bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that Runt Acts as a Counter-Repressor of Groucho duringDrosophila melanogasterPrimary Sex Determination
Authors: Mahadeveraju Sharvani , Erickson James W. 
Published: May 2019

AbstractRunx proteins are bifunctional transcription factors that both repress and activate transcription in animal cells. Typically Runx proteins work in concert with other transcriptional regulators, including co-activators and co-repressors to mediate their biological effects. InDrosophila melanogasterthe archetypal Runx protein, Runt, functions in numerous processes including segmentation, neurogenesis and sex determination. During primary sex determination Runt acts as one of four X-linked signal element (XSE) proteins that direct female-specific activation of the establishmen promoter (Pe) of the master regulatory geneSex-lethal (Sxl). Successful activation ofSxlPerequires that the XSE proteins overcome the repressive effects of maternally deposited Groucho (Gro), a potent co-repressor of the Gro/TLE family. Runx proteins, including Runt, contain a C-terminal peptide, VWRPY, known to bind to Gro/TLE proteins to mediate transcriptional repression. We show that Runt’s VWRPY co-repressor-interaction domain is needed for Runt to activateSxlPe. Deletion of the Gro-interaction domain eliminates Runt-ability to activateSxlPe, whereas replacement with a higher affinity, VWRPW, sequence promotes Runt-mediated transcription. This suggest that Runt activatesSxlPeby antagonizing Gro function, a conclusion consist with earlier findings that Runt is needed forSxlexpression only in embryonic regions with high Gro activity. Surprisingly we found that Runt is not required for the initial activation activation ofSxlPe. Instead, Runt is needed to keepSxlPeactive during the subsequent period of high-levelSxltranscription suggesting that Runt helps amplfy the difference between female and male XSE signals by counterrepressing Gro in female, but not in male, embryos.
Adipocyte vesicles: ‘all-in-one’ packages that stimulate tumor mitochondrial metabolism and dynamics
Authors: Clement Emily , Lazar Ikrame , Attané Camille , Carrié Lorry , Dauvillier Stéphanie , Ducoux-Petit Manuelle , Menneteau Thomas , Moutahir Mohamed , Gonidec Sophie Le , Dalle Stéphane , Valet Philippe , Burlet-Schiltz Odile , Muller Catherine , Nieto Laurence 
Published: May 2019

AbstractExtracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes promote melanoma aggressiveness through fatty acid oxidation, with a heightened effect in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation after release through lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance in obesity.
Novel method to determine diagnosis-defining refraction points
Authors: Yamauchi Tsuneto , Ohshima Mitsuhiro , Yamaguchi Yoko , Konishi Kazunori , Kappert Kai , Nakano Shigeru 
Published: May 2019

AbstractDiagnosis of a certain disease generally relies on definitions established by professional medical societies and comprise the patient’s history, physical examination, and test results. These include physical compositions such as body mass index (BMI), and laboratory tests such as serum creatinine and albumin in urine samples. In general, laboratory tests are based on mathematical methods,e.g.defining critical values from the mean ± kσ of a population, where k is a natural number and the standard deviation is σ (“mean ± kσ-method”). In most cases k is defined as 2, leading to reference ranges defining 95% of test results as normal. However, this method mostly depends on a normal distribution of values.Here we applied a novel method (“SoFR-method”) based on data sorting to define refraction points, which carry informative value as diagnostic criteria. Applying the SoFR-method, standard measures such as critical BMI-values are categorized by equal robustness as by the mean ± kσ-method. However, the SoFR-method showed higher validity when analyzing non-normalized values such as creatinine and albumin, as well as hepatocyte growth factor (HGF) and hemoglobin in a novel Perioscreen assay in saliva of diabetic and non-diabetic patients.Taken together, we defined a novel method based on data sorting of test results from patients to effectively define refraction points which might guide more accurately clinical diagnoses and define relevant thresholds.
Pyrenophora teresandRhynchosporium secalisinfections in malt barley as influenced by genotype, spatial and temporal effects and nitrogen fertilization
Authors: Vahamidis Petros , Stefopoulou Angeliki , Lagogianni Christina S. , Economou Garyfalia , Dercas Nicholas , Kotoulas Vassilis , Kalivas Dionissios , Tsitsigiannis Dimitrios I. 
Published: May 2019

SummaryNet form net blotch (NFNB) and barley leaf scald are among the most important barley diseases worldwide and particularly in Greece. Their occurrence in malt barley can exert a significant negative effect on malt barley grain yield and quality. An experimental trial across two growing seasons was implemented in Greece in order i) to assess the epidemiology of NFNB and leaf scald in a barley disease free area when the initial inoculation of field occurs through infected seeds, and ii) to further explore the relationship among nitrogen rate, grain yield, quality variables (i.e. grain protein content and grain size) and disease severity and epidemiology. It was demonstrated that both NFNB and leaf scald can be carried over from one season to the next on infected seed under Mediterranean conditions. However, disease severity was more pronounced after barley tillering phase when soil had been successfully inoculated first. When nitrogen rate and genotype were the main sources of variation the epidemiology assessment was implemented with hotspot and Anselin Local Moran’s I analysis. It was found that the location of hotspots was modified during growing season. Soil and plant variables were assessed for the explanation of this variability. According to commonality analysis the effect of distance from the locations with the highest disease infections was a better predictor of disease severity (for both diseases) compared to nitrogen rate during pre-anthesis period. However, disease severity after anthesis was best explained by nitrogen rate only for the most susceptible cultivars to NFNB. The effect of disease infections on yield, grain size and grain protein content varied in relation to genotype, pathogen and stage of crop development. The importance of crop residues on the evolution of both diseases was also highlighted.
Cooperativity between the 3’ untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus
Authors: Trobaugh Derek W. , Sun Chengqun , Bhalla Nishank , Gardner Christina L. , Dunn Matthew , Klimstra William B. 
Published: May 2019

AbstractEastern equine encephalitis virus (EEEV), a mosquito-borne RNA virus, is one of the most acutely virulent viruses endemic to the Americas, causing between 30% and 70% mortality in symptomatic human cases. A major factor in the virulence of EEEV is the presence of four binding sites for the hematopoietic cell-specific microRNA, miR-142-3p, in the 3’ untranslated region (3’ UTR) of the virus. Three of the sites are “canonical” with all 8 seed sequence residues complimentary to miR-142-3p while one is “non-canonical” and has a seed sequence mismatch. Interaction of the EEEV genome with miR-142-3p limits virus replication in myeloid cells and suppresses the systemic innate immune response, greatly exacerbating EEEV neurovirulence. The presence of the miRNA binding sequences is also required for efficient EEEV replication in mosquitoes and, therefore, essential for transmission of the virus. In the current studies, we have examined the role of each binding site by point mutagenesis of seed sequences in all combinations of sites followed by infection of mammalian myeloid cells, mosquito cells and mice. The resulting data indicate that both canonical and non-canonical sites contribute to cell infection and animal virulence, however, surprisingly, all sites are rapidly deleted from EEEV genomes shortly after infection of myeloid cells or mice. Finally, we show that the virulence of a related encephalitis virus, western equine encephalitis virus, is also dependent upon miR-142-3p binding sites.Author SummaryEastern equine encephalitis virus (EEEV) is one of the most acutely virulent mosquito-borne viruses in the Americas. A major determinant of EEEV virulence is a mammalian microRNA (miRNA) that is primarily expressed in myeloid cells, miR-142-3p. Like miRNA suppression of host mRNA, miR-142-3p binds to the 3’ untranslated region (UTR) of the EEEV genome only in myeloid cells suppressing virus replication and the induction of the innate immune response. In this study, we used point mutations in all four miR-142-3p binding sites in the EEEV 3’ UTR to understand the mechanism behind this miRNA suppression. We observed that decreasing the number of miR-142-3p binding sites leads to virus escape and ultimately attenuation in vivo. Furthermore, another virus, western equine encephalitis virus, also encodes miR-142-3p binding sites that contribute to virulence in vivo. These results provide insight into the mechanism of how cell-specific miRNAs can mediate suppression of virus replication.
From cells to tissue: How cell scale heterogeneity impacts glioblastoma growth and treatment response
Authors: Gallaher Jill A. , Massey Susan C. , Hawkins-Daarud Andrea , Noticewala Sonal S. , Rockne Russell C. , Johnston Sandra K. , Gonzalez-Cuyar Luis , Juliano Joseph , Gil Orlando , Swanson Kristin R. , Canoll Peter , Anderson Alexander R. A. 
Published: May 2019

AbstractGlioblastomas are aggressive primary brain tumors known for their inter- and intratumor heterogeneity. This disease is uniformly fatal, with intratumor heterogeneity the major reason for treatment failure and recurrence. Just like the nature vs nurture debate, heterogeneity can arise from heritable or environmental influences. Whilst it is impossible to clinically separate observed behavior of cells from their environmental context, using a mathematical framework combined with multiscale data gives us insight into the relative roles of variation from inherited and environmental sources.To better understand the implications of intratumor heterogeneity on therapeutic outcomes, we created a hybrid agent-based mathematical model that captures both the overall tumor kinetics and the individual cellular behavior. We track single cells as agents, cell density on a coarser scale, and growth factor diffusion and dynamics on a finer scale over time and space. Our model parameters were fit utilizing serial MRI imaging and cell tracking data from ex vivo tissue slices acquired from a growth-factor driven glioblastoma murine model.When fitting our model to serial imaging only, there was a spectrum of equally-good parameter fits corresponding to a wide range of phenotypic behaviors. This wide spectrum of in silico tumors also had a wide variety of responses to an application of an antiproliferative treatment. Recurrent tumors were generally less proliferative than pre-treatment tumors as measured via the model simulations and validated from human GBM patient histology. When fitting our model using imaging and cell scale data, we determined that heritable heterogeneity is required to capture the observed migration behavior. Further, we found that all tumors increased in size after an anti-migratory treatment, and some tumors were larger after a combination treatment than with an anti-proliferative treatment alone. Together our results emphasize the need to understand the underlying phenotypes and tumor heterogeneity in designing therapeutic regimens.
Structural and Functional Responses of Soil Microbial Communities to Biodegradable Plastic Film Mulching in Two Agroecosystems
Authors: Bandopadhyay Sreejata , Sintim Henry Y. , DeBruyn Jennifer M. 
Published: May 2019

AbstractPolyethylene (PE) plastic mulch films are used globally in crop production but incur considerable disposal and environmental pollution issues. Biodegradable plastic mulch films (BDMs), an alternative to PE-based films, are designed to be tilled into the soil where they are expected to be mineralized to carbon dioxide, water and microbial biomass. However inadequate research regarding the impacts of repeated incorporation of BDMs on soil microbial communities has partly contributed to limited adoption of BDMs. In this study, we evaluated the effects of BDM incorporation on soil microbial community structure and function over two years in two geographical locations: Knoxville, TN, and in Mount Vernon, WA. Treatments included four plastic BDMs, a completely biodegradable cellulose mulch, a non-biodegradable PE mulch and a no mulch plot. Bacterial community structure determined using 16S rRNA amplicon sequencing revealed significant differences by location and season. Differences in bacterial communities by mulch treatment were not significant for any season in either location, except for Fall 2015 in WA where differences were observed between BDMs and no-mulch plots. Extracellular enzyme rate assays were used to characterize communities functionally, revealing significant differences by location and sampling season in both TN and WA but minimal differences between BDMs and PE treatments. Limited effects of BDM incorporation on soil bacterial community structure and soil enzyme activities when compared to PE suggest that BDMs have comparable influences on soil microbial communities, and therefore could be considered an alternative to PE.ImportancePlastic film mulches increase crop yields and improve fruit quality. Most plastic mulches are made of polyethylene (PE), which is poorly degradable, resulting in undesirable end-of-life outcomes. Biodegradable mulches (BDMs) may be a sustainable alternative to PE. BDMs are made of polymers which can be degraded by soil microbial enzymes, and are meant to be tilled into soil after use. However, uncertainty about impacts of tilled-in BDMs on soil health has restricted adoption of BDMs. Our previous research showed BDMs did not have a major effect on a wide range of soil quality indicators (Sintim et al. 2019); here we focus on soil microbial communities, showing that BDMs do not have detectable effects on soil microbial communities and their functions, at least over the short term. This informs growers and regulators about use of BDMs in crop production, paving a way for an agricultural practice that reduces environmental plastic pollution.
Inhibition of fatty acid oxidation as a new target to treat Primary Amoebic Meningoencephalitis by repurposing two well-known drugs
Authors: Sarink Maarten J. , Verbon Annelies , Tielens Aloysius G.M. , van Hellemond Jaap J. 
Published: May 2019

AbstractPrimary Amoebic Meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living amoebaNaegleria fowleri. The disease mostly affects healthy children and young adults after contaminated water enters the nose, generally during recreational water activities. The amoeba migrate along the olfactory nerve to the brain, resulting in seizures, coma and eventually death. Previous research has shown thatNaegleria gruberi, a close relative ofN. fowleri, prefers lipids over glucose as an energy source. Therefore, we tested several inhibitors of fatty acid oxidation alongside the currently used drugs amphotericin B and miltefosine. Our data demonstrate that etomoxir, orlistat, perhexiline, thioridazine and valproic acid inhibited growth ofN. gruberi. Furthermore, additive effects were seen when drugs were combined. Both thioridazine and valproic acid inhibit in vitro growth ofN. gruberiin concentrations that can be obtained at the site of infection, which is doubtful with the currently used drugs amphotericin B and miltefosine. Both thioridazine and valproic acid have already been used for other diseases. As the development of new drugs and randomized controlled trials for this rare disease is nearly impossible, repurposing drugs is the most promising way to obtain additional drugs to combat PAM. Thioridazine and valproic acid are available drugs without major side-effects and can, therefore, be used as new complementary options in PAM therapy.
Expression of 9-O- and 7,9-O-acetyl modified sialic acid in cells and their effects on influenza viruses
Authors: Barnard Karen N. , Wasik Brian R. , LaClair Justin R. , Weichert Wendy S. , Lawrence Brynn K. , Parrish Colin R. 
Published: May 2019

ABSTRACTSialic acids (Sia) are widely displayed on the surfaces of cells and tissues. Sia come in a variety of chemically modified forms, including those with acetyl modifications at the C7, C8, and C9 positions. Here, we analyzed the distribution and amounts of these acetyl modifications in different human and canine cells. As Sia or their variant forms are receptors for influenza A and influenza C viruses, we examined the effects of these modifications on virus infections. We confirmed that 9-O-acetyl and 7,9-O-acetyl modified Sia are widely but variably expressed across cell lines from both humans and canines. While they were expressed on the cell surface of canine MDCK cell lines, they were located primarily within the Golgi compartment of human HEK-293 and A549 cells. The O-acetyl modified Sia were expressed at low levels of 1-2% of total Sia in these cell lines. We knocked out and over-expressed the sialate O-acetyltransferase gene (CasD1), and knocked out the sialate O-acetylesterase gene (SIAE) using CRISPR/Cas9 editing. Knocking out CasD1 removed 7,9-O- and 9-O-acetyl Sia expression, confirming previous reports. However, over-expression of CasD1 and knockout of SIAE gave only modest increases in 9-O-acetyl levels in cells and no change in 7,9-O-acetyl levels, indicating that there are complex regulations of these modifications. These modifications were essential for influenza C infection, but had no obvious effect on influenza A infection.IMPORTANCESialic acids are key glycans that are involved in many different normal cellular functions, as well as being receptors for many pathogens. However, Sia come in diverse chemically modified forms. Here we examined and manipulated the expression of 7,9-O- and 9-O-acetyl modified Sia on cells commonly used in influenza virus and other research by engineering the enzymes that produce or remove the acetyl groups.
Environmentally induced lipidome adaptation in the bacterial model organismM. extorquens
Authors: Chwastek Grzegorz , Surma Michal A. , Rizk Sandra , Grosser Daniel , Lavrynenko Oksana , Rucińska Magdalena , Jambor Helena , Sáenz James 
Published: May 2019

AbstractCells, from microbes to man, adapt their membranes in response to the environment to maintain their properties and functions. To adapt, lipid composition is homeostatically regulated to conserve optimal membrane properties. Global patterns of lipidome remodelling are poorly understood, particularly in model organisms with simple lipid compositions that can provide insight into fundamental principles underlying membrane adaptation. Using shotgun lipidomics, we examined the simple yet adaptive lipidome of the plant-associated Gram-negative bacteriumMethylobacterium extorquensover varying temperature, hyperosmotic and detergent stress, carbon sources, and cell density. We observed that as few as ten lipids account for 90% of the total changes, thus constraining the upper limit of variable lipids required for an adaptive living membrane. Across all conditions, the highest degree of lipidomic variability was observed for changing growth temperature. We also revealed that variations in lipid structural features are not monotonic over a given range of conditions and are heterogeneous across lipid classes. Interestingly, phosphotidylcholine showed the most extreme acyl chain remodeling among all lipid classes, suggesting a new link to its importance in bacterial-host interactions and pathogenicity. These patterns in lipidomic remodeling suggest a highly adaptive mechanism with many degrees of freedom and constrain the lipidomic requirements for an adaptive membrane.
Trochodendron aralioides, the first chromosome-level draft genome in Trochodendrales and a valuable resource for basal eudicot research
Authors: Strijk Joeri S. , Hinsinger Damien D. , Zhang Feng-Ping , Cao KunFang 
Published: May 2019

AbstractBackgroundThe wheel tree (Trochodendron aralioides) is one of only two species in the basal eudicot order Trochodendrales. Together with Tetracentron sinense, the family is unique in having secondary xylem without vessel elements, long considered to be a primitive character also found in Amborella and Winteraceae. Recent studies however have shown that Trochodendraceae belong to basal eudicots and demonstrate this represents an evolutionary reversal for the group. Trochodendron aralioides is widespread in cultivation and popular for use in gardens and parks.FindingsWe assembled the T. aralioides genome using a total of 679.56 Gb of clean reads that were generated using both PacBio and Illumina short-reads in combination with 10XGenomics and Hi-C data. Nineteen scaffolds corresponding to 19 chromosomes were assembled to a final size of 1.614 Gb with a scaffold N50 of 73.37 Mb in addition to 1,534 contigs. Repeat sequences accounted for 64.226% of the genome, and 35,328 protein-coding genes with an average of 5.09 exons per gene were annotated using de novo, RNA-seq, and homology-based approaches. According to a phylogenetic analysis of protein-coding genes, T. aralioides diverged in a basal position relatively to core eudicots, approximately 121.8-125.8 million years ago.ConclusionsTrochodendron aralioides is the first chromosome-scale genome assembled in the order Trochodendrales. It represents the largest genome assembled to date in the basal eudicot grade, as well as the closest order relative to the core-eudicots, as the position of Buxales remains unresolved. This genome will support further studies of wood morphology and floral evolution, and will be an essential resource for understanding rapid changes that took place at the base of the Eudicot tree. Finally, it can serve as a valuable source to aid both the acceleration of genome-assisted improvement for cultivation and conservation efforts of the wheel tree.