bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinase-mediated integration of a multigene cassette in rice leads to stable expression and inheritance of the stacked locus
Authors: Pathak Bhuvan , Srivastava Vibha 
Published: April 2020

SummaryEfficient methods for multigene transformation are important for developing novel crop varieties. Methods based on random integrations of multiple genes have been successfully used for metabolic engineering in plants. However, efficiency of co-integration and co-expression of the genes could present a bottleneck. Recombinase-mediated integration into the engineered target sites is arguably a more efficient method of targeted integration that leads to the generation of stable transgenic lines at a high rate. This method has the potential to streamline multigene transformation for metabolic engineering and trait stacking in plants. Therefore, empirical testing of transgene(s) stability from the multigene site-specific integration locus is needed. Here, the recombinase technology based on Cre-loxrecombination was evaluated for developing multigenic lines harboring constitutively-expressed and inducible genes. Targeted integration of a 5 genes cassette in the rice genome generated a precise full-length integration of the cassette at a high rate, and the resulting multigenic lines expressed each gene reliably as defined by their promoter activity. The stable constitutive or inducible expression was faithfully transmitted to the progeny, indicating inheritance-stability of the multigene locus. Co-localization of two distinctly inducible genes by heat or cold with the strongly constitutive genes did not appear to interfere with each other’s expression pattern. In summary, high rate of co-integration and co-expression of the multigene cassette installed by the recombinase technology in rice shows that this approach is appropriate for multigene transformation and introduction of co-segregating traits.Significance StatementRecombinase-mediated site-specific integration approach was found to be highly efficacious in multigene transformation of rice showing proper regulation of each gene driven by constitutive or inducible promoter. This approach holds promise for streamlining gene stacking in crops and expressing complex multigenic traits.
Species-specific quorum sensing represses the chitobiose utilization locus inVibrio cholerae
Authors: Klancher Catherine A. , Newman Jane D. , Ball Alyssa S. , van Kessel Julia C. , Dalia Ankur B. 
Published: April 2020

AbstractThe marine facultative pathogenVibrio choleraeforms complex multicellular communities on the chitinous shells of crustacean zooplankton in its aquatic reservoir.V. cholerae-chitin interactions are critical for the growth, evolution, and waterborne transmission of cholera. This is due, in part, to chitin-induced changes in gene expression in this pathogen. Here, we sought to identify factors that influence chitin-induced expression of one locus, the chitobiose utilization operon (chb), which is required for the uptake and catabolism of the chitin disaccharide. Through a series of genetic screens, we identified that the master regulator of quorum sensing, HapR, is a direct repressor of thechboperon. We also found that the levels of HapR inV. choleraeare regulated by the ClpAP protease. Furthermore, we show that the canonical quorum sensing cascade inV. choleraeregulateschbexpression in a HapR-dependent manner. Through this analysis we found that signaling via the species-specific autoinducer CAI-1, but not the inter-species autoinducer AI-2, influenceschbexpression. This phenomenon of species-specific regulation may enhance the fitness of this pathogen in its environmental niche.ImportanceIn nature, bacteria live in multicellular and multispecies communities. Microbial species can sense the density and composition of their community through chemical cues using a process called quorum sensing (QS). The marine pathogenVibrio choleraeis found in communities on the chitinous shells of crustaceans in its aquatic reservoir.V. choleraeinteractions with chitin are critical for the survival, evolution, and waterborne transmission of this pathogen. Here, we show thatV. choleraeuses QS to regulate the expression of one locus required forV. cholerae-chitin interactions.
Automatic Landmark-guided Bijective Brain Image Registration by Composing Region-based Locally Diffeomorphic Warpings
Authors: He Hengda , Razlighi Qolamreza R. 
Published: April 2020

AbstractAs the size of the neuroimaging cohorts being increased to address key questions in the field of cognitive neuroscience, cognitive aging, and neurodegenerative diseases, the accuracy of the spatial normalization as an essential pre-processing step becomes extremely important in the neuroimaging processing pipeline. Existing spatial normalization methods have poor accuracy particularly when dealing with the highly convoluted human cerebral cortex and when brain morphology is severely altered (e.g. clinical and aging populations). To address this shortcoming, we propose to implement and evaluate a novel landmark-guided region-based spatial normalization technique that takes advantage of the existing surface-based human brain parcellation to automatically identify and match regional landmarks. To simplify the non-linear whole brain registration, the identified landmarks of each region and their counterparts are registered independently with large diffeomorphic (topology preserving) deformation via geodesic shooting. The regional diffeomorphic warping fields were combined by an inverse distance weighted interpolation technique to have a smooth global warping field for the whole brain. To ensure that the final warping field is diffeomorphic, we used simultaneously forward and reverse maps with certain symmetric constraints to yield bijectivity. We have evaluated our proposed method using both simulated and real (structural and functional) human brain images. Our evaluation shows that our method can enhance structural correspondence up to around 86%, a 67% improvement compared to the existing state-of-the-art method. Such improvement also increases the sensitivity and specificity of the functional imaging studies by about 17%, reducing the required number of subjects and subsequent costs. We conclude that our proposed method can effectively substitute existing substandard spatial normalization methods to deal with the demand of large cohorts and the need for investigating clinical and aging populations.
Suppression of MicroRNA-144 Promotes CXCR4 and CXCL12 Expression and Downregulates Apoptosis in Ovarian Cancer Cells
Authors: Turut Fatma Aysun , Acidereli Hilal , Cevik Ozge 
Published: April 2020

AbstractMicroRNAs are important regulators in the growth and metastasis of ovarian cancers. Many assays were established to identify the role of miR-144-3p in ovarian cancer cells and its interaction with COX-2 and chemokines (CXCR4 and CXCL12). The ovarian cancer cells (OVCAR-3 and SKOV-3) were transfected with Anti-miR-144 to downregulate the miR-144-3p and cultured for 36 h. We herein examined the cell viability, colony formation, cell migration, COX-2 reporter activity, the protein expressions of CXCR4, CXCL12, COX-2, VEGF, Caspase-3, BAX and Bcl-2. We have observed that the suppression of miR-144-3p significantly increased the cell proliferation and migration and decreased the apoptosis. Moreover, the downregulation of miR-144-3p markedly increased the COX-2, CXCR4, CXCL12 and VEGF expression in OVCAR-3 and SKOV-3 ovarian cancer cells. In conclusion, miR-144-3p may play important roles in the regulation of chemokine receptor CXCR4 and its ligand CXCL12 in the progressive ovarian tumors expressing COX2. These data suggests that miR-144 has the novel therapeutic targets for the cancer therapy and cancer prevention.
Functional properties of powders produced from either or not fermented mealworm (Tenebrio molitor) paste
Authors: Borremans A. , Bußler S. , Sagu T. S , Rawel H.M. , Schlüter O. , Van Campenhout L. 
Published: April 2020

AbstractThe aim of this study was to determine the effect of fermentation of mealworms (Tenebrio molitor) with commercial meat starters cultures on the functional properties of powders produced from the larvae. Full fat and defatted powder samples were prepared from non-fermented and fermented mealworm pastes. Then the crude protein, crude fat and dry matter contents, pH, bulk density, colour, water and oil binding capacity, foaming capacity and stability, emulsion capacity and stability, protein solubility, quantity of free amino groups and protein composition of the powders were evaluated. Regardless of the starter culture used, fermentation significantly (p < 0.05) reduced the crude and soluble protein content of the non-defatted mealworm powders and in general impaired their water and oil binding, foaming- and emulsifying properties. Defatting of the powders improved most functional properties studied, except the protein solubility, water binding capacity, foaming capacity and emulsion stability. The o-phthaldialdehyd assay revealed that the amount of free amino groups increased during fermentation, which may be attributed to proteolysis of mealworm proteins by the starters. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the soluble proteins of fermented powders were composed of molecules of lower molecular mass compared to non-fermented powders. As the molecular sizes of the soluble proteins decreased, it is clear that also the protein structure was modified by the fermentation process, which in turn led to changes in functional properties. It was concluded that fermentation of mealworms in general does not contribute to the functional properties studied in this work. Nevertheless, the results confirmed that the properties of non-fermented powders are comparable to other food protein sources.
linus: Conveniently explore, share, and present large-scale biological trajectory data from a web browser
Authors: Waschke Johannes , Hlawitschka Mario , Anlas Kerim , Trivedi Vikas , Roeder Ingo , Huisken Jan , Scherf Nico 
Published: April 2020

AbstractIn biology, we are often confronted with information-rich, large-scale trajectory data, but exploring and communicating patterns in such data is often a cumbersome task. Ideally, the data should be wrapped with an interactive visualisation in one concise package that makes it straightforward to create and test hypotheses collaboratively. To address these challenges, we have developed a tool,linus, which makes the process of exploring and sharing 3D trajectories as easy as browsing a website. We provide a python script that reads trajectory data and enriches them with additional features, such as edge bundling or custom axes and generates an interactive web-based visualisation that can be shared offline and online. The goal oflinusis to facilitate the collaborative discovery of patterns in complex trajectory data.
The activity of human enhancers is modulated by the splicing of their associated lncRNAs
Authors: Tan Jennifer Y. , Marques Ana C. 
Published: April 2020

ABSTRACTPervasive enhancer transcription is at the origin of more than half of all long noncoding RNAs in humans. Transcription of enhancer-associated long noncoding RNAs (elncRNA) contribute to their cognate enhancer activity and gene expression regulation incis.Recently, splicing of elncRNAs was shown to be associated with elevated enhancer activity. However, whether splicing of elncRNA transcripts is a mere consequence of accessibility at highly active enhancers or if elncRNA splicing directly impacts enhancer function, remains unanswered.We analysed genetically driven changes in elncRNA expression, in humans, to address this outstanding question. We showed that splicing related motifs within multi-exonic elncRNAs evolved under selective constraints during human evolution, suggesting the processing of these transcripts is unlikely to have resulted from transcription across spurious splice sites. Using a genome-wide and unbiased approach, we used nucleotide variants as independent genetic factors to directly assess the causal relationship that underpin elncRNA splicing and their cognate enhancer activity. We found that the splicing of most elncRNAs is associated with changes in chromatin signatures at cognate enhancers and target mRNA expression.We conclude that efficient and conserved processing of enhancer-associated elncRNAs contributes to enhancer activity.
Dense encoding of developmental regulatory information may constrain evolvability
Authors: Fuqua Timothy , Jordan Jeff , van Breugel Maria Elize , Halavatyi Aliaksandr , Tischer Christian , Polidoro Peter , Abe Namiko , Tsai Albert , Mann Richard S. , Stern David L. , Crocker Justin 
Published: April 2020

AbstractGene regulatory changes underlie much of phenotypic evolution. However, the evolutionary potential of regulatory evolution is unknown, because most evidence comes from either natural variation or limited experimental perturbations. Surveying an unbiased mutation library for a developmental enhancer inDrosophila melanogasterusing an automated robotics pipeline, we found that most mutations alter gene expression. Our results suggest that regulatory information is distributed throughout most of a developmental enhancer and that parameters of gene expression—levels, location, and state—are convolved. The widespread pleiotropic effects of most mutations and the codependency of outputs may constrain the evolvability of developmental enhancers. Consistent with these observations, comparisons of diverse drosophilids reveal mainly stasis and apparent biases in the phenotypes influenced by this enhancer. Developmental enhancers may encode a much higher density of regulatory information than has been appreciated previously, which may impose constraints on regulatory evolution.Quote“Rock, robot rockRock, robot rockRock, robot rock”Daft Punk (2005)
Cloning andIn silicocharacterization of Heat shock factor (Hsf2) from Wheat (Triticum aestivum L.)
Authors: Dubey Kavita , Goswami Suneha , Kumar Narendra , Kumar Ranjeet R. , Niraj Ravi RK 
Published: April 2020

ABSTRACTA gene that encodes for Heat Shock Factor (Hsf) was characterized and designated as TaHsf2 (Gen Bank ID: KP063542) from wheat. The genomic sequence was found to be 1551bp long with open reading frame of length1123bp. The amino acid sequence so concluded showed to have HSF domain having high degree of similarity (homology) with other HSF coding gene of related species. We have reported in-silico three-dimensional model of TaHsf2 and evaluation of the predicted model, analysed with various tools. The sudden climatic variations over the years especially elevation in temperature has adversely affected the growth and productivity of winter wheat (Triticum aestivumL.). A very less number of HSFs is being reported and characterized in wheat and the data so available for wheat calls for investigation and characterization of more HSP’s coding HSFs. In our present study we have cloned one of the novel HSFs and have characterized it throughin silicotools.
Potentiating TMEM16A channel function has no effect on airway goblet cells or bronchial and pulmonary vascular smooth muscle function
Authors: Danahay Henry , Fox Roy , Lilley Sarah , Charlton Holly , Adley Kathryn , Christie Lee , Ansari Ejaz , Ehre Camille , Flen Alexis , Tuvim Michael J. , Dickey Burton F. , Williams Colin , Beaudoin Sarah , Collingwood Stephen P , Gosling Martin 
Published: April 2020

AbstractThe calcium-activated chloride channel TMEM16A enables chloride secretion across several transporting epithelia, including in the airway where it represents a therapeutic target for the treatment of cystic fibrosis. Additional roles for TMEM16A have also been proposed, including enhancing goblet cell exocytosis, increasing goblet cell numbers and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, both potentiation and inhibition, could affect any of these proposed biological roles.In vitro, a recently described potent and selective TMEM16A potentiator (ETX001) failed to stimulate mucin release from primary human bronchial epithelial (HBE) cells over a 24h exposure period using both biochemical and imaging endpoints. In addition, treatment of HBE cells with ETX001 or a potent and selective TMEM16A inhibitor (Ani9) for 4 days did not influence mucin release or goblet cell formation. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 driven goblet cell metaplasia model.Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats.Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.
Tail-Robust Quantile Normalization
Authors: Brombacher Eva , Schad Ariane , Kreutz Clemens 
Published: April 2020

AbstractHigh-throughput biological data – such as mass spectrometry-based proteomics data – suffer from systematic non-biological variance, which is introduced by systematic errors such as batch effects. This hinders the estimation of ‘real’ biological signals and, thus, decreases the power of statistical tests and biases the identification of differentially expressed sample classes. To remove such unintended variation, while retaining the biological signal of interest, the analysis workflows for mass spectrometry-based quantification typically comprises normalization steps prior to the statistical analysis of the data. Several normalization methods, such as quantile normalization, have originally been developed for microarray data. However, unlike microarray data, proteomics data may contain features, in the form of protein intensities, that are consistently highly abundant across experimental conditions and, hence, are encountered in the tails of the protein intensity distribution. If such proteins are present, statistical inferences of the intensity profiles of the normalized features are impeded through the increased number of false positive findings due to the biased estimation of the variance of the data. Thus, we developed a, freely available, novel approach: ‘tail-robust quantile normalization’. It extends the traditional quantile normalization to preserve the biological signals of features in the tails of the distribution over experimental conditions and to account for sample-dependent missing values.
JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps
Authors: Dukart Juergen , Holiga Stefan , Rullmann Michael , Lanzenberger Rupert , Hawkins Peter C.T. , Mehta Mitul A. , Hesse Swen , Barthel Henryk , Sabri Osama , Jech Robert , Eickhoff Simon B. 
Published: April 2020

AbstractRecent studies have shown that drug-induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross-modal correlation of MRI- based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma- aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson’s disease patients (PD) and risperidone-induced changes in rsfMRI and cerebral blood flow (CBF). Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD and dopaminergic (D2) and serotonergic systems (5-HT1b). Risperidone induced CBF alterations were correlated with its main targets in serotonergic and dopaminergic systems. JuSpace provides a biologically meaningful framework for linking neuroimaging to underlying neurotransmitter information.
SRF is a non-histone methylation target of KDM2B and SET7 in the regulation of myogenesis
Authors: Joung Hosouk , Kang Joo-Young , Kim Ji-Young , Kwon Duk-Hwa , Jeong Anna , Min Hyun-Ki , Shin Sera , Lee Yun-Gyeong , Kim Young-Kook , Seo Sang-Beom , Kook Hyun 
Published: April 2020

AbstractDemethylation of histone lysines, one of the most important modifications in transcriptional regulation, is associated with various physiological states. KDM2B is a histone H3K4, H3K36, and H3K79 demethylase associated with the repression of transcription. Here, we present a novel mechanism by which KDM2B demethylates serum response factor (SRF) K165 to negatively regulate muscle differentiation, which is counteracted by histone methyltransferase SET7. We show that KDM2B inhibited skeletal muscle differentiation by inhibiting the transcription of SRF-dependent genes. Both KDM2B and SET7 regulated the balance of SRF K165 methylation. SRF K165 methylation was required for the transcriptional activation of SRF and for the promoter occupancy of SRF-dependent genes. SET7 inhibitors blocked muscle cell differentiation. Taken together, these data indicate that SRF is a non-histone target of KDM2B and that the methylation balance of SRF maintained by KDM2B and SET7 plays an important role in muscle cell differentiation.
Lipopolysaccharide administration alters extracellular vesicles in human lung-cancer cells and mice
Authors: Jones Leandra B. , Kumar Sanjay , Bell Courtnee’ R. , Crenshaw Brennetta J. , Coats Mamie T. , Sims Brian , Matthews Qiana L. 
Published: April 2020

AbstractExtracellular vesicles (EVs) play a fundamental role in cell and infection biology and have the potential to act as biomarkers for novel diagnostic tools. In this study, we explored thein vitroimpact of bacterial lipopolysaccharide administration on a cell line that represents a target for bacterial infection in the host. Administration of lipopolysaccharide at varying concentrations to this A549 cell line caused only modest changes in cell death, but EV numbers were significantly changed. After treatment with the highest concentration of lipopolysaccharide, EVs derived from A549 cells packaged significantly less interleukin-6 and lysosomal-associated membrane protein 1. We also examined the impact of lipopolysaccharide administration on exosome biogenesis and cargo composition in BALB/c mice. Serum-isolated EVs from lipopolysaccharide-treated mice showed significantly increased lysosomal-associated membrane protein 1 and toll-like receptor 4 levels compared with EVs from control mice. In summary, this study demonstrated that EV numbers and cargo were altered using thesein vitroandin vivomodels of bacterial infection.