bluuebunny/crossref_metadata_2025_split huggingface dataset:
TransgeneR: a one-stop tool for transgene integration and rearrangement discovery using sequencing data
Authors: Meng Guofeng 
Published: November 2018

AbstractGenetically modified organisms are widely used in lifescience research, agriculture and in commercial products. However, in most cases, the genetic modification in the host genome is often less well characterized with respect to integration location, copy number and host gene expression. The application of next generation sequencing technologies has enabled the characterization of transgene events but still limited by the lack of computational tools. We present a one-stop R tool, transgeneR, as a general computational tool for discovering transgene integration and rearrangement in the host genome. It especially considers the properties of transgene events, such as the homologous transgene sequences, complex genetic structure and multiple copies of transgene insertion. Using this tool, we have successfully mapped the chromosomal transgene integration loci and transgene rearrangements in an artificially simulated MAPT transgene mice genome as well as in a newly generated human tau (MAPT, 0N4R) transgene mice. When unbiased sequencing data such as the whole genome sequencing data, were provided as input, transgeneR integrated multiple information, including integration location, direction, split- and nonsplit-reads, to predict the transgene fragments and their copy number. Overall, our initial evaluation indicates that the transgeneR package is an effective tool for the identification and characterization of transgene integration and rearrangements events, especially in transgene genome with complex genetic structure. TransgeneR is publicly available: https://github.com/menggf/transgeneR
High levels of antibiotic resistance gene expression among birds living in a wastewater treatment plant
Authors: Marcelino Vanessa R. , Wille Michelle , Hurt Aeron C. , González-Acuña Daniel , Klaassen Marcel , Eden John-Sebastian , Shi Mang , Iredell Jonathan R. , Sorrell Tania C. , Holmes Edward C. 
Published: November 2018

AbstractAntibiotic resistance is rendering common bacterial infections untreatable. Wildlife can incorporate and disperse antibiotic resistant bacteria in the environment, such as water systems, which in turn serve as reservoirs of resistance genes for human pathogens. We used bulk RNA-sequencing (meta-transcriptomics) to assess the diversity and expression levels of functionally active resistance genes in the microbiome of birds with aquatic behavior. We sampled birds across a range of habitats, from penguins in Antarctica to ducks in a wastewater treatment plant in Australia. This revealed 81 antibiotic resistance genes in birds from all localities, including β-lactam, tetracycline and chloramphenicol resistance in Antarctica, and genes typically associated with multidrug resistance plasmids in areas with high human impact. Notably, birds feeding at a wastewater treatment plant carried the greatest resistance gene burden, suggesting that human waste, even if it undergoes treatment, contributes to the spread of antibiotic resistance genes to the wild. Differences in resistance gene burden also reflected the birds’ ecology, taxonomic group and microbial functioning. Ducks, which feed by dabbling, carried a higher abundance and diversity of resistance genes than turnstones, avocets and penguins, that usually prey on more pristine waters. In sum, this study helps to reveal the complex factors explaining the distribution of resistance genes and their exchange routes between humans and wildlife.
Structure and function of a bacterial gap junction analog
Authors: Weiss Gregor L. , Kieninger Ann-Katrin , Maldener Iris , Forchhammer Karl , Pilhofer Martin 
Published: November 2018

SummaryMulticellular lifestyle requires cell-cell connections. In multicellular cyanobacteria, septal junctions enable molecular exchange between sister cells and are required for cellular differentiation. The structure of septal junctions is poorly understood and it is unknown whether they regulate intercellular communication.Here we resolved thein situarchitecture of septal junctions by electron cryotomography of cryo-focused ion beam-milled cyanobacteria. Septal junctions consisted of a tube traversing the septal peptidoglycan. Each tube end comprised a plug that was covered by a cytoplasmic cap. Fluorescence recovery after photobleaching showed that intercellular communication was blocked upon stress. This gating was accompanied by a conformational change of the septal junctions, mediated by the proteins FraC/D.We provide the mechanistic framework for a cell junction that predates eukaryotic gap junctions by a billion years. The conservation of a gated dynamic mechanism across different domains of life emphasizes the importance of controlling molecular exchange, e.g. upon injury.
Inter-organ growth coordination is mediated by the Xrp1/Dilp8 axis in Drosophila
Authors: Boulan Laura , Andersen Ditte , Colombani Julien , Boone Emilie , Léopold Pierre 
Published: November 2018

ABSTRACTHow organs scale with other body parts is not mechanistically understood. We have addressed this question using the Drosophila imaginal disc model. When growth of one disc domain is perturbed, other parts of the disc and other discs slow down their growth, maintaining proper inter-disc and intra-disc proportions. We show here that the relaxin-like Dilp8 is required for this inter-organ coordination. Our work also reveals that the stress-response transcription factor Xrp1 plays a key role upstream of dilp8 in linking organ growth status with non-autonomous/systemic growth response. In addition, we show that the small ribosomal subunit protein RpS12 is required to trigger Xrp1-dependent non-autonomous response. Our work demonstrates that RpS12, Xrp1 and Dilp8 constitute a new, independent regulatory module that ensures intra- and inter-organ growth coordination during development.
Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study
Authors: McGrory Sarah , Ballerini Lucia , Doubal Fergus N. , Staals Julie , Allerhand Mike , Valdes-Hernandez Maria del C. , Wang Xin , MacGillivray Thomas J. , Doney Alex S.F. , Dhillon Baljean , Starr John M. , Bastin Mark E. , Trucco Emanuele , Deary Ian J. , Wardlaw Joanna M. 
Published: November 2018

ABSTRACTResearch has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936; and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study. Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. We assessed associations between retinal and brain measurements using structural equation modelling and regression analysis. In the Lothian Birth Cohort 1936 arteriolar fractal dimension accounted for 4% of the variance in WMH load. In the Mild Stroke Study lower arteriolar fractal dimension was associated with deep WMH scores (odds ratio [OR] 0.53; 95% CI, 0.32-0.87). No other retinal measure was associated with SVD. Reduced fractal dimension, a measure of vascular complexity, is related to SVD imaging features in older people. The results provide some support for the use of the retinal vasculature in the study of brain microvascular disease.
Prolonged quiescence delays somatic stem cell-like division inCaenorhabditis elegansand is controlled by insulin signalling
Authors: Olmedo María , Mata-Cabana Alejandro , Rodríguez-Palero María Jesús , García-Sánchez Sabas , Fernández-Yañez Antonio , Merrow Martha , Artal-Sanz Marta 
Published: November 2018

SummaryCells can enter quiescence in adverse conditions and resume proliferation when the environment becomes favourable. Prolonged quiescence comes with a cost, reducing proliferation potential and survival. Interestingly, cellular quiescence also occurs in normal development, with many cells spending most of their lifetime at this state. Elucidating the mechanisms involved in surviving long-term quiescence and in maintenance of cellular proliferation potential will contribute to a better understanding of the process of tissue regeneration. Developmental arrest ofC. elegansat the L1 stage is an emerging model for the study of cellular quiescence and reactivation. During arrest, L1 larvae undergo a process that shares phenotypic hallmarks with the ageing of the adult. Interestingly, insulin signalling, a prominent pathway in the regulation of ageing, also balances cell proliferation and activation of stress resistance pathways during quiescence, becoming a candidate regulator of proliferation potential. Here we report that prolonged L1 quiescence delays reactivation of blast cell divisions inC. elegans, leading to a delay in the initiation of postembryonic development. This delay is accompanied by increased inter-individual variability. We propose that the delay in cell division results from the decline that animals suffer during L1 arrest. To that end, we show that insulin signalling modulates the rate of L1 ageing, affecting proliferative potential after quiescence. These findings support that the insulin signalling pathway has a comparable role in L1 arrest to that in ageing adults. Furthermore, we show that variable yolk provisioning to the embryos as a consequence of maternal age is one of the sources of inter-individual variability in recovery after quiescence of genetically identical animals. Taken together, these results support the relevance of L1 arrest as a model to studyin vivoproliferation after quiescence and to understand the mechanisms for maintenance of proliferation potential.
Stress-induced neuron remodeling reveals differential interplay between neurexin and environmental factors
Authors: Hart Michael P. 
Published: November 2018

ABSTRACTNeurexins are neuronal adhesion molecules important for synapse maturation, function, and plasticity. Neurexins have been genetically associated with neurodevelopmental disorders including autism spectrum disorders (ASDs) and schizophrenia, but can have variable penetrance and phenotypic severity. Heritability studies indicate that a significant percentage of risk for ASD and schizophrenia includes environmental factors, highlighting the poorly understood interplay between genetic and environmental factors in pathogenesis of these disorders. The singularC. elegansortholog of human neurexins,nrx-1, controls experience-dependent morphologic remodeling of a GABAergic neuron in adult males. Here I show that this GABAergic neuron’s morphology is altered in response to each of three environmental stressors (nutritional, heat, or genotoxic stress) applied during sexual maturation, but not during adulthood. Increased outgrowth of axon-like neurites following adolescent stress results from an altered morphologic plasticity that occurs upon entry into adulthood. Despite axonal remodeling being induced by each of the three stressors, only nutritional stress (starvation) impacts behavior and is dependent on neurexin/nrx-1. Heat or genotoxic stress during sexual maturation did not alter behavior despite inducing GABAergic neuron remodeling, and this remodeling was independent of neurexin/nrx-1. Remodeling induced by starvation stress was found be dependent on neuroligin/nlg-1, the canonical binding partner for neurexin/nrx-1, as well as the stress signaling transcription factorsFOXO/daf-16andHSF1/hsf-1, each of which was also found to have unique roles in remodeling induced by heat and UV stress. The differential molecular mechanisms underlying GABAergic neuron remodeling in response to different stressors, and the disparate effects of stressors on behavior, is a novel paradigm for understanding how genetics, environmental exposures, and plasticity may contribute to brain dysfunction in ASDs and schizophrenia.
Bridging the translational gap: Implementation of multimodal small animal imaging strategies for tumor burden assessment in a co-clinical trial
Authors: Blocker S.J. , Mowery Y.M. , Holbrook M. D. , Qi Y. , Kirsch D.G. , Johnson G.A. , Badea C.T. 
Published: November 2018

AbstractIn designing co-clinical cancer studies, preclinical imaging brings unique challenges that emphasize the gap between man and mouse. Our group is developing quantitative imaging methods for the preclinical arm of a co-clinical trial studying immunotherapy and radiotherapy in a soft tissue sarcoma model. In line with treatment for patients enrolled in the clinical trial SU2C-SARC032, primary mouse sarcomas are imaged with multi-contrast micro-MRI (T1 weighted, T2 weighted, and T1 with contrast) before and after immune checkpoint inhibition and pre-operative radiation therapy. Similar to the patients, after surgery the mice will be screened for lung metastases with micro-CT using respiratory gating. A systems evaluation was undertaken to establish a quantitative baseline for both the MR and micro-CT systems against which others systems might be compared. We have constructed imaging protocols which provide clinically-relevant resolution and contrast in a genetically engineered mouse model of sarcoma. We have employed tools in 3D Slicer for semi-automated segmentation of both MR and micro-CT images to measure tumor volumes efficiently and reliably in a large number of animals. Assessment of tumor burden in the resulting images was precise, repeatable, and reproducible. Furthermore, we have implemented a publicly accessible platform for sharing imaging data collected during the study, as well as protocols, supporting information, and data analyses. In doing so, we aim to improve the clinical relevance of small animal imaging and begin establishing standards for preclinical imaging of tumors from the perspective of a co-clinical trial.
eUTOPIA: Solution for omics data preprocessing and analysis
Authors: Marwah Veer Singh , Scala Giovanni , Kinaret Pia Anneli Sofia , Serra Angela , Alenius Harri , Fortino Vittorio , Greco Dario 
Published: November 2018

AbstractApplication of microarrays in omics technologies enables quantification of many biomolecules simultaneously. It is widely applied to observe the positive or negative effect on biomolecule activity in perturbed versus the steady state by quantitative comparison. Community resources, such as Bioconductor and CRAN, host tools based on R that have become standard for high-throughput analytics. However, there is a need for intuitive and easy-to-use platform to process omics data, visualize, and interpret results, which is computational skill neutral. We propose an integrated software solution, eUTOPIA, that implements a set of essential processing steps as a guided workflow presented to the user as an R Shiny application. eUTOPIA allows researchers to perform preprocessing and analysis of microarray data via a simple and intuitive graphical interface while using state of the art methods. eUTOPIA is free for academic use and can be obtained from the GitHub repository https://github.com/Greco-Lab/eUTOPIA.
Establishment and characteristic of an orthotopic implantation model of human hepatocellular carcinoma with Luc-GFP-labeled in nude mice
Authors: Zhang Jing-jing , Xu Min-hua , Wang Jie , Jin Xiao-bao , Ma Yan 
Published: November 2018

AbstractAimTo construct Luc-GFP-labeled human hepatocellular carcinoma (HCC) cell line with high metastatic potential. And to establish a spontaneous metastasis and conveniently monitored orthotopic model of hepatocellular carcinoma in nude mice. Methods: HCCLM3-Luc-GFP cell line stably expressing luciferase (Luc) and green fluorescent protein (GFP) was constructed by lentivirus transfection. The orthotopic xenograft model was established though cell suspension injection method and tumor fragment implanted method. The growth and metastasis of the tumors were observed by in vivo imaging and pathology. Results: HCCLM3-Luc-GFP, a highly metastatic HCC cell line with GFP expression and Luc activity, was obtained. The tumorigenic rates both of two approaches were 100%, but the lung metastatic rate was higher the former than the latter. Conclusion: The orthotopic model of highly metastatic and Luc-GFP-labeled HCC in nude mice was successfully established by above approaches, called as cell suspension injection method and tumor fragment implanted method, respectively. This study provides a new and effective means to monitor the growth of tumors in vivo and to evaluate the efficacy of anti-metastatic drugs against HCC.
STAT6 mRNA and protein knockdown using multiple siRNA sequences inhibits proliferation and induces apoptosis of the human colon adenocarcinoma cell line, HT-29
Authors: Salguero-Aranda C. , Sancho-Mensat D. , Sultan S. , Reginald A. , Chapman L. 
Published: November 2018

AbstractThe transcription factor STAT6 is strongly expressed in various tumours and is most highly expressed in malignant lymphomas and pancreatic, colorectal, prostate and breast cancers. STAT6 expression in colorectal cancer is associated with an increased malignancy, poor prognosis and poor survival rates. Colorectal cancer has an incidence of approximately 1,361,000 patientsper annumworldwide and approximately 60% of those cancers show STAT6 expression. Techniques aimed at reducing or blocking STAT6 expression may be useful in treating colorectal cancers. Celixir’s four proprietary STAT6 specific small interfering RNA (siRNA) sequences were testedin vitrousing the human colon adenocarcinoma cell line, HT-29. The four sequences were introduced individually and in combination into HT-29 cells at different concentrations (10 to 200 nM). Decreases in STAT6 mRNA and protein levels were analysed to confirm the transfection was successful. STAT6 knockdown effects were measured by analysing cell proliferation and apoptosis. Results showed that 100nM siRNA concentration was the most effective and all four individual sequences knocked-down STAT6 mRNA and protein by more than 50%. Although all individual sequences were capable of significantly inhibiting cell proliferation, STAT6.1 and STAT6.4 were the best. STAT6 silencing also significantly induced late and total apoptotic events. In conclusion, these results demonstrate that STAT6 siRNA sequences are capable of inhibiting the proliferation, and inducing late apoptosis, of HT-29 colon cancer cells and, in some instances, halving the number of cancer cells. These experiments will be repeated using xenografts of STAT6-expressing colon cancer cells in immunocompromised mice and the STAT6 siRNA sequences will be tested in other cancers in which STAT6 is expressed. The STAT6 siRNA sequences therefore represent a potential treatment for the most serious colorectal cancers and a wide variety of STAT6-expressing cancers.
A more physiological approach to lipid metabolism alterations in cancer: CRC-like organoids assessment
Authors: Cruz-Gil Silvia , Sanchez-Martinez Ruth , Wagner-Reguero Sonia , Stange Daniel , Schölch Sebastian , Werner Kristin , Ramirez de Molina Ana 
Published: November 2018

AbstractPrecision medicine might be the response to the recent questioning of the use of metformin as an anticancer drug in colorectal cancer (CRC). Thus, in order to establish properly its benefits, its application need to be assayed on the different progression stages of CRC. In this way, organoids imply a more physiological tool, representing a new therapeutic opportunity for CRC personalized treatment to assay tumor stage-dependent drugs effects. Since the lipid metabolism-related axis, ACSL/SCD, stimulates colon cancer progression and Metformin is able to rescuing the invasive and migratory phenotype conferred to cancer cells upon this axis overexpression; we checked ACSL/SCD status, its regulatory miRNAs and the effect of Metformin treatment in organoids as a model for specific and personalized treatment. Despite ACSL4 expression is upregulated in CRC-like organoids, Metformin is able to downregulate it, especially in the first stages. Besides, organoids are clearly more sensitive in this first stage (Apc mutated) to Metformin than current chemotherapeutic drugs such as fluorouracil (5-FU). Metformin performs an independent “Warburg effect” blockade to cancer progression and is able to reduce crypt stem cell markers expression such as Lgr5+. These results suggest a putative increased efficiency of the use of Metformin in the first stages of CRC than in advanced disease.
The spermidine acetyltransferase SpeG regulates transcription of the small RNA RprA
Authors: Hu Linda I. , Filippova Ekaterina V. , Dang Joseph , Pshenychnyi Sergii , Ruan Jiapeng , Kiryukhina Olga , Anderson Wayne F. , Kuhn Misty L. , Wolfe Alan J. 
Published: November 2018

AbstractSpermidineN-acetyltransferase (SpeG) acetylates and thus neutralizes toxic polyamines. Studies indicate that SpeG plays an important role in virulence and pathogenicity of many bacteria, which have evolved SpeG-dependent strategies to control polyamine concentrations and survive in their hosts. InEscherichia coli, the two-component response regulator RcsB is reported to be subject to Nε-acetylation on several lysine residues, resulting in reduced DNA binding affinity and reduced transcription of the small RNArprA; however, the physiological acetylation mechanism responsible for this behavior has not been fully determined. Here, we performed an acetyltransferase screen and found that SpeG inhibitsrprApromoter activity in an acetylation-independent manner. Surface plasmon resonance analysis revealed that SpeG can physically interact with the DNA-binding carboxyl domain of RcsB. We hypothesize that SpeG interacts with the DNA-binding domain of RcsB and that this interaction might be responsible for SpeG-dependent inhibition of RcsB-dependentrprAtranscription. This work provides a model for SpeG as a modulator ofE. colitranscription through its ability to interact with the transcription factor RcsB. This is the first study to provide evidence that an enzyme involved in polyamine metabolism can influence the function of the global regulator RcsB, which integrates information concerning envelope stresses and central metabolic status to regulate diverse behaviors.
Phylogeny of the AustralianSolanum dioicumgroup using seven nuclear genes: Testing Symon’s fruit and seed dispersal hypotheses
Authors: Martine Christopher T. , Jordon-Thaden Ingrid E. , McDonnell Angela J. , Cantley Jason T. , Hayes Daniel S. , Roche Morgan D. , Frawley Emma S. , Gilman Ian S. , Tank David C. 
Published: November 2018

AbstractThe dioecious and andromonoeciousSolanumtaxa (previously described as the “S. dioicumgroup”) of the Australian Monsoon Tropics have been the subject of phylogenetic and taxonomic study for decades, yet much of their basic biology is still unknown. This is especially true for plant-animal interactions, including the influence of fruit form and calyx morphology on seed dispersal. We combine field/greenhouse observations and specimen-based study with phylogenetic analysis of seven nuclear regions obtained via a microfluidic PCR-based enrichment strategy and high-throughput sequencing, and present the first intron-containing nuclear gene dataset in the genusSolanumand the first species-tree hypothesis for theS. dioicumgroup. Our results suggest that epizoochorous trample burr seed dispersal (strongly linked to calyx accrescence) is far more common among AustralianSolanumthan previously thought and support the hypothesis that the combination of large fleshy fruits and endozoochorous dispersal represents a reversal in this study group. The general lack of direct evidence related to biotic dispersal (epizoochorous or endozoochorous) may be a function of declines and/or extinctions of vertebrate dispersers. Because of this, some taxa might now rely on secondary dispersal mechanisms (e.g. shakers, tumbleweeds, rafting) as a means to maintain current populations and establish new ones.