bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrative piRNA analysis of mouse gametes and zygotes reveals new potential origins and gene regulatory roles
Authors: Larriba Eduardo , del Mazo Jesús 
Published: August 2018

AbstractPiwi-interacting RNAs (piRNAs) are a subclass of the small non-coding RNAs (sncRNAs). Their main reported function was to exert control over transposable elements (TEs) in mammalian germline. In this study undertaking a deeper bioinformatics analysis of piRNAs present in mouse oocytes, sperm cells and zygotes, we first elaborated a new piRNA database based on sequences identified as piRNAs by immunoprecipitation with PIWI proteins. Our bioinformatics analysis revealed that, at least in gametes and zygotes, piRNAs could encompass multifunctional cell-dependent regulatory molecules. Indeed, genome analysis of the piRNA mapping density (reads/kb) evidenced in all samples an enrichment of intron-derived piRNAs. Further, piRNA population was classified into sequences not associated to TEs or repeats (NRapiRNAs) and associated to repetitive genome elements (RapiRNAs). In oocytes most of the NRapiRNAs mapped to the 5′UTRs of coding mRNAs, while higher proportion of NRapiRNAs was detected in sperm cells associated to the 3′UTRs of mRNAs. This piRNA complementarity to mRNA UTRs suggests key post-transcriptional regulatory roles over mRNAs such as those encoding MHC genes. In addition, a striking association of RapiRNA with long non-coding RNAs (lncRNAs) was identified. piRNAs associated with relevant lncRNAs such as: Rab26os and GAS5 and key mRNAs, were particularly assessed.
Analyses of ovarian activity reveal repeated evolution of post-reproductive lifespans in toothed whales
Authors: Ellis Samuel , Franks Daniel W. , Nattrass Stuart , Currie Thomas E. , Cant Michael A. , Giles Deborah , Balcomb Kenneth C. , Croft Darren P. 
Published: August 2018

AbstractIn most species the reproductive system ages at the same rate as somatic tissue and individuals continue reproducing until death. However, females of three species – humans, killer whales and short-finned pilot whales – have been shown to display a markedly increased rate of reproductive senescence relative to somatic ageing. In these species, a significant proportion of females live beyond their reproductive lifespan: they have a post-reproductive lifespan. Research into this puzzling life-history strategy is hindered by the difficulties of quantifying the rate of reproductive senescence in wild populations. Here we present a method for measuring the relative rate of reproductive senescence in toothed whales using published physiological data. Of the sixteen species for which data are available (which does not include killer whales), we find that three have a significant post-reproductive lifespan: short-finned pilot whales, beluga whales and narwhals. Phylogenetic reconstruction suggests that female post-reproductive lifespans have evolved several times independently in toothed whales. Our study is the first evidence of a significant post-reproductive lifespan in beluga whales and narwhals which, when taken together with the evidence for post-reproductive lifespan in killer whales, doubles the number of non-human mammals known to exhibit post-reproductive lifespans in the wild.
The ABD on the nascent polypeptide and PH domain are required for the precise Anillin localization in Drosophila syncytial blastoderm
Authors: Hirashima Tomoki , Tanaka Ryo , Yamaguchi Masamitsu , Yoshida Hideki 
Published: August 2018

AbstractTargeting proteins to regions where they are required is essential for proper development of organisms. For achievement of this, subcellular mRNA localization is one of the critical mechanisms. Subcellular mRNA localization is an evolutionarily conserved phenomenon from E. coli to human and contributes to limiting the regions at which its products function and efficiently supplies substrates for protein translation. During early Drosophila embryogenesis, while 71% of the 3370 mRNAs analyzed have shown prominent subcellular localization, the underlying molecular mechanisms have not been elucidated. Here, we reveal that anillin mRNA, one of the localized mRNAs in early Drosophila embryo, localizes to the tip of the pseudo-cleavage furrow in the Drosophila syncytial blastoderm using in situ hybridization combined with immunohistochemistry. Localization analyses with transgenic fly lines carrying a series of deletion mRNAs indicate that this localization is dependent on its own nascent polypeptides including the actin binding domain (ABD). In addition to the mRNA localization, it is revealed that the pleckstrin homology (PH) domain of Anillin protein is also required for its proper localization. Thus, we indicate that the precise localization of Anillin protein is tightly regulated by the ABD on the nascent polypeptide and PH domain in the Drosophila syncytial blastoderm.
Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue
Authors: Stebe-Frick Sabrina , Ostaff Maureen J. , Stange Eduard F. , Malek Nisar P. , Wehkamp Jan 
Published: August 2018

AbstractHistone deacetylase inhibition (HDACi) has been suggested as a promising approach to bolster TLR-mediated induction of antimicrobial peptides such as human β-defensin 2 (hBD2). In inflammatory bowel disease (IBD), Crohn’s disease (CD) patients display an attenuated expression of hBD2 as compared to ulcerative colitis (UC). Here, we aimed to study if combining HDACi with the therapeutic E. coli Nissle 1917 (EcN), a strong hBD2 inducer, might be a feasible strategy to further modify protective immune responses. Monolayer epithelial cell lines versus cultured human biopsies from healthy controls and CD and UC patients showed diverse effects. In mono-cell systems, we observed a strong NF-kB-dependent enhancement of TLR- but also IL1β-mediated hBD2 induction after HDACi. In contrast, multicellular colonic biopsy culture showed the opposite result and HDACi was associated with an abolished TLR-mediated hBD2 induction in all tested patient groups. Of note, CD patients showed an attenuated induction of hBD2 by E. coli Nissle as compared to UC. We conclude that the role of HDACs in hBD2 regulation is context-dependent and likely modified by different cell types. Differential induction in different IBD entities suggests different clinical response patterns based on still unknown hBD2-associated mechanisms.
Solvent-Antisolvent Ambient Processed Large Grain Size Perovskite Thin Films for High-Performance Solar Cells
Authors: Gedamu Dawit , Asuo Ivy M. , Benetti Daniele , Basti Matteo , Ka Ibrahima , Cloutier Sylvain G. , Rosei Federico , Nechache Riad 
Published: August 2018

AbstractIn recent years, hybrid organic-inorganic halide perovskites have been widely studied for the low-cost fabrication of a wide range of optoelectronic devices, including impressive perovskite-based solar cells. Amongst the key factors influencing the performance of these devices, recent efforts have focused on tailoring the granularity and microstructure of the perovskite films. Albeit, a cost-effective technique allowing to carefully control their microstructure in ambient environmental conditions has not been realized. We report on a solvent-antisolvent ambient processed CH3NH3PbI3−xClx based thin films using a simple and robust solvent engineering technique to achieve large grains (>5 µm) having excellent crystalline quality and surface coverage with very low pinhole density. Using optimized treatment (75% chlorobenzene and 25% ethanol), we achieve highly-compact perovskite films with 99.97% surface coverage to produce solar cells with power conversion efficiencies (PCEs) up-to 14.0%. In these planar solar cells, we find that the density and size of the pinholes are the dominant factors that affect their overall performances. This work provides a promising solvent treatment technique in ambient conditions and paves the way for further optimization of large area thin films and high performance perovskite solar cells.
Decreased Gray Matter Volume of Cuneus and Lingual Gyrus in Schizophrenia Patients with Tardive Dyskinesia is Associated with Abnormal Involuntary Movement
Authors: Yu Ting , Li Yanli , Fan Fengmei , Cao Hongbao , Luo Xingguang , Tan Shuping , Yang Fude , Zhang Xiangyang , Shugart Yin Yao , Hong L. Elliot , Li Chiang-Shan R. , Tan Yunlong 
Published: August 2018

AbstractTardive dyskinesia (TD) is a devastating motor disorder associated with the etiological process of schizophrenia or antipsychotic medication treatments. To examine whether cerebral morphological changes may manifest in TD, we used voxel-based morphometry to analyze high-resolution T1-weighted brain structural magnetic resonance images from 32 schizophrenics with TD (TD group), 31 schizophrenics without TD (non-TD group), and 32 healthy controls (HC group). We also assessed psychopathological symptoms with the Positive and Negative Syndrome Scale (PANSS), and TD severity with the Abnormal Involuntary Movement Scale (AIMS). We compared gray matter volumes (GMVs) among groups, and tested for correlations between GMV changes and psychopathological symptoms or TD severity. The results showed significant differences in GMV in the frontal and temporal cortices, insula and cerebellum among the three groups. Brainstem and inferior frontal and precentral gyri GMVs were significantly larger, whereas cuneus and lingual gyrus GMVs were significantly smaller in the TD group as compared to non-TD group. Further, the cuneus and lingual gyrus GMVs were positively correlated with AIMS scores in the TD group. The current results suggest that TD may be associated with the alterations in GMV that are different from that of schizophrenics without TD. Further studies are needed to confirm and to examine the functional significance of these structural findings.
Antrodia cinnamomea boosts the anti-tumor activity of sorafenib in xenograft models of human hepatocellular carcinoma
Authors: Wu Wei-De , Chen Pin-Shern , Omar Hany A. , Arafa El-Shaimaa A. , Pan Hung-Wei , Jeng Jingyueh , Hung Jui-Hsiang 
Published: August 2018

AbstractHepatocellular carcinoma (HCC) has been recognized worldwide as one of the major causes of cancer death. The medicinal fungus Antrodia cinnamomea (A. cinnamomea) has been served as a functional food for liver protection. The aim of the present study was to investigate the potential activity of A. cinnamomea extracts as a safe booster for the anticancer activity of sorafenib, a multi-kinase inhibitor approved for the treatment of HCC. The biologically active triterpenoids in the ethanolic extracts of A. cinnamomea (EAC) were initially identified by HPLC/LC/MS then the different extracts and sorafenib were assessed in vitro and in vivo. EAC could effectively sensitize HCC cells to low doses of sorafenib, which was perceived via the ability of the combination to repress cell viability and to induce cell cycle arrest and apoptosis in HCC cells. The ability of EAC to enhance sorafenib activity was mediated through targeting mitogen-activated protein (MAP) kinases, modulating cyclin proteins expression and inhibiting cancer cell invasion. Moreover, the proposed combination significantly suppressed ectopic tumor growth in mice with high safety margins compared to single-agent treatment. Thus, this study highlights the advantage of combining EAC with sorafenib as a potential adjuvant therapeutic strategy against HCC.
B2 microglobulin is a novel prognostic marker of Angioimmunoblastic T-cell lymphoma
Authors: Shang Yufeng , Fu Xiaorui , Chang Yu , Li Yanan , Zhang Mingzhi 
Published: August 2018

AbstractThe aim of the present study was to analyze features and explore parameters that can help to predict prognosis for angioimmunoblastic T-cell lymphoma (AITL). A total of 117 patients with AITL were retrospectively analyzed. Multivariate analysis showed that β2 microglobulin (β2-M) ≥4.0 mg/L (P = 0.020), rash/pruritus (P = 0.004), performance status (PS) ≥2 (P = 0.006), age >60 years (P = 0.006) and extranodal sites (ENSs) >1 (P = 0.029) were independent risk factors for OS. Rash/pruritus (P = 0.007), age >60 years (P = 0.035) and ENSs >1 (P = 0.006) were independent risk factors for PFS. A novel prognostic model consisting of β2-M, rash/pruritus, PS, age and ENSs >1 was constructed. The model classified patients into 3 risk stratifications: low risk (0 or 1 factor), intermediate risk (2 factors), high risk (≥3 factors) and significantly stratified patients with AITL (P < 0.001). In conclusion, except for PS ≥2, age >60 years and ENSs >1 used in IPI, β2-M and rash/pruritus also indicated adverse prognosis. That we constructed model was commendably prognostic for OS and PFS.
Efficient derivation of sympathetic neurons from human pluripotent stem cells with a defined condition
Authors: Kirino Kosuke , Nakahata Tatsutoshi , Taguchi Tomoaki , Saito Megumu K. 
Published: August 2018

AbstractSympathetic neurons (SNs) are an essential component of the autonomic nervous system. They control vital bodily functions and are responsible for various autonomic disorders. However, obtaining SNs from living humans for in vitro study has not been accomplished. Although human pluripotent stem cell (hPSC)-derived SNs could be useful for elucidating the pathophysiology of human autonomic neurons, the differentiation efficiency remains low and reporter-based cell sorting is usually required for the subsequent pathophysiological analysis. To improve the efficiency, we refined each differentiation stage using PHOX2B::eGFP reporter hPSC lines to establish a robust and efficient protocol to derive functional SNs via neuromesodermal progenitor-like cells and trunk neural crest cells. Sympathetic neuronal progenitors could be expanded and stocked during differentiation. Our protocol can selectively enrich sympathetic lineage-committed cells at high-purity (≈80%) from reporter-free hPSC lines. Our system provides a platform for diverse applications, such as developmental studies and the modeling of SN-associated diseases.
A Survival Metadata Analysis Responsive Tool (SMART) for web-based analysis of patient survival and risk
Authors: Chu Yuan-Chia , Kuo Wen-Tsung , Cheng Yuan-Ren , Lee Chung-Yuan , Shiau Cheng-Ying , Tarng Der-Cherng , Lai Feipei 
Published: August 2018

AbstractHealth information systems contain extensive amounts of patient data. Information relevant to public health and individuals’ medical histories are both available. In clinical research, the prediction of patient survival rates and identification of prognosis factors are major challenges. To alleviate the difficulties related to these factors, Metadata Utilities was developed to help researchers manage column definitions and information such as import/query/generator Metadata files. These utilities also include an automatic update mechanism to ensure consistency between the data and parameters of the batch produced in the conversion procedure. Survival Metadata Analysis Responsive Tool (SMART) provides a comprehensive set of statistical tests that are easy to understand, including support for analyzing nominal variables, ordinal variables, interval variables or ratio variables as means, standard deviations, maximum values, minimum values, and percentages. In this article, the development of a raw data source and transfer mechanism, Extract-Transform-Load (ETL), is described for data cleansing, extraction, transformation and loading. We also built a handy method for data presentation, which can be customized to the trial design. As demonstrated here, SMART is useful for risk-adjusted baseline cohort and randomized controlled trials.
Definitive radiotherapy dose escalation with chemotherapy for treating non-metastatic oesophageal cancer
Authors: Fan Chao-Yueh , Su Yu-Fu , Huang Wen-Yen , Chao Hsing-Lung , Lin Kuen-Tze , Lin Chun-Shu 
Published: August 2018

AbstractThe locoregional failure rate remains high after concurrent chemoradiotherapy with standard-dose radiotherapy (RT, 50–50.4 Gy) for oesophageal cancer (EC). This retrospective study evaluated whether RT dose escalation was effective among 115 consecutive patients with non-metastatic EC (July 2003 to November 2016). Forty-four patients received an RT dose of <66 Gy and 71 patients received ≥66 Gy, with most patients receiving concurrent cisplatin plus fluorouracil. The median follow-up was 12 months for all patients (52 months for 18 surviving patients). The ≥66 Gy group had significantly higher 3-year rates of overall survival (17.9% vs. 32.1%, p = 0.026) and local progression-free survival (46.1% vs. 72.1%, p = 0.005), but not disease progression-free survival (11.4% vs. 21.9%, p = 0.059) and distant metastasis-free survival (49% vs. 52.6%, p = 0.852). The ≥66 Gy group also had significantly better 5-year overall survival compared with 41.4–65.9 Gy. The only significant difference in treatment-related toxicities involved acute dermatitis (7% vs. 28%, p = 0.009). Inferior overall survival was associated with poor performance status, clinical N2–3 stage and not receiving maintenance chemotherapy. In conclusion, patients with inoperable EC experienced better survival outcomes and acceptable toxicities if they received higher dose RT (≥66 Gy) rather than lower dose RT (<66 Gy).
Specific Alterations in Astrocyte Properties via the GluA2-GAPDH Complex Associated with Multiple Sclerosis
Authors: Lee Frankie H. F. , Zhang Hailong , Jiang Anlong , Zai Clement C. , Liu Fang 
Published: August 2018

AbstractThere is strong evidence indicating neuroinflammation is an important mediator in multiple sclerosis (MS), with astrogliosis playing a significant role in this process. Surprisingly, astrocytes exert paradoxical roles during disease development, but the mechanisms remain unknown. Previously, we have reported that administering an interfering peptide (GluA2-G-Gpep) which specifically disrupts the GluA2-GAPDH interaction rescued neurological symptoms in the EAE mouse model of MS. In this study, we validated that the GluA2-GAPDH complex was elevated in LPS-induced primary reactive astrocytes, and GluA2-G-Gpep treatment significantly reduced GFAP expression levels in both EAE mice and reactive astrocytes. Further in vivo and in vitro analyses revealed that GluA2-G-Gpep administration normalized EAAT1 and EAAT2 expression, rescued compromised blood-brain barrier integrity via AQP4, promoted actin reorganization and changed mitochondrial dynamics. These alterations may partially be explained by changes in the nuclear GAPDH and p53 transcription pathways. Our findings provide critical implications for understanding the astrocyte properties regulated by GluA2-GAPDH associated with MS, and insights for novel treatment options targeting at astrocytes.
Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment
Authors: Shu Shin La , Yang Yunchen , Allen Cheryl L. , Maguire Orla , Minderman Hans , Sen Arindam , Ciesielski Michael J. , Collins Katherine A. , Bush Peter J. , Singh Prashant , Wang Xue , Morgan Martin , Qu Jun , Bankert Richard B. , Whiteside Theresa L. , Wu Yun , Ernstoff Marc S. 
Published: August 2018

AbstractLocal acidification of stroma is proposed to favour pre-metastatic niche formation but the mechanism of initiation is unclear. We investigated whether Human Melanoma-derived exosomes (HMEX) could reprogram human adult dermal fibroblasts (HADF) and cause extracellular acidification. HMEX were isolated from supernatants of six melanoma cell lines (3 BRAF V600E mutant cell lines and 3 BRAF wild-type cell lines) using ultracentrifugation or Size Exclusion Chromatography (SEC). Rapid uptake of exosomes by HADF was demonstrated following 18 hours co-incubation. Exposure of HDAF to HMEX leads to an increase in aerobic glycolysis and decrease in oxidative phosphorylation (OXPHOS) in HADF, consequently increasing extracellular acidification. Using a novel immuno-biochip, exosomal miR-155 and miR-210 were detected in HMEX. These miRNAs were present in HMEX from all six melanoma cell lines and were instrumental in promoting glycolysis and inhibiting OXPHOS in tumour cells. Inhibition of miR-155 and miR-210 activity by transfection of miRNA inhibitors into HMEX reversed the exosome-induced metabolic reprogramming of HADF. The data indicate that melanoma-derived exosomes modulate stromal cell metabolism and may contribute to the creation of a pre-metastatic niche that promotes the development of metastasis.
Reliability improvements in SOI‐like MOSFET with ESD and self‐heating effect
Authors: Cao Fei , Shan Chan , Wang Ying , Luo Xin , Yu Cheng‐hao 
Published: August 2018

A new structure of N‐type Silicon‐on‐insulator (SOI)‐Like Bulk Silicon (N‐SL‐BS) metal–oxide–semiconductor field‐effect transistor (MOSFET) is proposed to improve the reliability of SOI MOSFET mainly with regards to their self‐heating effect and electro‐static discharge (ESD) events based on two‐dimensional numerical simulation. The new device employs p/n–/p + structure on Si, in which the n‐layer is made of Si carbide (SiC), a wide bandgap material. The built‐in electric field fully depletes the n‐SiC layer and forms an SOI‐like feature with a p + layer underneath. Simulations are first implemented in self‐heating conditions, to investigate their drain current and temperature ramping. More importantly, ESD pulses assuming the human body model are applied to test their response and observe which device was first to fail using an I–V curve and hole current density distribution. Results show that the new device exhibits superior reliability when compared with a traditional SOI MOSFET. The avalanche breakdown voltage improves nearly 33% and the highest temperature of the global device is more than three times lower than that of an SOI MOSFET subjected to ESD pulses with a peak current of 7 mA.
Investigating hot-Jupiter inflated radii with hierarchical Bayesian modelling
Authors: Sestovic Marko , Demory Brice-Olivier , Queloz Didier 
Published: August 2018

Context.As of today, hundreds of hot Jupiters have been found, yet the inflated radii of a large fraction of them remain unexplained. A number of mechanisms have been proposed to explain these anomalous radii, however most of these can only work under certain conditions and may not be sufficient to explain the most extreme cases. It is still unclear whether a single mechanism can sufficiently explain the entire distribution of radii, or whether a combination of these mechanisms is needed.Aims.We seek to understand the relationship of radius with stellar irradiation and mass and to find the range of masses over which hot Jupiters are inflated. We also aim to find the intrinsic physical scatter in their radii, caused by unobservable parameters, and to constrain the fraction of hot Jupiters that exhibit inflation.Methods.By constructing a hierarchical Bayesian model, we inferred the probabilistic relation between planet radius, mass, and incident flux for a sample of 286 gas giants. We separately incorporated the observational uncertainties of the data and the intrinsic physical scatter in the population. This allowed us to treat the intrinsic physical scatter in radii, due to latent parameters such as the heavy element fraction, as a parameter to be inferred.Results.We find that the planetary mass plays a key role in the inflation extent and that planets in the range ~0.37−0.98 MJshow the most inflated radii. At higher masses, the radius response to incident flux begins to decrease. Below a threshold of 0.37 ± 0.03 MJwe find that giant exoplanets as a population are unable to maintain inflated radii ≿1.4 RJbut instead exhibit smaller sizes as the incident flux is increased beyond 106W m−2. We also find that below 1 MJ, there is a cut-off point at high incident flux beyond which we find no more inflated planets, and that this cut-off point decreases as the mass decreases. At incident fluxes higher than ~1.6 × 106W m−2and in a mass range 0.37−0.98 MJ, we find no evidence for a population of non-inflated hot Jupiters. Our study sheds a fresh light on one of the key questions in the field and demonstrates the importance of population-level analysis to grasp the underlying properties of exoplanets.