bluuebunny/crossref_metadata_2025 huggingface dataset:
An analysis and comparison of keyword recommendation methods for scientific data
Authors: Ishida Youichi , Shimizu Toshiyuki , Yoshikawa Masatoshi
Published: February 2020

To classify and search various kinds of scientific data, it is useful to annotate those data with keywords from a controlled vocabulary. Data providers, such as researchers, annotate their own data with keywords from the provided vocabulary. However, for the selection of suitable keywords, extensive knowledge of both the research domain and the controlled vocabulary is required. Therefore, the annotation of scientific data with keywords from a controlled vocabulary is a time-consuming task for data providers. In this paper, we discuss methods for recommending relevant keywords from a controlled vocabulary for the annotation of scientific data through their metadata. Many previous studies have proposed approaches based on keywords in similar existing metadata; we call this the indirect method. However, when the quality of the existing metadata set is insufficient, the indirect method tends to be ineffective. Because the controlled vocabularies for scientific data usually provide definition sentences for each keyword, it is also possible to recommend keywords based on the target metadata and the keyword definitions; we call this the direct method. The direct method does not utilize the existing metadata set and therefore is independent of its quality. Also, for the evaluation of keyword recommendation methods, we propose evaluation metrics based on a hierarchical vocabulary structure, which is a distinctive feature of most controlled vocabularies. Using our proposed evaluation metrics, we can evaluate keyword recommendation methods with an emphasis on keywords that are more difficult for data providers to select. In experiments using real earth science datasets, we compare the direct and indirect methods to verify their effectiveness, and observe how the indirect method depends on the quality of the existing metadata set. The results show the importance of metadata quality in recommending keywords.
Role of oral pathogens in the pathogenesis of intracranial aneurysm: review of existing evidence and potential mechanisms
Authors: Hallikainen Joona , Keränen Sara , Savolainen Jarno , Närhi Matti , Suominen Anna Liisa , Ylöstalo Pekka , Kellokoski Jari , Pyysalo Mikko , Pussinen Pirkko , Rauramaa Tuomas , Frösen Juhana
Published: February 2020

Degeneration of intracranial aneurysm wall is under active research and recent studies indicate an increased risk of rupture of intracranial aneurysm among patients with periodontal diseases. In addition, oral bacterial DNA has been identified from wall samples of ruptured and unruptured aneurysms. These novel findings led us to evaluate if oral diseases could predispose to pathological changes seen on intracranial aneurysm walls eventually leading to subarachnoid hemorrhage. The aim of this review is to consider mechanisms on the relationship between periodontitis and aneurysm rupture, focusing on recent evidence.
Aspects of Self-Awareness in Meditators and Meditation-Naïve Participants: Self-Report Versus Task Performance
Authors: Nyklíček Ivan
Published: February 2020

Objectives

Meditation may be viewed as a way to enhance mindfulness and self-awareness. To date, most studies have relied on instruments based on self-evaluations. The aim of this study was to explore aspects of self-awareness in experienced meditators compared to non-meditators using a multi-method approach.

Methods

Thirty-five experienced meditators and 47 matched control participants completed tests ranging from self-report questionnaires of mindfulness skills and psychological mindedness to emotion reports in a scenario task and a behavioral task in which spontaneous momentary experiences are verbally reported.

Results

Compared to controls, meditators scored higher on self-reported introspective interest and mindfulness skills, but not on emotional awareness. Meditators also showed higher interoception scores during the spontaneous verbal reports task. Interestingly, while mindfulness/Vipassana meditators scored lower on a self-reported mindfulness skill compared to transcendental meditators, they reported more momentary interoceptive and exteroceptive phenomena during the task, the differences being large.

Conclusions

Different methods assessing complementary aspects of self-awareness show partially mutually opposing results when meditator and non-meditator groups are compared. These results indicate the added value of behavioral tasks when assessing awareness-related phenomena.
Giant Multistep Crystalline vs. Osmotic Swelling of Synthetic Hectorite in Aqueous Acetonitrile
Authors: Kunz Raphael , Amschler Sonja , Edenharter Andreas , Mayr Lina , Herlitz Sebastian , Rosenfeldt Sabine , Breu Josef
Published: February 2020

Intercalation of large organocations into 2:1 clay minerals may be hampered by two problems: on one hand, the solubility of organocations in water is limited and the resulting high selectivity for adsorption in the polar solvent may lead to non-equilibrium structures. On the other hand, the large expansion of the interlayer space will slow down kinetics of ion exchange considerably. The best workaround for these obstacles is to suspend the clay minerals in mixtures of water with more hydrophobic organic solvents that nevertheless trigger a considerable expansion of the interlayer space by swelling. This in turn fosters ion exchange. The current study, therefore, revisited pioneering work by Bradley (1945) and investigated the swelling behavior of synthetic sodium hectorite (Na-hec) as a function of the composition of the swelling solvent, a mixture of acetonitrile and water. Up to a maximum acetonitrile content of 65 vol.%, delamination by osmotic swelling occurred. At even higher acetonitrile concentrations, swelling was limited to the crystalline swelling regime where a step-like adjustment of the d value was observed. Several mixtures were identified yielding a well defined and uniform interlayer height as evidenced by rational 00l-series with the d spacing decreasing with increasing acetonitrile content. Surprisingly, for a specific acetonitrile:water ratio even an ordered interstratification of two strictly alternating interlayer heights with distinctly different solvent compositions was observed.
Other-Than-Human Persons, Mishipishu, and Danger in the Late Woodland Inland Waterway Landscape of Northern Michigan
Authors: Howey Meghan C. L.
Published: February 2020

Other-than-human persons and the role they play in transforming social, economic, and ideological material realities is an area of expanding interest in archaeology. Although the Anishinaabeg were an early and vital focus of cultural anthropological studies on nonhumans given their significant relationships with other-than-human persons, known to them asmanitou, emerging archaeologies advancing this topic are not largely centered on ancestral Anishinaabeg sites and artifacts. This article analyzes a set of nonvessel ceramic artifacts from Late Woodland archaeological sites in the Inland Waterway in northern Michigan, which are interpreted to be ceramic renderings of manitou. I argue that these were manitou-in-clay, vibrant relational entities that are brought into being for and through use in ceremonial perspective practices related to Mishipishu—a complexly powerful, seductive, and dangerous nonhuman being known as the head of all water spirits. I contextualize the making and breaking of Mishipishu manitou-in-clay as acts of petition by hunter-fishers who had been seduced by this manitou in dreams, as they headed out on necessary but high-risk early-spring resource harvesting in the inland lakes of the Inland Waterway. This case advances insights into how relationships with other-than-human persons were coproductive of the world in the northern Great Lakes region during the Late Woodland period.
Injustice in Food-Related Public Health Problems: A Matter of Corporate Responsibility
Authors: Tempels Tjidde , Blok Vincent , Verweij Marcel
Published: February 2020

The responsibility of the food and beverage industry for noncommunicable diseases is a controversial topic. Public health scholars identify the food and beverage industry as one of the main contributors to the rise of these diseases. We argue that aside from moral duties like not doing harm and respecting consumer autonomy, the food industry also has a responsibility for addressing the structural injustices involved in food-related health problems. Drawing on the work of Iris Marion Young, this article first shows how food-related public health problems can be understood as structural injustices. Second, it makes clear how the industry is sustaining these health injustices, and that due to this connection, corporate actors share responsibility for addressing food-related health problems. Finally, three criteria (capacity, benefit, and vulnerability) are discussed as grounds for attributing responsibility, allowing for further specification on what taking responsibility for food-related health problems can entail in corporate practice.
The South's demographic transition and international capital flows in a financially integrated world economy
Authors: Gannon Frédéric , Le Garrec Gilles , Touzé Vincent
Published: February 2020

In the coming decades, the countries of the South will be facing the aging of the population faster than the countries of the North. This will have long-term economic consequences for the South but also for the North through the changing of international capital flows. To study the latter, we build a simple two-region two-period overlapping generations (OLG) model, assuming fully integrated financial markets. This allows us to determine the analytical expression of the world interest rate dynamics at general equilibrium and the resulting capital flows accruing to each of the two regions (the North and the South). From there, we analyze how a reduction in either fertility or mortality alters the magnitude of the international capital flows. Contradictory effects are evidenced. To clear-up any ambiguity and to study the South's demographic transition, which involves a succession of shocks, we propose numerical simulations. Even if the results stress that the institutional context and technological catching-up may matter, they suggest in a rather general way that the declines in both fertility and mortality tend to reduce the relative capital needs of the Southern economies and consequently their capital inflows. This, in turn, would be beneficial to the North's productive capacity, which should then hold more capital.
Dinocysts as a Tool for Palaeoenvironmental Reconstruction in Vitória Bay, Brazil
Authors: de Freitas Alex da Silva , Escamilla Javier Helenes , Barreto Cintia Ferreira , Bastos Alex Cardoso , da Fonseca Estefan Monteiro , Baptista Neto José Antônio
Published: February 2020

Micropaleontological and geochemical data were applied to sediments from southeastern Brazil to study the hydrodynamics associated with the Holocene sea level rise. Sediment cores were taken around Vitória Bay, examined for dinoflagellate cysts and subjected to isotopic analysis. The cyst assemblage mainly dominated by autotrophic species most notablyO. centrocarpum,L. machaerophorumandT. vancampoae. The influence of the marine transgression and subsequent regression observed during the Holocene along the coast of Brazil could have initially favored the establishment of an oligotrophic and higher energy environment. The inflow of continental water from tributaries combined with a higher inflow of saline water into the estuarine system could have favored the establishment and subsequent deposition of the dinocysts.
The Effect of Melt Pond Geometry on the Distribution of Solar Energy Under First‐Year Sea Ice
Authors: Horvat C. , Flocco D. , Rees Jones D. W. , Roach L. , Golden K. M.
Published: February 2020

Sea ice plays a critical role in the climate system through its albedo, which constrains light transmission into the upper ocean. In spring and summer, light transmission through sea ice is influenced by its iconic blue melt ponds, which significantly reduce surface albedo. We show that the geometry of surface melt ponds plays an important role in the partitioning of instantaneous solar radiation under sea ice by modeling the three‐dimensional light field under ponded sea ice. We find that aggregate properties of the instantaneous sub‐ice light field, such as the enhancement of available solar energy under bare ice regions, can be described using a new parameter closely related to pond fractal geometry. We then explore the influence of pond geometry on the ecological and thermodynamic sea ice processes that depend on solar radiation.
Nonlinear Interactions Between Radiation Belt Electrons and Chorus Waves: Dependence on Wave Amplitude Modulation
Authors: Gan L. , Li W. , Ma Q. , Albert J. M. , Artemyev A. V. , Bortnik J.
Published: February 2020

We use test particle simulations to model the interaction between radiation belt electrons and whistler mode chorus waves by focusing on wave amplitude modulations. We quantify the pitch angle and energy changes due to phase trapping and phase bunching (including both advection and scattering) for electrons with various initial energies and pitch angles. Three nonlinear regimes are identified in a broad range of pitch angle‐energy space systematically, each indicating different nonlinear effects. Our simulation results show that wave amplitude modulations can extend the nonlinear regimes, while significantly reducing electron acceleration by phase trapping. By including amplitude modulations, the “advective” changes in pitch angle and energy caused by phase bunching are reduced, while the “diffusive” scattering due to phase bunching is enhanced. Our study demonstrates the importance of wave amplitude modulations in nonlinear effects and suggests that they need to be properly incorporated into future theoretical and numerical studies.
The Challenges and Rewards of Running a Geospace Environment Modeling Challenge
Authors: Hietala H. , Dimmock A. P. , Zou Y. , Garcia‐Sage K.
Published: February 2020

Geospace Environment Modeling (GEM) is a community‐driven, National Science Foundation‐sponsored research program investigating the physics of the Earth's magnetosphere and its coupling to the solar wind and the atmosphere. This commentary provides an introduction to a Special Issue collating recent studies related to a GEM Challenge on kinetic plasma processes in the dayside magnetosphere during southward interplanetary magnetic field conditions. We also recount our experiences of organizing such a collaborative activity, where modelers and observers compare their results, that is, of the human side of bringing researchers together. We give suggestions on planning, managing, funding, and documenting these activities, which provide valuable opportunities to advance the field.
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

Silicic 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

Mouse 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

Highly 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

Recent 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

Invading 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

Nitrification, 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

The 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

Extracellular 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

Relatively 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

RNA 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

Human 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

Our 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

Genome-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.
Publisher Correction: Detection of introduced and resident marine species using environmental DNA metabarcoding of sediment and water
Authors: Holman Luke E. , Bruyn Mark de , Creer Simon , Carvalho Gary , Robidart Julie , Rius Marc
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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

Transplacental 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

The 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

While 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.
Context-Dependent Role of Vinculin in Neutrophil Adhesion, Motility and Trafficking
Authors: Wilson Zachary S. , Witt Hadley , Hazlett Lauren , Harman Michael , Neumann Brittany M. , Whitman Andrew , Patel Mohak , Ross Robert S. , Franck Christian , Reichner Jonathan S. , Lefort Craig T.
Published: February 2020

Neutrophils are innate immune effector cells that traffic from the circulation to extravascular sites of inflammation. β2 integrins are important mediators of the processes involved in neutrophil recruitment. Although neutrophils express the cytoskeletal protein vinculin, they do not form mature focal adhesions. Here, we characterize the role of vinculin in β2 integrin-dependent neutrophil adhesion, migration, mechanosensing, and recruitment. We observe that knockout of vinculin attenuates, but does not completely abrogate, neutrophil adhesion, spreading, and crawling under static conditions. However, we also found that vinculin deficiency does not affect these behaviors in the presence of forces from fluid flow. In addition, we identify a role for vinculin in mechanosensing, as vinculin-deficient neutrophils exhibit attenuated spreading on stiff, but not soft, substrates. Consistent with these findings, we observe that in vivo neutrophil recruitment into the inflamed peritoneum of mice remains intact in the absence of vinculin. Together, these data suggest that while vinculin regulates some aspects of neutrophil adhesion and spreading, it may be dispensable for β2 integrin-dependent neutrophil recruitment in vivo.
Cerebellar Ataxia Caused by Type II Unipolar Brush Cell Dysfunction in the Asic5 Knockout Mouse
Authors: Kreko-Pierce Tabita , Boiko Nina , Harbidge Donald G. , Marcus Daniel C. , Stockand James D. , Pugh Jason R.
Published: February 2020

Unipolar brush cells (UBCs) are excitatory granular layer interneurons in the vestibulocerebellum. Here we assessed motor coordination and balance to investigate if deletion of acid-sensing ion channel 5 (Asic5), which is richly expressed in type II UBCs, is sufficient to cause ataxia. The possible cellular mechanism underpinning ataxia in this global Asic5 knockout model was elaborated using brain slice electrophysiology. Asic5 deletion impaired motor performance and decreased intrinsic UBC excitability, reducing spontaneous action potential firing by slowing maximum depolarization rate. Reduced intrinsic excitability in UBCs was partially compensated by suppression of the magnitude and duration of delayed hyperpolarizing K+ currents triggered by glutamate. Glutamate typically stimulates burst firing subsequent to this hyperpolarization in normal type II UBCs. Burst firing frequency was elevated in knockout type II UBCs because it was initiated from a more depolarized potential compared to normal cells. Findings indicate that Asic5 is important for type II UBC activity and that loss of Asic5 contributes to impaired movement, likely, at least in part, due to altered temporal processing of vestibular input.
Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization
Authors: Nguyen Anne Quynh-Nhu , Denault André Y. , Théoret Yves , Perrault Louis P. , Varin France
Published: February 2020

Inhaled milrinone administered before cardiopulmonary bypass (CPB) reduces the severity of pulmonary hypertension during cardiac surgery. However, milrinone pharmacokinetics has not been determined for this route of administration. The objective of this study was to investigate inhaled milrinone dosing in vitro and early plasma concentrations in vivo after jet and mesh nebulization. Twelve pulmonary hypertensive patients scheduled for cardiac surgery were randomized to receive milrinone (5 mg) by inhalation before CPB using a jet or mesh nebulizer. In vitro experiments were conducted to determine the inhaled dose delivered with either jet or mesh nebulization. In vivo experiments involved hemodynamic monitoring and blood samples drawn from patients for the first 15 min after the end of inhalation to determine early plasma concentrations. After mesh nebulization, the mean in vitro inhaled dose was almost 3-fold higher compared to jet nebulization (46.4% vs 16.6% for mesh and jet, respectively; mean difference, 29.8%; 95% CI, 14.1 to 45.5; P = 0.006). Consistent with this, the early plasma concentrations in vivo were also 2–3 fold higher after mesh nebulization (P = 0.002–0.005). After inhalation (jet or mesh nebulization), milrinone early plasma concentrations remained within the therapeutic range. No systemic hypotension was reported in our patients.
Mint companion plants enhance the attraction of the generalist predator Nesidiocoris tenuis according to its experiences of conspecific mint volatiles
Authors: Rim Hojun , Hattori Sayaka , Arimura Gen-ichiro
Published: February 2020

Mint plants enable improvement of pest management by attracting herbivore enemies to constitutively released mint volatiles. The generalist predator Nesidiocoris tenuis is used worldwide to control agricultural pests, but little is known about whether mint can serve as a companion plant that attracts this predator. To examine this, olfactory responses of N. tenuis were assessed using apple mint, candy mint, and spearmint as odor sources. Of the volatiles released by these mint species, candy mint volatiles alone were more attractive than those from undamaged eggplant, and were as attractive as volatiles from eggplant damaged with Spodoptera litura larvae. However, no prominent preference for particular volatile(s) among the mint volatiles was shown by O. strigicollis. When N. tenuis had been previously exposed to candy mint, the predator showed a stronger preference for candy mint volatiles than damaged eggplant volatiles. It was, however, irrelevant whether the predator received benefit or not by predating animal prey during the mint-experience period. In contrast, spearmint-experience increased the preference for spearmint volatiles only when the predator acquired prey during the mint-experience period. These findings suggest that previous exposure of N. tenuis to some particular mint species can increase its preference for volatiles from the conspecific mints.
TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis
Authors: An Ju-Hyun , Li Qiang , Bhang Dong-Ha , Song Woo-Jin , Youn Hwa-Young
Published: February 2020

The inflammatory bowel diseases (IBD) are characterized by relapsing inflammation and immune activation diseases of the gastrointestinal tract. Extracellular vesicles, which elicit similar biological activity to the stem cell themselves, have been used experimentally to treat dextran sulfate sodium (DSS)-induced colitis in murine models though immunosuppressive potential. In this study, we investigated whether the Extracellular vesicles (EVs) obtained by stimulating inflammatory cytokine on canine adipose mesenchymal stem cells (cASC) improved anti-inflammatory and/or immunosuppressive potential of EVs, and/or their ability to alleviate inflammation in colitis. We also explored the correlation between immune cells and the inflammatory repressive effect of primed EVs. Pro-inflammatory cytokines such as TNF-α and IFN-γ increased immunosuppressive protein such as HGF, TSG-6, PGE2 and TGF-β in EVs. Moreover, the anti-inflammatory effect of EVs was improved through pretreatment with inflammatory cytokines. Importantly, EVs obtained from primed stem cells effectively induced macrophage polarization toward an anti-inflammatory M2 phenotype and suppressed activated immunity by enhancing regulatory T cells in inflamed colon in mice. Our results provide a new and effective therapy for the EVs obtained from ASC stimulated with TNF-α and IFN-γ against not only IBD, but also immune-mediated disease.
The Golgi Glycoprotein MGAT4D is an Intrinsic Protector of Testicular Germ Cells From Mild Heat Stress
Authors: Akintayo Ayodele , Liang Meng , Bartholdy Boris , Batista Frank , Aguilan Jennifer , Prendergast Jillian , Sabrin Afsana , Sundaram Subha , Stanley Pamela
Published: February 2020

Male germ cells are sensitive to heat stress and testes must be maintained outside the body for optimal fertility. However, no germ cell intrinsic mechanism that protects from heat has been reported. Here, we identify the germ cell specific Golgi glycoprotein MGAT4D as a protector of male germ cells from heat stress. Mgat4d is highly expressed in spermatocytes and spermatids. Unexpectedly, when the Mgat4d gene was inactivated globally or conditionally in spermatogonia, or mis-expressed in spermatogonia, spermatocytes or spermatids, neither spermatogenesis nor fertility were affected. On the other hand, when males were subjected to mild heat stress of the testis (43 °C for 25 min), germ cells with inactivated Mgat4d were markedly more sensitive to the effects of heat stress, and transgenic mice expressing Mgat4d were partially protected from heat stress. Germ cells lacking Mgat4d generally mounted a similar heat shock response to control germ cells, but could not maintain that response. Several pathways activated by heat stress in wild type were induced to a lesser extent in Mgat4d[−/−] heat-stressed germ cells (NFκB response, TNF and TGFβ signaling, Hif1α and Myc genes). Thus, the Golgi glycoprotein MGAT4D is a novel, intrinsic protector of male germ cells from heat stress.