bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells
Authors:   The International Stem Cell Initiative, Allison Thomas F. , Andrews Peter W. , Avior Yishai , Barbaric Ivana , Benvenisty Nissim , Bock Christoph , Brehm Jennifer , Brüstle Oliver , Damjanov Ivan , Elefanty Andrew , Felkner Daniel , Gokhale Paul J. , Halbritter Florian , Healy Lyn E. , Hu Tim X. , Knowles Barbara B. , Loring Jeanne F. , Ludwig Tenneille E. , Mayberry Robyn , Micallef Suzanne , Mohamed Jameelah S. , Müller Franz-Josef , Mummery Christine L. , Nakatsuji Norio , Ng Elizabeth S. , Oh Steve K. W. , O’Shea Orla , Pera Martin F. , Reubinoff Benjamin , Robson Paul , Rossant Janet , Schuldt Bernhard M. , Solter Davor , Sourris Koula , Stacey Glyn , Stanley Edouard G. , Suemori Hirofumi , Takahashi Kazutoshi , Yamanaka Shinya 
Published: May 2018

AbstractThe International Stem Cell Initiative compared several commonly used approaches to assess human pluripotent stem cells (PSC). PluriTest predicts pluripotency through bioinformatic analysis of the transcriptomes of undifferentiated cells, whereas, embryoid body (EB) formation in vitro and teratoma formation in vivo provide direct tests of differentiation. Here we report that EB assays, analyzed after differentiation under neutral conditions and under conditions promoting differentiation to ectoderm, mesoderm, or endoderm lineages, are sufficient to assess the differentiation potential of PSCs. However, teratoma analysis by histologic examination and by TeratoScore, which estimates differential gene expression in each tumor, not only measures differentiation but also allows insight into a PSC’s malignant potential. Each of the assays can be used to predict pluripotent differentiation potential but, at this stage of assay development, only the teratoma assay provides an assessment of pluripotency and malignant potential, which are both relevant to the pre-clinical safety assessment of PSCs.
Efficacy of a respiratory syncytial virus vaccine candidate in a maternal immunization model
Authors: Blanco Jorge C. G. , Pletneva Lioubov M. , McGinnes-Cullen Lori , Otoa Raymonde O. , Patel Mira C. , Fernando Lurds R. , Boukhvalova Marina S. , Morrison Trudy G. 
Published: May 2018

AbstractRespiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or purified subunit F protein vaccines, giving an advantage on mothers’ protection. VLP immunization of dams provides significant protection to pups from RSV challenge and reduced pulmonary inflammation. Collectively, our results show that a VLP vaccine with RSV F and G proteins is safe and effective for maternal and adult vaccination.
B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation
Authors: Barwick Benjamin G. , Scharer Christopher D. , Martinez Ryan J. , Price Madeline J. , Wein Alexander N. , Haines Robert R. , Bally Alexander P. R. , Kohlmeier Jacob E. , Boss Jeremy M. 
Published: May 2018

AbstractB cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization. Gene expression is mostly unaltered in naive and germinal center B cells, but dysregulated in Dnmt3-deficient plasma cells. Differences in gene expression are proximal to Dnmt3-dependent DNA methylation and chromatin changes, both of which coincide with E2A and PU.1-IRF composite-binding motifs. Thus, de novo DNA methylation limits B cell activation, represses the plasma cell chromatin state, and regulates plasma cell differentiation.
Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer
Authors: Kang Myoung-Hee , Choi Hyunji , Oshima Masanobu , Cheong Jae-Ho , Kim Seokho , Lee Jung Hoon , Park Young Soo , Choi Hueng-Sik , Kweon Mi-Na , Pack Chan-Gi , Lee Ju-Seog , Mills Gordon B. , Myung Seung-Jae , Park Yun-Yong 
Published: May 2018

AbstractThe principle factors underlying gastric cancer (GC) development and outcomes are not well characterized resulting in a paucity of validated therapeutic targets. To identify potential molecular targets, we analyze gene expression data from GC patients and identify the nuclear receptor ESRRG as a candidate tumor suppressor. ESRRG expression is decreased in GC and is a predictor of a poor clinical outcome. Importantly, ESRRG suppresses GC cell growth and tumorigenesis. Gene expression profiling suggests that ESRRG antagonizes Wnt signaling via the suppression of TCF4/LEF1 binding to the CCND1 promoter. Indeed, ESRRG levels are found to be inversely correlated with Wnt signaling-associated genes in GC patients. Strikingly, the ESRRG agonist DY131 suppresses cancer growth and represses the expression of Wnt signaling genes. Our present findings thus demonstrate that ESRRG functions as a negative regulator of the Wnt signaling pathway in GC and is a potential therapeutic target for this cancer.
The CRISPR tool kit for genome editing and beyond
Authors: Adli Mazhar 
Published: May 2018

AbstractCRISPR is becoming an indispensable tool in biological research. Once known as the bacterial immune system against invading viruses, the programmable capacity of the Cas9 enzyme is now revolutionizing diverse fields of medical research, biotechnology, and agriculture. CRISPR-Cas9 is no longer just a gene-editing tool; the application areas of catalytically impaired inactive Cas9, including gene regulation, epigenetic editing, chromatin engineering, and imaging, now exceed the gene-editing functionality of WT Cas9. Here, we will present a brief history of gene-editing tools and describe the wide range of CRISPR-based genome-targeting tools. We will conclude with future directions and the broader impact of CRISPR technologies.
Solvent-assisted programming of flat polymer sheets into reconfigurable and self-healing 3D structures
Authors: Yang Yang , Terentjev Eugene M. , Wei Yen , Ji Yan 
Published: May 2018

AbstractIt is extremely challenging, yet critically desirable to convert 2D plastic films into 3D structures without any assisting equipment. Taking the advantage of solvent-induced bond-exchange reaction and elastic-plastic transition, shape programming of flat vitrimer polymer sheets offers a new way to obtain 3D structures or topologies, which are hard for traditional molding to achieve. Here we show that such programming can be achieved with a pipette, a hair dryer, and a bottle of solvent. The polymer used here is very similar to the commercial epoxy, except that a small percentage of a specific catalyst is involved to facilitate the bond-exchange reaction. The programmed 3D structures can later be erased, reprogrammed, welded with others, and healed again and again, using the same solvent-assisted technique. The 3D structures can also be recycled by hot-pressing into new sheets, which can still be repeatedly programmed.
Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease
Authors: Wang Liqun , Xia Jing , Li Jonathan , Hagemann Tracy L. , Jones Jeffrey R. , Fraenkel Ernest , Weitz David A. , Zhang Su-Chun , Messing Albee , Feany Mel B. 
Published: May 2018

AbstractGlial cells have increasingly been implicated as active participants in the pathogenesis of neurological diseases, but critical pathways and mechanisms controlling glial function and secondary non-cell autonomous neuronal injury remain incompletely defined. Here we use models of Alexander disease, a severe brain disorder caused by gain-of-function mutations in GFAP, to demonstrate that misregulation of GFAP leads to activation of a mechanosensitive signaling cascade characterized by activation of the Hippo pathway and consequent increased expression of A-type lamin. Importantly, we use genetics to verify a functional role for dysregulated mechanotransduction signaling in promoting behavioral abnormalities and non-cell autonomous neurodegeneration. Further, we take cell biological and biophysical approaches to suggest that brain tissue stiffness is increased in Alexander disease. Our findings implicate altered mechanotransduction signaling as a key pathological cascade driving neuronal dysfunction and neurodegeneration in Alexander disease, and possibly also in other brain disorders characterized by gliosis.
Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages
Authors: Bunnik Evelien M. , Cook Kate B. , Varoquaux Nelle , Batugedara Gayani , Prudhomme Jacques , Cort Anthony , Shi Lirong , Andolina Chiara , Ross Leila S. , Brady Declan , Fidock David A. , Nosten Francois , Tewari Rita , Sinnis Photini , Ay Ferhat , Vert Jean-Philippe , Noble William Stafford , Le Roch Karine G. 
Published: May 2018

AbstractThe development of malaria parasites throughout their various life cycle stages is coordinated by changes in gene expression. We previously showed that the three-dimensional organization of the Plasmodium falciparum genome is strongly associated with gene expression during its replication cycle inside red blood cells. Here, we analyze genome organization in the P. falciparum and P. vivax transmission stages. Major changes occur in the localization and interactions of genes involved in pathogenesis and immune evasion, host cell invasion, sexual differentiation, and master regulation of gene expression. Furthermore, we observe reorganization of subtelomeric heterochromatin around genes involved in host cell remodeling. Depletion of heterochromatin protein 1 (PfHP1) resulted in loss of interactions between virulence genes, confirming that PfHP1 is essential for maintenance of the repressive center. Our results suggest that the three-dimensional genome structure of human malaria parasites is strongly connected with transcriptional activity of specific gene families throughout the life cycle.
Emergent superconductivity in an iron-based honeycomb lattice initiated by pressure-driven spin-crossover
Authors: Wang Yonggang , Ying Jianjun , Zhou Zhengyang , Sun Junliang , Wen Ting , Zhou Yannan , Li Nana , Zhang Qian , Han Fei , Xiao Yuming , Chow Paul , Yang Wenge , Struzhkin Viktor V. , Zhao Yusheng , Mao Ho-kwang 
Published: May 2018

AbstractThe discovery of iron-based superconductors (FeSCs), with the highest transition temperature (Tc) up to 55 K, has attracted worldwide research efforts over the past ten years. So far, all these FeSCs structurally adopt FeSe-type layers with a square iron lattice and superconductivity can be generated by either chemical doping or external pressure. Herein, we report the observation of superconductivity in an iron-based honeycomb lattice via pressure-driven spin-crossover. Under compression, the layered FePX3 (X = S, Se) simultaneously undergo large in-plane lattice collapses, abrupt spin-crossovers, and insulator-metal transitions. Superconductivity emerges in FePSe3 along with the structural transition and vanishing of magnetic moment with a starting Tc ~ 2.5 K at 9.0 GPa and the maximum Tc ~ 5.5 K around 30 GPa. The discovery of superconductivity in iron-based honeycomb lattice provides a demonstration for the pursuit of transition-metal-based superconductors via pressure-driven spin-crossover.
Daily rhythmicity in coastal microbial mats
Authors: Hörnlein Christine , Confurius-Guns Veronique , Stal Lucas J. , Bolhuis Henk 
Published: May 2018

AbstractCyanobacteria are major primary producers in coastal microbial mats and provide biochemical energy, organic carbon, and bound nitrogen to the mat community through oxygenic photosynthesis and dinitrogen fixation. In order to anticipate the specific requirements to optimize their metabolism and growth during a day-and-night cycle, Cyanobacteria possess a unique molecular timing mechanism known as the circadian clock that is well-studied under laboratory conditions but little is known about its function in a natural complex community. Here, we investigated daily rhythmicity of gene expression in a coastal microbial mat community sampled at 6 time points during a 24-h period. In order to identify diel expressed genes, meta-transcriptome data was fitted to periodic functions. Out of 24,035 conserved gene transcript clusters, approximately 7% revealed a significant rhythmic expression pattern. These rhythmic genes were assigned to phototrophic micro-eukaryotes, Cyanobacteria but also to Proteobacteria and Bacteroidetes. Analysis of MG-RAST annotated genes and mRNA recruitment analysis of two cyanobacterial and three proteobacterial microbial mat members confirmed that homologs of the cyanobacterial circadian clock genes were also found in other bacterial members of the microbial mat community. These results suggest that various microbial mat members other than Cyanobacteria have their own molecular clock, which can be entrained by a cocktail of Zeitgebers such as light, temperature or metabolites from neighboring species. Hence, microbial mats can be compared to a complex organism consisting of multiple sub-systems that have to be entrained in a cooperative way such that the corpus functions optimally.
Critical amino acids for the insecticidal activity of Vip3Af from Bacillus thuringiensis: Inference on structural aspects
Authors: Banyuls N. , Hernández-Rodríguez C. S. , Van Rie J. , Ferré J. 
Published: May 2018

AbstractVip3 vegetative insecticidal proteins from Bacillus thuringiensis are an important tool for crop protection against caterpillar pests in IPM strategies. While there is wide consensus on their general mode of action, the details of their mode of action are not completely elucidated and their structure remains unknown. In this work the alanine scanning technique was performed on 558 out of the total of 788 amino acids of the Vip3Af1 protein. From the 558 residue substitutions, 19 impaired protein expression and other 19 substitutions severely compromised the insecticidal activity against Spodoptera frugiperda. The latter 19 substitutions mainly clustered in two regions of the protein sequence (amino acids 167–272 and amino acids 689–741). Most of these substitutions also decreased the activity to Agrotis segetum. The characterisation of the sensitivity to proteases of the mutant proteins displaying decreased insecticidal activity revealed 6 different band patterns as evaluated by SDS-PAGE. The study of the intrinsic fluorescence of most selected mutants revealed only slight shifts in the emission peak, likely indicating only minor changes in the tertiary structure. An in silico modelled 3D structure of Vip3Af1 is proposed for the first time.
Distinguishing mirtrons from canonical miRNAs with data exploration and machine learning methods
Authors: Rorbach Grzegorz , Unold Olgierd , Konopka Bogumil M. 
Published: May 2018

AbstractMirtrons are non-canonical microRNAs encoded in introns the biogenesis of which starts with splicing. They are not processed by Drosha and enter the canonical pathway at the Exportin-5 level. Mirtrons are much less evolutionary conserved than canonical miRNAs. Due to the differences, canonical miRNA predictors are not applicable to mirtron prediction. Identification of differences is important for designing mirtron prediction algorithms and may help to improve the understanding of mirtron functioning. So far, only simple, single-feature comparisons were reported. These are insensitive to complex feature relations. We quantified miRNAs with 25 features and showed that it is impossible to distinguish the two miRNA species using simple thresholds on any single feature. However, when using the Principal Component Analysis mirtrons and canonical miRNAs are grouped separately. Moreover, several methodologically diverse machine learning classifiers delivered high classification performance. Using feature selection algorithms we found features (e.g. bulges in the stem region), previously reported divergent in two classes, that did not contribute to improving classification accuracy, which suggests that they are not biologically meaningful. Finally, we proposed a combination of the most important features (including Guanine content, hairpin free energy and hairpin length) which convey a specific pattern, crucial for identifying mirtrons.
Generation of ultrahigh field by micro-bubble implosion
Authors: Murakami M. , Arefiev A. , Zosa M. A. 
Published: May 2018

AbstractBreaking the 100-MeV barrier for proton acceleration will help elucidate fundamental physics and advance practical applications from inertial confinement fusion to tumour therapy. Herein we propose a novel concept of bubble implosions. A bubble implosion combines micro-bubbles and ultraintense laser pulses of 1020–1022 W cm−2 to generate ultrahigh fields and relativistic protons. The bubble wall protons undergo volumetric acceleration toward the centre due to the spherically symmetric Coulomb force and the innermost protons accumulate at the centre with a density comparable to the interior of a white dwarf. Then an unprecedentedly high electric field is formed, which produces an energetic proton flash. Three-dimensional particle simulations confirm the robustness of Coulomb-imploded bubbles, which behave as nano-pulsars with repeated implosions and explosions to emit protons. Current technologies should be sufficient to experimentally verify concept of bubble implosions.
Chemical and structural analysis on magnetic tunnel junctions using a decelerated scanning electron beam
Authors: Jackson Edward , Sun Mingling , Kubota Takahide , Takanashi Koki , Hirohata Atsufumi 
Published: May 2018

AbstractCurrent information technology relies on the advancement of nanofabrication techniques. For instance, the latest computer memories and hard disk drive read heads are designed with a 12 nm node and 20 nm wide architectures, respectively. With matured nanofabrication processes, a yield of such nanoelectronic devices is typically up to about 90%. To date the yield has been compensated with redundant hardware and software error corrections. In the latest memories, approximately 5% redundancy and parity bits for error corrections are used, which increase the total production cost of the devices. This means the yield directly affects the device costs. It is hence critical to increase the yield in nanofabrication. In this paper, we have applied our recently developed method to image buried interfaces in combination with chemical analysis to evaluate magnetic tunnel junctions and have revealed their different magnetoresistance ratios caused by the presence of materials formed at the junction edges. The formation of these materials can be avoided by optimising the junction patterning process to remove residual carbon introduced from resist. Our imaging method with chemical analysis have demonstrated a significant potential for the improvement of junction performance, resulting in higher yields. This can be used as a quality assurance tool in a nanoelectronic device production line.
Non-alcoholic fatty liver disease incidence, remission and risk factors among a general Chinese population with a 6-year follow-up
Authors: Wu Jing , He Shumei , Xu Hongqin , Chi Xiumei , Sun Jie , Wang Xiaomei , Gao Xiuzhu , Wu Ruihong , Shao Mingbai , Zhao Heng , Jia Jing , Wang Chunyan , Niu Junqi 
Published: May 2018

AbstractThis study aimed to investigate the incidence, remission and risk factors of non-alcoholic fatty liver disease (NAFLD) among a general population with a 6-year follow-up. In total, 691 individuals from the general population in Jilin, China aged 20–75 years participated in two independent cross-sectional surveys carried out in 2007 and 2013. After excluding patients with alcoholism, viral hepatitis and other liver diseases, 646 individuals were finally enrolled in our study. Of the 646 subjects, 512 did not have NAFLD at baseline, while 134 did. Of the 512 individuals without NAFLD at baseline, 188 (36.7%) developed NAFLD during the six-year follow-up period. The baseline body mass index (BMI, OR = 1.49, 1.36–1.64), high-density lipoprotein cholesterol level(HDL-C) (OR = 0.35, 0.16–0.76) and weight gain (OR = 1.22, 1.16–1.29) were independent predictors for NAFLD incidence. Of the 134 subjects with NAFLD at baseline, 33 (24.6%) had no evidence of NAFLD after 6 years. Males (OR = 4.85, 1.98–11.92) and baseline BMI levels (OR = 0.81, 0.70–0.94) were associated with NAFLD remission. Among the general population, the incidence of NAFLD mainly depended on baseline weight and weight gain. Subjects with mild baseline weights and male subjects were prone to NAFLD remission.
New birthweight percentiles by sex and gestational age in Southern China and its comparison with the INTERGROWTH-21st Standard
Authors: Yao Fei , Miao Huazhang , Li Bing , Wu Yuntao , Zhao Qingguo 
Published: May 2018

AbstractWe first showed the sex- and gestational age (week)-specific birthweight distributions from primiparous and multiparous mothers. Birthweight percentiles were created by using the Lambda Mu Sigma (LMS) method. We established the birthweight percentiles in Southern China and provide clinicians and researchers with up-to-date population norms of birthweight percentiles. Then we use the data from Birth Certificate System between Jan 1st, 2017 and Oct 31st, 2017, which included 1,245,364 live births to calculate SGA and LGA ratio by these three birthweight references- the new INTERGROWTH-21st standard, China’s 2015 research standard and our birthweight percentiles. The overall prevalence of SGA estimated by our standards, the China’s 2015 research standards and INTERGROWTH-21st standards, were 10.21%, 12.93% and 7.98%, respectively, whereas the overall prevalence of LGA was 9.88%, 4.48% and 8.37%, respectively.
Pilot-scale study on catalytic ozonation of bio-treated dyeing and finishing wastewater using recycled waste iron shavings as a catalyst
Authors: Ma Jieting , Chen Yunlu , Nie Jianxin , Ma Luming , Huang Yuanxing , Li Liang , Liu Yan , Guo Zhigang 
Published: May 2018

AbstractA pilot scale reactor with an effective volume of 2.93 m3 was built in-situ and run in both batch and continuous modes to investigate the removal for organic pollutants in bio-treated dyeing and finishing wastewater by heterogeneous catalytic ozonation under neutral pH with waste iron shavings as a catalyst. Experimental results showed that both running modes were able to reduce the chemical oxygen demand (COD) from 132–148 mg/L to a level below the discharge criteria (<80 mg/L) within 15–30 mins under several conditions. Specifically, significantly organic removal was observed with COD, soluble COD (sCOD) and dissolved organic carbon (DOC) decreased from the initial 165, 93 and 76 mg/L to 54, 28 and 16 mg/L respectively, when treated by 10.2 g-O3/min of ozone dosage at a hydraulic retention time of 30 mins under continuous mode. 80% proteins and 85% polysaccharides were removed with a decrease in their contribution to sCOD from 69% to 43%. Mineralization as well as conversion of high molecular organic compounds was observed through Gas Chromatography-Mass Spectrometer (GC-MS) & Liquid Chromatography-Mass Spectrometer (LC-MS) analysis, which led to a decrease of inhibitory effect from 29% to 25%, suggesting a reduction in the acute toxicity.