bluuebunny/crossref_metadata_2025_split huggingface dataset:
Particle‐in‐Cell Simulation of Electron Cyclotron Harmonic Waves Driven by a Loss Cone Distribution
Authors: Wu Yifan , Tao Xin , Liu Xu , Chen Lunjin , Xie Huasheng , Liu Kaijun , Horne Richard, B. 
Published: April 2020

AbstractElectron Cyclotron Harmonic (ECH) waves driven by a loss cone distribution are studied in this work by self‐consistent particle‐in‐cell simulations. These waves have been suggested to play an important role in diffuse auroral precipitation in the outer magnetosphere. However, particle simulation of this instability is difficult because the saturation amplitude of the wave driven by a realistic size loss cone distribution is very small. In this work we use an extraordinarily large number of particles to reduce simulation noise so that the growth and saturation of ECH waves can be investigated. Our simulation results are consistent with linear theory in terms of growth rate, and with observation in terms of wave amplitude. We demonstrate that the heating of cold electrons is negligible and nonresonant, different from previous conclusions, and suggest that the saturation of the wave is caused by the filling of the loss cone of hot electrons.
A Parameterization of Local and Remote Tidal Mixing
Authors: de Lavergne C. , Vic C. , Madec G. , Roquet F. , Waterhouse A. F. , Whalen C. B. , Cuypers Y. , Bouruet‐Aubertot P. , Ferron B. , Hibiya T. 
Published: April 2020

AbstractVertical mixing is often regarded as the Achilles' heel of ocean models. In particular, few models include a comprehensive and energy‐constrained parameterization of mixing by internal ocean tides. Here, we present an energy‐conserving mixing scheme which accounts for the local breaking of high‐mode internal tides and the distant dissipation of low‐mode internal tides. The scheme relies on four static two‐dimensional maps of internal tide dissipation, constructed using mode‐by‐mode Lagrangian tracking of energy beams from sources to sinks. Each map is associated with a distinct dissipative process and a corresponding vertical structure. Applied to an observational climatology of stratification, the scheme produces a global three‐dimensional map of dissipation which compares well with available microstructure observations and with upper‐ocean finestructure mixing estimates. This relative agreement, both in magnitude and spatial structure across ocean basins, suggests that internal tides underpin most of observed dissipation in the ocean interior at the global scale. The proposed parameterization is therefore expected to improve understanding, mapping, and modeling of ocean mixing.
Nonlinear increase, invisibility, and sign inversion of a localized fs-laser-induced refractive index change in crystals and glasses
Authors: Lapointe Jerome , Bérubé Jean-Philippe , Ledemi Yannick , Dupont Albert , Fortin Vincent , Messaddeq Younes , Vallée Réal 
Published: April 2020

AbstractMultiphoton absorption via ultrafast laser focusing is the only technology that allows a three-dimensional structural modification of transparent materials. However, the magnitude of the refractive index change is rather limited, preventing the technology from being a tool of choice for the manufacture of compact photonic integrated circuits. We propose to address this issue by employing a femtosecond-laser-induced electronic band-gap shift (FLIBGS), which has an exponential impact on the refractive index change for propagating wavelengths approaching the material electronic resonance, as predicted by the Kramers–Kronig relations. Supported by theoretical calculations, based on a modified Sellmeier equation, the Tauc law, and waveguide bend loss calculations, we experimentally show that several applications could take advantage of this phenomenon. First, we demonstrate waveguide bends down to a submillimeter radius, which is of great interest for higher-density integration of fs-laser-written quantum and photonic circuits. We also demonstrate that the refractive index contrast can be switched from negative to positive, allowing direct waveguide inscription in crystals. Finally, the effect of the FLIBGS can compensate for the fs-laser-induced negative refractive index change, resulting in a zero refractive index change at specific wavelengths, paving the way for new invisibility applications.
Host-microbiota interaction helps to explain the bottom-up effects of climate change on a small rodent species
Authors: Li Guoliang , Yin Baofa , Li Jing , Wang Jun , Wei Wanhong , Bolnick Daniel I , Wan Xinrong , Zhu Baoli , Zhang Zhibin 
Published: April 2020

Abstract
The population cycles of small rodents have puzzled biologists for centuries. There is a growing recognition of the cascading effects of climate change on the population dynamics of rodents. However, the ultimate cause for the bottom-up effects of precipitation is poorly understood, from a microbial perspective. Here, we conducted a precipitation manipulation experiment in the field, and three feeding trials with controlled diets in the laboratory. We found precipitation supplementation facilitated the recovery of a perennial rhizomatous grass (Leymus chinensis) species, which altered the diet composition and increase the intake of fructose and fructooligosaccharides for Brandt’s vole. Lab results showed that this nutrient shift was accompanied by the modulation of gut microbiota composition and functional pathways (especially for the degradation or biosynthesis of L-histidine). Particularly, the relative abundance of Eubacterium hallii was consistently increased after feeding voles with more L. chinensis, fructose or fructooligosaccharide. These modulations ultimately increased the production of short chain fatty acids (SCFAs) and boosted the growth of vole. This study provides evidence that the precipitation pulses cascades through the plant community to affect rodent gut microbiome. Our results highlight the importance of considering host-microbiota interaction when investigating rodent population responses to climate change.
Neurovegetative symptom subtypes in young people with major depressive disorder and their structural brain correlates
Authors: Toenders Yara J. , Schmaal Lianne , Harrison Ben J. , Dinga Richard , Berk Michael , Davey Christopher G. 
Published: April 2020

AbstractDepression is a leading cause of burden of disease among young people. Current treatments are not uniformly effective, in part due to the heterogeneous nature of major depressive disorder (MDD). Refining MDD into more homogeneous subtypes is an important step towards identifying underlying pathophysiological mechanisms and improving treatment of young people. In adults, symptom-based subtypes of depression identified using data-driven methods mainly differed in patterns of neurovegetative symptoms (sleep and appetite/weight). These subtypes have been associated with differential biological mechanisms, including immuno-metabolic markers, genetics and brain alterations (mainly in the ventral striatum, medial orbitofrontal cortex, insular cortex, anterior cingulate cortex amygdala and hippocampus). K-means clustering was applied to individual depressive symptoms from the Quick Inventory of Depressive Symptoms (QIDS) in 275 young people (15–25 years old) with MDD to identify symptom-based subtypes, and in 244 young people from an independent dataset (a subsample of the STAR*D dataset). Cortical surface area and thickness and subcortical volume were compared between the subtypes and 100 healthy controls using structural MRI. Three subtypes were identified in the discovery dataset and replicated in the independent dataset; severe depression with increased appetite, severe depression with decreased appetite and severe insomnia, and moderate depression. The severe increased appetite subtype showed lower surface area in the anterior insula compared to both healthy controls. Our findings in young people replicate the previously identified symptom-based depression subtypes in adults. The structural alterations of the anterior insular cortex add to the existing evidence of different pathophysiological mechanisms involved in this subtype.
The SCFSkp2 ubiquitin ligase complex modulates TRAIL-R2-induced apoptosis by regulating FLIP(L)
Authors: Roberts Jamie Z. , Holohan Caitriona , Sessler Tamas , Fox Jennifer , Crawford Nyree , Riley Joel S. , Khawaja Hajrah , Majkut Joanna , Evergren Emma , Humphreys Luke M. , Ferris Jennifer , Higgins Catherine , Espona-Fiedler Margarita , Moynagh Paul , McDade Simon S. , Longley Daniel B. 
Published: April 2020

AbstractTRAIL-R2 (DR5) is a clinically-relevant therapeutic target and a key target for immune effector cells. Herein, we identify a novel interaction between TRAIL-R2 and the Skp1-Cullin-1-F-box (SCF) Cullin-Ring E3 Ubiquitin Ligase complex containing Skp2 (SCFSkp2). We find that SCFSkp2 can interact with both TRAIL-R2’s pre-ligand association complex (PLAC) and ligand-activated death-inducing signalling complex (DISC). Moreover, Cullin-1 interacts with TRAIL-R2 in its active NEDDylated form. Inhibiting Cullin-1’s DISC recruitment using the NEDDylation inhibitor MLN4924 (Pevonedistat) or siRNA increased apoptosis induction in response to TRAIL. This correlated with enhanced levels of the caspase-8 regulator FLIP at the TRAIL-R2 DISC, particularly the long splice form, FLIP(L). We subsequently found that FLIP(L) (but not FLIP(S), caspase-8, nor the other core DISC component FADD) interacts with Cullin-1 and Skp2. Importantly, this interaction is enhanced when FLIP(L) is in its DISC-associated, C-terminally truncated p43-form. Prevention of FLIP(L) processing to its p43-form stabilises the protein, suggesting that by enhancing its interaction with SCFSkp2, cleavage to the p43-form is a critical step in FLIP(L) turnover. In support of this, we found that silencing any of the components of the SCFSkp2 complex inhibits FLIP ubiquitination, while overexpressing Cullin-1/Skp2 enhances its ubiquitination in a NEDDylation-dependent manner. DISC recruitment of TRAF2, previously identified as an E3 ligase for caspase-8 at the DISC, was also enhanced when Cullin-1’s recruitment was inhibited, although its interaction with Cullin-1 was found to be mediated indirectly via FLIP(L). Notably, the interaction of p43-FLIP(L) with Cullin-1 disrupts its ability to interact with FADD, caspase-8 and TRAF2. Collectively, our results suggest that processing of FLIP(L) to p43-FLIP(L) at the TRAIL-R2 DISC enhances its interaction with co-localised SCFSkp2, leading to disruption of p43-FLIP(L)’s interactions with other DISC components and promoting its ubiquitination and degradation, thereby modulating TRAIL-R2-mediated apoptosis.
Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways
Authors: Duan Chenyang , Kuang Lei , Xiang Xinming , Zhang Jie , Zhu Yu , Wu Yue , Yan Qingguang , Liu Liangming , Li Tao 
Published: April 2020

Abstract
The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of ischemia. Drp1 appeared to inhibit mitophagy by upregulating mito-Clec16a, which suppressed mito-Parkin recruitment and subsequently impaired the formation of autophagosomes in vascular tissues after ischemic injury. Moreover, ischemia-induced Drp1 activation enhanced apoptosis through inducing mitochondrial translocation of BAX and thereby increasing release of Cytochrome C to activate caspase-3/-9 signalling. Furthermore, Drp1 mediated metabolic disorders and inhibited the levels of mitochondrial glutathione to impair free radical scavenging, leading to further increases in ROS and the exacerbation of mitochondrial dysfunction after ischemic injury. Together, our data suggest a critical role for Drp1 in ischemic injury.
P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint
Authors: Wang Yang , Tian Jing , Huang Chao , Ma Jiao , Hu Gaolei , Chen Yalan , Wang Tianshi , Cai Rong , Zuo Yong , Tan Hongsheng , Fan Qiuju , Dong Baijun , Xue Wei , Yi Jing , Chen Guoqiang , Tu Jun , Cheng Jinke 
Published: April 2020

AbstractIn response to DNA damage, p53-mediated signaling is regulated by protein phosphorylation and ubiquitination to precisely control G2 checkpoint. Here we demonstrated that protein SUMOylation also engaged in regulation of p53-mediated G2 checkpoint. We found that G2 DNA damage suppressed SENP3 phosphorylation at G2/M phases in p53-dependent manner. We further found that the suppression of SENP3 phosphorylation was crucial for efficient DNA damage/p53-induced G2 checkpoint and G2 arrest. Mechanistically, we identified Cdh1, a subunit of APC/C complex, was a SUMOylated protein at G2/M phase. SENP3 could de-SUMOylate Cdh1. DNA damage/p53-induced suppression of SENP3 phosphorylation activated SENP3 de-SUMOylation of Cdh. De-SUMOylation promoted Cdh1 de-phosphorylation by phosphatase Cdc14B, and then activated APC/CCdh1 E3 ligase activity to ubiquitate and degrade Polo-like kinase 1 (Plk1) in process of G2 checkpoint. These data reveal that p53-mediated inhibition of SENP3 phosphorylation regulates the activation of Cdc14b-APC/CCdh1-Plk1 axis to control DNA damage-induced G2 checkpoint.
Duchenne muscular dystrophy–like phenotype in an LGMD2I patient with novel FKRP gene variants
Authors: Okazaki Tetsuya , Matsuura Kaori , Kasagi Noriko , Adachi Kaori , Kai Masachika , Okubo Mariko , Nishino Ichizo , Nanba Eiji , Maegaki Yoshihiro 
Published: April 2020

AbstractA 32-year-old man initially received a diagnosis of Duchenne muscular dystrophy (DMD). Genetic analysis revealed two novel heterozygous FKRP variants: c.169G>A (p.Glu57Lys) and c.692G>A (p.Trp231*). These results indicated that the patient had limb-girdle muscular dystrophy type 2I (LGMD2I) caused by recessive FKRP variants. Patients with LGMD2I and DMD have many overlapping phenotypes. LGMD2I should be considered in patients who have a DMD phenotype but not a DMD pathogenic variant.
Wnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord
Authors: Zhang Jun , Chandrasekaran Gopalakrishnan , Li Wenting , Kim Dong-Young , Jeong In Young , Lee So-Hyun , Liang Ting , Bae Jin Young , Choi Isaac , Kang Hyuno , Maeng Jin-Soo , Kim Myeong-Kyu , Lee Taewon , Park Seung Woo , Kim Min Jung , Kim Hyung-Seok , Ro Hyunju , Bae Yong Chul , Park Hae-Chul , Choi Eun Young , Choi Seok-Yong 
Published: April 2020

AbstractEpendymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.
α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease
Authors: Lindestam Arlehamn Cecilia S. , Dhanwani Rekha , Pham John , Kuan Rebecca , Frazier April , Rezende Dutra Juliana , Phillips Elizabeth , Mallal Simon , Roederer Mario , Marder Karen S. , Amara Amy W. , Standaert David G. , Goldman Jennifer G. , Litvan Irene , Peters Bjoern , Sulzer David , Sette Alessandro 
Published: April 2020

AbstractA diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.
A fungal pathogen induces systemic susceptibility and systemic shifts in wheat metabolome and microbiome composition
Authors: Seybold Heike , Demetrowitsch Tobias J. , Hassani M. Amine , Szymczak Silke , Reim Ekaterina , Haueisen Janine , Lübbers Luisa , Rühlemann Malte , Franke Andre , Schwarz Karin , Stukenbrock Eva H. 
Published: April 2020

AbstractYield losses caused by fungal pathogens represent a major threat to global food production. One of the most devastating fungal wheat pathogens isZymoseptoria tritici. Despite the importance of this fungus, the underlying mechanisms of plant–pathogen interactions are poorly understood. Here we present a conceptual framework based on coinfection assays, comparative metabolomics, and microbiome profiling to study the interaction ofZ. triticiin susceptible and resistant wheat. We demonstrate thatZ. triticisuppresses the production of immune-related metabolites in a susceptible cultivar. Remarkably, this fungus-induced immune suppression spreads within the leaf and even to other leaves, a phenomenon that we term “systemic induced susceptibility”. Using a comparative metabolomics approach, we identify defense-related biosynthetic pathways that are suppressed and induced in susceptible and resistant cultivars, respectively. We show that these fungus-induced changes correlate with changes in the wheat leaf microbiome. Our findings suggest that immune suppression by this hemibiotrophic pathogen impacts specialized plant metabolism, alters its associated microbial communities, and renders wheat vulnerable to further infections.
High throughput pMHC-I tetramer library production using chaperone-mediated peptide exchange
Authors: Overall Sarah A. , Toor Jugmohit S. , Hao Stephanie , Yarmarkovich Mark , Sara M. O’Rourke  , Morozov Giora I. , Nguyen Son , Japp Alberto Sada , Gonzalez Nicolas , Moschidi Danai , Betts Michael R. , Maris John M. , Smibert Peter , Sgourakis Nikolaos G. 
Published: April 2020

AbstractPeptide exchange technologies are essential for the generation of pMHC-multimer libraries used to probe diverse, polyclonal TCR repertoires in various settings. Here, using the molecular chaperone TAPBPR, we develop a robust method for the capture of stable, empty MHC-I molecules comprising murine H2 and human HLA alleles, which can be readily tetramerized and loaded with peptides of choice in a high-throughput manner. Alternatively, catalytic amounts of TAPBPR can be used to exchange placeholder peptides with high affinity peptides of interest. Using the same system, we describe high throughput assays to validate binding of multiple candidate peptides on empty MHC-I/TAPBPR complexes. Combined with tetramer-barcoding via a multi-modal cellular indexing technology, ECCITE-seq, our approach allows a combined analysis of TCR repertoires and other T cell transcription profiles together with their cognate antigen specificities in a single experiment. The new approach allows TCR/pMHC interactions to be interrogated easily at large scale.
Rapid subduction initiation and magmatism in the Western Pacific driven by internal vertical forces
Authors: Maunder B. , Prytulak J. , Goes S. , Reagan M. 
Published: April 2020

AbstractPlate tectonics requires the formation of plate boundaries. Particularly important is the enigmatic initiation of subduction: the sliding of one plate below the other, and the primary driver of plate tectonics. A continuous, in situ record of subduction initiation was recovered by the International Ocean Discovery Program Expedition 352, which drilled a segment of the fore-arc of the Izu-Bonin-Mariana subduction system, revealing a distinct magmatic progression with a rapid timescale (approximately 1 million years). Here, using numerical models, we demonstrate that these observations cannot be produced by previously proposed horizontal external forcing. Instead a geodynamic evolution that is dominated by internal, vertical forces produces both the temporal and spatial distribution of magmatic products, and progresses to self-sustained subduction. Such a primarily internally driven initiation event is necessarily whole-plate scale and the rock sequence generated (also found along the Tethyan margin) may be considered as a smoking gun for this type of event.
Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin
Authors: Jacques Laura C. , Panagiotou Stavros , Baltazar Murielle , Senghore Madikay , Khandaker Shadia , Xu Rong , Bricio-Moreno Laura , Yang Marie , Dowson Christopher G. , Everett Dean B. , Neill Daniel R. , Kadioglu Aras 
Published: April 2020

AbstractStreptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1.
A fully orthogonal system for protein synthesis in bacterial cells
Authors: Aleksashin Nikolay A. , Szal Teresa , d’Aquino Anne E. , Jewett Michael C. , Vázquez-Laslop Nora , Mankin Alexander S. 
Published: April 2020

AbstractRibosome engineering is a powerful approach for expanding the catalytic potential of the protein synthesis apparatus. Due to the potential detriment the properties of the engineered ribosome may have on the cell, the designer ribosome needs to be functionally isolated from the translation machinery synthesizing cellular proteins. One solution to this problem was offered by Ribo-T, an engineered ribosome with tethered subunits which, while producing a desired protein, could be excluded from general translation. Here, we provide a conceptually different design of a cell with two orthogonal protein synthesis systems, where Ribo-T produces the proteome, while the dissociable ribosome is committed to the translation of a specific mRNA. The utility of this system is illustrated by generating a comprehensive collection of mutants with alterations at every rRNA nucleotide of the peptidyl transferase center and isolating gain-of-function variants that enable the ribosome to overcome the translation termination blockage imposed by an arrest peptide.