bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated GIS software for computing landscape visibility metrics
Authors: Sahraoui Yohan , Vuidel Gilles , Joly Daniel , Foltête Jean‐Christophe 
Published: August 2018

AbstractAs an important component of the quality of the living environment, landscape is increasingly addressed in terms of its visual dimension. In contrast to the point‐like character of in situ observations and photographic analyses, the modeling of landscape visibility from digital data has the advantage of scanning geographical space in a systematic way. However, the tools currently available for visibility modeling are limited to the mapping of viewsheds. They require complementary operations for a complete landscape assessment, including direct and easy computation of landscape metrics. Furthermore, none of those tools integrates recent technical advances to better characterize the visible landscape by tangential vision (i.e., from ground level as opposed to vision by viewshed from above). Starting from this, PixScape software proposes to integrate a large set of functions for modeling landscape visibility while remaining interfaced with GIS software. This software can be used to perform a complete landscape assessment by computing a wide range of original landscape metrics. It performs tangential analysis in addition to viewshed analysis, which can produce more realistic outcomes. Because landscape visibility analysis over large areas implies significant computation time, the software also integrates a multi‐resolution process intended to speed up calculations while also taking into account the cognitive abilities of human vision.
Variation in the regulatory region of FZP causes increases in secondary inflorescence branching and grain yield in rice domestication
Authors: Huang Yongyu , Zhao Shuangshuang , Fu Yongcai , Sun Hengdi , Ma Xin , Tan Lubin , Liu Fengxia , Sun Xianyou , Sun Hongying , Gu Ping , Xie Daoxin , Sun Chuanqing , Zhu Zuofeng 
Published: August 2018

SummaryInflorescence branching is a key agronomic trait determining rice yield. The primary branch of the ancestral wild rice (Oryza rufipogon Griff.) bears few grains, due to minimal secondary branching. By contrast, Oryza sativa cultivars have been selected to produce large panicles with more secondary branches. Here we showed that the CONTROL OF SECONDARY BRANCH 1 (COS1) gene, which is identical to FRIZZY PANICLE (FZP), plays an important role in the key transition from few secondary branches in wild rice to more secondary branches in domesticated rice cultivars. A 4‐bp tandem repeat deletion approximately 2.7 kb upstream of FZP may affect the binding activities of auxin response factors to the FZP promoter, decrease the expression level of FZP and significantly enhance the number of secondary branches and grain yield in cultivated rice. Functional analyses showed that NARROW LEAF 1 (NAL1), a trypsin‐like serine and cysteine protease, interacted with FZP and promoted its degradation. Consistently, downregulating FZP expression or upregulating NAL1 expression in the commercial cultivar Zhonghua 17 increased the number of secondary branches per panicle, grain number per panicle and grain yield per plant. Our findings not only provide insights into the molecular mechanism of increasing grain number and yield during rice domestication, but also offer favorable genes for improving the grain yield of rice.
The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage
Authors: Wilmaerts Dorien , Bayoumi Mariam , Dewachter Liselot , Knapen Wouter , Mika Jacek T. , Hofkens Johan , Dedecker Peter , Maglia Giovanni , Verstraeten Natalie , Michiels Jan 
Published: August 2018

ABSTRACT

Bacterial populations harbor a small fraction of cells that display transient multidrug tolerance. These so-called persister cells are extremely difficult to eradicate and contribute to the recalcitrance of chronic infections. Several signaling pathways leading to persistence have been identified. However, it is poorly understood how the effectors of these pathways function at the molecular level. In a previous study, we reported that the conserved GTPase Obg induces persistence in
Escherichia coli
via transcriptional upregulation of the toxin HokB. In the present study, we demonstrate that HokB inserts in the cytoplasmic membrane where it forms pores. The pore-forming capacity of the HokB peptide is demonstrated by
in vitro
conductance measurements on synthetic and natural lipid bilayers, revealing an asymmetrical conductance profile. Pore formation is directly linked to persistence and results in leakage of intracellular ATP. HokB-induced persistence is strongly impeded in the presence of a channel blocker, thereby providing a direct link between pore functioning and persistence. Furthermore, the activity of HokB pores is sensitive to the membrane potential. This sensitivity presumably results from the formation of either intermediate or mature pore types depending on the membrane potential. Taken together, these results provide a detailed view on the mechanistic basis of persister formation through the effector HokB.

IMPORTANCE
There is increasing awareness of the clinical importance of persistence. Indeed, persistence is linked to the recalcitrance of chronic infections, and evidence is accumulating that persister cells constitute a pool of viable cells from which resistant mutants can emerge. Unfortunately, persistence is a poorly understood process at the mechanistic level. In this study, we unraveled the pore-forming activity of HokB in
E. coli
and discovered that these pores lead to leakage of intracellular ATP, which is correlated with the induction of persistence. Moreover, we established a link between persistence and pore activity, as the number of HokB-induced persister cells was strongly reduced using a channel blocker. The latter opens opportunities to reduce the number of persister cells in a clinical setting.
Inhibition of EGFR Signaling Protects from Mucormycosis
Authors: Watkins Tonya N. , Gebremariam Teclegiorgis , Swidergall Marc , Shetty Amol C. , Graf Karen T. , Alqarihi Abdullah , Alkhazraji Sondus , Alsaadi Abrar I. , Edwards Vonetta L. , Filler Scott G. , Ibrahim Ashraf S. , Bruno Vincent M. 
Published: August 2018

ABSTRACT

Mucormycosis is a life-threatening, invasive fungal infection that is caused by various species belonging to the order Mucorales.
Rhizopus
species are the most common cause of the disease, responsible for approximately 70% of all cases of mucormycosis. During pulmonary mucormycosis, inhaled
Rhizopus
spores must adhere to and invade airway epithelial cells in order to establish infection. The molecular mechanisms that govern this interaction are poorly understood. We performed an unbiased survey of the host transcriptional response during early stages of
Rhizopus arrhizus
var.
delemar
(
R. delemar
) infection in a murine model of pulmonary mucormycosis using transcriptome sequencing (RNA-seq). Network analysis revealed activation of the host’s epidermal growth factor receptor (EGFR) signaling. Consistent with the RNA-seq results, EGFR became phosphorylated upon
in vitro
infection of human alveolar epithelial cells with several members of the Mucorales, and this phosphorylated, activated form of EGFR colocalized with
R. delemar
spores. Inhibition of EGFR signaling with cetuximab or gefitinib, specific FDA-approved inhibitors of EGFR, significantly reduced the ability of
R. delemar
to invade and damage airway epithelial cells. Furthermore, gefitinib treatment significantly prolonged survival of mice with pulmonary mucormycosis, reduced tissue fungal burden, and attenuated the activation of EGFR in response to pulmonary mucormycosis. These results indicate EGFR represents a novel host target to block invasion of alveolar epithelial cells by
R. delemar
, and inhibition of EGFR signaling provides a novel approach for treating mucormycosis by repurposing an FDA-approved drug.

IMPORTANCE
Mucormycosis is an increasingly common, highly lethal fungal infection with very limited treatment options. Using a combination of
in vivo
animal models, transcriptomics, cell biology, and pharmacological approaches, we have demonstrated that Mucorales fungi activate EGFR signaling to induce fungal uptake into airway epithelial cells. Inhibition of EGFR signaling with existing FDA-approved drugs significantly increased survival following
R. arrhizus
var.
delemar
infection in mice. This study enhances our understanding of how Mucorales fungi invade host cells during the establishment of pulmonary mucormycosis and provides a proof-of-concept for the repurposing of FDA-approved drugs that target EGFR function.
Exposure to Arsenite in CD-1 Mice during Juvenile and Adult Stages: Effects on Intestinal Microbiota and Gut-Associated Immune Status
Authors: Gokulan Kuppan , Arnold Matthew G. , Jensen Jake , Vanlandingham Michelle , Twaddle Nathan C. , Doerge Daniel R. , Cerniglia Carl E. , Khare Sangeeta 
Published: August 2018

ABSTRACTIntestinal microbiota composition and gut-associated immune response can contribute to the toxicity of arsenic. We investigated the potential toxicity of short-term arsenic exposure on gut microbiome composition, intestinal immune status, microbial arsenic resistance gene, and arsenic metabolic profiles in adult and developmental stages of CD-1 mice. The potential toxicity of arsenite [As(III)] was determined for two life stages: (i) adult animals at 24 or 48 h after single gavage (0.05 mg/kg body weight [b.w.] [low dose], 0.1 mg/kg b.w. [medium dose], and 0.2 mg/kg b.w. [high dose]) and repeated exposure at 1 mg/liter for 8 days and (ii) postnatal day 10 (PND10) and PND21 after single gavage (0.05 mg/kg b.w.). Dose- and time-dependent responses in bacterial recovery/microbial composition were observed in adults after a single gavage. Repeated exposure caused a transient decrease in the recovery of intestinal bacteria, a shift in the bacterial population with abundance of arsenic resistance genes, and evidence for host metabolism of arsenite into less-reactive trivalent methylated species. Arsenic exposure in adult animals induced high levels of CC chemokines and of proinflammatory and anti-inflammatory cytokine secretion in intestine. Arsenic exposure at PND21 resulted in the development of distinct bacterial populations. Results of this study highlight significant changes in the intestinal microbiome and gut-associated immune status during a single or repeated exposure to arsenic in juvenile and adult animals. The data warrant investigation of the long-term effects of oral arsenic exposure on the microbiome and of immune system development and responses.IMPORTANCETransformation of organic arsenic to toxic inorganic arsenic (iAs) is likely carried out by intestinal bacteria, and iAs may alter the viability of certain microbial populations. This study addressed the impact of arsenic exposure on intestinal microbiota diversity and host gut-associated immune mediators during early development or adulthood using scenarios of acute or repeated doses. During acute arsenic exposure, animals developed defense functions characterized by higher abundances of bacteria that are involved in arsenic resistance or detoxification mechanisms. Arsenite had a negative effect on the abundance of bacterial species that are involved in the conversion of protein to butyrate, which is an alternative energy source in the intestine. The intestinal mucosal immune cytokine profile reflected a mechanism of protection from arsenic toxicity.
Communication quality between the medical team and the head coach/manager is associated with injury burden and player availability in elite football clubs
Authors: Ekstrand Jan , Lundqvist Daniel , Davison Michael , D’Hooghe Michel , Pensgaard Anne Marte 
Published: August 2018

ObjectivesWe investigated medical staff interpretations and descriptions of internal communication quality in elite football teams to determine whether internal communication was correlated with injuries and/or player availability at training and matches.MethodsMedical staff from 36 elite football clubs across 17 European countries produced 77 reports at four postseason meetings to provide their perceptions of internal communications in their teams. They also recorded data on individual players’ exposure to football and time-loss injuries.ResultsThe injury burden and incidence of severe injuries were significantly higher in teams with low quality of communication between the head coach/manager and the medical team (scores of 1–2 on a 5-point Likert scale) compared with teams with moderate or high-quality scores (scores of 3–5; p=0.008 for both). Teams with low scores had 4%–5% lower training attendance (76% vs 83%, p=0.001) and less availability at matches (82% vs 88%, p=0.004) compared with teams with moderate or high communication quality scores.ConclusionsThe quality of internal communication within a team was correlated with injury rates, training attendance and match availability.
Association between subjective tinnitus and cognitive performance: protocol for systematic review and meta-analysis
Authors: Clarke Nathan A , Akeroyd Michael A , Henshaw Helen , Hoare Derek J 
Published: August 2018

IntroductionSubjective tinnitus is very common and has a number of comorbid associations including depression, sleep disturbance and concentration difficulties. Concentration difficulties may be observable in people with tinnitus through poorer behavioural performance in tasks thought to measure specific cognitive domains such as attention and memory (ie, cognitive performance). Several reviews have discussed the association between tinnitus and cognition; however, none to date have investigated the association between tinnitus and cognitive performance through meta-analysis with reference to an established theoretical taxonomy. Furthermore, there has been little overlap between sets of studies that have been included in previous reviews, potentially contributing to the typically mixed findings that are reported.Methods and analysisThis systematic review aims to comprehensively review the literature using an established theoretical taxonomy and quantitatively synthesise relevant data to determine associations between subjective tinnitus and cognitive performance. Methods are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. All study designs will be eligible for inclusion with no date restrictions on searches. Studies eligible for inclusion must contain adult participants (≥18 years) with subjective tinnitus and a behavioural measure of cognitive performance. Meta-analysis will be reported via correlation for the association between tinnitus and cognitive performance.Ethics and disseminationNo ethical issues are foreseen. Findings will be reported in a student thesis, at national and international , ear, nose and throat/audiology conferences and by peer-reviewed publication.PROSPERO registration numberCRD42018085528.
Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages
Authors: Scott Aaron , Lugg Sebastian T , Aldridge Kerrie , Lewis Keir E , Bowden Allen , Mahida Rahul Y , Grudzinska Frances Susanna , Dosanjh Davinder , Parekh Dhruv , Foronjy Robert , Sapey Elizabeth , Naidu Babu , Thickett David R 
Published: August 2018

ObjectiveVaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function.MethodsAMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed.ResultsMacrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function.ConclusionsECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.
Paclitaxel Reduces Tumor Growth by Reprogramming Tumor-Associated Macrophages to an M1 Profile in a TLR4-Dependent Manner
Authors: Wanderley Carlos W. , Colón David F. , Luiz João Paulo M. , Oliveira Francisco F. , Viacava Paula R. , Leite Caio A. , Pereira Janaina A. , Silva Camila M. , Silva Cassia R. , Silva Rangel L. , Speck-Hernandez Cesar A. , Mota José M. , Alves-Filho José C. , Lima-Junior Roberto C. , Cunha Thiago M. , Cunha Fernando Q. 
Published: August 2018

Abstract
Paclitaxel is an antineoplastic agent widely used to treat several solid tumor types. The primary mechanism of action of paclitaxel is based on microtubule stabilization inducing cell-cycle arrest. Here, we use several tumor models to show that paclitaxel not only induces tumor cell-cycle arrest, but also promotes antitumor immunity. In vitro, paclitaxel reprogrammed M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. Paclitaxel also modulated the tumor-associated macrophage (TAM) profile in mouse models of breast and melanoma tumors; gene expression analysis showed that paclitaxel altered the M2-like signature of TAMs toward an M1-like profile. In mice selectively lacking TLR4 on myeloid cells, for example, macrophages (LysM-Cre+/−/TLR4fl/fl), the antitumor effect of paclitaxel was attenuated. Gene expression analysis of tumor samples from patients with ovarian cancer before and after treatment with paclitaxel detected an enrichment of genes linked to the M1 macrophage activation profile (IFNγ-stimulated macrophages). These findings indicate that paclitaxel skews TAMs toward an immunocompetent profile via TLR4, which might contribute to the antitumor effect of paclitaxel and provide a rationale for new combination regimens comprising paclitaxel and immunotherapies as an anticancer treatment.
Significance: This study provides new evidence that the antitumor effect of paclitaxel occurs in part via reactivation of the immune response against cancer, guiding tumor-associated macrophages toward the M1-like antitumor phenotype.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5891/F1.large.jpg. Cancer Res; 78(20); 5891–900. ©2018 AACR.
See related commentary by Garassino et al., p. 5729
Early application of an intermittent pneumatic compression device assists dilation of radiocephalic fistulas
Authors: Sullivan Breanna , Desai Sanjay , Singh Tej M , Mitra Amit 
Published: August 2018

Introduction: Radiocephalic fistulas are the preferred type of arteriovenous fistula due to their advantageous location. However, radiocephalic fistula maturation has historically been inferior to brachiocephalic fistulas. Research indicates that intermittent compression may aid in forearm vein dilation. Early use of a compression device may assist radiocephalic fistula maturation. Objectives: This prospective, randomized, placebo controlled study evaluates device safety and the effect of intermittent compression on vein size of radiocephalic fistulas and brachiocephalic fistulas. Methods: This was an institutional review board–approved study. After fistula creation, a novel, intermittent pneumatic compression device (Fist Assist®) was worn 15 cm proximal to fistulas 6 h daily for 30 days. Those in the treatment group (n = 43) wore Fist Assist® (24 with brachiocephalic fistulas and 19 with radiocephalic fistulas). Clinical controls (n = 16) wore a sham device. Vein diameter was measured at 0 and 30 days by duplex measurement. Percentage increase was recorded and tested for significance. Results: After 30 days, the mean percentage increase in vein diameter in the radiocephalic fistula treatment group was significantly larger than brachiocephalic fistulas in the treatment group at all proximal locations from the anastomosis. Increases in percentage vein dilation for those in the radiocephalic fistula treatment group were significantly larger than those in the control group. All fistulas treated with Fist Assist® are still functional with no reported complications. Conclusion: Early application of the Fist Assist® device may be more effective at helping radiocephalic fistula mature as compared to brachiocephalic fistulas. Successful radiocephalic fistula maturation may decrease vascular access costs, reduce complications, and preserve upper arm veins for future use in vascular access.