bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring cytosolic H2O2 fluctuations arising from altered plasma membrane gradients or from mitochondrial activity
Authors: Carmona Mercè , de Cubas Laura , Bautista Eric , Moral-Blanch Marta , Medraño-Fernández Iria , Sitia Roberto , Boronat Susanna , Ayté José , Hidalgo Elena 
Published: October 2019

AbstractGenetically encoded probes monitoring H2O2 fluctuations in living organisms are key to decipher redox signaling events. Here we use a new probe, roGFP2-Tpx1.C169S, to monitor pre-toxic fluctuations of peroxides in fission yeast, where the concentrations linked to signaling or to toxicity have been established. This probe is able to detect nanomolar fluctuations of intracellular H2O2 caused by extracellular peroxides; expression of human aquaporin 8 channels H2O2 entry into fission yeast decreasing membrane gradients. The probe also detects H2O2 bursts from mitochondria after addition of electron transport chain inhibitors, the extent of probe oxidation being proportional to the mitochondrial activity. The oxidation of this probe is an indicator of steady-state levels of H2O2 in different genetic backgrounds. Metabolic reprogramming during growth in low-glucose media causes probe reduction due to the activation of antioxidant cascades. We demonstrate how peroxiredoxin-based probes can be used to monitor physiological H2O2 fluctuations.
De novo identification of essential protein domains from CRISPR-Cas9 tiling-sgRNA knockout screens
Authors: He Wei , Zhang Liang , Villarreal Oscar D. , Fu Rongjie , Bedford Ella , Dou Jingzhuang , Patel Anish Y. , Bedford Mark T. , Shi Xiaobing , Chen Taiping , Bartholomew Blaine , Xu Han 
Published: October 2019

AbstractHigh-throughput CRISPR-Cas9 knockout screens using a tiling-sgRNA design permit in situ evaluation of protein domain function. Here, to facilitate de novo identification of essential protein domains from such screens, we propose ProTiler, a computational method for the robust mapping of CRISPR knockout hyper-sensitive (CKHS) regions, which refer to the protein regions associated with a strong sgRNA dropout effect in the screens. Applied to a published CRISPR tiling screen dataset, ProTiler identifies 175 CKHS regions in 83 proteins. Of these CKHS regions, more than 80% overlap with annotated Pfam domains, including all of the 15 known drug targets in the dataset. ProTiler also reveals unannotated essential domains, including the N-terminus of the SWI/SNF subunit SMARCB1, which is validated experimentally. Surprisingly, the CKHS regions are negatively correlated with phosphorylation and acetylation sites, suggesting that protein domains and post-translational modification sites have distinct sensitivities to CRISPR-Cas9 mediated amino acids loss.
The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis
Authors: Capalbo Luisa , Bassi Zuni I. , Geymonat Marco , Todesca Sofia , Copoiu Liviu , Enright Anton J. , Callaini Giuliano , Riparbelli Maria Giovanna , Yu Lu , Choudhary Jyoti S. , Ferrero Enrico , Wheatley Sally , Douglas Max E. , Mishima Masanori , D’Avino Pier Paolo 
Published: October 2019

AbstractThe midbody is an organelle assembled at the intercellular bridge between the two daughter cells at the end of mitosis. It controls the final separation of the daughter cells and has been involved in cell fate, polarity, tissue organization, and cilium and lumen formation. Here, we report the characterization of the intricate midbody protein-protein interaction network (interactome), which identifies many previously unknown interactions and provides an extremely valuable resource for dissecting the multiple roles of the midbody. Initial analysis of this interactome revealed that PP1β-MYPT1 phosphatase regulates microtubule dynamics in late cytokinesis and de-phosphorylates the kinesin component MKLP1/KIF23 of the centralspindlin complex. This de-phosphorylation antagonizes Aurora B kinase to modify the functions and interactions of centralspindlin in late cytokinesis. Our findings expand the repertoire of PP1 functions during mitosis and indicate that spatiotemporal changes in the distribution of kinases and counteracting phosphatases finely tune the activity of cytokinesis proteins.
Archaeal lipid biomarker constraints on the Paleocene-Eocene carbon isotope excursion
Authors: Elling Felix J. , Gottschalk Julia , Doeana Katiana D. , Kusch Stephanie , Hurley Sarah J. , Pearson Ann 
Published: October 2019

AbstractA negative carbon isotope excursion recorded in terrestrial and marine archives reflects massive carbon emissions into the exogenic carbon reservoir during the Paleocene-Eocene Thermal Maximum. Yet, discrepancies in carbon isotope excursion estimates from different sample types lead to substantial uncertainties in the source, scale, and timing of carbon emissions. Here we show that membrane lipids of marine planktonic archaea reliably record both the carbon isotope excursion and surface ocean warming during the Paleocene-Eocene Thermal Maximum. Novel records of the isotopic composition of crenarchaeol constrain the global carbon isotope excursion magnitude to −4.0 ± 0.4‰, consistent with emission of >3000 Pg C from methane hydrate dissociation or >4400 Pg C for scenarios involving emissions from geothermal heating or oxidation of sedimentary organic matter. A pre-onset excursion in the isotopic composition of crenarchaeol and ocean temperature highlights the susceptibility of the late Paleocene carbon cycle to perturbations and suggests that climate instability preceded the Paleocene-Eocene Thermal Maximum.
A Modified Collagen Dressing Induces Transition of Inflammatory to Reparative Phenotype of Wound Macrophages
Authors: Das Amitava , Abas Motaz , Biswas Nirupam , Banerjee Pradipta , Ghosh Nandini , Rawat Atul , Khanna Savita , Roy Sashwati , Sen Chandan K. 
Published: October 2019

AbstractCollagen containing wound-care dressings are extensively used. However, the mechanism of action of these dressings remain unclear. Earlier studies utilizing a modified collagen gel (MCG) dressing demonstrated improved vascularization of ischemic wounds and better healing outcomes. Wound macrophages are pivotal in facilitating wound angiogenesis and timely healing. The current study was designed to investigate the effect of MCG on wound macrophage phenotype and function. MCG augmented recruitment of macrophage at the wound-site, attenuated pro-inflammatory and promoted anti-inflammatory macrophage polarization. Additionally, MCG increased anti-inflammatory IL-10, IL-4 and pro-angiogenic VEGF production, indicating a direct role of MCG in resolving wound inflammation and improving angiogenesis. At the wound-site, impairment in clearance of apoptotic cell bioburden enables chronic inflammation. Engulfment of apoptotic cells by macrophages (efferocytosis) resolves inflammationviaa miR-21-PDCD4-IL-10 pathway. MCG-treated wound macrophages exhibited a significantly bolstered efferocytosis index. Such favorable outcome significantly induced miR-21 expression. MCG-mediated IL-10 production was dampened under conditions of miR-21 knockdown pointing towards miR-21 as a causative factor. Pharmacological inhibition of JNK attenuated IL-10 production by MCG, implicating miR-21-JNK pathway in MCG-mediated IL-10 production by macrophages. This work provides direct evidence demonstrating that a collagen-based wound-care dressing may influence wound macrophage function and therefore modify wound inflammation outcomes.
Mutational analysis of renal angiomyolipoma associated with tuberous sclerosis complex and the outcome of short-term everolimus therapy
Authors: Ni Jianxin , Yan Fengqi , Qin Weijun , Yu Lei , Zhang Geng , Liu Fei , Yang Xiaojian , Yang Bo , Hao Chunlin , Wang Teng , Liu Pengfei , Yuan Jianlin , Wu Guojun 
Published: October 2019

AbstractTo identify clinical characteristics and mutation spectra in Chinese patients with renal angiomyolipoma (AML) associated with the tuberous sclerosis complex (TSC, TSC-AML), examined the efficacy and safety of short-term everolimus therapy (12 weeks). We analyzed the frequency distribution of each TSC-related clinical feature and investigated gene mutations by genetic testing. Some subjects received everolimus for 12 weeks at a dose of 10 mg/day, and the efficacy and safety of short-term everolimus therapy were examined. Finally, 82 TSC-AML patients were enrolled for analysis in this study. Of the 47 patients who underwent genetic testing, 22 patients (46.81%) had at least one detectable mutation in the TSC1 or TSC2 gene: 7 were TSC1 gene mutations, 13 were TSC2 gene mutations, and 2 were found in both TSC1 and TSC2. Everolimus treatment had a statistically significant effect on the renal AML volume reduction during follow-up (P < 0.05), and the mean reduction rate of volume for all cases was 56.47 ± 23.32% over 12 weeks. However, 7 patients (7/25; 28.00%) experienced an increase in renal AML tumor volume within 12 weeks after discontinuation of the everolimus treatment. Although most patients (27/30, 90.00%) experienced some adverse events during the treatment period, all such events were mild, and no patients discontinued or needed dose reduction because of adverse events. Overall, in this study, the mutation rate of TSC-AML patients is much lower than other reports. Short-term everolimus treatment for TSC-AML is effective and safe, but the stability is much lower than long-term therapy.
Winding number selection on merons by Gaussian curvature’s sign
Authors: Elías Ricardo Gabriel , Vidal-Silva Nicolás , Carvalho-Santos Vagson L. 
Published: October 2019

AbstractWe study the relationship between the winding number of magnetic merons and the Gaussian curvature of two-dimensional magnetic surfaces. We show that positive (negative) Gaussian curvatures privilege merons with positive (negative) winding number. As in the case of unidimensional domain walls, we found that chirality is connected to the polarity of the core. Both effects allow to predict the topological properties of metastable states knowing the geometry of the surface. These features are related with the recently predicted Dzyaloshinskii-Moriya emergent term of curved surfaces. The presented results are at our knowledge the first ones drawing attention about a direct relation between geometric properties of the surfaces and the topology of the hosted solitons.
Ozone-assisted catalytic oxidation of aqueous nitrite ions on HZSM-5 zeolites
Authors: Ying Mengyue , Zhang Mengdi , Liu Yue , Wu Zhongbiao 
Published: October 2019

AbstractSimultaneous removal of NOx and SO2 during the wet absorption process has made it possible for nitrogen resource utilization. However, nitrites formation at high ratio in absorption solution would limit its application. In this study, the catalytic oxidation behaviors of aqueous nitrite ions assisted by ozone on HZSM-5 zeolites with different SiO2/Al2O3 ratios have been investigated. The experimental results revealed that the oxidation and disproportionation reactions of nitrite ions took place competitively, both of which were accelerated under acidic condition. Moreover, the introduction of HZSM-5 zeolites and ozone would significantly improve the nitrite oxidation rate, where the zeolites with high SiO2/Al2O3 ratios were found to be more effective owing to the enhanced adsorption of nitrite ions and ozone. Based on the results under different operating conditions (such as O3 concentration, HZSM-5 dosage, pH values and presence of radical scavengers etc.), the reaction mechanism was then proposed. The disproportionation reaction of nitrite ions mainly occurred in the bulk solution. And the catalytic oxidation of nitrite ions over zeolites proceeded via a non-radical surface reaction between the adsorbed nitrite ions and ozone/oxygen molecular.
Biosynthesis of silver nanoparticles employing Trichoderma harzianum with enzymatic stimulation for the control of Sclerotinia sclerotiorum
Authors: Guilger-Casagrande Mariana , Germano-Costa Tais , Pasquoto-Stigliani Tatiane , Fraceto Leonardo Fernandes , Lima Renata de 
Published: October 2019

AbstractBiogenic synthesis of silver nanoparticles employing fungi offers advantages, including the formation of a capping from fungal biomolecules, which provides stability and can contribute to biological activity. In this work, silver nanoparticles were synthesized usingTrichoderma harzianumcultivated with (AgNP-TS) and without enzymatic stimulation (AgNP-T) by the cell wall ofSclerotinia sclerotiorum. The nanoparticles were evaluated for the control ofS.sclerotiorum. The specific activity of theT.harzianumhydrolytic enzymes were determined in the filtrates and nanoparticles. Cytotoxicity and genotoxicity were also evaluated. Both the nanoparticles exhibited inhibitory activity towardsS.sclerotiorum, with no new sclerotia development, however AgNP-TS was more effective against mycelial growth. Both the filtrates and the nanoparticles showed specific enzymatic activity. Low levels of cytotoxicity and genotoxicity were observed. This study opens perspectives for further exploration of fungal biogenic nanoparticles, indicating their use for the control ofS.sclerotiorumand other agricultural pests.
TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DCAF11 and promoting phosphorylation of p62
Authors: Park Jee-Yun , Kim Sunhyo , Sohn Hee Young , Koh Young Ho , Jo Chulman 
Published: October 2019

AbstractTranscriptional factor EB (TFEB) and nuclear factor E2-related factor 2 (Nrf2) play crucial roles in the biological response against cellular stressors; however, their relationship has not yet been investigated. Here, we constructed human neuroglioma cell lines stably expressing TFEB. The expression of Nrf2-response genes, including heme oxygenase (HO)-1, glutathione-s-transferase-mu1 (GSTM1), and p62, was induced in the cell line, independent of oxidative stress. Of note, the protein level of Nrf2 was significantly increased, and its ubiquitinated fraction was reduced in stable cells compared to that in the control cells. Among E3 ubiquitin ligases known to be involved in the ubiquitination of Nrf2, DDB1 and Cullin4 associated factor 11 (DCAF11) was down-regulated at both protein and mRNA levels in stable cells, indicating that the repression of DCAF11 by TFEB may be mainly involved in the stabilization of Nrf2. In addition, the level of phosphorylated p62 at S349 was highly increased in stable cells compared to that in control cells, which could allow it to interfere with the association of Keap1 and Nrf2, thus stabilizing Nrf2. We suggest for the first time that TFEB could activate Nrf2 by increasing its stability under conditions devoid of oxidative stress.
Mechanical strain promotes skin fibrosis through LRG-1 induction mediated by ELK1 and ERK signalling
Authors: Gao Ya , Zhou Jia , Xie Zhibo , Wang Jing , Ho Chia-kang , Zhang Yifan , Li Qingfeng 
Published: October 2019

AbstractBiomechanical force and pathological angiogenesis are dominant features in fibro-proliferative disorders. Understanding the role and regulation of the mechanical microenvironment in which pathological angiogenesis occurs is an important challenge when investigating numerous angiogenesis-related diseases. In skin fibrosis, dermal fibroblasts and vascular endothelial cells are integral to hypertrophic scar formation. However, few studies have been conducted to closely investigate their relationship. Here we show, that leucine-rich-alpha-2-glycoprotein 1 (LRG-1) a regulator of pathological angiogenesis, links biomechanical force to angiogenesis in skin fibrosis. We discover that LRG-1 is overexpressed in hypertrophic scar tissues, and that depletion of Lrg-1 in mouse skin causes mild neovascularization and skin fibrosis formation in a hypertrophic scarring model. Inhibition of FAK or ERK attenuates LRG-1 expression through the ELK1 transcription factor, which binds to the LRG-1 promoter region after transcription initiation by mechanical force. Using LRG-1 to uncouple mechanical force from angiogenesis may prove clinically successful in treating fibro-proliferative disorders.
Early stage prion assembly involves two subpopulations with different quaternary structures and a secondary templating pathway
Authors: Igel-Egalon Angélique , Laferrière Florent , Moudjou Mohammed , Bohl Jan , Mezache Mathieu , Knäpple Tina , Herzog Laetitia , Reine Fabienne , Jas-Duval Christelle , Doumic Marie , Rezaei Human , Béringue Vincent 
Published: October 2019

AbstractThe dynamics of aggregation and structural diversification of misfolded, host-encoded proteins in neurodegenerative diseases are poorly understood. In many of these disorders, including Alzheimer’s, Parkinson’s and prion diseases, the misfolded proteins are self-organized into conformationally distinct assemblies or strains. The existence of intrastrain structural heterogeneity is increasingly recognized. However, the underlying processes of emergence and coevolution of structurally distinct assemblies are not mechanistically understood. Here, we show that early prion replication generates two subsets of structurally different assemblies by two sequential processes of formation, regardless of the strain considered. The first process corresponds to a quaternary structural convergence, by reducing the parental strain polydispersity to generate small oligomers. The second process transforms these oligomers into larger ones, by a secondary autocatalytic templating pathway requiring the prion protein. This pathway provides mechanistic insights into prion structural diversification, a key determinant for prion adaptation and toxicity.
Eruptions and flaring activity in emerging quadrupolar regions
Authors: Syntelis P. , Lee E. J. , Fairbairn C. W. , Archontis V. , Hood A. W. 
Published: October 2019

Context. Solar observations suggest that some of the most dynamic active regions are associated with complex photospheric magnetic configurations such as quadrupolar regions, and especially those that have a δ-spot configuration and a strong polarity inversion line (PIL).
Aims. We study the formation and eruption of magnetic flux ropes in quadrupolar regions.
Methods. We performed 3D magnetohydrodynamics simulations of the partial emergence of a highly twisted flux tube from the solar interior into a non-magnetised stratified atmosphere. We introduced a density deficit at two places along the length of the subphotospheric flux tube to emerge as two Ω-shaped loops, forming a quadrupolar region.
Results. At the photosphere, the emerging flux forms two initially separated bipoles, which later come in contact, forming a δ-spot central region. Above the two bipoles, two magnetic lobes expand and interact through a series of current sheets at the interface between them. Two recurrent confined eruptions are produced. In both cases, the reconnection between sheared low-lying field lines forms a flux rope. The reconnection between the two lobes higher in the atmosphere forms field lines that retract down and push against the flux rope, creating a current sheet between them. It also forms field lines that create a third magnetic lobe between the two emerged lobes, that later acts as a strapping field. The flux rope eruptions are triggered when the reconnection between the flux ropes and the field above the ropes becomes efficient enough to remove the tension of the overlying field. These reconnection events occur internally in the quadrupolar system, as the atmosphere is non-magnetised. The flux rope of the first, weaker, eruption almost fully reconnects with the overlying field. The flux rope of the second, more energetic, eruption is confined by the overlying strapping field. During the second eruption, the flux rope is enhanced in size, flux, and twist, similar to confined-flare-to-flux-rope observations. Proxies of the emission reveal the two erupting filaments channels. A flare arcade is only formed in the second eruption owing to the longer lasting and more efficient reconnection at the current sheet below the flux rope.
Overview of non-transientγ-ray binaries and prospects for the Cherenkov Telescope Array
Authors: Chernyakova M. , Malyshev D. , Paizis A. , La Palombara N. , Balbo M. , Walter R. , Hnatyk B. , van Soelen B. , Romano P. , Munar-Adrover P. , Vovk Ie. , Piano G. , Capitanio F. , Falceta-Gonçalves D. , Landoni M. , Luque-Escamilla P. L. , Martí J. , Paredes J. M. , Ribó M. , Safi-Harb S. , Saha L. , Sidoli L. , Vercellone S. 
Published: October 2019

Aims.Despite recent progress in the field, there are still many open questions regardingγ-ray binaries. In this paper we provide an overview of non-transientγ-ray binaries and discuss how observations with the Cherenkov Telescope Array (CTA) will contribute to their study.Methods.We simulated the spectral behaviour of the non-transientγ-ray binaries using archival observations as a reference. With this we tested the CTA capability to measure the spectral parameters of the sources and detect variability on various timescales.Results.We review the known properties ofγ-ray binaries and the theoretical models that have been used to describe their spectral and timing characteristics. We show that the CTA is capable of studying these sources on timescales comparable to their characteristic variability timescales. For most of the binaries, the unprecedented sensitivity of the CTA will allow studying the spectral evolution on a timescale as short as 30 min. This will enable a direct comparison of the TeV and lower energy (radio to GeV) properties of these sources from simultaneous observations. We also review the source-specific questions that can be addressed with these high-accuracy CTA measurements.
Influenza Infections and Emergent Viral Infections in Intensive Care Unit
Authors: Cantan Ben , Luyt Charles-Edouard , Martin-Loeches Ignacio 
Published: October 2019

AbstractCritically ill patients are admitted to an intensive care unit (ICU) for multiple reasons. In this study, we aim to analyze the current evidence and findings associated with influenza and other emergent viral infections, namely, herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV).Among medical conditions, community-acquired respiratory infections are the most frequent reason for ventilatory support in ICUs. Community-acquired pneumonia in a severe form including the need of invasive mechanical ventilation and/or vasopressors is associated with high mortality rates. However, after the pandemic that occurred in 2009 by H1N1 influenza, the number of cases being admitted to ICUs with viral infections is on the rise. Patients in whom an etiology would not have been identified in the past are currently being tested with more sensitive viral molecular diagnostic tools, and patients being admitted to ICUs have more preexisting medical conditions that can predispose to viral infections. Viral infections can trigger the dysregulation of the immune system by inducing a massive cytokine response. This cytokine storm can cause endothelial damage and dysfunction, deregulation of coagulation, and, consequently, alteration of microvascular permeability, tissue edema, and shock. In severe influenza, this vascular hyperpermeability can lead to acute lung injury, multiorgan failure, and encephalopathy. In immunocompetent patients, the most common viral infections are respiratory, and influenza should be considered in patients with severe respiratory failure being admitted to ICU. Seasonality and coinfection are two important features when considering influenza as a pathogen in critically ill patients.Herpesviridae (HSV, CMV, and EBV) may reactivate in ICU patients, and their reactivation is associated with morbidity/mortality. However, whether a specific treatment may impact on outcome remains to be determined.