bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breath acetone as a marker of energy balance: an exploratory study in healthy humans
Authors: Bovey Fabian , Cros Jérémy , Tuzson Béla , Seyssel Kevin , Schneiter Philippe , Emmenegger Lukas , Tappy Luc 
Published: September 2018

AbstractAn exploratory study was performed on eight healthy volunteers to assess how short-term changes in energy balance and dietary carbohydrate content impact breath acetone concentrations. Participants were studied on three occasions: on each occasion, they remained fasted and in resting conditions during the first 2 h to assess basal breath acetone and blood beta-hydroxybutyrate (BOHB). During the next 6 h, they remained fasted on one occasion (F), or were fed hourly high carbohydrate (HC) or low-carbohydrate (LC) meals to induce a positive energy balance on the other two occasions. They remained in resting conditions during 4 h, then performed a 2-hour low intensity exercise (25 W) inducing a negative energy balance. In resting conditions, breath acetone and blood BOHB concentrations increased progressively compared to basal values in F, but decreased and remained low throughout the test in HC. With LC, breath acetone increased progressively, while blood BOHB decreased. This exploratory study indicates that breath acetone reliably detects a stimulation of ketogenesis during a short-term fast. It also suggests that LC and HC differentially impact BOHB and acetone production and utilization, and reveals possible limitations to the use of breath acetone as a marker of energy balance.
HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα
Authors: Di Rita Anthea , Peschiaroli Angelo , D′Acunzo Pasquale , Strobbe Daniela , Hu Zehan , Gruber Jens , Nygaard Mads , Lambrughi Matteo , Melino Gerry , Papaleo Elena , Dengjel Jörn , El Alaoui Said , Campanella Michelangelo , Dötsch Volker , Rogov Vladimir V. , Strappazzon Flavie , Cecconi Francesco 
Published: September 2018

AbstractThe selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells.
Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure
Authors: de Leeuw Christiaan A. , Stringer Sven , Dekkers Ilona A. , Heskes Tom , Posthuma Danielle 
Published: September 2018

AbstractGene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype. But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because one property may be statistically associated even if biologically irrelevant to the phenotype, by being correlated with gene properties that are relevant. To address this issue we present a novel conditional and interaction gene-set analysis approach, which attains considerable functional refinement of its conclusions compared to traditional gene-set analysis. We applied our approach to blood pressure phenotypes in the UK Biobank data (N = 360,243), the results of which we report here. We confirm and further refine several associations with multiple processes involved in heart and blood vessel formation but also identify novel interactions, among others with cardiovascular tissues involved in regulatory pathways of blood pressure homoeostasis.
A self-improving triboelectric nanogenerator with improved charge density and increased charge accumulation speed
Authors: Cheng Li , Xu Qi , Zheng Youbin , Jia Xiaofeng , Qin Yong 
Published: September 2018

AbstractCharge density is one of the most important parameters of triboelectric nanogenerators since it directly determines performance; unfortunately, it is largely restricted by the phenomenon of air breakdown. Here, we design a self-improving triboelectric nanogenerator with improved charge density. A maximum effective charge density of 490 μC m−2 is obtained, which is about two times higher than the highest reported charge density of a triboelectric nanogenerator that operates in an air environment. At the beginning of the working process, the charge accumulation speed is increased 5.8 times in comparison with a triboelectric nanogenerator that is incorporated into the self-improving device. The self-improving triboelectric nanogenerator overcomes the restriction of air breakdown and exhibits an increased effective charge density, which contributes to the improvement of the output performance, and the increase of charge accumulation speed will accelerate the increase of the output power at the start of operation.
Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments
Authors: Yoshitomi Hiroyuki , Kobayashi Shio , Miyagawa-Hayashino Aya , Okahata Akinori , Doi Kohei , Nishitani Kohei , Murata Koichi , Ito Hiromu , Tsuruyama Tatsuaki , Haga Hironori , Matsuda Shuichi , Toguchida Junya 
Published: September 2018

AbstractIn human inflammatory sites, PD-1hiCXCR5−CD4+ T cells are involved in the formation of ectopic lymphoid-like structures (ELSs) by the secretion of chemokine CXCL13, but how the transcription of CXCL13 is regulated in CD4+ T cells is still unclear. Here we show that Sox4 is a key transcription factor for CXCL13 production in human CD4+ T cells under inflammatory conditions. In vitro TGF-β+, IL-2-neutralizing culture conditions give rise to PD-1hiCXCR5−CD4+ T cells that preferentially express CXCL13, and transcriptome analysis and lentiviral overexpression indicate Sox4 association with the CXCL13 transcription. In vivo, Sox4 is significantly upregulated in synovial CD4+ T cells, when compared with blood CD4+ T cells, from patients with rheumatoid arthritis (RA), and further correlates with ELS formation in RA synovium. Overall, our studies suggest that Sox4 contributes to CXCL13 production and ELS formation at inflammatory sites in humans.
Predicting nutrient content of ray-finned fishes using phylogenetic information
Authors: Vaitla Bapu , Collar David , Smith Matthew R. , Myers Samuel S. , Rice Benjamin L. , Golden Christopher D. 
Published: September 2018

AbstractHuman food and nutrition security is dependent on marine ecosystems threatened by overfishing, climate change, and other processes. The consequences on human nutritional status are uncertain, in part because current methods of analyzing fish nutrient content are expensive. Here, we evaluate the possibility of predicting nutrient content of ray-finned fishes using existing phylogenetic and life history information. We focus on nutrients for which fish are important sources: protein, total fat, omega-3 and omega-6 fatty acids, iron, zinc, vitamin A, vitamin B12, and vitamin D. Our results show that life history traits are weak predictors of species nutrient content, but phylogenetic relatedness is associated with similar nutrient profiles. Further, we develop a method for predicting the nutrient content of 7500+ species based on phylogenetic relationships to species with known nutrient content. Our approach is a cost-effective means for estimating potential changes in human nutrient intake associated with altered access to ray-finned fishes.
Nanomaterials design for super-degenerate electronic state beyond the limit of geometrical symmetry
Authors: Haruta Naoki , Tsukamoto Takamasa , Kuzume Akiyoshi , Kambe Tetsuya , Yamamoto Kimihisa 
Published: September 2018

AbstractSpherical atoms have the highest geometrical symmetry. Due to this symmetry, atomic orbitals are highly degenerate, leading to closed-shell stability and magnetism. No substances with greater degrees of degeneracy are known, due to geometrical limitations. We now propose that realistic magnesium, zinc, and cadmium clusters having a specific tetrahedral framework possess anomalous higher-fold degeneracies than spherical symmetry. Combining density functional theory calculations with simple tight-binding models, we demonstrate that these degeneracies can be attributed to dynamical symmetry. The degeneracy condition is fully identified as an elegant mathematical sequence involving interatomic parameters. The introduction of dynamical symmetry will lead to the discovery of a novel category of substances with super-degenerate orbitals.
The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation
Authors: Mi Wenyi , Zhang Yi , Lyu Jie , Wang Xiaolu , Tong Qiong , Peng Danni , Xue Yongming , Tencer Adam H. , Wen Hong , Li Wei , Kutateladze Tatiana G. , Shi Xiaobing 
Published: September 2018

AbstractRecognition of histones by epigenetic readers is a fundamental mechanism for the regulation of chromatin and transcription. Most reader modules target specific post-translational modifications on histones. Here, we report the identification of a reader of histone H3, the ZZ-type zinc finger (ZZ) domain of ZZZ3, a subunit of the Ada-two-A-containing (ATAC) histone acetyltransferase complex. The solution NMR structure of the ZZ in complex with the H3 peptide reveals a unique binding mechanism involving caging of the N-terminal Alanine 1 of histone H3 in an acidic cavity of the ZZ domain, indicating a specific recognition of H3 versus other histones. Depletion of ZZZ3 or disruption of the ZZ-H3 interaction dampens ATAC-dependent promoter histone H3K9 acetylation and target gene expression. Overall, our study identifies the ZZ domain of ZZZ3 as a histone H3 reader that is required for the ATAC complex-mediated maintenance of histone acetylation and gene activation.
Chromatin swelling drives neutrophil extracellular trap release
Authors: Neubert Elsa , Meyer Daniel , Rocca Francesco , Günay Gökhan , Kwaczala-Tessmann Anja , Grandke Julia , Senger-Sander Susanne , Geisler Claudia , Egner Alexander , Schön Michael P. , Erpenbeck Luise , Kruss Sebastian 
Published: September 2018

AbstractNeutrophilic granulocytes are able to release their own DNA as neutrophil extracellular traps (NETs) to capture and eliminate pathogens. DNA expulsion (NETosis) has also been documented for other cells and organisms, thus highlighting the evolutionary conservation of this process. Moreover, dysregulated NETosis has been implicated in many diseases, including cancer and inflammatory disorders. During NETosis, neutrophils undergo dynamic and dramatic alterations of their cellular as well as sub-cellular morphology whose biophysical basis is poorly understood. Here we investigate NETosis in real-time on the single-cell level using fluorescence and atomic force microscopy. Our results show that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status. Entropic chromatin swelling is the major physical driving force that causes cell morphology changes and the rupture of both nuclear envelope and plasma membrane. Through its material properties, chromatin thus directly orchestrates this complex biological process.
Macrophage-secreted interleukin-35 regulates cancer cell plasticity to facilitate metastatic colonization
Authors: Lee Chih-Chan , Lin Jiunn-Chang , Hwang Wei-Lun , Kuo Ying-Ju , Chen Hung-Kai , Tai Shyh-Kuan , Lin Chun-Chi , Yang Muh-Hwa 
Published: September 2018

AbstractA favorable interplay between cancer cells and the tumor microenvironment (TME) facilitates the outgrowth of metastatic tumors. Because of the distinct initiating processes between primary and metastatic tumors, we investigate the differences in tumor-associated macrophages (TAMs) from primary and metastatic cancers. Here we show that dual expression of M1 and M2 markers is noted in TAMs from primary tumors, whereas predominant expression of M2 markers is shown in metastatic TAMs. At metastatic sites, TAMs secrete interleukin-35 (IL-35) to facilitate metastatic colonization through activation of JAK2–STAT6-GATA3 signaling to reverse epithelial–mesenchymal transition (EMT) in cancer cells. In primary tumors, inflammation-induced EMT upregulates IL12Rβ2, a subunit of the IL-35 receptor, in cancer cells to help them respond to IL-35 during metastasis. Neutralization of IL-35 or knockout of IL-35 in macrophages reduces metastatic colonization. These results indicate the distinct TMEs of primary and metastatic tumors and provide potential targets for intercepting metastasis.
Skin color-specific and spectrally-selective naked-eye dosimetry of UVA, B and C radiations
Authors: Zou Wenyue , González Ana , Jampaiah Deshetti , Ramanathan Rajesh , Taha Mohammad , Walia Sumeet , Sriram Sharath , Bhaskaran Madhu , Dominguez-Vera José M. , Bansal Vipul 
Published: September 2018

AbstractSpectrally–selective monitoring of ultraviolet radiations (UVR) is of paramount importance across diverse fields, including effective monitoring of excessive solar exposure. Current UV sensors cannot differentiate between UVA, B, and C, each of which has a remarkably different impact on human health. Here we show spectrally selective colorimetric monitoring of UVR by developing a photoelectrochromic ink that consists of a multi-redox polyoxometalate and an e−donor. We combine this ink with simple components such as filter paper and transparency sheets to fabricate low-cost sensors that provide naked-eye monitoring of UVR, even at low doses typically encountered during solar exposure. Importantly, the diverse UV tolerance of different skin colors demands personalized sensors. In this spirit, we demonstrate the customized design of robust real-time solar UV dosimeters to meet the specific need of different skin phototypes. These spectrally–selective UV sensors offer remarkable potential in managing the impact of UVR in our day-to-day life.
The last-born daughter cell contributes to division orientation of Drosophila larval neuroblasts
Authors: Loyer Nicolas , Januschke Jens 
Published: September 2018

AbstractControlling the orientation of cell division is important in the context of cell fate choices and tissue morphogenesis. However, the mechanisms providing the required positional information remain incompletely understood. Here we use stem cells of the Drosophila larval brain that stably maintain their axis of polarity and division between cell cycles to identify cues that orient cell division. Using live cell imaging of cultured brains, laser ablation and genetics, we reveal that division axis maintenance relies on their last-born daughter cell. We propose that, in addition to known intrinsic cues, stem cells in the developing fly brain are polarized by an extrinsic signal. We further find that division axis maintenance allows neuroblasts to maximize their contact area with glial cells known to provide protective and proliferative signals to neuroblasts.
Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells
Authors: Chen Xufeng , Zhao Jingyao , Gu Chan , Cui Yu , Dai Yuling , Song Guangrong , Liu Haifeng , Shen Hao , Liu Yuanhua , Wang Yuya , Xing Huayue , Zhu Xiaoyan , Hao Pei , Guo Fan , Liu Xiaolong 
Published: September 2018

AbstractIn response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is downregulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identify Med23 as a gatekeeper of myeloid potential of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid potential of HSCs and HSC activation upon stresses.
Differences in the intrinsic chondrogenic potential of equine umbilical cord matrix and cord blood mesenchymal stromal/stem cells for cartilage regeneration
Authors: Rakic Rodolphe , Bourdon Bastien , Demoor Magali , Maddens Stéphane , Saulnier Nathalie , Galéra Philippe 
Published: September 2018

AbstractUmbilical cord blood mesenchymal stromal/stem cells (UCB-MSCs) and umbilical cord matrix MSCs (UCM-MSCs) have chondrogenic potential and are alternative sources to standard surgically derived bone marrow or adipose tissue collection for cartilage engineering. However, the majority of comparative studies explore neonatal MSCs potential only on ISCT benchmark assays accounting for some bias in the reproducibility between in vitro and in clinical studies. Therefore, we characterized equine UCB-MSCs and UCM-MSCs and investigated with particular attention their chondrogenesis potential in 3D culture with BMP-2 + TGF-ß1 in normoxia or hypoxia. We carried out an exhaustive characterization of the extracellular matrix generated by both these two types of MSCs after the induction of chondrogenesis through evaluation of hyaline cartilage, hypertrophic and osteogenic markers (mRNA, protein and histology levels). Some differences in hypoxia sensitivity and chondrogenesis were observed. UCB-MSCs differentiated into chondrocytes express an abundant, dense and a hyaline-like cartilage matrix. By contrast, despite their expression of cartilage markers, UCM-MSCs failed to express a relevant cartilage matrix after chondrogenic induction. Both MSCs types also displayed intrinsic differences at their undifferentiated basal status, UCB-MSCs expressing higher levels of chondrogenic markers whereas UCM-MSCs synthesizing higher amounts of osteogenic markers. Our results suggest that UCB-MSCs should be preferred for ex-vivo horse cartilage engineering. How those results should be translated to in vivo direct cartilage regeneration remains to be determined through dedicated study.
A leaky voltage sensor domain of cardiac sodium channels causes arrhythmias associated with dilated cardiomyopathy
Authors: Moreau Adrien , Gosselin-Badaroudine Pascal , Mercier Aurélie , Burger Bettina , Keller Dagmar I. , Chahine Mohamed 
Published: September 2018

AbstractDilated cardiomyopathy (DCM) is a structural heart disease that causes dilatation of cardiac chambers and impairs cardiac contractility. The SCN5A gene encodes Nav1.5, the predominant cardiac sodium channel alpha subunit. SCN5A mutations have been identified in patients with arrhythmic disorders associated with DCM. The characterization of Nav1.5 mutations located in the voltage sensor domain (VSD) and associated with DCM revealed divergent biophysical defects that do not fully explain the pathologies observed in these patients. The purpose of this study was to characterize the pathological consequences of a gating pore in the heart arising from the Nav1.5/R219H mutation in a patient with complex cardiac arrhythmias and DCM. We report its properties using cardiomyocytes derived from patient-specific human induced pluripotent stem cells. We showed that this mutation generates a proton leak (called gating pore current). We also described disrupted ionic homeostasis, altered cellular morphology, electrical properties, and contractile function, most probably linked to the proton leak. We thus propose a novel link between SCN5A mutation and the complex pathogenesis of cardiac arrhythmias and DCM. Furthermore, we suggest that leaky channels would constitute a common pathological mechanism underlying several neuronal, neuromuscular, and cardiac pathologies.
High-throughput sequencing revealed that microRNAs were involved in the development of superior and inferior grains in bread wheat
Authors: Wang Yongyan , Shi Chaonan , Yang Tianxiao , Zhao Lei , Chen Jianhui , Zhang Ning , Ren Yan , Tang Guiliang , Cui Dangqun , Chen Feng 
Published: September 2018

AbstractHigh-throughput sequencing was employed to investigate the expression of miRNAs and their target genes in superior and inferior seeds of Aikang 58. Small RNA sequencing revealed 620 conserved and 64 novel miRNAs in superior grains, and 623 conserved and 66 novel miRNAs in inferior grains. Among these, 97 known miRNAs, and eight novel miRNAs showed differential expression between the superior and inferior seeds. Degradome sequencing revealed at least 140 candidate target genes associated with 35 miRNA families during the development of superior and inferior seeds. GO and KEGG pathway analysis showed that the differentially expressed miRNAs, both conserved and novel, were likely involved in hormone production, carbohydrate metabolic pathways, and cell division. We validated eight known and four novel grain development-related miRNAs and their target genes by quantitative real-time polymerase chain reaction to ensure the reliability of small RNA and degradome-seq results. Of these, miR160 and miR165/166 were knocked down in Arabidopsis using short-tandem target mimic (STTM160 and STTM165/166) technology, which confirmed their roles in seed development. Specifically, STTM160 showed significantly smaller grain size, lower grain weight, shorter siliques length, shorter plant height, and more serrated leaves, whereas STTM165/166 showed decreased seed number, disabled siliques, and curled upward leaves.
Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging
Authors: Hainfeld James F. , Ridwan Sharif M. , Stanishevskiy Yaroslav , Smilowitz Nathaniel R. , Davis James , Smilowitz Henry M. 
Published: September 2018

AbstractStandard clinical X-ray contrast agents are small iodine-containing molecules that are rapidly cleared by the kidneys and provide robust imaging for only a few seconds, thereby limiting more extensive vascular and tissue biodistribution imaging as well as optimal tumor uptake. They are also not generally useful for preclinical microCT imaging where longer scan times are required for high resolution image acquisition. We here describe a new iodine nanoparticle contrast agent that has a unique combination of properties: 20 nm hydrodynamic diameter, covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body weight after intravenous administration in mice. These characteristics are unique among the other iodine nanoparticles that have been previously reported and provide extended-time high contrast vascular imaging and tumor loading. As such, it is useful for preclinical MicroCT animal studies. Potential human applications might include X-ray radiation dose enhancement for cancer therapy and vascular imaging for life-threatening situations where high levels of contrast are needed for extended periods of time.