidizingp- andm-alkylated phenols in a controllable manner, overcoming the challenges faced by similar chemical oxidation. The structural and bioinformatics analyses of the central P450 biocatalyst CreJ suggest that its substrate flexibility and reaction selectivity could be further leveraged. This novel alkylphenol biooxidation system may hold great potential for application in pharmaceutical, biomanufacturing, and environmental industries once upscaled systems can be further developed in the future.
Trigger loop of RNA polymerase is a positional, not acid–base, catalyst for both transcription and proofreading
Authors: Mishanina Tatiana V. , Palo Michael Z. , Nayak Dhananjaya , Mooney Rachel A. , Landick Robert
Published: June 2017

Significance

Synthesis of new RNA and removal of incorrect nucleotides during proofreading by RNA polymerase involve the transfer of two protons. Here, we show that a polymerase component, the trigger loop, does not directly mediate proton transfer during these reactions, as previously proposed. Instead, the trigger loop plays a central role in transcription as a positional catalyst, by orienting the reactants and promoting the polymerase backtracking necessary for proofreading. This positional-catalyst model of trigger-loop function explains its diverse effects on polymerase catalysis and reconciles contradictory reports in the literature. By establishing that the trigger loop is not an acid–base catalyst, our results also guide the search for alternative proton donors and acceptors for reactions in the active site of polymerase.
Bioengineered silkworms with butterfly cytotoxin-modified silk glands produce sericin cocoons with a utility for a new biomaterial
Authors: Otsuki Ryosuke , Yamamoto Masafumi , Matsumoto Erika , Iwamoto Shin-ichi , Sezutsu Hideki , Suzui Masumi , Takaki Keiko , Wakabayashi Keiji , Mori Hajime , Kotani Eiji
Published: June 2017

Significance

Specific gene functions have been successfully suppressed by gene silencing or editing in many organisms. However, genetic manipulation to suppress the function of a target tissue has not been achieved using cytotoxin genes. We established transgenic silkworms with posterior silk glands (PSGs) that express the enzymatic domain of the cytotoxin pierisin-1A (P1A). The larvae with the modified PSGs produced the sericin cocoons with potential utilities in tissue engineering. The targeted P1A expression was found to cause site-specific repression of certain protein synthesis that appeared to have no impact on the developmental stages of individuals. Thus, the new approach through targeted P1A expression could be applicable to the development of biologically useful model organisms with tissue-specific dysfunction.
Adaptor protein mediates dynamic pump assembly for bacterial metal efflux
Authors: Santiago Ace George , Chen Tai-Yen , Genova Lauren A. , Jung Won , George Thompson Alayna M. , McEvoy Megan M. , Chen Peng
Published: June 2017

Significance

Multicomponent efflux pumps confer clinically relevant drug resistance in Gram-negative bacteria. These pumps, once assembled to function, traverse the periplasm linking inner and outer membranes tightly. However, little is known on how these pumps can operate efficiently without compromising periplasmic plasticity. We show here that in
Escherichia coli
, the tripartite complex CusCBA for Cu
+
and Ag
+
efflux exists as a dynamic structure and shifts toward the assembled form in response to metal stress. Unexpectedly, the periplasmic adaptor protein CusB is a key metal-sensing protein that mediates the complex assembly. This adaptor protein-mediated dynamic pump assembly allows the bacterial cell for efficient efflux on cellular demand while still maintaining periplasmic plasticity; it can be broadly relevant to other multicomponent efflux systems.
Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry
Authors: Lounková Anna , Kosla Jan , Přikryl David , Štafl Kryštof , Kučerová Dana , Svoboda Jan
Published: June 2017

Significance

The emergence of novel infectious diseases is often associated with cross-species virus transmission. Virus host range is owed, in large part, to genetic variation of its envelope gene. The illustrative example presented here is based on a structural study of the Rous sarcoma virus (RSV) avian retrovirus passaged twice through rodents. RSV heterotransmission was enabled by spontaneous envelope gene mutations, which allow virus entry even into human and other receptor-free cells. Through three independent biochemical assays, we established that these mutations caused conformational change similar to the one that follows virus–receptor interaction. The newly identified envelope mutations responsible for the broad retrovirus host range contribute to our understanding of retroviruses’ pathogenicity and their ability to cross the transclass barriers.
Maintenance of antiangiogenic and antitumor effects by orally active low-dose capecitabine for long-term cancer therapy
Authors: Zhang Yin , Sun Meili , Huang Guichun , Yin Linlin , Lai Qinghua , Yang Yunlong , Xing Xiaoming , Yu Guohua , Sun Yuping , Wang Xinsheng , Nie Guohui , Liu Yizhi , Cao Yihai
Published: June 2017

Significance

Withdrawal of antiangiogenic drugs leads to tumor revascularization, even rebound effects of tumor angiogenesis, and potential metastasis. Long-term maintenance therapy with antiangiogenic drugs is crucial for achieving maximal clinical benefits for cancer patients. There are no antiangiogenic drugs that are clinically available for maintenance therapy. We show that orally active capecitabine at an extremely low and nontoxic dose displays a potent antiangiogenic effect that can be used for maintenance therapy. Importantly, the low-dose capecitabine in a sequentially therapeutic setting following anti-VEGF drugs produces remarkable anticancer effects. If successfully proven in clinical settings, our therapeutic regimen would be beneficial for millions of cancer patients. Our findings will shift the paradigm of current antiangiogenic therapy for treatment of human cancer patients.
Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5
Authors: Zhang Duanwu , Tomisato Wataru , Su Lijing , Sun Lei , Choi Jin Huk , Zhang Zhao , Wang Kuan-wen , Zhan Xiaoming , Choi Mihwa , Li Xiaohong , Tang Miao , Castro-Perez Jose M. , Hildebrand Sara , Murray Anne R. , Moresco Eva Marie Y. , Beutler Bruce
Published: June 2017

Significance

We discovered a previously unrecognized regulator of cholesterol biosynthesis, glycerol kinase 5 (GK5), which functions exclusively in the skin independently of cholesterol regulation in other tissues. GK5 negatively regulates the processing and nuclear localization of sterol regulatory element binding proteins, transcription factors that control expression of virtually all cholesterol synthesis enzymes. Excessive amounts of cholesterol, triglycerides, and ceramides were found in the skin of GK5-deficient mice. These mice displayed alopecia (hair loss) caused by impaired hair growth and maintenance, for which proper amounts of cholesterol and other skin lipids are necessary.
Structural studies of viperin, an antiviral radical SAM enzyme
Authors: Fenwick Michael K. , Li Yue , Cresswell Peter , Modis Yorgo , Ealick Steven E.
Published: June 2017

Significance

We report structures of viperin, an antiviral radicalS-adenosylmethionine (SAM) enzyme. The overall structure shows a canonical radical SAM enzyme fold that harbors a [4Fe-4S] cluster. Structures with a bound SAM analog or SAM cleavage products are consistent with a conventional mechanism of radical formation. Sequence alignments guided by the putative active site residues of viperin reveal viperin-like enzymes in species from all kingdoms of life. Structural alignments show similarity between viperin and the molybdenum cofactor biosynthetic enzyme MoaA and show that the active site architecture of viperin is consistent with a nucleoside triphosphate substrate.
Prostaglandin E2 is essential for efficacious skeletal muscle stem-cell function, augmenting regeneration and strength
Authors: Ho Andrew T. V. , Palla Adelaida R. , Blake Matthew R. , Yucel Nora D. , Wang Yu Xin , Magnusson Klas E. G. , Holbrook Colin A. , Kraft Peggy E. , Delp Scott L. , Blau Helen M.
Published: June 2017

Significance

Muscle repair after injury entails an immune response that orchestrates efficacious regeneration. Here we identify Prostaglandin E2 (PGE2) as a crucial inflammatory mediator of muscle stem cells (MuSCs), the building blocks of muscle regeneration. PGE2 is synthesized and secreted into the stem-cell niche in response to injury, leading to robust MuSC proliferation, key to myofiber repair. EP4 is the receptor that mediates PGE2 signaling in MuSCs, and genetically engineered mice that lack EP4 in MuSCs have impaired regeneration. Nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used to treat pain after muscle injury, inhibit PGE2 synthesis, hinder muscle regeneration, and lead to weakened muscles. Importantly, a single treatment of injured muscles with PGE2 dramatically accelerates muscle repair and recovery of strength.
Dynamic maps of UV damage formation and repair for the human genome
Authors: Hu Jinchuan , Adebali Ogun , Adar Sheera , Sancar Aziz
Published: June 2017

Significance

Nucleotide excision repair removes DNA damage caused by carcinogens, such as UV and anticancer drugs, such as cisplatin. We have developed two methods, high-sensitivity damage sequencing and excision repair sequencing that map the formation and repair of damage in the human genome at single-nucleotide resolution. The combination of dynamic damage and repair maps provides a holistic perspective of UV damage and repair of the human genome and has potential applications in cancer prevention and chemotherapy.
Broken flow symmetry explains the dynamics of small particles in deterministic lateral displacement arrays
Authors: Kim Sung-Cheol , Wunsch Benjamin H. , Hu Huan , Smith Joshua T. , Austin Robert H. , Stolovitzky Gustavo
Published: June 2017

Significance

Deterministic lateral displacement (DLD) is a technique for size fractionation of particles in continuous flow that has shown great potential for biological and clinical applications. Several theoretical models have been proposed to explain the trajectories of different-sized particles in relation to the geometry of the pillar array, but experimental evidence has demonstrated that a rich class of intermediate migration behavior exists, which is not predicted by models. In this work, we present a unified theoretical framework to infer the trajectory of particles in the whole array on the basis of trajectories in the unit cell. This framework explains many of the unexpected particle trajectories reported in literature and can be used to design arrays for the fractionation of particles, even at the smallest scales reaching the molecular realm. We also performed experiments that verified our predictions, even at the nanoscales. Using our model as a set of design rules, we developed a condenser structure that achieves full particle separation with a single fluidic input.
Interface-induced multiferroism by design in complex oxide superlattices
Authors: Guo Hangwen , Wang Zhen , Dong Shuai , Ghosh Saurabh , Saghayezhian Mohammad , Chen Lina , Weng Yakui , Herklotz Andreas , Ward Thomas Z. , Jin Rongying , Pantelides Sokrates T. , Zhu Yimei , Zhang Jiandi , Plummer E. W.
Published: June 2017

Significance

Developments in synthesis and characterizing artificially structured materials have greatly advanced the possibility to explore new states of matter in material science. Recent discoveries show that new quantum states can be achieved at heterointerfaces with various electric and mechanical boundary conditions. It remains an open question of how to design ultrathin layers with properties inaccessible in bulk phases that are amenable to technological applications. In this work, we grow heterostructures with extremely high-quality interfaces shown by state-of-the-art atomically resolved electron microscopy and spectroscopy. This combination allows us to identify an interface-induced structure that stabilizes ferromagnetism. Coupled with theory, we provide a conceptually useful recipe to design low-dimensional materials with unique functionalities, in line with the loop “make, measure, model.”
Hydroacoustic Assessment of Behavioral Responses by Fish Passing Near an Operating Tidal Turbine in the East River, New York
Authors: Bevelhimer Mark , Scherelis Constantin , Colby Jonathan , Adonizio Mary Ann
Published: June 2017

An important environmental issue facing the marine and hydrokinetic energy industry is whether fish that encounter underwater energy devices are likely to be struck and injured by moving components, primarily rotating turbine blades. The automated analysis of nearly 3 weeks of multibeam hydroacoustics data identified about 35,000 tracks of fish passing a tidal turbine in the East River, New York. These tracks included both individual fish and schools during periods with the turbine absent, the turbine present and operating, and the turbine present but not operating. The density of fish in the sampled area when the turbine was absent was roughly twice the density observed when the turbine was in place, particularly when the turbine was operating. This suggests that some avoidance occurred before fish were close enough to the turbine to be observed by the hydroacoustics system. Various measures of swimming behavior (direction, velocity, and linearity) were calculated for each track and evaluated for indication of behavioral responses to turbine presence and operation. Fish tracks were grouped based on tidal cycle, current velocity, and swimming direction and were evaluated with respect to turbine presence and operation and with respect to distance from the turbine. Nonparametric tests (Kolmogorov–Smirnov test) and multivariate analysis (canonical discriminant analysis) found significant differences among groups with respect to turbine presence and operation, suggesting that some fish responded to the turbine by adjusting swimming behavior, such as making small adjustments to swimming direction and velocity as they passed near the turbine. We found no evidence that fish were being struck by rotating blades, but there did appear to be large‐scale avoidance initiated out of the range of the hydroacoustics detection system. More study is needed to determine whether such avoidance behavior has significant ramifications for normal fish movement patterns, bioenergetics, seasonal migrations, and predator exposure.

Received October 28, 2016; accepted May 29, 2017 Published online August 2, 2017
“Art is a Sincere Martyrdom”: Circumventing Censorship by Encryption in the Work of Alireza Espahbod
Authors: Foroutan Aida
Published: June 2017

This paper focuses on various aspects of Alireza Espahbod’s style of painting that encrypt his work. The period considered is from the just after the Iranian revolution until the artist’s death in 2007: in these years censorship had become severe, resulting in banning prohibition on his work being exhibited. Apart from the striking symbols that recur throughout his work, it is noticeable that he favors certain visual metaphors for encryption of humanitarian and satirical meanings. The discussion also focuses on the ways in which sequences of his individual paintings create narratives, like scenes in a play or a film. Unlike some preceding modernists, Espahbod is firmly rooted in his Iranian cultural milieu, and is in a line of artists who have used surrealism, beginning with Sadegh Hedayat in the modern literary world. He also follows a much older tradition that goes back to classical poetry and miniature art, in which image and word coalesce and are interchangeable, and where literature and visual art reflect one another. He uses these older techniques to comment allusively on the dramatic events and conditions of his own time. It is argued that his work amounts to more than that of an artist who merely fought against censorship, as his art rises above it and responds to it with a positive message for his audience.
Assembling effective industrial policy in Africa: an agenda for action
Authors: Carmody Pádraig
Published: June 2017

Actor–network theory can be used to help understand effective industrialisation strategies. This paper deploys and develops this theory through the idea of multiple axes of strategic coupling, with reference to Ethiopia in particular.
Ferulic acid and its water-soluble derivatives inhibit nitric oxide production and inducible nitric oxide synthase expression in rat primary astrocytes
Authors: Kikugawa Masaki , Ida Tomoaki , Ihara Hideshi , Sakamoto Tatsuji
Published: June 2017

We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-β–induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives’ ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The results showed that these compounds inhibited NO production and iNOS expression in a concentration-dependent manner and that the mechanism underlying these effects was the suppression of the nuclear factor-κB pathway. This evidence suggests that FA and its derivatives may be effective neuroprotective agents and could be useful in the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.