bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Treatment Strategies for Esophageal Perforation
Authors: Horvath Philipp , Lange Jessica , Stüker Dietmar , Wichmann Dörte , Hilbert Julia , Götz Martin , Königsrainer Alfred , von Feilitzsch Maximilian , Zdichavsky Marty
Published: July 2018

Purpose:

Esophageal perforation constitutes a potentially life-threatening condition, and this study aimed to evaluate the indications and outcome for the different treatment modalities.

Patients and Methods:

In total, 43 patients with esophageal perforation were considered for this retrospective analysis. Age, sex, length of hospital stay and intensive care treatment, in-hospital mortality, localization of perforation and etiology, treatment modality, and 90-day morbidity were analyzed.

Results:

Most patients suffered from Boerhaave syndrome and from iatrogenic esophageal perforation. In total, 63% of patients (26/41) received successful nonoperative treatment, whereas 36% required additional surgery. Two patients (5%) underwent primary surgery. In all cases no esophagectomy was necessary. In-hospital mortality was 7%. During the 90-day follow-up 1 patient with stenosis required repetitive dilatations.

Conclusions:

Initial endoscopic treatment, either by stent or by endosponge, alone or combined with an additional operative treatment, seems feasible in patients suffering from esophageal perforation. In all patients, there was no need for esophagectomy.
A Simple Method to Aid Safe Resection Margin During Sleeve Gastrectomy in Patients With Incidental Gastric Lesions
Authors: Yerdel Mehmet Ali , Özgen Görkem
Published: July 2018

In contrast to colonic tattooing, data on dye-marking before gastric operations are scarce. A simple method of gastric tattooing before sleeve gastrectomy (SG) is presented. SG, under tattoo guidance has never been reported. Submucosa of the lesion is injected with 1 to 2 mL of carbon particles (Spot, PA) 24 hours before SG. At surgery, serosal dye stain is identified and stapling achieved with care to remove all dye-stained segment. Dye spread on the serosal surface differed significantly. However, as all the dye-stained segments were avoidable during stapling, 2 neuroendocrine tumors, 2 leiomyomas, and 1 benign ulcer were resected with clear histologic margins. The method presented herein may decrease the need for operative gastroscopy, mucosal resection, or laparoscopic gastrotomy in a number of patients. Because of the problem of the dye spreading, its utilization may be inappropriate in lesions that are closer to the minor curvature and incisura angularis in particular.
Short-term Outcomes of Laparoscopic Versus Open Treatment of Internal Enteric Fistulae: A Logistic Regression Analysis
Authors: Huang Renee , Harzman Alan , Arnold Mark , Hendrickson Nyle , Abdel-Rasoul Mahmoud , Husain Syed
Published: July 2018

Although laparoscopy improves outcomes for common general surgical procedures, its role in complex colorectal procedures is not clearly defined. We sought to evaluate whether laparoscopy retains its short-term benefits when used for treatment of complex intra-abdominal fistulae. A retrospective analysis was conducted including patients undergoing surgeries for enteric fistulas over a 7-year period. The χ2 tests, the Fisher exact tests, and Student t tests were used. Logistic regression models were used to assess the relationship between outcome and predictors. A total of 74 patients (31 open, 43 laparoscopic) were included. There was no difference in age, sex, body mass index, and comorbidities between the 2 groups. The laparoscopic group had significantly shorter length of stay, estimated blood loss, and significantly lower incidence of major complications compared with open group. Our findings suggest that laparoscopy is safe and retains its short-term benefits for treatment of complex colorectal and small bowel procedures.
Congenital Oculonasal Synkinesis
Authors: Torrado Laura A. , Hamilton Grant S. , Brodsky Michael C.
Published: July 2018

A 4-year-old girl with maxillary hypoplasia, intermittent exotropia, and high myopia displayed congenital oculonasal synkinesis. We examine the implications for pathogenesis of these disparate craniofacial findings.
Segmentation of Myelin-like Signals on Clinical MR Images for Age Estimation in Preterm Infants
Authors: Deprez Maria , Wang Siying , Ledig Christian , Hajnal Joseph V. , Counsell Serena J. , Schnabel Julia A.
Published: July 2018

Myelination is considered to be an important developmental process during human brain maturation and closely correlated with gestational age. Assessment of the myelination status requires dedicated imaging, but the conventional T2-weighted scans routinely acquired during clinical imaging of neonates carry signatures that are thought to be associated with myelination. In this work, we propose a new segmentation method for myelin-like signals on T2-weighted magnetic resonance images that could be used to assess neonatal brain maturation in clinical practice. Firstly we define a segmentation protocol for myelin-like signals, and delineate manual annotations according to this protocol. We then develop an expectation-maximization framework through which we obtain the automatic segmentations of myelin-like signals. We incorporate an explicit class for partial volume voxels whose locations are configured in relation to the composing pure tissues via second-order Markov random fields. We conduct experiments in the thalami and brainstem where the majority of myelination occurs during the perinatal period for 16 test subjects aged between 29 and 44 gestational weeks. The proposed method performs accurately and robustly in both regions with respect to the manual annotations over a range of intensity percentile thresholds that are used to generate the initial segmentation estimates. Finally, we construct spatio-temporal growth models for myelin-like signals in the thalami and brain-stem to demonstrate the applicability of the proposed method for age estimation in preterm infants.
Preparing for the worst: Evidence that older adults proactively downregulate negative affect
Authors: Corbett Brittany , Rajah M. Natasha , Duarte Audrey
Published: July 2018

Age-related differences in processing emotional stimuli are well established. However, previous studies have only assessed the impact of age on emotional processing and encoding in response to, not in anticipation of, emotional stimuli. In the current study, we investigated age-related differences in the impact of emotional anticipation on affective responses and episodic memory for emotional images. Young and older were scanned while encoding negative and neutral images preceded by cues that were either valid or invalid predictors of image valence. Participants were asked to rate the emotional intensity of the images and to complete an episodic recognition task immediately after scanning. Using multivariate behavioral partial least squares (PLS) analysis, we found that young and older adults recruit the same set of brain regions to differentially support emotional processing during the anticipation of emotional images. Specifically, anticipatory recruitment of the amygdala, ventromedial PFC, and hippocampus in older adults predicts reduced memory for negative than neutral images for older adults and the opposite for young adults. Seed PLS analyses further show inverse coupling between the amygdala and ventromedial PFC activation following negative cues, consistent with the top-down spontaneous suppression of negative affect. To the best of our knowledge, this is the first study to provide evidence that the “positivity effect” seen in older adults’ memory performance is related to the spontaneous suppression of negative affect in anticipation of, not just in response to, negative stimuli.
Context Dependence of Biological Circuits
Authors: Catanach Thomas A. , McCardell Reed , Baetica Ania-Ariadna , Murray Richard M.
Published: July 2018

It has been an ongoing scientific debate whether biological parameters are conserved across experimental setups with different media, pH values, and other experimental conditions. Our work explores this question using Bayesian probability as a rigorous framework to assess the biological context of parameters in a model of the cell growth controller in Youet al. When this growth controller is uninduced, theE. colicell population grows to carrying capacity; however, when the circuit is induced, the cell population growth is regulated to remain well below carrying capacity. This growth control controller regulates theE. colicell population by cell–cell communication using the signaling molecule AHL and by cell death using the bacterial toxin CcdB.

To evaluate the context dependence of parameters such as the cell growth rate, the carrying capacity, the AHL degradation rate, the leakiness of AHL, the leakiness of toxin CcdB, and the IPTG induction factor, we collect experimental data from the growth control circuit in two different media, at two different pH values, and with several induction levels. We define a set of possible context-dependencies that describe how these parameters may differ with the experimental conditions and we develop mathematical models of the growth controller across the different experimental contexts. We then determine whether these parameters are shared across experimental contexts or whether they are context-dependent. For each of these possible context-dependencies, we use Bayesian inference to assess its plausibility and to estimate the growth controller’s parameters assuming this context-dependency. Ultimately, we find that there is significant experimental context-dependence in this circuit. Moreover, we also find that the estimated parameter values are sensitive to our assumption of a context relationship.
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

The 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

Low-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

Prokaryotes 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.

IMPORTANCE

Prokaryotic 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

In 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

Central 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 Statement

Studies 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

Placozoans, 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

The 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

The 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

Objective

To 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.

Methods

Ten 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).

Results

Three 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.

Conclusions

We 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

A 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

Emergence 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

Objectives

To 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 Methods

RIP (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 Conclusions

Per 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.
The Big Five, Self-efficacy, and Self-control in Boxers
Authors: Chen Xin , Li Bing , Xie Jiaqiong , Li Yun , Zhang Guodong
Published: July 2018

Inviting 210 boxers of national athletes in China as participants, this study applied the NEO Five-Factor Inventory and self-control and self-efficacy scales for athletes to examine the relationship between personality traits and self-control, as well as any effect of self-efficacy as a mediator between the two variables. The data analysis indicated that, firstly, the boxers’ overall level of self-control is high, and the higher the competitive level, the higher the level of self-control. Secondly, there were significant correlations among the Big Five, self-control, and self-efficacy. Thirdly, the mediation model showed that self-efficacy has a significant mediating effect between the Big Five and self-control. These results suggest that formulating training and intervention programs based on the personality traits of boxers and focusing on training their self-efficacy (1) to help them enhance their self-control ability, thereby improving athletic performance and promoting physical and mental health, and (2) to support the inclusion of personality traits, self-efficacy, and self-control among psychological indicators to be assessed in boxers.
Analysis of genetic control and QTL mapping of essential wheat grain quality traits in a recombinant inbred population
Authors: Goel Sonia , Singh Kalpana , Singh Balwant , Grewal Sapna , Dwivedi Neeta , Alqarawi Abdulaziz A. , Abd_Allah Elsayed Fathi , Singh N. K. , Ahmad Parvaiz
Published: July 2018

Wheat cultivars are genetically crossed for improving end use quality for apt traits as per need of baking industry and broad consumer’s preferences. The processing and baking qualities of bread wheat underlie into genetic make-up of a variety and influence by environmental factors and their interactions. WL711 and C306 derived recombinant inbred lines (RILs) population of 206 was used for phenotyping of quality related traits in three different environmental conditions. The genetic analysis of quality traits showed considerable variation for measurable quality traits with normal distribution and transgressive segregation across the years. From the 206 RIL, few RILs found to be superior to those of the parental cultivars for key quality traitsindicating their potential usefor improvement of end use quality and also suggestingprobability of finding new alleles and allelic combinations from the RIL population. A genetic linkage map including 346 markers was constructed withtotal map distance of 4526.8cM andinterval distance between adjacent markersof 12.9cM. Mapping analysis identified 38 putative QTLs for 13 quality related traits with QTLs explaining 7.9% - 16.8% phenotypic variation spanning over 14 chromosomes i.e. 1A, 1B, 1D, 2A, 2D, 3B, 3D, 4A, 4B, 4D, 5D, 6A, 7A and 7B. Major novel QTLs regions for quality traits have been identified on several chromosome in studied RIL population posing their potential role in marker assisted selection for better bread making quality after validation.
Unsupervised phenotypic analysis of cellular images with multi-scale convolutional neural networks
Authors: Godinez William J. , Hossain Imtiaz , Zhang Xian
Published: July 2018

Large-scale cellular imaging and phenotyping is a widely adopted strategy for understanding biological systems and chemical perturbations. Quantitative analysis of cellular images for identifying phenotypic changes is a key challenge within this strategy, and has recently seen promising progress with approaches based on deep neural networks. However, studies so far require either pre-segmented images as input or manual phenotype annotations for training, or both. To address these limitations, we have developed an unsupervised approach that exploits the inherent groupings within cellular imaging datasets to define surrogate classes that are used to train a multi-scale convolutional neural network. The trained network takes as input full-resolution microscopy images, and, without the need for segmentation, yields as output feature vectors that support phenotypic profiling. Benchmarked on two diverse benchmark datasets, the proposed approach yields accurate phenotypic predictions as well as compound potency estimates comparable to the state-of-the-art. More importantly, we show that the approach identifies novel cellular phenotypes not included in the manual annotation nor detected by previous studies.

Author summary

Cellular microscopy images provide detailed information about how cells respond to genetic or chemical treatments, and have been widely and successfully used in basic research and drug discovery. The recent breakthrough of deep learning methods for natural imaging recognition tasks has triggered the development and application of deep learning methods to cellular images to understand how cells change upon perturbation. Although successful, deep learning studies so far either can only take images of individual cells as input or require human experts to label a large amount of images. In this paper, we present an unsupervised deep learning approach that, without any human annotation, analyzes directly full-resolution microscopy images displaying typically hundreds of cells. We apply the approach to two benchmark datasets, and show that the approach identifies novel visual phenotypes not detected by previous studies.
RibonucleaseH1-targeted R-loops in surface antigen gene expression sites can direct trypanosome immune evasion
Authors: Briggs Emma , Crouch Kathryn , Lemgruber Leandro , Lapsley Craig , McCulloch Richard
Published: July 2018

Switching of the Variant Surface Glycoprotein (VSG) inTrypanosoma bruceiprovides a crucial host immune evasion strategy that is catalysed both by transcription and recombination reactions, each operating within specialised telomeric VSG expression sites (ES). VSG switching is likely triggered by events focused on the single actively transcribed ES, from a repertoire of around 15, but the nature of such events is unclear. Here we show that RNA-DNA hybrids, called R-loops, form preferentially within sequences termed the 70 bp repeats in the actively transcribed ES, but spread throughout the active and inactive ES in the absence of RNase H1, which degrades R-loops. Loss of RNase H1 also leads to increased levels of VSG coat switching and replication-associated genome damage, some of which accumulates within the active ES. This work indicates VSG ES architecture elicits R-loop formation, and that these RNA-DNA hybrids connectT. bruceiimmune evasion by transcription and recombination.

Author summary

All pathogens must survive eradication by the host immune response in order to continue infections and be passed on to a new host. Changes in the proteins expressed on the surface of the pathogen, or on the surface of the cells the pathogen infects, is a widely used strategy to escape immune elimination. Understanding how this survival strategy, termed antigenic variation, operates in any pathogen is critical, both to understand interaction between the pathogen and host and disease progression. A key event in antigenic variation is the initiation of the change in expression of the surface protein gene, though how this occurs has been detailed in very few pathogens. Here we examine how changes in expression of the surface coat of the African trypanosome, which causes sleeping sickness disease, are initiated. We reveal that specialised nucleic acid structures, termed R-loops, form around the expressed trypanosome surface protein gene and increase in abundance after mutation of an enzyme that removes them, leading to increased changes in the surface coat in trypanosome cells that are dividing. We therefore shed light on the earliest acting events in trypanosome antigenic variation.
Genetically modified pigs are protected from classical swine fever virus
Authors: Xie Zicong , Pang Daxin , Yuan Hongming , Jiao Huping , Lu Chao , Wang Kankan , Yang Qiangbing , Li Mengjing , Chen Xue , Yu Tingting , Chen Xinrong , Dai Zhen , Peng Yani , Tang Xiaochun , Li Zhanjun , Wang Tiedong , Guo Huancheng , Li Li , Tu Changchun , Lai Liangxue , Ouyang Hongsheng
Published: July 2018

Classical swine fever (CSF) caused by classical swine fever virus (CSFV) is among the most detrimental diseases, and leads to significant economic losses in the swine industry. Despite efforts by many government authorities try to stamp out the disease from national pig populations, the disease remains widespread. Here, antiviral small hairpin RNAs (shRNAs) were selected and then inserted at the porcine ROSA26 (pROSA26) locus via a CRISPR/Cas9-mediated knock-in strategy. Finally, anti-CSFV transgenic (TG) pigs were produced by somatic nuclear transfer (SCNT). Importantly, in vitro and in vivo viral challenge assays demonstrated that these TG pigs could effectively limit the growth of CSFV and reduced CSFV-associated clinical signs and mortality, and the disease resistance was stably transmitted to F1-generation. The use of these TG pigs can improve the well-being of livestock and substantially reduce virus-related economic losses. Additionally, this antiviral approach may provide a reference for future antiviral research.

Author summary

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), and is a highly contagious, often fatal porcine disease with significant economic losses. Due to its economic importance to the pig industry, the biology and pathogenesis of CSFV have been investigated extensively. Despite efforts by many government authorities to stamp out the disease from national pig populations, the disease remains widespread in some regions and seems to be waiting for the reintroduction and the next round of disease outbreaks. These highlight the necessity and urgency of developing more effective approaches to eradicate the challenging CSFV. In this study, we successfully produced anti-CSFV transgenic pigs and confirmed that these transgenic pigs could effectively limit the growth of CSFV in vivo and in vitro and that the disease resistance traits in the TG founders can be stably transmitted to their F1-generation offspring. This study suggests that these TG pigs can improve the well-being of livestock and contribute to offer potential benefits over commercial vaccination. The use of these TG pigs can improve the well-being of livestock and substantially reduce CSFV-related economic losses.
Sequencing and characterization of the complete mitochondrial genome of Critically Endangered Black Soft-shell Turtle (Nilssonia nigricans)
Authors: Kundu Shantanu , Kumar Vikas , Tyagi Kaomud , Chakraborty Rajasree , Singha Devkant , Rahaman Iftikar , Pakrashi Avas , Chandra Kailash
Published: July 2018

The complete mitochondrial genome (16796 bp) of an endangered freshwater turtle,Nilssonia nigricanswas firstly sequenced and annotated. The mitogenome was encoded by 37 genes and a major non-coding Control Region (CR). The mitogenome was A+T biased (62.16%) and spread with six overlapping and 19 intergenic spacer regions. The initiation codons were exceptionally changed as ATA, ATT, and ATC in three Protein-coding genes (PCGs) and a single base (A, T, and C) incomplete termination codons in nine PCGs. The Relative synonymous codon usage (RSCU) value was consistent among all the studied species; exception with significant reduction of Serine (S) frequency inN. nigricans,N. formosa, andR. swinhoei. The secondary structure ofN. nigricansshowed a lack of conventional dihydrouridine (DHU) arm intrnS(GCT), as well as formed a small loop structure in the acceptor stem of bothtrnR(TCG) andtrnH(GTG). The mitogenome ofN. nigricansalso revealed two unique tandem repeats (ATTAT)8, and (TATTA)20in CR. Further, the average Ka/Ks values of 13 PCGs were indicating a strong natural selection in the studied Trionychidae species. The constructed Maximum Likelihood (ML) phylogeny by PCGs shows cohesive clustering ofN. nigricanswithN. formosa. The resulted phylogeny illustrated the similar topology by all studied species from different taxonomic ranks and supported the previous taxonomic classification. Moreover, further taxon sampling from different taxonomic hierarchy, and their mitogenomics study is vital to reconcile the Testudines phylogeny and assure their evolutionary relationship.
Of puzzles and pavements: a quantitative exploration of leaf epidermal cell shape
Authors: Vőfély Róza V. , Gallagher Joseph , Pisano Grace D. , Bartlett Madelaine , Braybrook Siobhan A.
Published: July 2018

The epidermal cells of leaves lend themselves readily to observation and display many shapes and types: tabular pavement cells, complex trichomes, and stomatal complexes1. Pavement cells fromZea mays(maize) andArabidopsis thaliana(arabidopsis) both have highly undulate anticlinal walls and are held as representative of monocots and eudicots, respectively. In these two model species, we have a nuanced understanding of the molecular mechanisms that generate undulating pavement cell shape2–9. This model-system dominance has led to two common assumptions: first, that particular plant lineages are characterized by particular pavement cell shapes; and second, that undulatory pavement cell shapes are common enough to be model shapes. To test these assumptions, we quantified pavement cell shape in the leaves of 278 vascular plant taxa and assessed cell shape metrics across large taxonomic groups. We settled on two metrics that described cell shape diversity well in this dataset: aspect ratio (degree of cell elongation) and solidity (a proxy for margin undulation). We found that pavement cells in the monocots tended to have weakly undulating margins, pavement cells in ferns had strongly undulating margins, and pavement cells in the eudicots showed no particular degree of undulation. Indeed, we found that cells with strongly undulating margins, like those of arabidopsis and maize, were in the minority in seed plants. At the organ level, we found a trend towards cells with more undulating margins on the abaxial leaf surface vs. the adaxial surface. We also detected a correlation between cell and leaf aspect ratio: highly elongated leaves tended to have highly elongated cells (low aspect ratio), but not in the eudicots. This indicates that while plant anatomy and plant morphology can be connected, superficially similar leaves can develop through very different underlying growth dynamics (cell expansion and division patterns). This work reveals the striking diversity of pavement cell shapes across vascular plants, and lays the quantitative groundwork for testing hypotheses about pavement cell form and function.