bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐Speed Video Observations of Natural Lightning Attachment Process With Framing Rates up to Half a Million Frames per Second
Authors: Qi Qi , Lyu Weitao , Ma Ying , Wu Bin , Chen Lyuwen , Jiang Ruijiao , Zhu Yanan , Rakov Vladimir A. 
Published: October 2019

AbstractUsing high‐speed video cameras operating with framing rates of 20 and 525 kfps, we imaged the attachment process of a natural negative cloud‐to‐ground flash, occurring at a distance of 490 m. Nine upward leaders were observed. A total of 12 space stems/leaders in 47 steps of the downward negative stepped leader were captured. The two‐dimensional length of them was between 2.0 and 5.9 m, with an average of 3.0 m. The average interstep interval, step length, and two‐dimensional speed of the downward negative leader and that of upward positive leader were statistically analyzed. The last step of the downward negative leader making contact with the upward connecting leader was recorded. The two‐dimensional length of the final imaged gap between the tips of opposite‐polarity leaders was estimated to be about 13 m.
Invariant NKT cells facilitate cytotoxic T-cell activation via direct recognition of CD1d on T cells
Authors: Qin Yingyu , Oh Sejin , Lim Sojung , Shin Jung Hoon , Yoon Min Sang , Park Se-Ho 
Published: October 2019

AbstractInvariant natural killer T (iNKT) cells are a major subset of NKT cells that recognize foreign and endogenous lipid antigens presented by CD1d. Although iNKT cells are characteristically autoreactive to self-antigens, the role of iNKT cells in the regulation of cytotoxic T lymphocytes (CTL) has been elucidated using α-galactosylceramide (α-GalCer), a strong synthetic glycolipid that is presented by professional antigen presenting cells (APCs), such as dendritic cells. Despite the well-known effects of α-GalCer and dendritic cells on lipid antigen presentation, the physiological role of endogenous antigens presented by CTLs during crosstalk with iNKT cells has not yet been addressed. In this study, we found that antigen-primed CTLs with transient CD1d upregulation could present lipid self-antigens to activate the iNKT cell production of IFN-γ. CTL-mediated iNKT cell activation in turn enhanced IFN-γ production and the proliferation and cytotoxicity of CTLs. We also found that the direct interaction of iNKT cells and CTLs enhanced the antitumor immune responses of CTLs. This partially explains the functional role of iNKT cells in CTL-mediated antitumor immunity. Our findings suggest that in the absence of exogenous iNKT cell ligands, iNKT cells enhanced the CTL production of IFN-γ and CTL proliferation and cytotoxicity via direct interaction with CD1d expressed on T cells without interacting with APCs.
Lysosome restoration to activate podocyte autophagy: a new therapeutic strategy for diabetic kidney disease
Authors: Liu Wei Jing , Gan Yu , Huang Wei Fang , Wu Hong-luan , Zhang Xue-qin , Zheng Hui Juan , Liu Hua-feng 
Published: October 2019

AbstractAutophagy, the intracellular lysosomal degradation process plays a pivotal role in podocyte homeostasis in diabetic kidney disease (DKD). Lysosomal function, autophagic activity, and their actions were investigated in vitro and in vivo. We found that LC3-II- and p62-positive vacuoles accumulated in podocytes of patients with DKD. Moreover, we found that advanced glycation end products (AGEs) could increase the protein expression of LC3-II and p62 in a dose- and time-dependent manner in cultured podocytes. However, the mRNA expression of LC3B, Beclin-1 or ATG7, as well as the protein level of Beclin-1 or ATG7 did not change significantly in the AGE-treated cells compared with that in control groups, suggesting that AGEs did not induce autophagy. In addition, AGEs led to an increase in the number of autophagosomes but not autolysosomes, accompanied with a failure in lysosomal turnover of LC3-II or p62, indicating that the degradation of autophagic vacuoles was blocked. Furthermore, we observed a dramatic decrease in the enzymatic activities, and the degradation of DQ-ovalbumin was significantly suppressed after podocytes were treated with AGEs. Plasma-irregular lysosomal-associated membrane protein 1 granules accompanied with the diffusion of cathepsin D expression and acridine orange redistribution were observed in AGE-treated podocytes, indicating that the lysosomal membrane permeability was triggered. Interestingly, we also found that AGEs-induced autophagic inhibition and podocyte injury were mimicked by the specific lysosomotropic agent, l-leucyl-l-leucine methyl ester. The exacerbated apoptosis and Rac-1-dependent actin-cytoskeletal disorganization were alleviated by an improvement in the lysosomal-dependent autophagic pathway by resveratrol plus vitamin E treatment in AGE-treated podocytes. However, the rescued effects were reversed by the addition of leupeptin, a lysosomal inhibitor. It suggests that restoring lysosomal function to activate autophagy may contribute to the development of new therapeutic strategies for DKD.
PROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis
Authors: Shi Chengcheng , Zhang Huapeng , Wang Penglei , Wang Kai , Xu Denghui , Wang Haitao , Yin Li , Zhang Shuijun , Zhang Yi 
Published: October 2019

AbstractTargeting oncogenic proteins for degradation using proteolysis-targeting chimera (PROTAC) recently has drawn increasing attention in the field of cancer research. Bromodomain and extra-terminal (BET) family proteins are newly identified cancer-related epigenetic regulators, which have a role in the pathogenesis and progression of osteosarcoma. In this study, we investigated the in vitro and in vivo anti-osteosarcoma activity by targeting BET with a PROTAC molecule BETd-260. The results showed that BETd-260 completely depletes BET proteins and potently suppresses cell viability in MNNG/HOS, Saos-2, MG-63, and SJSA-1 osteosarcoma cell lines. Compared with BET inhibitors HJB-97 and JQ1, the activity of BETd-260 increased over 1000 times. Moreover, BETd-260 substantially inhibited the expression of anti-apoptotic Mcl-1, Bcl-xl while increased the expression of pro-apoptotic Noxa, which resulted in massive apoptosis in osteosarcoma cells within hours. In addition, pro-oncogenic protein c-Myc also was substantially inhibited by BETd-260 in the OS cells. Of note, BETd-260 induced degradation of BET proteins, triggered apoptosis in xenograft osteosarcoma tumor tissue, and profoundly inhibited the growth of cell-derived and patient-derived osteosarcoma xenografts in mice. Our findings indicate that BET PROTACs represent a promising therapeutic agent for human osteosarcoma.
Data driven discovery of cyber physical systems
Authors: Yuan Ye , Tang Xiuchuan , Zhou Wei , Pan Wei , Li Xiuting , Zhang Hai-Tao , Ding Han , Goncalves Jorge 
Published: October 2019

AbstractCyber-physical systems embed software into the physical world. They appear in a wide range of applications such as smart grids, robotics, and intelligent manufacturing. Cyber-physical systems have proved resistant to modeling due to their intrinsic complexity arising from the combination of physical and cyber components and the interaction between them. This study proposes a general framework for discovering cyber-physical systems directly from data. The framework involves the identification of physical systems as well as the inference of transition logics. It has been applied successfully to a number of real-world examples. The novel framework seeks to understand the underlying mechanism of cyber-physical systems as well as make predictions concerning their state trajectories based on the discovered models. Such information has been proven essential for the assessment of the performance of cyber-physical systems; it can potentially help debug in the implementation procedure and guide the redesign to achieve the required performance.
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering
Authors: Milanese Chiara , Bombardieri Cíntia R. , Sepe Sara , Barnhoorn Sander , Payán-Goméz César , Caruso Donatella , Audano Matteo , Pedretti Silvia , Vermeij Wilbert P. , Brandt Renata M. C. , Gyenis Akos , Wamelink Mirjam M. , de Wit Annelieke S. , Janssens Roel C. , Leen René , van Kuilenburg André B. P. , Mitro Nico , Hoeijmakers Jan H. J. , Mastroberardino Pier G. 
Published: October 2019

AbstractAccumulation of DNA lesions causing transcription stress is associated with natural and accelerated aging and culminates with profound metabolic alterations. Our understanding of the mechanisms governing metabolic redesign upon genomic instability, however, is highly rudimentary. Using Ercc1-defective mice and Xpg knock-out mice, we demonstrate that combined defects in transcription-coupled DNA repair (TCR) and in nucleotide excision repair (NER) directly affect bioenergetics due to declined transcription, leading to increased ATP levels. This in turn inhibits glycolysis allosterically and favors glucose rerouting through the pentose phosphate shunt, eventually enhancing production of NADPH-reducing equivalents. In NER/TCR-defective mutants, augmented NADPH is not counterbalanced by increased production of pro-oxidants and thus pentose phosphate potentiation culminates in an over-reduced redox state. Skin fibroblasts from the TCR disease Cockayne syndrome confirm results in animal models. Overall, these findings unravel a mechanism connecting DNA damage and transcriptional stress to metabolic redesign and protective antioxidant defenses.
Anomalous hydrogen evolution behavior in high-pH environment induced by locally generated hydronium ions
Authors: Wang Xuesi , Xu Chaochen , Jaroniec Mietek , Zheng Yao , Qiao Shi-Zhang 
Published: October 2019

AbstractMost fundamental studies of electrocatalysis are based on the experimental and simulation results obtained for bulk model materials. Some of these mechanistic understandings are inapplicable for more active nanostructured electrocatalysts. Herein, considering the simplest and most typical electrocatalytic process, the hydrogen evolution reaction, an alternative reaction mechanism is proposed for nanomaterials based on the identification of a new intermediate, which differs from those commonly known for the bulk counterparts. In-situ Raman spectroscopy and electrochemical thermal/kinetic measurements were conducted on a series of nanomaterials under different conditions. In high-pH electrolytes with negligible hydronium (H3O+) concentration in bulk phase, massive H3O+ intermediates are found generating on the catalytic surface during water dissociation and hydrogen adsorption processes. These H3O+ intermediates create a unique acid-like local reaction environment on nanostructured catalytic surfaces and cut the energy barrier of the overall reaction. Such phenomena on nanostructured electrocatalysts explain their widely observed anomalously high activity under high-pH conditions.
Cortical astrocytes develop in a plastic manner at both clonal and cellular levels
Authors: Clavreul Solène , Abdeladim Lamiae , Hernández-Garzón Edwin , Niculescu Dragos , Durand Jason , Ieng Sio-Hoï , Barry Raphaëlle , Bonvento Gilles , Beaurepaire Emmanuel , Livet Jean , Loulier Karine 
Published: October 2019

AbstractAstrocytes play essential roles in the neural tissue where they form a continuous network, while displaying important local heterogeneity. Here, we performed multiclonal lineage tracing using combinatorial genetic markers together with a new large volume color imaging approach to study astrocyte development in the mouse cortex. We show that cortical astrocyte clones intermix with their neighbors and display extensive variability in terms of spatial organization, number and subtypes of cells generated. Clones develop through 3D spatial dispersion, while at the individual level astrocytes acquire progressively their complex morphology. Furthermore, we find that the astroglial network is supplied both before and after birth by ventricular progenitors that scatter in the neocortex and can give rise to protoplasmic as well as pial astrocyte subtypes. Altogether, these data suggest a model in which astrocyte precursors colonize the neocortex perinatally in a non-ordered manner, with local environment likely determining astrocyte clonal expansion and final morphotype.
High-performance chemical- and light-inducible recombinases in mammalian cells and mice
Authors: Weinberg Benjamin H. , Cho Jang Hwan , Agarwal Yash , Pham N. T. Hang , Caraballo Leidy D. , Walkosz Maciej , Ortega Charina , Trexler Micaela , Tague Nathan , Law Billy , Benman William K. J. , Letendre Justin , Beal Jacob , Wong Wilson W. 
Published: October 2019

AbstractSite-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.
Prophages and satellite prophages are widespread in Streptococcus and may play a role in pneumococcal pathogenesis
Authors: Rezaei Javan Reza , Ramos-Sevillano Elisa , Akter Asma , Brown Jeremy , Brueggemann Angela B. 
Published: October 2019

AbstractProphages (viral genomes integrated within a host bacterial genome) can confer various phenotypic traits to their hosts, such as enhanced pathogenicity. Here we analyse >1300 genomes of 70 different Streptococcus species and identify nearly 800 prophages and satellite prophages (prophages that do not encode their own structural components but rely on the bacterial host and another helper prophage for survival). We show that prophages and satellite prophages are widely distributed among streptococci in a structured manner, and constitute two distinct entities with little effective genetic exchange between them. Cross-species transmission of prophages is not uncommon. Furthermore, a satellite prophage is associated with virulence in a mouse model of Streptococcus pneumoniae infection. Our findings highlight the potential importance of prophages in streptococcal biology and pathogenesis.
Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders
Authors: Oetjens M. T. , Kelly M. A. , Sturm A. C. , Martin C. L. , Ledbetter D. H. 
Published: October 2019

AbstractRare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals, a disease characteristic termed variable expressivity. Recently, the aggregate effect of common variation, quantified as polygenic scores (PGSs), has emerged as an effective tool for predictions of disease risk and trait variation in the general population. Here, we measure the effect of PGSs on 11 RGDs including four sex-chromosome aneuploidies (47,XXX; 47,XXY; 47,XYY; 45,X) that affect height; two copy-number variant (CNV) disorders (16p11.2 deletions and duplications) and a Mendelian disease (melanocortin 4 receptor deficiency (MC4R)) that affect BMI; and two Mendelian diseases affecting cholesterol: familial hypercholesterolemia (FH;LDLRandAPOB) and familial hypobetalipoproteinemia (FHBL;PCSK9andAPOB). Our results demonstrate that common, polygenic factors of relevant complex traits frequently contribute to variable expressivity of RGDs and that PGSs may be a useful metric for predicting clinical severity in affected individuals and for risk stratification.
The geometry of masking in neural populations
Authors: Ringach Dario L. 
Published: October 2019

AbstractThe normalization model provides an elegant account of contextual modulation in individual neurons of primary visual cortex. Understanding the implications of normalization at the population level is hindered by the heterogeneity of cortical neurons, which differ in the composition of their normalization pools and semi-saturation constants. Here we introduce a geometric approach to investigate contextual modulation in neural populations and study how the representation of stimulus orientation is transformed by the presence of a mask. We find that population responses can be embedded in a low-dimensional space and that an affine transform can account for the effects of masking. The geometric analysis further reveals a link between changes in discriminability and bias induced by the mask. We propose the geometric approach can yield new insights into the image processing computations taking place in early visual cortex at the population level while coping with the heterogeneity of single cell behavior.
Acid selective pro-dye for cellular compartments
Authors: Czaplińska Barbara , Malarz Katarzyna , Mrozek-Wilczkiewicz Anna , Musiol Robert 
Published: October 2019

AbstractA novel pro-dye approach for the acid-selective staining of the subcellular compartments for better permeability and selectivity was applied. The designed sensor has suitable physicochemical properties such as a large Stokes shift and a long-lived intracellular fluorescence. The Schiff base fragment was used for the acid-sensitive release of a fluorophore without affecting the overall stability of the biological systems. Due to the presence of an imine bond in its structure and its unique fluorescent properties, it can be presented as a “pro-dye” for acidic structures such as lysosomes. As a result of an imine bond cleavage, a new fluorescent compound is released, whose substantially shifted excitation and emission wavelengths enable a more selective and effective imaging of lysosomes and endosomes. The presented report provides the chemical, physicochemical and optical profiles as well as biological assays and theoretical calculations.
Anthracene phytotoxicity in the freshwater flagellate alga Euglena agilis Carter
Authors: Kottuparambil Sreejith , Park Jihae 
Published: October 2019

AbstractThe freshwater flagellate alga Euglena agilis Carter was exposed to the polycyclic aromatic hydrocarbon (PAH) anthracene for 96 h under optimal photosynthetically active radiation (PAR), and responses of growth, photosynthetic pigment production, and photosynthetic efficiency were assessed. Anthracene reduced the growth rate (μ) and levels of chlorophyll a (Chl a), chlorophyll b (Chl b), and total carotenoids. The growth rate was more sensitive than photosynthetic parameters, with a median effective concentration (EC50) of 4.28 mg L−1. Between 5 and 15 mg L−1, anthracene inhibited the maximum quantum yield (Fv/Fm) of photosystem II (PSII) and the maximum photosynthetic electron transport rate through PSII (rETRmax) with EC50 values of 14.88 and 11.8 mg L−1, respectively. At all anthracene concentrations, intracellular reactive oxygen species (ROS) were elevated, indicating increased oxidative stress. Anthracene presumably reduced the PSII efficiency of photochemical energy regulation and altered the photochemistry through intracellular ROS formation. Acute exposure to PAHs may induce severe physiological changes in phytoplankton cells, which may influence vital ecological processes within the aquatic environments. Additionally, growth and Chl a content may serve as sensitive risk assessment parameters of anthracene toxicity in water management since EC50 values for both overlap with anthracene levels (8.3 mg L−1) permitted by the US Environmental Protection Agency (USEPA).
Bioprocessing of common pulses changed seed microstructures, and improved dipeptidyl peptidase-IV and α-glucosidase inhibitory activities
Authors: Di Stefano Elisa , Tsopmo Apollinaire , Oliviero Teresa , Fogliano Vincenzo , Udenigwe Chibuike C. 
Published: October 2019

AbstractType 2 diabetes mellitus (T2DM) is a leading cause of death globally. T2DM patients experience glucose intolerance, and inhibitors of dipeptidyl peptidase IV (DPP-IV) and α-glucosidase are used as drugs for T2DM management. DPP-IV and α-glucosidase inhibitors are also naturally contained in foods, but their potency can be affected by the food matrix and processing methods. In this study, germination and solid-state fermentation (SSF) were used to alter pulse seed microstructures, to convert compounds into more bioactive forms, and to improve their bioaccessibility. Germination substantially modified the seed microstructure, protein digestibility, contents and profiles of phenolic compounds in all the pulses. It also increased DPP-IV and α-glucosidase inhibitory activities in chickpeas, faba beans and yellow peas. Compared to germination, SSF withLactobacillus plantarumchanged the content and the profile of phenolic compounds mainly in yellow peas and green lentils because of greater disruption of the seed cell wall. In the same pulses, heat treatment and SSF of flour increased DPP-IV and α-glucosidase inhibitory activities. The results of this study suggest that germination and SSF withL. plantarumare effective and simple methods for modulating phenolic and protein profiles of common pulses and improve the action on DPP-IV and α-glucosidase.
Potential scrapie-associated polymorphisms of the prion protein gene (PRNP) in Korean native black goats
Authors: Kim Seon-Kwan , Kim Yong-Chan , Won Sae-Young , Jeong Byung-Hoon 
Published: October 2019

AbstractSmall ruminants, including sheep and goats are natural hosts of scrapie, and the progression of scrapie pathogenesis is strongly influenced by polymorphisms in the prion protein gene (PRNP). Although Korean native goats have been consumed as meat and health food, the evaluation of the susceptibility to scrapie in these goats has not been performed thus far. Therefore, we investigated the genotype and allele frequencies of PRNP polymorphisms in 211 Korean native goats and compared them with those in scrapie-affected animals from previous studies. We found a total of 12 single nucleotide polymorphisms (SNPs) including 10 nonsynonymous and 2 synonymous SNPs in Korean native goats. Significant differences in allele frequencies of PRNP codons 143 and 146 were found between scrapie-affected goats and Korean native goats (p < 0.01). By contrast, in PRNP codons 168, 211 and 222, there were no significant differences in the genotype and allele frequencies between scrapie-affected animals and Korean native goats. To evaluate structural changes caused by nonsynonymous SNPs, PolyPhen-2, PROVEAN and AMYCO analyses were performed. PolyPhen-2 predicted “possibly damaging” for W102G and R154H, “probably damaging” for G127S. AMYCO predicted relatively low for amyloid propensity of prion protein in Korean native black goats. This is the first study to evaluate the scrapie sensitivity and the first in silico evaluation of nonsynonymous SNPs in Korean native black goats.