bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide triggers the assembly of “type II” stress granules linked to decreased cell viability
Authors: Aulas Anaïs , Lyons Shawn M. , Fay Marta M. , Anderson Paul , Ivanov Pavel 
Published: November 2018

AbstractWe show that 3-morpholinosydnonimine (SIN-1)-induced nitric oxide (NO) triggers the formation of SGs. Whereas the composition of NO-induced SGs is initially similar to sodium arsenite (SA)-induced type I (cytoprotective) SGs, the progressive loss of eIF3 over time converts them into pro-death (type II) SGs. NO-induced SG assembly requires the phosphorylation of eIF2α, but the transition to type II SGs is temporally linked to the mTOR-regulated displacement of eIF4F complexes from the m7 guanine cap. Whereas SA does not affect mitochondrial morphology or function, NO alters mitochondrial integrity and function, resulting in increased ROS production, decreased cytoplasmic ATP, and plasma membrane permeabilization, all of which are supported by type II SG assembly. Thus, cellular energy balance is linked to the composition and function of NO-induced SGs in ways that determine whether cells live or die.
Continuous negative-to-positive tuning of thermal expansion achieved by controlled gas sorption in porous coordination frameworks
Authors: Auckett Josie E. , Barkhordarian Arnold A. , Ogilvie Stephen H. , Duyker Samuel G. , Chevreau Hubert , Peterson Vanessa K. , Kepert Cameron J. 
Published: November 2018

AbstractControl of the thermomechanical properties of functional materials is of great fundamental and technological significance, with the achievement of zero or negative thermal expansion behavior being a key goal for various applications. A dynamic, reversible mode of control is demonstrated for the first time in two Prussian blue derivative frameworks whose coefficients of thermal expansion are tuned continuously from negative to positive values by varying the concentration of adsorbed CO2. A simple empirical model that captures site-specific guest contributions to the framework expansion is derived, and displays excellent agreement with the observed lattice behaviour.
Intellectual synthesis in mentorship determines success in academic careers
Authors: Liénard Jean F. , Achakulvisut Titipat , Acuna Daniel E. , David Stephen V. 
Published: November 2018

AbstractAs academic careers become more competitive, junior scientists need to understand the value that mentorship brings to their success in academia. Previous research has found that, unsurprisingly, successful mentors tend to train successful students. But what characteristics of this relationship predict success, and how? We analyzed an open-access database of 18,856 researchers who have undergone both graduate and postdoctoral training, compiled across several fields of biomedical science with an emphasis on neuroscience. Our results show that postdoctoral mentors were more instrumental to trainees’ success compared to graduate mentors. Trainees’ success in academia was also predicted by the degree of intellectual synthesis between their graduate and postdoctoral mentors. Researchers were more likely to succeed if they trained under mentors with disparate expertise and integrated that expertise into their own work. This pattern has held up over at least 40 years, despite fluctuations in the number of students and availability of independent research positions.
Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy
Authors: Gayi Elinam , Neff Laurence A. , Massana Muñoz Xènia , Ismail Hesham M. , Sierra Marta , Mercier Thomas , Décosterd Laurent A. , Laporte Jocelyn , Cowling Belinda S. , Dorchies Olivier M. , Scapozza Leonardo 
Published: November 2018

AbstractX-linked myotubular myopathy (XLMTM, also known as XLCNM) is a severe congenital muscular disorder due to mutations in the myotubularin gene, MTM1. It is characterized by generalized hypotonia, leading to neonatal death of most patients. No specific treatment exists. Here, we show that tamoxifen, a well-known drug used against breast cancer, rescues the phenotype of Mtm1-deficient mice. Tamoxifen increases lifespan several-fold while improving overall motor function and preventing disease progression including lower limb paralysis. Tamoxifen corrects functional, histological and molecular hallmarks of XLMTM, with improved force output, myonuclei positioning, myofibrillar structure, triad number, and excitation-contraction coupling. Tamoxifen normalizes the expression level of the XLMTM disease modifiers DNM2 and PI3KC2B, likely contributing to the phenotypic rescue. Our findings demonstrate that tamoxifen is a promising candidate for clinical evaluation in XLMTM patients.
Palladium concave nanocrystals with high-index facets accelerate ascorbate oxidation in cancer treatment
Authors: Chong Yu , Dai Xing , Fang Ge , Wu Renfei , Zhao Lin , Ma Xiaochuan , Tian Xin , Lee Sangyun , Zhang Chao , Chen Chunying , Chai Zhifang , Ge Cuicui , Zhou Ruhong 
Published: November 2018

AbstractIntravenous pharmacological dose of ascorbate has been proposed as a potential antitumor therapy; however, its therapeutic efficacy is limited due to the slow autoxidation. Here, we report that palladium (Pd) nanocrystals, which possess intrinsic oxidase-like activity, accelerate the autoxidation of ascorbate, leading to the enhancement of its antitumor efficacy. The oxidase-like activity of Pd nanocrystals was facet-dependent, with the concave nanostructure enclosed by high-index facets catalyzing ascorbate autoxidation more efficiently than the planar nanostructure enclosed by low-index facets. Our first-principles calculations provide the underlying molecular mechanisms for the facet-dependent activation of O2 molecule and subsequent ascorbate oxidation. Further in vitro and in vivo assays demonstrate the enhancement of the antitumor efficacy of ascorbate with these Pd concave nanocubes. Our animal experiments also indicate the combined approach with both ascorbate and Pd concave nanocubes displays an even better efficacy than currently available clinical medicines, with no obvious cytotoxicity to normal cells.
Competitive repopulation of an empty microglial niche yields functionally distinct subsets of microglia-like cells
Authors: Lund Harald , Pieber Melanie , Parsa Roham , Han Jinming , Grommisch David , Ewing Ewoud , Kular Lara , Needhamsen Maria , Espinosa Alexander , Nilsson Emma , Överby Anna K. , Butovsky Oleg , Jagodic Maja , Zhang Xing-Mei , Harris Robert A. 
Published: November 2018

AbstractCirculating monocytes can compete for virtually any tissue macrophage niche and become long-lived replacements that are phenotypically indistinguishable from their embryonic counterparts. As the factors regulating this process are incompletely understood, we studied niche competition in the brain by depleting microglia with >95% efficiency using Cx3cr1CreER/+R26DTA/+ mice and monitored long-term repopulation. Here we show that the microglial niche is repopulated within weeks by a combination of local proliferation of CX3CR1+F4/80lowClec12a– microglia and infiltration of CX3CR1+F4/80hiClec12a+ macrophages that arise directly from Ly6Chi monocytes. This colonization is independent of blood brain barrier breakdown, paralleled by vascular activation, and regulated by type I interferon. Ly6Chi monocytes upregulate microglia gene expression and adopt microglia DNA methylation signatures, but retain a distinct gene signature from proliferating microglia, displaying altered surface marker expression, phagocytic capacity and cytokine production. Our results demonstrate that monocytes are imprinted by the CNS microenvironment but remain transcriptionally, epigenetically and functionally distinct.
Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
Authors: Aulicino Anna , Rue-Albrecht Kevin C. , Preciado-Llanes Lorena , Napolitani Giorgio , Ashley Neil , Cribbs Adam , Koth Jana , Lagerholm B. Christoffer , Ambrose Tim , Gordon Melita A. , Sims David , Simmons Alison 
Published: November 2018

AbstractNon-typhoidalSalmonella(NTS) are highly prevalent food-borne pathogens. Recently, a highly invasive, multi-drug resistantS. Typhimurium, ST313, emerged as a major cause of bacteraemia in children and immunosuppressed adults, however the pathogenic mechanisms remain unclear. Here, we utilize invasive and non-invasiveSalmonellastrains combined with single-cell RNA-sequencing to study the transcriptome of individual infected and bystander monocyte-derived dendritic cells (MoDCs) implicated in disseminating invasive ST313. Compared with non-invasiveSalmonella, ST313 directs a highly heterogeneous innate immune response. Bystander MoDCs exhibit a hyper-activated profile potentially diverting adaptive immunity away from infected cells. MoDCs harbouring invasiveSalmonelladisplay higher expression ofIL10andMARCH1concomitant with lower expression ofCD83to evade adaptive immune detection. Finally, we demonstrate how these mechanisms conjointly restrain MoDC-mediated activation ofSalmonella-specific CD4+T cell clones. Here, we show how invasive ST313 exploits discrete evasion strategies within infected and bystander MoDCs to mediate its dissemination in vivo.
Manipulation of the dephasing time by strong coupling between localized and propagating surface plasmon modes
Authors: Yang Jinghuan , Sun Quan , Ueno Kosei , Shi Xu , Oshikiri Tomoya , Misawa Hiroaki , Gong Qihuang 
Published: November 2018

AbstractStrong coupling between two resonance modes leads to the formation of new hybrid modes exhibiting disparate characteristics owing to the reversible exchange of information between different uncoupled modes. Here, we realize the strong coupling between the localized surface plasmon resonance and surface plasmon polariton Bloch wave using multilayer nanostructures. An anticrossing behavior with a splitting energy of 144 meV can be observed from the far-field spectra. More importantly, we investigate the near-field properties in both the frequency and time domains using photoemission electron microscopy. In the frequency domain, the near-field spectra visually demonstrate normal-mode splitting and display the extent of coupling. Importantly, the variation of the dephasing time of the hybrid modes against the detuning is observed directly in the time domain. These findings signify the evolution of the dissipation and the exchange of information in plasmonic strong coupling systems and pave the way to manipulate the dephasing time of plasmon modes, which can benefit many applications of plasmonics.
Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4-indeuced M2a-subtype macrophage activation in obesity
Authors: Kubota Tetsuya , Inoue Mariko , Kubota Naoto , Takamoto Iseki , Mineyama Tomoka , Iwayama Kaito , Tokuyama Kumpei , Moroi Masao , Ueki Kohjiro , Yamauchi Toshimasa , Kadowaki Takashi 
Published: November 2018

AbstractM2a-subtype macrophage activation is known to be impaired in obesity, although the underlying mechanisms remain poorly understood. Herein, we demonstrate that, the IL-4/Irs2/Akt pathway is selectively impaired, along with decreased macrophage Irs2 expression, although IL-4/STAT6 pathway is maintained. Indeed, myeloid cell-specific Irs2-deficient mice show impairment of IL-4-induced M2a-subtype macrophage activation, as a result of stabilization of the FoxO1/HDAC3/NCoR1 corepressor complex, resulting in insulin resistance under the HF diet condition. Moreover, the reduction of macrophage Irs2 expression is mediated by hyperinsulinemia via the insulin receptor (IR). In myeloid cell-specific IR-deficient mice, the IL-4/Irs2 pathway is preserved in the macrophages, which results in a reduced degree of insulin resistance, because of the lack of IR-mediated downregulation of Irs2. We conclude that downregulation of Irs2 in macrophages caused by hyperinsulinemia is responsible for systemic insulin resistance via impairment of M2a-subtype macrophage activation in obesity.
Apoptosis of intestinal epithelial cells restricts Clostridium difficile infection in a model of pseudomembranous colitis
Authors: Saavedra Pedro H. V. , Huang Linyan , Ghazavi Farzaneh , Kourula Stephanie , Vanden Berghe Tom , Takahashi Nozomi , Vandenabeele Peter , Lamkanfi Mohamed 
Published: November 2018

AbstractClostridium difficile is the leading cause of pseudomembranous colitis in hospitalized patients. C. difficile enterotoxins TcdA and TcdB promote this inflammatory condition via a cytotoxic response on intestinal epithelial cells (IECs), but the underlying mechanisms are incompletely understood. Additionally, TcdA and TcdB engage the Pyrin inflammasome in macrophages, but whether Pyrin modulates CDI pathophysiology is unknown. Here we show that the Pyrin inflammasome is not functional in IECs and that Pyrin signaling is dispensable for CDI-associated IEC death and for in vivo pathogenesis. Instead, our studies establish that C. difficile enterotoxins induce activation of executioner caspases 3/7 via the intrinsic apoptosis pathway, and demonstrate that caspase-3/7-mediated IEC apoptosis is critical for in vivo host defense during early stages of CDI. In conclusion, our findings dismiss a critical role for inflammasomes in CDI pathogenesis, and identify IEC apoptosis as a host defense mechanism that restricts C. difficile infection in vivo.
The 27 kDa Trypanosoma brucei Pentatricopeptide Repeat Protein is a G-tract Specific RNA Binding Protein
Authors: Kamba Pakoyo F. , Dickson David A. , White Neil A. , Ekstrom Jennifer L. , Koslowsky Donna J. , Hoogstraten Charles G. 
Published: November 2018

AbstractPentatricopeptide repeat (PPR) proteins, a helical repeat family of organellar RNA binding proteins, play essential roles in post-transcriptional RNA processing. In Trypanosoma brucei, an expanded family of PPR proteins localize to the parasite’s single mitochondrion, where they are believed to perform important roles in both RNA processing and translation. We studied the RNA binding specificity of the simplest T. brucei PPR protein (KRIPP11) using electrophoretic mobility shift assays, fluorescence anisotropy, circular dichroism spectroscopy, and in vitro selection. We found KRIPP11 to be an RNA binding protein with specificity for sequences of four or more consecutive guanosine residues (G-tracts). Such G-tracts are dramatically enriched in T. brucei mitochondrial transcripts that are destined for extensive uridine insertion/deletion editing but are not present in mRNAs following editing. We further found that the quadruplex oligoguanosine RNA conformation is preferentially recognized by KRIPP11 over other conformational forms, and is bound without disruption of the quadruplex structure. In combination with prior data demonstrating association of KRIPP11 with the small ribosomal subunit, these results suggest possible roles for KRIPP11 in bridging mRNA maturation and translation or in facilitating translation of unusual dual-coded open reading frames.
Electrophysiological properties of human beta-cell lines EndoC-βH1 and -βH2 conform with human beta-cells
Authors: Hastoy Benoît , Godazgar Mahdieh , Clark Anne , Nylander Vibe , Spiliotis Ioannis , van de Bunt Martijn , Chibalina Margarita V. , Barrett Amy , Burrows Carla , Tarasov Andrei I. , Scharfmann Raphael , Gloyn Anna L. , Rorsman Patrik 
Published: November 2018

AbstractLimited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-βH1 and EndoC-βH2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+]i, membrane depolarisation and increased action potential firing. Similar to human primary beta cells, KATP channel activity is low at 1 mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the KATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electron-dense core surrounded by a thin clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and thus represent a useful experimental model.
Microfluidic Assay Measures Increased Neutrophil Extracellular Traps Circulating in Blood after Burn Injuries
Authors: Otawara Masayuki , Roushan Maedeh , Wang Xiao , Ellett Felix , Yu Yong-Ming , Irimia Daniel 
Published: November 2018

AbstractCell-free DNA (cf-DNA) concentration in human plasma is often increased after burn and trauma injuries. Two major sources of cf-DNA are the parenchymal cells damaged by the injury and various circulating cells indirectly altered by the response to injury. The cf-DNA originating from neutrophils, also known as circulating neutrophil extracellular traps (cNETs), is of notable interest because cNETs have been associated with pathological processes in other conditions, including cancer, autoimmunity, etc. Both intact chromatin and oligonucleotides, which are the by-product of cf-DNA degradation, are assumed to contribute to the cf-DNA in patients. However, traditional assays for cf-DNA quantification do not distinguish between cNETs and cf-DNA of other origins and do not differentiate between intact chromatin and oligonucleotides. Here we measure the amount of intact cNETs in the circulation, using a microfluidic device that mechanically traps chromatin fibers directly from blood and an immunofluorescence protocol that detects neutrophil-specific proteins associated with chromatin. In a rat model of burn injury, we determined that the chromatin fibers in the circulation after injury originate exclusively from neutrophils and are cNETs. We found that the concentration of cNETs surges the first day after injury and then decreases slowly over several days. In a secondary sepsis model, which involved a burn injury followed by cecal-ligation-puncture, we measured additional increases in cNETs in the days after sepsis was induced. These results validate a microfluidic assay for the quantification of cNETs and will facilitate fruther studies probing the contribution of cNETs to complications after burns and sepsis.
Trends and regional variations in the administrative prevalence of attention-deficit/hyperactivity disorder among children and adolescents in Germany
Authors: Akmatov M. K. , Steffen A. , Holstiege J. , Hering R. , Schulz M. , Bätzing J. 
Published: November 2018

AbstractThere is a controversy regarding temporal trends in prevalence of attention-deficit/hyperactivity disorder (ADHD). Using nationwide claims data containing data for approximately six million statutory health insured children we aimed to examine a) trends of ADHD administrative prevalence during 2009–2016; b) regional variations in prevalence, and c) factors associated with an increased chance of ADHD diagnosis. The ICD-10 code ‘F90-hyperkinetic disorder’ was used to define an ADHD case. Global and Local Moran’s I tests were used to examine the spatial autocorrelation and k-means-cluster analysis to examine the course of ADHD prevalence in administrative districts over years. Two-level logistic regression was applied to examine individual- and district-level factors associated with ADHD diagnosis. The administrative prevalence of ADHD was 4.33% (95% CI: 4.31–4.34%). We observed pronounced small-area differences on the district level with prevalences ranging between 1.6% and 9.7%. There was evidence of strong spatial autocorrelation (Global Moran’s I: 0.46, p < 0.0001). The k-means-method identified six clusters of different size; all with a stagnating trend in the prevalence over the observation period of eight years. On the district level, a lower proportion of foreign citizens, and a higher density of paediatric psychiatrists and paediatricians were positively associated with ADHD with a more pronounced effect in urban districts.
An altered gene expression profile in tyramine-exposed intestinal cell cultures supports the genotoxicity of this biogenic amine at dietary concentrations
Authors: del Rio Beatriz , Redruello Begoña , Ladero Victor , Cal Santiago , Obaya Alvaro J. , Alvarez Miguel A. 
Published: November 2018

AbstractTyramine, histamine and putrescine are the most commonly detected and most abundant biogenic amines (BA) in food. The consumption of food with high concentrations of these BA is discouraged by the main food safety agencies, but legal limits have only been set for histamine. The present work reports a transcriptomic investigation of the oncogenic potential of the above-mentioned BA, as assessed in the HT29 human intestinal epithelial cell line. Tyramine had a greater effect on the expression of genes involved in tumorigenesis than did histamine or putrescine. Since some of the genes that showed altered expression in tyramine-exposed cells are involved in DNA damage and repair, the effect of this BA on the expression of other genes involved in the DNA damage response was investigated. The results suggest that tyramine might be genotoxic for intestinal cells at concentrations easily found in BA-rich food. Moreover, a role in promoting intestinal cancer cannot be excluded.
Taxon-specific responses to different forestry treatments in a temperate forest
Authors: Elek Zoltán , Kovács Bence , Aszalós Réka , Boros Gergely , Samu Ferenc , Tinya Flóra , Ódor Péter 
Published: November 2018

AbstractThere are only few studies that explore the ecological consequences of forest management on several organism groups. We studied the short-term effects of four forestry treatments including preparation cutting, clear-cutting, retention tree group and gap-cutting in a temperate managed forest on the assemblage structure of understory plants, enchytraeid worms, spiders and ground beetles. Here we show, that the effect of treatments on the different facets of assemblage structure was taxon-specific. Clear-cutting and retention tree group strongly impoverished enchytraeids assemblages. Even if the species richness and cover of plants increased in clear-cutting and gap-cutting, their species composition moderately changed after treatments. For spiders only their species composition was influenced by the treatments, while the response of ground beetles was slightly affected. Short-term effect of forest management interventions on biodiversity might be compensated by the dispersal (spiders, ground beetles) and resilience (plants) of organism groups, however sedentary soil organism showed high sensitivity.