bluuebunny/crossref_metadata_2025_split huggingface dataset:
FMN-dependent oligomerization of putative lactate oxidase fromPediococcus acidilactici
Authors: Ashok Yashwanth , Maksimainen Mirko M. , Kallio Tuija , Kilpeläinen Pekka , Lehtiö Lari 
Published: October 2019

AbstractLactate oxidases belong to a group of FMN-dependent enzymes and they catalyze a conversion of lactate to pyruvate with a release of hydrogen peroxide. Hydrogen peroxide is also utilized as a read out in biosensors to quantitate lactate levels in biological samples.Aerococcus viridanslactate oxidase is the best characterized lactate oxidase and our knowledge of lactate oxidases relies largely to studies conducted with that particular enzyme.Pediococcus acidilacticilactate oxidase is also commercially available for e.g. lactate measurements, but this enzyme has not been characterized before in detail. Here we report structural characterization of the recombinant enzyme and its co-factor dependent oligomerization. The crystal structures revealed two distinct conformations in the loop closing the active site, consistent with previous biochemical studies implicating the role of loop in catalysis. Despite the structural conservation of active site residues when compared toAerococcus viridanslactate oxidase we were not able to detect either oxidase or monooxygenase activity when L-lactate or other potential alpha hydroxyl acids were used as a substrate.Pediococcus acidilacticilactate oxidase is therefore an example of a misannotation of an FMN-dependent enzyme, which catalyzes likely a so far unknown oxidation reaction.
Modeling Dragons: Using linked mechanistic physiological and microclimate models to explore environmental, physiological, and morphological constraints on the early evolution of dinosaurs
Authors: Lovelace David M. , Hartman Scott A. , Mathewson Paul D. , Linzmeier Benjamin J. , Porter Warren P. 
Published: October 2019

AbstractWe employed the widely-tested biophysiological modeling software, Niche Mapper™ to investigate the metabolic function of Late Triassic dinosaursPlateosaurusandCoelophysisduring global greenhouse conditions. We tested them under a variety of assumptions about resting metabolic rate, evaluated within six microclimate models that bound paleoenvironmental conditions at 12° N paleolatitude, as determined by sedimentological and isotopic proxies for climate within the Chinle Formation of the southwestern United States. Sensitivity testing of metabolic variables and simulated “metabolic chamber” analyses support elevated “ratite-like” metabolic rates and intermediate “monotreme-like” core temperature ranges in these species of early saurischian dinosaur. Our results suggest small theropods may have needed partial to full epidermal insulation in temperate environments, while fully grown prosauropods would have likely been heat stressed in open, hot environments and should have been restricted to cooler microclimates such as dense forests (under any vegitative cover) or those seen at higher latitudes and elevations. This is in agreement with the Late Triassic fossil record and may have contributed to the latitudinal gap in the Triassic prosauropod record.
The dynamics and interactions of respiratory pathogen carriage among French pilgrims during the 2018 Hajj
Authors: Hoang Van-Thuan , Dao Thi-Loi , Ly Tran Duc Anh , Belhouchat Khadidja , Chaht Kamel Larbi , Gaudart Jean , Mrenda Bakridine Mmadi , Drali Tassadit , Yezli Saber , Alotaibi Badriah , Fournier Pierre-Edouard , Raoult Didier , Parola Philippe , de Santi Vincent Pommier , Gautret Philippe 
Published: October 2019

AbstractRespiratory tract infections are frequent among Hajj pilgrims. We conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (LRTI) among French pilgrims during the 2018 Hajj. Pilgrims from Marseille who were participating in the Hajj were recruited. Each participant underwent four successive systematic nasopharyngeal swabs before and during their stay in Saudi Arabia. Carriage of the main respiratory pathogens was assessed by PCR. 121 pilgrims were included and 93.4% reported respiratory symptoms during the study period. Polymicrobial carriage was observed in 73.8% samples. The acquisition of rhinovirus, coronaviruses and Staphylococcus aureus occurred soon after arrival in Saudi Arabia and rates decreased gradually after days 5 and 6. In contrast, Streptococcus pneumoniae and Klebsiella pneumoniae carriage increased progressively until the end of the stay in Saudi Arabia. Haemophilus influenzae and Moraxella catarrhalis carriage increased starting around days 12 and 13, following an initial clearance. Influenza viruses were rarely isolated. We observed an independent positive mutual association between S. aureus and rhinovirus carriage and between H. influenzae and M. catarrhalis carriage. Dual carriage of H. influenzae and M. catarrhalis was strongly associated with S. pneumoniae carriage (OR = 6.22, 95%CI [2.04-19.01]). Finally, our model showed that M. catarrhalis carriage was negatively associated with K. pneumoniae carriage. Chronic respiratory disease was associated with symptoms of LRTI. K. pneumoniae, M. catarrhalis-S. aureus and H. influenzae-rhinovirus dual carriage was associated with LRTI symptoms. Our data suggest that RTIs at the Hajj are a result of complex interactions between a number of respiratory viruses and bacteria.Author summaryDespite the recommendation to take individual preventive measures to prevent respiratory tract infections, these infections remain common among Hajj pilgrims. Respiratory pathogens acquired during the Hajj are usually studied individually, although in their natural environment they often compete or coexist with multiple microbial species. A better understanding of polymicrobial interactions in the nasopharynx among Hajj pilgrims is important. Our study describes the dynamics of the acquisition of respiratory pathogens and their potential interactions among pilgrims during the Hajj. We found that polymicrobial carriage was observed in most individuals and that some pathogens associated positively while other did not. Some pathogen associations correlated with symptoms of lower respiratory tract infections.
A wave of embryonic bipotent T/lymphoid tissue inducer progenitors regulates the maturation of medullary thymic epithelial cells
Authors: Elsaid Ramy , Meunier Sylvain , Burlen-Defranoux Odile , Soares-da-Silva Francisca , Perchet Thibaut , Iturri Lorea , Freyer Laina , Vieira Paulo , Pereira Pablo , Golub Rachel , Bandeira Antonio , Perdiguero Elisa Gomez , Cumano Ana 
Published: October 2019

SUMMARYMultiple waves of hematopoietic progenitors with distinct lineage potentials are differentially regulated in time and space. We show that the first thymic seeding progenitors comprise a unique population of bipotent cells that generate lymphoid tissue inducer and invariant Vγ5+ T cells. Both populations are of embryonic origin and induce the maturation of medullary thymic epithelial cells. Indeed, temporal depletion of the first wave of thymocytes results in a five-fold reduction of mature medullary thymic epithelial cells, after birth. We further show that these progenitors are of hematopoietic stem cell, and not, of yolk sac origin, despite the temporal overlap between the onset of lymphopoiesis and the transient expression of lymphoid transcripts in yolk sac precursors, that does not impact their strict erythro-myeloid potential. Our work highlights the relevance of the developmental timing on the emergence of different lymphoid subsets required for the establishment of a functionally diverse immune system.
Multiple environmental signaling pathways control the differentiation of RORγt-expressing regulatory T cells
Authors: Hussein Hind , Denanglaire Sébastien , Van Gool Frédéric , Azouz Abdulkader , Ajouaou Yousra , El-Khatib Hana , Oldenhove Guillaume , Leo Oberdan , Andris Fabienne 
Published: October 2019

AbstractRORγt-expressing Tregs form a specialized subset of intestinal CD4+ Foxp3+ cells which is essential to maintain gut homeostasis and tolerance to commensal microbiota. Recently, c-Maf emerged as a critical factor in the regulation of RORγt expression in Tregs. However, aside from c-Maf signaling, the signaling pathways involved in the differentiation of RORγt+ Tregs and their possible interplay with c-Maf in this process are largely unknown. We show that RORγt+ Treg development is controlled by positive as well as negative signals. Along with c-Maf signaling, signals derived from a complex microbiota, as well as IL-6/STAT3- and TGF-β-derived signals act in favor of RORγt+ Treg development. Ectopic expression of c-Maf did not rescue RORγt expression in STAT3-deficient Tregs, indicating the presence of additional effectors downstream of STAT3. Moreover, we show that an inflammatory IFN-γ/STAT1 signaling pathway acts as a negative regulator of RORγt+ Treg differentiation in a c-Maf independent fashion.These data thus argue for a complex integrative signaling network that finely tunes RORγt expression in Tregs. The finding that type 1 inflammation impedes RORγt+ Treg development even in the presence of an active IL-6/STAT3 pathway further suggests a dominant negative effect of STAT1 over STAT3 in this process.
Context dependency of biotic interactions and its relation to plant rarity
Authors: Kempel Anne , Vincent Hugo , Prati Daniel , Fischer Markus 
Published: October 2019

AbstractAimBiotic interactions can determine rarity and commonness of species, however evidence that rare and common species respond differently to biotic stress is scarce. This is because biotic interactions are notoriously context-dependent and traits leading to success in one habitat might be costly or unimportant in another. We aim to identify plant characteristics that are related to biotic interactions and may drive patterns of rarity and commonness, taking environmental context into account.LocationSwitzerlandMethodsIn a multi-species experiment, we compared the response to biotic interactions of 19 rare and 21 widespread congeneric plant species in Switzerland, while also accounting for variation in environmental conditions of the species’ origin.ResultsOur results restrict the long-standing hypothesis that widespread species are superior competitors to rare species to only those species originating from resource rich habitats, in which competition is usually strong. Tolerance to herbivory and ambient herbivore damage on the other hand, did not differ between widespread and rare species. In accordance to the resource-availability hypothesis, widespread species from resource rich habitats where more damaged by herbivores (less defended) than widespread species from resource poor habitats – such a growth-defense tradeoff was lacking in rare species. This indicates that the evolutionary important tradeoff between traits increasing competitive-ability and defence is present in widespread species but may have been lost in rare species.Main conclusionsOur results indicate that biotic interactions, above all competition, might indeed set range limits, and underlines the importance of including context-dependency in studies comparing traits of common and rare or invasive and non-invasive species.
Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats
Authors: Freels Timothy G. , Baxter-Potter Lydia N. , Lugo Janelle M. , Glodosky Nicholas C. , Wright Hayden R. , Baglot Samantha L. , Petrie Gavin N. , Yu Z , Clowers Brian H. , Cuttler Carrie , Fuchs Rita A. , Hill Matthew N. , McLaughlin Ryan J. 
Published: October 2019

ABSTRACTRecent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.
ATP-driven separation of liquid phase condensates in bacteria
Authors: Guilhas B. , Walter J.C. , Rech J. , David G. , Walliser N.-O. , Palmeri J. , Mathieu-Demaziere C. , Parmeggiani A. , Bouet J.Y. , Le Gall A. , Nollmann M. 
Published: October 2019

AbstractLiquid-liquid phase separated (LLPS) states are key to compartmentalise components in the absence of membranes, however it is unclear whether LLPS condensates are actively and specifically organized in the sub-cellular space and by which mechanisms. Here, we address this question by focusing on the ParABSDNA segregation system, composed of a centromeric-like sequence (parS), a DNA-binding protein (ParB) and a motor (ParA). We show thatparS-ParB associate to form nanometer-sized, round condensates. ParB molecules diffuse rapidly within the nucleoid volume, but display confined motions when trapped inside ParB condensates. Single ParB molecules are able to rapidly diffuse between different condensates, and nucleation is strongly favoured byparS. Notably, the ParA motor is required to prevent the fusion of ParB condensates. These results describe a novel active mechanism that splits, segregates and localises non-canonical LLPS condensates in the sub-cellular space.
Effects of Substrate Stiffness on Neutrophil Adhesion over L-selectin Coated Endothelial
Authors: Guillory Claude , Dufour Alice O. 
Published: October 2019

AbstractRolling of a cell under a hydrodynamic flow like the blood flow and the mechanism for the adhesion of a cell to the blood vessel is one of the fundamental process in many pathological and biological processes. An important example of these processes is inflammatory response and moving of the leukocytes to the sites of inflammation. While the blood-borne cells travel with the blood flow, they can interact with the inner endothelium’s wall, which is composed of a soft layer of endothelial cells. Not until recently, the effect of endothelial stiffness was poorly understood. Recent in-vitro and computational models, like modified Adhesive Dynamics, have shown that the elasticity of the underlying substrate can alter the rolling and adhesion of a cell. In this study, we investigate the effects of the substrate stiffness on the rolling and adhesion of a cell with neutrophil ligands by using the Adhesive Dynamic simulation. The vessel is modeled as an elastic surface coated with L-selectin molecules, which can form bonds with the ligands. In our simulation, the Young modulus of the surface ranges between 5 to 80 kPa. The results show that the softer substrate helps to capture the cell with neutrophil ligands. These results help us to understand how the state of adhesion changes for the neutrophil adhesion over L-selectin.
NASH patient liver derived organoids exhibit patient specific NASH phenotypes and drug responses
Authors: McCarron S. , Bathon B. , Abbey D. , Conlon D. M. , Rader D.J. , Olthoff K. , Shaked A. , Raabe T.D. 
Published: October 2019

AbstractTo determine if patient liver derived organoids can in principle be a useful experimental model for non alcoholic staetohepatitis (NASH), we derived to our knowledge for the first time bipotent ductal organoids from endstage NASH patient livers, and for comparison from normal donor livers. We found that all tested NASH liver derived organoids exhibited a profound failure to dedifferentiate from the hepatic state back to the biliary state, consistent with the known poor regenerative capacity of NASH livers. Indeed, RNAseq on all tested NASH organoid populations confirmed down regulation of multiple cell cycle pathways. NASH liver derived hepatically differentiated organoids can slowly expand as monolayers, significantly simplifying microscopic quantitation: The monolayers show variable, but overall significantly increased lipid droplet accumulation in response to free fatty acids. Transcriptome analysis of NASH organoids reveals strong upregulation of a wide variety of pro inflammatory pathways in a NASH patient specific manner. Surprisingly, NASH liver derived organoids are highly diverse not only regarding their cytochrome cytochrome p450 metabolism and inflammatory response, but also react differentially to known antisteatotic, anti inflammatory and antifibrotic drugs, raising the possibility of using NASH patient liver biopsy derived organoids for personalized drug screening and therapy.One Sentence SummaryNASH patient liver derived organoids replicate NASH liver phenotypes in a patient specific manner and exhibit profound differences in their response to drugs that are currently used in NASH clinical trials.
MicroRNA miR-7 regulates synthesis and secretion of insulin-like peptides
Authors: Agbu Pamela , Cassidy Justin J. , Braverman Jonathan , Jacobson Alec , Carthew Richard W 
Published: October 2019

AbstractThe insulin/IGF pathway is essential for linking nutritional status to growth and metabolism. MicroRNAs (miRNAs) are short RNAs that are players in the regulation of this process. The miRNA miR-7 shows highly conserved expression in insulin-producing cells across the animal kingdom, however, its conserved functions in regulation of insulin-like peptides (ILPs) remains unknown. Using Drosophila as a model, we demonstrate that miR-7 limits ILP availability by inhibiting its production and secretion. Increasing miR-7 alters body growth and metabolism in an ILP-dependent manner, elevating circulating sugars and total body triglycerides, while decreasing animal growth. These effects are not due to direct targeting of ILP mRNA, but instead arise through alternate targets that affect the function of ILP-producing cells. The Drosophila F-actin capping protein, CPA, is a direct target of miR-7, and knockdown of CPA in IPCs phenocopies the effects of miR-7 on ILP secretion. This regulation of CPA is conserved in mammals, with the mouse ortholog Capza1 also targeted by miR-7 in β-islet cells. Taken together, these results support a role for miR-7 regulation of an actin capping protein in insulin regulation, and highlight a conserved mechanism of action for an evolutionarily ancient microRNA.Disclosure StatementPA, JB, AJ and RWC have nothing to declare. JJC is an employee of Sg2, LLC, a healthcare consulting company.
Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender
Authors: Fleming Stephen J. , Chaffin Mark D. , Arduini Alessandro , Akkad Amer-Denis , Banks Eric , Marioni John C. , Philippakis Anthony A. , Ellinor Patrick T. , Babadi Mehrtash 
Published: October 2019

AbstractDroplet-based single-cell assays, including scRNA-seq, snRNA-seq, and CITE-seq, produce a significant amount of background noise counts, the hallmark of which is non-zero counts in cell-free droplets and off-target gene expression in unexpected cell types. The presence of such systematic background noise is a potential source of batch effect and spurious differential gene expression. Here we develop a deep generative model for noise-contaminated data that is structured to reflect the phenomenology of background noise generation in droplet-based single-cell assays. The proposed model successfully distinguishes cell-containing from cell-free droplets without supervision, learns the profile of background noise, and retrieves a noise-free quantification in an end-to-end fashion. We present a scalable and robust implementation of our method as a module in the open-source software package CellBender. We show that CellBender operates close to the theoretically optimal denoising limit in simulated datasets, and present extensive evaluations using real datasets and experimental benchmarks drawn from different tissues, protocols, and modalities to show that CellBender significantly improves the agreement of droplet-based single-cell data with established gene expression patterns, and that the learned background noise profile provides evidence for degraded or uncaptured cell types.
Modeling of combustion of moving porous magnesium particle considering variable particle size
Authors: Maghsoudi Peyman , Bidabadi Mehdi 
Published: October 2019

Purpose
The purpose of this study is to describe the combustion of a magnesium particle falling into a hot oxidizer medium.

Design/methodology/approach
The governing equations, including mass, momentum and energy conservation equations, are numerically solved. Afterward, the influences of effective parameters on the temperature distribution and burning time are investigated. Artificial neural network (ANN) is applied to approximate the particle temperature as a function of time, diameter and porosity factor. To obtain the best arrangement of the ANN structure, an optimization process is conducted.

Findings
The results show that by considering variations of the particle size, the maximum temperature increases compared to the case in which the particle diameter is constant. Also, the ignition and burning times and the maximum temperature of the moving particle are lower than those of the motionless particle. Optimum network has the best values of regression coefficient and mean relative error whose values are found to be 0.99991 and 1.58 per cent, respectively.

Originality/value
In this study, particle size varies over the combustion process that leads to calculation of particle burning time. In addition, the effects of the motion and porosity of the particle are examined.