bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen and Soy Isoflavonoids Decrease Sensitivity of Medulloblastoma and Central Nervous System Primitive Neuroectodermal Tumor Cells to Chemotherapeutic Cytotoxicity
Authors: Belcher Scott M. , Burton Caleb C. , Cookman Clifford J. , Kirby Michelle , Miranda Gabriel L. , Saeed Fatima , Wray Kathleen E. 
Published: January 2017

AbstractBackgroundOur previous studies demonstrated that growth and migration of medulloblastoma (MB), the most common malignant brain tumor in children, are stimulated by 17β-estradiol. The growth stimulating effects of estrogens are mediated through ERβ and insulin-like growth factor 1 signaling to inhibit caspase 3 activity and reduce tumor cell apoptosis. The objective of this study was to determine whether estrogens decreased sensitivity of MB cells to cytotoxic actions of chemotherapeutic drugs.MethodsUsingin vitrocell viability and clonogenic survival assays, concentration response analysis was used to determine whether the cytoprotective effects of estradiol protected human D283 Med MB cells from the cytotoxic actions of the MB chemotherapeutic drugs cisplatin, vincristine, or lomustine. Additional experiments were done to determine whether the ER antagonist fulvestrant or the selective ER modulator tamoxifen blocked the cytoprotective actions of estradiol. ER-selective agonists and antagonists were used to define receptor specificity, and the impacts of the soy-derived phytoestrogens genistein, daidzein, and s-equol on chemosensitivity were evaluated.ResultsIn D283 Med cells the presence of 10 nM estradiol increased the IC50for cisplatin-induced inhibition of viability 2-fold from ~5 μM to >10 μM. In clonogenic survival assays estradiol decreased the chemosensitivity of D283 Med exposed to cisplatin, lomustine and vincristine. The ERβ selective agonist DPN and low physiological concentrations of the soy-derived phytoestrogens genistein, daidzein, and s-equol also decreased sensitivity of D283 Med cells to cisplatin. The protective effects of estradiol were blocked by the antiestrogens 4-hydroxytamoxifen, fulvestrant (ICI 182,780) and the ERβ selective antagonist PPHTP. Whereas estradiol also decreased chemosensitivity of PFSK1 cells, estradiol increased sensitivity of Daoy cell to cisplatin, suggesting that ERβ mediated effects may vary in different subtypes of MB.ConclusionsThese findings demonstrate that E2 and environmental estrogens decrease sensitivity of MB to cytotoxic chemotherapeutics, and that ERβ selective and non-selective inhibition of estrogen receptor activity blocks these cytoprotective actions. These findings support the therapeutic potential of antiestrogen adjuvant therapies for MB, and findings that soy phytoestrogens also decrease sensitivity of MB cells to cytotoxic chemotherapeutics suggest that decreased exposure to environmental estrogens may benefit MB patient responses to chemotherapy.
A high density linkage map reveals sexual dimorphism in recombination landscapes in red deer (Cervus elaphus)
Authors: Johnston Susan E. , Huisman Jisca , Ellis Philip A. , Pemberton Josephine M. 
Published: January 2017

AbstractHigh density linkage maps are an important tool to gain insight into the genetic architecture of traits of evolutionary and economic interest, and provide a resource to characterise variation in recombination landscapes. Here, we used information from the cattle genome and the 50K Cervine Illumina BeadChip to inform and refine a high density linkage map in a wild population of red deer (Cervus elaphus). We constructed a predicted linkage map of 38,038 SNPs and a skeleton map of 10,835 SNPs across 34 linkage groups. We identified several chromosomal rearrangements in the deer lineage relative to sheep and cattle, including six chromosome fissions, one fusion and two large inversions. Otherwise, our findings showed strong concordance with map orders in the cattle genome. The sex-averaged linkage map length was 2739.7cM and the genome-wide autosomal recombination rate was 1.04cM per Mb. The female autosomal map length was 1.21 longer than that of males (2767.4cM vs 2280.8cM, respectively). Sex differences in map length were driven by high female recombination rates in peri-centromeric regions, a pattern that is unusual relative to other mammal species. This effect was more pronounced in fission chromosomes that would have had to produce new centromeres. We propose two hypotheses to explain this effect: (1) that this mechanism may have evolved to counteract centromeric drive associated with meiotic asymmetry in oocyte production; and/or (2) that sequence and structural characteristics suppressing recombination in close proximity to the centromere may not have yet evolved at neo-centromeres. Our study provides insight into how recombination landscapes vary and evolve in mammals, and will provide a valuable resource for studies of evolution, genetic improvement and population management in red deer and related species.Article SummaryWe present a high density linkage map (>38,000 markers) in a wild population of Red deer(Cervus elaphus).Our investigation of the recombination landscape showed a marked difference in recombination rates between the sexes in proximity to the centromere, with females showing an unusually elevated rate relative to other mammal species. This effect is most pronounced in chromosomes that would have produced a new centromere in the deer lineage. We propose that the observed effects have evolved to counteract selfish genetic elements associated with asymmetrical female meiosis.
An Improved Crystal Violet Assay for Biofilm Quantification in 96-Well Microtitre Plate
Authors: Shukla Sudhir K. , Rao T. Subba 
Published: January 2017

AbstractMicroplates are essential tools for biofilm research since it allows high throughput screening of biofilm forming strains or in the assay of anti-biofilm drugs. However, 96 well microtitre plate based assays share the issue of “edge effect”. The primary cause of the “edge effect” phenomenon is evaporation. As edge effect causes a significant increase in plate rejection rate by introducing experimental error, we improvised the classical crystal violet assay to reduce water loss from the peripheral wells. The improvised method showed a significant reduction in edge effect and minimised error in crystal violet assay
Repression of YdaS Toxin is Mediated by Transcriptional Repressor RacR in the cryptic rac prophage of Escherichia coli-K12
Authors: Krishnamurthi Revathy , Ghosh Swagatha , Khedkar Supriya , Seshasayee Aswin Sai Narain 
Published: January 2017

AbstractHorizontal gene transfer is a major driving force behind the genomic diversity seen in prokaryotes. Theracprophage inE.coliK12 encodes a putative transcription factor RacR, whose deletion is lethal. We have shown that the essentiality ofracRinE.coliK12 is attributed to its role in transcriptionally repressing a toxin gene calledydaS, which is coded adjacent and divergently toracR.
Semaphorin4D induces inhibitory synapse formation by rapid stabilization of presynaptic boutons via MET co-activation
Authors: Frias Cátia P. , Bresser Tom , Scheefhals Lisa , Yin Hu Hai , van Bergen en Henegouwen Paul M. P. , Hoogenraad Casper C. , Wierenga Corette J. 
Published: January 2017

ABSTRACTChanges in inhibitory connections are essential for experience-dependent circuit adaptations. Defects in inhibitory synapses are linked to neurodevelopmental disorders, but the molecular processes underlying inhibitory synapse formation are not well understood. Here we use high resolution two-photon microscopy in organotypic hippocampal slices to examine the signaling pathways induced by the postsynaptic signaling molecule Semaphorin4D (Sema4D) during inhibitory synapse formation. By monitoring changes in individual GFP-labeled presynaptic boutons we found that the primary action of Sema4D is to induce stabilization of presynaptic boutons within tens of minutes. Stabilizing boutons rapidly recruited synaptic vesicles, which was followed by accumulation of postsynaptic gephyrin. Newly formed inhibitory synapses were complete and functional after 24 hours, as determined by electrophysiology and immunohistochemistry. We further showed that Sema4D signaling is regulated by network activity and can induce a local increase in bouton density, suggesting a possible role in circuit adaptation. We further examined the intracellular signaling cascade triggered by Sema4D and found that bouton stabilization occurred through rapid remodeling of actin, and this could be mimicked by the actin-depolymerizing drug Latrunculin B or by reducing ROCK activity. The intracellular signaling cascade required activation of the receptor tyrosine kinase MET, which is a well-known autism risk factor. Our immunohistochemistry data suggests that MET may be localized to presynaptic inhibitory axons. Together, our data yield important insights in the molecular pathway underlying activity-dependent Sema4D-induced synapse formation and reveal a novel role for MET in inhibitory synapses.Significance StatementGABAergic synapses provide the main inhibitory control of neuronal activity in the brain. We make important steps in unraveling the molecular processes that take place when formation of inhibitory synapses is triggered by a specific signaling molecule, Sema4D. We find that this process depends on network activity and involves specific remodeling of the intracellular actin cytoskeleton. We also reveal a previously unknown role for MET in inhibitory synapses. As defects in GABAergic synapses have been implied in many brain disorders, and mutations in MET are strong risk factors for autism, our findings urge for a further investigation of the role of MET at inhibitory synapses.
A Network Integration Approach for Drug-Target Interaction Prediction and Computational Drug Repositioning from Heterogeneous Information
Authors: Luo Yunan , Zhao Xinbin , Zhou Jingtian , Yang Jinglin , Zhang Yanqing , Kuang Wenhua , Peng Jian , Chen Ligong , Zeng Jianyang 
Published: January 2017

AbstractThe emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery and repositioning. Systematic integration of these heterogeneous data not only serves as a promising tool for identifying new drug-target interactions (DTIs), which is an important step in drug development, but also provides a more complete understanding of the molecular mechanisms of drug action. In this work, we integrate diverse drug-related information, including drugs, proteins, diseases and side-effects, together with their interactions, associations or similarities, to construct a heterogeneous network with 12,015 nodes and 1,895,445 edges. We then develop a new computational pipeline, called DTINet, to predict novel drug-target interactions from the constructed heterogeneous network. Specifically, DTINet focuses on learning a low-dimensional vector representation of features for each node, which accurately explains the topological properties of individual nodes in the heterogeneous network, and then predicts the likelihood of a new DTI based on these representations via a vector space projection scheme. DTINet achieves substantial performance improvement over other state-of-the-art methods for DTI prediction. Moreover, we have experimentally validated the novel interactions between three drugs and the cyclooxygenase (COX) protein family predicted by DTINet, and demonstrated the new potential applications of these identified COX inhibitors in preventing inflammatory diseases. These results indicate that DTINet can provide a practically useful tool for integrating heterogeneous information to predict new drug-target interactions and repurpose existing drugs. The source code of DTINet and the input heterogeneous network data can be downloaded fromhttp://github.com/luoyunan/DTINet.
Barriers to access to opioid medicines for patients with opioid dependence: a review of legislation and regulations in eleven central and eastern European countries
Authors: Vranken Marjolein J. M. , Mantel‐Teeuwisse Aukje K. , Jünger Saskia , Radbruch Lukas , Scholten Willem , Lisman John A. , Subataite Marija , Schutjens Marie‐Hélène D. B. 
Published: January 2017

AbstractBackground and aimsBarriers linked to drug control systems are considered to contribute to inequitable access to controlled medicines, leaving millions of people in pain and suffering. Most studies focus on access to opioids for the treatment of severe (cancer) pain. This study aims to identify specific access barriers for patients with opioid dependence in legislation and regulations of 11 central and eastern European countries.MethodsThis study builds on a previous analysis of legislation and regulations as part of the EU 7th Framework Access To Opioid Medication in Europe (ATOME) project. An in‐depth analysis was undertaken to determine specific barriers for patients with opioid dependence in need of opioid analgesics or opioid agonist therapy (OAT). For each country, the number and nature of specific potential barriers for these patients were assessed according to eight categories: prescribing; dispensing; manufacturing; usage; trade and distribution; affordability; penalties; and other. An additional keyword search was conducted to minimize the omission of barriers. Barriers in an additional category, language, were recorded qualitatively. Countries included Bulgaria, Cyprus, Estonia, Greece, Hungary, Latvia, Lithuania, Serbia, Slovakia, Slovenia and Turkey.ResultsTen of the 11 countries (all except Estonia) showed specific potential barriers in their legislation and regulations. The total number of barriers varied from two (Slovenia) to 46 (Lithuania); the number of categories varied from one (Slovenia) to five (Lithuania). Most specific potential barriers were shown in the categories ‘prescribing’, ‘usage’ and ‘other’. The total number in a single category varied from one to 18 (Lithuania, prescribing). Individual differences between countries in the same specific potential barrier were shown; for example, variation in minimum age criteria for admission to OAT ranging from 15 (Lithuania, in special cases) to 20 years (Greece). All countries had stigmatizing language in their legislation.ConclusionsPatients with opioid dependence are likely to experience specific barriers to accessing opioids in addition to those experienced by other non‐dependent patients.
Migration as an Adaptation Strategy for Atoll Island States
Authors: Yamamoto Lilian , Esteban Miguel 
Published: January 2017

AbstractAdopting a policy of migration can be one possible adaptation strategy against climate change. It has been forecasted that if the worst predictions regarding climate change and sea level rise become reality atolls around the world could become submerged in the future. This would render them uninhabitable and could lead to questions about whether Atoll Island States could still be considered as States. The international community has been avoiding any commitment to create a convention that would protect people displaced by climate change. In order to solve such potential problems, the authors will argue that a framework of bilateral agreements, initiatives, and national policies could constitute a viable solution for the various interested parties. The article will discuss the characteristics of Atoll Island States, touching on possible solutions for climate change displacement which have been discussed by the governments and civil society of the affected States.
Integration by Stealth: How the European Union Gained Competence over Foreign Direct Investment
Authors: Meunier Sophie 
Published: January 2017

AbstractHow are policy competences allocated between different actors? This article contributes to the literature on institutional development through an in‐depth case‐study of the conditions under which the competence over the negotiation of agreements on foreign direct investment (FDI) was transferred from the national level to the European Union (EU) in the 2009 Lisbon Treaty. Most analysts assume that this competence shift was a rationally designed delegation, intended to maximize European bargaining power in international investment negotiations and conceived as an important element of a teleological drive to make the EU a meaningful external actor. This article tells a different story – one where the competence shift happened by stealth as a result of a combination of neo‐functionalist Commission entrepreneurship and historical accident, against the preferences of the Member States. The article also assesses whether the conditions under which the competence was transferred have implications for the implementation of the new policy.
Prophylactic tributyrin treatment mitigates chronic‐binge ethanol‐induced intestinal barrier and liver injury
Authors: Cresci Gail A , Glueck Bryan , McMullen Megan R , Xin Wei , Allende Daniella , Nagy Laura E 
Published: January 2017

AbstractBackground and AimImpaired gut‐liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic‐binge ethanol exposure.MethodsC57BL/6J mice exposed to 5% v/v ethanol‐containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 h before euthanasia. Control mice were isocalorically pair‐fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction (TJ) proteins, toll‐like receptors, and tumor necrosis factor‐alpha were assessed. Caco‐2 monolayers with or without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity.ResultsChronic‐binge ethanol feeding impaired intestinal TJ protein co‐localization staining; however, tributyrin co‐treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco‐2 monolayers, but butyrate co‐treatment reduced these effects. Hepatic toll‐like receptor mRNA expression and tumor necrosis factor‐alpha protein expression was induced by ethanol; however, the response was significantly dampened in mice co‐treated with tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: Leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol‐only treated mice, whereas localization predominated around the central vein in ethanol‐tributyrin mice.ConclusionsProphylactic tributyrin supplementation mitigated effects of combined chronic‐binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury.
Association of granulomas in mesenteric lymph nodes in Crohn's disease with younger age and transmural inflammation
Authors: Sun Xingwen , Yuan Lisi , Li Yi , Shen Bo , Xie Hao , Liu Xiuli 
Published: January 2017

AbstractBackground and AimsMesenteric lymph nodes were usually removed during bowel resection surgery for Crohn's disease (CD). Mesenteric lymph node (MLN) granuloma predicted postoperative disease recurrence in patients with CD after ileocolic resection (ICR). This study was aimed to identify factors associated with MLN granulomas in a cohort of CD patients who underwent ICR.MethodsThe study group consisted of 18 patients with CD who underwent the index ICR between 2004 and 2012 and had MLN granulomas. The control group included 32 cases negative for MLN granulomas, which were randomly selected from the same period. Clinicodemographic and histological features were compared in these two groups.ResultsThe presence of MLN granuloma was associated with younger age, perianal disease, and ileocolic disease. Gender, body mass index, smoking status, disease duration, extraintestinal manifestation, length of bowel resected, total number of nodes examined, medical treatment, and indications for surgery were not significantly different between the groups. The presence of MLN granuloma was associated with mural granuloma, transmural inflammation, mural abscess, hypertrophy of the muscularis propria, fibrosis of the muscularis propria, and serosal fibrosis in the small bowel. The multivariable analysis confirms that MLN granuloma was associated with age and transmural inflammation.ConclusionsIn CD patients who underwent the index ICR, the presence of MLN granuloma was associated with younger age and transmural inflammation. Our current results suggest that the detection of MLN granulomas may be enhanced in patients at higher risk, that is, younger patients or those with transmural inflammation on imaging or histopathology.
Established and emerging methods for assessment of small and large intestinal motility
Authors: Grønlund D. , Poulsen J. L. , Sandberg T. H. , Olesen A. E. , Madzak A. , Krogh K. , Frøkjær J. B. , Drewes A. M. 
Published: January 2017

AbstractBackgroundGastrointestinal symptoms are common in the general population and may originate from disturbances in gut motility. However, fundamental mechanistic understanding of motility remains inadequate, especially of the less accessible regions of the small bowel and colon. Hence, refinement and validation of objective methods to evaluate motility of the whole gut is important. Such techniques may be applied in clinical settings as diagnostic tools, in research to elucidate underlying mechanisms of diseases, and to evaluate how the gut responds to various drugs. A wide array of such methods exists; however, a limited number are used universally due to drawbacks like radiation exposure, lack of standardization, and difficulties interpreting data. In recent years, several new methods such as the 3D‐Transit system and magnetic resonance imaging assessments on small bowel and colonic motility have emerged, with the advantages that they are less invasive, use no radiation, and provide much more detailed information.PurposeThis review outlines well‐established and emerging methods to evaluate small bowel and colonic motility in clinical settings and in research. The latter include the 3D‐Transit system, magnetic resonance imaging assessments, and high‐resolution manometry. Procedures, indications, and the relative strengths and weaknesses of each method are summarized.
Gastrointestinal disorders in joint hypermobility syndrome/Ehlers‐Danlos syndrome hypermobility type: A review for the gastroenterologist
Authors: Beckers A. B. , Keszthelyi D. , Fikree A. , Vork L. , Masclee A. , Farmer A. D. , Aziz Q. 
Published: January 2017

AbstractBackgroundJoint hypermobility syndrome (JHS)/Ehlers‐Danlos syndrome hypermobility type (EDS‐HT) is the most common hereditary non‐inflammatory disorder of connective tissue, characterized by a wide range of symptoms, mainly joint hyperextensibility and musculoskeletal symptoms. A majority of patients also experiences gastrointestinal (GI) symptoms. Furthermore, JHS/EDS‐HT has specifically been shown to be highly prevalent in patients with functional GI disorders, such as functional dyspepsia and irritable bowel syndrome.PurposeThe aim of this review was to examine the nature of GI symptoms and their underlying pathophysiology in JHS/EDS‐HT. In addition, we consider the clinical implications of the diagnosis and treatment of JHS/EDS‐HT for practicing clinicians in gastroenterology. Observations summarized in this review may furthermore represent the first step toward the identification of a new pathophysiological basis for a substantial subgroup of patients with functional GI disorders.