bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dehydroabietic oximes halt pancreatic cancer cell growth in the G1 phase through induction of p27 and downregulation of cyclin D1
Authors: Kolsi Laura E. , Leal Ana S. , Yli-Kauhaluoma Jari , Liby Karen T. , Moreira Vânia M. 
Published: October 2018

AbstractLow 5-year survival rates, increasing incidence, as well as the specific challenges of targeting pancreatic cancer, clearly support an urgent need for new multifunctional drugs for the prevention and treatment of this fatal disease. Natural products, such as abietane-type diterpenoids, are widely studied as promiscuous anticancer agents. In this study, dehydroabietic oximes were identified as potential compounds to target pancreatic cancer and cancer-related inflammation. The compounds inhibited the growth of human pancreatic cancer Aspc-1 cells with IC50 values in the low micromolar range and showed anti-inflammatory activity, measured as the inhibition of nitric oxide production, an important inflammatory mediator in the tumour microenvironment. Further studies revealed that the compounds were able to induce cancer cell differentiation and concomitantly downregulate cyclin D1 expression with upregulation of p27 levels, consistent with cell cycle arrest at the G1 phase. Moreover, a kinase profiling study showed that one of the compounds has isoform-selective, however modest, inhibitory activity on RSK2, an AGC kinase that has been implicated in cellular invasion and metastasis.
Extraordinary Mechanical Properties of Composite Silk Through Hereditable Transgenic Silkworm Expressing Recombinant Major Ampullate Spidroin
Authors: You Zhengying , Ye Xiaogang , Ye Lupeng , Qian Qiujie , Wu Meiyu , Song Jia , Che Jiaqian , Zhong Boxiong 
Published: October 2018

AbstractSpider dragline silk is a remarkable material that shows excellent mechanical properties, diverse applications, biocompatibility and biodegradability. Transgenic silkworm technology was used to obtain four types of chimeric silkworm/spider (termed composite) silk fibres, including different lengths of recombinant Major ampullate Spidroin1 (re-MaSp1) or recombinant Major ampullate Spidroin2 (re-MaSp2) from the black widow spider, Latrodectus hesperus. The results showed that the overall mechanical properties of composite silk fibres improved as the re-MaSp1 chain length increased, and there were significant linear relationships between the mechanical properties and the re-MaSp1 chain length (p < 0.01). Additionally, a stronger tensile strength was observed for the composite silk fibres that included re-MaSp1, which only contained one type of repetitive motif, (GA)n/An, to provide tensile strength, compared with the silk fibres that includedre-MaSp2, which has the same protein chain length as re-MaSp1 but contains multiple types of repetitive motifs, GPGXX and (GA)n/An. Therefore, the results indicated that the nature of various repetitive motifs in the primary structure played an important role in imparting excellent mechanical properties to the protein-based silk fibres. A silk protein with a single type of repetitive motif and sufficiently long chains was determined to be an additional indispensable factor. Thus, this study forms a foundation for designing and optimizing the structure of re-silk protein using a heterologous expression system.
Lipopolysaccharide shock reveals the immune function of indoleamine 2,3-dioxygenase 2 through the regulation of IL-6/stat3 signalling
Authors: Yamamoto Yasuko , Yamasuge Wakana , Imai Shinjiro , Kunisawa Kazuo , Hoshi Masato , Fujigaki Hidetsugu , Mouri Akihiro , Nabeshima Toshitaka , Saito Kuniaki 
Published: October 2018

AbstractIndoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified catalytic enzyme in the tryptophan-kynurenine pathway that is expressed primarily in monocytes and dendritic cells. To elucidate the biological role of Ido2 in immune function, we introduced lipopolysaccharide (LPS) endotoxin shock to Ido2 knockout (Ido2 KO) mice, which led to higher mortality than that in the wild type (WT) mice. LPS-treated Ido2 KO mice had increased production of inflammatory cytokines (including interleukin-6; IL-6) in serum and signal transducer and activator of transcription 3 (stat3) phosphorylation in the spleen. Moreover, the peritoneal macrophages of LPS-treated Ido2 KO mice produced more cytokines than did the WT mice. By contrast, the overexpression of Ido2 in the murine macrophage cell line (RAW) suppressed cytokine production and decreased stat3 expression. Finally, RAW cells overexpressing Ido2 did not alter nuclear factor κB (NF-κB) or stat1 expression, but IL-6 and stat3 expression decreased relative to the control cell line. These results reveal that Ido2 modulates IL-6/stat3 signalling and is induced by LPS, providing novel options for the treatment of immune disorders.
Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties
Authors: Leroux Louis-Philippe , Nasr Mohamad , Valanparambil Rajesh , Tam Mifong , Rosa Bruce A. , Siciliani Elizabeth , Hill Dolores E. , Zarlenga Dante S. , Jaramillo Maritza , Weinstock Joel V. , Geary Timothy G. , Stevenson Mary M. , Urban Joseph F. , Mitreva Makedonka , Jardim Armando 
Published: October 2018

AbstractParasitic worms have a remarkable ability to modulate host immune responses through several mechanisms including excreted/secreted proteins (ESP), yet the exact nature of these proteins and their targets often remains elusive. Here, we performed mass spectrometry analyses of ESP (TsESP) from larval and adult stages of the pig whipwormTrichuris suis(Ts) and identified ~350 proteins. Transcriptomic analyses revealed large subsets of differentially expressed genes in the various life cycle stages of the parasite. Exposure of bone marrow-derived macrophages and dendritic cells to TsESP markedly diminished secretion of the pro-inflammatory cytokines TNFα and IL-12p70. Conversely, TsESP exposure strongly induced release of the anti-inflammatory cytokine IL-10, and also induced high levels of nitric oxide (NO) and upregulated arginase activity in macrophages. Interestingly, TsESP failed to directly induce CD4+CD25+FoxP3+regulatory T cells (Tregcells), while OVA-pulsed TsESP-treated dendritic cells suppressed antigen-specific OT-II CD4+T cell proliferation. Fractionation of TsESP identified a subset of proteins that promoted anti-inflammatory functions, an activity that was recapitulated using recombinantT. suistriosephosphate isomerase (TPI) and nucleoside diphosphate kinase (NDK). Our study helps illuminate the intricate balance that is characteristic of parasite-host interactions at the immunological interface, and further establishes the principle that specific parasite-derived proteins can modulate immune cell functions.
Complex hybridization patterns in European pond turtles (Emys orbicularis) in the Pyrenean Region
Authors: Pöschel Julia , Heltai Botond , Graciá Eva , Quintana Marc Franch , Velo-Antón Guillermo , Arribas Oscar , Valdeón Aitor , Wink Michael , Fritz Uwe , Vamberger Melita 
Published: October 2018

AbstractHybrid zones are natural laboratories allowing insights in genetic processes like lineage diversification, speciation and introgression. Using large sampling, 15 microsatellite loci and a mitochondrial marker, we examined the Pyrenean contact zone of three pond turtle taxa (Emys orbicularis orbicularis,E.o.galloitalica,E.o.occidentalis). The Pyrenees are a biogeographically important region separating many lineages endemic to the Iberian Peninsula from their Western European counterparts. We discovered limited admixture, reflecting a complex biogeographic scenario. Simulations using Approximate Bayesian Computing supported thatE.o.orbicularisinvaded the Iberian Peninsula in the Holocene, circumventing the Pyrenees along the Mediterranean coast, and hybridized in the northern peninsula with the local coastal subspeciesgalloitalica, and to a lesser extent, withoccidentalis. WhileE.o.occidentalis, and in particularE.o.orbicularis, expanded their ranges considerably during Holocene warming,E.o.galloitalicaremained largely confined to its former Iberian refuge. Admixture among the three taxa is surprisingly low, and a future taxonomic investigation that includes the unstudied subspecies ofE.orbicularisfrom North Africa, Eastern Europe and Asia has to determine whether their current status properly reflects their evolutionary divergence or whether certain taxa should be regarded as full species.
Non-invasive genotyping with a massively parallel sequencing panel for the detection of SNPs in HPA-axis genes
Authors: Gutleb D. R. , Ostner J. , Schülke O. , Wajjwalku W. , Sukmak M. , Roos C. , Noll A. 
Published: October 2018

AbstractWe designed a genotyping panel for the investigation of the genetic underpinnings of inter-individual differences in aggression and the physiological stress response. The panel builds on single nucleotide polymorphisms (SNPs) in genes involved in the three subsystems of the hypothalamic-pituitary-adrenal (HPA)-axis: the catecholamine, serotonin and corticoid metabolism. To promote the pipeline for use with wild animal populations, we used non-invasively collected faecal samples from a wild population of Assamese macaques (Macaca assamensis). We targeted loci of 46 previously reported SNPs in 21 candidate genes coding for elements of the HPA-axis and amplified and sequenced them using next-generation Illumina sequencing technology. We compared multiple bioinformatics pipelines for variant calling and variant effect prediction. Based on this strategy and the application of different quality thresholds, we identified up to 159 SNPs with different types of predicted functional effects among our natural study population. This study provides a massively parallel sequencing panel that will facilitate integrating large-scale SNP data into behavioural and physiological studies. Such a multi-faceted approach will promote understanding of flexibility and constraints of animal behaviour and hormone physiology.
Fibroblast Growth Factor Binding Protein 3 (FGFBP3) impacts carbohydrate and lipid metabolism
Authors: Tassi Elena , Garman Khalid A. , Schmidt Marcel O. , Ma Xiaoting , Kabbara Khaled W. , Uren Aykut , Tomita York , Goetz Regina , Mohammadi Moosa , Wilcox Christopher S. , Riegel Anna T. , Carlstrom Mattias , Wellstein Anton 
Published: October 2018

AbstractSecreted FGF binding proteins (FGFBP) mobilize locally-acting paracrine FGFs from their extracellular storage. Here, we report that FGFBP3 (BP3) modulates fat and glucose metabolism in mouse models of metabolic syndrome. BP3 knockout mice exhibited altered lipid metabolism pathways with reduced hepatic and serum triglycerides. In obese mice the expression of exogenous BP3 reduced hyperglycemia, hepatosteatosis and weight gain, blunted de novo lipogenesis in liver and adipose tissues, increased circulating adiponectin and decreased NEFA. The BP3 protein interacts with endocrine FGFs through its C-terminus and thus enhances their signaling. We propose that BP3 may constitute a new therapeutic to reverse the pathology associated with metabolic syndrome that includes nonalcoholic fatty liver disease and type 2 diabetes mellitus.
Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson’s disease
Authors: Jeong Jin Seok , Piao Ying , Kang Sora , Son Minuk , Kang Young Cheol , Du Xiao Fei , Ryu Jayoung , Cho Young Woong , Jiang Hai-Hua , Oh Myung Sook , Hong Seon-Pyo , Oh Young J. , Pak Youngmi Kim 
Published: October 2018

AbstractMoutan cortex, Angelica Dahurica root, and Bupleurum root are traditional herbal medicines used in Asian countries to treat various diseases caused by oxidative stress or inflammation. Parkinson’s disease (PD) has been associated with mitochondrial dysfunction, but no effective treatment for mitochondrial dysfunction has yet been identified. In this study we investigated the neuroprotective effects of the triple herbal extract DA-9805 in experimental models of PD. DA-9805 was prepared by extracting three dried plant materials (Moutan cortex, Angelica Dahurica root, and Bupleurum root in a 1:1:1 mixture) with 90% ethanol on a stirring plate for 24 h at room temperature and fingerprinted using high-performance liquid chromatography. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), which both exert neurotoxic effects on dopaminergic neurons by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) complex I, were used to make experimental models of PD. In MPP+-treated SH-SY5Y cells, DA-9805 ameliorated the suppression of tyrosine hydroxylase expression and mitochondrial damage on OXPHOS complex 1 activity, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and oxygen consumption rate. In the MPTP-induced subacute PD model mice, oral administration of DA-9805 recovered dopamine content as well as bradykinesia, as determined by the rotarod test. DA-9805 protected against neuronal damage in the substantia nigra pars compacta (SNpc) and striatum. In both in vitro and in vivo models of PD, DA-9805 normalized the phosphorylation of AKT at S473 and T308 on the insulin signaling pathway and the expression of mitochondria-related genes. These results demonstrate that the triple herbal extract DA-9805 showed neuroprotective effects via alleviating mitochondria damage in experimental models of PD. We propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics for PD.
A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism
Authors: Mahaweni Niken M. , Olieslagers Timo I. , Rivas Ivan Olivares , Molenbroeck Stefan J. J. , Groeneweg Mathijs , Bos Gerard M. J. , Tilanus Marcel G. J. , Voorter Christina E. M. , Wieten Lotte 
Published: October 2018

AbstractTheFCGR3Agene encodes for the receptor important for antibody-dependent natural killer cell-mediated cytotoxicity.FCGR3Agene polymorphisms could affect the success of monoclonal antibody therapy. Although polymorphisms, such as the FcγRIIIA-V158F and -48L/R/H, have been studied extensively, an overview of other polymorphisms within this gene is lacking. To provide an overview ofFCGR3Apolymorphisms, we analysed the 1000 Genomes project database and found a total of 234 polymorphisms within theFCGR3Agene, of which 69%, 16%, and 15% occur in the intron, UTR, and exon regions respectively. Additionally, only 16% of all polymorphisms had a minor allele frequency (MAF) > 0.01. To facilitate (full-length) analysis ofFCGR3Agene polymorphism, we developed aFCGR3Agene-specific amplification and sequencing protocol for Sanger sequencing and MinION (Nanopore Technologies). First, we used the Sanger sequencing protocol to study the presence of the V158F polymorphism in 76 individuals resulting in frequencies of 38% homozygous T/T, 7% homozygous G/G and 55% heterozygous. Next, we performed a pilot with both Sanger sequencing and MinION based sequencing of 14 DNA samples which showed a good concordance between Sanger- and MinION sequencing. Additionally, we detected 13 SNPs listed in the 1000 Genome Project, from which 11 had MAF > 0.01, and 10 SNPs were not listed in 1000 Genome Project. In summary, we demonstrated thatFCGR3Agene is more polymorphic than previously described. As most novel polymorphisms are located in non-coding regions, their functional relevance needs to be studied in future functional studies.
Deep sequencing and miRNA profiles in alcohol-induced neuroinflammation and the TLR4 response in mice cerebral cortex
Authors: Ureña-Peralta J. R. , Alfonso-Loeches S. , Cuesta-Diaz C. M. , García-García F. , Guerri C. 
Published: October 2018

AbstractAlcohol abuse can induce brain injury and neurodegeneration, and recent evidence shows the participation of immune receptors toll-like in the neuroinflammation and brain damage. We evaluated the role of miRNAs as potential modulators of the neuroinflammation associated with alcohol abuse and the influence of the TLR4 response. Using mice cerebral cortex and next-generation sequencing (NGS), we identified miRNAs that were differentially expressed in the chronic alcohol-treated versus untreated WT or TLR4-KO mice. We observed a differentially expression of miR-183 Cluster (C) (miR-96/-182/-183), miR-200a and miR-200b, which were down-regulated, while mirR-125b was up-regulated in alcohol-treated WT versus (vs.) untreated mice. These miRNAs modulate targets genes related to the voltage-gated sodium channel, neuron hyperexcitability (Nav1.3, Trpv1, Smad3 and PP1-γ), as well as genes associated with innate immune TLR4 signaling response (Il1r1, Mapk14, Sirt1, Lrp6 and Bdnf). Functional enrichment of the miR-183C and miR-200a/b family target genes, revealed neuroinflammatory pathways networks involved in TLR4 signaling and alcohol abuse. The changes in the neuroinflammatory targets genes associated with alcohol abuse were mostly abolished in the TLR4-KO mice. Our results show the relationship between alcohol intake and miRNAs expression and open up new therapeutically targets to prevent deleterious effects of alcohol on the brain.
Lymphovascular invasion have a similar prognostic value as lymph node involvement in patients undergoing radical cystectomy with urothelial carcinoma
Authors: Yuk Hyeong Dong , Jeong Chang Wook , Kwak Cheol , Kim Hyeon Hoe , Ku Ja Hyeon 
Published: October 2018

AbstractTo determine the prognostic value of lymphovascular invasion (LVI) in patients with bladder cancer who underwent radical cystectomy. Total of 747 patients underwent radical cystectomy; of these, only 164 did not undergo lymph node dissection (LND). The patients were divided into 4 groups: N0, N1, LVI without LND, and non-LVI without LND. Patients in the N1 and LVI groups had significantly higher T stages and grades, as well 1.5- to 2-fold higher recurrence and mortality rates. Overall survival (OS) was significantly poorer in the N1 group, compared with the N0 and non-LVI groups (p = 0.001 and 0.012), and in the LVI group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001). Recurrence-free survival (RFS) was also significantly poorer in the N1 group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001), and in the LVI group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001). Among patients undergoing radical cystectomy, the clinical results predicted by LVI were similar to those predicted by lymph node involvement. Therefore, the role of adjuvant chemotherapy or immunotherapy may need to be prospectively evaluated in LVI-positive patients regardless of T stage after radical cystectomy.
OPTICS-based Unsupervised Method for Flaking Degree Evaluation on the Murals in Mogao Grottoes
Authors: Li Pan , Sun Meijun , Wang Zheng , Chai Bolong 
Published: October 2018

AbstractIn recent years, the preventive protection and restoration work of the murals in Mogao Grottoes has received extensive attention. Due to the fragility and detachment of the murals, it is necessary to study non-contact disease detection and prevention methods. In this paper, we propose an unsupervised method to accurately predict the degree of mural flaking diseases in Mogao Grottoes. The hyperspectral image (HSI) is captured by V10-PS hyperspectral camera. The proposed method includes three main steps: (1) extract the spectral features of the HSI by Principal Component Analysis (PCA) and Sparse Auto-Encoder (SAE) respectively; (2) cluster the extracted features by the Ordering Points to Identify the Clustering Structure (OPTICS) algorithm based on the density; (3) calculate the distance between the cluster core point and the other points in the feature space and visualize the final classification result. Different from other existing hyperspectral classification works, the research proposed in this paper is the degree detection of flaking of murals. Since the degree of flaking is continuous and the work is conducted without any supervision information, the entire workflow is complex and challenging. The experimental results show the effectiveness of our method.
Fearful dogs have increased plasma glutamine and γ-glutamyl glutamine
Authors: Puurunen Jenni , Tiira Katriina , Vapalahti Katariina , Lehtonen Marko , Hanhineva Kati , Lohi Hannes 
Published: October 2018

AbstractAnxiety-related disorders, including fearfulness are common and leading welfare problems among the worldwide dog population. The etiology of anxieties is complex and affected by genetic and environmental factors. Thus, there is a need for more comprehensive approaches, such as metabolomics, to understand the causes of anxiety and to identify anxiety-related biomarkers for more efficient diagnostic and treatment options. To study metabolic alterations related to canine fearfulness, a non-targeted plasma metabolite profiling was performed in a cohort of 20 fearful and 21 non-fearful dogs. The results showed that nine metabolic features were significantly associated with fearfulness. The most prominent change included increased plasma glutamine and γ-glutamyl glutamine (γ-Glu Gln) in fearful dogs across breeds. Alterations in glutamine metabolism have previously been associated with several psychiatric disorders, indicating the relevance of this finding also in dogs. In addition, we describe a novel breed-specific association between renal biomarker symmetric dimethylarginine (SDMA) and canine fearfulness. These observed metabolic alterations may result from high levels of prolonged psychological stress in fearful dogs.
Mediterranean forested wetlands are yeast hotspots for bioremediation: a case study using azo dyes
Authors: Sampaio Ana C. , Bezerra Rui M. F. , Dias Albino A. 
Published: October 2018

AbstractForested wetlands are interfaces between terrestrial and aquatic environments. These ecosystems play an important role in the hydrology, chemistry and biodiversity maintenance. Despite their high microbial diversity, there has been a lack of attention to the potential of their yeast communities. The purpose of this study is to evaluate the potential of yeasts isolated from a Mediterranean forested wetlands in decolorizing azo dyes. Azo dyes are synthetic, and highly recalcitrant to degradation. Ninety-two out of 560 isolates were randomly chosen to assess their ability to decolorize five azo dyes. Hierarchical clustering based on medium color changes during incubations was used to evaluate the isolates’ decolorization performance. All of the isolates that best degraded the 5 dyes tested were identified as Basidiomycota (Filobasidiales, Tremellales and Sporidiobolales). This work identifies new azo dye-degrading yeast species, and supports the hypothesis that forested wetlands are a niche for yeasts with bioremediation potential - namely azo dyes removal.
A conceptual view on inertial internal waves in relation to the subinertial flow on the central west Florida shelf
Authors: Maksimova Ekaterina V. 
Published: October 2018

AbstractThe study reported here focuses on inertial internal wave currents on the west Florida midshelf in 50 m depth. In situ observations showed that the seasonal shifts in stratification change both the frequency range of inertial internal waves and their modulation time scales. According to the analysis, the subinertial flow evolution time scales also undergo compatible seasonal variations, and the inertial internal wave currents appear to be temporally and spatially related to the subinertial flow. Specifically, the subinertial flow evolving on frontal-/quasi-geostrophic time scales appears to be accompanied by the near-inertial oscillations/inertia-gravity waves in corresponding small/finite Burger number regimes, respectively. The quasi-geostrophic subinertial currents on the west Florida shelf are probably associated with the synoptic wind-forced flow, whereas the frontal-geostrophic currents are related to the evolution of density fronts. Further details of this conceptual view should, however, be elucidated in the future.