bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in Sprague-Dawley and Wistar rats
Authors: Taffe Michael A. , Creehan K. M. , Vandewater Sophia A. , Kerr Tony M. , Cole Maury 
Published: February 2019

AbstractA novel inhalation system based on e-cigarette technology has been recently shown to produce hypothermic and anti-nociceptive effects of Δ9-tetrahydrocannabinol (THC) in rats. Indirect comparison of some prior investigations suggested differential impact of inhaled THC between Wistar (WI) and Sprague-Dawley (SD) rats, thus this study was conducted to directly compare the strains.Groups (N=8 per strain) of age matched male SD and WI rats were prepared with radiotelemetry devices to measure temperature and then exposed to vapor from the propylene glycol (PG) vehicle or THC (25, 100, 200 mg/mL of PG) for 30 or 40 minutes. Additional studies evaluated plasma THC levels and anti-nociceptive effects after THC inhalation as well as the thermoregulatory effect of intraperitoneal injection of THC (5-30 mg/kg).Hypothermic effects of inhaled THC was more pronounced in SD rats however plasma levels of THC were identical across strains under either fixed inhalation conditions or injection of a mg/kg equivalent dose. Strain differences in hypothermia were even more pronounced after i.p. injection of THC with SD rats exhibiting dose-dependent temperature reduction after 5 or 10 mg/kg, i.p. and the WI rats only exhibiting significant hypothermia after 20 mg/kg, i.p. The anti-nociceptive effects of inhaled THC (100, 200 mg/mL) did not differ significantly across the strains. These studies confirm an insensitivity of WI rats, compared with SD rats, to the hypothermia induced by THC following inhalation conditions that produced identical plasma THC and anti-nociception. Thus strain differences were not due to differential THC delivery via vapor inhalation.
Quantitative prediction of enhancer-promoter interactions
Authors: Belokopytova P.S. , Mozheiko E.A. , Nuriddinov M.A. , Fishman D. , Fishman V. 
Published: February 2019

AbstractRecent experimental and computational efforts provided large datasets describing 3-dimensional organization of mouse and human genomes and showed interconnection between expression profile, epigenetic status and spatial interactions of loci. These interconnections were utilized to infer spatial organization of chromatin, including enhancer-promoter contacts, from 1-dimensional epigenetic marks. Here we showed that predictive power of some of these algorithms is overestimated due to peculiar properties of biological data. We proposed an alternative approach, which gives high-quality predictions of chromatin interactions using only information about gene expression and CTCF-binding. Using multiple metrics, we confirmed that our algorithm could efficiently predict 3-dimensional architecture of normal and rearranged genomes.
Will climate change affect sugar beet establishment of the 21st century? Insights from a simulation study using a crop emergence model
Authors: Lamichhane Jay Ram , Constantin Julie , Aubertot Jean-Noël , Dürr Carolyne 
Published: February 2019

AbstractOngoing climate change has been reported to have far-reaching impact on crop development and yield in many regions of the globe including Europe. However, little is known about the potential impact of climate change on specific stages of the crop cycle including crop establishment, although it is a crucial stage of the annual crop cycles. For the first time, we performed a simulation study to pinpoint how sugar beet sowing conditions of the next eight decades will be altered under future climate change and if these variations will affect sowing dates, germination and emergence as well as bolting rates of this crop. We chose Northern France as an important study site, representative of sugar beet growing basin in Northern Europe. Sugar beet emergence simulations were performed for a period between 2020 and 2100, taking into account five sowing dates (mid-February, 1st March, mid-March, 1st April and mid-April). Soil water contents and temperatures in the 0-10 cm soil horizon were first simulated with the STICS soil-crop model using the most pessimistic IPCC scenario (RCP 8.5) to feed the SIMPLE crop emergence model. We also evaluated the probability of field access for the earlier sowings, based on the amount of cumulated rainfall during February and March. When analyzed by sowing date and for successive 20-year period from 2020 to 2100, there was a significant increase in seedbed temperatures by 2°C after 2060 while no change in cumulative rainfall was found before and after sowings, compared with the past. Emergence rate was generally higher for 2081-2100, while time to reach the maximum emergence rate decreased by about one week, compared with other periods, due to higher average seedbed temperatures. The rate of non-germinated seeds decreased, especially for the earlier sowing dates, but the frequency of non-emergence due to water stress increased after 2060 for all sowing dates, including the mid-February sowing. Bolting remains a risk for sowings before mid-March although this risk will be markedly decreased after 2060. The changes in seedbed conditions will be significant after 2060 in terms of temperatures. However, the possibility of field access will be a main limiting factor for earlier sowings, as no significant changes in cumulative rainfall, compared with the past, will occur under future climate change. When field access is not a constraint, an anticipation of the sowing date, compared to the currently practiced sowing (i.e. mid-March), will lead to decreased risks for the sugar beet crop establishment and bolting. The use of future climate scenarios coupled with a crop model allows a precise insight into the future sowing conditions, and provide helpful information to better project future farming systems.
Characterization of Pch2 localization determinants reveals a nucleolar-independent role in the meiotic recombination checkpoint
Authors: Herruzo Esther , Santos Beatriz , Freire Raimundo , Carballo Jesús A. , San-Segundo Pedro A. 
Published: February 2019

ABSTRACTThe meiotic recombination checkpoint blocks meiotic cell cycle progression in response to synapsis and/or recombination defects to prevent aberrant chromosome segregation. The evolutionarily-conserved budding yeast Pch2TRIP13AAA+ ATPase participates in this pathway by supporting phosphorylation of the Hop1HORMADadaptor at T318. In the wild type, Pch2 localizes to synapsed chromosomes and to the unsynapsed rDNA region (nucleolus), excluding Hop1. In contrast, in synaptonemal complex (SC)-defectivezip1Δmutants, which undergo checkpoint activation, Pch2 is detected only on the nucleolus. Alterations in some epigenetic marks that lead to Pch2 dispersion from the nucleolus suppresszip1Δ-induced checkpoint arrest. These observations have led to the notion that Pch2 nucleolar localization could be important for the meiotic recombination checkpoint. Here we investigate how Pch2 chromosomal distribution impacts on checkpoint function. We have generated and characterized several mutations that alter Pch2 localization pattern resulting in aberrant Hop1 distribution and compromised meiotic checkpoint response. Besides the AAA+ signature, we have identified a basic motif in the extended N-terminal domain critical for Pch2’s checkpoint function and localization. We have also examined the functional relevance of the described Orc1-Pch2 interaction. Both proteins colocalize in the rDNA, and Orc1 depletion during meiotic prophase prevents Pch2 targeting to the rDNA allowing unwanted Hop1 accumulation on this region. However, Pch2 association with SC components remains intact in the absence of Orc1. We finally show that checkpoint activation is not affected by the lack of Orc1 demonstrating that, in contrast to previous hypotheses, nucleolar localization of Pch2 is actually dispensable for the meiotic checkpoint.
An ex vivo tissue model of cartilage degradation suggests that cartilage state can be determined from secreted key protein patterns
Authors: Neidlin Michael , Chantzi Efthymia , Macheras George , Gustafsson Mats G , Alexopoulos Leonidas G 
Published: February 2019

AbstractThe pathophysiology of osteoarthritis (OA) involves dysregulation of anabolic and catabolic processes associated with a broad panel of cytokines and other secreted proteins and ultimately lead to cartilage degradation. An increased understanding about the interactions of these proteins by means of systematic in vitro analyses may give new ideas regarding pharmaceutical candidates for treatment of OA and related cartilage degradation.Therefore, first an ex vivo tissue model of cartilage degradation was established by culturing full thickness tissue explants with bacterial collagenase II. Then responses of healthy and degrading cartilage were analyzed by measuring protein abundance in tissue supernatant with a 26-multiplex protein profiling assay, after exposing them to a panel of 55 protein stimulations present in synovial joints of OA patients. Multivariate data analysis including exhaustive pairwise variable subset selection was used to identify the most outstanding changes in the measured protein secretions. This revealed that the MMP9 response is outstandingly low in degraded compared to healthy cartilage and that there are several protein pairs like IFNG and MMP9 that can be used for successful discrimination between degraded and healthy samples.Taken together, the results show that the characteristic changes in protein responses discovered seem promising for accurate detection/diagnosis of degrading cartilage in general and OA in particular. More generally the employed ex vivo tissue model seems promising for drug discovery and development projects related to cartilage degradation, for example when trying to uncover the unknown interactions between secreted proteins in healthy and degraded tissues.
Efficient Electric Field Simulations for Transcranial Brain Stimulation
Authors: Saturnino Guilherme B , Madsen Kristoffer H , Thielscher Axel 
Published: February 2019

AbstractObjectiveTranscranial magnetic stimulation (TMS) and transcranial electric stimulation (TES) modulate brain activity non-invasively by generating electric fields either by electromagnetic induction or by injecting currents via skin electrodes. Numerical simulations based on anatomically detailed head models of the TMS and TES electric fields can help us to understand and optimize the spatial stimulation pattern in the brain. However, most realistic simulations are still slow, and their numerical accuracy and the factors that influence it have not been evaluated in detail so far.ApproachWe present and validate a new implementation of the Finite Element Method (FEM) for TMS and TES that is based on modern algorithms and libraries. We also evaluate the convergence of the simulations and give estimates for the discretization errors.Main resultsComparisons with analytical solutions for spherical head models validate our new FEM implementation. It is five to ten times faster than previous implementations. The convergence results suggest that accurately capturing the tissue geometry in addition to choosing a sufficiently high mesh density is of fundamental importance for accurate simulations.SignificanceThe new implementation allows for a substantial increase in computational efficiency of TMS and TES simulations. This is especially relevant for applications such as the systematic assessment of model uncertainty and the optimization of multi-electrode TES montages. The results of our systematic error analysis allow the user to select the best tradeoff between model resolution and simulation speed for a specific application. The new FEM code will be made openly available as a part of our open-source software SimNIBS 3.0.
Rectal swabs in critically-ill patients provide discordant representations of the gut microbiome compared to stool samples: a brief methodologic report
Authors: Fair Katherine , Dunlap Daniel G. , Fitch Adam , Morris Alison , McVerry Bryan J. , Kitsios Georgios D. 
Published: February 2019

AbstractThe role of the gut microbiome in critical illness is being actively investigated, but the optimal sampling methods for sequencing studies of gut microbiota remain unknown. Stool samples are generally considered gold-standard but are not practical to obtain in the intensive care unit (ICU), and thus, rectal swabs are often used. However, the reliability of rectal swabs for gut microbiome profiling has not been established in this clinical setting. In this study, we compared 16S rRNA gene sequencing results between rectal swab and stool samples collected at three timepoints in mechanically-ventilated critically-ill adults. Rectal swabs comprised 89% of samples collected at the baseline timepoint, but stool samples became more available at later time-points. Significant differences in alpha and beta-diversity between rectal swabs and stool samples were observed (p<0.003), but these differences were primarily due to baseline samples. Higher relative abundance of Actinobacteria phyla (typically skin microbes) was present in rectal swabs compared to stool samples (p<0.02), a difference that was attenuated overtime. The progressive similarity of rectal swabs and stool samples likely results from increasing stool coating of the rectal vault and direct soiling of the rectal swabs taken at later time points. Therefore, inferences about the role of the gut microbiome in critical illness should be drawn cautiously and take into account the actual type and timing of samples analyzed.Statement of ImportanceRectal swabs are considered reliable alternatives to stool samples for gut microbiome profiling in outpatients or healthy adults, but their reliability in critically-ill patients has not been defined. Because stool sampling is not practical or often feasible in the intensive care unit, we performed a detailed comparison of gut microbial sequencing profiles between rectal swabs vs. stool samples in a longitudinal cohort of critically-ill patients. We identified systematic differences in gut microbial profiles between rectal swabs and stool samples, and highlighted that timing of rectal swabbing had a significant impact on sequencing results. Our methodological findings should inform future investigations of the role of the gut microbiome in critical illness.
Conservation and flexibility in the gene regulatory landscape of Heliconiine butterfly wings
Authors: Hanly Joseph J , Wallbank Richard WR , McMillan W Owen , Jiggins Chris D 
Published: February 2019

AbstractBackgroundMany traits evolve bycis-regulatory modification, by which changes to non-coding sequences affect the binding affinity for available transcription factors and thus modify the expression profile of genes. Multiple examples ofcis-regulatory evolution have been described at pattern switch genes responsible for butterfly wing pattern polymorphism, including in the diverse neotropical genusHeliconius, but the identities of the factors that can regulate these switch genes have not been identified.ResultsWe investigated the spatial transcriptomic landscape across the wings of three closely related butterfly species, two of which have a convergently-evolved, co-mimetic pattern, the other having a divergent pattern. We identified candidate factors for regulating the expression of wing patterning genes, including transcription factors with a conserved expression profile in all three species, and others, including both transcription factors and Wnt pathway genes, with markedly different profiles in each of the three species. We verified the conserved expression profile of the transcription factor homothorax by immunofluorescence, and showed that its expression profile strongly correlates with that of the selector gene optix in butterflies with the Amazonian forewing pattern element ‘dennis’.ConclusionsHere we show that, in addition to factors with conserved expression profiles like homothorax, there are also a variety of transcription factors and signaling pathway components that appear to vary in their expression profiles between closely related butterfly species, highlighting the importance of genome-wide regulatory evolution between species.
‘Simultaneous tracking of cell motility in liquid and at the solid-liquid interface’
Authors: Hook Andrew L. , Flewellen James L. , Zaid Irwin M. , Berry Richard M. , Dubern Jean-Frédéric , Carabelli Alessandro , Wildman Ricky , Russell Noah , Williams Paul , Alexander Morgan R. 
Published: February 2019

1.AbstractTo better understand key behaviors of living cells, such as bacterial biofilm formation, they must be observed above surfaces and at the interface between the surface and liquid medium. We have established a methodology for label-free imaging and tracking of individual cells simultaneously at both the solid-liquid interface and within the bulk, utilizing imaging modes of digital holographic microscopy (DHM) in 3D, differential interference contrast (DIC) and total internal reflectance microscopy (TIRM) in 2D as well as analysis protocols using a bespoke software package. We illustrate the power of this method by making detailed single cell measurements ofPseudomonas aeruginosain the first minutes of their interaction with a glass surface, focusing on the role of the flagella stators,motABandmotCD. Using this new method we have determined their relative contributions to bulk and near surface motion for populations of cells at the single cell level.
Cell entry-independent role for the reovirus μ1 protein in regulating necroptosis and the accumulation of viral gene products
Authors: Roebke Katherine E , Danthi Pranav 
Published: February 2019

ABSTRACTThe reovirus outer capsid protein μ1 regulates cell death in infected cells. To distinguish between the role of incoming, capsid-associated and newly synthesized μ1, we used siRNA-mediated knockdown. Loss of newly synthesized μ1 protein does not impact apoptotic cell death in HeLa cells but enhances necroptosis in L929 cells. Knockdown of μ1 also impacts aspects of viral replication. We found that while μ1 knockdown results in diminished release of infectious viral progeny from infected cells, viral minus strand RNA, plus strand RNA, and proteins that are not targeted by the μ1 siRNA accumulate to a greater extent when compared to control siRNA-treated cells. Furthermore, we observe a decrease in sensitivity of these viral products to inhibition by GuHCl (which targets minus strand synthesis to produce dsRNA) when μ1 is knocked down. Following μ1 knockdown, cell death is also less sensitive to treatment with GuHCl. Our studies suggest that the absence of μ1 allows enhanced transcriptional activity of newly synthesized cores and the consequent accumulation of viral gene products. We speculate that enhanced accumulation and detection of these gene products due to a μ1 knockdown potentiates RIP3 dependent cell death.IMPORTANCEWe use mammalian reovirus as a model to study how virus infections result in cell death. Here, we sought to determine how viral factors regulate cell death. Our work highlights a previously unknown role for reovirus outer capsid protein μ1 in limiting the induction of a necrotic form of cell death called necroptosis. Induction of cell death by necroptosis requires the detection of viral gene products late in infection. μ1 limits cell death by this mechanism because it prevents excessive accumulation of viral gene products that trigger cell death.
Diet induces reproducible alterations in the mouse and human gut microbiome
Authors: Bisanz Jordan E. , Upadhyay Vaibhav , Turnbaugh Jessie A. , Ly Kimberly , Turnbaugh Peter J. 
Published: February 2019

SummaryThe degree to which diet reproducibly alters the human and mouse gut microbiota remains unclear. Here, we focus on the consumption of a high-fat diet (HFD), one of the most frequently studied dietary interventions in mice. We employed a subject-level meta-analysis framework for unbiased collection and analysis of publicly available 16S rRNA gene and metagenomic sequencing data from studies examining HFD in rodent models. In total, we re-analyzed 27 studies, 1101 samples, and 106 million reads mapping to 16S rRNA gene sequences. We report reproducible changes in gut microbial community structure both within and between studies, including a significant increase in the Firmicutes phylum and decrease in the Bacteroidetes phylum; however, reduced alpha diversity is not a consistent feature of HFD. Finer taxonomic analysis revealed that the strongest signal of HFD on microbiota species composition is Lactococcus spp., which we demonstrate is a common dietary contaminant through the molecular testing of dietary ingredients, culturing, microscopy, and germ-free mouse experiments. After in silico removal of Lactococcus spp., we employed machine learning to define a unique operational taxonomic unit (OTU)-based signature capable of predicting the dietary intake of mice and demonstrate that phylogenetic and gene-family transformations of this model are capable of accurately predicting human samples in controlled feeding settings (area under the receiver operator curve = 0.75 and 0.88 respectively). Together, these results demonstrate the utility of microbiome meta-analyses in identifying robust bacterial signals for mechanistic studies and creates a framework for the routine meta-analysis of microbiome studies in preclinical models.
Epistasis Detection using Model Based Multifactor Dimensionality Reduction in Structured Populations
Authors: Abegaz Fentaw , Van Lishout François , Mahachie John Jestinah M , Chiachoompu Kridsadakorn , Bhardwaj Archana , Gusareva Elena S. , Wei Zhi , Hakonarson Hakon , Van Steen Kristel 
Published: February 2019

AbstractIn genome-wide association studies, the extent and impact of confounding due population structure have been well recognized. Inadequate handling of such confounding is likely to lead to spurious associations, hampering replication and the identification of causal variants. Several strategies have been developed for protecting associations against confounding, the most popular one is based on Principal Component Analysis. In contrast, the extent and impact of confounding due to population structure in gene-gene interaction association epistasis studies are much less investigated and understood. In particular, the role of non-linear genetic population substructure in epistasis detection is largely under-investigated, especially outside a regression framework. In order to identify causal variants in synergy, to improve interpretability and replicability of epistasis results, we introduce three strategies based on model-based multifactor dimensionality reduction (MB-MDR) approach for structured populations. We demonstrate through extensive simulation studies the effect of various degrees of genetic population structure and relatedness on epistasis detection and propose appropriate remedial measures based on linear and non-linear sample genetic similarity.Authors SummaryOne of the biggest challenges in human genetics is to understand the genetic basis of complex diseases such as cancer, diabetes, heart disease, depression, asthma, inflammatory bowel disease and hypertension, for instance via identifying genes, gene-gene and gene-environment interactions in association studies. Over the years, a more prominent role has been given to gene-gene interaction (epistasis) detection, in view of precision medicine and the hunt for novel drug targets and biomarkers. However, the increasing number of consortium-based epistasis studies that are marked by heterogeneous sample collections due to population structure or shared genetic ancestry are likely to be prone to spurious association and low power detection of associated or causal genes. In this work we introduced various strategies in epistasis studies with correction for confounding due to population structure. Based on extensive simulation studies we demonstrated the effect of genetic population structure on epistasis detection and investigated remedial measures to confounding by linear and nonlinear sample genetic similarity.