bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of Felsic Rocks in Oceanic Crust: Implications From the Neoproterozoic Plagiogranites Within the Northeast Jiangxi Ophiolite, Southern China
Authors: Sun Zi‐Ming , Wang Xiao‐Lei , Zhang Feng‐Feng , Xie Hang‐Qiang , Zhao Kai , Li Jun‐Yong 
Published: February 2020

AbstractSilicic igneous rocks in the oceanic crust provide insights into the formation of proto‐continental crust, which can be investigated by studying rare silicic rocks within ophiolite complexes. This study focuses on plagiogranites that crop out as lenses and blocks in the northeast Jiangxi ophiolite (NJO), located in the eastern segment of the Neoproterozoic Jiangnan Orogen, southern China. The plagiogranites yield a mean SHRIMP U‐Pb zircon crystallization age of ca. 995 Ma and also record a late thermal event at ca. 220 Ma. The plagiogranites have high Na, very low K, and highly variable rare earth element (REE) concentrations from extremely depleted total REEs to strong enrichment in light REEs. Some samples have adakitic characteristics. Zircons from the plagiogranites have positive εHf(t) values (9.96 to 16.6) and mantle‐like δ18O values (5.13 ± 0.21‰), indicating a juvenile crustal or mantle source. Based on REE modeling, we propose a two‐stage model for the formation of the geochemically variable NJO plagiogranites: (1) High‐REE adakitic magmas plagiogranites were generated by 20% partial melting of basaltic oceanic crust; and (2) subsequent fractional crystallization (up to 50%) of these magmas and crystal accumulation produced the low‐REE plagiogranites. Our results show that granitic magmas can become highly differentiated in an oceanic setting. The diversity of silicic rocks in the oceanic crust is mainly the result of partial melting of subducted basaltic rocks and subsequent differentiation rather than just fractional crystallization of basaltic magmas.
Pten-mediated Gsk3β modulates the naïve pluripotency maintenance in embryonic stem cells
Authors: Wang Wuming , Lu Gang , Su Xianwei , Tang Chengcheng , Li Hongjian , Xiong Zhiqiang , Leung Chi-Kwan , Wong Man-Sze , Liu Hongbin , Ma Jin-Long , Cheung Hoi-Hung , Kung Hsiang-Fu , Chen Zi-Jiang , Chan Wai-Yee 
Published: February 2020

AbstractMouse embryonic stem cells (ESCs) are isolated from the inner cell mass of blastocysts, and they exist in different states of pluripotency—naïve and primed states. Pten is a well-known tumor suppressor. Here, we generated Pten−/− mouse ESCs with the CRISPR-Cas9 system and verified that Pten−/− ESCs maintained naïve pluripotency by blocking Gsk3β activity. Serum/LIF and 2i (MAPK and GSK3 inhibitors) conditions are commonly used for ESC maintenance. We show that the Pten-inhibitor SF1670 contributed to sustaining mouse ESCs and that Pten activation by the S380A, T382A, and T383A mutations (Pten-A3) suppressed the pluripotency of ESCs. The in vivo teratoma formation ability of SF1670-treated ESCs increased, while the Pten-A3 mutations suppressed teratoma formation. Furthermore, the embryoid bodies derived from Pten-deficient ESCs or SF1670-treated wild-type ESCs showed greater expression of ectoderm and pluripotency markers. These results suggest that Pten-mediated Gsk3β modulates the naïve pluripotency of ESCs and that Pten ablation regulates the lineage-specific differentiation.
Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes
Authors: Shen Xuzhong , Chen Xu , Chen Jieping , Sun Yufeng , Cheng Zhaoyang , Lu Zhan 
Published: February 2020

AbstractHighly regio- and enantioselective intermolecular hydroamination of alkenes is a challenging process potentially leading to valuable chiral amines. Hydroamination of alkenes via metal-catalyzed hydrogen atom transfer (HAT) with good regioselectivity and functional group tolerance has been reported, however, high enantioselectivity has not been achieved due to the lack of suitable ligands. Here we report a ligand-promoted cobalt-catalyzed Markovnikov-type selective radical hydroamination of alkenes with diazo compounds. This operationally simple protocol uses unsymmetric NNN-tridentate (UNT) ligand, readily available alkenes and hydrosilanes to construct hydrazones with good functional group tolerance. The hydrazones can undergo nitrogen–nitrogen bond cleavage smoothly to deliver valuable amine derivatives. Additionally, asymmetric intermolecular hydroamination of unactivated aliphatic terminal alkenes using chiral N-imidazolinylphenyl 8-aminoquinoline (IPAQ) ligands has also been achieved to afford chiral amine derivatives with good enantioselectivities.
De novo emergence of adaptive membrane proteins from thymine-rich genomic sequences
Authors: Vakirlis Nikolaos , Acar Omer , Hsu Brian , Castilho Coelho Nelson , Van Oss S. Branden , Wacholder Aaron , Medetgul-Ernar Kate , Bowman Ray W. , Hines Cameron P. , Iannotta John , Parikh Saurin Bipin , McLysaght Aoife , Camacho Carlos J. , O’Donnell Allyson F. , Ideker Trey , Carvunis Anne-Ruxandra 
Published: February 2020

AbstractRecent evidence demonstrates that novel protein-coding genes can arise de novo from non-genic loci. This evolutionary innovation is thought to be facilitated by the pervasive translation of non-genic transcripts, which exposes a reservoir of variable polypeptides to natural selection. Here, we systematically characterize how these de novo emerging coding sequences impact fitness in budding yeast. Disruption of emerging sequences is generally inconsequential for fitness in the laboratory and in natural populations. Overexpression of emerging sequences, however, is enriched in adaptive fitness effects compared to overexpression of established genes. We find that adaptive emerging sequences tend to encode putative transmembrane domains, and that thymine-rich intergenic regions harbor a widespread potential to produce transmembrane domains. These findings, together with in-depth examination of the de novo emergingYBR196C-Alocus, suggest a novel evolutionary model whereby adaptive transmembrane polypeptides emerge de novo from thymine-rich non-genic regions and subsequently accumulate changes molded by natural selection.
TBC1D9 regulates TBK1 activation through Ca2+ signaling in selective autophagy
Authors: Nozawa Takashi , Sano Shunsuke , Minowa-Nozawa Atsuko , Toh Hirotaka , Nakajima Shintaro , Murase Kazunori , Aikawa Chihiro , Nakagawa Ichiro 
Published: February 2020

AbstractInvading microbial pathogens can be eliminated selectively by xenophagy. Ubiquitin-mediated autophagy receptors are phosphorylated by TANK-binding kinase 1 (TBK1) and recruited to ubiquitinated bacteria to facilitate autophagosome formation during xenophagy, but the molecular mechanism underlying TBK1 activation in response to microbial infection is not clear. Here, we show that bacterial infection increases Ca2+ levels to activate TBK1 for xenophagy via the Ca2+-binding protein TBC1 domain family member 9 (TBC1D9). Mechanistically, the ubiquitin-binding region (UBR) and Ca2+-binding motif of TBC1D9 mediate its binding with ubiquitin-positive bacteria, and TBC1D9 knockout suppresses TBK1 activation and subsequent recruitment of the ULK1 complex. Treatment with a Ca2+ chelator impairs TBC1D9–ubiquitin interactions and TBK1 activation during xenophagy. TBC1D9 is also recruited to damaged mitochondria through its UBR and Ca2+-binding motif, and is required for TBK1 activation during mitophagy. These results indicate that TBC1D9 controls TBK1 activation during xenophagy and mitophagy through Ca2+-dependent ubiquitin-recognition.
Single cell analyses reveal contrasting life strategies of the two main nitrifiers in the ocean
Authors: Kitzinger Katharina , Marchant Hannah K. , Bristow Laura A. , Herbold Craig W. , Padilla Cory C. , Kidane Abiel T. , Littmann Sten , Daims Holger , Pjevac Petra , Stewart Frank J. , Wagner Michael , Kuypers Marcel M. M. 
Published: February 2020

AbstractNitrification, the oxidation of ammonia via nitrite to nitrate, is a key process in marine nitrogen (N) cycling. Although oceanic ammonia and nitrite oxidation are balanced, ammonia-oxidizing archaea (AOA) vastly outnumber the main nitrite oxidizers, the bacterial Nitrospinae. The ecophysiological reasons for this discrepancy in abundance are unclear. Here, we compare substrate utilization and growth of Nitrospinae to AOA in the Gulf of Mexico. Based on our results, more than half of the Nitrospinae cellular N-demand is met by the organic-N compounds urea and cyanate, while AOA mainly assimilate ammonium. Nitrospinae have, under in situ conditions, around four-times higher biomass yield and five-times higher growth rates than AOA, despite their ten-fold lower abundance. Our combined results indicate that differences in mortality between Nitrospinae and AOA, rather than thermodynamics, biomass yield and cell size, determine the abundances of these main marine nitrifiers. Furthermore, there is no need to invoke yet undiscovered, abundant nitrite oxidizers to explain nitrification rates in the ocean.
Dispersion tuning and route reconfiguration of acoustic waves in valley topological phononic crystals
Authors: Tian Zhenhua , Shen Chen , Li Junfei , Reit Eric , Bachman Hunter , Socolar Joshua E. S. , Cummer Steven A. , Jun Huang Tony 
Published: February 2020

AbstractThe valley degree of freedom in crystals offers great potential for manipulating classical waves, however, few studies have investigated valley states with complex wavenumbers, valley states in graded systems, or dispersion tuning for valley states. Here, we present tunable valley phononic crystals (PCs) composed of hybrid channel-cavity cells with three tunable parameters. Our PCs support valley states and Dirac cones with complex wavenumbers. They can be configured to form chirped valley PCs in which edge modes are slowed to zero group velocity states, where the energy at different frequencies accumulates at different designated locations. They enable multiple functionalities, including tuning of dispersion relations for valley states, robust routing of surface acoustic waves, and spatial modulation of group velocities. This work may spark future investigations of topological states with complex wavenumbers in other classical systems, further study of topological states in graded materials, and the development of acoustic devices.
C/EBPɑ is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition
Authors: Lourenço Ana Rita , Roukens M. Guy , Seinstra Danielle , Frederiks Cynthia L. , Pals Cornelieke E. , Vervoort Stephin J. , Margarido Andreia S. , van Rheenen Jacco , Coffer Paul J. 
Published: February 2020

AbstractExtracellular signals such as TGF-β can induce epithelial-to-mesenchymal transition (EMT) in cancers of epithelial origin, promoting molecular and phenotypical changes resulting in pro-metastatic characteristics. We identified C/EBPα as one of the most TGF-β-mediated downregulated transcription factors in human mammary epithelial cells. C/EBPα expression prevents TGF-β-driven EMT by inhibiting expression of known EMT factors. Depletion of C/EBPα is sufficient to induce mesenchymal-like morphology and molecular features, while cells that had undergone TGF-β-induced EMT reverted to an epithelial-like state upon C/EBPα re-expression. In vivo, mice injected with C/EBPα-expressing breast tumor organoids display a dramatic reduction of metastatic lesions. Collectively, our results show that C/EBPα is required for maintaining epithelial homeostasis by repressing the expression of key mesenchymal markers, thereby preventing EMT-mediated tumorigenesis. These data suggest that C/EBPα is a master epithelial “gatekeeper” whose expression is required to prevent unwarranted mesenchymal transition, supporting an important role for EMT in mediating breast cancer metastasis.
Sequence-selective dynamic covalent assembly of information-bearing oligomers
Authors: Leguizamon Samuel C. , Scott Timothy F. 
Published: February 2020

AbstractRelatively robust dynamic covalent interactions have been employed extensively to mediate molecular self-assembly reactions; however, these assembly processes often do not converge to a thermodynamic equilibrium, instead yielding mixtures of kinetically-trapped species. Here, we report a dynamic covalent self-assembly process that mitigates kinetic trapping such that multiple unique oligomers bearing covalently coreactive pendant groups are able to undergo simultaneous, sequence-selective hybridization with their complementary strands to afford biomimetic, in-registry molecular ladders with covalent rungs. Analogous to the thermal cycling commonly employed for nucleic acid melting and annealing, this is achieved by raising and lowering the concentration of a multi-role reagent to effect quantitative dissociation and subsequently catalyze covalent bond rearrangement, affording selective assembly of the oligomeric sequences. The hybridization specificity afforded by this process further enabled information encoded in oligomers to be retrieved through selective hybridization with complementary, mass-labeled sequences.
Cis- and trans-regulations of pre-mRNA splicing by RNA editing enzymes influence cancer development
Authors: Tang Sze Jing , Shen Haoqing , An Omer , Hong HuiQi , Li Jia , Song Yangyang , Han Jian , Tay Daryl Jin Tai , Ng Vanessa Hui En , Bellido Molias Fernando , Leong Ka Wai , Pitcheshwar Priyankaa , Yang Henry , Chen Leilei 
Published: February 2020

AbstractRNA editing and splicing are the two major processes that dynamically regulate human transcriptome diversity. Despite growing evidence of crosstalk between RNA editing enzymes (mainly ADAR1) and splicing machineries, detailed mechanistic explanations and their biological importance in diseases, such as cancer are still lacking. Herein, we identify approximately a hundred high-confidence splicing events altered by ADAR1 and/or ADAR2, and ADAR1 or ADAR2 protein can regulate cassette exons in both directions. We unravel a binding tendency of ADARs to dsRNAs that involves GA-rich sequences for editing and splicing regulation. ADAR1 edits an intronic splicing silencer, leading to recruitment of SRSF7 and repression of exon inclusion. We also present a mechanism through which ADAR2 binds to dsRNA formed between GA-rich sequences and polypyrimidine (Py)-tract and precludes access of U2AF65 to 3′ splice site. Furthermore, we find these ADARs-regulated splicing changes per se influence tumorigenesis, not merely byproducts of ADARs editing and binding.
Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets
Authors: Richard Mathilde , van den Brand Judith M. A. , Bestebroer Theo M. , Lexmond Pascal , de Meulder Dennis , Fouchier Ron A. M. , Lowen Anice C. , Herfst Sander 
Published: February 2020

AbstractHuman influenza A viruses are known to be transmitted via the air from person to person. It is unknown from which anatomical site of the respiratory tract influenza A virus transmission occurs. Here, pairs of genetically tagged and untagged influenza A/H1N1, A/H3N2 and A/H5N1 viruses that are transmissible via the air are used to co-infect donor ferrets via the intranasal and intratracheal routes to cause an upper and lower respiratory tract infection, respectively. In all transmission cases, we observe that the viruses in the recipient ferrets are of the same genotype as the viruses inoculated intranasally, demonstrating that they are expelled from the upper respiratory tract of ferrets rather than from trachea or the lower airways. Moreover, influenza A viruses that are transmissible via the air preferentially infect ferret and human nasal respiratory epithelium. These results indicate that virus replication in the upper respiratory tract, the nasal respiratory epithelium in particular, of donors is a driver for transmission of influenza A viruses via the air.
IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche
Authors: Wamaitha Sissy E. , Grybel Katarzyna J. , Alanis-Lobato Gregorio , Gerri Claudia , Ogushi Sugako , McCarthy Afshan , Mahadevaiah Shantha K. , Healy Lyn , Lea Rebecca A. , Molina-Arcas Miriam , Devito Liani G. , Elder Kay , Snell Phil , Christie Leila , Downward Julian , Turner James M. A. , Niakan Kathy K. 
Published: February 2020

AbstractOur understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human embryo and identify expression for the insulin and insulin growth factor 1 (IGF1) receptors, along with IGF1 ligand. Consequently, we generate a minimal chemically-defined culture medium in which IGF1 together with Activin maintain self-renewal in the absence of fibroblast growth factor (FGF) signalling. Under these conditions, we derive several pluripotent stem cell lines that express pluripotency-associated genes, retain high viability and a normal karyotype, and can be genetically modified or differentiated into multiple cell lineages. We also identify active phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling in early human embryos, and in both primed and naïve pluripotent culture conditions. This demonstrates that signalling insights from human blastocysts can be used to define culture conditions that more closely recapitulate the embryonic niche.
Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia
Authors: Sanchez Robersy , Mackenzie Sally A. 
Published: February 2020

AbstractGenome-wide DNA methylation and gene expression are commonly altered in pediatric acute lymphoblastic leukemia (PALL). Integrated network analysis of cytosine methylation and expression datasets has the potential to provide deeper insights into the complex disease states and their causes than individual disconnected analyses. With the purpose of identifying reliable cancer-associated methylation signal in gene regions from leukemia patients, we present an integrative network analysis of differentially methylated (DMGs) and differentially expressed genes (DEGs). The application of a novel signal detection-machine learning approach to methylation analysis of whole genome bisulfite sequencing (WGBS) data permitted a high level of methylation signal resolution in cancer-associated genes and pathways. This integrative network analysis approach revealed that gene expression and methylation consistently targeted the same gene pathways relevant to cancer:Pathways in cancer, Ras signaling pathway,PI3K-Akt signaling pathway, andRap1 signaling pathway, among others. Detected gene hubs and hub sub-networks were integrated by signature loci associated with cancer that include, for example,NOTCH1, RAC1, PIK3CD, BCL2, andEGFR. Statistical analysis disclosed a stochastic deterministic relationship between methylation and gene expression within the set of genes simultaneously identified as DEGs and DMGs, where larger values of gene expression changes were probabilistically associated with larger values of methylation changes. Concordance analysis of the overlap between enriched pathways in DEG and DMG datasets revealed statistically significant agreement between gene expression and methylation changes. These results support the potential identification of reliable and stable methylation biomarkers at genes for cancer diagnosis and prognosis.
Virological, immunological and pathological findings of transplacentally transmitted bluetongue virus serotype 1 in IFNAR1-blocked mice during early and mid gestation
Authors: Saminathan M. , Singh K. P. , Vineetha S. , Maity Madhulina , Biswas S. K. , Manjunathareddy G. B. , Chauhan H. C. , Milton A. A. P. , Ramakrishnan M. A. , Maan Sushila , Maan N. S. , Hemadri D. , Chandel B. S. , Gupta V. K. , Mertens P. P. C. 
Published: February 2020

AbstractTransplacental transmission (TPT) of wild-type Indian BTV-1 had never been experimentally proved. This study was first time investigated TPT of Indian BTV-1 (isolated from aborted and stillborn goat fetal spleens). The sequential pathology, virological and immune cell kinetics (CD4+, CD8+T-lymphocytes and NK cells in spleen and PBMCs), and apoptosis in IFNAR1-blocked pregnant mice during early (infected on 1 GD) and mid (infected on 8 GD) gestation have been studied. There was higher rate of TPT during mid stage (71.43%) than early (57.14%) stage. In early stage reduced implantation sites, early embryonic deaths, abortions, and necro-haemorrhagic lesions had observed. Mid stage, congenital defects and neurological lesions in foetuses like haemorrhages, diffuse cerebral edema, necrotizing encephalitis and decreased bone size (Alizarin red staining) were noticed. BTV-1 antigen was first time demonstrable in cells of mesometrium, decidua of embryos, placenta, uterus, ovary, and brain of foetuses by immunohistochemistry and quantified by real-time qRT-PCR. BTV-inoculated mice were seroconverted by 7 and 5 dpi, and reached peak levels by 15 and 9 dpi in early and mid gestation, respectively. CD4+and CD8+cells were significantly decreased (increased ratio) on 7 dpi but subsequently increased on 15 dpi in early gestation. In mid gestation, increased CD8+cells (decreased ratio) were observed. Apoptotic cells in PBMCs and tissues increased during peak viral load. This first time TPT of wild-type Indian BTV-1 deserves to be reported for implementation of control strategies. This model will be very suitable for further research into mechanisms of TPT, overwintering, and vaccination strategies.
Concatenated Composite Pulses Applied to Liquid-State Nuclear Magnetic Resonance Spectroscopy
Authors: Bando Masamitsu , Ichikawa Tsubasa , Kondo Yasushi , Nemoto Nobuaki , Nakahara Mikio , Shikano Yutaka 
Published: February 2020

AbstractThe error-robust and short composite operations named ConCatenated Composite Pulses (CCCPs), developed as high-precision unitary operations in quantum information processing (QIP), are derived from composite pulses widely employed in nuclear magnetic resonance (NMR). CCCPs simultaneously compensate for two types of systematic errors, which was not possible with the known composite pulses in NMR. Our experiments demonstrate that CCCPs are powerful and versatile tools not only in QIP but also in NMR.
Large-for-gestational-age phenotypes and obesity risk in adulthood: a study of 195,936 women
Authors: Derraik José G. B. , Maessen Sarah E. , Gibbins John D. , Cutfield Wayne S. , Lundgren Maria , Ahlsson Fredrik 
Published: February 2020

AbstractWhile there is evidence that being born large-for-gestational-age (LGA) is associated with an increased risk of obesity later in life, the data are conflicting. Thus, we aimed to examine the associations between proportionality at birth and later obesity risk in adulthood. This was a retrospective study using data recorded in the Swedish Birth Register. Anthropometry in adulthood was assessed in 195,936 pregnant women at 10–12 weeks of gestation. All women were born at term (37–41 weeks of gestation). LGA was defined as birth weight and/or length ≥2.0 SDS. Women were separated into four groups: appropriate-for-gestational-age according to both weight and length (AGA – reference group; n = 183,662), LGA by weight only (n = 4,026), LGA by length only (n = 5,465), and LGA by both weight and length (n = 2,783). Women born LGA based on length, weight, or both had BMI 0.12, 1.16, and 1.08 kg/m2 greater than women born AGA, respectively. The adjusted relative risk (aRR) of obesity was 1.50 times higher for those born LGA by weight and 1.51 times for LGA by both weight and height. Length at birth was not associated with obesity risk. Similarly, women born LGA by ponderal index had BMI 1.0 kg/m2 greater and an aRR of obesity 1.39 times higher than those born AGA. Swedish women born LGA by weight or ponderal index had an increased risk of obesity in adulthood, irrespective of their birth length. Thus, increased risk of adult obesity seems to be identifiable from birth weight and ignoring proportionality.