bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitat filtering differentially modulates phylogenetic vs functional diversity relationships between dominant ground-dwelling arthropods in salt marshes
Authors: Ridel Aurélien , Lafage Denis , Devogel Pierre , Lacoue-Labarthe Thomas , Pétillon Julien 
Published: June 2020

AbstractWhile mechanisms underlying biological diversities at different scales received huge attention over the last decades, whether local abiotic factors driving functional and phylogenetic diversities can differ among ecologically and phylogenetically closely related taxa remains under-investigated. In this study, we compared correlations and drivers of functional (FD) and phylogenetic (PD) diversities between two dominant taxa of ground-dwelling arthropods in salt marshes, spiders and carabids. Pitfall trapping in two sampling sites of N-W France resulted in the collection and identification of more than 7000 individuals belonging to 67 species. Morphological and behavioral traits, as well as molecular sequences of COI gene, were attributed to all species for calculating functional and phylogenetic diversities respectively. Both taxa exhibited high correlation between FD and PD, which was even higher in carabids probably due to their lower species richness. Analyses using Bayesian framework and structural equation modeling revealed that FD and PD were positively influenced by taxonomic diversity in spiders and carabids, but abiotic factors driving FD and PD differed between taxa. Salinity especially drove the taxonomic diversity of carabids, but not that of spiders, suggesting that spiders are more plastic and less selected by this factor. Phylogenetic diversity was conversely influenced by salinity in spiders but not in carabids. This interesting result can be interpreted by different evolutionary history and colonization process of salt marshes between the two model taxa. Our study finally highlights that, even in taxa of the same phylum and occupying the same niche in a highly constrained habitat, functional and phylogenetic diversities can have different drivers, showing different filtering mechanisms and evolutionary history at small spatial and temporal scales.
Glutamine metabolism modulates azole susceptibility inTrypanosoma cruziamastigotes
Authors: Dumoulin Peter C. , Vollrath Joshua , Wang Jennifer X. , Burleigh Barbara A. 
Published: June 2020

AbstractThe mechanisms underlying resistance of the Chagas disease parasite,Trypanosoma cruzi,to current therapies are not well understood, including the potential role of metabolic heterogeneity in modulating susceptibility of intracellular amastigotes to trypanocidal compounds. We found that limiting exogenous glutamine protects actively dividing amastigotes from ergosterol biosynthesis inhibitors (azoles), independent of parasite growth rate. The antiparasitic properties of azoles are derived from inhibition of lanosterol 14α-demethylase (CYP51) in the endogenous sterol synthesis pathway. We find that carbons from13C-glutamine feed into amastigote sterols and into metabolic intermediates that accumulate upon CYP51 inhibition. Consistent with a model that decreased flux through the sterol biosynthetic pathway is protective for intracellular amastigotes exposed to azoles, we find that amastigotes become re-sensitized to azoles following addition of metabolites upstream of CYP51. Our results highlight the potential role of metabolic heterogeneity in recalcitrantT. cruziinfection, an avenue that is currently underexplored.
A novel gonorrhea vaccine composed of MetQ lipoprotein formulated with CpG shortens experimental murine infection
Authors: Sikora Aleksandra E. , Gomez Carolina , Le Van Adriana , Baarda Benjamin I. , Darnell Stephen , Martinez Fabian G. , Zielke Ryszard A. , Bonventre Josephine A. , Jerse Ann E. 
Published: June 2020

ABSTRACTBacterial surface lipoproteins are emerging as attractive vaccine candidates due to their biological importance and the feasibility of their large-scale production for vaccine manufacturing. The global prevalence of gonorrhea, resistance to antibiotics, and serious consequences to reproductive and neonatal health necessitate development of effective vaccines. Reverse vaccinology identified the surface-displayed L-methionine binding lipoprotein MetQ (NGO2139) and its homolog GNA1946 (NMB1946) as gonococcal and meningococcal vaccine candidates, respectively. Here, we assessed the suitability of MetQ for inclusion in a gonorrhea vaccine by examining MetQ conservation, its function inNeisseria gonorrhoeae(Ng) pathogenesis, and its ability to induce protective immune responses using a female murine model of lower genital tract infection. In-depth bioinformatics, phylogenetics and mapping the most prevalentNgpolymorphic amino acids to the GNA1946 crystal structure revealed remarkable MetQ conservation: ~97%Ngisolates worldwide possess a single MetQ variant. Mice immunized with rMetQ-CpG (n=40), a vaccine containing a tag-free version of MetQ formulated with CpG, exhibited robust, antigen-specific antibody responses in serum and at the vaginal mucosae including secretory IgA. Consistent with the activity of CpG as a Th1-stimulating adjuvant, the serum IgG1/IgG2a ratio of 0.38 indicated a Th1 bias. Combined data from two independent challenge experiments demonstrated that rMetQ-CpG immunized mice cleared infection faster than control animals (vehicle,p<0.0001; CpG,p=0.002) and had lowerNgburden (vehicle,p=0.03; CpG,p<0.0001). We conclude rMetQ-CpG induces a protective immune response that accelerates bacterial clearance from the murine lower genital tract and represents an attractive component of a gonorrhea subunit vaccine.
Glucocorticoid treatment exacerbates mycobacterial infection by reducing the phagocytic capacity of macrophages Glucocorticoids and zebrafish TB
Authors: Xie Yufei , Meijer Annemarie H. , Schaaf Marcel J.M. 
Published: June 2020

AbstractGlucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this study, we have used a larval zebrafish model for tuberculosis, based onMycobacterium marinum(Mm) infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemicMminfection. The exacerbatedMminfection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific forMm, since it was also observed upon infection withSalmonellaTyphimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.Summary statementUsing a zebrafish tuberculosis model, we show that glucocorticoids decrease phagocytosis by macrophages, thereby increasing the bacterial burden. This may explain the glucocorticoid-induced increase in susceptibility to tuberculosis in humans.
Exposure duration modulates the response of Caribbean corals to global change stressors
Authors: Aichelman HE , Bove CB , Castillo KD , Boulton JM , Knowlton AC , Nieves OC , Ries JB , Davies SW 
Published: June 2020

AbstractGlobal change is threatening coral reefs, with rising temperatures leading to repeat bleaching events (dysbiosis of coral hosts and their symbiotic algae) and ocean acidification reducing net coral calcification. Although global-scale mass bleaching events are revealing fine-scale patterns of coral resistance and resilience, traits that lead to persistence under environmental stress remain elusive. Here, we conducted a 95-day controlled-laboratory experiment to investigate how duration of exposure to ocean warming (28, 31°C), acidification (pCO2= 400–2800 μatm), and their interaction influence the physiological responses of two Caribbean reef-building coral species (Siderastrea siderea,Pseudodiploria strigosa) from two reef zones of the Belize Mesoamerican Barrier Reef System. Every 30 days, calcification rate, total host protein and carbohydrate, chlorophyllapigment concentration, and symbiont cell density were quantified for the same coral colony to characterize acclimatory responses of each genotype. Physiologies of the two species were differentially affected by these stressors, with exposure duration modulating responses.Siderastrea sidereawas most affected by extremepCO2(~2800 μatm), which resulted in reduced calcification rate, symbiont density, and chlorophyllaconcentration. Siderastrea sidereacalcification rate initially declined under extremepCO2but recovered by the final time point, and overall demonstrated resistance to next-centurypCO2and temperature stress. In contrast,P. strigosawas more negatively impacted by elevated temperature (31°C). Reductions inP. strigosacalcification rate and total carbohydrates were consistently observed over time regardless ofpCO2treatment, with the greatest reductions observed under elevated temperature. However, nearshore colonies ofP. strigosamaintained calcification rates under elevated temperature throughout all exposure durations, suggesting individuals from this environment may be locally adapted to the warmer temperatures characterizing their natal reef zone. This experiment highlights how tracking individual coral colony physiology across broad exposure durations can capture acclimatory responses of corals to global change stressors.
Strongyle-resistant sheep express their potential across environments and leave limited scope for parasite plasticity
Authors: Sallé G. , Deiss V. , Marquis C. , Tosser-Klopp G. , Cortet J. , Serreau D. , Koch C. , Marcon D. , Bouvier F. , Jacquiet P. , Holroyd N. , Blanchard A. , Cotton J.A. , Mialon M.M. , Moreno-Romieux C. 
Published: June 2020

AbstractIntroductionDrug-resistant parasites threaten livestock production. Breeding more resistant hosts could be a sustainable control strategy. Environmental variation may however alter the expression of genetic potential and directional selection toward host resistance could initiate an arms race between the host and its parasites.Methods and ResultsWe created sheep lines with high or low resistance toHaemonchus contortus. We first exposed both lines to chronic stress or to the infection by another parasiteTrichostrongylus colubriformis, to test for genotype-by-environment and genotype-by-parasite species interactions respectively. Overall, between-line divergence remained significant across environmental perturbations. But we found that the impact of chronic stress onH. contortusinfection varied among families and that divergence was reduced during infection byT. colubriformis. Second, we quantified genomic and transcriptomic differences inH. contortusworms collected from both lines to identify components of an arms race. We found no evidence of genetic differentiation between worms from each line. But survival to more resistant hosts was associated with enhanced expression of cuticle collagen coding genes.DiscussionBreeding for resistance hence remains a sustainable strategy that requires to anticipate the effects of environmental perturbations and to monitor worm populations.
SNARE Complex Alters the Interactions of the Ca2+sensor Synaptotagmin 1 with Lipid Bilayers
Authors: Bykhovskaia Maria 
Published: June 2020

AbstractRelease of neuronal transmitters from nerve terminals is triggered by the molecular Ca2+sensor Synaptotagmin 1 (Syt1). Syt1 is a transmembrane protein attached to the synaptic vesicle (SV), and its cytosolic region comprises two domains, C2A and C2B, which are thought to penetrate into lipid bilayers upon Ca2+binding. Prior to fusion, SVs become attached to the presynaptic membrane (PM) by the four-helical SNARE complex, which binds the C2B domain of Syt1. To understand how the interactions of Syt1 with lipid bilayers and the SNARE complex trigger fusion, we performed molecular dynamics (MD) simulations at a microsecond scale. The MD simulations showed that the C2AB tandem of Syt1 can either bridge SV and PM or immerse into PM, and that the latter configuration is more favorable energetically. Surprisingly, C2 domains did not cooperate in penetrating into PM, but instead mutually hindered the lipid penetration. To test whether the interaction of Syt1 with lipid bilayers could be affected by the C2B-SNARE attachment, we performed systematic conformational analysis of the Syt1-SNARE complex. Notably, we found that the C2B-SNARE interface precludes the coupling of C2 domains of Syt1 and promotes the immersion of both domains into the PM bilayer. Subsequently, we simulated this pre-fusion protein complex between lipid bilayers imitating PM and SV and found that the immersion of Syt1 into the PM bilayer within this complex promotes PM curvature and leads to lipid merging. Altogether, our MD simulations elucidated the role of the Syt1-SNARE interactions in the fusion process and produced the dynamic all-atom model of the prefusion protein-lipid complex.Statement of SignificanceNeuronal transmitters are packed in synaptic vesicles (SVs) and released by fusion of SVs with the presynaptic membrane (PM). SVs are attached to PM by the SNARE protein complex, and fusion is triggered by the Ca2+sensor Synaptotagmin 1 (Syt1). Although Syt1 and SNARE proteins have been extensively studied, it is not yet fully understood how the interactions of Syt1 with lipids and the SNARE complex induce fusion. To address this fundamental problem, we took advantage of Anton2 supercomputer, a unique computational environment, which enables simulating the dynamics of molecular systems at a scale of microseconds. Our simulations produced a dynamic all-atom model of the prefusion protein-lipid complex and demonstratedin silicohow the Syt1-SNARE complex triggers fusion.
Spatial structure and pathogen epidemics: the influence of management and stochasticity in agroecosystems
Authors: Hajian-Forooshani Zachary , Vandermeer John 
Published: June 2020

AbstractOrganisms susceptible to disease, from humans to crops, inevitably have spatial geometry that influence disease dynamics. Understanding how spatial structure emerges through time in ecological systems and how that structure influences disease dynamics is of practical importance for natural and human management systems. Here we use the annual crop, coffee,Coffea arabica, along with its pathogen, the coffee leaf rust,Haemelia vastatrix, as a model system to understand how spatial structure is created in agroecosystems and its subsequent influence on the dynamics of the system.Here, we create a simple null model of the socio-ecological process of death and stochastic replanting of coffee plants on a plot. We then use spatial networks to quantify the spatial structures and make comparisons of our stochastic null model to empirically observed spatial distributions of coffee. We then present a simple model of pathogen spread on spatial networks across a range of spatial geometries emerging from our null model and show how both local and regional management of agroecosystems interact with space and time to alter disease dynamics.Our results suggest that our null model of evolving spatial structure can capture many critical features of how the spatial arrangement of plants changes through time in coffee agroecosystems. Additionally, we find that small changes in management practices that influence the scale of pathogen transmission, such as shade tree removal, can result in a rapid transition to epidemics with lattice-like spatial arrangements but not irregular planting geometries.The results presented here may have practical implications for farmers in Latin America who are in the process of replanting and overhauling management of their coffee farms in response to a coffee leaf rust epidemic in 2013. We suggest that shade reduction in conjunction with more lattice-like planting schemes may result in coffee being more prone to epidemic-like dynamics of the coffee leaf rust in the future.
An empirical model to predict survival curve and relative biological effectiveness after helium and carbon ion irradiation based solely on the cell survival after photon irradiation
Authors: Flint David B. , Bright Scott J. , McFadden Conor H. , Konishi Teruaki , Ohsawa Daisuke , Kobayashi Alisa , Shaitelman Simona F. , Sawakuchi Gabriel O. 
Published: June 2020

ABSTRACTPurposeTo develop an empirical model to predict radiosensitivity and relative biological effectiveness (RBE) after helium (He) and carbon (C) ion irradiation with or without DNA repair inhibitors.MethodsWe characterized survival in eight human cancer cell lines exposed to 6 MV photons and to He- and C-ions with linear energy transfer (LET) values of 2.2-60.5 keV/μm to verify that the radiosensitivity parameters (D5%, D10%, D20%, D37%, D50%and SF2Gy) correlate linearly between photon and ion radiation with or without DNA-PKcs or ATR inhibitors. Then, we parameterized the LET response of the parameters governing these linear correlations up to LET values of 225 keV/μm using the data in the Particle Irradiation Data Ensemble (PIDE) v3.2 database, creating a model that predicts a cell’s ion radiosensitivity, RBE and ion survival curve for a given LET on the basis of the cell’s photon radiosensitivity. We then trained this model using the PIDE database as a training dataset, and validated it by predicting the radiosensitivity of the cell lines we exposed to He- and C- ions with LET ranging from 2.2-60.5 keV/μm.ResultsRadiosensitivity to ions depended linearly with radiosensitivity of photons in the range of investigated LET values and the slopes and intercepts of these linear relationships within the PIDE database vary exponentially and linearly, respectively. Our model predicted ion radiosensitivity (e.g., D10%) within 5.1–21.3%, RBED10%within 5.0-17.1%, and ion mean inactivation dose within 6.7-25.1% for He- and C-ion LET ranging from 2.2-60.5 keV/μm.ConclusionsRadiosensitivity to He- and C-ions depend linearly with radiosensitivity to photons and can be used to predict ion radiosensitivity, RBE and cell survival curves for clinically relevant LET values from 2.2–60.5 keV/μm, with or without drug treatment.SUMMARYWe present a new empirical model capable of predicting clonogenic cell survival of cell lines exposed to helium and carbon ion beams. Our model is based on an observed linear correlation between radiosensitivity to ions and photons across a wide range of LET values. This linear correlation can be used to predict ion RBE, radiosensitivity, and the cell survival curve for a given LET all based on a cell’s photon survival curve.
Lineage-Specific Silencing ofPSAT1Induces Serine Auxotrophy and Sensitivity to Dietary Serine Starvation in Luminal Breast Tumors
Authors: Choi Bo-Hyun , Conger Kelly O. , Selfors Laura M. , Coloff Jonathan L. 
Published: June 2020

SUMMARYA major challenge of targeting metabolism for cancer therapy is pathway redundancy, where multiple sources of critical nutrients can limit the effectiveness of some metabolism-targeted therapies. Here, we analyzed lineage-dependent gene expression in human breast tumors to identify differences in metabolic gene expression that may limit pathway redundancy and create therapeutic vulnerabilities. We found that the serine synthesis pathway genePSAT1is the most depleted metabolic gene in luminal breast tumors relative to basal tumors. Low PSAT1 preventsde novoserine biosynthesis and sensitizes luminal breast cancer cells to serine and glycine starvationin vitroandin vivo. ThisPSAT1expression disparity—which pre-exists in the putative cells-of-origin of basal and luminal tumors—is due to luminal-specific hypermethylation of thePSAT1gene. Together, our data demonstrates that luminal breast tumors are auxotrophic for serine and may be uniquely sensitive to dietary serine starvation.
Lung at a Glance: an integrative web toolset of lung ontology, imaging and single cell omics
Authors: Du Yina , Ouyang Weichen , Kitzmiller Joseph A , Guo Minzhe , Zhao Shuyang , Whitsett Jeffrey A , Xu Yan 
Published: June 2020

ABSTRACTRecent advances in single-cell omics and high-resolution imaging have provided unanticipated data resources for the elucidation of genes underlying the complex biological processes critical for organ formation and function. However, processing and integrating large amounts of single-cell omics and imaging data presents a major challenge for most researchers. There is a critical need for ready-to-use computational tools for data/knowledge integration and visualization. Here we present “Lung-at-a-glance”, an easy-to-use web toolset for visualizing and interoperating complex omics and imaging data, providing an interactive web interface to bridge lung anatomic ontology classifications to lung histology and immunofluorescence confocal images, and cell-type-specific gene expression. “Lung-at-a-glance” contains three interactive components: 1) “Region at a glance”, 2) “Cell at a glance” and 3) “Gene at a glance”. “Lung-at-a-glance” and other newly developed web tools for lung-related data query, integration and visualization are publicly available on LGEA web portal v3https://research.cchmc.org/pbge/lunggens/mainportal.html.
The instantaneous multi-pronged defense system of latex against general plant enemies
Authors: Salomé-Abarca Luis Francisco , Gođevac Dejan , Kim Min Sun , Hwang Geum-Sook , Park Sang Cheol , Jang Young Pyo , Cees A. M. J. J. van den Hondel , Verpoorte Robert , Klinkhamer Peter G. L. , Choi Young Hae 
Published: June 2020

AbstractBased on the hypothesis that variation of the metabolomes of latex is a response to selective pressure and should thus be affected differently from other organs, their variation could provide insight into the defensive chemical selection of plants. Metabolic profiling was utilized to compare tissues ofEuphorbiaspecies collected in various regions. The metabolic variation of latexes was much more limited than that of other organs. In all of the species, the levels of polyisoprenes and terpenoids were found to be much higher in latexes than in leaves and roots. Polyisoprenes were also observed to physically delay the contact and growth of pathogens with plant tissues. A secondary barrier composed of terpenes and, in particular, 24-methylenecycloartanol, exhibited antifungal activity. These results, together with the known roles of the enzymes also present in latexes, demonstrate that they are part of a cooperative defense system that comprises both biochemical and physical elements.