bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of lateral hypothalamic group III mGluRs suppresses drug-seeking following abstinence and cocaine-associated increases in excitatory drive to orexin/hypocretin cells
Authors: Yeoh Jiann W. , James Morgan H. , Adams Cameron D. , Bains Jaideep S. , Sakurai Takeshi , Aston-Jones Gary , Graham Brett A. , Dayas Christopher V. 
Published: July 2018

AbstractThe perifornical/lateral hypothalamic area (LHA) orexin (hypocretin) system is involved in drug-seeking behavior elicited by drug-associated stimuli. Cocaine exposure is associated with presynaptic plasticity at LHA orexin cells such that excitatory input to orexin cells is enhanced, both acutely and into withdrawal. These changes may augment orexin cell reactivity to drug-related cues during abstinence and contribute to relapse-like behavior. Studies in hypothalamic slices from drug-naïve animals indicate that agonism of group III metabotropic glutamate receptors (mGluRs) reduces presynaptic glutamate release onto orexin cells. Therefore, we examined the group III mGluR system as a potential target to reduce orexin cell excitabilityin-vivo, and tested whether activating these receptors could normalize orexin cell activity following cocaine and reduce cocaine-seeking elicited by drug-associated stimuli during abstinence. First, we verified that group III mGluRs regulate orexin cell activityin vivoby showing that intra-LHA infusions of the selective agonist L-(+)-2-Amino-4-phosphonobutyric acid (L-AP4) reduces Fos expression in orexin cells following 24h food deprivation. Next, we extended these findings to show that intra-LHA L-AP4 infusions reduced discriminative stimulus-driven cocaine-seeking following withdrawal. L-AP4 had no effect on general motor activity of sucrose self-administration. Finally, using whole-cell patch clamp recordings from identified orexin cells in orexin-GFP transgenic mice, we show that enhanced presynaptic drive to orexin cells persists for up to 14d into withdrawal and that this plasticity is normalized by L-AP4. L-AP4 had no effect on measures of postsynaptic plasticity in cocaine-exposed animals. Together, these data indicate that agonism of LHA group III mGluRs reduces orexin cell activityin-vivoand is an effective strategy to suppress cocaine-seeking behavior following withdrawal. These effects are likely mediated, at least in part, by normalization of presynaptic plasticity at orexin cells that occurs as a result of cocaine exposure.
Visual features contribute differently to preferences for different item categories
Authors: Oren Shiran , Sela Tal , Levy Dino J. , Schonberg Tom 
Published: July 2018

AbstractLow-level visual features have been known to play a role in value-based decision-making. However, thus far, mainly single features were tested on one type of item using one method of measurement. Here, we test the contribution of low-level visual features on three items types: fractal-art images, faces, and snack food items. We test the role of visual features on preferences using both subjective ratings and choices. We show that low-level visual features contribute to value-based decision-making even after controlling for higher level configural features of faces like eye-distance and market features of snacks like calories. Importantly, we show that while low-level visual features consistently contribute to value-based decision-making, different features contribute to different types of items when using different measurement methods. Our study highlights the necessity of using multiple item types and multiple measurement methods to construct a unifying framework regarding the contribution of low-level features to value-based decision-making.
BacStalk: a comprehensive and interactive image analysis software tool for bacterial cell biology
Authors: Hartmann Raimo , van Teeseling Muriel C.F. , Thanbichler Martin , Drescher Knut 
Published: July 2018

ABSTRACTProkaryotes display a remarkable spatiotemporal organization of processes within individual cells. Investigations of the underlying mechanisms rely extensively on the analysis of microscopy images. Advanced image analysis software has revolutionized the cell-biological studies of established model organisms with largely symmetric rod-like cell shapes. However’ algorithms suitable for analyzing features of morphologically more complex model species are lacking’ although such unusually shaped organisms have emerged as treasure-troves of new molecular mechanisms and diversity in prokaryotic cell biology. To address this problem’ we developed BacStalk’ a simple’ interactive’ and easy-to-use MatLab-based software tool for quantitatively analyzing images of commonly and uncommonly shaped bacteria’ including stalked (budding) bacteria. BacStalk automatically detects the separate parts of the cells (cell body’ stalk’ bud’ or appendage) as well as their connections’ thereby allowing in-depth analyses of the organization of morphologically complex bacteria over time. BacStalk features the generation and visualization of concatenated fluorescence profiles along cells’ stalks’ appendages’ and buds to trace the spatiotemporal dynamics of fluorescent markers. Cells are interactively linked to demographs’ kymographs’ cell lineage analyses’ and scatterplots’ which enables intuitive and fast data exploration and’ thus’ significantly speeds up the image analysis process. Furthermore’ BacStalk introduces a 2D representation of demo- and kymographs’ enabling data representations in which the two spatial dimensions of the cell are preserved. The software was developed to handle large data sets and to generate publication-grade figures that can be easily edited. BacStalk therefore provides an advanced image analysis platform that extends the spectrum of model organisms for prokaryotic cell biology to bacteria with multiple morphologies and life cycles.IMPORTANCEProkaryotic cells show a striking degree of subcellular organization. Studies of the underlying mechanisms and their variation among different species greatly enhance our understanding of prokaryotic cell biology. The image analysis software tool BacStalk extracts an unprecedented amount of information from images of stalked bacteria, by generating interactive demographs, kymographs, cell lineages, and scatter plots that aid fast and thorough data analysis and representation. Notably, BacStalk can preserve the two spatial dimensions of cells when generating demographs and kymographs to accurately and intuitively reflect the intracellular organization. BacStalk also performs well on established, non-stalked model organisms with common or uncommon shapes. BacStalk therefore contributes to the advancement of prokaryotic cell biology, as it widens the spectrum of easily accessible model organisms and enables a more intuitive and interactive data analysis and visualization.
Predicting audiovisual speech: Early combined effects of sentential and visual constraints
Authors: Økland Heidi Solberg , Todorović Ana , Lüttke Claudia S. , McQueen James M. , de Lange Floris P. 
Published: July 2018

AbstractIn language comprehension, a variety of contextual cues act in unison to render upcoming words more or less predictable. As a sentence unfolds, we use prior context (sentential constraints) to predict what the next words might be. Additionally, in a conversation, we can predict upcoming sounds through observing the mouth movements of a speaker (visual constraints). In electrophysiological studies, effects of visual salience have typically been observed early in language processing, while effects of sentential constraints have typically been observed later. We hypothesized that the visual and the sentential constraints might feed into the same predictive process such that effects of sentential constraints might also be detectable early in language processing through modulations of the early effects of visual salience. We presented participants with audiovisual speech while recording their brain activity with magnetoencephalography. Participants saw videos of a person saying sentences where the last word was either sententially constrained or not, and began with a salient or non-salient mouth movement. We found that sentential constraints indeed exerted an early (N1) influence on language processing. Sentential modulations of the N1 visual predictability effect were visible in brain areas associated with semantic processing, and were differently expressed in the two hemispheres. In the left hemisphere, visual and sentential constraints jointly suppressed the auditory evoked field, while the right hemisphere was sensitive to visual constraints only in the absence of strong sentential constraints. These results suggest that sentential and visual constraints can jointly influence even very early stages of audiovisual speech comprehension.
Timing between cortical slow oscillations and heart rate bursts during sleep predicts perceptual speed, but not offline consolidation
Authors: Naji Mohsen , Krishnan Giri P , McDevitt Elizabeth A , Bazhenov Maxim , Mednick Sara C 
Published: July 2018

AbstractCentral and autonomic nervous system activity are coupled during sleep. Cortical slow oscillations (SOs, <1Hz) coincide with brief bursts in heart rate (HR), but the functional consequence of this coupling in cognition remains elusive. We measured SO-HR temporal coupling (i.e., the peak-to-peak interval between downstate of SO event and HR burst) during a daytime nap, and asked whether this SO-HR timing measure was associated with perceptual speed and learning on a texture discrimination task, by testing subjects before and after a nap. The coherence of SO-HR events during sleep strongly correlated with an individual’s perceptual speed in the morning and evening test sessions, but not with their change in performance after the nap (i.e., consolidation). We confirmed this result in two additional experimental visits, and also discovered that this association was visit-specific, indicating a reliable state (not trait) marker. Thus, we introduce a novel physiological index that may be a useful marker of state-dependent processing speed of an individual.Significance StatementStudies show that autonomic and central nervous system activity is coupled. For example, increases in heart rate follow cortical slow oscillations during sleep. However, the functional significance of this coupling for cognition is not understood. In three experimental visits, we show that the timing between these sleep events (the peak-to-peak delay between the slow oscillation and the heart rate burst) is highly correlated with waking perceptual processing speed. This reliable individual difference measure may be a useful marker of generalized processing speed.
High cell diversity and complex peptidergic signalling underlie placozoan behaviour
Authors: Varoqueaux Frédérique , Williams Elizabeth A , Grandemange Susie , Truscello Luca , Kamm Kai , Schierwater Bernd , Jékely Gáspár , Fasshauer Dirk 
Published: July 2018

SUMMARYPlacozoans, together with sponges, are the only animals devoid of a nervous system and muscles, yet both respond to sensory stimulation in a coordinated manner. How behavioural control in these free-living animals is achieved in the absence of neurons and, more fundamentally, how the first neurons evolved from more primitive communication cells during the rise of animals is not yet understood [1–5]. The placozoan Trichoplax adhaerens is a millimeter-wide, flat, free-living marine animal composed of six morphologically identified cell types distributed across a simple bodyplan [6–9]: a flat upper epithelium and a cylindrical lower epithelium interspersed with a loose layer of fiber cells. Its genome encodes several proneuropeptide genes and genes involved in neurosecretion in animals with a nervous system [10–12]. Here we investigate neuropeptide signalling in Trichoplax adhaerens. We found specific expression of several neuropeptides in non-overlapping cell populations distributed over the three cell layers, revealing an unsuspected cell-type diversity of Trichoplax adhaerens. Using live imaging, we uncovered that treatments with 11 different neuropeptides elicited striking and consistent effects on the animals’ shape, patterns of movement and velocity that we categorized under three main types: (i) crinkling, (ii) turning, and (iii) flattening and churning. Together, the data demonstrate a crucial role for peptidergic signalling in nerveless placozoans and suggest that peptidergic volume signalling may have predated synaptic signalling in the evolution of nervous systems.
Comparison of genotoxic vs. non-genotoxic stabilization of p53 provides insight into parallel stress-responsive transcriptional networks
Authors: Catizone Allison N. , Berger Shelley L. , Sammons Morgan A. 
Published: July 2018

AbstractThe tumor suppressor protein p53 is activated in response to diverse intrinsic and extrinsic cellular stresses and controls a broad cell-protective gene network. Whether p53:DNA binding and subsequent transcriptional activation differs downstream of these diverse intrinsic and extrinsic activators within the same cell type is controversial. Using primary human fibroblasts, we assessed the genome-wide profile of p53 binding, chromatin structure, and transcriptional dynamics after either genotoxic or non-genotoxic activation of p53. Activation of p53 by treatment with either etoposide or the small molecule MDM2 inhibitor nutlin 3A yields strikingly similar genome-wide binding of p53 and concomitant changes to local chromatin modifications and structure. DNA damage, but not p53 activation per se, leads to increased expression of genes in an inflammatory cytokine pathway. Etoposide-mediated activation of this inflammation signature is inhibited by treatment with the NF-kB pathway inhibitor Bay 11-7082, but does not affect expression of canonical p53 target genes. Our data demonstrate that differential activation of p53 within the same cell type leads to highly similar genome-wide binding, chromatin dynamics, and gene expression dynamics, and that DNA damage-mediated signaling through NF-κB likely controls the observed pro-inflammatory cytokine gene expression pattern.
Self beyond the body: task-relevant distal cues modulate performance and body ownership
Authors: Grechuta Klaudia , Ulysse Laura , Ballester Belén Rubio , Verschure Paul F.M.J. 
Published: July 2018

AbstractThe understanding of Body Ownership (BO) largely relies on the Rubber Hand Illusion (RHI) where synchronous stroking of real and Rubber Hands (RH) leads to an illusion of ownership of RH provided physical, anatomical, postural and spatial plausibility of the two body-parts. RHI also occurs during visuomotor synchrony, in particular, when the visual feedback of virtual arm movements follows the trajectory of the instantiated motor command. Hence BO seems to result from a bottom-up integration of afferent and efferent proximal multisensory evidence, and top-down prediction of both externally and self-generated signals, which occurs when the predictions about upcoming sensory signals are accurate. In motor control, the differential processing of predicted and actual sensory consequences of self-generated actions is addressed by, the so-called, Forward Model (FM). Based on an efference copy or corollary discharge, FM issues predictions about the sensory consequences of motor commands and compares them with the actual outcome. The discrepancies (Sensory Prediction Errors, SPEs) are used to correct the action on the consecutive trial and provide new estimates of the current state of the body and the environment. Here, we propose that BO might be computed by FMs, and therefore, it might depend on their consistency, specifically, in contexts where the sensory feedback is self-generated. Crucially, to reduce SPE, FMs integrate both proximal (proprioceptive) and distal (vision, audition) sensory cues relevant to the task. Thus, if BO depends on the consistency of FMs, it would be compromised by the incongruency of not only proximal but also distal cues. To test our hypothesis, we devised an embodied VR-based task where action outcomes were signaled by distinct auditory cues. By manipulating the cues with respect to their spatiotemporal congruency and valence, we show that distal feedback which violates predictions about action outcomes compromises both BO and performance. These results demonstrate that BO is influenced by not only efferent and afferent cues which pertain to the body itself but also those arising outside of the body and suggest that in goal-oriented tasks BO might result from a computation of FM.
Different obesity phenotypes correlated with the PI3K-AKT signaling pathway in tree shrews
Authors: Han Yuanyuan , Zhang Huatang , Dai Jiejie , Chen Yang 
Published: July 2018

AbstractObjectiveTo identify the meaningful co-expressed gene network in mRNA extracted from adipose tissue representing different obesity phenotypes in a new tree shrew model. Furthermore, to locate the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity.MethodsTen tree shrews were selected from F1 populations and divided into 3 groups based on their Lee’s index for mRNA sequencing. We identified clusters of highly correlated genes (modules) by weighted gene co-expression network analysis (WGCNA).ResultsThree modules were strongly correlated with not less than one obesity phenotype (associations ranging from −0.94 to 0.85, P < 0.01). The ribosome, lysosome and ubiquitin-mediated proteolysis pathways were the most enriched pathways of the blue (including 481 genes), brown (389 genes) and turquoise (1781 genes) modules, respectively. The hub genes were determined, including UBA52 in the blue module, AKT1 in the brown module and LRRK2 in the turquoise module.ConclusionsWe characterized different obesity phenotypes in tree shrews for the first time. The most represented gene AKT1 indicated the vital role of the PI3K-AKT pathway through interactions with downstream pathways and differentially expressed genes (DEGs). The work will help provide new insight into the prevention and treatment strategies of obesity.
A phenotypic small-molecule screen identifies halogenated salicylanilides as inhibitors of fungal morphogenesis, biofilm formation and host cell invasion
Authors: Garcia Carlos , Burgain Anaïs , Chaillot Julien , Pic Émilie , Khemiri Inès , Sellam Adnane 
Published: July 2018

AbstractA poorly exploited paradigm in the antimicrobial therapy field is to target virulence traits for drug development. In contrast to target-focused approaches, antivirulence phenotypic screens enable identification of bioactive molecules that induce a desirable biological readout without makinga prioriassumption about the cellular target. Here, we screened a chemical library of 678 small molecules against the invasive hyphal growth of the human opportunistic yeastCandida albicans. We found that a halogenated salicylanilide (N1-(3,5-dichlorophenyl)-5-chloro-2-hydroxybenzamide) and one of its analog, Niclosamide, an FDA-approved anthelmintic in humans, exhibited both antifilamentation and antibiofilm activities againstC. albicansand the multi-resistant yeastC. auris. The antivirulence activity of halogenated salicylanilides were also expanded toC. albicansresistant strains with different resistance mechanisms. We also found that Niclosamide protected the intestinal epithelial cells against invasion byC. albicans. Transcriptional profiling ofC. albicanschallenged with Niclosamide exhibited a signature that is characteristic of the mitochondria-to-nucleus retrograde response. Our chemogenomic analysis showed that halogenated salicylanilides compromise the potential-dependant mitochondrial protein translocon machinery. Given the fact that the safety of Niclosamide is well established in humans, this molecule could represent the first clinically approved antivirulence agent against a pathogenic fungus.
High proportion of multiple copies of Plasmodium falciparum Plasmepsin-2 gene in African isolates: Is piperaquine resistance emerging in Africa?
Authors: Leroy D. , Macintyre F. , Adamy M. , Laurijssens B. , Klopper R. , Khim N. , Legrand E , Wells T.N. , Ménard D. 
Published: July 2018

AbstractEmergence of Plasmodium falciparum resistance to antimalarial drugs is currently the primary rationale supporting the development of new and well-tolerated drugs. In 2014-2015, a phase 2b clinical study was conducted to evaluate the efficacy of a single oral dose of Artefenomel (OZ439)-piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria. Blood samples collected before treatment offered the opportunity to investigate the proportion of multidrug resistant parasite genotypes including P. falciparum Kelch13 mutations and copy number variation of both P. falciparum plasmepsin2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes. Validated Kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated to PPQ resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (>30%).Our findings sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to decipher the genetic background associated with PPQ resistance in Africa by investigating in vitro susceptibilities to PPQ of isolates with multiple copies of the Pfpm2 gene and the urgent need to assess the risk of development of PPQ resistance, along with the efficacy of both current frontline therapies and new antimalarial combinations.
The Association between Cigarette Affordability and Consumption
Authors: He Yanyun , Shang Ce , Chaloupka Frank J. 
Published: July 2018

AbstractObjectivesTo calculate cigarette affordability for 78 countries worldwide from 2001 to 2014 using the Relative Income Price (RIP) ratio defined as the percentage of per capita GDP required to purchase 100 packs of cigarettes using the lowest price from Economist Intelligence Unit (EIU) database, examine the association between cigarette affordability and cigarette consumption, and calculate the affordability elasticity of demand.Design and MethodsRIP (2001-2014) was calculated for 16 low-income economies, 19 lower middle-income economies, 13 upper middle-income economies, and 30 high-income economies. Ordinary least square regressions were used to analyze the association between cigarette affordability and consumption.Results and ConclusionsPer capita consumption continued to rise in low-income countries and decreased slightly in lower middle-income countries as the RIP of cigarette consistently declined in low- and lower middle-income economies from 2001 to 2014. The real cigarette prices continued to decline in low- and lower middle-income countries and continued to rise in upper middle- and high-income countries. Though cigarettes were more expensive in HICs than were in LMICs, cigarettes were more affordable in HICs than were in LMICs. The regression results show a 10% increase in the RIP of cigarettes led to a 2% decrease in per capita consumption. The affordability elasticity of demand differed significantly between HICs and LMICs. However, the effect of cigarette affordability on consumption has not changed over time. To control the smoking epidemic, low- and lower middle-income countries should further increase cigarette prices. The rate of price increase should exceed the rate of economic growth and outpace the inflation rate to make cigarettes less affordable and thereby reducing tobacco use.