bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Fire Blight Using Pre-bloom Application of Prohexadione-Calcium
Authors: Wallis Anna E. , Cox Kerik D.
Published: November 2019

Fire blight, a bacterial disease of rosaceous plants caused by Erwinia amylovora, is one of the most important diseases affecting commercial apple production worldwide. Antibiotics, applied at bloom to protect against blossom infection, are the most effective means of management but raise concern due to the potential for antibiotic resistance in both the pathogen population and nontarget organisms. In addition, most fire blight outbreaks in New York State often emerge in late June to July as shoot blight, calling into question the role of blossom infections and the antibiotic applications made to manage them. Prohexadione-calcium (PhCa) is a gibberellic acid inhibitor used post-bloom to control shoot vigor and to manage shoot blight. However, the magnitude of shoot blight management is directly related to the suppression of shoot growth, which is undesirable, especially in young orchards during establishment years. PhCa is believed to control shoot blight by thickening cell walls in cortical parenchyma, preventing invasion of host tissues by E. amylovora. We hypothesize that PhCa applied pre-bloom could similarly prevent invasion of blossom pedicels following infection, leading to reduced disease incidence. We evaluated novel pre-bloom PhCa programs for their effects on disease management (blossom and shoot blight) as well as their impact on shoot growth for three years in a mature ‘Gala’ orchard in New York. In all three years of the study, all PhCa programs resulted in less than 27% incidence (71% control) of blossom blight and less than 13% incidence (77% control) of shoot blight with minimal effect on tree growth. Inclusion of a biopesticide during bloom further reduced the incidence of blossom blight in one year of three. Using light microscopy, we found that cell walls in the cortical parenchyma of fruitlet pedicels on trees receiving pre-bloom PhCa applications were significantly thicker than those of untreated trees 40 days after full bloom and inoculation. Overall, we found that pre-bloom applications of PhCa had utility in reducing blossom blight and shoot blight with minimal impacts on tree growth. These pre-bloom programs would fit with standard production practices and may contribute toward the development of fire blight management programs without the use of antibiotics.
A single ‘weight-lifting’ game covers all kinds of games
Authors: Yamamoto Tatsuki , Ito Hiromu , Nii Momoka , Okabe Takuya , Morita Satoru , Yoshimura Jin
Published: November 2019

Game theory has been studied extensively to answer why cooperation is promoted in human and animal societies. All games are classified into five games: the Prisoner's Dilemma, chicken game (including hawk–dove game), stag hunt game and two trivial games of either all cooperation or all defect, which are studied separately. Here, we propose a new game that covers all five game categories: the weight-lifting game. The player choose either to (1) carry a weight (cooperate: pay a cost) or (2) pretend to carry it (defect: pay no cost). The probability of success in carrying the weight depends on the number of cooperators, and the players either gain the success reward or pay the failure penalty. All five game categories appear in this game depending on the success probabilities for the number of cooperators. We prove that this game is exactly equivalent to the combination of all five games in terms of a pay-off matrix. This game thus provides a unified framework for studying all five types of games.
Ice sheet flow with thermally activated sliding. Part 2: the stability of subtemperate regions
Authors: Mantelli E. , Schoof C.
Published: November 2019

The onset of sliding in ice sheets may not take the form of a sharp boundary between regions at the melting point, in which sliding is permitted, and regions below that temperature, in which there is no slip. Such a hard switch leads to the paradox of the bed naturally wanting to refreeze as soon as sliding has commenced. A potential alternative structure is a region of subtemperate sliding. Here temperatures are marginally below the melting point and sliding velocities slower than they would if the bed was fully temperate. Rather than being controlled by a standard sliding law, sliding velocities are then constrained by the need to maintain energy balance. This thermal structure arises in temperature-dependent sliding laws in the limit of strong sensitivity to temperature. Here, we analyse the stability of such subtemperate regions, showing that they are subject to a set of instabilities that occur at all length scales between ice thickness and ice sheet length. The fate of these instabilities is to cause the formation of patches of frozen bed, raising the possibility of highly complicated cold-to-temperate transitions with spatial structures at short length scales that cannot be resolved in large-scale ice sheet simulation codes.
Theory of the flow-induced deformation of shallow compliant microchannels with thick walls
Authors: Wang Xiaojia , Christov Ivan C.
Published: November 2019

Long, shallow microchannels embedded in thick, soft materials are widely used in microfluidic devices for lab-on-a-chip applications. However, the bulging effect caused by fluid–structure interactions between the internal viscous flow and the soft walls has not been completely understood. Previous models either contain a fitting parameter or are specialized to channels with plate-like walls. This work is a theoretical study of the steady-state response of a compliant microchannel with a thick wall. Using lubrication theory for low-Reynolds-number flows and the theory for linearly elastic isotropic solids, we obtain perturbative solutions for the flow and deformation. Specifically, only the channel's top wall deformation is considered, and the ratio between its thicknesstand widthwis assumed to be (t/w)2≫1. We show that the deformation at each stream-wise cross section can be considered independently, and that the top wall can be regarded as a simply supported rectangle subject to uniform pressure at its bottom. The stress and displacement fields are found using Fourier series, based on which the channel shape and the hydrodynamic resistance are calculated, yielding a new flow rate–pressure drop relation without fitting parameters. Our results agree favourably with, and thus rationalize, previous experiments.
The what, why and how of curly hair: a review
Authors: Cloete Elsabe , Khumalo Nonhlanhla P. , Ngoepe Malebogo N.
Published: November 2019

An attempt to understand and explain a peculiarity that was observed for curly fibres during experimentation revealed disparate literature reporting on several key issues. The phenotypical nature of curly fibres is only accurately understood within the larger scope of hair fibres, which are highly complex biological structures. A brief literature search produced thousands of research items. Besides the large amount of information on the topic, there was also great variability in research focus. From our review, it appeared that the complexity of hair biology, combined with the variety of research subtopics, often results in uncertainty when relating different aspects of investigation. During the literature investigation, we systematically categorized elements of curly hair research into three basic topics: essentially asking why fibres curl, what the curly fibre looks like and how the curly fibre behaves. These categories were subsequently formalized into a curvature fibre model that is composed of successive but distinctive tiers comprising the elements in curly hair research. The purpose of this paper is twofold: namely to present (i) a literature review that explores the different aspects of curly human scalp hair and (ii) the curvature fibre model as a systemized approach to investigating curly hair.
A drop does not fall in a straight line: a rationale for the width of stalagmites
Authors: Parmentier J. , Lejeune S. , Maréchal M. , Bourges F. , Genty D. , Terrapon V. , Maréchal J.-C. , Gilet T.
Published: November 2019

Drops loaded in calcium ions detach from stalactites and impact the underlying stalagmites, thereby allowing these latter to grow through calcite precipitation. Nevertheless, little is known about the influence of the drop free fall and splash dynamics on stalagmite shape and width. Through high-speed imaging of impacting drops on stalagmites from several caves, we observed that the impact point position of the drops is scattered, sometimes over several centimetres. We show that this dispersal has no external cause and must, therefore, be self-induced. Using a Langevin-like equation, we then propose a prediction of the impact point dispersal as a function of the falling height travelled by the drops. We finally show that measured stalagmite widths are correlated to the dispersal in the impact point position of the drop.
The inherited bacterial symbiont
Hamiltonella
influences the sex ratio of an insect host
Authors: Shan Hong-Wei , Luan Jun-Bo , Liu Yin-Quan , Douglas Angela E. , Liu Shu-Sheng
Published: November 2019

In many intracellular symbioses, the microbial symbionts provide nutrients advantageous to the host. However, the function of
Hamiltonella defensa
, a symbiotic bacterium localized in specialized host cells (bacteriocytes) of a whitefly
Bemisia tabaci
, is uncertain. We eliminate this bacterium from its whitefly host by two alternative methods: heat treatment and antibiotics. The sex ratio of the host progeny and subsequent generations of
Hamiltonella
-free females was skewed from 1 : 1 (male : female) to an excess of males, often exceeding a ratio of 20 : 1.
B. tabaci
is haplodiploid, with diploid females derived from fertilized eggs and haploid males from unfertilized eggs. The
Hamiltonella
status of the insect did not affect copulation frequency or sperm reserve in the spermathecae, indicating that the male-biased sex ratio is unlikely due to the limitation of sperm but likely to be associated with events subsequent to sperm transfer to the female insects, such as failure in fertilization. The host reproductive response to
Hamiltonella
elimination is consistent with two alternative processes: adaptive shift in sex allocation by females and a constitutive compensatory response of the insect to
Hamiltonella
-mediated manipulation. Our findings suggest that a bacteriocyte symbiont influences the reproductive output of female progeny in a haplodiploid insect.
Microbial evolution and ecological opportunity in the gut environment
Authors: Scanlan Pauline D.
Published: November 2019

Recent genomic and metagenomic studies have highlighted the presence of rapidly evolving microbial populations in the human gut. However, despite the fundamental implications of this intuitive finding for both basic and applied gut microbiome research, very little is known about the mode, tempo and potential functional consequences of microbial evolution in the guts of individual human hosts over a lifetime. Here I assess the potential relevance of ecological opportunity to bacterial adaptation, colonization and persistence in the neonate and germ-free mammalian gut environment as well as over the course of an individual lifetime using data emerging from mouse models as well as human studies to provide examples where possible. I then briefly outline how the continued development and application of experimental evolution approaches coupled to genomic and metagenomic analysis is essential to disentangling drift from selection and identifying specific drivers of evolution in the gut microbiome within and between individual human hosts and populations.
Changing environments and genetic variation: natural variation in inbreeding does not compromise short-term physiological responses
Authors: Buckley James , Daly Rónán , Cobbold Christina A. , Burgess Karl , Mable Barbara K.
Published: November 2019

Selfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce their long-term evolutionary potential. However, appropriate short-term plastic responses to new environmental conditions might not require high levels of standing genetic variation. In this study, we tested whether mating system variation among populations, and associated changes in genetic variability, affected short-term responses to environmental challenges. We compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a perennial plant,Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range. We found no effect of inbreeding on survival, flowering phenology or short-term physiological responses. Specifically, naturally occurring inbreeding had no significant effects on the plasticity of metabolome profiles, using either multivariate approaches or analysis of variation in individual metabolites, with inbreeding populations showing similar physiological responses to outbreeding populations over time in both growing environments. We conclude that low genetic diversity in naturally inbred populations may not always compromise fitness or short-term physiological capacity to respond to environmental change, which could help to explain the global success of selfing mating strategies.
Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage
Authors: Cao Bo , Wu Xiaolin , Zhou Jieliang , Wu Hang , DeMott Michael S. , Gu Chen , Wang Lianrong , You Delin , Dedon Peter C.
Published: November 2019

Here we present the Nick-seq platform for quantitative mapping of DNA modifications and damage at single-nucleotide resolution across genomes. Pre-existing breaks are blocked and DNA structures converted to strand-breaks for 3’-extension by nick-translation to produce nuclease-resistant oligonucleotides, and 3’-capture by terminal transferase tailing. Libraries from both products are subjected to next-generation sequencing. Nick-seq is a generally applicable method illustrated with quantitative profiling of single-strand-breaks, phosphorothioate modifications, and DNA oxidation.
Verifying molecular clusters by 2-color localization microscopy and significance testing
Authors: Arnold Andreas M. , Schneider Magdalena C. , Hüsson Christoph , Sablatnig Robert , Brameshuber Mario , Baumgart Florian , Schütz Gerhard J.
Published: November 2019

While single-molecule localization microscopy (SMLM) offers the invaluable prospect to visualize cellular structures below the diffraction limit of light microscopy, its potential could not be fully capitalized due to its inherent susceptibility to blinking artifacts. Particularly, overcounting of single molecule localizations has impeded a reliable and sensitive detection of biomolecular nanoclusters. Here we introduce a 2-Color Localization microscopy And Significance Testing Approach (2-CLASTA), providing a parameter-free statistical framework for the analysis of SMLM data via significance testing methods. 2-CLASTA yields p-values for the null hypothesis of random biomolecular distributions, independent of the blinking behavior of the chosen fluorescent labels. We validated the method both by computer simulations as well as experimentally, using protein concatemers as a mimicry of biomolecular clustering. As the new approach it is not affected by overcounting artifacts, it is able to detect biomolecular clustering of various shapes at high sensitivity down to a level of dimers.
Phytohormonal cross-talk modulate Bipolaris sorokiniana (Scc.)interaction with Zea mays
Authors: Yousaf Muhammad Junaid , Hussain Anwar , Hamayun Muhammad , Iqbal Amjad , Irshad Muhammad , Ahmad Ayaz , Lee In-Jung
Published: November 2019

Besides acting as growth inducing molecule, Gibberellin (GA3) also confers the compatibility of microbial interactions with host. We inoculated 11 days oldZ. maysseedlings grown under hydroponic conditions and high GA3levels withBipolaris sorokiniana(BIPOL) at the spore density (SD) of OD0.6. The high level of GA3negatively affected the growth of the seedlings, accompanied by the high level of stress deducing secondary metabolites (proline, total flavanoids, phenylpropanoids, and glucosinolides). Moreover, high level of GA3produced a hypersensitive response (HR) in the seedlings. The HR developed cross talks with IAA and trans-zeatins and triggered higher production of hypersensitive inducing biomolecules. The other HR co-related biological processes were demonstrated by high phytoalexins level and high protease activities. Such activities ultimately inhibited the colonization of BIPOL on the roots of maize seedlings. The products of the genes expressed at high GA3also conferred the deterrence of BIPOL colonization at SD = OD0.6. Intriguingly, when we inhibited GA3biosynthesis in the seedlings with aerially sprayed uniconizole, prior to BIPOL treatment, the BIPOL colonized and subsequently promoted the seedling growth. This low level of GA3after BIPOL treatment checked the high level of secondary metabolites and hypersensitivity inducing molecules. The results, thus suggested that the aforementioned processes only happened in the BIPOL at SD (OD0.6), whereas the SD at lower levels (OD0.2or OD0.4) neither promoted the growth of uniconizole pre-treated seedlings nor produced HR in control seedlings of maize plant.
Strand asymmetry influences mismatch resolution during single-strand annealing
Authors: Pokusaeva Victoria O. , Diez Aránzazu Rosado , Espinar Lorena , Filion Guillaume J.
Published: November 2019

Background

Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. However, such biases have not yet been measured in chromatin for lack of technologies.

Results

Here we develop a genome-wide assay whereby the same DNA lesion is repaired in different chromatin contexts. We insert thousands of barcoded transposons carrying a reporter of DNA mismatch repair in the genome of mouse embryonic stem cells. Upon inducing a double-strand break between tandem repeats, a mismatch is generated when the single strand annealing repair pathway is used. Regardless of the mismatch, we observed a 60-80% bias in the resolution in favor of one strand. The location of the lesion in the genome and the type of mismatch had little influence on the bias in this context. Instead, changing the position of the double-strand break in the reporter gave a complete reversion of the bias.

Conclusion

These results suggest that the processing of the double-strand break has a major influence on the repair of mismatches during single-strand annealing, irrespective of the surrounding chromatin context.
Quantitative high-resolution imaging of live microbial cells at high hydrostatic pressure
Authors: Bourges A. C. , Lazarev A. , Declerck N. , Rogers K. L. , Royer C. A.
Published: November 2019

The majority of the Earth’s microbial biomass exists in the Deep Biosphere, in the deep ocean and within the Earth’s crust. While other physical parameters in these environments, such as temperature or pH, can differ substantially, they are all under high-pressures. Beyond emerging genomic information, little is known about the molecular mechanisms underlying the ability of these organisms to survive and grow at pressures that can reach over 1000-fold pressure on the Earth’s surface. The mechanisms of pressure adaptation are also important to in food safety, with the increasing use of high-pressure food processing. Advanced imaging represents an important tool for exploring microbial adaptation and response to environmental changes. Here we describe implementation of a high-pressure sample chamber with a 2-photon scanning microscope system allowing for the first time, quantitative high-resolution two-photon imaging at 100 MPa of living microbes from all three kingdoms of life. We adapted this setup for Fluorescence Lifetime Imaging Microscopy with Phasor analysis (FLIM/Phasor) and investigated metabolic responses to pressure of live cells from mesophilic yeast and bacterial strains, as well as the piezophilic archaeon,Archaeoglobus fulgidus. We also monitored by fluorescence intensity fluctuation-based methods (scanning Number and Brightness (sN&B) and Raster scanning Imaging Correlation Spectroscopy (RICS)) the effect of pressure on the chromosome-associated protein HU and on the ParB partition protein inE. coli, revealing partially reversible dissociation of ParB foci and concomitant nucleoid condensation.

SIGNIFICANCE

The majority of the Earth’s microbial biomass exists in high-pressure environments where pressures can reach over 100 MPa. The molecular mechanisms that allow microbes to flourish under such extreme conditions remain to be discovered. The high pressure, high resolution imaging system presented here revealed pressure dependent changes in metabolism and protein interactions in live microbial cells, demonstrating great promise for understanding deep life.
An in vivo KRAS allelic series reveals distinct phenotypes of common oncogenic variants
Authors: Zafra Maria Paz , Alonso-Curbelo Direna , Goswami Sukanya , Schatoff Emma M , Han Teng , Wilkinson John E , Dow Lukas E
Published: November 2019

KRAS is the most frequently mutated oncogene in cancer. Tumor sequencing has revealed a complex spectrum of KRAS mutations across different cancer types, yet there is little understanding how specific KRAS alterations impact tumor in initiation, progression, or therapy response. Using high-fidelity CRISPR-based engineering, we created an allelic series of new LSL-Kras mutant mice, reflecting codon 12 and 13 mutations that are highly prevalent in lung (KRASG12C), pancreas (KRASG12R) and colon (KRASG13D) cancers. Induction of each mutation in the developing mouse pancreas reveal striking quantitative and qualitative differences in the degree of ductal transformation and pre-malignant progression. Further, using organoid models we show that KRASG13D mutants respond to EGFR inhibition, while the anti-proliferative effect of KRASG12C-selective inhibitors can be overcome by upstream EGFR signaling. Together, these new mouse strains provide an ideal for investigating KRAS biology in vivo, and for developing pre-clinical precision oncology models of KRAS-mutant pancreas (G12R), colon (G13D), and lung (G12C) cancers.
Structural characterization of the N-terminal domain of theDictyostelium discoideummitochondrial calcium uniporter
Authors: Yuan Yuan , Cao Chan , Wen Maorong , Li Min , Dong Ying , Wu Lijie , Wu Jian , Cui Tanxing , Li Dianfan , Chou James J. , OuYang Bo
Published: November 2019

The mitochondrial calcium uniporter (MCU) plays a critical role in the mitochondrial calcium uptake into the matrix. In metazoans, the uniporter is a tightly regulated multi-component system including the pore-forming subunit MCU and several regulators (MICU1, MICU2, EMRE). The calcium-conducting activity of metazoan MCU requires the single-transmembrane protein EMRE.Dictyostelium discoideum(Dd), however, developed a simplified uniporter for which the pore-forming MCU (DdMCU) alone is necessary and sufficient for calcium influx. Here, we report a crystal structure of the N-terminal domain (NTD) of DdMCU at 1.7 Å resolution. The DdMCU-NTD contains four helices and two strands arranged in a fold that is completely different from the known structures of other MCU-NTD homologs. Biochemical and biophysical analyses of DdMCU-NTD in solution indicated that the domain exists as oligomers, most probably as a pentamer or hexamer. Mutagenesis showed that the acidic residues Asp60, Glu72 and Glu74, which appeared to mediate the parallel interface as observed in the crystal structure, participated in the self-assembly of DdMCU-NTD. Intriguingly, the oligomeric complex readily dissociated to lower-order oligomers in the presence of calcium. We propose that the calcium-triggered dissociation of NTD regulates the channel activity of DdMCU by a yet unknown mechanism.
Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training
Authors: Yon-Seng Khoo Shaun , Uhrig Alexandra , Samaha Anne-Noël , Chaudhri Nadia
Published: November 2019

The dopamine system is important for incentive salience attribution, where motivational value is assigned to conditioned cues that predict appetitive reinforcers. However, the role of dopamine in this process may change with extended training. We tested the effects of dopamine D1-like and D2-like receptor antagonism on the expression of sign-tracking and goal-tracking conditioned responses following extended Pavlovian conditioned approach (PCA) training. We also tested if amphetamine-induced psychomotor sensitization accelerates the enhanced acquisition of sign-tracking that is observed with extended training. In experiment 1, 24 male Long-Evans rats received 20 PCA sessions in which one lever (CS+, 10 s) predicted 0.2 mL sucrose (10%, w/v) delivery and the other lever (CS−) did not. SCH-23390 (D1-like antagonist) or eticlopride (D2-like antagonist) were administered before non-reinforced behavioural tests at doses of 0, 0.01, and 0.1 mg/kg (s.c.). In experiment 2, rats received vehicle or 2 mg/kg amphetamine (i.p.) for 7 days (n = 12/group). Ten days later, they received 16 PCA training sessions. Both doses of SCH-23390 reduced sign- and goal-tracking, but also reduced locomotor behaviour. A low dose of eticlopride (0.01 mg/kg) selectively reduced goal-tracking, without affecting sign-tracking or locomotor behaviour. Amphetamine produced psychomotor sensitization, and this did not affect the acquisition of sign- or goal-tracking. Following extended PCA training, dopamine D2-like receptor activity is required for the expression of goal-tracking but not sign-tracking. Psychomotor sensitization to amphetamine did not impact incentive salience attribution; however, more selective manipulations of the dopamine system may be needed.
Insect egg-killing: a new front on the evolutionary arms-race between Brassicaceae plants and Pierid butterflies
Authors: Griese Eddie , Caarls Lotte , Mohammadin Setareh , Bassetti Niccolò , Bukovinszkine’Kiss Gabriella , Breman Floris C. , Poelman Erik H. , Gols Rieta , Eric Schranz M. , Fatouros Nina E.
Published: November 2019

Evolutionary arms-races between plants and herbivores have been proposed to generate key innovations that can drive diversification of the interacting species. Recent studies reveal that plant traits that target herbivore insect eggs are widespread throughout the plant kingdom. Within the Brassicaceae family, some plants express a hypersensitive response (HR)-like necrosis underneath the eggs of specialist cabbage white butterflies (Pieridae) that leads to eggs desiccating or dropping of the leaf. Here, we studied the evolutionary basis of this trait, its egg-killing effect on and elicitation by specialist butterflies, by screening 31 Brassicaceae species and nine Pieridae species. We show that induction of HR-like necrosis by pierid egg deposition is clade-specific in the economically important Brassiceae tribe (Brassica crops and close-relatives) and in the first-branching genus Aethionema. The necrosis is elicited only by pierid butterflies that feed on Brassicaceae plants; four Pieris and Anthocharis cardamines butterflies, of which the larvae are specialists on Brassicaceae, elicited a HR-like necrosis. Eggs of pierid butterflies that feed on Rhamnaceae (Gonepteryx rhamni) or Fabaceae (Colias spp.) however, did not elicit such a leaf necrosis. Finally, eggs of Aglais io, a species of the sister group Nymphalidae, did not elicit any visible response. Counter-adaptations to HR-like necrosis might have evolved by insect deposition of eggs in clusters or on inflorescences. Our findings suggest that the plants’ egg-killing trait is a new front on the evolutionary arms-race between Brassicaceae and pierid butterflies beyond the well-studied chemical defence traits against caterpillars.
Learning of complex auditory patterns changes intrinsic and feedforward effective connectivity between Heschl’s gyrus and planum temporale
Authors: Lumaca Massimo , Dietz Martin J. , Hansen Niels Chr. , Quiroga-Martinez David R. , Vuust Peter
Published: November 2019

Learning of complex auditory sequences such as language and music can be thought of as the continuous optimisation of internal predictive representations of sound-pattern regularities, driven by prediction errors. In predictive coding (PC), this occurs through changes in the intrinsic and extrinsic connectivity of the relevant cortical networks, whereby minimization of precision-weighted prediction error signals improves the accuracy of future predictions. Here, we employed Dynamic Causal Modelling (DCM) on functional magnetic resonance (fMRI) data acquired during the presentation of complex auditory patterns. In an oddball paradigm, we presented 52 volunteers (non-musicians) with isochronous 5-tone melodic patterns (standards), randomly interleaved with rare novel patterns comprising contour or pitch interval changes (deviants). Here, listeners must update their standard melodic models whenever they encounter unexpected deviant stimuli. Contour deviants induced an increased BOLD response, as compared to standards, in primary (Heschl’s gyrus, HG) and secondary auditory cortices (planum temporale, PT). Within this network, we found a left-lateralized increase in feedforward connectivity from HG to PT for deviant responses and a concomitant disinhibition within left HG. Consistent with PC, our results suggest that model updating in auditory pattern perception and learning is associated with specific changes in the excitatory feedforward connections encoding prediction errors and in the intrinsic connections that encode the precision of these errors and modulate their gain.

Significance statement

The learning of complex auditory stimuli such as music and speech can be thought of as the continuous optimisation of brain predictive models driven by prediction errors. Using dynamic causal modelling on fMRI data acquired during a melodic oddball paradigm, we here show that brain responses to unexpected sounds were best explained by an increase in excitation within Heschl’s gyrus and an increase in forward connections from Heschl’s gyrus to planum temporale. Our results are consistent with a predictive coding account of sensory learning, whereby prediction error responses to new sounds drive model adjustments via feedforward connections and intrinsic connections encode the confidence of these prediction errors.
The Role of the Ovarian Cancer G -Coupled Receptor (OGR1) in Idiopathic Pulmonary Fibrosis
Authors: Nagel David J. , Clough Ryan , Bell Tyler J. , Ku Wei-Yao , Sime Patricia J. , Kottmann R. M.
Published: November 2019

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by irreversible scarring of the lung that is associated with significant mortality and morbidity. The pathophysiology is incompletely understood but it is well-established that fibroblast to myofibroblast differentiation is a key feature of pulmonary fibrosis. Our lab has established that a reduction in extracellular pH is one of several important pathways responsible for the activation of latent TGF-β in the extracellular space. TGF-β activation further decreases extracellular pH and creates a feed-forward mechanism that stimulates myofibroblast differentiation and activation of additional TGF-β. Given the importance of TGF-β and extracellular acidification to the progression of pulmonary fibrosis, we sought to identify novel mechanisms that are involved in pH-dependent fibrotic signaling. The proton sensing G-Protein Coupled family of receptors are activated in acidic environments, but their role in fibrotic signaling has not been studied. Here we report that the Ovarian Cancer G-Protein Coupled Receptor1 (OGR1 or GPR68), a member of the family of proton sensing G-Protein Coupled Receptors, negatively regulates pro-fibrotic signaling. We demonstrate that OGR1 expression is significantly reduced in lung tissue from patients with IPF and TGF-β decreases OGR1 expression. In fibroblasts, a reduction in expression of OGR1 (OGR knockout lung fibroblasts) and knockdown (OGR siRNA), promotes in vitro myofibroblast differentiation. In contrast, OGR1 overexpression inhibits myofibroblast differentiation. Finally, we demonstrate that OGR1 negatively regulates TGF-β stimulation through inhibition of focal adhesion kinase (FAK) phosphorylation. Our results suggest that preserving OGR1 expression may represent a novel therapeutic strategy in pulmonary fibrosis.
THE SPATIAL REGULATION OF CONDENSIN ACTIVITY IN CHROMOSOME CONDENSATION
Authors: Lamothe Rebecca , Costantino Lorenzo , Koshland Douglas E
Published: November 2019

Condensin mediates chromosome condensation, which is essential for proper chromosome segregation during mitosis. Prior to anaphase of budding yeast, the ribosomal DNA (RDN) condenses to a thin loop that is distinct from the rest of the chromosomes. We provide evidence that the establishment and maintenance of this RDN condensation require the regulation of condensin by Cdc5p (polo) kinase. We show that Cdc5p is recruited to the site of condensin binding in the RDN by cohesin, a complex related to condensin. Cdc5p and cohesin prevent condensin from misfolding the RDN into an irreversibly decondensed state. From these and other observations, we propose that the spatial regulation of Cdc5p by cohesin modulates condensin activity to ensure proper RDN folding into a thin loop. This mechanism may be evolutionarily conserved, promoting the thinly condensed constrictions that occur at centromeres and RDN of mitotic chromosomes in plants and animals.
Kinome-centric pharmacoproteomics identifies signaling pathways underlying cellular responses to targeted cancer drugs
Authors: Golkowski Martin , Lau Ho-Tak , Chan Marina , Kenerson Heidi , Vidadala Venkata Narayana , Shoemaker Anna , Maly Dustin J. , Yeung Raymond S. , Gujral Taranjit S. , Ong Shao-En
Published: November 2019

Kinase-dependent signaling networks are frequently dysregulated in cancer, driving disease progression. While kinase inhibition has become an important therapeutic approach many cancers resist drug treatment. Therefore, we need both reliable biomarkers that predict drug responses and new targets to overcome drug resistance. Determining the kinase(s) that control cancer progression in individual cancers can pose a significant challenge. Genomics has identified important, yet limited numbers of kinase driver mutations. Transcriptomics can quantify aberrant gene expression, but it cannot measure the protein phosphorylation that regulates kinase-dependent signaling network activity. Proteomics measures protein expression and phosphorylation and, therefore, quantifies aberrant signaling network activity directly. We developed a kinome-centric pharmacoproteomics platform to study signaling pathways that determine cancer drug response. Using hepatocellular carcinoma (HCC) as our model, we determined kinome activity with kinobead/LC-MS profiling, and screened 299 kinase inhibitors for growth inhibition. Integrating kinome activity with drug responses, we obtained a comprehensive database of predictive biomarkers, and kinase targets that promote drug sensitivity and resistance. Our dataset specified pathway-based biomarkers for the clinical HCC drugs sorafenib, regorafenib and lenvatinib, and we found these biomarkers enriched in human HCC specimens. Strikingly, our database also revealed signaling pathways that promote HCC cell epithelial-mesenchymal transition (EMT) and drug resistance, and that NUAK1 and NUAK2 regulate these pathways. Inhibition of these kinases reversed the EMT and sensitized HCC cells to kinase inhibition. These results demonstrate that our kinome pharmacoproteomics platform discovers both predictive biomarkers for personalized oncology and novel cancer drug targets.
Life Minus Violence-Enhanced (LMV-E) with women in custody: single-case experimental design
Authors: McKeown Annette , McCrory Sarah
Published: November 2019

Purpose

The purpose of this single-case experimental design paper is to examine the efficacy of the high-dosage Life Minus Violence – Enhanced (LMV-E) programme with a small sample of four violent women in custody. All participants were undertaking LMV-E as one component of their treatment pathway in an Offender Personality Disorder (OPD) treatment service for women with personality disorder. The methodology employed an AB baseline design with a six-month baseline period, nine-month treatment period and six-month follow-up. Levels of direct and indirect aggression were recorded throughout the baseline, intervention, and follow-up period. In the follow-up period, women were engaging in further treatment. Psychometric measures linked to treatment domains were used to explore clinically significant and reliable change following the intervention. Clinical and reliable change was indicated in some treatment domains for each participant following the intervention. The pattern of these reductions varied between the women. The patterns of findings are discussed and recommendations presented.

Design/methodology/approach

The methodology employed an AB baseline design with a six-month baseline period, nine-month treatment period and six-month follow-up. Levels of direct and indirect aggression were recorded throughout the baseline, intervention and follow-up period. In the follow-up period, women were engaging in further treatment. Psychometric measures linked to treatment domains were used to explore clinically significant and reliable change following the intervention.

Findings

Clinical and reliable change was indicated in some treatment domains for each participant following the intervention. The pattern of these reductions varied between the female offenders. The patterns of findings are discussed and recommendations presented.

Practical implications

The LMV-E programme was associated with some positive improvements in treatment domains measured in a small sample of female violent offenders. Improvements to some degree were most commonly found in the domains of anger, emotional control and components of criminal thinking. It would be clinically useful to examine characteristics of individuals that appear to benefit most from particular interventions.

Originality/value

There are no existing published findings related to the implementation of LMV-E with females. Therefore, this paper provides preliminary contribution to the evidence base in this area.
The search and matching process in the housing market
Authors: Lisi Gaetano
Published: November 2019

Purpose

This paper aims to study the phenomenon known as “house price dispersion”, one of the most important distinctive features of housing markets. House price dispersion refers to the phenomenon of selling two houses with very similar attributes and in near locations at the same time but at very different prices.

Design/methodology/approach

This theoretical paper makes use of a search and matching model of the housing market. The search and matching models are the benchmark models of the “matching” markets, such as the labour market and the housing market, where trade is a decentralised, uncoordinated and time-consuming economic activity.

Findings

Unlike the previous related literature that attributes to the heterogeneity of buyers and sellers a significant part of the price volatility, in this paper, the house price dispersion depends on the housing tenure status of home-seekers in the house search process. Indeed, in the presence of different housing tenure status of home-seekers, the house search process leads to different types of matching. In turn, this implies different surpluses (the sum of the net gains of the parties involved in the trade), and eventually, different surpluses produce different prices of equilibrium.

Research limitations/implications

An interesting research agenda for future works would be an extension of the model to study the effect of “online housing search” on the house search and matching process, and thus, on the house price dispersion.

Practical implications

The main practical implication of this work is that the house price dispersion is an inherent phenomenon in the house search and matching process.

Originality/value

None of the existing and related works of research have considered how to take advantage of the search and matching approach to deal with the phenomenon known as “house price dispersion”, without relying on theex anteheterogeneity of the parties but looking at the “core” of the house search and matching process.
Martin Creed: The Light
Authors: Holmboe Rye Dag
Published: November 2019

This essay examines Martin Creed's work through the lens of psychoanalytic theories of neurosis and hypochondria. It considers Creed's performances and installations, arguing that in both seriality functions as an armour or defence against the perceived threat of omnipotent mothers. The essay also thinks about questions of interiority – psychic, corporeal, aesthetic – and argues that, even at their most scatological, Creed's works can be seen as rites of purification, and as attempts to make things whole.
Denis Diderot and the Masturbating Girl
Authors: McAlpin Mary
Published: November 2019

In Diderot's Le Rêve de D’Alembert (1769), a character based on the vitalist physician and theorist Théophile de Bordeu (1722‐1776) proposes masturbation as a life‐saving cure for a pubescent girl. Her excessive virtue, he explains, has resulted in a dangerous overabundance of seminal fluid; but he adds that any man suspected of recommending this medical intervention should be shunned by society. The contradictions surrounding Diderot's masturbating girl make her an emblem for a discourse, born in the eighteenth century, by which women naturally resist sexual knowledge, and thus require an enlightenment available only through the agency of men.
A Primer on Global Environmental Change
Authors: Linnenluecke Martina K. , Smith Tom
Published: November 2019

This paper sets out the science behind global environmental change, defined by the US Global Change Research Act as ‘changes in the global environment (including alterations in climate, land productivity, oceans or other water resources, atmospheric chemistry, and ecological systems) that may alter the capacity of the Earth to sustain life’. We explain why there is still scepticism about the science in the business world and introduce eight gestalt shifts that are likely to change how executives think about environmental change and the threats and opportunities such changes present. The paper concludes with future research directions on business and global environmental change and outlines how the business case for investment in clean technology means that the transition to clean tech is inevitable.
Global metabolic profiling to model biological processes of aging in twins
Authors: Bunning Bryan J. , Contrepois Kévin , Lee‐McMullen Brittany , Dhondalay Gopal Krishna R. , Zhang Wenming , Tupa Dana , Raeber Olivia , Desai Manisha , Nadeau Kari C. , Snyder Michael P. , Andorf Sandra
Published: November 2019

Aging is intimately linked to system‐wide metabolic changes that can be captured in blood. Understanding biological processes of aging in humans could help maintain a healthy aging trajectory and promote longevity. We performed untargeted plasma metabolomics quantifying 770 metabolites on a cross‐sectional cohort of 268 healthy individuals including 125 twin pairs covering human lifespan (from 6 months to 82 years). Unsupervised clustering of metabolic profiles revealed 6 main aging trajectories throughout life that were associated with key metabolic pathways such as progestin steroids, xanthine metabolism, and long‐chain fatty acids. A random forest (RF) model was successful to predict age in adult subjects (≥16 years) using 52 metabolites (R2 = .97). Another RF model selected 54 metabolites to classify pediatric and adult participants (out‐of‐bag error = 8.58%). These RF models in combination with correlation network analysis were used to explore biological processes of healthy aging. The models highlighted established metabolites, like steroids, amino acids, and free fatty acids as well as novel metabolites and pathways. Finally, we show that metabolic profiles of twins become more dissimilar with age which provides insights into nongenetic age‐related variability in metabolic profiles in response to environmental exposure.
Arrhythmic events in Brugada syndrome patients induced by fever
Authors: Roterberg Gretje , El‐Battrawy Ibrahim , Veith Michael , Liebe Volker , Ansari Uzair , Lang Siegfried , Zhou Xiaobo , Akin Ibrahim , Borggrefe Martin
Published: November 2019

Introduction

The Brugada syndrome is associated with arrhythmic events, which may even lead to sudden cardiac death (SCD) as it causes arrhythmic events. A typical Brugada syndrome ECG type I can be triggered at fever situations. The aim of this pooled meta‐analysis is to further explore the baseline characteristics and the association of fever to BrS‐related arrhythmic events.

Methods

We compiled data from a search of databases (PubMed, Web of Science, Cochrane Library, and Google Scholar). We included 17 studies including 14 case reports and a total of 53 patients.

Results

Our population including 53 patients showed a male predominance of 92% with a mean age of 40.6 ± 17.7 years. 58% of patients had a family history of SCD or BrS. Genetic screening was performed in 14 patients (26%) and revealed a SCN5A mutation in 21% of the patients. ICD implantation was initiated in six patients. 75% (n = 39) of patients did not have symptoms before the fever event. Symptoms at fever included life‐threatening arrhythmia such as ventricular fibrillation (VF) or ventricular tachycardia (VT; 17%), syncope (13%), and cardiac arrest or aborted SCD (13%). One patient developed electrical storm which led to not aborted SCD.

Conclusion

Fever is a great risk factor for arrhythmia events in BrS patients. Patients with known fever triggered Brugada syndrome should be surveilled closely during fever and be started on antipyretic therapy as soon as possible.
General, Work‐Specific, and Work‐Role Conscientiousness Measures in Predicting Work Criteria: A Comparative Perspective
Authors: Wang Qiang , Liao Yi , Burns Gary N.
Published: November 2019

The current study compared general, work‐specific, and work‐role measures of conscientiousness as predictors of job satisfaction, organizational commitment, turnover intention, job engagement, and task performance. As expected, work‐role conscientiousness yielded stronger relationships with five of the ten work‐related criteria than general conscientiousness, and with six of the ten criteria than work‐specific conscientiousness. More importantly, work‐role conscientiousness displayed incremental validity in predicting nearly all work‐related criteria, when controlling for general and work‐specific conscientiousness alone or in combination. It is also worth noting that six of ten analyses found that work‐role conscientiousness demonstrated greater relative importance compared to its counterparts. Finally, we found that the context in which the items were completed moderated the relationships between work‐role conscientiousness and two work‐related criteria (i.e., job satisfaction and organizational commitment). Together, these results suggest that researchers should consider the work‐role measure of conscientiousness in the prediction of work criteria.