bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological antagonism of kainate receptor rescues dysfunction and loss of dopamine neurons in a mouse model of human parkin-induced toxicity
Authors: Regoni Maria , Cattaneo Stefano , Mercatelli Daniela , Novello Salvatore , Passoni Alice , Bagnati Renzo , Davoli Enrico , Croci Laura , Consalez Gian Giacomo , Albanese Federica , Zanetti Letizia , Passafaro Maria , Serratto Giulia Maia , Di Fonzo Alessio , Valtorta Flavia , Ciammola Andrea , Taverna Stefano , Morari Michele , Sassone Jenny 
Published: November 2020

AbstractMutations in the PARK2 gene encoding the protein parkin cause autosomal recessive juvenile Parkinsonism (ARJP), a neurodegenerative disease characterized by dysfunction and death of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Since a neuroprotective therapy for ARJP does not exist, research efforts aimed at discovering targets for neuroprotection are critically needed. A previous study demonstrated that loss of parkin function or expression of parkin mutants associated with ARJP causes an accumulation of glutamate kainate receptors (KARs) in human brain tissues and an increase of KAR-mediated currents in neurons in vitro. Based on the hypothesis that such KAR hyperactivation may contribute to the death of nigral DA neurons, we investigated the effect of KAR antagonism on the DA neuron dysfunction and death that occur in the parkinQ311X mouse, a model of human parkin-induced toxicity. We found that early accumulation of KARs occurs in the DA neurons of the parkinQ311X mouse, and that chronic administration of the KAR antagonist UBP310 prevents DA neuron loss. This neuroprotective effect is associated with the rescue of the abnormal firing rate of nigral DA neurons and downregulation of GluK2, the key KAR subunit. This study provides novel evidence of a causal role of glutamate KARs in the DA neuron dysfunction and loss occurring in a mouse model of human parkin-induced toxicity. Our results support KAR as a potential target in the development of neuroprotective therapy for ARJP.
The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response
Authors: Gu Zhiwen , Chen Xueying , Yang Wenyong , Qi Yu , Yu Hui , Wang Xiaomeng , Gong Yanqiu , Chen Qianqian , Zhong Bo , Dai Lunzhi , Qi Shiqian , Zhang Zhiqiang , Zhang Huiyuan , Hu Hongbo 
Published: November 2020

AbstractActivation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications, including ubiquitination, SUMOylation, and phosphorylation; however, the underlying molecular mechanism is not fully understood. In this study, TRIM60 negatively regulated the formation and activation of the TAK1 signalosome. Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation, accompanied by elevated levels of proinflammatory cytokines but not IFN-I. Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination, resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways. The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562; substitution of these lysines with arginines abolished the SUMOylation of TAB2. In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock andL. monocytogenesinfection. Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response, potentially paving the way for a new strategy to control antibacterial immune responses.
Akt1 and dCIZ1 promote cell survival from apoptotic caspase activation during regeneration and oncogenic overgrowth
Authors: Sun Gongping , Ding Xun Austin , Argaw Yewubdar , Guo Xiaoran , Montell Denise J. 
Published: November 2020

AbstractApoptosis is an ancient and evolutionarily conserved cell suicide program. During apoptosis, executioner caspase enzyme activation has been considered a point of no return. However, emerging evidence suggests that some cells can survive caspase activation following exposure to apoptosis-inducing stresses, raising questions as to the physiological significance and underlying molecular mechanisms of this unexpected phenomenon. Here, we show that, following severe tissue injury, Drosophila wing disc cells that survive executioner caspase activation contribute to tissue regeneration. Through RNAi screening, we identify akt1 and a previously uncharacterized Drosophila gene CG8108, which is homologous to the human gene CIZ1, as essential for survival from the executioner caspase activation. We also show that cells expressing activated oncogenes experience apoptotic caspase activation, and that Akt1 and dCIZ1 are required for their survival and overgrowth. Thus, survival following executioner caspase activation is a normal tissue repair mechanism usurped to promote oncogene-driven overgrowth.
Brightness modulations of our nearest terrestrial planet Venus reveal atmospheric super-rotation rather than surface features
Authors: Lee Y. J. , García Muñoz A. , Imamura T. , Yamada M. , Satoh T. , Yamazaki A. , Watanabe S. 
Published: November 2020

AbstractTerrestrial exoplanets orbiting within or near their host stars’ habitable zone are potentially apt for life. It has been proposed that time-series measurements of reflected starlight from such planets will reveal their rotational period, main surface features and some atmospheric information. From imagery obtained with the Akatsuki spacecraft, here we show that Venus’ brightness at 283, 365, and 2020 nm is modulated by one or both of two periods of 3.7 and 4.6 days, and typical amplitudes <10% but occasional events of 20–40%. The modulations are unrelated to the solid-body rotation; they are caused by planetary-scale waves superimposed on the super-rotating winds. Here we propose that two modulation periods whose ratio of large-to-small values is not an integer number imply the existence of an atmosphere if detected at an exoplanet, but it remains ambiguous whether the atmosphere is optically thin or thick, as for Earth or Venus respectively. Multi-wavelength and long temporal baseline observations may be required to decide between these scenarios. Ultimately, Venus represents a false positive for interpretations of brightness modulations of terrestrial exoplanets in terms of surface features.
Developmental divergence of sensory stimulus representation in cortical interneurons
Authors: Kastli Rahel , Vighagen Rasmus , van der Bourg Alexander , Argunsah Ali Özgür , Iqbal Asim , Voigt Fabian F. , Kirschenbaum Daniel , Aguzzi Adriano , Helmchen Fritjof , Karayannis Theofanis 
Published: November 2020

AbstractVasocative-intestinal-peptide (VIP+) and somatostatin (SST+) interneurons are involved in modulating barrel cortex activity and perception during active whisking. Here we identify a developmental transition point of structural and functional rearrangements onto these interneurons around the start of active sensation at P14. Using in vivo two-photon Ca2+ imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP+ cells losing their multi-whisker preference and SST+ neurons enhancing theirs. Additionally, we find that Ca2+ signaling dynamics increase in precision as the cells and network mature. Rabies virus tracings followed by tissue clearing, as well as photostimulation-coupled electrophysiology reveal that SST+ cells receive higher cross-barrel inputs compared to VIP+ neurons at both time points. In addition, whereas prior to P14 both cell types receive direct input from the sensory thalamus, after P14 VIP+ cells show reduced inputs and SST+ cells largely shift to motor-related thalamic nuclei.
Collider bias undermines our understanding of COVID-19 disease risk and severity
Authors: Griffith Gareth J. , Morris Tim T. , Tudball Matthew J. , Herbert Annie , Mancano Giulia , Pike Lindsey , Sharp Gemma C. , Sterne Jonathan , Palmer Tom M. , Davey Smith George , Tilling Kate , Zuccolo Luisa , Davies Neil M. , Hemani Gibran 
Published: November 2020

AbstractNumerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, we highlight the challenge of interpreting observational evidence from such non-representative samples. Collider bias can induce associations between two or more variables which affect the likelihood of an individual being sampled, distorting associations between these variables in the sample. Analysing UK Biobank data, compared to the wider cohort the participants tested for COVID-19 were highly selected for a range of genetic, behavioural, cardiovascular, demographic, and anthropometric traits. We discuss the mechanisms inducing these problems, and approaches that could help mitigate them. While collider bias should be explored in existing studies, the optimal way to mitigate the problem is to use appropriate sampling strategies at the study design stage.
Artificially innervated self-healing foams as synthetic piezo-impedance sensor skins
Authors: Guo Hongchen , Tan Yu Jun , Chen Ge , Wang Zifeng , Susanto Glenys Jocelin , See Hian Hian , Yang Zijie , Lim Zi Wei , Yang Le , Tee Benjamin C. K. 
Published: November 2020

AbstractHuman skin is a self-healing mechanosensory system that detects various mechanical contact forces efficiently through three-dimensional innervations. Here, we propose a biomimetic artificially innervated foam by embedding three-dimensional electrodes within a new low-modulus self-healing foam material. The foam material is synthesized from a one-step self-foaming process. By tuning the concentration of conductive metal particles in the foam at near-percolation, we demonstrate that it can operate as a piezo-impedance sensor in both piezoresistive and piezocapacitive sensing modes without the need for an encapsulation layer. The sensor is sensitive to an object’s contact force directions as well as to human proximity. Moreover, the foam material self-heals autonomously with immediate function restoration despite mechanical damage. It further recovers from mechanical bifurcations with gentle heating (70 °C). We anticipate that this material will be useful as damage robust human-machine interfaces.
The sino-nasal warzone: transcriptomic and genomic studies on sino-nasal aspergillosis in dogs
Authors: Valdes I. D. , Hart de Ruijter A. B. P. , Torres C. J. , Breuker J. C. A. , Wösten H. A. B. , de Cock H. 
Published: November 2020

AbstractWe previously showed that each dog with chronic non-invasive sino-nasal aspergillosis (SNA) was infected with a single genotype of Aspergillus fumigatus. Here, we studied the transcriptome of this fungal pathogen and the canine host within the biofilm resulting from the infection. We describe here transcriptomes resulting from natural infections in animal species with A. fumigatus. The host transcriptome showed high expression of IL-8 and alarmins, uncontrolled inflammatory reaction and dysregulation of the Th17 response. The fungal transcriptome showed in particular expression of genes involved in secondary metabolites and nutrient acquisition. Single-nucleotide polymorphism analysis of fungal isolates from the biofilms showed large genetic variability and changes related with adaptation to host environmental factors. This was accompanied with large phenotypic variability in in vitro stress assays, even between isolates from the same canine patient. Our analysis provides insights in genetic and phenotypic variability of Aspergillus fumigatus in biofilms of naturally infected dogs reflecting in-host adaptation. Absence of a Th17 response and dampening of the Th1 response contributes to the formation of a chronic sino-nasal warzone.
The joint automated repository for various integrated simulations (JARVIS) for data-driven materials design
Authors: Choudhary Kamal , Garrity Kevin F. , Reid Andrew C. E. , DeCost Brian , Biacchi Adam J. , Hight Walker Angela R. , Trautt Zachary , Hattrick-Simpers Jason , Kusne A. Gilad , Centrone Andrea , Davydov Albert , Jiang Jie , Pachter Ruth , Cheon Gowoon , Reed Evan , Agrawal Ankit , Qian Xiaofeng , Sharma Vinit , Zhuang Houlong , Kalinin Sergei V. , Sumpter Bobby G. , Pilania Ghanshyam , Acar Pinar , Mandal Subhasish , Haule Kristjan , Vanderbilt David , Rabe Karin , Tavazza Francesca 
Published: November 2020

AbstractThe Joint Automated Repository for Various Integrated Simulations (JARVIS) is an integrated infrastructure to accelerate materials discovery and design using density functional theory (DFT), classical force-fields (FF), and machine learning (ML) techniques. JARVIS is motivated by the Materials Genome Initiative (MGI) principles of developing open-access databases and tools to reduce the cost and development time of materials discovery, optimization, and deployment. The major features of JARVIS are: JARVIS-DFT, JARVIS-FF, JARVIS-ML, and JARVIS-tools. To date, JARVIS consists of ≈40,000 materials and ≈1 million calculated properties in JARVIS-DFT, ≈500 materials and ≈110 force-fields in JARVIS-FF, and ≈25 ML models for material-property predictions in JARVIS-ML, all of which are continuously expanding. JARVIS-tools provides scripts and workflows for running and analyzing various simulations. We compare our computational data to experiments or high-fidelity computational methods wherever applicable to evaluate error/uncertainty in predictions. In addition to the existing workflows, the infrastructure can support a wide variety of other technologically important applications as part of the data-driven materials design paradigm. The JARVIS datasets and tools are publicly available at the website: https://jarvis.nist.gov.
Potential-pH diagrams considering complex oxide solution phases for understanding aqueous corrosion of multi-principal element alloys
Authors: Wang Kang , Han Junsoo , Gerard Angela Yu , Scully John R. , Zhou Bi-Cheng 
Published: November 2020

AbstractThe potential-pH diagram, a graphical representation of the thermodynamically predominant reaction products in aqueous corrosion, is originally proposed for the corrosion of pure metals. The original approach only leads to stoichiometric oxides and hydroxides as the oxidation products. However, numerous experiments show that non-stoichiometric oxide scales are prevalent in the aqueous corrosion of alloys. In the present study, a room temperature potential-pH diagram considering oxide solid solutions, as a generalization of the traditional potential-pH diagram with stoichiometric oxides, is constructed for an FCC single-phase multi-principal element alloy (MPEA) based on the CALculation of PHAse Diagram method. The predominant reaction products, the ions in aqueous solution, and the cation distribution in oxides are predicted. The oxide solid solution is stabilized by the mixing free energy (or mixing entropy) and the stabilizing effect becomes more significant as the temperature increases. Consequently, solid solution oxides are stable in large regions of the potential-pH diagram and the mixing free energy mostly affects the equilibrium composition of the stable oxides, while the shape of stable regions for oxides is mostly determined by the structure of the stable oxides. Agreements are found for Ni2+, Fe2+, and Mn2+ between the atomic emission spectroelectrochemistry measurements and thermodynamic calculations, while deviations exist for Cr3+ and Co2+ possibly due to surface complexation with species such as Cl− and the oxide dissolution. By incorporating the solution models of oxides, the current work presents a general and more accurate way to analyze the reaction products during aqueous corrosion of MPEAs.
A nanoparticle vaccine that targets neoantigen peptides to lymphoid tissues elicits robust antitumor T cell responses
Authors: Arbelaez Carlos A. , Estrada Juan , Gessner Melissa A. , Glaus Charles , Morales Agnieszka B. , Mohn Deanna , Phee Hyewon , Lipford J. Russell , Johnston James A. 
Published: November 2020

AbstractCancer vaccines using synthetic long peptides (SLP) targeting tumor antigens have been tested in the clinic but the outcomes have been unimpressive, perhaps because these peptides elicit predominantly CD4+ T cell responses. We hypothesized that enhanced delivery of peptide antigens to, and uptake in, secondary lymphoid tissues should elicit more robust CD8+ and CD4+ T cell responses and improved anti-tumor responses. Here, we have designed SLP-containing cationic lipoplexes (SLP–Lpx) that improve delivery of peptides to myeloid cells in the spleen and lymphatics. Using the G12D KRAS mutations as neoantigens, we found that vaccination of mice with naked synthetic peptides harboring the G12D mutation with CpG adjuvant stimulated mainly CD4+ T cell responses with limited tumor growth inhibition. On the other hand, immunization with SLP–Lpx stimulated both CD4+ and CD8+ T cells and suppressed tumor growth in a CD8+ T cell-dependent manner. Combination of the SLP–Lpx vaccines with a checkpoint inhibitor led to profound growth suppression of established tumors. These studies suggest that preferential targeting of peptides derived from neoantigens to the spleen via lipoplexes elicits potent CD4+ and CD8+ T cell responses that inhibit tumor growth.
Mucosal delivery of a multistage subunit vaccine promotes development of lung-resident memory T cells and affords interleukin-17-dependent protection against pulmonary tuberculosis
Authors: Counoupas Claudio , Ferrell Kia C. , Ashhurst Anneliese , Bhattacharyya Nayan D. , Nagalingam Gayathri , Stewart Erica L. , Feng Carl G. , Petrovsky Nikolai , Britton Warwick J. , Triccas James A. 
Published: November 2020

AbstractThe development of effective vaccines against bacterial lung infections requires the induction of protective, pathogen-specific immune responses without deleterious inflammation within the pulmonary environment. Here, we made use of a polysaccharide-adjuvanted vaccine approach to elicit resident pulmonary T cells to protect against aerosol Mycobacterium tuberculosis infection. Intratracheal administration of the multistage fusion protein CysVac2 and the delta-inulin adjuvant Advax™ (formulated with a TLR9 agonist) provided superior protection against aerosol M. tuberculosis infection in mice, compared to parenteral delivery. Surprisingly, removal of the TLR9 agonist did not impact vaccine protection despite a reduction in cytokine-secreting T cell subsets, particularly CD4+IFN-γ+IL-2+TNF+ multifunctional T cells. CysVac2/Advax-mediated protection was associated with the induction of lung-resident, antigen-specific memory CD4+ T cells that expressed IL-17 and RORγT, the master transcriptional regulator of Th17 differentiation. IL-17 was identified as a key mediator of vaccine efficacy, with blocking of IL-17 during M. tuberculosis challenge reducing phagocyte influx, suppressing priming of pathogen-specific CD4+ T cells in local lymph nodes and ablating vaccine-induced protection. These findings suggest that tuberculosis vaccines such as CysVac2/Advax that are capable of eliciting Th17 lung-resident memory T cells are promising candidates for progression to human trials.
A comprehensive spectral assay library to quantify the Escherichia coli proteome by DIA/SWATH-MS
Authors: Midha Mukul K. , Kusebauch Ulrike , Shteynberg David , Kapil Charu , Bader Samuel L. , Reddy Panga Jaipal , Campbell David S. , Baliga Nitin S. , Moritz Robert L. 
Published: November 2020

AbstractData-Independent Acquisition (DIA) is a method to improve consistent identification and precise quantitation of peptides and proteins by mass spectrometry (MS). The targeted data analysis strategy in DIA relies on spectral assay libraries that are generally derived from a priori measurements of peptides for each species. Although Escherichia coli (E. coli) is among the best studied model organisms, so far there is no spectral assay library for the bacterium publicly available. Here, we generated a spectral assay library for 4,014 of the 4,389 annotated E. coli proteins using one- and two-dimensional fractionated samples, and ion mobility separation enabling deep proteome coverage. We demonstrate the utility of this high-quality library with robustness in quantitation of the E. coli proteome and with rapid-chromatography to enhance throughput by targeted DIA-MS. The spectral assay library supports the detection and quantification of 91.5% of all E. coli proteins at high-confidence with 56,182 proteotypic peptides, making it a valuable resource for the scientific community. Data and spectral libraries are available via ProteomeXchange (PXD020761, PXD020785) and SWATHAtlas (SAL00222-28).
Engineering bioactive surfaces on nanoparticles and their biological interactions
Authors: Matur Meghana , Madhyastha Harishkumar , Shruthi T. S. , Madhyastha Radha , Srinivas S. P. , Navya P. N. , Daima Hemant Kumar 
Published: November 2020

AbstractThe successful integration of nanoparticles into biomedical applications requires modulation of their surface properties so that the interaction with biological systems is regulated to minimize toxicity for biological function. In the present work, we have engineered bioactive surfaces on gold (Au) and silver (Ag) nanoparticles and subsequently evaluated their interaction with mouse skin fibroblasts and macrophages. The Au and Ag nanoparticles were synthesized using tyrosine, tryptophan, isonicotinylhydrazide, epigallocatechin gallate, and curcumin as reducing and stabilizing agents. The nanoparticles thus prepared showed surface corona and exhibited free radical scavenging and enzyme activities with limited cytotoxicity and genotoxicity. We have thus developed avenues for engineering the surface of nanoparticles for biological applications.
Formation of α-tocopherol hydroperoxide and α-tocopheroxyl radical: relevance for photooxidative stress in Arabidopsis
Authors: Kumar Aditya , Prasad Ankush , Pospíšil Pavel 
Published: November 2020

AbstractTocopherols, lipid-soluble antioxidants play a crucial role in the antioxidant defense system in higher plants. The antioxidant function of α-tocopherol has been widely studied; however, experimental data on the formation of its oxidation products is missing. In this study, we attempt to provide spectroscopic evidence on the detection of oxidation products of α-tocopherol formed by its interaction with singlet oxygen and lipid peroxyl radical. Singlet oxygen was formed using photosensitizer rose bengal and thylakoid membranes isolated from Arabidopsis thaliana. Singlet oxygen reacts with polyunsaturated fatty acid forming lipid hydroperoxide which is oxidized by ferric iron to lipid peroxyl radical. The addition of singlet oxygen to double bond carbon on the chromanol head of α-tocopherol forms α-tocopherol hydroperoxide detected using fluorescent probe swallow-tailed perylene derivative. The decomposition of α-tocopherol hydroperoxide forms α-tocopherol quinone. The hydrogen abstraction from α-tocopherol by lipid peroxyl radical forms α-tocopheroxyl radical detected by electron paramagnetic resonance. Quantification of lipid and protein hydroperoxide from the wild type and tocopherol deficient (vte1) mutant Arabidopsis leaves using a colorimetric ferrous oxidation-xylenol orange assay reveals that α-tocopherol prevents formation of both lipid and protein hydroperoxides at high light. Identification of oxidation products of α-tocopherol might contribute to a better understanding of the protective role of α-tocopherol in the prevention of oxidative damage in higher plants at high light.