bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heme Impairs Alveolar Epithelial Sodium Channels Post Toxic Gas Inhalation
Authors: Aggarwal Saurabh , Lazrak Ahmed , Ahmad Israr , Yu Zhihong , Bryant Ayesha , Mobley James A. , Ford David A. , Matalon Sadis 
Published: January 2020

ABSTRACTWe previously reported that cell-free heme (CFH) is increased in the plasma of patients with acute and chronic lung injury and causes pulmonary edema in animal model of acute respiratory distress syndrome (ARDS) post inhalation of halogen gas. However, the mechanisms by which CFH causes pulmonary edema are unclear. Herein we report for the first time the presence of CFH and chlorinated lipids (formed by the interaction of halogen gas, Cl2, with plasmalogens) in the plasma of patients and mice exposed to Cl2gas.Ex vivoincubation of red blood cells (RBC) with halogenated lipids caused oxidative damage to RBC cytoskeletal protein spectrin, resulting in hemolysis and release of CFH. A single intramuscular injection of the heme-scavenging protein hemopexin (4 µg/kg body weight) in mice, one hour post halogen exposure, reversed RBC fragility and decreased CFH levels to those of air controls. Patch clamp and short circuit current measurements revealed that CFH inhibited the activity of amiloride-sensitive (ENaC) and cation sodium (Na+) channels in mouse alveolar cells and trans-epithelial Na+transport across human airway cells with EC50of 125 nM and 500 nM, respectively. Molecular modeling identified 22 putative heme-docking sites on ENaC (energy of binding range: 86-1563 kJ/mol) with at least 2 sites within its narrow transmembrane pore, potentially capable of blocking Na+transport across the channel. In conclusion, results suggested that CFH mediated inhibition of ENaC activity may be responsible for pulmonary edema post inhalation injury.
Super elongation complex as a targetable dependency in diffuse midline glioma
Authors: Dahl Nathan A. , Danis Etienne , Balakrishnan Ilango , Wang Dong , Pierce Angela , Walker Faye M. , Gilani Ahmed , Serkova Natalie J. , Madhavan Krishna , Fosmire Susan , Green Adam L. , Foreman Nicholas K. , Venkataraman Sujatha , Vibhakar Rajeev 
Published: January 2020

AbstractMutations in the histone 3 gene (H3K27M) are the eponymous drivers in diffuse intrinsic pontine gliomas (DIPGs) and other diffuse midline gliomas (DMGs), aggressive pediatric brain cancers for which no curative therapy currently exists. The salient molecular consequence of these recurrent oncohistones is a global loss of repressive H3K27me3 residues and broad epigenetic dysregulation. In order to identify specific, therapeutically targetable epigenetic dependencies within this disease context, we performed an shRNA screen targeting 408 genes classified as epigenetic/chromatin-associated molecules in patient-derived DMG cultures. This approach identified AFF4, the scaffold protein of the super elongation complex (SEC), as a previously-undescribed dependency in DMG. Interrogation of SEC function demonstrated a key role for maintaining DMG cell viability and clonogenic potential while promoting self-renewal of DMG tumor stem cells. Small-molecule inhibition of the SEC with the highly-specific, clinically relevant CDK9 inhibitors atuveciclib and AZD4573 restores regulatory RNA polymerase II pausing, promotes cellular differentiation, and leads to potent anti-tumor effect bothin vitroand in patient-derived xenograft models. These studies present a biologic rationale for translational exploration of CDK9 inhibition as a promising therapeutic approach in a disease which currently has no effective medical therapies.
Visualization and normalization of drift effect across batches in metabolome-wide association studies
Authors: Bararpour Nasim , Gilardi Federica , Carmeli Cristian , Sidibe Jonathan , Ivanisevic Julijana , Caputo Tiziana , Augsburger Marc , Grabherr Silke , Desvergne Béatrice , Guex Nicolas , Bochud Murielle , Thomas Aurelien 
Published: January 2020

AbstractAs a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and identification of metabolites having regulatory effect in various biological processes. While MS-based metabolomics assays are endowed with high-throughput and sensitivity, large-scale MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of true biologically relevant changes.We developed “dbnorm”, a package in R environment, which allows visualization and removal of signal heterogeneity from large metabolomics datasets. “dbnorm” integrates advanced statistical tools to inspect dataset structure, at both macroscopic (sample batch) and microscopic (metabolic features) scales. To compare model performance on data correction, “dbnorm” assigns a score, which allows the straightforward identification of the best fitting model for each dataset. Herein, we show how “dbnorm” efficiently removes signal drift among batches to capture the true biological heterogeneity of data in two large-scale metabolomics studies.
Arachidonic acid promotes the binding of 5-lipoxygenase on nanodiscs containing 5-lipoxygenase activating protein in the absence of calcium-ions
Authors: Kumar Ramakrishnan B. , Purhonen Pasi , Hebert Hans , Jegerschöld Caroline 
Published: January 2020

AbstractAmong the first steps in inflammation is the conversion of arachidonic acid (AA) stored in the cell membranes into leukotrienes. This occurs mainly in leukocytes and depends on the interaction of two proteins: 5-lipoxygenase (5LO), stored away from the nuclear membranes until use and 5-lipoxygenase activating protein (FLAP), a transmembrane, homotrimeric protein, constitutively present in nuclear membrane. We could earlier visualize the binding of 5LO to nanodiscs in the presence of Ca2+-ions by the use of transmission electron microscopy (TEM) on samples negatively stained by sodium phosphotungstate. In the absence of Ca2+-ions 5LO did not bind to the membrane. In the present communication, FLAP reconstituted in the nanodiscs which could be purified if the His-tag was located on the FLAP C-terminus but not the N-terminus. Our aim was to find out if 1) 5LO would bind in a Ca2+-dependent manner also when FLAP is present? 2) Would the substrate (AA) have effects on 5LO binding to FLAP-nanodiscs? TEM was used to assess the complex formation between 5LO and FLAP-nanodiscs along with, sucrose gradient purification, gel-electrophoresis and mass spectroscopy. It was found that presence of AA by itself induces complex formation in the absence of added calcium. This finding corroborates that AA is necessary for the complex formation and that a Ca2+-flush is mainly needed for the recruitment of 5LO to the membrane. Our results also showed that the addition of Ca2+-ions promoted binding of 5LO on the FLAP-nanodiscs as was also the case for nanodiscs without FLAP incorporated. In the absence of added substances no 5LO-FLAP complex was formed. Another finding is that the formation of a 5LO-FLAP complex appears to induce fragmentation of 5LOin vitro.
Establishing ProbioticSaccharomyces boulardiias a Model Organism for Synthesis and Delivery of Biomolecules
Authors: Durmusoglu Deniz , Al’Abri Ibrahim , Collins Scott P. , Beisel Chase , Crook Nathan 
Published: January 2020

AbstractSaccharomyces boulardiiis a widely used yeast probiotic which can counteract various gastrointestinal disorders1. As a relative ofSaccharomyces cerevisiae,S. boulardiiexhibits rapid growth and is easy to transform2and thus represents a promising chassis for the engineered secretion of biomolecules. To establishS. boulardiias a platform for delivery of biomolecules to the mammalian gut, we measured the amount and variance in protein expression enabled by promoters, terminators, selective markers, and copy number control elements in this organism. These genetic elements were characterized in plasmidic and genomic contexts, revealing strategies for tunable control of gene expression and CRISPR-mediated genome editing in this strain. We then leveraged this set of genetic parts to combinatorially assemble pathways enabling a wide range of drug and vitamin titers. Finally, we measuredS. boulardii’s residence time in the gastrointestinal tracts of germ-free and antibiotic-treated mice, revealing the relationships between dosing strategy and colonization level. This work establishesS. boulardiias a genetically tractable commensal fungus and provides a set of strategies for engineeringS. boulardiito synthesize and deliver biomolecules during gut colonization.
AStarix: Fast and Optimal Sequence-to-Graph Alignment
Authors: Ivanov Pesho , Bichsel Benjamin , Mustafa Harun , Kahles André , Rätsch Gunnar , Vechev Martin 
Published: January 2020

AbstractWe present an algorithm for theoptimal alignmentof sequences togenome graphs. It works by phrasing the edit distance minimization task as finding a shortest path on an implicit alignment graph. To find a shortest path, we instantiate the A⋆paradigm with a novel domain-specific heuristic function that accounts for the upcoming subsequence in the query to be aligned, resulting in a provably optimal alignment algorithm called AStarix.Experimental evaluation of AStarixshows that it is 1–2 orders of magnitude faster than state-of-the-art optimal algorithms on the task of aligning Illumina reads to reference genome graphs. Implementations and evaluations are available athttps://github.com/eth-sri/astarix.
Gasdermin-D-dependent IL-1αrelease from microglia promotes protective immunity during chronicToxoplasma gondiiinfection
Authors: Batista Samantha J. , Still Katherine M. , Johanson David , Thompson Jeremy A. , O’Brien Carleigh A. , Lukens John R. , Harris Tajie H. 
Published: January 2020

AbstractMicroglia, the resident immune cells of the brain parenchyma, are thought to be first-line defenders against CNS infections. We sought to identify specific roles of microglia in the control of the eukaryotic parasiteToxoplasma gondii, an opportunistic infection that can cause severe neurological disease. In order to identify the specific function of microglia in the brain during infection, we sorted microglia and infiltrating myeloid cells from infected microglia reporter mice. Using RNA-sequencing, we find strong NF-κB and inflammatory cytokine signatures overrepresented in blood-derived macrophages versus microglia. Interestingly, we also find that IL-1αis enriched in microglia and IL-1βin macrophages, which was also evident at the protein level. We find that mice lacking IL-1R1 or IL-1α, but not IL-1β, have impaired parasite control and immune cell infiltration specifically within the brain. Further, by sorting purified populations from infected brains, we show that microglia, not peripheral myeloid cells, release IL-1α ex vivo. Finally, using knockout mice as well as chemical inhibition, we show thatex vivoIL-1αrelease is gasdermin-D dependent, and that gasdermin-D and caspase-1/11 deficient mice show deficits in immune infiltration into the brain and parasite control. These results demonstrate that microglia and macrophages are differently equipped to propagate inflammation, and that in chronicT. gondiiinfection, microglia specifically can release the alarmin IL-1α, a cytokine that promotes neuroinflammation and parasite control.
Characterization of mating type genes in heterothallicNeonectriaspecies with emphasis onN. coccinea, N. ditissima,andN. faginata
Authors: Stauder Cameron M. , Garnas Jeff R. , Morrison Eric W. , Salgado-Salazar Catalina , Kasson Matt T. 
Published: January 2020

AbstractNeonectria ditissimaandN. faginataare canker pathogens involved in an insect-fungus disease complex of American beech (Fagus grandifolia) commonly known as beech bark disease (BBD). In Europe, bothN. ditissimaandN. coccineaare involved in BBD on European beech (Fagus sylvatica). Field observations across the range of BBD indicate that new infections occur primarily via ascospores. Both heterothallic (self-sterile) and homothallic (self-fertile) mating strategies have been reported forNeonectriafungi. As such, investigations into mating strategy are important for understanding both the disease cycle and population genetics ofNeonectria. This is particularly important in the U.S. given that over timeN. faginatadominates the BBD pathosystem despite high densities of non-beech hosts forN. ditissima. This study utilized whole-genome sequences of BBD-associatedNeonectriaspp. along with other publicly availableNeonectriaandCorinectriagenomes andin vitromating assays to characterize mating type (MAT) loci and confirm thallism for select members ofNeonectriaandCorinectria. MAT gene-specific primer pairs were developed to efficiently characterize the mating types of additional single ascospore strains ofN. ditissima,N. faginata, andN. coccineaand several other related species lacking genomic data.In vitromating assays were used in combination with molecular results to confirm thallism. These assays also comfirmed the sexual compatibility amongN. ditissimastrains from different plant hosts. Maximum likelihood phylogenetic analysis of both MAT1-1-1 and MAT1-2-1 sequences recovered trees with similar topology to previously published phylogenies ofNeonectriaandCorinectria. The results of this study indicate that allNeonectriaandCorinectriatested are heterothallic based on our limited sampling and, as such, thallism cannot help explain the inevitable dominance ofN. faginatain the BBD pathosystem.
Influence of consumer decision-making styles on use of mobile shopping applications
Authors: Sarkar Subhro , Khare Arpita , Sadachar Amrut 
Published: January 2020

Purpose
The purpose of this paper is to validate the consumer styles inventory (CSI) scale for understanding the decision-making styles of shopping app users. The validated scales are used to examine the relationship between consumers’ decision-making styles and factors affecting the use of mobile shopping apps.

Design/methodology/approach
A total of 428 valid responses are collected from the users of the five most popular shopping apps. The mobile shopping apps are selected based on a popularity study. Data are collected from mobile app shoppers through an online survey.

Findings
Findings reveal a new set of factors that can be used for understanding use of mobile shopping apps. Decision-making styles influence the adoption of mobile apps for shopping. Factors responsible for the adoption of mobile shopping apps such as usefulness and risk perceptions differ across consumers with different decision-making styles.

Practical implications
The findings would facilitate online retailers in building focused marketing strategies for segmenting and targeting the consumers having different decision-making styles.

Originality/value
The current research is the first of its kind to examine the applicability of the CSI scale in the context of mobile app shoppers in an emerging economy. The findings enrich the existing literature by providing empirical support to the relationship between decision-making styles and factors affecting adoption of shopping using mobile apps.
A kind of new method of intelligent trust engineering metrics (ITEM) for application of mobilead hocnetwork
Authors: Zhang Degan , Gong Changle , Jiang Kaiwen , Zhang Xiaodan , Zhang Ting 
Published: January 2020

PurposeThis paper aims to put forward a kind of new method of intelligent trust engineering metrics for application of mobilead hocnetwork (MANET).Design/methodology/approachThe new method calculates the communication trust by using the number of data packets among the nodes of MANET, predicts intelligently the trust and calculates the comprehensive trust based on the historical trust; then calculates the energy trust based on the residual energy of the nodes of MANET, calculates the direct trust based on the communication trust and energy trust. The new method calculates the recommendation trust based on the recommendation reliability; adopts the adaptive weighting to calculate the integrated direct trust by considering the direct trust with recommendation trust.FindingsBased on the integrated direct trust and the factor of trust propagation distance, the indirect trust among the nodes of MANET is calculated. The above process can be optimized based on the dynamic machine learning presented in this study. The advantage of the new method is its intelligent ability to discover malicious nodes.Originality/valueThe advantage of the new method is its intelligent ability to discover malicious nodes which can partition the network by falsely reporting other nodes as misbehaving and proceeds to protect the network. The authors have done the experiments based on the tool kits such as NS3, QualNet, OMNET++ and MATLAB. The experimental results show that this study’s approach can effectively avoid the attacks of malicious nodes, and more conformable to the actual engineering application of MANET.
Estimating the change in regional scale distribution of seagrass and macroalgal beds using discrete local distribution data analyzed from aerial images
Authors: Hamaoka Hideki , Kamiyama Takashi , Hori Masakazu 
Published: January 2020

AbstractThe sensitivity of vegetated habitats to climate change and catastrophic disturbance, as well as their benefits to human beings, motivate efforts to estimate regional changes in distribution. This study examined the regional changes in the distribution of submerged macrophyte vegetation using aerial and satellite images from before and after the 2011 tsunami disturbance along the Pacific coast of northeastern Japan. We conducted an estimation of the change in the distribution of seagrass and macroalgal beds after the tsunami along the whole coastline (1,635 km). This was based on vegetation change in the 13 local areas (each <40 km) spanning 27% of the coastline and included 28% of the macroalgal area and 59% of the seagrass area documented in satellite imagery before the tsunami, using generalized linear modeling (GLM). We found that in the 13 local areas 716.8 and 1,990.3 ha of macroalgal beds and seagrass beds had disappeared, respectively, suggesting that seagrass beds were more impacted by the tsunami than macroalgal beds. Significant predictors in GLM indicated that more seagrass beds disappeared in geographically complex coastal areas, whereas macroalgal beds were only marginally affected in such areas. It was estimated that the total decline in seagrass beds was at least 76% along the whole coastline, whereas macroalgal beds decreased only by about 20%. The magnitude and predictors of losses in these two vegetated habitats were similar to earlier estimates, suggesting that our simplified method with GLM is sufficient to extrapolate monitoring data to a regional scale.
Male flowers in Tulipa pumila Moench (Liliaceae) potentially originate from gender diphasy
Authors: Astuti Giovanni , Pratesi Sandro , Carta Angelino , Peruzzi Lorenzo 
Published: January 2020

AbstractWe found functionally male individuals in an otherwise hermaphroditic population of Tulipa pumila (Liliaceae) located in Tuscany (central Italy). We investigated the sex ratio of this population, followed by morphometric analyses of the scape, leaves and flowers, and tests on pollen germinability and seed number and mass, in order to infer which sexual strategy produced the observed co‐occurrence of male and hermaphrodite individuals. We found that sex ratio deviated from 1:1, and functionally male individuals showed a smaller plant size and a reduced pollen fitness (germinability and siring ability) compared to hermaphrodites. These findings point to a resource‐dependent sexual allocation strategy, probably associated with gender diphasy.
Mindfetalness to increase women’s awareness of fetal movements and pregnancy outcomes: a cluster‐randomised controlled trial including 39 865 women
Authors: Akselsson A , Lindgren H , Georgsson S , Pettersson K , Steineck G , Skokic V , Rådestad I 
Published: January 2020

ObjectiveTo examine whether a method for raising women's awareness of fetal movements, Mindfetalness, can affect pregnancy outcomes.DesignCluster‐randomised controlled trial.SettingSixty‐seven maternity clinics in Stockholm, Sweden.PopulationWomen with singleton pregnancy with birth from 32 weeks’ gestation.MethodsWomen registered at a clinic randomised to Mindfetalness were assigned to receive a leaflet about Mindfetalness (n = 19 639) in comparison with routine care (n = 20 226). Data were collected from a population‐based register.Main outcome measuresApgar score <7 at 5 minutes after birth, visit to healthcare due to decrease in fetal movements. Other outcomes: Apgar score <4 at 5 minutes after birth, small‐for‐gestational‐age and mode of delivery.ResultsNo difference (1.1 versus 1.1%, relative risk [RR] 1.0; 95% CI 0.8–1.2) was found between the Mindfetalness group and the Routine care group for a 5‐minute Apgar score <7. Women in the Mindfetalness group contacted healthcare more often due to decreased fetal movements (6.6 versus 3.8%, RR 1.72; 95% CI 1.57–1.87). Mindfetalness was associated with a reduction of babies born small‐for‐gestational‐age (RR 0.95, 95% CI 0.90–1.00), babies born after gestational week 41+6 (RR 0.91, 95% CI 0.83–0.98) and caesarean sections (19.0 versus 20.0%, RR 0.95; 95% CI 0.91–0.99).ConclusionsMindfetalness did not reduce the number of babies born with an Apgar score <7. However, Mindfetalness was associated with the health benefits of decreased incidence of caesarean section and fewer children born small‐for‐gestational‐age.Tweetable abstractIntroducing Mindfetalness in maternity care decreased caesarean sections but had no effect on the occurrence of Apgar scores <7.
The Impact of Corporate Sustainability and Digitalization on International Banks’ Performance
Authors: Forcadell Francisco Javier , Aracil Elisa , Úbeda Fernando 
Published: January 2020

AbstractWe analyse the implications for international banks of two contemporary megatrends: corporate sustainability (CS) and digitalization. The digital environment and the availability of massive data from customers generate asymmetric information for banks to the detriment of customers, who experience individual vulnerabilities such as privacy rights. This can hinder the positive influence of digitalization in banks’ performance, with relevant managerial and political implications. In this context, the reputation generated by CS strategies can constitute a credence factor that reduces customers’ fears of opportunistic behavior and information asymmetries. We test and find support for our hypothesis over a panel data of large international banks from developed countries. Our findings shed light on the mutual reinforcement of CS and digitalization strategies in enhancing banks’ market performance and efficiency.
Banca March: The Fundamentals of a Bank Linked to Its Customers and Committed to Society
Authors: Rodríguez Arrojo Rita 
Published: January 2020

AbstractBanca March’s history dates back almost a hundred years. It was founded in 1926 by Juan March Ordinas. We are the only family‐owned bank left in Spain; 100 per cent of the bank’s shares are owned by the March family. We are an unlisted bank, with a unique business model that sets us apart from the rest. Our unique approach is rooted in our business philosophy, shared growth, which has remained unchanged since our foundation. This philosophy allowed us to weather the turbulence of the 20th century and to emerge stronger than ever from the last financial crisis. Our long‐held motto is shared growth with all stakeholders.