bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLATO software provides analytic framework for investigating complexity beyond genome-wide association studies
Authors: Hall Molly A. , Wallace John , Lucas Anastasia , Kim Dokyoon , Basile Anna O. , Verma Shefali S. , McCarty Cathy A. , Brilliant Murray H. , Peissig Peggy L. , Kitchner Terrie E. , Verma Anurag , Pendergrass Sarah A. , Dudek Scott M. , Moore Jason H. , Ritchie Marylyn D. 
Published: October 2017

AbstractGenome-wide, imputed, sequence, and structural data are now available for exceedingly large sample sizes. The needs for data management, handling population structure and related samples, and performing associations have largely been met. However, the infrastructure to support analyses involving complexity beyond genome-wide association studies is not standardized or centralized. We provide the PLatform for the Analysis, Translation, and Organization of large-scale data (PLATO), a software tool equipped to handle multi-omic data for hundreds of thousands of samples to explore complexity using genetic interactions, environment-wide association studies and gene–environment interactions, phenome-wide association studies, as well as copy number and rare variant analyses. Using the data from the Marshfield Personalized Medicine Research Project, a site in the electronic Medical Records and Genomics Network, we apply each feature of PLATO to type 2 diabetes and demonstrate how PLATO can be used to uncover the complex etiology of common traits.
Coding and noncoding landscape of extracellular RNA released by human glioma stem cells
Authors: Wei Zhiyun , Batagov Arsen O. , Schinelli Sergio , Wang Jintu , Wang Yang , El Fatimy Rachid , Rabinovsky Rosalia , Balaj Leonora , Chen Clark C. , Hochberg Fred , Carter Bob , Breakefield Xandra O. , Krichevsky Anna M. 
Published: October 2017

AbstractTumor-released RNA may mediate intercellular communication and serve as biomarkers. Here we develop a protocol enabling quantitative, minimally biased analysis of extracellular RNAs (exRNAs) associated with microvesicles, exosomes (collectively called EVs), and ribonucleoproteins (RNPs). The exRNA complexes isolated from patient-derived glioma stem-like cultures exhibit distinct compositions, with microvesicles most closely reflecting cellular transcriptome. exRNA is enriched in small ncRNAs, such as miRNAs in exosomes, and precisely processed tRNA and Y RNA fragments in EVs and exRNPs. EV-enclosed mRNAs are mostly fragmented, and UTRs enriched; nevertheless, some full-length mRNAs are present. Overall, there is less than one copy of non-rRNA per EV. Our results suggest that massive EV/exRNA uptake would be required to ensure functional impact of transferred RNA on brain recipient cells and predict the most impactful miRNAs in such conditions. This study also provides a catalog of diverse exRNAs useful for biomarker discovery and validates its feasibility on cerebrospinal fluid.
miR-1199-5p and Zeb1 function in a double-negative feedback loop potentially coordinating EMT and tumour metastasis
Authors: Diepenbruck Maren , Tiede Stefanie , Saxena Meera , Ivanek Robert , Kalathur Ravi Kiran Reddy , Lüönd Fabiana , Meyer-Schaller Nathalie , Christofori Gerhard 
Published: October 2017

AbstractEpithelial tumour cells can gain invasive and metastatic capabilities by undergoing an epithelial–mesenchymal transition. Transcriptional regulators and post-transcriptional effectors like microRNAs orchestrate this process of high cellular plasticity and its malignant consequences. Here, using microRNA sequencing in a time-resolved manner and functional validation, we have identified microRNAs that are critical for the regulation of an epithelial–mesenchymal transition and of mesenchymal tumour cell migration. We report that miR-1199-5p is downregulated in its expression during an epithelial–mesenchymal transition, while its forced expression prevents an epithelial–mesenchymal transition, tumour cell migration and invasion in vitro, and lung metastasis in vivo. Mechanistically, miR-1199-5p acts in a reciprocal double-negative feedback loop with the epithelial–mesenchymal transition transcription factor Zeb1. This function resembles the activities of miR-200 family members, guardians of an epithelial cell phenotype. However, miR-1199-5p and miR-200 family members share only six target genes, indicating that, besides regulating Zeb1 expression, they exert distinct functions during an epithelial–mesenchymal transition.
Site-specific identification and quantitation of endogenous SUMO modifications under native conditions
Authors: Lumpkin Ryan J. , Gu Hongbo , Zhu Yiying , Leonard Marilyn , Ahmad Alla S. , Clauser Karl R. , Meyer Jesse G. , Bennett Eric J. , Komives Elizabeth A. 
Published: October 2017

AbstractSmall ubiquitin-like modifier (SUMO) modification regulates numerous cellular processes. Unlike ubiquitin, detection of endogenous SUMOylated proteins is limited by the lack of naturally occurring protease sites in the C-terminal tail of SUMO proteins. Proteome-wide detection of SUMOylation sites on target proteins typically requires ectopic expression of mutant SUMOs with introduced tryptic sites. Here, we report a method for proteome-wide, site-level detection of endogenous SUMOylation that uses α-lytic protease, WaLP. WaLP digestion of SUMOylated proteins generates peptides containing SUMO-remnant diglycyl-lysine (KGG) at the site of SUMO modification. Using previously developed immuno-affinity isolation of KGG-containing peptides followed by mass spectrometry, we identified 1209 unique endogenous SUMO modification sites. We also demonstrate the impact of proteasome inhibition on ubiquitin and SUMO-modified proteomes using parallel quantitation of ubiquitylated and SUMOylated peptides. This methodological advancement enables determination of endogenous SUMOylated proteins under completely native conditions.
CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation
Authors: Li Xuan , Wu Xiao-Qi , Deng Rong , Li Dan-Dan , Tang Jun , Chen Wen-Dan , Chen Jing-Hong , Ji Jiao , Jiao Lin , Jiang Shan , Yang Fen , Feng Gong-Kan , Senthilkumar Ravichandran , Yue Fei , Zhang Hai-Liang , Wu Rui-Yan , Yu Yan , Xu Xue-Lian , Mai Jia , Li Zhi-Ling , Peng Xiao-Dan , Huang Yun , Huang Xiang , Ma Ning-Fang , Tao Qian , Zeng Yi-Xin , Zhu Xiao-Feng 
Published: October 2017

AbstractAutophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. Meanwhile, CaMKII can also promote K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6. Ubiquitinated Id-1/Id-2 can then bind to p62 and be transported to autolysosomes for degradation. Id degradation promotes the differentiation of neuroblastoma cells and reduces the proportion of stem-like cells. Our study proposes a mechanism by which autophagic degradation of Id proteins can regulate cell differentiation. This suggests that targeting of CaMKII and the regulation of autophagic degradation of Id may be an effective therapeutic strategy to induce cell differentiation in neuroblastoma.
Coupled circumferential and axial tension driven by actin and myosin influences in vivo axon diameter
Authors: Fan Anthony , Tofangchi Alireza , Kandel Mikhail , Popescu Gabriel , Saif Taher 
Published: October 2017

AbstractIt has long been known that neuronal axons are contractile. They actively maintain rest tension along the longitudinal direction both in vitro and in vivo. Here we show evidence that embryonic drosophila axons also actively maintain contractility/tension along the circumferential direction. We used confocal microscopy and spatial light interference microscopy to monitor axonal diameter along their length. We observed a decrease in diameter when microtubules are disrupted and an increase in diameter when actin filaments or myosin II are disrupted. Interestingly, active diameter reduction occurred consistently when axons were subjected to manipulations known to increase axial tension, suggesting that tension can be coupled in the axial and circumferential direction. This is further supported by the remarkably similar time constants for diameter reduction and rest tension increase of slackened axons. We infer that the actomyosin-driven circumferential contraction/hoop tension applies a squeezing force on the microtubule bundle of the axons. This hoop tension is balanced by the restoring force of the microtubule bundle. Therefore, axonal diameter increased when actin/myosin disrupting drugs relaxed the hoop tension and decreased when microtubule disrupting drug relaxed the restoring force. Circumferential tension thus can regulate axonal diameter and volume, as well as potentially microtubules alignment, inter-tubular spacing, and, by extension, axonal transport.
Ants’ navigation in an unfamiliar environment is influenced by their experience of a familiar route
Authors: Schwarz Sebastian , Wystrach Antoine , Cheng Ken 
Published: October 2017

AbstractWhen displaced experimentally from a food source (feeder) to unfamiliar terrain, ants run off a portion of the homeward vector or its entirety, depending on species and conditions, and then search systematically, turning in loops of ever increasing size. The Australian desert ant Melophorus bagoti runs off a smaller portion of its vector if the test site is more dissimilar to its nest area. Here we manipulated familiarity with the training route between a feeder and the ants’ nest to examine its effects when the ants were displaced to a distant site from the feeder. Naïve ants that arrived at an experimentally provided feeder for the first time were compared with experienced ants that had travelled the route for two days. At the unfamiliar test site, naïve ants ran off a longer portion of their vector from path integration than did experienced ants. Naïve ants also spread out in their systematic search slower than did experienced ants. We conclude that as ants learn the views encountered on their familiar route better, they identify more readily unfamiliar views. A scene distant from their nest area may not look as unfamiliar to a naïve ant as it does to an experienced ant.
Experiments On Sublimating Carbon Dioxide Ice And Implications For Contemporary Surface Processes On Mars
Authors: Mc Keown L. E. , Bourke M. C. , McElwaine J. N. 
Published: October 2017

AbstractCarbon dioxide is Mars’ primary atmospheric constituent and is an active driver of Martian surface evolution. CO2ice sublimation mechanisms have been proposed for a host of features that form in the contemporary Martian climate. However, there has been very little experimental work or quantitative modelling to test the validity of these hypotheses. Here we present the results of the first laboratory experiments undertaken to investigate if the interaction between sublimating CO2ice blocks and a warm, porous, mobile regolith can generate features similar in morphology to those forming on Martian dunes today. We find that CO2sublimation can mobilise grains to form (i) pits and (ii) furrows. We have documented new detached pits at the termini of linear gullies on Martian dunes. Based on their geomorphic similarity to the features observed in our laboratory experiments, and on scaling arguments, we propose a new hypothesis that detached pits are formed by the impact of granular jets generated by sublimating CO2. We also study the erosion patterns formed underneath a sublimating block of CO2ice and demonstrate that these resemble furrow patterns on Mars, suggesting similar formation mechanisms.
Higher body mass index is associated with an increased risk of multiplicity in surveillance colonoscopy within 5 years
Authors: Tae Chung Hyun , Moon Chang Mo , Jung Sung-Ae , Eun Chang Soo , Park Jae Jun , Seo Geom Seog , Cha Jae Myung , Park Sung Chul , Chun Jaeyoung , Lee Hyun Jung , Jung Yunho , Kim Jin Oh , Joo Young-Eun , Boo Sun-Jin , Il Park Dong 
Published: October 2017

AbstractWe aimed to evaluate whether obesity was associated with a certain clinicopathologic characteristics of metachronous CRA. This retrospective longitudinal cohort study included 2,904 subjects who had at least one resected CRA at index colonoscopy and who subsequently underwent one or more surveillance colonoscopies within 5 years. Of the 2,904 subjects, 60.9% (n = 1,769) were normal, 35.8% (n = 1,040) were overweight, and 3.3% (n = 95) were obese. Patients with any metachronous CRA were 53.7% (n = 1,559). In multivariate analyses, higher BMI at index colonoscopy was significantly associated with any metachronous CRA (overweight, OR = 1.07; obese, OR = 1.82; p for trend = 0.049). Regarding the multiplicity, the ORs of ≥ 3, ≥ 4 and ≥ 5 metachronous CRAs significantly increased as index BMI increased (p for trend < 0.001, = 0.007 and = 0.004, respectively). In negative binomial regression regarding the incidence for total number of metachronous CRA, the higher BMI the subject has at the time of index colonoscopy, the more metachronous CRAs the subject will have at the surveillance colonoscopy (p for trend = 0.016). Higher index BMI was significantly associated with the risk of multiple metachronous CRAs on surveillance colonoscopy within 5 years.
Enhanced conversion efficiency in Si solar cells employing photoluminescent down-shifting CdSe/CdS core/shell quantum dots
Authors: Lopez-Delgado R. , Zhou Y. , Zazueta-Raynaud A. , Zhao H. , Pelayo J. E. , Vomiero A. , Álvarez-Ramos M. E. , Rosei F. , Ayon A. 
Published: October 2017

AbstractSilicon solar cells have captured a large portion of the total market of photovoltaic devices mostly due to their relatively high efficiency. However, Silicon exhibits limitations in ultraviolet absorption because high-energy photons are absorbed at the surface of the solar cell, in the heavily doped region, and the photo-generated electron-hole pairs need to diffuse into the junction region, resulting in significant carrier recombination. One of the alternatives to improve the absorption range involves the use of down-shifting nano-structures able to interact with the aforementioned high energy photons. Here, as a proof of concept, we use downshifting CdSe/CdS quantum dots to improve the performance of a silicon solar cell. The incorporation of these nanostructures triggered improvements in the short circuit current density (Jsc, from 32.5 to 37.0 mA/cm2). This improvement led to a ∼13% increase in the power conversion efficiency (PCE), from 12.0 to 13.5%. Our results demonstrate that the application of down-shifting materials is a viable strategy to improve the efficiency of Silicon solar cells with mass-compatible techniques that could serve to promote their widespread utilization.
Antitumor activities of Liver-targeting peptide modified Recombinant human Endostatin in BALB/c-nu mice with Hepatocellular carcinoma
Authors: Yan Ma , Dongmei Bao , Jingjing Zhang , Xiaobao Jin , Jie Wang , Yan Wang , Jiayong Zhu 
Published: October 2017

AbstractIn our previous study, a liver-targeting peptide CSP I-plus modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed and showed potent antiangiogenic capability and could specifically bind to human hepatocellular carcinoma cells to make a direct inhibition in vitro. In this study, the biological activities of rES-CSP in vivo were evaluated by subcutaneous and orthotopic xenograft nude mice model of human hepatocellular carcinoma cells HepG2. We found that rES-CSP significantly decreased tumor volume to 54.9% in the nude mice with subcutaneous xenograft compared with the control. In orthotopic xenograft model, rES-CSP not only decreased tumor volume (to 39.6% compared with the control) and tumor weight, it also increased its biodistribution in the liver tissue and hepatoma tissue. Moreover, lower microvessel density (MVD) and higher apoptotic index (AI) were also observed in the tumor tissues. It had no significant side-effects on the heart, liver, spleen, lung and kidney of mice. Results indicated CSP I-plus modified Endostar may be a potential candidate for a targeting therapy on hepatocellular carcinoma.
Flexible PVDF membranes with exceptional robust superwetting surface for continuous separation of oil/water emulsions
Authors: Xiong Zhu , Lin Haibo , Liu Fu , Xiao Peng , Wu Ziyang , Li Tiantian , Li Dehong 
Published: October 2017

AbstractInstability of superwetting surface is the stumbling block of flexible polymeric membranes for continuous separation of water-in-oil or oil-in-water emulsions. Manipulation of rigid superwetting nano-TiO2 on hierarchical poly(vinylidene fluoride) (PVDF) membrane by mimicking the plant roots holding soil behaviour enabled the generation of robust superwetting surface withstanding the harshly physical and chemical torture. The unique interface combination, which fabricated by a compacted nano-layer with the thickness of ~20 μm, was disclosed by systematic structure characterization. As demonstrated by SEM, LSCM and nano-CT, the pristine PVDF membrane with large quantities of cilia-like micro/nano-fibrils can function as the plant roots to capture, cage and confine the nanoparticles to form a robustly rigid nano-coating. The as-prepared membranes showed excellent durable separation performance both in varieties of stabilized water-in-oil and oil-in-water emulsion separation for a long term with few nanoparticles loss in a continuous crossflow mode. The strategy of assembling rigid inorganic nano-particles on flexible surface offers a window of opportunity for preparation of robust organic-inorganic hybrid membranes not only for continuous oil/water emulsion separation, but also for other functional application, such as electric conduction, heat conduction, ion exchange, and in membrane catalytic reactors etc.
Learning from soil gas change and isotopic signatures during 2012 Emilia seismic sequence
Authors: Sciarra Alessandra , Cantucci Barbara , Coltorti Massimo 
Published: October 2017

AbstractSoil surveys were performed in Medolla (Italy), a peculiar area characterized by spotty high soil temperature, gas vent, and lack of vegetation, to determine the migration mechanisms and spatial behavior of gas species. Hereby we present soil gas measurements and their isotopic ratios measured between 2008 and 2015, including the 2012 Emilia-Romagna seismic sequence. We found that soil gas concentrations markedly changed during the main shocks of May 20 and 29, 2012 (Mw 6.1 and 6.0, respectively), highlighting the presence of a buried fault intersecting the gas vents. We suggest that crustal dilation associated with seismic activity favored the uprising of geogas towards the surface. Changes in the isotopic signature highlight the contribution of two distinct sources, one deeper, thermogenic and another superficial related to organic-rich layer, whose relative contribution varied before, during and after the earthquake. We suppose an increase of microbial component likely due to the ground shaking of shallower layers linked to seismic sequence, which masks the thermogenic contribution. Although the changes we detect are specific for an alluvial plain, we deduce that analogous processes may be active elsewhere, and that soil gas geochemistry represents an useful tool to discriminate the gas migration related to seismic activity.
Dynamic Pseudorotaxane Crystals Containing Metallocene Complexes
Authors: Chen Kai-Jen , Chen Pei-Lin , Horie Masaki 
Published: October 2017

AbstractMolecular machines and switches composed of flexible pseudorotaxanes respond to external stimuli, transducing incident energy into mechanical motions. This study presents thermo- and photoresponsive dynamic pseudorotaxane crystals composed of axle molecules containing ferrocene or ruthenocene groups threaded through dibenzo[24]crown-8 ether rings. The ruthenocene-containing pseudorotaxane exhibits a crystal-to-crystal thermal phase transition at 86 °C, which is much lower than that of the ferrocene-containing pseudorotaxane (128 °C). Single-crystal X-ray crystallography at various temperatures reveals the details of the structural changes, and shows that the bulky ruthenocene provides distortion in the pseudorotaxane structure to facilitate twisting of the axle molecule. A mixed ferrocene and ruthenocene pseudorotaxane crystal is applied to photomechanical conversion under 405 nm laser irradiation at 85 °C and provides a lifting force 6,400-times the weight of the crystal itself upon phase transition.
In vivo and ex vivo methods of growing a liver bud through tissue connection
Authors: Yanagi Yusuke , Nakayama Koichi , Taguchi Tomoaki , Enosawa Shin , Tamura Tadashi , Yoshimaru Koichiro , Matsuura Toshiharu , Hayashida Makoto , Kohashi Kenichi , Oda Yoshinao , Yamaza Takayoshi , Kobayashi Eiji 
Published: October 2017

AbstractCell-based therapy has been proposed as an alternative to orthotopic liver transplantation. The novel transplantation of an in vitro-generated liver bud might have therapeutic potential. In vivo and ex vivo methods for growing a liver bud are essential for paving the way for the clinical translation of liver bud transplantation. We herein report a novel transplantation method for liver buds that are grown in vivo involving orthotopic transplantation on the transected parenchyma of the liver, which showed long engraftment and marked growth in comparison to heterotopic transplantation. Furthermore, this study demonstrates a method for rapidly fabricating scalable liver-like tissue by fusing hundreds of liver bud-like spheroids using a 3D bioprinter. Its system to fix the shape of the 3D tissue with the needle-array system enabled the fabrication of elaborate geometry and the immediate execution of culture circulation after 3D printing—thereby avoiding an ischemic environment ex vivo. The ex vivo-fabricated human liver-like tissue exhibited self-tissue organization ex vivo and engraftment on the liver of nude rats. These achievements conclusively show both in vivo and ex vivo methods for growing in vitro-generated liver buds. These methods provide a new approach for in vitro-generated liver organoids transplantation.
Somatic mutation driven codon transition bias in human cancer
Authors: Son Hyeonju , Kang Hyundeok , Kim Hyun Seok , Kim Sangwoo 
Published: October 2017

AbstractAccumulation of DNA mutations alters amino acid sequence in the key domains of oncoproteins, leading to cellular malignant transformation. Due to redundancy of the genetic code, the same amino acid alteration can be achieved by multiple distinct genetic mutations, which are considered functionally identical and not actively distinguished in the current cancer genome research. For the first time, we analyzed the distribution of codon level transitions acquired by somatic mutations in human cancers. By analyzing the ~2.5 million nonsynonymous somatic single nucleotide variations (SNVs) found in the COSMIC database, we found 41 recurrent amino acid alterations whose DNA changes are significantly biased toward a specific codon transition. Additional analyses partially identified functional discrepancies between the favored and avoided codon transitions in terms of mutational process, codon usage, alternative splicing, and mRNA stability.