bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of resistive switching properties in nitride based CBRAM device by inserting an Al2O3 thin layer
Authors: Kumar Dayanand , Aluguri Rakesh , Chand Umesh , Tseng Tseung-Yuen
Published: May 2017

In this letter, we propose a method to enhance resistive switching properties in SiCN-based conductive-bridge resistive switching memory (CBRAM) devices by inserting a thin Al2O3 layer between the SiCN resistive switching layer and the TiN bottom electrode. Compared with the Cu/Ta/SiCN/TiN single-layer device, the Cu/Ta/SiCN/Al2O3/TiN double layer device exhibits uniform resistive switching, long stable endurance cycles (>1.6 × 104), and stable retention (104 s) at 125 °C. These substantial improvements in the resistive switching properties are attributed to the location of the formation and rupture of conductive filaments that can be precisely controlled in the device after introducing the Al2O3 layer. Moreover, a multilevel resistive switching characteristic is observed in the Cu/Ta/SiCN/Al2O3/TiN double layer CBRAM device. The distinct six-level resistance states are obtained in double layer devices by varying the compliance current. The highly stable retention characteristics (>104) of the Cu/Ta/SiCN/Al2O3/TiN double layer device with multilevel resistance states are also demonstrated.
Light-induced “plasmonic” properties of organic materials: Surface polaritons and switching waves in bistable organic thin films
Authors: Fainberg B. D. , Rosanov N. N. , Veretenov N. A.
Published: May 2017

Purely organic materials with negative and near-zero dielectric permittivity can be easily fabricated, and the propagation of surface polaritons at the material/air interface was demonstrated. Here, we develop a theory of nonlinear light-induced “plasmonic” properties of organic materials. We predict the generation of switching waves or kinks in the bistable organic thin films that enable us to observe a bistable behaviour of the surface polaritons at the organic thin film/dielectric interface under laser irradiation. We present the alternating-sign dependence of the switching wave velocity on pump intensity and discuss a possibility of controlling the polariton propagation by switching waves.
Edge transport bifurcation in plasma resistive interchange turbulence
Authors: Li B. , Wang X. Y. , Sun C. K. , Meng C. , Zhou A. , Liu D.
Published: May 2017

Transport bifurcation and mean E×B shear flow generation in resistive interchange turbulence are explored with self-consistent fluid simulations in a flux-driven system with both closed and open field line regions. The nonlinear evolution of resistive interchange modes shows the presence of two confinement regimes characterized by low and high mean E×B shear flows. By increasing the heat flux above a threshold, large-amplitude fluctuations are induced in the plasma edge region and a transition to the state of reduced turbulent transport occurs as the Reynolds power exceeds the fluctuation energy input rate for a sufficient time period. The flux-gradient relationship shows a sharp bifurcation in the plasma edge transport.
Are we underestimating the impact of rising summer temperatures on dormancy loss in hard-seeded species?
Authors: Cochrane Anne
Published: May 2017

Short duration dry heat shock similar to the heat of fire is known to be effective in alleviating physical dormancy in seeds, but are we underestimating the impact of the cumulative heat dose of summer soil temperatures on dormancy loss in hard-seeded species in the context of a changing climate? This study investigated short and long duration dry heat treatments in seeds of four Acacia species (Fabaceae) from South-West Western Australia. Seeds were treated at 90, 100, 110 and 120°C for 10 and 180 min (‘fire’) and at fluctuating temperatures of 30/20, 55/20, 65/20°C for 14, 28, 56 and 112 days (‘summer’). The non-dormant seed fraction of each species was low, but seeds were highly viable after scarification. The results indicate the presence of species-specific temperature thresholds for dormancy loss with duration of heating slightly less important than temperature for dormancy break. Seeds remained highly viable after all long duration treatments but short duration heat shock treatments above 110°C resulted in increased seed mortality. Although cumulative periods of lower fluctuating temperatures were less effective in breaking physical dormancy than the heat of fire in three of the four species, more than 40% of seeds of Acacia nigricans (Labill.) R.Br. lost dormancy after 28 days at 65/20°C. These potentially disturbing findings suggest that long hot summer conditions may compromise soil seed bank longevity over time and may be detrimental to the bet-hedging ability afforded by a hard seed coat in some species in the face of climate warming forecasts for the region.
What we know about skilled, beginning, and older readers from monitoring their eye movements
Authors: Leinenger Mallorie , Rayner Keith
Published: May 2017

In this chapter, we will discuss research conducted over the past 40 years dealing with the eye movements during reading of skilled readers as compared to poor readers, as well as beginning and older readers. We will discuss issues related to the perceptual span (or area of effective vision), preview benefit, basic characteristics of eye movements, and eye movement control across the different groups – asking what we can infer about each group’s reading behavior from their eye movements. We will then discuss attempts to model different stages of reading development over the lifespan. Finally, we will discuss the implications that this research has for teaching children to read.
Reading comprehension in the early years
Authors: Van Boekel Martin , Kendeou Panayiota , Fletcher Charles R.
Published: May 2017

The relation between comprehension and reading comprehension is strong at all ages and levels of proficiency. Even though there are reciprocal influences on one another, comprehension remains a strong predictor for reading comprehension performance across development. In this chapter, we will review current research advances on comprehension development, with an emphasis in the early years, specifically from preschool to early elementary school. We view comprehension as a multidimensional construct that includes broader oral language skills. This view has implications for the early diagnosis of comprehension difficulties, assessment of comprehension, and instruction of comprehension skills in the early years.
Five building blocks for comprehension strategy instruction
Authors: Allen Laura K. , McNamara Danielle S.
Published: May 2017

Comprehension is a complex task that is integral to success in academics and the workplace. Unfortunately, it is not a task that comes easily to all students. Hence, an important question faced by educators and researchers is how to most effectively provide students with instruction to improve comprehension, particularly on how to understand and learn from challenging texts. One promising approach is to provide students with training to use comprehension strategies. Strategies are intended to help students overcome skill and knowledge deficits by using overt techniques that mimic or support the processes integral to successful comprehension, including understanding the words and sentences in the text, making connections between sentences, and making connections to what the student already knows (i.e., prior knowledge). In this chapter, we approach these research questions by building upon the 4-pronged comprehension strategy framework proposed by McNamara, Ozuru, Best, and O’Reilly (2007). This framework describes five types of strategies that can help to scaffold reading and comprehension. We expand upon this framework by describing various contextual factors that may influence comprehension and strategy use. Further, we discuss methods to enhance strategy instruction, introducing five building blocks for effective comprehension strategy training.
Turkic poetic heritage as symbol and spectacle of identity: observations on Turkmenistan's Year of Magtymguly celebrations
Authors: Taylor Paul Michael
Published: May 2017

This paper presents one case study of state-sponsored cultural activities that occurred throughout 2014, Turkmenistan's Year of Magtymguly, the 290th anniversary of this Turkmen poet's birth. Such activities constitute examples of public culture; they can organize representations of a society's past and present to reaffirm for participants the values and power structure of their society and revalidate its philosophical underpinnings. After examining this Turkic poet's iconicity, this paper compiles 2014's celebratory events from disparate sources, complementing broader general literature on Central Asia's spectacles of public culture and their role in nation-building and identity-formation. Rather than merely resulting from any top-down decision specifying required activities nationwide, the year's events involved numerous synergies as artists, museum and theater administrators, composers, and other cultural-sector workers benefited by responding to the potential of aligning their work with a theme as broad, as widely appreciated, and as eligible for various forms of support as this one. In addition, Turkmenistan's strong central leadership benefited from this widely shared and highly visible celebration, especially emphasizing one element within Magtymguly's eighteenth-century vision, an end to his people's tribal conflicts within a unified Turkmenistan under one leader.
Reactive friction-stir processing of nanocomposites: Effects of thermal history on microstructure–mechanical property relationships
Authors: Khodabakhshi F. , Kokabi A. H. , Simchi A.
Published: May 2017

The effects of thermal history on the microstructure and mechanical properties of a friction-stir-processed Al–Mg–TiO2 (3 vol.-%, 20 nm) nanocomposite were studied. It is shown that, with increases in peak temperature, a more uniform distribution of nanoparticles in the metal matrix, and a refined grain structure, are attained. Transmission electron microscopy indicated that the mechanism of grain refinement is influenced by the hard inclusions, changing from discontinuous to continuous dynamic recrystallisation. A fine-grained nanocomposite (average grain size of 3 µm) with a uniform distribution of nanoparticles is obtained after four fully-overlapping passes at 1200 rev min−1 and 100 mm min−1. Under these circumstances the mechanical properties, including yield stress (95%), tensile strength (36%) and hardness (72%) are significantly enhanced relative to the untreated alloy.
Analysis on bainite transformation in reheated low-carbon bainite weld metals
Authors: Mao Gaojun , Cao Rui , Chen Jianhong
Published: May 2017

A combination of laser scanning confocal microscopy (LSCM) and dilatometry was utilised to simultaneously qualitatively analyse the morphological evolution of bainite by examination of in situ observed micrographs and to quantitatively investigate the amount of bainite transformation by studying dilatometry data. Shorter bainite structures form for smaller prior austenite grain sizes and lower cooling rates, which causes greater bainite transformation to occur in the latter stages of the transformation process. On the other hand, the amount of lath-shape sub-structure increases due to a higher cooling rate. In addition, the surface relief presents greater height and the peak and valley values stay farther away from the horizontal line for specimens at a higher cooling rate. In addition, a lower strain energy per unit volume gives rise to greater bainite transformation compared to that from abundant driving forces.
Influence of Cu addition on the structures and properties of Ti15SnxCu alloys
Authors: Tsao L. C. , Chang S. Y.
Published: May 2017

In this study, Ti15Sn xCu alloys were synthesised using an argon-arc melting and casting method. The as-cast alloy ingot was heat-treated for 2 h at 1000°C and then quenched in water to investigate the effects of heat treatment on the microstructure and corrosion behaviour of the Ti15Sn xCu alloys. In comparison to the heat-treated Ti15Sn alloy, the average size of cellular grains ( dG), the lamellar length ( λL), and the lamellar thickness ( λT) in heat-treated Ti15Sn2Cu alloy were refined by approximately 36, 30, and 36%, respectively. The corrosion behaviour of heat-treated Ti15Sn xCu alloys was made nobler by adding 2 wt-% Cu content. The precipitation of large amounts of nobler (Ti, Sn)2Cu nanoparticles hindered grain growth, improved the UTS, 0.2YS, microhardness and good corrosion resistance.
Choosing the right response to ER stress
Authors: Short Ben
Published: May 2017

Cells use distinct unfolded protein response transducers to export different collagens during development.
RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis
Authors: Xia Yan , Yang Weiwei , Fa Ming , Li Xinjian , Wang Yugang , Jiang Yuhui , Zheng Yanhua , Lee Jong-Ho , Li Jing , Lu Zhimin
Published: May 2017

Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2–phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription. RNF8-mediated histone H3 polyubiquitylation promotes tumor cell glycolysis and proliferation and brain tumorigenesis. Our findings uncover the role of RNF8-mediated histone H3 polyubiquitylation in the regulation of histone H3 stability and chromatin modification, paving the way to gene expression regulation and tumorigenesis.
Calretinin interneuron density in the caudate nucleus is lower in autism spectrum disorder
Authors: Adorjan Istvan , Ahmed Bashir , Feher Virginia , Torso Mario , Krug Kristine , Esiri Margaret , Chance Steven A , Szele Francis G
Published: May 2017

Autism spectrum disorder is a debilitating condition with possible neurodevelopmental origins but unknown neuroanatomical correlates. Whereas investigators have paid much attention to the cerebral cortex, few studies have detailed the basal ganglia in autism. The caudate nucleus may be involved in the repetitive movements and limbic changes of autism. We used immunohistochemistry for calretinin and neuropeptide Y in 24 age- and gender-matched patients with autism spectrum disorder and control subjects ranging in age from 13 to 69 years. Patients with autism had a 35% lower density of calretinin+ interneurons in the caudate that was driven by loss of small calretinin+ neurons. This was not caused by altered size of the caudate, as its cross-sectional surface areas were similar between diagnostic groups. Controls exhibited an age-dependent increase in the density of medium and large calretinin+ neurons, whereas subjects with autism did not. Diagnostic groups did not differ regarding ionized calcium-binding adapter molecule 1+ immunoreactivity for microglia, suggesting chronic inflammation did not cause the decreased calretinin+ density. There was no statistically significant difference in the density of neuropeptide Y+ neurons between subjects with autism and controls. The decreased calretinin+ density may disrupt the excitation/inhibition balance in the caudate leading to dysfunctional corticostriatal circuits. The description of such changes in autism spectrum disorder may clarify pathomechanisms and thereby help identify targets for drug intervention and novel therapeutic strategies.
Mechanisms governing inflammasome activation, assembly and pyroptosis induction
Authors: Kesavardhana Sannula , Kanneganti Thirumala-Devi
Published: May 2017

Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein—apoptosis-associated speck-like protein containing a caspase-activation and -recruitment domain (ASC)—activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens. Beyond infectious diseases, the importance of inflammasomes is implicated in a variety of clinical conditions such as auto-inflammatory diseases, neuro-degeneration and metabolic disorders and the development of cancers. Understanding inflammasome activation and its molecular regulation can unveil therapeutic targets for controlling inflammasome-mediated disorders. In this review, we describe recent advances in inflammasome biology and discuss its activation, structural insights into inflammasome assembly and mechanisms for the execution of pyroptosis.
Outcomes of Elective Cerebral Aneurysm Treatment Performed by Attending Neurosurgeons after Night Work
Authors: Bekelis Kimon , Missios Symeon , MacKenzie Todd A
Published: May 2017

BACKGROUND

The association between long work hours and outcomes among attending surgeons remains an issue of debate.

OBJECTIVE

To investigate whether operating emergently the night before an elective case was associated with inferior outcomes among attending neurosurgeons.

METHODS

We executed a cohort study with unruptured cerebral aneurysm patients, who underwent endovascular coiling or surgical clipping from 2009 to 2013 and were registered in the Statewide Planning and Research Cooperative System database. We investigated the association of treatment by surgeons performing emergency procedures the night before with outcomes of elective cerebral aneurysm treatment using an instrumental variable analysis.

RESULTS

Overall, 4700 patients underwent treatment for unruptured cerebral aneurysms. There was no difference in inpatient mortality (adjusted difference, –0.7%; 95% confidence interval [CI], –1.4% to 0.02%), discharge to a facility (adjusted difference, –0.1%; 95% CI, –1.2% to 1.2%), or length of stay (adjusted difference, –0.58; 95% CI, –1.66 to 0.50) between patients undergoing elective cerebral aneurysm treatment by surgeons who performed emergency procedures the night before, and those who did not.

CONCLUSION

Using a comprehensive patient cohort in New York State for elective treatment of unruptured cerebral aneurysms, we did not identify an association of treatment by surgeons performing emergency procedures the night before, with mortality, discharge to a facility, or length of stay. Our study had 80% power to detect differences in mortality (our primary outcome), as small as 4.1%. The results of the present study do not support the argument for regulation of attending work hours.
Over-expression of the RieskeFeS protein increases electron transport rates and yield inArabidopsis
Authors: Simkin Andrew J. , McAusland Lorna , Lawson Tracy , Raines Christine A.
Published: May 2017

In this study we have generated transgenic Arabidopsis plants over-expressing the Rieske FeS protein (PetC), a component of the cytochromeb6f(cytb6f) complex. Increasing the levels of this protein, resulted in the concomitant increase in the levels of cytf(PetA) and cytb6(PetB), core proteins of the cytb6fcomplex. Interestingly, an increase in the levels of proteins in both the PSI and PSII complexes was also seen in the Rieske FeS ox plants. Although the mechanisms leading to these changes remain to be identified, the transgenic plants presented here provide novel tools to explore this. Importantly, the overexpression of the Rieske FeS protein resulted in a substantial and significant impact on the quantum efficiency of PSI and PSII, electron transport, biomass and seed yield in Arabidopsis plants. These results demonstrate the potential for manipulating electron transport processes to increase crop productivity.

One-sentence summary

Over-expression of the Rieske FeS protein results in significant increases in the quantum efficiencies or PSI and PSII, increases in Amaxand has the potential to increase crop productivity
Activation of Piezo1 but not NaV1.2 Channels by Ultrasound at 43 MHz
Authors: Prieto Martin Loynaz , Firouzi Kamyar , Khuri-Yakub Butrus T. , Maduke Merritt
Published: May 2017

Ultrasound (US) can modulate the electrical activity of the excitable tissues but the mechanisms underlying this effect are not understood at the molecular level or in terms of the physical modality through which US exerts its effects. Here we report an experimental system that allows for stable patch-clamp recording in the presence of US at 43 MHz, a frequency known to stimulate neural activity. We describe the effects of US on two ion channels proposed to be involved in the response of excitable cells to US: the mechanosensitive Piezo1 channel and the voltage-gated sodium channel NaV1.2. Our patch-clamp recordings, together with finite-element simulations of acoustic field parameters indicate that Piezo1 channels are activated by continuous wave US at 43 MHz and 50 or 90 W/cm2through cell membrane stress caused by acoustic streaming. NaV1.2 channels were not affected through this mechanism at these intensities, but their kinetics could be accelerated by US-induced heating.
CytoCensus: mapping cell identity and division in tissues and organs using machine learning
Authors: Hailstone Martin , Waithe Dominic , Samuels Tamsin J , Yang Lu , Costello Ita , Arava Yoav , Robertson Elizabeth J , Parton Richard M , Davis Ilan
Published: May 2017

A major challenge in cell and developmental biology is the automated identification and quantitation of cells in complex multilayered tissues. We developed CytoCensus: an easily deployed implementation of supervised machine learning that extends convenient 2D “point- and-click” user training to 3D detection of cells in challenging datasets with ill-defined cell boundaries. In tests on these datasets, CytoCensus outperforms other freely available image analysis software in accuracy and speed of cell detection. We used CytoCensus to count stem cells and their progeny, and to quantify individual cell divisions from time-lapse movies of explantedDrosophilalarval brains, comparing wild-type and mutant phenotypes. We further illustrate the general utility and future potential of CytoCensus by analysing the 3D organisation of multiple cell classes in Zebrafish retinal organoids and cell distributions in mouse embryos. CytoCensus opens the possibility of straightforward and robust automated analysis of developmental phenotypes in complex tissues.

Hailstoneet al. develop CytoCensus, a “point-and-click” supervised machine-learning image analysis software to quantitatively identify defined cell classes and divisions from large multidimensional data sets of complex tissues. They demonstrate its utility in analysing challenging developmental phenotypes in living explantedDrosophilalarval brains, mammalian embryos and zebrafish organoids. They further show, in comparative tests, a significant improvement in performance over existing easy-to-use image analysis software.

Highlights

CytoCensus: machine learning quantitation of cell types in complex 3D tissues

Single cell analysis of division rates from movies of livingDrosophilabrains in 3D

Diverse applications in the analysis of developing vertebrate tissues and organoids

Outperforms other image analysis software on challenging, low SNR datasets tested
Functional architecture of deleterious genetic variants in the Wrangel Island mammoth genome
Authors: Fry Erin , Kim Sun K. , Chigurapti Sravanthi , Mika Katelyn M. , Ratan Aakrosh , Dammermann Alexander , Mitchell Brian J. , Miller Webb , Lynch Vincent J.
Published: May 2017

Woolly mammoths were among the most abundant cold adapted species during the Pleistocene. Their once large populations went extinct in two waves, an end-Pleistocene extinction of continental populations followed by the mid-Holocene extinction of relict populations on St. Paul Island ~5,600 years ago and Wrangel Island ~4,000 years ago. Wrangel Island mammoths experienced an episode of rapid demographic decline coincident with their isolation, leading to a small population, reduced genetic diversity, and the fixation of putatively deleterious alleles, but the functional consequences of these processes are unclear. Here we show that the Wrangel Island mammoth accumulated many putative deleterious mutations that are predicted to cause diverse behavioral and developmental defects. Resurrection and functional characterization of Wrangel Island mammoth genes carrying these substitutions identified both loss and gain of function mutations in genes associated with developmental defects (HYLS1), oligozoospermia and reduced male fertility (NKD1), diabetes (NEUROG3), and the ability to detect floral scents (OR5A1). These results suggest that Wrangel Island mammoths may have suffered adverse consequences from their reduced population sizes and isolation.
Conformational dynamics in TRPV1 channels reported by an encoded coumarin amino acid
Authors: Steinberg Ximena , Kasimova Marina A. , Cabezas-Bratesco Deny , Galpin Jason , Ladrón-de-Guevara Ernesto , Villa Federica , Carnevale Vincenzo , Islas Leon D. , Ahern Christopher A. , Brauchi Sebastian E.
Published: May 2017

Transient Receptor Potential Vanilloid (TRPV1) channels support the detection and integration of nociceptive input. Currently available functional and structural data suggest that that TRPV1 channels have two potential gates within their cation selective permeation pathway: a barrier formed by a ‘bundle crossing’ at the intracellular entrance and a second constriction created by the ion selectivity filter. To describe conformational changes associated with channel gating within the pore, the fluorescent non-canonical amino acid (f- ncAA) coumarin-tyrosine was genetically encoded at Y671, a residue proximal to the selectivity filter. TRPV1 channels expressing coumarin at either site displayed normal voltage- and agonist-dependent gating. Next, total internal reflection microscopy (TIRF) was performed to enable ultra-rapid, millisecond imaging of the conformational dynamics in single TRPV1 channels in live cells. Here, the data obtained from channels expressed in human derived cells show that optical fluctuations, photon counts, and variance of noise analysis from Y671 coumarin encoded in TRPV1 tetramers correlates closely with channel activation by capsaicin, thus providing an direct optical marker of channel activation at the selectivity filter. In companion molecular dynamics simulations, Y671 displays alternating solvent exposure between the closed and open states, giving support to the optical data. These calculations further suggest a direct involvement of Y671 in controlling the relative position of the pore helix and its role in supporting ionic conductance at the TRPV1 selectivity filter.
An oomycete effector protein induces shade avoidance inArabidopsisand attenuates salicylate signaling by binding to host proteins of the RADICAL-INDUCED CELL DEATH1 family
Authors: Wirthmueller Lennart , Asai Shuta , Rallapalli Ghanasyam , Sklenar Jan , Fabro Georgina , Kim Dae Sung , Lintermann Ruth , Jaspers Pinja , Wrzaczek Michael , Kangasjärvi Jaakko , MacLean Daniel , Menke Frank L. H. , Banfield Mark J. , Jones Jonathan D. G.
Published: May 2017

The oomycete pathogenHyaloperonospora arabidopsidis(Hpa) causes downy mildew disease onArabidopsis. During infection,Hpalike other biotrophic pathogens, suppresses activation of plant innate immunity by translocating effector proteins into host cells. Some of these effectors localize to the host cell nucleus where they may manipulate transcriptional reprogramming of plant defense genes. Here we report that the nuclear-localizedHpaeffector HaRxL106, when expressed inArabidopsis, induces shade avoidance and attenuates the transcriptional response to the defense signaling molecule salicylic acid. HaRxL106 interacts with RADICAL-INDUCED CELL DEATH1 (RCD1) and loss of RCD1 function rendersArabidopsisresilient against HaRxL106-mediated suppression of immunity. To further characterize the molecular functions of RCD1 we solved a crystal structure of RCD1’s Poly-(ADP-ribose)-Polymerase (PARP) domain and, based on non-conservation of amino acids constituting the active site of canonical PARPs, conclude that RCD1 has no PARP activity. We report that RCD1-type proteins are phosphorylated and identified histone-modifying Mut9-like kinases (MLKs) as RCD1-interacting proteins. Amlk1,3,4triple mutant exhibits stronger SA-induced defense marker gene expression compared to wild-type plants. Our data suggest that HaRxL106 suppressesArabidopsisinnate immunity by manipulating the function(s) of RCD1 in the host cell nucleus and point towards a role of RCD1 as a transcriptional co-regulator that integrates signals from light and pathogen sensors.
The algorithmic neuroanatomy of action-outcome learning
Authors: Morris Richard W. , Dezfouli Amir , Griffiths Kristi R , Le Pelley Mike E , Balleine Bernard W
Published: May 2017

Although it is well known that animals can encode the consequences of their actions and can use this information to control action selection and evaluation, it is not known what learning rules control action-outcome (AO) learning. Here we trained participants to encode specific AO associations whilst undergoing functional imaging (fMRI) and used computational modelling to evaluate competing models. This analysis revealed that a Kalman filter, which learned the unique causal effect of each action, best characterized AO learning and found the medial prefrontal cortex differentiated the unique effect of actions from background effects. We subsequently extended these findings to show that mPFC participated in a circuit with parietal cortex and caudate nucleus to segregate distinct contributions to AO learning. The results extend our understanding of goal-directed learning and demonstrate that sensitivity to the causal relationship between actions and outcomes guides goal-directed learning rather than contiguous state-action relations.
Rational Design of RNA Structures that Predictably Tune Eukaryotic Gene Expression
Authors: Weenink Tim , McKiernan Robert M. , Ellis Tom
Published: May 2017

Predictable tuning of gene expression is essential for engineering genetic circuits and for optimising enzyme levels in metabolic engineering projects. In bacteria, gene expression can be tuned at the stage of transcription, by exchanging the promoter, or at stage of translation by altering the ribosome binding site sequence. In eukaryotes, however, only promoter exchange is regularly used, as the tools to modulate translation are lacking. Working inS. cerevisiaeyeast, we here describe how hairpin RNA structures inserted into the 5’ untranslated region (5’UTR) of mRNAs can be used to tune expression levels by altering the efficiency of translation initiation. We demonstrate a direct link between the calculated free energy of folding in the 5’UTR and protein abundance, and show that this enables rational design of hairpin libraries that give predicted expression outputs. Our approach is modular, working with different promoters and protein coding sequences, and it outperforms promoter mutation as a way to predictably generate a library where a protein is induced to express at a range of different levels. With this tool, computational RNA sequence design can be used to predictably fine-tune protein production, providing a new way to modulate gene expression in eukaryotes.
The dynamic core microbiome: Structure, dynamics and stability
Authors: Björk Johannes R. , O’Hara Robert B. , Ribes Marta , Coma Rafel , Montoya José M.
Published: May 2017

The long-term stability of microbiomes is crucial as the persistent occurrence of beneficial microbes and their associated functions ensure host health and well-being. Microbiomes are highly diverse and dynamic, making them challenging to understand. Because many natural systems work as temporal networks, we present an approach that allows identifying meaningful ecological patterns within complex microbiomes: the dynamic core microbiome. On the basis of six marine sponge species sampled monthly over three years, we study the structure, dynamics and stability of their microbiomes. What emerge for each microbiome is a negative relationship between temporal variability and mean abundance. The notion of the dynamic core microbiome allowed us to determine a relevant functional attribute of the microbiome: temporal stability is not determined by the diversity of a host’s microbial assemblages, but rather by the density of those microbes that conform its core microbiome. The core microbial interaction network consisted of complementary members interacting weakly with dominance of comensal and amensal interactions that suggests self-regulation as a key determinant of the temporal stability of the microbiome. These interactions have likely coevolved to maintain host functionality and fitness over ecological, and even evolutionary time scales.
Expression of Pokeweed Antiviral Protein Isoform S1 (PAP-S1) and of Ricin-A-Chain/PAP-S1 novel fusion protein (RTA/PAP-S1) inEscherichia coliand their comparative inhibition of protein synthesisin vitro
Authors: Hassan Yasser , Ogg Sherry
Published: May 2017

Fusion protein therapeutics engineering is advancing to meet the need for novel medicine. Herein, we further characterize the development of novel RTA & PAP-S1 antiviral fusion proteins. In brief, RTA/PAP-S1 and PAP-S1/RTA fusion proteins were produced in both cell free andE. coli in vivoexpression systems, purified by His-tag affinity chromatography, and protein synthesis inhibitory activity assayed by comparison to the production of a control protein, CalmL3. Results showed that the RTA/PAP-S1 fusion protein is amenable to standardized production and purification and has both increased potency and less toxicity compared to either RTA or PAP-S1 alone. Thus, this research highlights the developmental potential of novel fusion proteins with reduced cytotoxic risk and increased potency.
Aminoglycoside antibiotics perturb physiologically important microRNA contributing to drug toxicity
Authors: Jayaraj Gopal Gunanathan , Ramasamy Soundhar , Bose Debojit , Suryawanshi Hemant , Lalwani Mukesh , Sivasubbu Sridhar , Maiti Souvik
Published: May 2017

miRNAs are key non-protein coding regulators of gene expression in various pathophysiological conditions. Targeting miRNA with small molecules offer an unconventional approach, where clinically active compounds with RNA binding activity can be tested for their ability to modulate miRNA levels and thus for drug repositioning. Aminoglycoside antibiotics are highly effective microbicidal RNA binding molecules that bind to prokaryotic rRNA secondary structures. Here, we report that specific subsets of miRNA can be modulated by aminoglycosides. However, ototoxicity (cochlear and vestibular) and nephrotoxicity of multiple origins resulting from prolonged use are a well-known disadvantage of aminoglycosides. Mature non-coding RNAs and their precursors can present off-target sites, by forming secondary structures that resemble ribosomal RNA, thus providing an additional molecular basis for the toxicity of aminoglycosides. Using in vitro, in cellulae and physiological responses, we provide evidence for the direct functional perturbation of the miR- 96 cluster leading to selective cell death in neuromasts- the zebrafish equivalent of cochlear hair cells, by Streptomycin, a prototype aminoglycoside antibiotic, thus contributing to the observed ototoxicity. Our observations, collectively underscore the importance of re- evaluating RNA binding drugs for their off-targeting effects in the context of miRNA and other functional non-coding RNA.
In depth analysis of kinase cross screening data to identify chemical starting points for inhibition of the nek family of kinases
Authors: Wells Carrow I. , Kapadia Nirav R. , Couñago Rafael M. , Drewry David H.
Published: May 2017

Potent, selective, and cell active small molecule kinase inhibitors are useful tools to help unravel the complexities of kinase signaling. As the biological functions of individual kinases become better understood, they can become targets of drug discovery efforts. The small molecules used to shed light on function can also then serve as chemical starting points in these drug discovery efforts. The Nek family of kinases has received very little attention, as judged by number of citations in PubMed, yet they appear to play many key roles and have been implicated in disease. Here we present our work to identify high quality chemical starting points that have emerged due to the increased incidence of broad kinome screening. We anticipate that this analysis will allow the community to progress towards the generation of chemical probes and eventually drugs that target members of the Nek family.
Dendritic sodium spikes endow neurons with inverse firing rate response to correlated synaptic activity
Authors: Górski Tomasz , Veltz Romain , Galtier Mathieu , Fragnaud Hélissande , Goldman Jennifer S. , Teleńczuk Bartosz , Destexhe Alain
Published: May 2017

Many neurons possess dendrites enriched with sodium channels and are capable of generating action potentials. However, the role of dendritic sodium spikes remain unclear. Here, we study computational models of neurons to investigate the functional effects of dendritic spikes. In agreement with previous studies, we found that point neurons or neurons with passive dendrites increase their somatic firing rate in response to the correlation of synaptic bombardment for a wide range of input conditions, i.e. input firing rates, synaptic conductances or refractory periods. However, neurons with active dendrites show the opposite behavior: for a wide range of conditions the firing rate decreases as a function of correlation. We found this property in three types of models of dendritic excitability: a Hodgkin-Huxley model of dendritic spikes, a model with integrate-and-fire dendrites, and a discrete-state dendritic model. We conclude that neurons equipped with with fast dendritic spikes confer much broader computational properties to neurons, sometimes opposite to that of point neurons.
Managerial perceptions of energy in logistics
Authors: Busse Christian , Regelmann Alexander , Chithambaram Hariganesh , Wagner Stephan M.
Published: May 2017

Purpose

Because of the major contribution of logistics to the greenhouse gas effect, logistics research has begun to address the topic of energy, but it has not yet targeted the role of energy within logistical decision-making processes. To facilitate such endeavors, the purpose of this paper is to explore the perceptions of energy which managers in logistics organizations portray.

Design/methodology/approach

This investigation is based on interviews with 17 managers. The findings are embedded in the theory of planned behavior (TPB) and stakeholder theory (SHT).

Findings

The study depicts initial insights on which energy-related perceptions exist, how they can be categorized into attitudes, subjective norms, and perceived behavioral controls (PBCs), and how different stakeholders seem to affect them.

Research limitations/implications

This research suggests a tentative comprehensive conceptual framework that describes the role of energy in logistical decision-making processes. The findings on attitudes and subjective norms appear to be unspecific to the logistics domain, whereas some of the PBCs are presumably unique to the logistics context. Future logistics research should hence focus its efforts on the PBCs. Generalizability and completeness of the managerial perceptions must be validated by future research.

Practical implications

The findings help logistics organizations in scrutinizing managerial perspectives on energy and in developing awareness-raising measures.

Originality/value

The behavioral perspective applied in this study can complement extant, more technically oriented views. The conceptual framework that integrates the TPB and SHT may also be useful for organizational research beyond the logistics domain.
How do financial constraints and financing costs affect inventories? An empirical supply chain perspective
Authors: Hoberg Kai , Protopappa-Sieke Margarita , Steinker Sebastian
Published: May 2017

Purpose

The purpose of this paper is to identify the interplay between a firm’s financial situation and its inventory ownership in a single-firm and a two-firm perspective.

Design/methodology/approach

The analysis uses different secondary data sources to quantify the effect of both financial constraints and cost of capital on inventory holdings of public US firms. The authors first adopt a single-firm perspective and analyze whether financial constraints and cost of capital do generally affect the amount of inventory held. Next, the authors adopt a two-firm perspective and analyze the inventory ownership in customer-supplier relationships.

Findings

Inventory levels are affected by financial constraints and cost of capital. Results indicate that higher costs of capital are weakly associated with lower inventories. However, contrary to the authors’ expectations, firms that are less financially constrained hold less inventories than firms that are more financially constrained. Finally, the authors find that customers hold the larger fraction of supply chain inventory in supplier-customer dyads.

Practical implications

The authors’ results indicate that financial considerations generally play a role in inventory management. However, inventory holdings seem to be influenced only slightly by financing costs and inventory holdings between supplier and customer seem to be less than optimal from a financial perspective. Considering those financial aspects can lead to relevant financial advantages.

Originality/value

In contrast to other recent research, the authors study how the financial situation of a firm affects its inventory levels (not vice versa) and also consider inventories from a two-firm perspective.
Maternal food availability affects offspring performance and survival in a viviparous lizard
Authors: Wang Yang , Li Shu‐Ran , Zeng Zhi‐Gao , Liang Liang , Du Wei‐Guo
Published: May 2017

Whether maternal effects are adaptive or not has been a long‐standing topic of discussion in evolutionary ecology. The effects of maternal diet on offspring have been addressed by several studies on diverse organisms, but results are typically conflicting or inconclusive.

In this study, we conducted food manipulation experiments with a factorial design (high and low maternal food conditions × high and low offspring food conditions) in a viviparous lacertid lizard (Eremias multiocellata) to test four competing hypotheses on the evolutionary significance of maternal effects: environmental matching hypothesis, low‐food compensation hypothesis, low‐food pathology hypothesis and no‐compensation hypothesis.

We found that offspring under the maternal low‐food treatment had higher growth and survival rates than those under the maternal high‐food treatment, supporting the low‐food compensation hypothesis rather than the environmental matching hypothesis, which has been widely accepted as an explanation for the adaptive significance of maternal effects.

Our study highlights the importance of testing multiple competing hypotheses that involve both adaptive and non‐adaptive explanations when studying the evolutionary significance of phenotypic plasticity.

Alay summaryis available for this article.
Resource stoichiometry and availability modulate species richness and biomass of tropical litter macro‐invertebrates
Authors: Jochum Malte , Barnes Andrew D. , Weigelt Patrick , Ott David , Rembold Katja , Farajallah Achmad , Brose Ulrich
Published: May 2017

High biodiversity and biomass of soil communities are crucial for litter decomposition in terrestrial ecosystems such as tropical forests. However, the leaf litter that these communities consume is of particularly poor quality as indicated by elemental stoichiometry. The impact of resource quantity, quality and other habitat parameters on species richness and biomass of consumer communities is often studied in isolation, although much can be learned from simultaneously studying both community characteristics.

Using a dataset of 780 macro‐invertebrate consumer species across 32 sites in tropical lowland rain forest and agricultural systems on Sumatra, Indonesia, we investigated the effects of basal resource stoichiometry (C:X ratios of N, P, K, Ca, Mg, Na, S in local leaf litter), litter mass (basal resource quantity and habitat space), plant species richness (surrogate for litter habitat heterogeneity), and soil pH (acidity) on consumer species richness and biomass across different consumer groups (i.e. 3 feeding guilds and 10 selected taxonomic groups).

In order to distinguish the most important predictors of consumer species richness and biomass, we applied a standardised model averaging approach investigating the effects of basal resource stoichiometry, litter mass, plant species richness and soil pH on both consumer community characteristics. This standardised approach enabled us to identify differences and similarities in the magnitude and importance of such effects on consumer species richness and biomass.

Across consumer groups, we found litter mass to be the most important predictor of both species richness and biomass. Resource stoichiometry had a more pronounced impact on consumer species richness than on their biomass. As expected, taxonomic groups differed in which resource and habitat parameters (basal resource stoichiometry, litter mass, plant species richness and pH) were most important for modulating their community characteristics.

The importance of litter mass for both species richness and biomass indicates that these tropical consumers strongly depend on habitat space and resource availability. Our study supports previous theoretical work indicating that consumer species richness is jointly influenced by resource availability and the balanced supply of multiple chemical elements in their resources.
An investigation of the anti‐inflammatory effects and a potential biomarker of PI3Kδ inhibition in COPD T cells
Authors: Khan Abid , Southworth Thomas , Worsley Sally , Sriskantharajah Srividya , Amour Augustin , Hessel Edith M , Singh Dave
Published: May 2017

Lymphocyte numbers are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. Phosphatidylinositol‐3‐kinase delta (PI3Kδ) is involved in lymphocyte activation. We investigated the effect of PI3Kδ inhibition on cytokine release from COPD lymphocytes. We also evaluated phosphorylated ribosomal S6 protein (rS6) as a potential biomarker of PI3Kδ activation. Peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells isolated from healthy never smokers (HNS), smokers (S) and COPD patients were stimulated to induce a T cell receptor response. The effects of a PI3Kδ specific inhibitor (GSK045) on cytokine release and rS6 phosphorylation were measured by Luminex and flow cytometry respectively. The effects of GSK045 on cytokine production from PHA stimulated chopped lung samples were investigated. GSK045 reduced cytokine release from PBMCs, BAL cells and chopped lung. Inhibition was greatest in the chopped lung model, with approximately 80% inhibition of interferon (IFN) γ, interleukin (IL)‐2, IL‐17 and IL‐10. PI3Kδ inhibition suppressed rS6 phosphorylation in unstimulated airway T‐lymphocytes by up to 60%. Inhibition of PI3Kδ suppressed T cell cytokine production in COPD patients. rS6 phosphorylation shows potential as a biomarker to assess PI3Kδ activity.