bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of miR-515-3p and its targets, vimentin and MMP3, as a key regulatory mechanism in esophageal cancer metastasis: functional and clinical significance
Authors: Hu Hui-Fang , Xu Wen Wen , Zhang Wei-Xia , Yan Xin , Li Yang-Jia , Li Bin , He Qing-Yu 
Published: November 2020

AbstractMetastasis is the main factor of treatment failure in cancer patients, but the underlying mechanism remains to be elucidated and effective new treatment strategies are urgently needed. This study aims to explore novel key metastasis-related microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). By comparing miRNA profiles of the highly metastatic ESCC cell sublines, we established through serial in vivo selection with the parental cells, we found that the expression level of miR-515-3p was lower in ESCC tumor tissues than adjacent normal tissues, further decreased in metastatic tumors, and moreover, markedly associated with advanced stage, metastasis and patient survival. The in vitro and in vivo assays suggested that miR-515-3p could increase the expression of the epithelial markers as well as decrease the expression of the mesenchymal markers, and more importantly, suppress invasion and metastasis of ESCC cells. Mechanistically, we revealed that miR-515-3p directly regulated vimentin and matrix metalloproteinase-3 (MMP3) expression by binding to the coding sequence and 3′untranslated region, respectively. In addition, the data from whole-genome methylation sequencing and methylation-specific PCR indicated that the CpG island within miR-515-3p promoter was markedly hypermethylated in ESCC cell lines and ESCC tumor tissues, which may lead to deregulation of miR-515-3p expression in ESCC. Furthermore, our preclinical experiment provides solid evidence that systemic delivery of miR-515-3p oligonucleotide obviously suppressed the metastasis of ESCC cells in nude mice. Taken together, this study demonstrates that miR-515-3p suppresses tumor metastasis and thus represents a promising prognostic biomarker and therapeutic strategy in ESCC.
Novel COL4A1 mutations identified in infants with congenital hemolytic anemia in association with brain malformations
Authors: Ogura Hiromi , Ohga Shouichi , Aoki Takako , Utsugisawa Taiju , Takahashi Hidehiro , Iwai Asayuki , Watanabe Kenichiro , Okuno Yusuke , Yoshida Kenichi , Ogawa Seishi , Miyano Satoru , Kojima Seiji , Yamamoto Toshiyuki , Yamamoto-Shimojima Keiko , Kanno Hitoshi 
Published: November 2020

AbstractGenetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients (21%). All patients were complicated with congenital malformations of the brain, such as porencephaly or schizencephaly. In these patients, hemolysis became less severe within 2 months after birth, and red cell transfusion was no longer required after 50 days, whereas chronic hemolysis continued.
3D motion tracking display enabled by magneto-interactive electroluminescence
Authors: Lee Seung Won , Baek Soyeon , Park Sung-Won , Koo Min , Kim Eui Hyuk , Lee Seokyeong , Jin Wookyeong , Kang Hansol , Park Chanho , Kim Gwangmook , Shin Heechang , Shim Wooyoung , Yang Sunggu , Ahn Jong-Hyun , Park Cheolmin 
Published: November 2020

AbstractDevelopment of a human-interactive display enabling the simultaneous sensing, visualisation, and memorisation of a magnetic field remains a challenge. Here we report a skin-patchable magneto-interactive electroluminescent display, which is capable of sensing, visualising, and storing magnetic field information, thereby enabling 3D motion tracking. A magnetic field-dependent conductive gate is employed in an alternating current electroluminescent display, which is used to produce non-volatile and rewritable magnetic field-dependent display. By constructing mechanically flexible arrays of magneto-interactive displays, a spin-patchable and pixelated platform is realised. The magnetic field varying along the z-axis enables the 3D motion tracking (monitoring and memorisation) on 2D pixelated display. This 3D motion tracking display is successfully used as a non-destructive surgery-path guiding, wherein a pathway for a surgical robotic arm with a magnetic probe is visualised and recorded on a display patched on the abdominal skin of a rat, thereby helping the robotic arm to find an optimal pathway.
Pan-cancer analysis demonstrates that integrating polygenic risk scores with modifiable risk factors improves risk prediction
Authors: Kachuri Linda , Graff Rebecca E. , Smith-Byrne Karl , Meyers Travis J. , Rashkin Sara R. , Ziv Elad , Witte John S. , Johansson Mattias 
Published: November 2020

AbstractCancer risk is determined by a complex interplay of environmental and heritable factors. Polygenic risk scores (PRS) provide a personalized genetic susceptibility profile that may be leveraged for disease prediction. Using data from the UK Biobank (413,753 individuals; 22,755 incident cancer cases), we quantify the added predictive value of integrating cancer-specific PRS with family history and modifiable risk factors for 16 cancers. We show that incorporating PRS measurably improves prediction accuracy for most cancers, but the magnitude of this improvement varies substantially. We also demonstrate that stratifying on levels of PRS identifies significantly divergent 5-year risk trajectories after accounting for family history and modifiable risk factors. At the population level, the top 20% of the PRS distribution accounts for 4.0% to 30.3% of incident cancer cases, exceeding the impact of many lifestyle-related factors. In summary, this study illustrates the potential for improving cancer risk assessment by integrating genetic risk scores.
Ubiquitous selection for mecA in community-associated MRSA across diverse chemical environments
Authors: Snitser Olga , Russ Dor , Stone Laura K. , Wang Kathy K. , Sharir Haleli , Kozer Noga , Cohen Galit , Barr Haim M. , Kishony Roy 
Published: November 2020

AbstractCommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is threatening public health as it spreads worldwide across diverse environments. Its genetic hallmark, the mecA gene, confers resistance to many β-lactam antibiotics. Here, we show that, in addition, mecA provides a broad selective advantage across diverse chemical environments. Competing fluorescently labelled wild-type and mecA-deleted CA-MRSA USA400 strains across ~57,000 compounds supplemented with subinhibitory levels of the β-lactam drug cefoxitin, we find that mecA provides a widespread advantage across β-lactam and non β-lactam antibiotics, non-antibiotic drugs and even diverse natural and synthetic compounds. This advantage depends on the presence of cefoxitin and is strongly associated with the compounds’ physicochemical properties, suggesting that it may be mediated by differential compounds permeability into the cell. Indeed, mecA protects the bacteria against increased cell-envelope permeability under subinhibitory cefoxitin treatment. Our findings suggest that CA-MRSA success might be driven by a cell-envelope mediated selective advantage across diverse chemical compounds.
MiCas9 increases large size gene knock-in rates and reduces undesirable on-target and off-target indel edits
Authors: Ma Linyuan , Ruan Jinxue , Song Jun , Wen Luan , Yang Dongshan , Zhao Jiangyang , Xia Xiaofeng , Chen Y. Eugene , Zhang Jifeng , Xu Jie 
Published: November 2020

AbstractGene editing nuclease represented by Cas9 efficiently generates DNA double strand breaks at the target locus, followed by repair through either the error-prone non-homologous end joining or the homology directed repair pathways. To improve Cas9’s homology directed repair capacity, here we report the development of miCas9 by fusing a minimal motif consisting of thirty-six amino acids to spCas9. MiCas9 binds RAD51 through this fusion motif and enriches RAD51 at the target locus. In comparison to spCas9, miCas9 enhances double-stranded DNA mediated large size gene knock-in rates, systematically reduces off-target insertion and deletion events, maintains or increases single-stranded oligodeoxynucleotides mediated precise gene editing rates, and effectively reduces on-target insertion and deletion rates in knock-in applications. Furthermore, we demonstrate that this fusion motif can work as a “plug and play” module, compatible and synergistic with other Cas9 variants. MiCas9 and the minimal fusion motif may find broad applications in gene editing research and therapeutics.
Large deep-sea zooplankton biomass mirrors primary production in the global ocean
Authors: Hernández-León S. , Koppelmann R. , Fraile-Nuez E. , Bode A. , Mompeán C. , Irigoien X. , Olivar M. P. , Echevarría F. , Fernández de Puelles M. L. , González-Gordillo J. I. , Cózar A. , Acuña J. L. , Agustí S. , Duarte C. M. 
Published: November 2020

AbstractThe biological pump transports organic carbon produced by photosynthesis to the meso- and bathypelagic zones, the latter removing carbon from exchanging with the atmosphere over centennial time scales. Organisms living in both zones are supported by a passive flux of particles, and carbon transported to the deep-sea through vertical zooplankton migrations. Here we report globally-coherent positive relationships between zooplankton biomass in the epi-, meso-, and bathypelagic layers and average net primary production (NPP). We do so based on a global assessment of available deep-sea zooplankton biomass data and large-scale estimates of average NPP. The relationships obtained imply that increased NPP leads to enhanced transference of organic carbon to the deep ocean. Estimated remineralization from respiration rates by deep-sea zooplankton requires a minimum supply of 0.44 Pg C y−1 transported into the bathypelagic ocean, comparable to the passive carbon sequestration. We suggest that the global coupling between NPP and bathypelagic zooplankton biomass must be also supported by an active transport mechanism associated to vertical zooplankton migration.
Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence
Authors: Olan Ioana , Parry Aled J. , Schoenfelder Stefan , Narita Masako , Ito Yoko , Chan Adelyne S. L. , Slater Guy St.C. , Bihary Dóra , Bando Masashige , Shirahige Katsuhiko , Kimura Hiroshi , Samarajiwa Shamith A. , Fraser Peter , Narita Masashi 
Published: November 2020

AbstractSenescence is a state of stable proliferative arrest, generally accompanied by the senescence-associated secretory phenotype, which modulates tissue homeostasis. Enhancer-promoter interactions, facilitated by chromatin loops, play a key role in gene regulation but their relevance in senescence remains elusive. Here, we use Hi-C to show that oncogenic RAS-induced senescence in human diploid fibroblasts is accompanied by extensive enhancer-promoter rewiring, which is closely connected with dynamic cohesin binding to the genome. We find de novo cohesin peaks often at the 3′ end of a subset of active genes. RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. Similar IL1B induction with de novo cohesin appearance and new loop formation are observed in terminally differentiated macrophages, but not TNFα-treated cells. These results suggest that RAS-induced senescence represents a cell fate determination-like process characterised by a unique gene expression profile and 3D genome folding signature, mediated in part through cohesin redistribution on chromatin.
β-Pix-dependent cellular protrusions propel collective mesoderm migration in the mouse embryo
Authors: Omelchenko Tatiana , Hall Alan , Anderson Kathryn V. 
Published: November 2020

AbstractCoordinated directional migration of cells in the mesoderm layer of the early embryo is essential for organization of the body plan. Here we show that mesoderm organization in mouse embryos depends on β-Pix (Arhgef7), a guanine nucleotide exchange factor for Rac1 and Cdc42. As early as E7.5, β-Pix mutants have an abnormally thick mesoderm layer; later, paraxial mesoderm fails to organize into somites. To define the mechanism of action of β-Pix in vivo, we optimize single-cell live-embryo imaging, cell tracking, and volumetric analysis of individual and groups of mesoderm cells. Use of these methods shows that wild-type cells move in the same direction as their neighbors, whereas adjacent β-Pix mutant cells move in random directions. Wild-type mesoderm cells have long polarized filopodia-like protrusions, which are absent in β-Pix mutants. The data indicate that β-Pix-dependent cellular protrusions drive and coordinate collective migration of the mesoderm in vivo.
High-frequency gas effusion through nanopores in suspended graphene
Authors: Rosłoń I. E. , Dolleman R. J. , Licona H. , Lee M. , Šiškins M. , Lebius H. , Madauß L. , Schleberger M. , Alijani F. , van der Zant H. S. J. , Steeneken P. G. 
Published: November 2020

AbstractPorous, atomically thin graphene membranes have interesting properties for filtration and sieving applications. Here, graphene membranes are used to pump gases through nanopores using optothermal forces, enabling the study of gas flow through nanopores at frequencies above 100 kHz. At these frequencies, the motion of graphene is closely linked to the dynamic gas flow through the nanopore and can thus be used to study gas permeation at the nanoscale. By monitoring the time delay between the actuation force and the membrane mechanical motion, the permeation time-constants of various gases through pores with diameters from 10–400 nm are shown to be significantly different. Thus, a method is presented for differentiating gases based on their molecular mass and for studying gas flow mechanisms. The presented microscopic effusion-based gas sensing methodology provides a nanomechanical alternative for large-scale mass-spectrometry and optical spectrometry based gas characterisation methods.
Two-dimensional electronic spectroscopy of bacteriochlorophyll a with synchronized dual mode-locked lasers
Authors: Kim JunWoo , Jeon Jonggu , Yoon Tai Hyun , Cho Minhaeng 
Published: November 2020

AbstractHow atoms and electrons in a molecule move during a chemical reaction and how rapidly energy is transferred to or from the surroundings can be studied with flashes of laser light. However, despite prolonged efforts to develop various coherent spectroscopic techniques, the lack of an all-encompassing method capable of both femtosecond time resolution and nanosecond relaxation measurement has hampered various applications of studying correlated electron dynamics and vibrational coherences in functional materials and biological systems. Here, we demonstrate that two broadband (>300 nm) synchronized mode-locked lasers enable two-dimensional electronic spectroscopy (2DES) study of chromophores such as bacteriochlorophyll a in condensed phases to measure both high-resolution coherent vibrational spectrum and nanosecond electronic relaxation. We thus anticipate that the dual mode-locked laser-based 2DES developed and demonstrated here would be of use for unveiling the correlation between the quantum coherence and exciton dynamics in light-harvesting protein complexes and semiconducting materials.
Reproductive phasiRNAs regulate reprogramming of gene expression and meiotic progression in rice
Authors: Zhang Yu-Chan , Lei Meng-Qi , Zhou Yan-Fei , Yang Yu-Wei , Lian Jian-Ping , Yu Yang , Feng Yan-Zhao , Zhou Ke-Ren , He Rui-Rui , He Huang , Zhang Zhi , Yang Jian-Hua , Chen Yue-Qin 
Published: November 2020

AbstractPlant spermatogenesis is a complex process that directly affects crop breeding. A rapid change in gene abundance occurs at early meiosis prophase, when gene regulation is selective. However, how these genes are regulated remains unknown. Here, we show that rice reproductive phasiRNAs are essential for the elimination of a specific set of RNAs during meiotic prophase I. These phasiRNAs cleave target mRNAs in a regulatory manner such that one phasiRNA can target more than one gene, and/or a single gene can be targeted by more than one phasiRNA to efficiently silence target genes. Our investigation of phasiRNA-knockdown and PHAS-edited transgenic plants demonstrates that phasiRNAs and their nucleotide variations are required for meiosis progression and fertility. This study highlights the importance of reproductive phasiRNAs for the reprogramming of gene expression during meiotic progression and establishes a basis for future studies on the roles of phasiRNAs with a goal of crop improvement.
Comparing the effects of climate change labelling on reactions of the Taiwanese public
Authors: Hung Li-San , Bayrak Mucahid Mustafa 
Published: November 2020

AbstractScientists and the media are increasingly using the terms ‘climate emergency’ or ‘climate crisis’ to urge timely responses from the public and private sectors to combat the irreversible consequences of climate change. However, whether the latest trend in climate change labelling can result in stronger climate change risk perceptions in the public is unclear. Here we used survey data collected from 1,892 individuals across Taiwan in 2019 to compare the public’s reaction to a series of questions regarding climate change beliefs, communication, and behavioural intentions under two labels: ‘climate change’ and ‘climate crisis.’ The respondents had very similar responses to the questions using the two labels. However, we observed labelling effects for specific subgroups, with some questions using the climate crisis label actually leading to backlash effects compared with the response when using the climate change label. Our results suggest that even though the two labels provoke similar reactions from the general public, on a subgroup level, some backlash effects may become apparent. For this reason, the label ‘climate crisis’ should be strategically chosen.
Temperature and composition dependent screw dislocation mobility in austenitic stainless steels from large-scale molecular dynamics
Authors: Chu Kevin , Foster Michael E. , Sills Ryan B. , Zhou Xiaowang , Zhu Ting , McDowell David L. 
Published: November 2020

AbstractExtensive molecular dynamics simulations are performed to determine screw dislocation mobility in austenitic Fe0.7NixCr0.3-x stainless steels as a function of temperature ranging from 100 to 1300 K, resolved shear stress from 30 to 140 MPa, and Ni composition from 0.0 to 30.0 at%. These mobility data are fitted to a linear mobility law with a nonzero stress offset, referred to as the threshold stress. We find that both the linear drag coefficient and the threshold stress increase with Ni composition. The drag coefficient increases with temperature, whereas the threshold stress decreases with temperature. Based on these calculations, we determine fitting functions for the linear solute drag coefficient as a function of temperature and composition. The mobility laws determined in this study may serve to inform dislocation dynamics simulations pertinent to dislocation network evolution at elevated temperatures for a wide composition range of austenitic stainless steels.
The dehydrins gene expression differs across ecotypes in Norway spruce and relates to weather fluctuations
Authors: Čepl Jaroslav , Stejskal Jan , Korecký Jiří , Hejtmánek Jakub , Faltinová Zuzana , Lstibůrek Milan , Gezan Salvador 
Published: November 2020

AbstractNorway spruce has a broad natural distribution range, which results in a substantial variety of its physiological and genetic variation. There are three distinct altitudinal ecotypes described in this tree species. The physiological optimum of each ecotype may be shifted due to ongoing climate change, especially in traits associated with water demand that might be crucial for adaptation. Dehydrins are proteins that help to mitigate the adverse effects of dehydration. Dehydrin gene expression patterns appeared to be a suitable marker for plant stress assessment. Genetically determined differences in response between individuals and populations were formerly studied, however, mainly in controlled conditions. We evaluated ecotypic variation in dehydrin gene expression in a clonal bank comprised of all three ecotypes. A genetic relationship among targeted trees was uncovered utilizing GBS (Genotyping by Sequencing) platform. We sampled 4–6 trees of each ecotype throughout 15 months period. Subsequently, we assessed the RNA expression of dehydrin genes by qRT-PCR. For this study, we deliberately selected dehydrins from different categories. Our findings detected significant differences among ecotypes in dehydrin expression. The association of recorded climatic variables and individual gene expression across the study period was evaluated and revealed, for certain genes, a correlation between dehydrin gene expression and precipitation, temperature, and day-length.
Surface coating and speckling of the human iliotibial tract does not affect its load-deformation properties
Authors: Zwirner Johann , Ondruschka Benjamin , Scholze Mario , Hammer Niels 
Published: November 2020

AbstractStochastic surface patterns form an important requirement to facilitate digital image correlation and to subsequently quantify material properties of various tissues when loaded and deformed without artefacts arising from material slippage. Depending on the samples’ natural colour, a surface pattern is created by speckling with colour or dye only, or it requires combined surface coating and speckling before to enhance the contrast, to facilitate high-quality data recording for mechanical evaluation. However, it is unclear to date if the colours deployed for coating and speckling do significantly alter the biomechanical properties of soft tissues. The given study investigated the biomechanical properties of 168 human iliotibial tract samples as a model for collagen-rich soft tissues, separated into four groups: untreated, graphite speckling only, water-based coating plus graphite speckling and solvent-based coating plus graphite speckling following a standardized approach of application and data acquisition. The results reveal that elastic modulus, ultimate tensile strength and strain at maximum force of all groups were similar and statistically non-different (p ≥ 0.69). Qualitatively, the speckle patterns revealed increasing contrast differences in the following order: untreated, graphite speckling only, water-based coating plus graphite speckling and solvent-based coating plus graphite speckling. Conclusively, both coating by water- and solvent-based paints, as well as exclusive graphite speckling, did not significantly influence the load-deformation parameters of the here used human iliotibial tract as a model for collagen-rich soft tissues. In consequence, water- and solvent-based coating paints seem equally suitable to coat collagen-rich soft tissues for digital image correlation, resulting in suitable speckle patterns and unbiased data acquisition.