bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bulk Liquid for the Skaergaard Intrusion and Its PGE-Au Mineralization: Composition, Correlation, Liquid Line of Descent, and Timing of Sulphide Saturation and Silicate–Silicate Immiscibility
Authors: Nielsen Troels F D , Brooks C Kent , Keiding Jakob K 
Published: November 2019

AbstractPreferred and modelled bulk composition of the Skaergaard intrusion are compared to coeval basaltic compositions in East Greenland and found to relate to the second evolved cycle of Geikie Plateau Formation lavas and coeval Skaergaard-like dikes in major and trace element (Mg# ∼45, Ce/Nb ∼2·5, (Dy/Yb)N ∼1·35), and precious metal composition (Pd/Pt ∼3, Au/Pt ∼2) as well as in age (∼56 Ma). Successful comparisons of precious metal compositions only occur with Skaergaard models based on mass balance. The bulk liquid of the intrusion evolved along the liquid line of descent to immiscibility between Si- and Fe-rich silicate liquids after ∼90% of crystallization (F = ∼0·10) in agreement with experimental constraints. Immiscibility led to accumulation and fractionation of the Fe-rich silicate melt in the mushy floor of the intrusion and continued accumulation of granophyre component in the remaining bulk liquid. The composition of plagioclase in the precious metal mineralized gabbro and modelling of Pd/Pt and Au/Pt in first formed droplets of sulphide melt suggest that sulphide saturation was reached in interstitial melts in crystal mushes in the floor and roof and in bulk liquid with a composition equivalent to that of the bulk liquid at lower UZa times and after crystallization of 82–85% of the bulk liquid (F = 0·19–0·16). Prior to sulphide saturation in UZa type melt, the precious metals ratios of the bulk liquid were controlled by the loss of Pt relative to Pd and Au in agreement with the low empirical and experimental solubility of Pt of ∼9ppb compared to a much higher value for Pd and Au. The relative timing between sulphide saturation (F = ∼0·18) and immiscibility between silicate melts (F = ∼0·10) and modelled precious metal ratios underpin the proposed multi-stage model for the mineralization, advocating initial accumulation in the mushy floor of the magma chamber controlled by sulphide saturation in mush melts rather than bulk melt, followed by redistribution of precious metals in a macro-rhythmic succession of gabbroic layers of the upward migrating crystallization zone.
Democratic Backsliding, Populism, and Public Administration
Authors: Bauer Michael W , Becker Stefan 
Published: November 2019

AbstractWhat happens to public administration when populists are elected into government? This article argues that populists seek to realize an anti-pluralist reform agenda, thereby fuelling trends of democratic backsliding. Against this background, the article discusses potential goals and strategies of populist public administration policy and introduces examples of how populists sought to capture (Orbán in Hungary), dismantle (Fujimori in Peru), sabotage (Trump in the United States), and reform (Blocher in Switzerland) the state bureaucracy. In doing so, populists in government aim at structures, resources, personnel, norms, and accountability relationships. The examples suggest that populist public administration policies can have profound impact on policymaking and democracy, underlining the need for a broader research agenda on this issue area.
Low-dose corticosteroid and mycophenolate for primary treatment of minimal change disease
Authors: Ma M K M , Yap D Y H , Li C L , Mok M M Y , Chan G C W , Kwan L P Y , Lai K N , Tang S C W 
Published: November 2019

Abstract

Background
Mycophenolate has been shown to be effective in glomerular disease. However, the role of mycophenolate in the first-line treatment of adult-onset idiopathic minimal change disease (MCD) has not been systematically studied in a randomized fashion.

Aim
To evaluate the therapeutic efficacy of enteric-coated mycophenolate sodium combined with low-dose corticosteroid as first-line treatment for MCNS.

Design
A prospective, open-label, randomized clinical trial.

Methods
Twenty adult patients with biopsy proven MCD were recruited and randomly assigned to receive either enteric-coated Mycophenolate Sodium (EC-MPS) plus low-dose prednisolone (Group 1: Prednisolone 0.25 mg/kg/day, n = 10) or standard-dose prednisolone (Group 2: Prednisolone 1 mg/kg/day, n = 10).

Results
After 24 weeks of therapy, eight patients in Group 1 vs. seven of patients in Group 2 achieved complete remission (P = 0.606). Both groups showed a significant reduction of urine protein excretion (P &lt; 0.05) and increased serum albumin (P &lt; 0.001) vs. baseline levels. However, no significant between-group differences were demonstrated. The relapse rate was also similar in both groups. Both treatment regimens were well tolerated but there were more patient reported adverse effects in the standard-dose prednisolone group.

Conclusion
EC-MPS plus low-dose prednisolone is non-inferior to standard-dose prednisolone therapy in inducing clinical remission and preventing relapse in adult-onset idiopathic MCD and is associated with better tolerability and less adverse effects. This trial is registered with the ClinicalTrials.gov number NCT01185197.
AGE DEPENDENCE OF INDIVIDUAL EXTERNAL DOSES IN AN EARLY STAGE AFTER THE FUKUSHIMA NUCLEAR ACCIDENT
Authors: Ishikawa Tetsuo , Yasumura Seiji , Akahane Keiichi , Yonai Shunsuke , Ohtsuru Akira , Sakai Akira , Ohira Tetsuya , Kamiya Kenji 
Published: November 2019

Abstract
Individual external doses for the first 4 months after the Fukushima accident have been estimated by the ‘Basic Survey’ of the Fukushima Health Management Survey. On the other hand, the UNSCEAR 2013 report presented the first-year effective dose due to external radiation for each municipality in nonevacuated areas of Fukushima Prefecture. In this study, the doses estimated by the Basic Survey were averaged for each of three age groups (infants, 0–5 y; children, 6–15 y; and adults, &gt;16 y), in accordance with the categories adopted by the UNSCEAR report. The average dose ratios (infants/adults and children/adults) obtained from the Basic Survey were 1.08 and 1.06 for nonevacuated areas, respectively. These were smaller than the estimation by the UNSCEAR report (1.7 and 1.4, respectively). Three factors (body size factor, location factor and occupancy factor) were discussed and the location and occupancy factors were likely to be reasons for the difference.
A hydrogel beads based platform for single-cell phenotypic analysis and digital molecular detection
Authors: Zhu Yanzhe , Li Jing , Lin Xingyu , Huang Xiao , Hoffmann Michael R. 
Published: November 2019

AbstractMicrofluidic platforms integrating phenotyping and genotyping approaches have the potential to advance the understanding of single cell genotype-to-phenotype correlations. These correlations can play a key role in tackling antibiotic heteroresistance, cancer cell heterogeneity, and other related fundamental problems. Herein, we report a novel platform that enables both high-throughput digital molecular detection and single-cell phenotypic analysis, utilizing nanoliter-sized biocompatible polyethylene glycol hydrogel beads produced by a convenient and disposable centrifugal droplet generation device. The hydrogel beads have been demonstrated enhanced thermal stability, and achieved uncompromised efficiencies in digital polymerase chain reaction, digital loop-mediated isothermal amplification, and single cell phenotyping. The crosslinked hydrogel network highlights the prospective linkage of various subsequent molecular analyses to address the genotypic differences between cellular subpopulations exhibiting distinct phenotypes. Our platform shows great potential for applications in clinical practice and medical research, and promises new perspectives in mechanism elucidation of environment-evolution interaction and other basic research areas.
Integrative genomic analysis unifying epigenetic inheritance in adaptation and canalization
Authors: Sharma Abhay 
Published: November 2019

AbstractEpigenetic inheritance, especially its biomedical and evolutionary significance, is an immensely interesting but highly controversial subject. Notably, a recent analysis of existing multi-omics has supported the mechanistic plausibility of epigenetic inheritance and its implications in disease and evolution. The evolutionary support stemmed from the specific finding that genes associated with cold induced inheritance and with latitudinal adaptation in mice are exceptionally common. Here, a similar gene set overlap analysis is presented that integrates cold induced inheritance with evolutionary adaptation and genetic canalization in cold environment in Drosophila. Genes showing differential expression in inheritance specifically overrepresent gene sets associated with differential and allele specific expression, though not with genome-wide genetic differentiation, in adaptation. On the other hand, the differentiated outliers uniquely overrepresent genes dysregulated by radicicol, a decanalization inducer. Both gene sets in turn exclusively show enrichment of genes that accumulate, in intended experimental lines, de novo mutations, a potential source of canalization. Successively, the three gene sets distinctively overrepresent genes exhibiting, between mutation accumulation lines, invariable expression, a potential signal for canalization. Sequentially, the four gene sets solely display enrichment of genes grouped in gene ontology under transcription factor activity, a signature of regulatory canalization. Cumulatively, the analysis suggests that epigenetic inheritance possibly contributes to evolutionary adaptation in the form of cis regulatory variations, with trans variations arising in the course of genetic canalization.
microRNA profiling in the Weddell Seal suggests novel regulatory mechanisms contributing to diving adaptation
Authors: Penso-Dolfin Luca , Haerty Wilfried , Hindle Allyson , Di Palma Federica 
Published: November 2019

ABSTRACTThe Weddell Seal (Leptonychotes weddelli) represents a remarkable example of adaptation to diving among marine mammals. This species is capable of diving >900 m deep and remaining underwater for more than 60 minutes. A number of key physiological specializations have been identified, including the low levels of aerobic, lipid-based metabolism under hypoxia, significant increase in oxygen storage in blood and muscle; high blood volume and extreme cardiovascular control. These adaptations have been linked to increased abundance of key proteins, suggesting an important, yet still understudied role for gene reprogramming.In this study, we investigate the possibility that post-transcriptional gene regulation by microRNAs (miRNAs) has contributed to the adaptive evolution of diving capacities in the Weddell Seal.Using small RNA data across 4 tissues (cortex, heart, muscle and plasma), in 3 biological replicates, we generate the first miRNA annotation in this species, consisting of 559 high confidence, manually curated miRNA loci. Evolutionary analyses of miRNA gain and loss highlight a high number of Weddell seal specific miRNAs.416 miRNAs were differentially expressed (DE) among tissues, whereas 83 miRNAs were differentially expressed (DE) across all tissues between pups and adults and 221 miRNAs demonstrated developmental changes in specific tissues only. mRNA targets of these altered miRNAs identify possible protective mechanisms in individual tissues, particularly relevant to hypoxia tolerance, anti-apoptotic pathways, and nitric oxide signal transduction. Novel, lineage-specific miRNAs associated with developmental changes target genes with roles in angiogenesis and vasoregulatory signaling.Altogether, we provide an overview of miRNA composition and evolution in the Weddell seal, and the first insights into their possible role in the specialization to diving.
Non-invasive neuromodulation using rTMS and the Electromagnetic-Perceptive Gene (EPG) facilitates plasticity after nerve injury
Authors: Cywiak Carolina , Ashbaugh Ryan C. , Metto Abigael C. , Udpa Lalita , Qian Chunqi , Gilad Assaf A. , Zhong Ming , Pelled Galit 
Published: November 2019

AbstractPeripheral nerve injury leads to altered cortical excitation-inhibition balance which is associated with sensory dysfunctions. We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which has shown to induce neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from Kryptopterrus bicirrhis and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. A battery of behavioral tests, fMRI and immunochemistry were performed in the weeks following limb denervation in rats. The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The study also identifies the acute post-injury phase as a critical time for intervention. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.
Dendritic cells require TMEM176A/B ion channels for optimal MHC II antigen presentation to naive CD4+ T cells
Authors: Lancien Melanie , Bienvenu Geraldine , Gueno Lucile , Salle Sonia , Merieau Emmanuel , Remy Severine , Even Amandine , Moreau Aurelie , Molle Alice , Fourgeux Cynthia , Coulon Flora , Beriou Gaelle , Bouchet-Delbos Laurence , Chiffoleau Elise , Kirstetter Peggy , Chan Susan , Kerfoot Steven , Abdu Rahiman Saeed , De Simone Veronica , Matteoli Gianluca , Boncompain Gaelle , Perez Franck , Josien Regis , Poschmann Jeremie , Cuturi Maria Cristina , Louvet Cedric 
Published: November 2019

SummaryIntracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. Here we investigated the role of the redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in RORγt+ cells and conventional dendritic cells (cDCs) using germline and conditional double knock-out (DKO) mice. While Tmem176a/b appeared surprisingly dispensable for the protective function of Th17 and group 3 innate lymphoid cells (ILC3s) in the intestinal mucosa, we found that they were required in cDCs for optimal antigen processing and presentation to CD4+ T cells. Using a real-time imaging method, we show that TMEM176A/B accumulate in dynamic post-Golgi vesicles preferentially linked to the late endolysosomal system and strongly colocalize with HLA-DM. Together, our results suggest that TMEM176A/B ion channels play a direct role in the MHC II compartment (MIIC) of DCs for the fine regulation of antigen presentation and naive CD4+ T cell priming.
DISTINCT ACTIN-DEPENDENT NANOSCALE ASSEMBLIES UNDERLIE THE DYNAMIC AND HIERARCHICAL ORGANIZATION OF E-CADHERIN
Authors: Chandran Rumamol , Kale Girish , Philippe Jean-Marc , Lecuit Thomas , Mayor Satyajit 
Published: November 2019

SUMMARYIntercellular adhesion mediated by E-cadherin is pivotal in maintaining epithelial tissue integrity and for tissue morphogenesis. Adhesion requires homophilic interactions between extracellular domains of E-cadherin molecules from neighboring cells. The interaction of its cytoplasmic domains with the cortical acto-myosin network, appears to strengthen adhesion, although, it is unclear how cortical actin affects the organization and function of E-cadherin dynamically. Here we use the ectopic expression ofDrosophilaE-cadherin (E-cad) in larval hemocytes, which lack endogenous E-cad, to recapitulate functional cell-cell junctions in a convenient model system. We used fluorescence emission anisotropy-based microscopy and Fluorescence Correlation Spectroscopy (FCS) to probe the nanoscale organization of E-cad. We find that E-cad at cell-cell junctions in hemocytes exhibits a clusteredtrans-paired organization, similar to that reported for the adherens junction in the developing embryonic epithelial tissue. Further, we find that extra-junctional E-cad is also organized as relatively immobile nanoclusters as well as diffusive and more loosely packed oligomers and monomers. These oligomers are promoted bycis-interactions of the ectodomain and, strikingly, their growth is constantly counteracted by cortical actomyosin. Oligomers in turn assist in generating nanoclusters that are stabilized by cortical acto-myosin. Thus, actin remodels oligomers and stabilizes nanoclusters, revealing a requirement for actin in the dynamic organization of E-cad at the nanoscale. This dynamic organization is also present at cell-cell contacts (junction), and its disruption affects junctional integrity in the hemocyte system, as well as in the embryo. Our observations uncover a hierarchical mechanism for the nanoscale organization of E-cad, which is necessary for dynamic adhesion and maintaining junctional integrity in the face of extensive remodeling.
CtcfHaploinsufficiency Mediates Intron Retention in A Tissue-specific Manner
Authors: Alharbi Adel B , Schmitz Ulf , Marshall Amy D , Vanichkina Darya , Nagarajah Rajini , Vellozzi Melissa , Wong Justin JL , Bailey Charles G , Rasko John EJ 
Published: November 2019

AbstractCTCF is a master regulator of gene transcription and chromatin organization with occupancy at thousands of DNA target sites. CTCF is essential for embryonic development and somatic cell viability and has been characterized as a haploinsufficient tumor suppressor. Increasing evidence demonstrates CTCF as a key player in several alternative splicing (AS) regulatory mechanisms, including transcription elongation, regulation of splicing factors, and epigenetic regulation. However, the genome-wide impact ofCtcfdosage on AS has not been investigated. We examined the effect ofCtcfhaploinsufficiency on gene expression and AS in multiple tissues fromCtcfhemizygous (Ctcf+/-) mice. Distinct tissue-specific differences in gene expression and AS were observed inCtcf+/-mice compared to wildtype mice. We observed a surprisingly large number of increased intron retention (IR) events inCtcf+/-liver and kidney, specifically in genes associated with cytoskeletal organization, splicing and metabolism. This study provides further evidence forCtcfdose-dependent and tissue-specific regulation of gene expression and AS. Our data provide a strong foundation for elucidating the mechanistic role of CTCF in AS regulation and its biological consequences.
A natural antisense to brain-derived neurotrophic factor impairs extinction of drug seeking
Authors: Youngson Neil A. , Castino Matthew R. , Stuart Angela , Kershaw Kelly A. , Holmes Nathan M. , Waters Paul D. , Morris Kevin V. , Clemens Kelly J. 
Published: November 2019

ABSTRACTBACKGROUNDBrain derived neurotrophic factor (BDNF) is critical for the extinction of drug-seeking. Expression of the Bdnf gene is highly regulated via interactions with non-coding RNA, which themselves are altered following drug exposure. Here we investigate whether a novel long non-coding RNA antisense to Bdnf prevents extinction of drug-seeking. METHODS: Strand-specific RNA sequencing identified a novel long non-coding RNA antisense to exon IV of the Bdnf gene in the ventromedial prefrontal cortex of 8 adult male rats. We then assessed asBdnf-IV expression using strand-specific reverse transcription and quantitative polymerase chain reaction following acquisition, extinction or abstinence from intravenous nicotine self-administration (N = 116). A functional role of the asBdnf-IV in extinction of nicotine-seeking was established by infusing gapmer oligonucleotides into the infralimbic cortex prior to extinction and testing for the effect of these infusions on reinstatement and reacquisition of nicotine-seeking (N = 36).RESULTSRNA sequencing identified the presence of a novel long non-coding RNA antisense to exon IV of the Bdnf gene (asBdnf-IV). Expression of asBdnf-IV was elevated following intravenous nicotine self-administration but not experimenter-administered nicotine. Elevated asBdnf-IV persisted across abstinence and to a greater extent following extinction training, suggesting an interaction between abstinence and extinction learning. In support of this, knockdown of the asBdnf-IV across extinction, but not abstinence, significantly attenuated nicotine-primed reinstatement of nicotine-seeking.CONCLUSIONSasBdnf-IV accumulates in the infralimbic cortex across self-administration training, interferes with the inhibitory learning that underpins extinction of drug-seeking, and predisposes animals to drug relapse.
Histone chaperone Nucleophosmin regulates transcription of key genes involved in oral tumorigenesis
Authors: Senapati Parijat , Dey Suchismita , Sudarshan Deepthi , Bhattacharya Aditya , G Shyla , Das Sadhan , Sudevan Surabhi , Maliekal Tessy Thomas , Kundu Tapas K. 
Published: November 2019

ABSTRACTNucleophosmin (NPM1) is a multifunctional histone chaperone that can activate RNA Polymerase II-driven chromatin transcription. Acetylation of NPM1 by acetyltransferase p300 has been shown to further enhance its transcription activation potential. Moreover, its total and acetylated pools are increased in oral squamous cell carcinoma. However, the role of NPM1 or its acetylated form (AcNPM1) in transcriptional regulation in cells is not fully elucidated. Using ChIP-seq analyses, we show that AcNPM1 co-occupies marks of active transcription at promoters and DNase I hypersensitive sites at enhancers. Moreover, NPM1 interacts with proteins involved in transcription, including RNA Pol II, general transcription factors, mediator subunits, histone acetyltransferase complexes, and chromatin remodelers. Moreover, its histone chaperone also contributes to transcriptional activation. We further show that AcNPM1 regulates key genes required for proliferation, migration and invasion potential of oral cancer cells and knockdown of NPM1 mitigates these processes in cells as well as orthotopic tumors in mice. Collectively, these results establish that AcNPM1 functions as a coactivator and regulates the expression of key genes involved in oral tumorigenesis.
Low membrane fluidity triggers lipid phase separation and protein segregation in vivo
Authors: Gohrbandt Marvin , Lipski André , Grimshaw James W. , Buttress Jessica A. , Baig Zunera , Herkenhoff Brigitte , Walter Stefan , Kurre Rainer , Deckers-Hebestreit Gabriele , Strahl Henrik 
Published: November 2019

AbstractAll living organisms adapt their membrane lipid composition in response to changes in their environment or diet. These conserved membrane-adaptive processes have been studied extensively. However, key concepts of membrane biology linked to regulation of lipid composition including homeoviscous adaptation maintaining stable levels of membrane fluidity, and gel-fluid phase separation resulting in domain formation, heavily rely upon in vitro studies with model membranes or lipid extracts. Using the bacterial model organisms Escherichia coli and Bacillus subtilis, we now show that inadequate in vivo membrane fluidity interferes with essential complex cellular processes including cytokinesis, envelope expansion, chromosome replication/segregation and maintenance of membrane potential. Furthermore, we demonstrate that very low membrane fluidity is indeed capable of triggering large-scale lipid phase separation and protein segregation in intact, protein-crowded membranes of living cells; a process that coincides with the minimal level of fluidity capable of supporting growth. Importantly, the in vivo lipid phase separation is not associated with a breakdown of the membrane diffusion barrier function, thus explaining why the phase-separation process induced by low fluidity is biologically reversible.