bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative mapping of the dog epigenome: reference annotation for comparative inter-tissue and cross-species studies
Authors: Son Keun Hong , Aldonza Mark Borris D. , Nam A-Reum , Lee Kang-Hoon , Lee Jeong-Woon , Shin Kyung-Ju , Kang Keunsoo , Cho Je-Yoel 
Published: July 2022

AbstractThe domestic dog has become a valuable model in exploring multifaceted diseases and biology important for human health. Large-scale dog genome projects produced high-quality draft references but still lack comprehensive annotation of encoded functional elements. Through the integrative next generation sequencing of transcriptomes paired with histone marks and DNA methylome profiling of 11 adult tissue types, implemented in a cross-species approach, we generated a reference epigenome of a domesticated dog. Using genome orthologues and synthenies, we deciphered the dog’s epigenetic code by defining distinct chromatin states, allowing for genome-wide, integratable data production. We then characterized somatic super-enhancer landscapes and showed that genes mapped on these regions are associated with a broad range of biological and disease traits and are traceable to their tissue-of-origin. Ultimately, we delineated conserved epigenomic changes at the tissue- and species-specific resolutions. Our study provides an epigenomic blueprint of the dog for comparative biology and medical research.
Benchmarking long-read RNA-sequencing analysis tools usingin silicomixtures
Authors: Dong Xueyi , Du Mei R. M. , Gouil Quentin , Tian Luyi , Jabbari Jafar S. , Bowden Rory , Baldoni Pedro L. , Chen Yunshun , Smyth Gordon K. , Amarasinghe Shanika L. , Law Charity W. , Ritchie Matthew E. 
Published: July 2022

AbstractThe current lack of benchmark datasets with inbuilt ground-truth makes it challenging to compare the performance of existing long-read isoform detection and differential expression analysis workflows. Here, we present a benchmark experiment using two human lung adenocarcinoma cell lines that were each profiled in triplicate together with synthetic, spliced, spike-in RNAs (“sequins”). Samples were deeply sequenced on both Illumina short-read and Oxford Nanopore Technologies long-read platforms. Alongside the ground-truth available via the sequins, we createdin silicomixture samples to allow performance assessment in the absence of true positives or true negatives. Our results show that,StringTie2andbambuoutperformed other tools from the 6 isoform detection tools tested,DESeq2, edgeRandlimma-voomwere best amongst the 5 differential transcript expression tools tested and there was no clear front-runner for performing differential transcript usage analysis between the 5 tools compared, which suggests further methods development is needed for this application.
Cytoflow: A Python Toolbox for Flow Cytometry
Authors: Teague Brian 
Published: July 2022

AbstractCytoflow is a free, open-source flow cytometry toolbox that enables quantitative and reproducible analyses of flow cytometry experiments. Comprised of a set of well-documented Python modules wrapped by a graphical user interface, Cytoflow allows both programmers and bench scientists to apply modern data analysis methods (including machine learning) to high-dimensional flow data sets. Modern analyses may also lead to new insight about the biological systems that are studied with this powerful technique.
Bioinformatics analysis of immune-related prognostic genes and immunotherapy in renal clear cell carcinoma
Authors: Pan Ziwen , Chang Sheng , Chen Song , Zhao Daqiang , Zou Zhiyu , Dai Linrui , Hou Yibo , Zhang Qianqian , Yang Yuanyuan , Chen Zhishui , Zhang Weijie , Zhao Yuanyuan 
Published: July 2022

AbstractClear cell renal cell carcinoma (ccRCC) is an immunogenic tumor and investigating the immunorelated genes is of great significance. To investigate the immunoprognostic genes of ccRCC, we analyzed the data assimilated from a public database (The Cancer Genome Atlas (TCGA) database and the gene expression omnibus (GEO) database) using bioinformatics. Then, a immunoprognosis model was constructed to identify 4 hub genes with moderate predictive values for the prognosis of ccRCC patients. Interestingly, these 4 genes were associated with the prognosis of ccRCC patients based on Oncomine and Gena Expression Profiling Interactive Analysis (GEPIA) databases. The correlation analysis between the immune infiltrate, immune checkpoints, and immunotherapy and this immunoprognosis model showed that immune infiltrate and could predict the immunotherapy effects. We also conducted a quantitative real-time polymerase chain reaction analysis and found that the expressions of 3 hub genes were associated with tumor progression (P<0.1). In conclusion, 4 genes that may serve as potential biomarkers in ccRCC were identified with respect to prognosis.
Utilizing a Cell-free Protein Synthesis Platform for Natural Product Synthesis
Authors: Ditzel Alex , Zhao Fanglong , Gao Xue , Phillips George N. 
Published: July 2022

AbstractNatural products are a great source of pharmaceuticals, providing a majority of all small molecule drugs that exist today. However, creating natural products through organic synthesis or in heterologous hosts can be difficult and time-consuming. Therefore, to allow for easier screening and production of natural products, we demonstrated the use of a cell-free protein synthesis (CFPS) system to partially assemble natural products in vitro using coupled enzyme reactions. The tea caffeine synthase TCS1 was utilized to synthesize caffeine within a CFPS system. Cell-free systems also provide the benefit of allowing the use of substrates that would normally be toxic in a cellular environment to synthesize novel products. The automation and reduced metabolic engineering requirements of CFPS systems combined with other synthesis methods can allow for the efficient generation of new compounds.
Drug repositioning with gender perspective focused on Adverse Drug Reactions
Authors: Otero Carrasco Belén , Pérez Pérez Aurora , Ruiz Ernestina Menasalvas , Caraça-Valente Hernández Juan Pedro , Prieto Santamaría Lucía , Rodríguez-González Alejandro 
Published: July 2022

AbstractDrug repositioning is a novel, useful, and crucial technique to find new uses for existing drugs. In this field of study, when the clinical trials necessary to obtain successful drug repositioning have been carried out, the female gender has not been given much consideration. Thus far, the participation of women in clinical trials has been very limited. There were several argued reasons to exclude them from trials, like the likelihood of pregnancy or sudden hormonal changes. This has meant that for a long time the adverse effects of a drug on women were unknown. Scientifically, it was known that due to the biological processes of pharmacokinetics and pharmacodynamics, the response to drugs was not the same in both genders, but despite this evidence, there is still no difference in the dosage or form of using a drug between men and women. In this study, we made a preliminary analysis where the main goal is to investigate gender differences within the drug repositioning field through the adverse effects produced by such treatments. A special section on specific cases of drug repositioning in rare diseases will also be considered to carry out the same verification previously mentioned in the text.
Cortical grey matter mediates increases in model-based control and learning from positive feedback from adolescence to adulthood
Authors: Scholz Vanessa , Waltmann Maria , Herzog Nadine , Reiter Andrea , Horstmann Annette , Deserno Lorenz 
Published: July 2022

AbstractAdolescents undergo maturation in cognition and brain structure. Model-based (MB) control is known to increase from childhood to young adulthood, which is mediated by cognitive abilities. Here, we asked two questions unaddressed in previous developmental studies: Firstly, what are the brain structural correlates of age-related increases in MB control? Secondly, how are age-related increases in MB control from adolescence to adulthood influenced by motivational context? A developmental sample (n=103, age: 12-42) completed structural MRI and an established task to capture MB control. The task was modified with respect to outcome valence by including (1) reward and punishment blocks to manipulate the motivational context and (2) an additional choice test to assess learning from positive vs. negative feedback. After replicating that an age-dependent increase in MB control is mediated by cognitive abilities, we demonstrate first-time evidence that grey matter density (GMD) in the parietal cortex mediates the increase of MB control with age. While motivational context did not relate to age-related changes in MB control, learning from positive feedback improved with age. Meanwhile, negative feedback learning showed no age effects. We present a first report that an age-related increase in learning from positive feedback was mediated by reduced GMD in the parietal, medial and dorsolateral prefrontal cortex. Our findings indicate that efficient brain maturation, as putatively reflected in lower GMD, in distinct and partially overlapping brain regions is a key developmental step towards age-related increases in planning and value-based choice.Significance StatementAdolescents undergo extensive maturation in cognition and brain structure. Interestingly, model-based decision-making is also known to increase from childhood to adulthood. Here, we demonstrate for the first time that grey matter density in the parietal cortex mediates an age-dependent increase in model-based control. An age-related increase in positive feedback learning was mediated by reduced grey matter density in the parietal, medial and dorsolateral prefrontal cortex. Interestingly, a manipulation of motivational context (gain reward vs. avoid punishment) did not impact age-related changes in model-based control. These findings highlight that efficient brain maturation in distinct and overlapping cortical brain regions constitutes a key developmental step towards increases in model-based planning and value-based choice.
Engineering of Pseudomonas putida for accelerated co-utilization of glucose and cellobiose yields aerobic overproduction of pyruvate explained by an upgraded metabolic model
Authors: Bujdoš Dalimil , Popelářová Barbora , Volke Daniel C. , Nikel Pablo. I. , Sonnenschein Nikolaus , Dvořák Pavel 
Published: July 2022

AbstractPseudomonas putida KT2440 is an attractive bacterial host for biotechnological production of valuable chemicals from renewable lignocellulosic feedstocks as it can valorize lignin-derived aromatics or cellulosic glucose. P. putida EM42, a genome-reduced variant of P. putida KT2440 endowed with advantageous physiological properties, was recently engineered for growth on cellobiose, a major cellooligosaccharide product of enzymatic cellulose hydrolysis. Co-utilization of cellobiose with glucose was achieved in a mutant lacking periplasmic glucose dehydrogenase Gcd (PP_1444). However, the cause of the observed co-utilization was not understood and the Δgcd strain suffered from a significant growth defect. In this study, we aimed to investigate the basis of the simultaneous uptake of the two sugars and accelerate the growth of P. putida EM42 Δgcd mutant for the bioproduction of valuable compounds from glucose and cellobiose. We show that the gcd deletion abolished the inhibition of the exogenous β-glucosidase BglC from Thermobifida fusca by the intermediates of the periplasmic glucose oxidation pathway. The additional deletion of the hexR gene, which encodes a repressor of the upper glycolysis genes, failed to restore the rapid growth on glucose. The reduced growth rate of the Δgcd mutant was partially compensated by the implantation of heterologous glucose (Glf from Zymomonas mobilis) and cellobiose (LacY from Escherichia coli) transporters. Remarkably, this intervention resulted in the accumulation of pyruvate in aerobic P. putida cultures. We demonstrated that the excess of this key metabolic intermediate can be redirected to the enhanced biosynthesis of ethanol and lactate. The overproduction of pyruvate was then unveiled by an upgraded genome-scale metabolic model constrained with proteomic and kinetic data. The model pointed to the saturation of glucose catabolism enzymes due to unregulated substrate uptake and it predicted improved bioproduction of pyruvate-derived chemicals by the engineered strain. This work sheds light on the co-metabolism of cellulosic sugars in an attractive biotechnological host and introduces a novel strategy for pyruvate overproduction in bacterial cultures under aerobic conditions.HighlightsCo-utilization of glucose and cellobiose achieved in P. putida EM42 Δgcd mutant.Growth defect of the mutant compensated by implanting exogenous sugar transporters.Enhanced influx of carbon caused aerobic overproduction of pyruvate and acetate.Carbon from excess pyruvate streamed into ethanol or L-lactate.Pyruvate overproduction unveiled by a mathematical model of P. putida metabolism.
Evaluation of the nemabiome approach for the study of equine strongylid communities
Authors: Courtot Élise , Boisseau Michel , Dhorne-Pollet Sophie , Serreau Delphine , Gesbert Amandine , Reigner Fabrice , Basiaga Marta , Kuzmina Tetiana , Lluch Jérôme , Annonay Gwenolah , Kuchly Claire , Diekmann Irina , Krücken Jürgen , Samson-Himmelstjerna Georg von , Mach Nuria , Sallé Guillaume 
Published: July 2022

AbstractBasic knowledge on the biology and epidemiology of equine strongylid species remains insufficient although it would contribute to the design of better parasite control strategies. Nemabiome is a convenient tool to quantify and to identify species in bulk samples that could overcome the hurdle that cyathostomin morphological identification represents. To date, this approach has relied on the internal transcribed spacer 2 (ITS-2) of the ribosomal RNA cistron and its predictive performance and associated biases both remain unaddressed.This study aimed to bridge this knowledge gap using cyathostomin mock communities and comparing performances of the ITS-2 and acytochrome c oxidase subunit I(COI) barcode newly developed in this study. The effects of bioinformatic parameters were investigated to determine the best analytical pipelines. Subsequently, barcode predictive abilities were compared across various mock community compositions. The replicability of the approach and the amplification biases of each barcode were estimated. Results were also compared between various types of biological samples, i.e. eggs, infective larvae or adults.Overall, the proposed COI barcode was suboptimal relative to the ITS-2 rDNA region, because of PCR amplification biases, a reduced sensitivity and higher divergence from the expected community composition. Metabarcoding yielded consistent community composition across the three sample types, although infective larvae may remain the most tractable in the field. Additional strategies to improve the COI barcode performances are discussed. These results underscore the critical need of mock communities for metabarcoding purposes.
Combined Scattering, Interferometric and Fluorescence Oblique Illumination for Live Cell Nanoscale Imaging
Authors: Zheng Yujie , Lim Yean Jin , Lin Hanqi , Xu Tienan , Longbottom Carmen , Delghingaro-Augusto Viviane , Thong Yee Lin , Parish Christopher R. , Gardiner Elizabeth E. , Lee Woei Ming 
Published: July 2022

ABSTRACTTo determine the molecular and/or mechanical basis of cell migration using live cell imaging tools, it is necessary to correlate multiple 3D spatiotemporal events simultaneously. Fluorescence nanoscopy and label free nanoscale imaging can complement each other by providing both molecular specificity and structural dynamics of sub-cellular structure. In doing so, a combined imaging system would permit quantitative 3D spatial temporal detail of individual cellular components. In this paper, we empirically determined a series of optimal azimuthal scanning angles and rotating beam to achieve simultaneous and label-free nanoscale and fluorescence imaging. Label-free nanoscale imaging here refers to interferometric, brightfield (BF) and darkfield (DF) rotating coherence scattering (ROCS) microscopy, while fluorescence refers to high inclined Laminated Oblique (HiLO) and total internal reflection fluorescence (TIRF) imaging. The combined capabilities of interferometric, scattering and fluorescence imaging enables (1) the identification of molecular targets (substrate or organelle), (2) quantification of 3D cell morphodynamics, and (3) tracking of intracellular organelles in 3D. This combined imaging tool was then used to characterize migrating platelets and adherent endothelial cells, both critical to the process of infection and wound healing. The combined imaging results of over ∼1000 platelets, suggested that serum albumin (bovine) was necessary for platelets to migrate and scavenge fibrin/fibrinogen. Furthermore, we determine new asynchronous membrane fluctuations between the leading and rear edge of a migrating platelet. We further demonstrated that interferometric imaging permitted the quantification of mitochondria dynamics on lung microvascular cells (HMVEC). Our data suggests that axial displacement of mitochondria is minimized when it is closer to the nucleus or the leading edge of a cell membrane that exhibits retrograde motion. Taken together, this combined imaging platform has proven to quantify multiple spatial temporal events of a migrating cell, that will undoubtedly open ways to new quantitative correlative nanoscale live cell imaging.
An immunoresponsive three-dimensional urine-tolerant human urothelial (3D-UHU) model to study urinary tract infection
Authors: Jafari Nazila V. , Rohn Jennifer L. 
Published: July 2022

AbstractMurine models of urinary tract infection (UTI) have significantly improved our understanding of host-pathogen interactions. However, given some differences between the rodent and human bladder which may modulate bacterial response, including certain biomarkers, urothelial thickness and the concentration of urine, the development of new human-based models is important to complement mouse studies and to provide a more complete picture of UTI in patients. We originally developed a human urothelial three-dimensional (3D) model which was urine tolerant and demonstrated several biomarkers of the urothelium, but it only achieved human thickness in heterogenous, multi-layered zones and did not demonstrate the comprehensive differentiation status needed to achieve barrier function. Here, we report an improved 3D urine-tolerant human urothelial (3D-UHU) model, which after 18-20 days of growth, stratifies uniformly to 7 layers. We confirmed by flow-cytometric analysis that the model is comprised of the three expected, distinct human cell types. The apical surface differentiated into large, CD227+ umbrella-like cells expressing uroplakin-1A, II, III, and cytokeratin 20, all of which are important terminal differentiation markers, and a glycosaminoglycan layer. Below this layer, several layers of intermediate cells were present, with a single underlying layer of CD271+ basal cells. The apical surface also expressed E-cadherin, ZO-1, claudin-1 and -3, necessary for barrier formation; barrier integrity was confirmed by transepithelial electrical resistance and FITC-dextran permeability assay. Infection with both Gram-negative and Gram-positive bacterial classes elicited elevated levels of pro-inflammatory cytokines and chemokines characteristic of urinary tract infection in humans, and caused a decrease in barrier function, suggesting that the 3D-UHU model holds promise for studying host-pathogen interactions and host innate immune response.
Evolutionary responses to acquiring a multidrug resistance plasmid are dominated by metabolic functions across diverse Escherichia coli lineages
Authors: Carrilero Laura , Dunn Steven , McNally Alan , Brockhurst Michael 
Published: July 2022

AbstractMultidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ∼700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions.
A large-scale brain network of species-specific dynamic human body perception
Authors: Li Baichen , Solanas Marta Poyo , Marrazzo Giuseppe , Raman Rajani , Taubert Nick , Giese Martin , Vogels Rufin , de Gelder Beatrice 
Published: July 2022

ABSTRACTThis ultrahigh field 7T fMRI study addressed the question of whether there exists a core network of brain areas at the service of different aspects of body perception. Participants viewed naturalistic videos of monkey and human faces, bodies, and objects along with mosaic-scrambled videos for control of low-level features. ICA-based network analysis was conducted to find body and species modulations at both the voxel and the network levels. Among the body areas, the highest species selectivity was found in the middle frontal gyrus and amygdala. Two large-scale networks were highly selective to bodies, dominated by the lateral occipital cortex and right superior temporal sulcus (STS) respectively. The right STS network showed high species selectivity, and its significant human body-induced node connectivity was focused around the extrastriate body area (EBA), STS, temporoparietal junction (TPJ), premotor cortex, and inferior frontal gyrus (IFG). The human body-specific network discovered here may serve as a brain-wide internal model of the human body serving as an entry point for a variety of processes relying on body descriptions as part of their more specific categorization, action, or expression recognition functions.