bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the spin hall magnetoresistance in Cr2O3/Pt bilayers close to the Néel temperature
Authors: Schlitz Richard , Kosub Tobias , Thomas Andy , Fabretti Savio , Nielsch Kornelius , Makarov Denys , Goennenwein Sebastian T. B.
Published: March 2018

We study the evolution of magnetoresistance with temperature in thin film bilayers consisting of platinum and antiferromagnet Cr2O3 with its easy axis out of the plane. We vary the temperature from 20 °C to 60 °C, in the vicinity of the Néel temperature of Cr2O3 of approximately 37 °C. The magnetoresistive response is recorded during rotations of the external magnetic field in three mutually orthogonal planes. A large magnetoresistance having a symmetry consistent with a positive spin Hall magnetoresistance is observed in the paramagnetic phase of Cr2O3, which however vanishes when cooling to below the Néel temperature. Compared to analogous experiments in a Gd3Ga5O12/Pt bilayer, we conclude that a paramagnetic moment in the insulator induced by an applied magnetic field is not sufficient to explain the observed magnetoresistance. We speculate that the type of magnetic moment at the interface qualitatively impacts the spin angular momentum transfer, with the 3d moments of Cr sinking angular momentum much more efficiently as compared to the more localized 4f moments of Gd.
Free microparticles—An inducing mechanism of pre-firing in high pressure gas switches for fast linear transformer drivers
Authors: Li Xiaoang , Pei Zhehao , Wu Zhicheng , Zhang Yuzhao , Liu Xuandong , Li Yongdong , Zhang Qiaogen
Published: March 2018

Microparticle initiated pre-firing of high pressure gas switches for fast linear transformer drivers (FLTDs) is experimentally and theoretically verified. First, a dual-electrode gas switch equipped with poly-methyl methacrylate baffles is used to capture and collect the microparticles. By analyzing the electrode surfaces and the collecting baffles by a laser scanning confocal microscope, microparticles ranging in size from tens of micrometers to over 100 μm are observed under the typical working conditions of FLTDs. The charging and movement of free microparticles in switch cavity are studied, and the strong DC electric field drives the microparticles to bounce off the electrode. Three different modes of free microparticle motion appear to be responsible for switch pre-firing. (i) Microparticles adhere to the electrode surface and act as a fixed protrusion which distorts the local electric field and initiates the breakdown in the gap. (ii) One particle escapes toward the opposite electrode and causes a near-electrode microdischarge, inducing the breakdown of the residual gap. (iii) Multiple moving microparticles are occasionally in cascade, leading to pre-firing. Finally, as experimental verification, repetitive discharges at ±90 kV are conducted in a three-electrode field-distortion gas switch, with two 8 mm gaps and pressurized with nitrogen. An ultrasonic probe is employed to monitor the bounce signals. In pre-firing incidents, the bounce is detected shortly before the collapse of the voltage waveform, which demonstrates that free microparticles contribute significantly to the mechanism that induces pre-firing in FLTD gas switches.
Optical properties of InGaN thin films in the entire composition range
Authors: Kazazis S. A. , Papadomanolaki E. , Androulidaki M. , Kayambaki M. , Iliopoulos E.
Published: March 2018

The optical properties of thick InGaN epilayers, with compositions spanning the entire ternary range, are studied in detail. High structural quality, single phase InxGa1-xN (0001) films were grown heteroepitaxially by radio-frequency plasma assisted molecular-beam epitaxy on freestanding GaN substrates. Their emission characteristics were investigated by low temperature photoluminescence spectroscopy, whereas variable angle spectroscopic ellipsometry was applied to determine the complex dielectric function of the films, in the 0.55–4.0 eV photon range. Photoluminescence lines were intense and narrow, in the range of 100 meV for Ga-rich InGaN films (x < 0.3), around 150 meV for mid-range composition films (0.3 < x < 0.6), and in the range of 50 meV for In-rich alloys (x > 0.6). The composition dependence of the strain-free emission energy was expressed by a bowing parameter of b = 2.70 ± 0.12 eV. The films' optical dielectric function dispersion was obtained by the analysis of the ellipsometric data employing a Kramers-Kronig consistent parameterized optical model. The refractive index dispersion was obtained for alloys in the entire composition range, and the corresponding values at the band edge show a parabolic dependence on the InN mole fraction expressed by a bowing parameter of b = 0.81 ± 0.04. The bowing parameter describing the fundamental energy bandgap was deduced to be equal to 1.66 ± 0.07 eV, consistent with the ab initio calculations for statistically random (non-clustered) InGaN alloys.
Phase control and Young’s modulus of tungsten thin film prepared by dual ion beam sputtering deposition
Authors: Zhu Fei , Xie Zheng , Zhang Zhengjun
Published: March 2018

In this letter, tungsten films of varying thickness from ∼20 nm to ∼80 nm were prepared at different deposition temperature by Dual ion beam sputtering deposition (DIBSD) method. The influence of thickness and deposition temperature on the films phase, microstructure and Young’s modulus was studied briefly. The experiments prove that a double-layer structure, formation takes place i.e. β phase tungsten layer (low crystallinity) forms adjacent to the substrate and α tungsten phase layer (high crystallinity) forms above β phase. The increase in both the thickness and deposition temperature promotes the transformation from β phase to α phase which initiates from the interface between two phases. There is a critical thickness of ∼20 nm below which the film is a pure β phase, and the minimum thickness of forming pure α phase is affected by the deposition temperature, with 74 nm at 450°C, and 58 nm at 600°C. Furthermore, the decrease Young’s modulus of the tungsten film is ascribed to the formation of β phase which possesses low crystallinity with low density.
Multiconfiguration pair-density functional theory investigation of the electronic spectrum of MnO4−
Authors: Sharma Prachi , Truhlar Donald G. , Gagliardi Laura
Published: March 2018

The electronic spectrum of permanganate ions contains various highly multiconfigurational ligand-to-metal charge transfer states and is notorious for being one of the most challenging systems to be treated by quantum-chemical methods. Here we studied the lowest nine vertical excitation energies using restricted active space second-order perturbation theory (RASPT2) and multiconfiguration pair-density functional theory (MC-PDFT) to test and compare these two theories in computing such a challenging spectrum. The results are compared to literature data, including time-dependent density functional theory, completely renormalized equation-of-motion couple-cluster theory with single and double excitations, symmetry-adapted-cluster configuration interaction, and experimental spectra in the gas phase and solution. Our results show that MC-PDFT accurately predicts the spectrum at a significantly reduced cost as compared to RASPT2.
Photon excitation enabled large aperture space-charge-controlled potassium tantalate niobate (KTN) beam deflector
Authors: Zhu Wenbin , Chao Ju-Hung , Chen Chang-Jiang , Shang Annan , Lee Yun Goo , Yin Shizhuo , Dubinskii Mark , Hoffman Robert C.
Published: March 2018

To overcome the depth limitation of the space-charge-controlled (SCC) potassium tantalate niobate (KTN) deflectors, we report in this paper a method of increasing the aperture of SCC-KTN deflectors by harnessing the physical mechanism of blue light photon excitation. The experimental results show that the deflection angle can be increased from 0.7 mrad without the blue light excitation to 2.5 mrad with the blue light excitation at a penetration depth of 5 mm under the same external applied voltage, which is consistent with the theoretical analysis. This represents a substantial increase in the deflection angle at a much deeper penetration depth, which can be very useful for applications such as high speed 3D printings and displays.
Joule-heating induced thermal voltages in graphene three-terminal nanojunctions
Authors: Butti Pascal , Brönnimann Rolf , Ensslin Klaus , Shorubalko Ivan
Published: March 2018

Intrinsic voltage rectification is investigated in a graphene three-terminal nanojunction (GTTJ) on Si/SiO2 at room temperature and 87 K. The room-temperature rectification efficiency (ratio of output against input voltage) reaches ≈40%, which is higher than most efficiencies reported in the literature. The observed efficiency is higher at room temperature than at 87 K, which is in contrast to field-effect simulations and indicates that other mechanisms contribute to the rectification effect. We propose an explanation based on Joule heating and thermal voltages, as the device is operated in regimes of substantial power dissipation. Predicted thermal voltages show temperature and bias- and gate-voltage dependences which are similar to those observed in our experiment. We conclude that Joule-heating effects need to be considered for GTTJ devices.
Strategies for advantageous differential transport of ions in magnetic fusion devices
Authors: Kolmes E. J. , Ochs I. E. , Fisch N. J.
Published: March 2018

In a variety of magnetized plasma geometries, it has long been known that highly charged impurities tend to accumulate in regions of higher density. This “collisional pinch” is modified in the presence of additional forces, such as those might be found in systems with gravity, fast rotation, or non-negligible space charge. In the case of a rotating, cylindrical plasma, there is a regime in which the radially outermost ion species is intermediate in both mass and charge. This could have implications for fusion devices and plasma mass filters.
Plasma may facilitate combining 61 laser beams into a single, collimated beam
Authors: Kim Meeri
Published: March 2018

Researchers at the National Ignition Facility describe their work to combine the radiant energy from 61 different laser beams into a single, collimated beam.
Composite Membrane with a Calixarene-Containing Polyamide Functional Layer
Authors: Ren Shun , Liu Dong-Qing , Miao Rui-Xiang , Zhu Ze-Xian , Zhang Yu-Feng
Published: March 2018

Monolayer thin films were prepared at the interface of hexane and water to investigate the film formation ability of monomers through interfacial polymerization (IP). A tetra-calix[4]arene chloride derivative (CC) and a diamino-terminated PEG-1000 (DAP) produced a high strength membrane among the tested monomers. IP is consequently proposed to prepare a composite membrane with CC and DAP on a polysulfone (PSF) bulk membrane used for ultrafiltration. The top layer was cross-linked by heat-treating at 60°C for 2 min, with DAP (2 wt.-%) in water and CC (0.05 wt.-%) in hexane. Attenuated total reflectance (ATR)-FTIR and X-ray photoelectron spectroscopy data confirmed that a polyamide was formed on the surface of the PSF substrate. The skin layer was a 3 μm thick smooth thin-film as determined by field emission scanning electron microscopy (FE-SEM), and was also compact without gaps. Pure water flux was ~80.5 L m−2 h−1 under 0.5 MPa. Rejection of MgSO4 was round 22 %, since the calixarene-containing network was a sparse grid, and also had an affinity for metal cations. Although the skin of the composite membrane was compact under SEM, it was easy for metal cations to transfer through. This composite membrane might have good performance in other separation areas as a result of the special structure imparted by using the calixarenes as cross-linking knots.
Colin Wesley Ward 1943–2017
Authors: Colman Peter M. , Burgess Antony W.
Published: March 2018

Colin Wesley Ward's professional life played out at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) laboratory on Royal Parade, Parkville, Victoria, where he was a scientist, leader, raconteur, colleague and friend to several generations of staff who worked there. Ward's scientific legacy encompasses large bodies of work on antigenic variation in influenza viruses, the taxonomy of plant viruses, veterinary vaccines and the structure and function of several growth factor receptors. On retirement from CSIRO he continued work on the insulin receptor with colleagues at the Walter and Eliza Hall Institute of Medical Research, conceived of and founded CSIRO pedia and compiled his family history.
National research planning accelerates relevance and immediacy of climate-adaptation science
Authors: Ling Scott D. , Hobday Alistair J.
Published: March 2018

Adapting to climate change is contingent on an ability to adjust before opportunity is lost. Given that research funding to understand adaptation is limited, rapid return on investment is critical. For Australian marine environments, climate-change impacts are well documented and adaptation opportunities have been identified across aquaculture, fisheries, conservation and tourism sectors. Here, we have evaluated the recent Australian scientific literature to determine (1) the degree to which climate-change impacts and adaptation have been addressed across sectors, and, specifically, (2) the role of a major research program instituted in 2009 to address priority climate-change questions for these sectors, namely, Australia’s ‘National Climate Change Adaptation Research Plan for Marine Biodiversity and Resources’ (MNARP). Although the number of priority questions addressed by the general scientific literature increased in the 2009–2015 period, there was a 92% increase in the number of priority questions addressed during the peak of MNARP (2013–2014). MNARP research also addressed a greater range of priority questions than did the general scientific literature, which showed consistency in the questions and study systems examined. Overall, structured research planning focussed attention on key climate-change questions, which is a critical consideration for enacting adaptation in the face of rapid climate change.
Dose and administration protocol for FSH used for ovarian stimulation affect gene expression in sheep cumulus–oocyte complexes
Authors: Bragança Gláucia M. , Batista Ribrio Ivan T. P. , Souza-Fabjan Joanna Maria G. , Alfradique Vivian A. P. , Arashiro Eduardo K. N. , Cosentino Isabel O. , Pinto Pedro Henrique N. , Camargo Luiz Sérgio A. , da Fonseca Jeferson F. , Brandão Felipe Z.
Published: March 2018

The present study evaluated the effect of four ovarian stimulation protocols on the follicular population and molecular status of cumulus–oocyte complexes (COCs). Twelve Santa Inês ewes (in a cross-over design) received 80 or 120 mg FSH alone in a multiple-dose (MD80 and MD120) regimen or in combination with 300 IU equine chorionic gonadotrophin (eCG) in a one-shot (OS80 and OS120) protocol. The follicular population, COC recovery rate, mean COCs per ewe and the rate of brilliant Cresyl blue-positive (BCB+) COCs were similar among treatments (P > 0.05). The expression of markers of oocyte competence (ZAR1, zygote arrest 1; MATER, maternal antigen that embryo requires; GDF9, growth differentiation factor 9; BMP15, bone morphogenetic protein 15; Bcl-2, B-cell lymphoma 2; BAX, Bcl-2 associated X protein) and the steroidogenic pathway (ERα, oestrogen receptor α; LHr, LH receptor; FSHr, FSH receptor; STAR, steroidogenic acute regulatory protein) was affected by stimulation. Specifically, the expression of markers of the steroidogenic pathway was reduced with increasing FSH dose in the OS protocol. FSH at a dose of 80 mg reduced the expression of FSHr and ERα in the OS versus MD protocol. Conversely, in MD protocol, only LHr was affected by increasing FSH dose. In conclusion, 80 mg FSH in the MD or OS protocol was sufficient to promote the development of multiple follicles and obtain fully grown (BCB+) oocytes. The MD protocol may be more appropriate for the production of better-quality oocytes.
Exploring the structural origins of cryptic sites on proteins
Authors: Beglov Dmitri , Hall David R. , Wakefield Amanda E. , Luo Lingqi , Allen Karen N. , Kozakov Dima , Whitty Adrian , Vajda Sandor
Published: March 2018

Significance

Cryptic binding sites are absent or occluded in unbound proteins but present in ligand-bound structures. They can provide druggable pockets in cases where the main functional site of the protein cannot be targeted with sufficient potency or specificity. We show that unbound structures of proteins with cryptic sites have strong binding hot spots and above-average flexibility around the incipient pockets. Binding hot spots can be easily identified computationally, and protein flexibility can often be assessed by the analysis of X-ray structures of the unbound protein, including structures with low resolution. The approach presented here helps to assess the potential druggability of cryptic sites prior to running expensive screening experiments and reveals information about how cryptic sites form.
Rapid enhancement of chemical weathering recorded by extremely light seawater lithium isotopes at the Permian–Triassic boundary
Authors: Sun He , Xiao Yilin , Gao Yongjun , Zhang Guijie , Casey John F. , Shen Yanan
Published: March 2018

Significance

Estimates of seawater Li isotopic composition at the Permian–Triassic boundary (PTB) reveal extremely light seawater Li isotopic signatures accompanying the most severe mass extinction in the history of animal life. Theoretical modeling indicates a rapid enhancement of continental weathering during this time, which was likely triggered by the eruption of the Siberian Traps, rapid global warming, and acid rains. Our results provide independent geochemical evidence for an enhanced continental chemical weathering at the PTB, illustrating that continental weathering may provide a key link between terrestrial and marine ecological crises.
Energetic tradeoffs control the size distribution of aquatic mammals
Authors: Gearty William , McClain Craig R. , Payne Jonathan L.
Published: March 2018

Significance

The reasons why aquatic mammals exhibit larger average sizes than their terrestrial relatives have long been debated. Most previous hypotheses have focused on releases from terrestrial constraints on large sizes. Through the analysis of mammal size distributions, we find the aquatic realm imposes stronger constraints on body size than does the terrestrial realm, driving and confining aquatic mammals to larger sizes. Calculations of energy intake and demand as a function of body size indicate heat loss imposes a strong lower bound on size, whereas the scaling of feeding rate versus metabolic rate imposes a constraint on maximum size. Rather than freeing animals from body size constraints, living in water appears to impose stronger selective pressures than does living on land.
Grassland biodiversity can pay
Authors: Binder Seth , Isbell Forest , Polasky Stephen , Catford Jane A. , Tilman David
Published: March 2018

Significance

Ecological research suggests that greater biodiversity could lead to greater economic value, even for private owners of “working” land. However, the studies from which such a conclusion might be inferred do not account for all relevant information in a coherent economic framework. Our paper applies standard economic theory to rigorously account for costs, quality, and risk. Results indicate that higher levels of biodiversity than are typically observed on commercial grasslands would maximize landowner value in the experimental grassland we study. Greater private benefits from biodiversity could encourage private investment in biodiversity and reduce the cost of public conservation efforts.
Cracking the social code of speech prosody using reverse correlation
Authors: Ponsot Emmanuel , Burred Juan José , Belin Pascal , Aucouturier Jean-Julien
Published: March 2018

Significance

In speech, social evaluations of a speaker’s dominance or trustworthiness are conveyed by distinguishing, but little-understood, pitch variations. This work describes how to combine state-of-the-art vocal pitch transformations with the psychophysical technique of reverse correlation and uses this methodology to uncover the prosodic prototypes that govern such social judgments in speech. This finding is of great significance, because the exact shape of these prototypes, and how they vary with sex, age, and culture, is virtually unknown, and because prototypes derived with the method can then be reapplied to arbitrary spoken utterances, thus providing a principled way to modulate personality impressions in speech.
IpdAB, a virulence factor in
Mycobacterium tuberculosis
, is a cholesterol ring-cleaving hydrolase
Authors: Crowe Adam M. , Workman Sean D. , Watanabe Nobuhiko , Worrall Liam J. , Strynadka Natalie C. J. , Eltis Lindsay D.
Published: March 2018

Significance

All steroid-degrading bacteria utilize IpdAB, a predicted CoA transferase (CoT) that has been implicated in the hydrolysis of a carbon–carbon bond, an unprecedented reaction in CoTs. In
Mycobacterium tuberculosis
, IpdAB is required for degrading host cholesterol and virulence. We used a combination of X-ray crystallographic and biochemical studies to elucidate the mechanism of IpdAB. Superposition of the IpdAB
Mtb
active site with those of CoTs reveals distinct architectural features which, in conjunction with the biochemical data, indicate that IpdAB catalyzes a retro-Claisen-like ring-opening reaction. This reaction is unique for a member of the CoT superfamily. This study provides insights into bacterial steroid catabolism and facilitates the development of potential antituberculosis therapeutics targeting IpdAB.
Escalation of competition into conflict in competitive networks of Formula One drivers
Authors: Piezunka Henning , Lee Wonjae , Haynes Richard , Bothner Matthew S.
Published: March 2018

Significance

Competition, while often seen as beneficial, can escalate into destructive conflict. This occurs, for instance, when athletes sabotage each other or when rival executives get caught up in a career-derailing fight. These escalations into conflict are especially likely among status-similar competitors, who are fraught with discordant understandings of who is superior to whom. We examine the link between status similarity and conflict as well as the conditions under which this link holds. We find that status-similar Formula One drivers are more prone to collide, especially when they are age-similar, perform well, are embedded in a stable role structure, and feel safe. Our inquiry deepens our understanding of when violent conflict emerges and can guide conflict prevention efforts.
Small proline-rich protein 2B drives stress-dependent p53 degradation and fibroblast proliferation in heart failure
Authors: Burke Ryan M. , Lighthouse Janet K. , Quijada Pearl , Dirkx Ronald A. , Rosenberg Alexander , Moravec Christine S. , Alexis Jeffrey D. , Small Eric M.
Published: March 2018

Significance

Heart disease is associated with the development of fibrosis, a type of scarring that impedes cardiac function. The primary cellular source of cardiac fibrosis is the resident cardiac fibroblast. We found that cardiac fibroblasts from human heart failure patients or a mouse model of heart disease express excessive amounts of the SPRR2B protein. We provide evidence that SPRR2B is a signal-responsive regulatory subunit of the p53 ubiquitination complex that stimulates the destruction of p53 and the accumulation of pathological fibroblasts. This study defines a unique mechanism of cell cycle control that is dysfunctional in heart disease and may drive the development pathological fibrosis.
Molecular and structural architecture of polyQ aggregates in yeast
Authors: Gruber Anselm , Hornburg Daniel , Antonin Matthias , Krahmer Natalie , Collado Javier , Schaffer Miroslava , Zubaite Greta , Lüchtenborg Christian , Sachsenheimer Timo , Brügger Britta , Mann Matthias , Baumeister Wolfgang , Hartl F. Ulrich , Hipp Mark S. , Fernández-Busnadiego Rubén
Published: March 2018

Significance

How protein aggregation leads to neurodegenerative disorders such as Huntington’s disease remains poorly understood. Here we show that polyglutamine (polyQ) aggregation in yeast results in the formation of amorphous inclusions and less frequent fibrils. This is accompanied by significant changes in proteome composition as well as distortions in mitochondria and lipid droplet morphology that do not arise from direct interactions of these organelles with polyQ inclusions or fibrils. This contrasts with recent observations in mammalian cells, where the same polyQ proteins formed amyloid-like fibrils that distort endoplasmic reticulum membranes. These results demonstrate that the same polyQ expansion protein can adopt different nonnative conformations that utilize distinct mechanisms to target a variety of cellular structures.
NAA80 is actin’s N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility
Authors: Drazic Adrian , Aksnes Henriette , Marie Michaël , Boczkowska Malgorzata , Varland Sylvia , Timmerman Evy , Foyn Håvard , Glomnes Nina , Rebowski Grzegorz , Impens Francis , Gevaert Kris , Dominguez Roberto , Arnesen Thomas
Published: March 2018

Significance

More than 80% of human proteins are N-terminal (Nt)–acetylated during translation. In contrast, actin, the most abundant protein in the cytoplasm of animal cells, is Nt-acetylated posttranslationally and following a unique multistep mechanism that has remained poorly characterized. Here, we describe the discovery of actin’s N-terminal acetyltransferase (NAT), NAA80. We further demonstrate that actin Nt-acetylation plays essential roles in filament assembly, cytoskeleton organization, and cell motility, resulting in a net increase in the ratio of monomeric to filamentous actin and fewer lamellipodia and filopodia. These effects converge to reduce cell hypermotility. This work establishes the role of Nt-acetylation for the most abundant cytoskeletal protein in animals and reveals a NAT acting posttranslationally and on a single dedicated substrate.
Mechanistic insights into staphylopine-mediated metal acquisition
Authors: Song Liqiang , Zhang Yifei , Chen Weizhong , Gu Tongnian , Zhang Shu-Yu , Ji Quanjiang
Published: March 2018

Significance

The major human pathogen,
Staphylococcus aureus
, produces a broad-spectrum metallophore, staphylopine (StP), to acquire transition metals under metal-limited conditions. The first step of the metal acquisition process is StP/metal recognition by the extracytoplasmic solute-binding protein CntA from the StP/metal transportation system. We determined the crystal structures of CntA/StP/metal (Ni
2+
, Co
2+
, and Zn
2+
) complexes and apo CntA, deciphering a sophisticated StP/metal-recognition mechanism. Moreover, we uncovered that StP/metal recognition is indispensable for StP-mediated metal acquisition. Because the StP-like biosynthetic and trafficking pathways are present in various pathogens, these discoveries provide critical insights into the investigations of metal-acquisition mechanisms in microbes.
RNA-mediated gene regulation is less evolvable than transcriptional regulation
Authors: Payne Joshua L. , Khalid Fahad , Wagner Andreas
Published: March 2018

Significance

Cells regulate the activity of genes in a variety of ways. For example, they regulate transcription through DNA binding proteins called transcription factors, and they regulate mRNA stability and processing through RNA binding proteins. Based on current knowledge, transcriptional regulation is more widespread and is involved in many more evolutionary adaptations than posttranscriptional regulation. The reason could be that transcriptional regulation is studied more intensely. We suggest instead that transcriptional regulation harbors an intrinsic evolutionary advantage: when mutations change transcriptional regulation, they are more likely to bring forth novel patterns of such regulation. That is, transcriptional regulation is more evolvable. Our analysis suggests a reason why a specific kind of gene regulation is especially abundant in the living world.
Split cGAL, an intersectional strategy using a split intein for refined spatiotemporal transgene control in
Caenorhabditis elegans
Authors: Wang Han , Liu Jonathan , Yuet Kai P. , Hill Andrew J. , Sternberg Paul W.
Published: March 2018

Significance

Discovering where a gene acts, when it is required, and the consequence of its perturbation are essential for understanding gene function. These tasks require genetic tools that allow precise control of gene expression at will. In this paper, we combine a split intein strategy and a bipartite expression system to develop a refined method of controlling transgene expression in
Caenorhabditis elegans
. The new system specifies transgene expression only in cells where two distinct promoters are active, allowing precise spatiotemporal control. Our work provides the
C. elegans
community with a new genetic tool for precise control of transgene expression. We speculate that a similar split intein strategy could also be applied to other bipartite expression systems in other genetic model organisms.
Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state
Authors: Zhang Xi , Wang Qifan , Wu Jianping , Wang Jiawei , Shi Yigong , Liu Minhao
Published: March 2018

Significance

Lysyl oxidases (LOXs) catalyze oxidative deamination of peptidyl lysines on collagen and elastin, generating a highly reactive aldehyde group to initiate intermolecular cross-linking. In humans, this reaction plays fundamental roles in the formation and repair of extracellular matrix fiber networks and the development of connective tissues. Moreover, a relationship between LOX proteins and tissue fibrosis and cancer has been established. Since the identification of prototypic LOX, the atomic structure of LOX protein has remained to be elucidated. Here, we present the high-resolution structure of human lysyl oxidase-like 2 protein. The zinc-bound precursor-state structure provides an important framework for understanding the structure–function relationship of the LOX family and for drug discovery that aims to block LTQ generation of LOX proteins.
Adeno-associated virus Rep proteins antagonize phosphatase PP1 to counteract KAP1 repression of the latent viral genome
Authors: Smith-Moore Sarah , Neil Stuart J. D. , Fraefel Cornel , Linden R. Michael , Bollen Mathieu , Rowe Helen M. , Henckaerts Els
Published: March 2018

Significance

In recent years, adeno-associated virus (AAV) has attracted considerable attention as a result of its success as a gene therapy vector. However, several aspects of its biology remain elusive. Given that AAV vectors mimic the latent phase of the viral life cycle, defining the mechanisms involved in the regulation of AAV latency is of particular importance. Our studies demonstrate that epigenetic processes are involved in the regulation of viral latency and reveal virus–host interactions and helper functions that are aimed at counteracting the epigenetic repression of the viral genome during the lytic phase of the viral life cycle. These observations will inform the design of future AAV vector technologies.
Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration
Authors: Bi Pengpeng , McAnally John R. , Shelton John M. , Sánchez-Ortiz Efrain , Bassel-Duby Rhonda , Olson Eric N.
Published: March 2018

Significance

Skeletal muscle damaged by injury or disease can regenerate new muscle fibers. The regenerative properties of skeletal muscle involve fusion of activated muscle stem cells (satellite cells). We recently discovered Myomixer, a conserved micropeptide that is specifically expressed during muscle formation. Myomixer, together with its partner Myomaker, another muscle-specific membrane protein, is necessary for muscle formation during embryogenesis. Here, we show the absolute requirement of Myomixer for the fusion of satellite cells and regeneration of adult muscle in response to injury. Our findings provide insights into the mechanisms of muscle formation and suggest opportunities for enhancing muscle regeneration through manipulation of Myomixer and Myomaker.
CSI1, PATROL1, and exocyst complex cooperate in delivery of cellulose synthase complexes to the plasma membrane
Authors: Zhu Xiaoyu , Li Shundai , Pan Songqin , Xin Xiaoran , Gu Ying
Published: March 2018

Significance

Cellulose is synthesized at the plasma membrane by cellulose synthase complexes (CSCs). The ability to deliver CSCs to discrete sites at the cell surface is critical for cellulose synthesis. We discovered that the de novo secretion of CSCs is mediated by cooperation among a recently identified cellulose synthase interacting protein, exocyst complex, and a plant-specific protein PATROL1 in
Arabidopsis thaliana
. We present a timeline of events for exocytosis of CSCs. CSCs represent unique cargo proteins that are not conserved in the mammalian or yeast system. Plants offer unique opportunities to characterize the function and regulation of exocytosis that may provide insight into the evolution of exocytosis in eukaryotes.
Single-nucleotide resolution dynamic repair maps of UV damage in
Saccharomyces cerevisiae
genome
Authors: Li Wentao , Adebali Ogun , Yang Yanyan , Selby Christopher P. , Sancar Aziz
Published: March 2018

Significance

The budding yeast
Saccharomyces cerevisiae
is one of the most commonly used model organisms in studying DNA damage and repair in eukaryotes. In this study, we adapted the recently invented excision repair-sequencing method to investigate the mode of in vivo repair of the two major UV-induced DNA lesions, the cyclobutane pyrimidine dimer and the (6-4) pyrimidine–pyrimidone photoproduct, and to generate the dynamic repair maps of the these two lesions at single-nucleotide resolution across the entire yeast genome. These data revealed a polarity of repair within genes and other effects of transcription and the time of repair on the repair pattern. Our findings should aid in research on carcinogenesis by UV and chemical carcinogens.
OSR1 regulates a subset of inward rectifier potassium channels via a binding motif variant
Authors: Taylor Clinton A. , An Sung-Wan , Kankanamalage Sachith Gallolu , Stippec Steve , Earnest Svetlana , Trivedi Ashesh T. , Yang Jonathan Zijiang , Mirzaei Hamid , Huang Chou-Long , Cobb Melanie H.
Published: March 2018

Significance

With-no-lysine (K) (WNK) protein kinases regulate ion transport. Mutations in WNKs 1 and 4 can cause a monogenic hypertension, pseudohypoaldosteronism type II (PHA2). The WNK-regulated protein kinases STE20/SPS1-related proline- and alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1) mediate actions of WNKs on cation chloride cotransporters. The conserved C-terminal domains (CCTs) of OSR1/SPAK recognize linear R-F-x-V/I motifs in transporters and other protein targets. We discovered that OSR1/SPAK CCTs also recognize a motif variant, R-x-F-x-V/I, found in 8 of 16 inward rectifier K
+
(IRK) channels. We show that WNK and OSR1 regulate IRK channels, dependent on the presence of the variant motif. WNK kinase activity-dependent regulation of ion channels reveals a previously unknown mechanism and expands knowledge of potential WNK-OSR1/SPAK actions in cardiac and renal physiology.
Early Modern Comedy and the Politics of Religion: Reconsidering Comedy in Rospigliosi's Il Sant'Alessio
Authors: Purciello Maria Anne
Published: March 2018

Giulio Rospigliosi and Stefano Landi's 1634 revisions of Il Sant'Alessio for the Barberini stage expanded the role of comedy within the opera. These revisions reveal an important juncture in the history of religious comedy and lay the foundation for the development of a comic rubric for the still-developing operatic genre. This article examines the legend of St Alexis and its potential for historic reinterpretation in light of the Barberini family's religious and political goals. Its consideration of the interrelationship of religion and comedy in early modern sacred drama provides the theoretical context for an analysis of scenes in the 1634 version featuring the comic pages Martio and Curtio. Operating as a mitigating force between the extreme ideologies presented by the characters of Sant'Alessio and the Devil, the pages’ comedy promotes a more widespread acceptance of key religious ideals and becomes the driving force behind a significant political statement for post-Tridentine Rome.
Utilizing Risk Index for Overdose Or Serious Opioid-Induced Respiratory Depression (RIOSORD) Scores to Prioritize Offer of Rescue Naloxone in An Outpatient Veteran Population: A Telephone-Based Project
Authors: Yates Derek , Frey Theresa , Montgomery Jean Charles
Published: March 2018

Background

Since 2014, the Department of Veterans Affairs (VA) has been working to address the ongoing opioid epidemic through opioid-education initiatives, the development of risk calculators, and other risk stratification tools. One primary focus of VA efforts has been the distribution of rescue naloxone kits to veterans at greatest risk of opioid-related adverse events. The purpose of this project was to identify primary care veterans at highest risk for serious opioid-related adverse events using the Risk Index for Overdose and Serious Opioid-Induced Respiratory Depression (RIOSORD) and offer rescue naloxone kits by telephone-based outreach. RIOSORD is a risk-stratification tool developed and validated within the veteran population.

Methods

Veterans identified at highest risk of overdose or opioid-related adverse effects were contacted by telephone or letter to offer to provide a rescue naloxone kit between November 1st, 2016 and February 1st, 2017. The primary outcome of the project was the percentage of patients contacted that agreed to a naloxone prescription. Secondary outcomes included comparative efficacy of phone versus letter contact and reasons for refusal of naloxone if the offer was declined.

Results

Of 41 veterans targeted by this project, most were successfully reached by telephone within three attempts (92.7%, n = 38). Approximately two-thirds of those reached by telephone agreed to a prescription for rescue naloxone (n = 26, 63.4%). The veterans that requested rescue naloxone selected the nasal formulation (n = 17) over the intramuscular auto-injector (n = 9).

Conclusions

This project demonstrated that telephone-based outreach can be one method of distributing rescue naloxone to a high-risk patient population without requiring an in-person visit to a provider.
Microbial symbionts regulate the primary Ig repertoire
Authors: Chen Yuezhou , Chaudhary Neha , Yang Nicole , Granato Alessandra , Turner Jacob A. , Howard Shannon L. , Devereaux Colby , Zuo Teng , Shrestha Akritee , Goel Rishi R. , Neuberg Donna , Wesemann Duane R.
Published: March 2018

The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal immune fitness. Early events that shape preimmune Ig repertoires, expressed on IgM+ IgD+ B cells as B cell receptors (BCRs), are poorly defined. Here, we studied germ-free mice and conventionalized littermates to explore the hypothesis that symbiotic microbes help shape the preimmune Ig repertoire. Ig-binding assays showed that exposure to conventional microbial symbionts enriched frequencies of antibacterial IgM+ IgD+ B cells in intestine and spleen. This enrichment affected follicular B cells, involving a diverse set of Ig-variable region gene segments, and was T cell–independent. Functionally, enrichment of microbe reactivity primed basal levels of small intestinal T cell–independent, symbiont-reactive IgA and enhanced systemic IgG responses to bacterial immunization. These results demonstrate that microbial symbionts influence host immunity by enriching frequencies of antibacterial specificities within preimmune B cell repertoires and that this may have consequences for mucosal and systemic immunity.
Discrimination and Collaboration in Science
Authors: Rubin Hannah , O’Connor Cailin
Published: March 2018

We use game theoretic models to take an in-depth look at the dynamics of discrimination and academic collaboration. We find that in collaboration networks, small minority groups may be more likely to end up being discriminated against while collaborating. We also find that discrimination can lead members of different social groups to mostly collaborate with in-group members, decreasing the effective diversity of the social network. Drawing on previous work, we discuss how decreases in the diversity of scientific collaborations might negatively affect the progress of epistemic communities.
Hypertrophic Scar Severity at Autograft Sites Is Associated With Increased Pain and Itch After Major Thermal Burn Injury
Authors: Mauck Matthew C , Shupp Jeffrey W , Williams Felicia , Villard Marie Ashley , Jones Samuel W , Hwang James , Smith Jennifer , Karlnoski Rachel , Smith David J , Cairns Bruce A , McLean Samuel A
Published: March 2018

Approximately three quarters of major thermal burn injury (MThBI) survivors suffer from hypertrophic scarring (HTS) and over half experience chronic pain or itch. In survivors of MThBI, HTS and chronic pain or itch are considered one of the greatest unmet challenges of postburn injury care and psychosocial reintegration. Although scarring, itch, and pain have been clinically associated, there are no prospective, multisite studies examining tissue autograft site pain or itch and scar outcomes. The authors collected a representative cohort (n = 56) of MThBI survivors who received autografting within 14 days of injury and evaluated graft-site pain or itch severity (0–10 Numeric Rating Scale) and HTS using a validated scar photograph assessment scale 6 months following MThBI. Given that stress is known to influence wound healing, the authors also assessed the relationship between previous trauma exposure, peritraumatic stress, preburn overall health (SF-12), scarring, and chronic pain or itch severity using Spearman’s correlation. Association between HTS and chronic pain or itch was significant in a linear regression model adjusted for age, sex, and ethnicity (β = 0.2, P = .033 for pain, β = 0.2, P = .019 for itch). Results indicate that prior trauma exposure is inversely correlated (r = −.363, P = .030) with scar severity, but not pain or itch severity 6 months after MThBI. Study results suggest that preburn chronic pain or itch is associated with pathological scarring 6 months following MThBI. Results also indicate that stress may improve scarring after MThBI. Further work to understand the mechanisms that underlie both HTS and chronic pain or itch and their relationship to chronic stress is critical to the development of novel therapies to assist burn survivors recover.
Cytochrome P450 2B diversity in a dietary specialist—the red tree vole (Arborimus longicaudus)
Authors: Kitanovic Smiljka , Marks-Fife Chad A , Parkes Quincy A , Wilderman P Ross , Halpert James R , Dearing M Denise
Published: March 2018

Although herbivores rely on liver enzymes to biotransform plant secondary metabolites ingested in plant-based diets, only a few enzymes from a handful of species have been characterized at the genomic level. In this study, we examined cytochrome P450 2B (CYP2B) sequence diversity and gene copy number in a conifer specialist, the red tree vole (Arborimus longicaudus). We fed captive individuals exclusively Douglas-fir (Pseudotsuga menziesii) foliage, cloned and sequenced their liver CYP2B cDNA, and estimated CYP2B gene copy number. We identified 21 unique CYP2B nucleotide sequences, and 20 unique CYP2B amino acid sequences. Gene copy number of CYP2B was estimated at 7.7 copies per haploid genome. We compared red tree vole CYP2B with CYP2B sequences of a generalist, the prairie vole (Microtus ochrogaster), found in GenBank. Our study revealed that the CYP2B enzymes of red tree voles possess unique sequences compared to CYP2B enzymes of other herbivorous species. The unique combination of amino acid residues at key substrate recognition sites of CYP2B enzymes may underlie the ability of the red tree vole to specialize on a highly toxic diet of Douglas-fir.
Tumor Specimen Biobanks: Data Gaps for Analyzing Health Inequities—the Case of Breast Cancer
Authors: Krieger Nancy , Jahn Jaquelyn L
Published: March 2018

Biobanks are increasingly recognized to be vital for analyzing tumor properties, treatment options, and clinical prognosis, yet few data exist on whether they are equipped to enable research on cancer inequities, that is, unfair and unnecessary social group differences in health. We conducted a systematic search of global biobanks, identified 46 that have breast tumor tissue and share data externally with academic researchers, and e-mailed and called to obtain data on the sociodemographic, socioeconomic, and geospatial data included, plus time span encompassed. Among the 32 biobank respondents, 91% housed specimens solely from the Global North, only 31% obtained socioeconomic data, 63% included racial/ethnic data (of which 55% lacked socioeconomic data), 44% included limited geographic data, and 55% had specimens dating back at most to 2000. To enable research to address cancer inequities, including trends over time, biobanks will need to address the data gaps documented by our study.
Explaining Global Trends in FDI in 2015 and Beyond
Authors: Ilan Strauss
Published: March 2018

This chapter discusses global trends in foreign direct investment (FDI). It first attempts to explain recorded FDI flows in 2015 relative to 2014, challenging 'traditional' explanations for FDI flows, such as changes in market size, the offshoring motive, and supply-side constraints. It then contextualizes FDI flows in 2015 as part of the longer-term trend of stagnating FDI since the 2007/8 financial crisis, and proposes that FDI increasingly reflects the intra-firm financing decision. The chapter argues that FDI flows increasingly record financing flows of debt and retained earnings within a corporate group, thereby reflecting the financing decision of the parent company with respect to its many affiliates. Data for most countries is unable to show this clearly, but as the size of their FDI stocks grow relative to their economies, so too should debt-FDI and retained-earnings FDI overwhelm any new large FDI equity investments.
The Outcomes of Investment Treaty Arbitration
Authors: Karen L Remmer
Published: March 2018

This chapter explores variations in dispute outcomes in investment treaty arbitration. Building on the literature on political institutions, the study places the theoretical importance of actor information about the rules of the game and the resources of the participants at the centre of analysis. Such information shapes the strategy of the players and their relative ability to compete successfully, establishing the basis for hypotheses about variations in dispute outcomes. Drawing on the universe of known disputes, the analysis relies on statistical models and data capable of addressing concurrently the full range of potential dispute outcomes rather than particular categories of wins and losses. States do not just win or lose treaty-based investment disputes; disputes can also be concluded by decisions to discontinue arbitral proceedings and by settlements negotiated between states and investors prior to an arbitral award. Consistent with theoretical expectation, the findings indicate that dispute outcomes vary in response to the evolution of the system of dispute settlement over time, sector of investment, and access to international legal expertise, thereby underlining the pivotal role of information flows in investment dispute settlement.