bluuebunny/crossref_metadata_2025 huggingface dataset:
A modified formulation of quasi-linear viscoelasticity for transversely isotropic materials under finite deformation
Authors: Balbi Valentina , Shearer Tom , Parnell William J.
Published: September 2018

The theory of quasi-linear viscoelasticity (QLV) is modified and developed for transversely isotropic (TI) materials under finite deformation. For the first time, distinct relaxation responses are incorporated into an integral formulation of nonlinear viscoelasticity, according to the physical mode of deformation. The theory is consistent with linear viscoelasticity in the small strain limit and makes use of relaxation functions that can be determined from small-strain experiments, given the time/deformation separability assumption. After considering the general constitutive form applicable to compressible materials, attention is restricted to incompressible media. This enables a compact form for the constitutive relation to be derived, which is used to illustrate the behaviour of the model under three key deformations: uniaxial extension, transverse shear and longitudinal shear. Finally, it is demonstrated that the Poynting effect is present in TI, neo-Hookean, modified QLV materials under transverse shear, in contrast to neo-Hookean
elastic
materials subjected to the same deformation. Its presence is explained by the anisotropic relaxation response of the medium.
Control and prediction of the organic solid state: a challenge to theory and experiment
Authors: Price Sarah L.
Published: September 2018

The ability of theoretical chemists to quantitatively model the weak forces between organic molecules is being exploited to predict their crystal structures and estimate their physical properties. Evolving crystal structure prediction methods are increasingly being used to aid the design of organic functional materials and provide information about thermodynamically plausible polymorphs of speciality organic materials to aid, for example, pharmaceutical development. However, the increasingly sophisticated experimental studies for detecting the range of organic solid-state behaviours provide many challenges for improving quantitative theories that form the basis for the computer modelling. It is challenging to calculate the relative thermodynamic stability of different organic crystal structures, let alone understand the kinetic effects that determine which polymorphs can be observed and are practically important. However, collaborations between experiment and theory are reaching the stage of devising experiments to target the first crystallization of new polymorphs or create novel organic molecular materials.
Testing hypotheses for the function of the carnivoran baculum using finite-element analysis
Authors: Brassey Charlotte A. , Gardiner James D. , Kitchener Andrew C.
Published: September 2018

The baculum (os penis) is a mineralized bone within the glans of the mammalian penis and is one of the most morphologically diverse structures in the mammal skeleton. Recent experimental work provides compelling evidence for sexual selection shaping the baculum, yet the functional mechanism by which this occurs remains unknown. Previous studies have tested biomechanical hypotheses for the role of the baculum based on simple metrics such as length and diameter, ignoring the wealth of additional shape complexity present. For the first time, to our knowledge, we apply a computational simulation approach (finite-element analysis; FEA) to quantify the three-dimensional biomechanical performance of carnivoran bacula (n= 74) based upon high-resolution micro-computed tomography scans. We find a marginally significant positive correlation between sexual size dimorphism and baculum stress under compressive loading, counter to the ‘vaginal friction’ hypothesis of bacula becoming more robust to overcome resistance during initial intromission. However, a highly significant negative relationship exists between intromission duration and baculum stress under dorsoventral bending. Furthermore, additional FEA simulations confirm that the presence of a ventral groove would reduce deformation of the urethra. We take this as evidence in support of the ‘prolonged intromission’ hypothesis, suggesting the carnivoran baculum has evolved in response to pressures on the duration of copulation and protection of the urethra.
Punctuated plastome reduction and host–parasite horizontal gene transfer in the holoparasitic plant genus
Aphyllon
Authors: Schneider Adam C. , Chun Harold , Stefanović Saša , Baldwin Bruce G.
Published: September 2018

Foundational studies of chloroplast genome (plastome) evolution in parasitic plants have focused on broad trends across large clades, particularly among the Orobanchaceae, a species-rich and ecologically diverse family of root parasites. However, the extent to which such patterns and processes of plastome evolution, such as stepwise gene loss following the complete loss of photosynthesis (shift to holoparasitism), are detectable at shallow evolutionary time scale is largely unknown. We used genome skimming to assemble eight chloroplast genomes representing complete taxonomic sampling of
Aphyllon
sect.
Aphyllon,
a small clade within the Orobanchaceae that evolved approximately 6 Ma, long after the origin of holoparasitism. We show substantial plastome reduction occurred in the stem lineage, but subsequent change in plastome size, gene content, and structure has been relatively minimal, albeit detectable. This lends additional fine-grained support to existing models of stepwise plastome reduction in holoparasitic plants. Additionally, we report phylogenetic evidence based on an
rbcL
gene tree and assembled 60+ kb fragments of the
Aphyllon epigalium
mitochondrial genome indicating host-to-parasite horizontal gene transfers (hpHGT) of several genes originating from the plastome of an ancient
Galium
host into the mitochondrial genome of a recent common ancestor of
A. epigalium
. Ecologically, this evidence of hpHGT suggests that the host–parasite associations between
Galium
and
A. epigalium
have been stable at least since its subspecies diverged hundreds of thousands of years ago.
Extinction risk in extant marine species integrating palaeontological and biodistributional data
Authors: Collins K. S. , Edie S. M. , Hunt G. , Roy K. , Jablonski D.
Published: September 2018

Extinction risk assessments of marine invertebrate species remain scarce, which hinders effective management of marine biodiversity in the face of anthropogenic impacts. To help close this information gap, in this paper we provide a metric of relative extinction risk that combines palaeontological data, in the form of extinction rates calculated from the fossil record, with two known correlates of risk in the modern day: geographical range size and realized thermal niche. We test the performance of this metric—Palaeontological Extinction Risk In Lineages (PERIL)—using survivorship analyses of Pliocene bivalve faunas from California and New Zealand, and then use it to identify present-day hotspots of extinction vulnerability for extant shallow-marine Bivalvia. Areas of the ocean where concentrations of bivalve species with higher PERIL scores overlap with high levels of climatic or anthropogenic stressors should be considered of most immediate concern for both conservation and management.
Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages
Authors: Beale Mathew A. , Marks Michael , Sahi Sharon K. , Tantalo Lauren C. , Nori Achyuta V. , French Patrick , Lukehart Sheila A. , Marra Christina M. , Thomson Nicholas R.
Published: September 2018

Syphilis is a sexually transmitted infection caused byTreponema pallidumsubspeciespallidumand may lead to severe complications. Recent years have seen striking increases in syphilis in many countries. Previous analyses have suggested one lineage of syphilis, SS14, may have expanded recently, indicating emergence of a single pandemic azithromycin-resistant cluster. We used direct sequencing ofT. pallidumcombined with phylogenomic analyses to show that both SS14- and Nichols-lineages are simultaneously circulating in clinically relevant populations in multiple countries. We correlate the appearance of genotypic macrolide resistance with multiple independently evolved SS14 sub-lineages and show that genotypically resistant and sensitive sub-lineages are spreading contemporaneously, incompatible with the notion that SS14-lineage expansion is driven purely by macrolide resistance. These findings inform our understanding of the current syphilis epidemic by demonstrating how macrolide resistance evolves inTreponemasubspecies and provide a warning on broader issues of antimicrobial resistance.
Predicting evolution using frequency-dependent selection in bacterial populations
Authors: Azarian Taj , Martinez Pamela P , Arnold Brian J , Grant Lindsay R , Corander Jukka , Fraser Christophe , Croucher Nicholas J , Hammitt Laura L , Reid Raymond , Santosham Mathuram , Weatherholtz Robert C , Bentley Stephen D , O’Brien Katherine L , Lipsitch Marc , Hanage William P
Published: September 2018

Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain estimated by an NFDS-based model at the time the vaccine is introduced enables to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.
Population Structure of Leishmania using POPSICLE reveals extensive dichotomy in zygosity and discloses the role of sex in diversity of the parasite
Authors: Shaik Jahangheer S.
Published: September 2018

Mosaic aneuploidy prevalent in organisms such as Leishmania and Fungi and in genomes of some neurological disorders and cancers manifest as non-integer haplotypes due to heterogeneity in somy across a population of cells. Thus, the tools designed for strictly haploid or diploid genomes are insufficient to study them. We addressed this issue by upgrading our population genetics tool POPSICLE for aneuploid genomes and studied the population structure of 50 strains of Leishmania to understand genetic diversity and the sexual strategies that predispose to that diversity. Leishmania showed enormous diversity but a dichotomic nature of extreme zygosities. To understand this dichotomy, we specifically studied two species, L. tropica that contained strains with both hetero and homozygosities and L. major that were mainly homozygous. The homozygosity in L. tropica was a consequence of extreme inbreeding while heterozygosity was due to recent hybridizations involving two different genotypes. In contrast, L. major also contained two different genotypes and products of extreme inbreeding but no recent hybridizations. The heterozygous strains of L. tropica that were geographically isolated from the homozygous strains were F1 hybrids that appeared sterile to each other while those in proximity to the homozygous strains were outcrosses involving multiple cycles of hybridization indicating their mating preference with homozygous strains. Development of POPSICLE for aneuploid genomes offers a unique tool for determining the shared ancestries and in reinforcing sex as one of the driving mechanisms for speciation as demonstrated for Leishmania. POPSICLE is a Java based utility available for free download at https://popsicle-admixture.sourceforge.io/
Host defense triggers rapid adaptive radiation in experimentally evolving parasites
Authors: Bush Sarah E. , Villa Scott M. , Altuna Juan C. , Johnson Kevin P. , Shapiro Michael D. , Clayton Dale H.
Published: September 2018

Adaptive radiation occurs when the members of a single lineage evolve different adaptive forms in response to selection imposed by competitors or predators. Iconic examples include Darwin’s finches, Caribbean anoles, and Hawaiian silverswords, all of which live on islands. Parasites, which live on host “islands,” show macroevolutionary patterns consistent with adaptive radiation in response to host-imposed selection. Here we show rapid adaptive divergence of experimentally evolving feather lice in response to preening, the main host defense. We demonstrate that host defense exerts strong phenotypic selection for crypsis in lice transferred to different colored rock pigeons (Columba livia). During four years of experimental evolution (∼60 generations), the lice evolved heritable differences in color. The color differences spanned the phenotypic distribution of congeneric species of lice adapted to other species of pigeons. Our results indicate that host-mediated selection triggers rapid divergence in the adaptive radiation of parasites, which are among the most diverse organisms on earth. Our research suggests that host defense should be included with competition and predation as a major mechanism driving the evolution of biodiversity by adaptive radiation.
High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway
Authors: Zhang Yuanping , Xi Xiaoting , Mei Yan , Zhao Xueying , Zhou Liqiong , Ma Minjun , Liu Sili , Zha Xu , Yang Yanni
Published: September 2018

Diabetic retinopathy (DR) caused visual performance degradation seriously endangers human beings’ health, uncovering the underlying mechanism might shed light on the discovery of DR therapeutic treatments. In this study, we found that the effects of glucose on retinal pigment epithelium (RPE) varies in a dose dependent manner, high-glucose promotes ROS generation and cell apoptosis, inhibits mitophagy as well as proliferative abilities, while low-glucose induces ROS production and cell mitophagy, but has little impacts on cell apoptosis and proliferation. Of note, the toxic effects of high-glucose on RPE are alleviated by ROS scavengers and aggravated by autophagy inhibitor 3-methyladenine (3-MA) or mitophagy inhibitor cyclosporin A (CsA). High-glucose induced ROS generation is merely eliminated by ROS scavengers instead of mitophagy or autophagy inhibitor. We also proved that high-glucose inhibits cell proliferation and promotes cell apoptosis by regulating ROS mediated inhibition of mitophagy. In addition, mitophagy associated proteins PINK1 and Parkin are downregulated by high-glucose or hydrogen peroxide treatments, which are reversed by ROS scavengers. Of note, Knock-down of PINK1 decreases phospharylated Parkin instead of total Parkin levels in RPE. Intriguingly, high-glucose’s inhibiting effects on cell mitophagy as well as proliferation and its promoting effects on cell apoptosis are reversed by either PINK1 or Parkin overexpression. Therefore, we concluded that high-glucose promotes RPE apoptosis and inhibits cell proliferation as well as mitophagy by regulating oxidative stress mediated inactivation of ROS/PINKl/Parkin signal pathway.
Ozone Treatment for Elimination of Bacteria and SARS-CoV-2 for Medical Environments
Authors: Westover Craig , Rahmatulloev Savlatjon , Danko David , Afshinnekoo Ebrahim , O’Hara Niamh B. , Ounit Rachid , Bezdan Daniela , Mason Christopher E.
Published: September 2018

Pathogenic bacteria and viruses in medical environments can lead to treatment complications and hospital-acquired infections (HAIs), and current cleaning protocols do not address hard-to-access areas or that may be beyond line-of-sight treatment such as with ultraviolet radiation. At the time of writing, the ongoing pandemic of the novel coronavirus known as novel coronavirus (2019-nCoV) has claimed over 4 million cases worldwide and is expected to have multiple peaks, with possible resurgences throughout 2020. It is therefore imperative that disinfection methods in the meantime be employed to keep up with the supply of personal protective equipment (PPE) and sterilize a wide array of surfaces as quarantine lockdowns begin to be lifted.

Here, we tested the efficacy of Sani Sport ozone devices as a means to treat hospital equipment and surfaces for killing bacteria, degrading synthetic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and RNA from non-replicative capsid enclosed SARS-CoV-2. We observed a rapid killing of medically-relevant and environmental bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtlis, and Deinococcus radiodurans) across four surfaces (blankets, catheter, remotes, and syringes) within 30 minutes, and up to a 99% reduction in viable bacteria at the end of 2-hour treatment cycles. Significant RNA degradation of synthetic SARS-CoV-2 RNA was seen an hour into the ozone treatment as compared to non-treated controls and a non-replicative form of the virus was shown to have significant RNA degradation at 30 minutes compared to a no treatment control and RNA degradation could be reliably detected at 10,000 and 1,000 copies of virus per sample. These results show the strong promise of ozone treatment for reducing risk of infection and HAIs.
Sfp1 regulates transcriptional networks driving cell growth and division through multiple promoter binding modes
Authors: Albert Benjamin , Tomassetti Susanna , Gloor Yvonne , Dilg Daniel , Mattarocci Stefano , Kubik Slawomir , Shore David
Published: September 2018

Understanding how transcriptional programs help to coordinate cell growth and division is an important unresolved problem. Here we report that the nutrient-and stress-regulated transcription factor Sfp1 is rate-limiting for expression of several large classes of genes involved in yeast cell growth, including ribosomal protein, ribosome biogenesis, and snoRNA genes. Remarkably, the spectrum of Sfp1 transcription effects is concordant with a combination of chromatin immunoprecipitation and chromatin endogenous cleavage binding analyses, which together provide evidence for two distinct modes of Sfp1 promoter binding, one requiring a co-factor and the other a specific DNA-recognition motif. In addition to growth-related genes, Sfp1 binds to and regulates the promoters of cell cycle “START” regulon genes, including the key G1/S cyclinsCLN1andCLN2. Our findings suggest that Sfp1 acts as a master regulator of cell growth and cell size by coordinating the expression of genes implicated in mass accumulation and cell division.
Polyacrylamide Bead Sensors forin vivoQuantification of Cell-Scale Stress in Zebrafish Development
Authors: Träber N. , Uhlmann K. , Girardo S. , Kesavan G. , Wagner K. , Friedrichs J. , Goswami R. , Bai K. , Brand M. , Werner C. , Balzani D. , Guck J.
Published: September 2018

Mechanical stress exerted and experienced by cells during tissue morphogenesis and organ formation plays an important role in embryonic development. While techniques to quantify mechanical stressesin vitroare available, few methods exist for studying stresses in living organisms. Here, we describe and characterize cell-like polyacrylamide (PAAm) bead sensors with well-defined elastic properties and size forin vivoquantification of cell-scale stresses. The beads were injected into developing zebrafish embryos and their deformations were computationally analyzed to delineate spatio-temporal local acting stresses. With this computational analysis-based cell-scale stress sensing (COMPAX) we are able to detect pulsatile pressure propagation in the developing neural rod potentially originating from polarized midline cell divisions and continuous tissue flow. COMPAX is expected to provide novel spatiotemporal insight into developmental processes at the local tissue level and to facilitate quantitative investigation and a better understanding of morphogenetic processes.
Signaling incentive and drive in the primate ventral pallidum for motivational control of goal-directed action
Authors: Fujimoto Atsushi , Hori Yukiko , Nagai Yuji , Kikuchi Erika , Oyama Kei , Suhara Tetsuya , Minamimoto Takafumi
Published: September 2018

Processing incentive and drive is essential for control of goal-directed behavior. The limbic part of the basal ganglia has been emphasized in these processes, yet the exact neuronal mechanism has remained elusive. In this study, we examined the neuronal activity of the ventral pallidum (VP) and its upstream area, the rostromedial caudate (rmCD), while two male macaque monkeys performed an instrumental lever-release task, in which a visual cue indicated the forthcoming reward size. We found that the activity of some neurons in VP and rmCD reflected the expected reward-size transiently following the cue. Reward-size coding appeared earlier and stronger in VP than in rmCD. We also found that the activity in these areas was modulated by the satiation level of monkeys, which also occurred more frequently in VP than in rmCD. The information regarding reward-size and satiation-level was independently signaled in the neuronal populations of these areas. The data thus highlighted the neuronal coding of key variables for goal-directed behavior in VP. Furthermore, pharmacological inactivation of VP induced more severe deficit of goal-directed behavior than inactivation of rmCD, which was indicated by abnormal error repetition and diminished satiation effect on the performance. These results suggest that VP encodes incentive value and internal drive, and plays a pivotal role in the control of motivation to promote goal-directed behavior.

Significance Statement

The limbic part of the basal ganglia has been emphasized in the motivational control of goal-directed action. Here, we investigated how the ventral pallidum (VP) and the rostromedial caudate (rmCD) encode incentive value and internal drive, and control goal-directed behavior. Neuronal recording and subsequent pharmacological inactivation revealed that VP had stronger coding of reward size and satiation level than rmCD. Reward size and satiation level were independently encoded in the neuronal population of these areas. Furthermore, VP inactivation impaired goal-directed behavior more severely than rmCD inactivation. These results highlighted the central role of VP in the motivational control of goal-directed action.
ProTargetMiner: A proteome signature library of anticancer molecules for functional discovery
Authors: Saei Amir Ata , Chernobrovkin Alexey , Sabatier Pierre , Zhang Bo , Beusch Christian , Tokat Ülkü Güler , Gaetani Massimiliano , Végvári Ákos , Zubarev Roman A.
Published: September 2018

We present a publicly available, expandable proteome signature library of anticancer molecules in A549 adenocarcinoma cells. Based on 287 proteomes affected by 56 drugs, the main dataset contains 7,328 proteins and 1,307,859 refined protein-drug pairs. By employing the specificity concept in partial least square modeling, deconvolution of drug targets and mechanistic proteins is achieved for most compounds, including some kinase inhibitors. We built the first protein co-regulation database that takes into account both protein expression and degradation. A surprising number of strong anti-correlations is found, underscoring the importance of protein repression in cell regulation. Our analysis uncovered a group of proteins with extremely steady expression which are likely essential for core cellular functions. These findings bring about deeper understanding of cell mechanics. Extension of the dataset to novel compounds will facilitate drug design. The introduced specificity concept and modeling scheme are beneficial in other analysis types as well.

Statement of Significance

ProTargetMiner is the first of its kind library of proteome responses of human cancer cells to anticancer molecules. This expandable resource facilitates the deconvolution of drug targets, action mechanisms, and cellular effects. It reveals death modalities, uncovers protein co-regulation and anti-correlation networks and defines the “untouchable” proteome essential for core cellular functionalities.
RELION-3: new tools for automated high-resolution cryo-EM structure determination
Authors: Zivanov Jasenko , Nakane Takanori , Forsberg Björn , Kimanius Dari , Hagen Wim J.H. , Lindahl Erik , Scheres Sjors H.W.
Published: September 2018

Here, we describe the third major release of relion. CPU-based vector acceleration has been added in addition to GPU support, which provides flexibility in use of resources and avoids memory limitations. Reference-free autopicking with Laplacian-of-Gaussian filtering and execution of jobs from python allows non-interactive processing during acquisition, including 2D-classification, de novo model generation and 3D-classification. Perparticle refinement of CTF parameters and correction of estimated beam tilt provides higher-resolution reconstructions when particles are at different heights in the ice, and/or coma-free alignment has not been optimal. Ewald sphere curvature correction improves resolution for large particles. We illustrate these developments with publicly available data sets: together with a Bayesian approach to beam-induced motion correction it leads to resolution improvements of 0.2-0.7 Å compared to previous relion versions.
The GATOR complex regulates an essential response to meiotic double-stranded breaks inDrosophila
Authors: Wei Youheng , Bettedi Lucia , Kim Kuikwon , Ting Chun-Yuan , Lilly Mary A.
Published: September 2018

The TORC1 inhibitor GATOR1/SEACIT controls meiotic entry and early meiotic events in yeast. However, how metabolic pathways influence meiotic progression in metazoans remains poorly understood. Here we report that the TORC1 regulators GATOR1 and GATOR2 mediate a response to meiotic double-stranded breaks (DSBs) duringDrosophilaoogenesis. We find that meiotic DSBs trigger the activation of a GATOR1 dependent pathway that downregulates TORC1 activity in the female germline. In GATOR1 mutants, high TORC1 activity results in the delayed repair of meiotic DSBs and the hyperactivation of p53. Conversely, the GATOR2 component Mio is required to attenuate GATOR1 activity, to ensure that meiotic DSBs do not trigger a permanent growth arrest. Unexpectedly, we found that GATOR1 inhibits retrotransposon expression in the presence of meiotic DSBs in a pathway that functions in parallel to p53. Our studies have revealed a link between the GATOR complex, the repair of meiotic DSBs and retrotransposon expression
Temporal resolution of single photon responses in primate rod photoreceptors and limits imposed by cellular noise
Authors: Field Greg D. , Uzzell Valerie , Chichilnisky E.J. , Rieke Fred
Published: September 2018

Sensory receptor noise corrupts sensory signals, contributing to imperfect perception and dictating central processing strategies. For example, noise in rod phototransduction limits our ability to detect light and minimizing the impact of this noise requires precisely tuned nonlinear processing by the retina. But detection sensitivity is only one aspect of night vision: prompt and accurate behavior also requires that rods reliably encode the timing of photon arrivals. We show here that the temporal resolution of responses of primate rods is much finer than the duration of the light response and identify the key limiting sources of transduction noise. We also find that the thermal activation rate of rhodopsin is lower than previous estimates, implying that other noise sources are more important than previously appreciated. A model of rod single-photon responses reveals that the limiting noise relevant for behavior depends critically on how rod signals are pooled by downstream neurons.
How the level of reward awareness changes the computational and electrophysiological signatures of reinforcement learning
Authors: Correa C.M.C. , Noorman S. , Jiang J. , Palminteri S. , Cohen M.X , Lebreton M. , van Gaal S
Published: September 2018

The extent to which subjective awareness influences reward processing, and thereby affects future decisions is currently largely unknown. In the present report, we investigated this question in a reinforcement-learning framework, combining perceptual masking, computational modeling and electroencephalographic recordings (human male and female participants). Our results indicate that degrading the visibility of the reward decreased -without completely obliterating- the ability of participants to learn from outcomes, but concurrently increased their tendency to repeat previous choices. We dissociated electrophysiological signatures evoked by the reward-based learning processes from those elicited by the reward-independent repetition of previous choices and showed that these neural activities were significantly modulated by reward visibility. Overall, this report sheds new light on the neural computations underlying reward-based learning and decision-making and highlights that awareness is beneficial for the trial-by-trial adjustment of decision-making strategies.

Significance statement

The notion of reward is strongly associated with subjective evaluation, related to conscious processes such as “pleasure”, “liking” and “wanting”. Here we show that degrading reward visibility in a reinforcement learning task decreases -without completely obliterating- the ability of participants to learn from outcomes, but concurrently increases subjects tendency to repeat previous choices. Electrophysiological recordings, in combination with computational modelling, show that neural activities were significantly modulated by reward visibility. Overall, we dissociate different neural computations underlying reward-based learning and decision-making, which highlights a beneficial role of reward awareness in adjusting decision-making strategies.
A non-spatial account of place and grid cells based on clustering models of concept learning
Authors: Mok Robert M. , Love Bradley C.
Published: September 2018

One view is that conceptual knowledge is organized using the circuitry in the medial temporal lobe (MTL) that supports spatial processing and navigation. In contrast, we find that a domain-general learning algorithm explains key findings in both spatial and conceptual domains. When the clustering model is applied to spatial navigation tasks, so called place and grid cell-like representations emerge because of the relatively uniform distribution of possible inputs in these tasks. The same mechanism applied to conceptual tasks, where the overall space can be higher-dimensional and sampling sparser, leads to representations more aligned with human conceptual knowledge. Although the types of memory supported by the MTL are superficially dissimilar, the information processing steps appear shared. Our account suggests that the MTL uses a general-purpose algorithm to learn and organize context-relevant information in a useful format, rather than relying on navigation-specific neural circuitry.
The elemental mechanism of transcriptional pausing
Authors: Saba Jason , Chua Xien , Mishanina Tatiana V. , Nayak Dhananjaya , Windgassen Tricia A. , Mooney Rachel A. , Landick Robert
Published: September 2018

Transcriptional pausing underpins regulation of cellular RNA biogenesis. A consensus pause sequence that acts on RNA polymerases (RNAPs) from bacteria to mammals halts RNAP in an elemental paused state from which longer-lived pauses can arise. Although the structural foundations of pauses prolonged by backtracking or nascent RNA hairpins are recognized, the fundamental mechanism of the elemental pause is less well-defined. Here we report a mechanistic dissection that establishes the elemental pause signal (i) is multipartite; (ii) causes a modest conformational shift that puts RNAP in an off-pathway state in which template base loading but not RNA translocation is inhibited; and (iii) can easily enter pretranslocated and one-base-pair backtracked states despite principally occupying the half-translocated state observed in cryo-EM structures of paused RNAPs. Our findings provide a mechanistic basis for the elemental pause and a framework to understand how pausing is modulated by sequence, cellular conditions, and regulators.
DNA polymerase ε-dependent modulation of the pausing property of the CMG helicase at the barrier
Authors: Hizume Kohji , Endo Shizuko , Muramatsu Sachiko , Kobayashi Takehiko , Araki Hiroyuki
Published: September 2018

The proper pausing of replication forks at barriers on chromosomes is important for genome integrity. However, the detailed mechanism underlying this process has not been well elucidated. Here, we successfully reconstituted fork-pausing reactions from purified yeast proteins on templates that had binding sites for the LacI, LexA, and/or Fob1 proteins; the forks paused specifically at the protein-bound sites. Moreover, although the replicative helicase Cdc45–Mcm2–7–GINS (CMG) complex alone unwound the protein-bound templates, the unwinding of the LacI-bound site was impeded by the presence of a main leading strand DNA polymerase: polymerase ε (Polε). This suggests that Polε modulates CMG to pause at these sites.
Young genes have distinct gene structure, epigenetic profiles, and transcriptional regulation
Authors: Werner Michael S. , Sieriebriennikov Bogdan , Prabh Neel , Loschko Tobias , Lanz Christa , Sommer Ralf J.
Published: September 2018

Species-specific, new, or “orphan” genes account for 10%–30% of eukaryotic genomes. Although initially considered to have limited function, an increasing number of orphan genes have been shown to provide important phenotypic innovation. How new genes acquire regulatory sequences for proper temporal and spatial expression is unknown. Orphan gene regulation may rely in part on origination in open chromatin adjacent to preexisting promoters, although this has not yet been assessed by genome-wide analysis of chromatin states. Here, we combine taxon-rich nematode phylogenies with Iso-Seq, RNA-seq, ChIP-seq, and ATAC-seq to identify the gene structure and epigenetic signature of orphan genes in the satellite model nematode Pristionchus pacificus. Consistent with previous findings, we find young genes are shorter, contain fewer exons, and are on average less strongly expressed than older genes. However, the subset of orphan genes that are expressed exhibit distinct chromatin states from similarly expressed conserved genes. Orphan gene transcription is determined by a lack of repressive histone modifications, confirming long-held hypotheses that open chromatin is important for new gene formation. Yet orphan gene start sites more closely resemble enhancers defined by H3K4me1, H3K27ac, and ATAC-seq peaks, in contrast to conserved genes that exhibit traditional promoters defined by H3K4me3 and H3K27ac. Although the majority of orphan genes are located on chromosome arms that contain high recombination rates and repressive histone marks, strongly expressed orphan genes are more randomly distributed. Our results support a model of new gene origination by rare integration into open chromatin near enhancers.
Public guarantees for mitigating interest rate risk in PPP projects
Authors: Pellegrino Roberta , Carbonara Nunzia , Costantino Nicola
Published: September 2018

Purpose

The purpose of this paper is to deal with the maximum interest rate guarantees (MIRGs), and develop a methodology for setting the optimal value of the interest rate cap, namely the maximum interest rate above which the private investor will obtain reimbursement from the government, which balances the interests of the parties involved in the project.

Design/methodology/approach

The mechanism underlying the MIRG is modeled through real options. Monte Carlo simulation is employed as the option-pricing method. The resulting real option-based model is applied to the case of the “Camionale di Bari” toll road (Southern Italy).

Findings

The application provides some insights for the policy maker called to define the proper forms of guarantees. Furthermore, the results support the negotiation process, allowing the different actors to structure the guarantee in a way that satisfies all the parties and fairly allocates risks between them according to different operational and financial conditions.

Originality/value

The novelty of the contribution is triple. First, the authors advance the state of the art on government supports by focusing on the interest rate guarantee. Second, the authors enrich the existing studies on MIRG by proposing a quantitative model to set the guarantee in compliance with the public–private win-win principle. The developed real option-based model supports the decision maker in finding the optimal value of the interest rate cap, which is able to satisfy the interests of the parties involved in the project. Third, the authors consider not only the private sponsor and the government, as traditionally made by the models developed for other guarantees, but also the lender.
Factors influencing career choice of tertiary students in Ghana
Authors: Owusu Godfred M.Y. , Essel-Anderson Anthony , Ossei Kwakye Teddy , Bekoe Rita Amoah , Ofori Charles Gyamfi
Published: September 2018

Purpose

The purpose of this paper is to investigate the factors that influence Ghanaian tertiary students’ career choices. The paper explores the dimensionality of the career choice factors within the Ghanaian context and also ascertains their degree of influence on students’ career choices.

Design/methodology/approach

The study employs survey method of research and a set of questionnaire was used to examine the factors that influence students’ career choices. A total of 354 undergraduate students from the Ashesi University College in Ghana participated in the study. Factor analysis was conducted on the career choice factors and differences in response between science and business students were ascertained by means of independent sample t-test.

Findings

The findings of this study indicate that university students in Ghana place much premium on intrinsic value and employability/financial prospect in their career choice decisions than such factors as prestige and desired working conditions.

Research limitations/implications

The findings of this study are relevant for policymakers and tertiary education providers interested in making the study of science an attractive option for university students in Ghana.

Originality/value

The findings of this paper highlight some of the underlining reasons for the unpopularity of the study of sciences among university students in Ghana.
“Warning! You’re entering a sick zone”
Authors: Mitchell Scott S.D.
Published: September 2018

Purpose

Traditional public health methods for tracking contagious diseases are increasingly complemented with digital tools, which use data mining, analytics and crowdsourcing to predict disease outbreaks. In recent years, alongside these public health tools, commercial mobile apps such as Sickweather have also been released. Sickweather collects information from across the web, as well as self-reports from users, so that people can see who is sick in their neighborhood. The purpose of this paper is to examine the privacy and surveillance implications of digital disease tracking tools.

Design/methodology/approach

The author performed a content and platform analysis of two apps, Sickweather and HealthMap, by using them for three months, taking regular screenshots and keeping a detailed user journal. This analysis was guided by the walkthrough method and a cultural-historical activity theory framework, taking note of imagery and other content, but also the app functionalities, including characteristics of membership, “rules” and parameters of community mobilization and engagement, monetization and moderation. This allowed me to study HealthMap and Sickweather as modes of governance that allow for (and depend upon) certain actions and particular activity systems.

Findings

Draw on concepts of network power, the surveillance assemblage, and Deleuze’s control societies, as well as the data gathered from the content and platform analysis, the author argues that disease tracking apps construct disease threat as omnipresent and urgent, compelling users to submit personal information – including sensitive health data – with little oversight or regulation.

Originality/value

Disease tracking mobile apps are growing in popularity yet have received little attention, particularly regarding privacy concerns or the construction of disease risk.
Professional associations can nurture interdisciplinary partnerships to better serve rural-dwelling older adults
Authors: Ford Cassandra D.
Published: September 2018

Purpose

The purpose of this paper is to present a case study that illustrates how professional associations can provide the context for development of formal and informal interdisciplinary collaboration and promote advancement and dissemination of useful knowledge among disciplines and across geographic boundaries. This paper reports the work of the Rural Aging Special Interest Group of the Gerontological Society of America to develop and disseminate approaches that leverage existing resources to address the challenges of providing services to rural – dwelling older adults. It describes the challenges and the roles of networks in developing and supporting these partnerships to better meet the challenges.

Design/methodology/approach

This paper describes how interdisciplinary partnerships can enhance existing resources to better meet the unique needs of rural older adults and describes an example of how a professional association facilitated the process of creation and dissemination of knowledge about this approach. An overview of the process is provided with additional information relating partnerships to improving programs and services for rural older adults.

Findings

While addressing the unique needs of rural older adults can sometimes prove challenging, a number of entities have developed successful interdisciplinary partnerships that have expanded resources and improved effectiveness in addressing these challenges.

Originality/value

This paper illustrates how a professional association can play a key role in supporting creative interdisciplinary and international problem solving.
Recovery capital: a framework for the contemporary Therapeutic Community?
Authors: Gosling Helena
Published: September 2018

Purpose

The purpose of this paper is to critically assess the extent to which recovery capital can provide a theoretical and practical way in which to explore, explain and communicate Therapeutic Community (TC) processes and practices.

Design/methodology/approach

This is a 31-month ethnographic study of one situated residential TC in England.

Findings

The findings are usefully thought out as parallels, process and progress. Parallels can be drawn between the recovery capital literature and longstanding TC principles and prescriptions. The term process is significant as it illustrates how concepts proposed by the recovery capital literature can be employed, alongside traditional TC ideals, to create a practice-focussed framework that is able to open up day-to-day processes and communicate (within and beyond the TC movement) how and why TCs provide an environment that is conducive to recovery. The ethos and application of the term progress illustrate the fundamental premise of this paper. Recovery capital provides a more contemporary way in which to understand and communicate the work that takes place in a TC.

Research limitations/implications

Synthesising the concepts proposed by both the TC and recovery capital literature provides a contemporary, practice-focussed framework for the TC, thus re-enforcing the modalities place within an increasingly competitive field.

Originality/value

Synthesising the concepts proposed by both the TC and recovery capital literature provides an original, contemporary, practice-focussed framework for the TC, thus re-enforcing the modalities place within an increasingly competitive field.
The school as a therapeutic community
Authors: Vaughan Joanne , Rodriguez Alison , Boduszek Daniel
Published: September 2018

Purpose

The purpose of this paper is to explore the facets of Self-Determination Theory (SDT) and the potential relationships with teaching satisfaction in a sample of secondary school teachers (n=1,288). The study explored the potential of the school environment in fostering a beneficial community in which personal needs could be met and investigated potential disparities between male and female teachers.

Design/methodology/approach

The study utilised an electronic quantitative questionnaire to collect data from a representative sample. Structural equation modelling was applied and permitted an exploration of potential relationships between the facets of SDT and teaching satisfaction, while controlling for specified covariates.

Findings

It was shown that the specified model could be effectively applied to both male and female teachers. The results demonstrate that only competence was related to teaching satisfaction in both samples.

Practical implications

Future studies should focus on factors which contribute to teachers’ sense of competence within the professional role. Schools need to facilitate this need in order to promote wellbeing within the educational environment.

Originality/value

This is the first known research to explore the specified relationships and the ability of the school environment to foster wellbeing and satisfaction. It is suggested that competence is the more prominent need with regards to teaching satisfaction.
Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work
Authors: Ho Po‐Han , Tsai Tsen‐Fang
Published: September 2018

Juvenile generalized pustular psoriasis (GPP) is rare and often resistant to conventional systemic therapy such as methotrexate, retinoic acid and cyclosporin A. GPP can be induced by deficiency of interleukin (IL)‐36 receptor antagonist (DITRA). No standardized guidelines are available for juvenile GPP or DITRA, and a uniformly safe and effective biologic agent has not been identified. However, multiple biologics approved for use in plaque‐type psoriasis have also been used in GPP. Herein, we report a case of a 6‐year‐old Taiwanese boy with GPP and homozygous mutation at c.115+6T>C within the IL‐36 receptor antagonist (IL36RN) gene, who was treated successfully with secukinumab after failure of prior methotrexate, acitretin, cyclosporin A, etanercept and adalimumab. Similar to two previously reported non‐adult cases of GPP successfully treated with secukinumab, our case also demonstrated a history of repeated treatment failures with several conventional oral systemic agents and biologics. Different from these two cases, however, ours is the first of juvenile GPP successfully treated with secukinumab monotherapy, without using other systemic agent concurrently during the use of secukinumab.