bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corilagin controls post-parasiticide schistosome egg-induced liver fibrosis by inhibiting Stat6 signalling pathway
Authors: Du Peng , Ma Qian , Xiong Jun , Wang Yao , Yang Fan , Jin Feng , Chen Yun-Fei , Shang Zhen-Zhong , Chen Zhi-Lin , Zhou Xuan , Li Hua-Rong , Zhao Lei 
Published: June 2018

AbstractThis study aims to explore the effect of Corilagin (Cor) on post-parasiticide schistosome egg-induced hepatic fibrosis through the Stat6 signalling pathway in vitro and in vivo. Cellular and animal models were established and treated by Corilagin. The inhibitory effect of Corilagin was also confirmed in RAW264.7 cells in which Stat6 was overexpressed based on the GV367-Stat6-EGFP lentiviral vector system and in which Stat6 was knock-downed by gene specific siRNAs. As a result, Corilagin prevented increases in the protein level of Phospho-Stat6 (P-Stat6). Both the mRNA and protein levels of the downstream mediators SOCS1, KLF4, and PPARγ/δ were markedly suppressed after Corilagin treatment. Expression of ARG1 and FIZZ1/Retnla, Ym1, TGF-β and PDGF in serum were also inhibited by Corilagin. The pathological changes, area of granulomas of liver sections, and degree of hepatic fibrosis were significantly alleviated in the Corilagin group. The areas of CD68- and CD206-positive cells stained by immunofluorescence were significantly decreased by Corilagin. In conclusion, Corilagin can suppress post-parasiticide schistosome egg-induced hepatic fibrosis by inhibiting the Stat6 signalling pathway and provide a new therapeutic strategy for schistosomiasis liver fibrosis.
The demographic history of African Drosophila melanogaster
Authors: Kapopoulou Adamandia , Pfeifer Susanne P. , Jensen Jeffrey D. , Laurent Stefan 
Published: June 2018

ABSTRACTAs one of the most commonly utilized organisms in the study of local adaptation, an accurate characterization of the demographic history of Drosophila melanogaster remains as an important research question. This owes both to the inherent interest in characterizing the population history of this model organism, as well as to the well-established importance of an accurate null demographic model for increasing power and decreasing false positive rates in genomic scans for positive selection. While considerable attention has been afforded to this issue in non-African populations, less is known about the demographic history of African populations, including from the ancestral range of the species. While qualitative predictions and hypotheses have previously been forwarded, we here present a quantitative model fitting of the population history characterizing both the ancestral Zambian population range as well as the subsequently colonized west African populations, which themselves served as the source of multiple non-African colonization events. These parameter estimates thus represent an important null model for future investigations in to African and non-African D. melanogaster populations alike.
Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury
Authors: Chen Chun-Yu , Tsai Yung-Fong , Huang Wei-Ju , Chang Shih-Hsin , Hwang Tsong-Long 
Published: June 2018

AbstractCritically ill patients have a high risk of sepsis. Various studies have demonstrated that propofol has anti-inflammatory effects that may benefit critically ill patients who require anesthesia. However, the mechanism and therapeutic effect remain incompletely understood. Our previous data suggest that propofol can act as a formyl peptide receptor 1 (FPR1) antagonist. Here, we hypothesize that propofol mitigates sepsis-induced acute lung injury (ALI) by inhibiting mitochondria-derivedN-formyl peptide-mediated neutrophil activation. In human neutrophils, propofol competitively reduced the release of elastase, superoxide, and reactive oxygen species induced by fMMYALF, a human mitochondria-derivedN-formyl peptide. In addition, propofol significantly inhibited fMMYALF-induced chemotaxis, calcium mobilization, and phosphorylation of protein kinase B and mitogen-activated protein kinases. These results indicate that propofol suppresses neutrophil activation by blocking the interaction between endogenousN-formyl peptide and its receptor, FPR1, thus inhibiting downstream signaling. Furthermore, propofol alleviated alveolar wall disruption, edematous changes, and neutrophil infiltration in lipopolysaccharide-induced ALI in mice. Noticeably, propofol improved the survival of sepsis mice. This study indicates that the anti-neutrophil effects of propofol may benefit critically ill septic patients.
Long-term acclimation to different stress types: revealing tradeoffs between mesophyll and stomatal conductance
Authors: Zait Yotam , Shtein Ilana , Schwartz Amnon 
Published: June 2018

AbstractZiziphus spina-christi, a thermophilic tree, became more abundant in the Mediterranean, presumably due to increased winter temperatures. In order to predict the plant acclimation to future climate changes, we attempted to understand which factors underlie photosynthetic stress acclimation.Stress acclimation to three major long-term abiotic stresses (drought, salinity and temperature) was investigated by measuring growth, gas exchange, chlorophyll fluorescence and leaf structure. We developed a stress index that allowed to precisely define stress level, enabling a comparison between stress types. For each stress, photosynthesis-limiting factors were compared: stomatal conductance (gs), mesophyll conductance (gm) and maximum capacity for Rubisco carboxylation (Vcmax).Photosynthesis under all stresses was limited mostly bygsandgm(80-90%); whereas biochemistry (Vcmax) made a minor contribution (10-20%). The relative contribution ofgsandgmon photosynthetic limitation was influenced by stress type. During acclimation to drought or salinity, photosynthesis was limited by a decline ings, while intolerance to low temperatures was driven by decline ingm. Low mesophyll-imposed limitation was the best predictor of abiotic stress tolerance.The results demonstrate how warming climate benefits thermophilic species. Moreover, current work gives methodology for stress studies, and defines the main factors underlying the plant response to climate change.HighlightWe have compared the photosynthesis limitation resulting from long-term acclimation to three major a-biotic stresses (drought, salinity and temperature) to understand which limiting-factor are dominant under each type of stress.
FluoEM: Virtual labeling of axons in 3-dimensional electron microscopy data for long-range connectomics
Authors: Drawitsch Florian , Karimi Ali , Boergens Kevin M. , Helmstaedter Moritz 
Published: June 2018

AbstractVolume electron microscopy (3D EM) has enabled the dense reconstruction of neuronal circuits in datasets that are so far about a few hundred micrometers in extent. In mammalian brains, most neuronal circuits are however highly non-local, such that a large fraction of the synapses in such a volume of neuropil originates from distant projection sources. The labeling and identification of such long-range axonal inputs from multiple sources within a densely reconstructed EM dataset has been notoriously difficult because of the limited color label space of EM. Here, we present FluoEM, a set of experimental and computational methods that allows the identification of multi-color fluorescently labeled axons in dense EM data without the need for artificially introduced fiducial marks or direct label conversion for EM. The approach is based on correlated imaging of the tissue and computational matching of neurite reconstructions, amounting to a virtual color labeling of axons in dense EM circuit data. We show that the identification of fluorescent light-microscopically (LM) imaged axons in 3D EM data from mouse cortex is faithfully possible as soon as the EM dataset is about 40-50 μm in extent, relying on the unique trajectories of axons in dense mammalian neuropil. The method is exemplified for the identification of longdistance axonal input into layer 1 of the mouse cerebral cortex.
Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium
Authors: Brandt Raphael , Sell Thomas , Lüthen Mareen , Uhlitz Florian , Klinger Bertram , Riemer Pamela , Giesecke-Thiel Claudia , Schulze Silvia , El-Shimy Ismail Amr , Kunkel Desiree , Fauler Beatrix , Mielke Thorsten , Mages Norbert , Herrmann Bernhard G , Sers Christine , Blüthgen Nils , Morkel Markus 
Published: June 2018

AbstractMutations activating the KRAS GTPase or the BRAF kinase are frequent in colorectal cancer and are thought to constitutively activate the terminal mitogen-activated protein kinase, ERK. Using mass cytometry, we found graded phosphorylation of ERK anti-correlated with cell differentiation in patient-derived colorectal cancer organoids, independent of KRAS mutational status. Reporter, single cell transcriptome and mass cytometry analyses showed that transgenic KRASG12V activated ERK in a cell type-specific pattern in mouse intestinal organoids. In contrast, transgenic BRAFV600E triggered high ERK activity and downstream gene expression in all intestinal cell types, followed by epithelial disorganisation. Quantitative network modelling from perturbation data revealed that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identified dual-specificity phosphatases as candidate modulators of ERK activity between intestinal cell types. Furthermore, we found that oncogenic KRAS, together with β-Catenin, favoured expansion of crypt cells with high ERK activity. Our experiments highlight key differences between ERK activity elicited by the BRAF or KRAS oncogenes in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Identifying Mechanisms of Regulation to Model Carbon Flux During Heat Stress And Generate Testable Hypotheses
Authors: Hubbard Allen H. , Zhang Xiaoke , Jastrebski Sara , Lamont Susan J. , Singh Abhyudai , Schmidt Carl 
Published: June 2018

AbstractUnderstanding biological response to stimuli requires identifying mechanisms that coordinate changes across pathways. One of the promises of multi-omics studies is achieving this level of insight by simultaneously identifying different levels of regulation. However, computational approaches to integrate multiple types of data are lacking. An effective systems biology approach would be one that uses statistical methods to detect signatures of relevant network motifs and then builds metabolic circuits from these components to model shifting regulatory dynamics. For example, transcriptome and metabolome data complement one another in terms of their ability to describe shifts in physiology. Here, we extend a previously described method used to identify single nucleotide polymorphism (SNP’s) associated with metabolic changes (Gieger et al., 2008). We apply this strategy to link changes in sulfur, amino acid and lipid production under heat stress by relating ratios of compounds to potential precursors and regulators. This approach provides integration of multi-omics data to link previously described, discrete units of regulation into functional pathways and hypothesizes novel biology relevant to the heat stress response.
Identification of Adomavirus Virion Proteins
Authors: Welch Nicole L. , Tisza Michael J. , Starrett Gabriel J. , Belford Anna K. , Pastrana Diana V. , Pang Yuk-Ying S. , Schiller John T. , An Ping , Cantalupo Paul G. , Pipas James M. , Koda Samantha , Subramaniam Kuttichantran , Waltzek Thomas B. , Bian Chao , Shi Qiong , Ruan Zhiqiang , Ng Terry Fei Fan , Buck Christopher B. 
Published: June 2018

AbstractAdenoviruses, papillomaviruses, and polyomaviruses are collectively known as small DNA tumor viruses. Although it has long been recognized that small DNA tumor virus oncoproteins and capsid proteins show a variety of structural and functional similarities, it is unclear whether these similarities reflect descent from a common ancestor, convergent evolution, horizontal gene transfer among virus lineages, or acquisition of genes from host cells. Here, we report the discovery of a dozen new members of an emerging virus family, the Adomaviridae, that unite a papillomavirus/polyomavirus-like replicase gene with an adenovirus-like virion maturational protease. Adomaviruses were initially discovered in a lethal disease outbreak among endangered Japanese eels. New adomavirus genomes were found in additional commercially important fish species, such as tilapia, as well as in reptiles. The search for adomavirus sequences also revealed an additional candidate virus family, which we refer to as xenomaviruses, in mollusk datasets. Analysis of native adomavirus virions and expression of recombinant proteins showed that the virion structural proteins of adomaviruses are homologous to those of both adenoviruses and another emerging animal virus family called adintoviruses. The results pave the way toward development of vaccines against adomaviruses and suggest a framework that ties small DNA tumor viruses into a shared evolutionary history.Author SummaryIn contrast to cellular organisms, viruses do not encode any universally conserved genes. Even within a given family of viruses, the amino acid sequences encoded by homologous genes can diverge to the point of unrecognizability. Although members of an emerging virus family, the Adomaviridae, encode replicative DNA helicase proteins that are recognizably similar to those of polyomaviruses and papillomaviruses, the functions of other adomavirus genes have been difficult to identify. Using a combination of laboratory and bioinformatic approaches, we identify the adomavirus virion structural proteins. The results link adomavirus virion protein operons to those of other midsize non-enveloped DNA viruses, including adenoviruses and adintoviruses.
Comprehensive 2D and 3D phenotypic characterization of human invasive lobular carcinoma cell lines
Authors: Tasdemir Nilgun , Bossart Emily , Li Zheqi , Li Zhu , Levine Kevin M. , Jacobsen Britta M. , Tseng George C. , Davidson Nancy E. , Oesterreich Steffi 
Published: June 2018

AbstractInvasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC) and characterized by the loss of E-cadherin-mediated adherens junctions. Despite displaying unique histological and clinical features, ILC still remains a chronically understudied disease with limited knowledge on the available laboratory research models. To this end, herein we report a comprehensive 2D and 3D phenotypic characterization of four Estrogen Receptor-positive human ILC cell lines - MDA-MB-134, SUM44, MDA-MB-330 and BCK4. Compared to the IDC cell lines MCF7, T47D and MDA-MB-231, ultra-low attachment culture conditions revealed a remarkable anchorage-independence ability that was unique to the ILC cells, a feature not evident in soft agar gels. 3D Collagen I and Matrigel culture indicated a generally loose morphology for the ILC cell lines, which exhibited differing preferences for adhesion to ECM proteins in 2D. Furthermore, ILC cells had limited migration and invasion ability in wound-scratch and transwell assays with the exception of haptotaxis to Collagen I. Transcriptional comparison of the cell lines confirmed the decreased cell proliferation and E-cadherin-mediated intercellular junctions in ILC, while uncovering the induction of novel pathways related to cyclic nucleotide phosphodiesterase activity, ion channels, drug metabolism and alternative cell adhesion molecules such as N-cadherin, some of which were also differentially regulated in ILC versus IDC tumors. Altogether, these studies will serve as an invaluable resource for the breast cancer research community and facilitate further functional discoveries towards understanding ILC, identifying novel drug targets and ultimately improving the outcome of patients with ILC.Authors’ ContributionsConception and design:N. Tasdemir, NE. Davidson, S. OesterreichDevelopment of methodology:N. Tasdemir, L. Zhu, GC. Tseng, S. OesterreichAcquisition of data (performed experiments, processed data, etc.):N. Tasdemir, E. Bossart, Z. Li, Z. LiAnalysis and interpretation of data (e.g. biological interpretation, statistical analysis, computational analysis):N. Tasdemir, Z. Li, KM. Levine, NE. Davidson, S. OesterreichWriting, review and/or revision of the manuscript:N. Tasdemir, Z. Li, KM. Levine, BM. Jacobson, GC. Tseng, NE. Davidson, S. OesterreichStudy supervision:NE. Davidson and S. Oesterreich
Identification of genes affecting saturated fat acid content in Elaeis guineensis by genome-wide association analysis
Authors: Xia Wei , Luo Tingting , Zhang Wei , Mason Annaliese S. , Huang Dongyi , Huang Xiaolong , Tang Wenqi , Dou Yajing , Zhang Chunyu , Xiao Yong 
Published: June 2018

AbstractOil palm is the highest yielding oil crop per unit area worldwide. Unfortunately, palm oil is often considered unhealthy. In particular, palmic acid (C16:0) is a major component of palm oil. In this study a total of 1 261 501 SNP markers were produced in a diversity panel of 200 oil palm individuals. Oil content in this population varied from 29.8% to 70.3%, palmic acid varied from 31.3% to 48.8%, and oleic acid varied from 31.3% to 50.1%. We identified 274 SNP markers significantly associated with fatty acid compositions; 44 candidate genes in the flanking regions of these SNPs were involved in fatty acid biosynthesis and metabolism. Among them, two acyl-ACP thioesterase B genes had differential expression patterns between the mesocarp and kernel, tissues which show different oil profiles in oil palm (high palmic acid and high lauric acid respectively). Overexpression of both genes caused a significant increase in palmic acid content, while overexpression of the EgFatB2 gene also caused an accumulation of lauric acid and myristic acid. Our research provides genome-wide SNPs, a set of markers significantly associated with fatty acid content, and validated candidate genes for future targeted breeding of lower saturated fat content in palm oil.
Epstein-Barr Virus May Contribute to Central Nervous System Involvement in HIV-positive Individuals
Authors: Lupia T , Milia MG , Atzori C , Audagnotto S , Imperiale D , Mighetto L , Pirriatore V , Gregori G , Lipani F , Ghisetti V , Bonora S , Di Perri G , Calcagno A 
Published: June 2018

AbstractEpstein-Barr virus (EBV) often accesses the central nervous system (CNS) where it may lead to blood brain barrier (BBB) integrity disruption, facilitating the migration of immune cells into brain parenchyma. Our aim was to study the association between cerebrospinal fluid (CSF) EBV DNA and HIV-1 compartmental replication. 281 HIV-positive adults undergoing lumbar punctures for clinical reasons (excluding those with lymphoproliferative disorders) and CSF samples were examined. CSF virological, neurodamage (tau, p-tau, 1-42 beta amyloid) and immune activation (neopterin and S100beta) markers were measured by immune-enzymatic, ELISA and PCR validated methods. Two hundred eighty one patients were included; 111 (40.5 %) were naïve for antiretroviral treatment. CSF EBV DNA was detectable in 25 (21.9%) naïve and 26 (16%) treated patients at low levels (<100 and 146 copies/mL). Naïve EBV+ subjects presented higher CSF HIV RNA, biomarkers (t-tau, p-tau, neopterin) and higher rates of pleocytosis. Treated EBV+ individuals showed pleocytosis, higher CSF HIV RNA, CSF to serum albumin ratio, IgG index and neopterin. No association was observed between detectable CSF EBV DNA and the rate of CSF escape. In patients with plasma HIV RNA <20 copies/mL (n=97) CSF EBV DNA was detectable in 13 subjects (13.4%) and it was associated with pleocytosis, higher CSF HIV RNA and neopterin levels. EBV DNA was detectable in a considerable proportion of HIV-positive patients and it was associated with higher levels of CSF HIV RNA and neuronal damage/inflammation biomarkers. The role of EBV reactivation in HIV-associated CNS disorders warrant further studies.ImportanceEBV is a human gamma-herpesvirus with a seroprevalence in adults approaches 95% and the pattern of clinical manifestations is very heterogeneous and varies from asymptomatic or mild viral infection to a tightly linked with several malignancies as nasopharyngeal carcinoma, Hodgkin’s lymphoma and Burkitt’s lymphoma. HIV-infected and immunocompetent patients were both at risk of primary infection and complications linked to EBV.Primary tropism of EBV is for lymphocytes (type B, T and NK), epithelial, endothelial and smooth muscle cells and establishes lifelong latent infection. Central nervous system could be affected by this herpesvirus in primary infection and reactivation and EBV-DNA is not an uncommon finding in CSF in HIV-infected population. The significance of our research is in identifying the presence of a link between HIV and EBV CNS replication.
A Fixed Moderate-dose Combination of Tiletamine+Zolazepam Outperforms Midazolam in Induction of Short-term Immobilization of Ball Pythons (Python regius)
Authors: Miller Lynn J. , Fetterer David P. , Lackemeyer Nicole L. , Lackemeyer Matthew G. , Donnelly Ginger C. , Steffens Jesse T. , Van Tongeren Sean A. , Fiallos Jimmy O. , Moore Joshua L. , Marko Shannon T. , Lugo-Roman Luis A. , Fedewa Greg , DeRisi Joseph L. , Kuhn Jens H. , Stahl Scott J. 
Published: June 2018

ABSTRACTLaboratory animals are commonly anesthetized to prevent pain and distress and to provide safe handling. Anesthesia procedures are well-developed for common laboratory mammals, but not as well established in reptiles. We assessed the performance of intramuscularly injected tiletamine (dissociative anesthetic) and zolazepam (benzodiazepine sedative) in fixed combination (2 mg/kg and 3 mg/kg) in comparison to 2 mg/kg of midazolam (benzodiazepine sedative) in ball pythons (Python regius). We measured heart and respiratory rates and quantified induction parameters (i.e., time to loss of righting reflex, time to loss of withdrawal reflex) and recovery parameters (i.e., time to regain righting reflex, withdrawal reflex, normal behavior). Mild decreases in heart and respiratory rates (median decrease of <10 beats per minute and <5 breaths per minute) were observed for most time points among all three anesthetic dose groups. No statistically significant difference between the median time to loss of righting reflex was observed among animals of any group (p = 0.783). However, the withdrawal reflex was lost in all snakes receiving 3mg/kg of tiletamine+zolazepam but not in all animals of the other two groups (p = 0.0004). In addition, the time for animals to regain the righting reflex and resume normal behavior was longer in the drug combination dose groups compared to the midazolam group (p = 0.0055). Our results indicate that midazolam is an adequate sedative for ball pythons but does not suffice to achieve reliable immobilization or anesthesia, whereas tiletamine+zolazepam achieves short-term anesthesia in a dose-dependent manner.