bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders
Authors: Berdasco María , Gómez Antonio , Rubio Marcos J. , Català-Mora Jaume , Zanón-Moreno Vicente , Lopez Miguel , Hernández Cristina , Yoshida Shigeo , Nakama Takahito , Ishikawa Keijiro , Ishibashi Tatsuro , Boubekeur Amina M. , Louhibi Lotfi , Pujana Miguel A , Sayols Sergi , Setien Fernando , Corella Dolores , de Torres Carmen , Parareda Andreu , Mora Jaume , Zhao Ling , Zhang Kang , Lleonart Matilde E. , Alonso Javier , Simó Rafael , Caminal Josep M. , Esteller Manel 
Published: September 2017

AbstractThis work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are epigenetically controlled in the fibrotic disorders involved in retinal detachment, but results also reinforced the contribution of neurovascularization (ETS1, HES5, PRDM16) in diabetic retinopathy. Finally, we had studied the methylome in the most frequent intraocular tumors in adults and children (uveal melanoma and retinoblastoma, respectively). We observed that hypermethylation of tumor suppressor genes is a frequent event in ocular tumors, but also unmethylation is associated with tumorogenesis. Interestingly, unmethylation of the proto-oncogen RAB31 was a predictor of metastasis risk in uveal melanoma. Loss of methylation of the oncogenic mir-17-92 cluster was detected in primary tissues but also in blood from patients.
Bilingual Cortical Control of Between- and Within-Language Competition
Authors: Marian Viorica , Bartolotti James , Rochanavibhata Sirada , Bradley Kailyn , Hernandez Arturo E. 
Published: September 2017

AbstractThe human capacity to master multiple languages is remarkable and leads to structural and functional changes in the brain. Understanding how the brain accommodates multiple languages simultaneously is crucial to developing a complete picture of our species’ linguistic capabilities. To examine the neural mechanisms involved in processing two languages, we looked at cortical activation in Spanish-English bilinguals in response to phonological competition either between two languages or within a language. Participants recognized spoken words in a visual world task while their brains were scanned using functional magnetic resonance imaging (fMRI). Results revealed that between-language competition recruited a larger network of frontal control and basal ganglia regions than within-language competition. Bilinguals also recruited more neural resources to manage between-language competition from the dominant language compared to competition from the less dominant language. Additionally, bilinguals’ activation of the basal ganglia was inversely correlated with their executive function ability, suggesting that bilinguals compensated for lower levels of cognitive control by recruiting a broader neural network to manage more difficult tasks. These results provide evidence for differences in neural responses to linguistic competition between versus within languages, and demonstrate the brain’s remarkable plasticity, where language experience can change neural processing.
Health amongst former rugby union players: A cross-sectional study of morbidity and health-related quality of life
Authors: Davies Madeleine A. M. , D. Judge Andrew , Delmestri Antonella , P.T. Kemp Simon , Stokes Keith A. , Arden Nigel K. , Newton Julia L. 
Published: September 2017

AbstractIn the general population, physical activity is associated with improved health outcomes. However, long-term sports participation may be associated with adverse outcomes, particularly at the elite level. The aims of this study were to assess morbidity and health-related quality of life (HrQoL) amongst former rugby players, compared to an age-standardised general population sample. A cross-sectional study of former elite, male, rugby players (n = 259) was undertaken, and standardised morbidity ratios (SMR) calculated, assessing morbidity prevalence relative to English Longitudinal Study of Aging participants (ELSA, n = 5186). HrQoL, measured using the EQ-5D, was compared to a Health Survey for England (HSE, n = 2981) sample. In SMR analyses of participants aged 50+, diabetes was significantly lower amongst former players, (0.28, 95% CI 0.11–0.66), whereas osteoarthritis (4.00, 95% CI 3.32–4.81), joint replacement (6.02, 95% CI 4.66–7.77), osteoporosis (2.69, 95% CI 1.35–5.38), and anxiety (2.00, 95% CI 1.11–3.61) were significantly higher. More problems in HrQoL were reported amongst former players within the domains of mobility (p < 0.001), self-care (p = 0.041), usual activities (p < 0.001) and pain/discomfort (p < 0.001). Morbidity and HrQoL differ between players and the general population, with higher musculoskeletal morbidity and lower diabetes amongst former players. The magnitude of musculoskeletal morbidity may warrant proactive osteoarthritis management within this population.
Comprehensive analysis of lncRNAs and mRNAs in skeletal muscle of rainbow trout (Oncorhynchus mykiss) exposed to estradiol
Authors: Wang Jian , Koganti Prasanthi P. , Yao Jianbo , Wei Shuo , Cleveland Beth 
Published: September 2017

AbstractEstradiol (E2) is a steroid hormone that negatively affects muscle growth in rainbow trout (Oncorhynchus mykiss), but the mechanisms directing with this response are not fully understood. To better characterize the effects of E2 in muscle, we identified differentially regulated mRNAs and lncRNAs in juvenile rainbow trout exposed to E2. Here, we performed next-generation RNA sequencing and comprehensive bioinformatics analyses to characterize the transcriptome profiles, including mRNAs and long noncoding RNAs (lncRNAs), in skeletal muscle of rainbow trout injected with E2. A total of 226 lncRNAs and 253 mRNAs were identified as differentially regulated. We identified crucial pathways, including several signal transduction pathways, hormone response, oxidative response and protein, carbon and fatty acid metabolism pathways. Subsequently, a functional lncRNA-mRNA co-expression network was constructed, which consisted of 681 co-expression relationships between 164 lncRNAs and 201 mRNAs. Moreover, a lncRNA-pathway network was constructed. A total of 65 key lncRNAs were identified that regulate 20 significantly enriched pathways. Overall, our analysis provides insights into mRNA and lncRNA networks in rainbow trout skeletal muscle and their regulation by E2 while understanding the molecular mechanism of lncRNAs.
Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine
Authors: Nakamura Yukiko K. , Janowitz Cathleen , Metea Christina , Asquith Mark , Karstens Lisa , Rosenbaum James T. , Lin Phoebe 
Published: September 2017

AbstractShort chain fatty acids (SCFA) are metabolites of intestinal bacteria resulting from fermentation of dietary fiber. SCFA are protective in various animal models of inflammatory disease. We investigated the effects of exogenous administration of SFCAs, particularly propionate, on uveitis using an inducible model of experimental autoimmune uveitis (EAU). Oral SCFA administration attenuated uveitis severity in a mouse strain-dependent manner through regulatory T cell induction among lymphocytes in the intestinal lamina propria (LPL) and cervical lymph nodes (CLN). SCFA also suppressed effector T cell induction in the CLN and mesenteric lymph nodes (MLN). Alterations in intestinal morphology and gene expression demonstrated in the EAU model prior to the onset of uveitis were blunted by oral SCFA administration. Using a Kaede transgenic mouse, we demonstrated enhanced leukocyte trafficking between the intestine and the eye in EAU. Propionate suppressed T effector cell migration between the intestine and the spleen in EAU Kaede mice. In conclusion, our findings support exogenous administration of SCFAs as a potential treatment strategy for uveitis through the stabilization of subclinical intestinal alterations that occur in inflammatory diseases including uveitis, as well as prevention of trafficking of leukocytes between the gastrointestinal tract and extra-intestinal tissues.
Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice
Authors: Liu Yicong , Wu Zhou , Nakanishi Yurika , Ni Junjun , Hayashi Yoshinori , Takayama Fumiko , Zhou Yanmin , Kadowaki Tomoko , Nakanishi Hiroshi 
Published: September 2017

AbstractDespite a clear correlation between periodontitis and cognitive decline in Alzheimer’s disease, the precise mechanism underlying the relationship remains unclear. The periodontal pathogen Porphyromonas gingivalis produces a unique class of cysteine proteinases termed gingipains that comprises Arg-gingipain (Rgp) and Lys-gingipain (Kgp). Rgp and Kgp are important in the bacterial mediated host cell responses and the subsequent intracellular signaling in infected cells. In the present study, we attempted to clarify the potential effects of Rgp and Kgp on the cellular activation of brain-resident microglia. We provide the first evidence that Rgp and Kgp cooperatively contribute to the P. gingivalis-induced cell migration and expression of proinflammatory mediators through the activation of protease-activated receptor 2. The subsequent activation of phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase/ERK pathways contributes to cell migration and inflammatory response of microglia.
Quantitative trait loci responsible for sharp eyespot resistance in common wheat CI12633
Authors: Wu Xujiang , Cheng Kai , Zhao Renhui , Zang Shujiang , Bie Tongde , Jiang Zhengning , Wu Ronglin , Gao Derong , Zhang Boqiao 
Published: September 2017

AbstractSharp eyespot is a major fungal disease of wheat caused by Rhizoctonia cerealis in cool and humid environments worldwide. In this study, 224 single seed descent derived F13, F14 and F15 recombinant inbred lines (RILs) from the cross between CI12633 (a resistant cultivar) and Yangmai 9 (a susceptible cultivar) were assessed for sharp eyespot resistance (R.cerealis isolate R0301) in field and greenhouse conditions in three growing seasons. Different agronomic characteristics were also evaluated in the field with no disease infection. All the lines were genotyped with the Illumina iSelect 90 K SNP wheat chip and 101 SSR markers. Sharp eyespot resistance was significantly negatively correlated with heading date and tiller angle, and significantly positively correlated with the diameter of the basal first internode and second internode. Five QTL with a likelihood of odds ratio score of higher than 3.0 were detected on chromosomes 2BS, 4BS, 5AL and 5BS, respectively. These identified QTL may be used in future wheat breeding programs through marker assisted selection for developing sharp eyespot resistant cultivars.
Towards Addressing the Body Electrolyte Environment via Sweat Analysis:Pilocarpine Iontophoresis Supports Assessment of Plasma Potassium Concentration
Authors: Vairo Donato , Bruzzese Laurie , Marlinge Marion , Fuster Lea , Adjriou Nabil , Kipson Nathalie , Brunet Philippe , Cautela Jennifer , Jammes Yves , Mottola Giovanna , Burtey Stephane , Ruf Jean , Guieu Regis , Fenouillet Emmanuel 
Published: September 2017

AbstractElectrolyte concentration in sweat depends on environmental context and physical condition but also on the pathophysiological status. Sweat analyzers may be therefore the future way for biological survey although how sweat electrolyte composition can reflect plasma composition remains unclear. We recruited 10 healthy subjects and 6 patients to have a broad range of plasma electrolyte concentrations (chloride, potassium and sodium) and pH. These variables were compared to those found in sweat produced following cycling exercise or pilocarpine iontophoresis, a condition compatible with operating a wearable device. We found no correlation between plasma and sweat parameters when exercise-induced sweat was analyzed, and we could identify a correlation only between plasma and sweat potassium concentration (R = 0.78, p < 0.01) when sweat was induced using pilocarpine iontophoresis. We tested measurement repeatability in sweat at 24hr-interval for 3 days in 4 subjects and found a great intra-individual variability regarding all parameters in exercise-induced sweat whereas similar electrolyte levels were measured in pilocarpine-induced sweat. Thus, electrolyte concentration in sweat sampled following physical activity does not reflect concentration in plasma while pilocarpine iontophoresis appears to be promising to reproducibly address sweat electrolytes, and to make an indirect evaluation of plasma potassium concentration in chronic kidney disease and arrhythmia.
Controllable Moderate Heating Enhances the Therapeutic Efficacy of Irreversible Electroporation for Pancreatic Cancer
Authors: Edelblute Chelsea M. , Hornef James , Burcus Niculina I. , Norman Thomas , Beebe Stephen J. , Schoenbach Karl , Heller Richard , Jiang Chunqi , Guo Siqi 
Published: September 2017

AbstractIrreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43 °C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.67-fold at 1500 V/cm. This amount of heating alone did not cause cell death. An integrated IRE system with controllable laser heating and tumor impedance monitoring was developed to treat mouse ectopic pancreatic cancer. With this novel IRE system, we were able to heat and maintain the temperature of a targeted tumor area at 42 °C during IRE treatment. Pre-heating the tumor greatly reduced the impedance of tumor and its fluctuation. Most importantly, MHIRE has been demonstrated to significantly extend median survival and achieve a high rate of complete tumor regression. Median survival was 43, 46 and 84 days, for control, IRE with 100 μs, 1 Hz, 90 pulses and electric fields 2000–2500 V/cm and MHIRE treatment respectively. 55.6% of tumor-bearing mice treated with MHIRE were tumor-free, whereas complete tumor regression was not observed in the control and IRE treatment groups.
Insights into the functionality of endophytic actinobacteria with a focus on their biosynthetic potential and secondary metabolites production
Authors: Passari Ajit Kumar , Mishra Vineet Kumar , Singh Garima , Singh Pratibha , Kumar Brijesh , Gupta Vijai Kumar , Sarma Rupak Kumar , Saikia Ratul , Donovan Anthonia O’. , Singh Bhim Pratap 
Published: September 2017

AbstractEndophytic actinobacteria play an important role in growth promotion and development of host plant by producing enormous quantities of novel bioactive natural products. In the present investigation, 169 endophytic actinobacteria were isolated from endospheric tissues ofRhynchotoechum ellipticum. Based on their antimicrobial potential, 81 strains were identified by 16rRNA gene analysis, which were taxonomically grouped into 15 genera. All identified strains were screened for their plant growth promoting attributes and, for the presence of modular polyketide synthases (PKSI, PKSII and nonribosomal peptide synthetase (NRPS) gene clusters to correlate the biosynthetic genes with their functional properties. Expression studies and antioxidant potential for four representative strains were evaluated using qRT-PCR and DPPH assay respectively. Additionally, six antibiotics (erythromycin, ketoconazole, fluconazole, chloramphenicol, rifampicin and miconazole) and nine phenolic compounds (catechin, kaempferol, chebulagic acid, chlorogenic acid, Asiatic acid, ferulic acid, arjunic acid, gallic acid and boswellic acid) were detected and quantified using UHPLC-QqQLIT-MS/MS. Furthermore, three strains (BPSAC77, 121 and 101) showed the presence of the anticancerous compound paclitaxel which was reported for the first time from endophytic actinobacteria. This study provides a holistic picture, that endophytic actinobacteria are rich bacterial resource for bioactive natural products, which has a great prospective in agriculture and pharmaceutical industries.
α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility
Authors: Arcos Alexis , de Paola Matilde , Gianetti Diego , Acuña Diego , Velásquez Zahady D. , Miró María Paz , Toro Gabriela , Hinrichsen Bryan , Muñoz Rosa Iris , Lin Yimo , Mardones Gonzalo A. , Ehrenfeld Pamela , Rivera Francisco J. , Michaut Marcela A. , Batiz Luis Federico 
Published: September 2017

AbstractThe balance between ovarian folliculogenesis and follicular atresia is critical for female fertility and is strictly regulated by a complex network of neuroendocrine and intra-ovarian signals. Despite the numerous functions executed by granulosa cells (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordinate/modulate several cellular pathways is unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (α-SNAP) is a multifunctional protein that participates in SNARE-mediated membrane fusion events. In addition, it regulates cell-to-cell adhesion, AMPK signaling, autophagy and apoptosis in different cell types. In this study we examined the expression pattern of α-SNAP in ovarian tissue and the consequences of α-SNAP (M105I) mutation (hyh mutation) in folliculogenesis and female fertility. Our results showed that α-SNAP protein is highly expressed in GCs and its expression is modulated by gonadotropin stimuli. On the other hand, α-SNAP-mutant mice show a reduction in α-SNAP protein levels. Moreover, increased apoptosis of GCs and follicular atresia, reduced ovulation rate, and a dramatic decline in fertility is observed in α-SNAP-mutant females. In conclusion, α-SNAP plays a critical role in the balance between follicular development and atresia. Consequently, a reduction in its expression/function (M105I mutation) causes early depletion of ovarian follicles and female subfertility.
Residual Ammonium Persulfate in Nanoparticles Has Cytotoxic Effects on Cells through Epithelial-Mesenchymal Transition
Authors: Song Chen , Wang Leyu , Ye Genlan , Song Xiaoping , He Yutong , Qiu Xiaozhong 
Published: September 2017

AbstractAmmonium persulfate (APS), a low molecular weight chemical compound with strong oxidizing properties, should to be totally removed during preparation of nanomaterials due to its cytotoxicity. APS exerts its oxidative stress effects mainly on cell membrane, but its intracellular influence remains unclear. Here, we designed a facile negatively-charged carboxylic gelatin-methyacrylate (carbox-GelMA) nanoparticle (NP) as a cargo-carrier through the catalytic and oxidizing action of APS in W/O system. The formed APS-loaded carbox-GelMA NPs (APS/NPs) were transported into the lysosome in MCF-7 breast cancer cells. The intracellular APS/NPs produced a high level of oxidative stress in lysosome and induced epithelial-mesenchymal transition (EMT). Consequently, the MCF-7 cells challenged with APS/NPs had a strong metastatic and invasive capability in vitro and in vivo. This study highlights that a facile APS-loaded nanocarrier has cyctotoxicity on cells through EMT. Unexpectedly, we found a novel pathway inducing EMT via lysosomal oxidative stress.
Discovery, Semisynthesis, Antiparasitic and Cytotoxic Evaluation of 14-Membered Resorcylic Acid Lactones and Their Derivatives
Authors: Zhang Xue-Qing , Spadafora Carmenza , Pineda Laura M. , Ng Michelle G. , Sun Ji-Hong , Wang Wei , Wang Chang-Yun , Gu Yu-Cheng , Shao Chang-Lun 
Published: September 2017

AbstractTen antifouling 14-membered resorcylic acid lactones 1–10 were isolated previously with low or trace natural abundance from the zoanthid-derived Cochliobolus lunatus fungus. Further optimization of fermentation conditions led to the isolation of two major natural compounds 7 and 8 with multi-gram quantities. By one or two steps, we semisynthesized the six trace natural compounds 1–6 and a series of derivatives 11–27 of compounds 7 and 8 with high yields (65–95%). Compounds 11–13 showed strong antiplasmodial activity against Plasmodium falciparum with IC50 values of 1.84, 8.36, and 6.95 μM, respectively. Very importantly, 11 and 12 were non-toxic with very safety and high therapeutic indices (CC50/IC50 > 180), and thus representing potential promising leads for antiplasmodial drug discovery. Furthermore, 11 was the only compound showed obvious antileishmanial activity against Leishmania donovani with an IC50 value of 9.22 μM. Compounds 11 and 12 showed the values of IC50 at 11.9 and 17.2 μM against neglected Chagas’ disease causing Trypanosoma cruzi, respectively.
Resolving the phylogenetic origin of glioblastoma via multifocal genomic analysis of pre-treatment and treatment-resistant autopsy specimens
Authors: Brastianos Priscilla K. , Nayyar Naema , Rosebrock Daniel , Leshchiner Ignaty , Gill Corey M. , Livitz Dimitri , Bertalan Mia S. , D’Andrea Megan , Hoang Kaitlin , Aquilanti Elisa , Chukwueke Ugonma N. , Kaneb Andrew , Chi Andrew , Plotkin Scott , Gerstner Elizabeth R. , Frosch Mathew P. , Suva Mario L. , Cahill Daniel P. , Getz Gad , Batchelor Tracy T. 
Published: September 2017

AbstractGlioblastomas are malignant neoplasms composed of diverse cell populations. This intratumoral diversity has an underlying architecture, with a hierarchical relationship through clonal evolution from a common ancestor. Therapies are limited by emergence of resistant subclones from this phylogenetic reservoir. To characterize this clonal ancestral origin of recurrent tumors, we determined phylogenetic relationships using whole exome sequencing of pre-treatment IDH1/2 wild-type glioblastoma specimens, matched to post-treatment autopsy samples (n = 9) and metastatic extracranial post-treatment autopsy samples (n = 3). We identified “truncal” genetic events common to the evolutionary ancestry of the initial specimen and later recurrences, thereby inferring the identity of the precursor cell population. Mutations were identified in a subset of cases in known glioblastoma genes such as NF1(n = 3), TP53(n = 4) and EGFR(n = 5). However, by phylogenetic analysis, there were no protein-coding mutations as recurrent truncal events across the majority of cases. In contrast, whole copy-loss of chromosome 10 (12 of 12 cases), copy-loss of chromosome 9p21 (11 of 12 cases) and copy-gain in chromosome 7 (10 of 12 cases) were identified as shared events in the majority of cases. Strikingly, mutations in the TERT promoter were also identified as shared events in all evaluated pairs (9 of 9). Thus, we define four truncal non-coding genomic alterations that represent early genomic events in gliomagenesis, that identify the persistent cellular reservoir from which glioblastoma recurrences emerge. Therapies to target these key early genomic events are needed. These findings offer an evolutionary explanation for why precision therapies that target protein-coding mutations lack efficacy in GBM.