bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYP4A/20-HETE regulates ischemia-induced neovascularization via its actions on endothelial progenitor and preexisting endothelial cells
Authors: Chen Li , Tang Samantha , Zhang Frank F. , Garcia Victor , Falck John R. , Schwartzman Michal L. , Arbab Ali S. , Guo Austin M. 
Published: April 2019

20-Hydroxyeicosatetraenoic acid (20-HETE) was recently identified as a novel contributor of ischemia-induced neovascularization based on the key observation that pharmacological interferences of CYP4A/20-HETE decrease ischemic neovascularization. The objective of the present study is to examine whether the underlying cellular mechanisms involve endothelial progenitor cells (EPCs) and preexisting endothelial cells (ECs). We found that ischemia leads to a time-dependent increase of cyp4a12 expression and 20-HETE production, which are endothelial in origin, using immunofluorescent microscopy, Western blot analysis, and LC-MS/MS. This is accompanied by increases in the tissue stromal cell-derived factor-1α (SDF-1α) expressions as well as SDF-1α plasma levels, EPC mobilization from bone marrow, and subsequent homing to ischemic tissues. Pharmacological interferences of CYP4A/20-HETE with a 20-HETE synthesis inhibitor, dibromo-dodecenyl-methylsulfimide (DDMS), or a 20-HETE antagonist, N-(20-hydroxyeicosa-6( Z), 15( Z)-dienoyl) glycine (6, 15-20-HEDGE), significantly attenuated these increases. Importantly, we also determined that 20-HETE plays a novel role in maintaining EPC functions and increasing the expression of Oct4, Sox2, and Nanog, which are indicative of increased progenitor cell stemness. Flow cytometric analysis revealed that pharmacological interferences of CYP4A/20-HETE decrease the EPC population in culture, whereas 20-HETE increases the cultured EPC population. Furthermore, ischemia also markedly increased the proliferation, oxidative stress, and ICAM-1 expression in the preexisting EC in the hindlimb gracilis muscles. We found that these increases were markedly negated by DDMS and 6, 15-20-HEDGE. Taken together, CYP4A/20-HETE regulates ischemia-induced compensatory neovascularization via its combined actions on promoting EPC and local preexisting EC responses that are associated with increased neovascularization. NEW & NOTEWORTHY CYP4A/20-hydroxyeicosatetraenoic acid (20-HETE) was recently discovered as a novel contributor of ischemia-induced neovascularization. However, the underlying molecular and cellular mechanisms are completely unknown. Here, we show that CYP4A/20-HETE regulates the ischemic neovascularization process via its combined actions on both endothelial progenitor cells (EPCs) and preexisting endothelial cells. Moreover, this is the first study, to the best of our knowledge, that associates CYP4A/20-HETE with EPC differentiation and stemness.
A novel traditional Chinese medicine ameliorates fatigue-induced cardiac hypertrophy and dysfunction via regulation of energy metabolism
Authors: Huang Rong , Cui Yuan-Chen , Wei Xiao-Hong , Pan Chun-Shui , Li Quan , He Shu-Ya , Fan Jing-Yu , Han Jing-Yan 
Published: April 2019

Prolonged exercise and exercise training can adversely affect cardiac function in some individuals. QiShenYiQi Pills (QSYQ), which are a compound Chinese medicine, have been previously shown to improve pressure overload-induced cardiac hypertrophy. We hypothesized that QSYQ can ameliorate as well the fatigue-induced cardiac hypertrophy. This study was to test this hypothesis and underlying mechanism with a focus on its role in energy regulation. Male Sprague-Dawley rats were used to establish exercise adaptation and fatigue model on a motorized rodent treadmill. Echocardiographic analysis and heart function test were performed to assess heart systolic function. Food-intake weight/body weight and heart weight/body weight were assessed, and hematoxylin and eosin staining and immunofluorescence staining of myocardium sections were performed. ATP synthase expression and activity and ATP, ADP, and AMP levels were assessed using Western blot and ELISA. Expression of proteins related to energy metabolism and IGF-1R signaling was determined using Western blot. QSYQ attenuated the food-intake weight/body weight decrease, improved myocardial structure and heart function, and restored the expression and distribution of myocardial connexin 43 after fatigue, concomitant with an increased ATP production and a restoration of metabolism-related protein expression. QSYQ upgraded the expression of IGF-1R, P-AMPK/AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, P-phosphatidylinositol 3-kinase (PI3K)/PI3K, and P-Akt/Akt thereby attenuated the dysregulation of IGF-1R signaling after fatigue. QSYQ relieved fatigue-induced cardiac hypertrophy and enhanced heart function, which is correlated with its potential to improve energy metabolism by regulating IGF-1R signaling. NEW & NOTEWORTHY Prolonged exercise may impact some people leading to pathological cardiac hypertrophy. This study using an animal model of fatigue-induced cardiac hypertrophy provides evidence showing the potential of QiShenYiQi Pills, a novel traditional Chinese medicine, to prevent the cardiac adaptive hypertrophy from development to pathological hypertrophy and demonstrates that this effect is correlated with its capacity for regulating energy metabolism through interacting with insulin-like growth factor-1 receptor.
Targeting the Temporal Dynamics of Hypoxia-Induced Tumor-Secreted Factors Halts Tumor Migration
Authors: Singh Manjulata , Tian Xiao-Jun , Donnenberg Vera S. , Watson Alan M. , Zhang JingYu , Stabile Laura P. , Watkins Simon C. , Xing Jianhua , Sant Shilpa 
Published: April 2019

Abstract

Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding of the emergence of migratory phenotypes impedes pharmaceutical drug development. Using our three-dimensional microtumor model with tight control over tumor size, we recapitulated the tumor size–induced hypoxic microenvironment and emergence of migratory phenotypes in microtumors from epithelial breast cells and patient-derived primary metastatic breast cancer cells, mesothelioma cells, and lung cancer xenograft cells. The microtumor models from various patient-derived tumor cells and patient-derived xenograft cells revealed upregulation of tumor-secreted factors, including matrix metalloproteinase-9 (MMP9), fibronectin (FN), and soluble E-cadherin, consistent with clinically reported elevated levels of FN and MMP9 in patient breast tumors compared with healthy mammary glands. Secreted factors in the conditioned media of large microtumors induced a migratory phenotype in nonhypoxic, nonmigratory small microtumors. Subsequent mathematical analyses identified a two-stage microtumor progression and migration mechanism whereby hypoxia induces a migratory phenotype in the initialization stage, which then becomes self-sustained through a positive feedback loop established among the tumor-secreted factors. Computational and experimental studies showed that inhibition of tumor-secreted factors effectively halts microtumor migration despite tumor-to-tumor variation in migration kinetics, while inhibition of hypoxia is effective only within a time window and is compromised by tumor-to-tumor variation, supporting our notion that hypoxia initiates migratory phenotypes but does not sustain it. In summary, we show that targeting temporal dynamics of evolving microenvironments, especially tumor-secreted factors during tumor progression, can halt tumor migration.

Significance:
This study uses state-of-the-art three-dimensional microtumor models and computational approaches to highlight the temporal dynamics of tumor-secreted microenvironmental factors in inducing tumor migration.
Estrogen Receptor Covalent Antagonists: The Best Is Yet to Come
Authors: Furman Craig , Hao Ming-Hong , Prajapati Sudeep , Reynolds Dominic , Rimkunas Victoria , Zheng Guo Z. , Zhu Ping , Korpal Manav 
Published: April 2019

Abstract
The development of tamoxifen and subsequent estrogen receptor alpha (ERα) antagonists represents a tremendous therapeutic breakthrough in the treatment of breast cancer. Despite the ability of ERα antagonists to increase survival rates, resistance to these therapies is an all-too-common occurrence. The majority of resistant tumors, including those with hotspot mutations in the ligand-binding domain of ERα, remain dependent on ERα signaling, indicating that either a more potent or novel class of antagonist could have clinical benefit. With this thought in mind, we developed a novel ERα antagonist that exhibits enhanced potency due to its ability to covalently target a unique cysteine in ER. This review describes the design of this antagonist, H3B-5942, and discusses opportunities for future improvements, which could reduce the risk of escape mutations to this therapeutic modality.
Dwelling and Hospitality: Heidegger and Hölderlin
Authors: Winkler Rafael 
Published: April 2019

Abstract
In this article, I focus on Heidegger’s conception of hospitality in his first and final lectures on Hölderlin’s Germania (1934/5), Remembrance (1941/2), and The Ister (1942). I argue that the hospitality of the foreigner for Heidegger is the condition of possibility of dwelling understood as the happening of history.
In the first section I analyze the notions of hospitality in Levinas and Derrida. The second section unpacks some of the senses of the earth in Heidegger as the site of man’s historical dwelling, whereas in the third section I focus on holy mourning as the disposition that reveals the earth as the uncanny ground of history. In the final section, I spell out Heidegger’s conception of hospitality, the greeting, and the foreign guest.
Textiles from the Museum of San Isidoro (León): New Evidence for Re-evaluating Their Chronology and Provenance
Authors: Cabrera Lafuente Ana 
Published: April 2019

Abstract
This paper presents the first in-depth analysis of the textiles held by the Museo de la Real Colegiata de San Isidoro de León, providing a careful investigation of textile features and raw materials, in addition to carbon-14 dating and archival research. These new data have allowed us to redate the fabrics, placing them within their tenth- through early thirteenth-century Mediterranean and European contexts. The result is a more complex image than was previously assumed, and it offers a significant starting point for further research into the roles played by textiles in medieval Iberia.
Demons and Diversity in León
Authors: Patton Pamela A. 
Published: April 2019

Abstract
This article examines a wall painting of the temptation of Saint Martin in the so-called Panteón de los Reyes of San Isidoro in León, focusing on its unorthodox portrayal of Satan as an Ethiopianized, dark-skinned figure wearing a robe reflective of Fatimid textile traditions. Tracing the scene’s divergent sources within the complex network of images, texts, and ideas then circulating in León, it argues that the unusually configured image constituted an innovative, intervisual response to the concerns of a palatine viewership that in the first decades of the twelfth century remained preoccupied with its own dynastic and political position, both within the Leonese kingdom and with reference to its wider European sphere.
Objectivity Discourse, the Protestant Secular, and the Decolonization of Religious Studies
Authors: Cooper Travis Warren 
Published: April 2019

Abstract
This article documents a complex genealogy of objectivity discourse that has shaped the study of religion in the modern academy. Analyzing data derived from a 2015 survey administered to Big 10, Research 1, and Ivy League religious studies institutions in the United States, the study posits a provisional taxonomy of neutrality language. The debates about positionality and self-disclosure in religion classrooms, as explored in the taxonomy, is evidence of the pervasive epistemic framework of the “Protestant secular.” The article proposes that religious studies, as a hybrid discipline, may address the status of the academy as an agent of the secular state by acknowledging its complicity in regimes of power and engaging in the rigorously critical, robustly ethnographic, and concertedly reflexive study of its own institutions and practices. Rather than removing objectivity discourse from religious studies, the article concludes by arguing for retaining a modified form of objectivist realism as a productive, decolonized ideal.
Aging Impairs Temporal Sensitivity, but not Perceptual Synchrony, Across Modalities
Authors: Scurry Alexandra N. , Vercillo Tiziana , Nicholson Alexis , Webster Michael , Jiang Fang 
Published: April 2019

Abstract
Encoding the temporal properties of external signals that comprise multimodal events is a major factor guiding everyday experience. However, during the natural aging process, impairments to sensory processing can profoundly affect multimodal temporal perception. Various mechanisms can contribute to temporal perception, and thus it is imperative to understand how each can be affected by age. In the current study, using three different temporal order judgement tasks (unisensory, multisensory, and sensorimotor), we investigated the effects of age on two separate temporal processes: synchronization and integration of multiple signals. These two processes rely on different aspects of temporal information, either the temporal alignment of processed signals or the integration/segregation of signals arising from different modalities, respectively. Results showed that the ability to integrate/segregate multiple signals decreased with age regardless of the task, and that the magnitude of such impairment correlated across tasks, suggesting a widespread mechanism affected by age. In contrast, perceptual synchrony remained stable with age, revealing a distinct intact mechanism. Overall, results from this study suggest that aging has differential effects on temporal processing, and general impairments with aging may impact global temporal sensitivity while context-dependent processes remain unaffected.
Deterioration of the cell wall in waterlogged wooden archeological artifacts, 2400 years old
Authors: Guo Juan , Xiao Lin , Han Liuyang , Wu Hao , Yang Tao , Wu Shunqing , Yin Yafang 
Published: April 2019

ABSTRACT
The relationship between the cell wall ultrastructure of waterlogged wooden archeological artifacts and the state of water bound to cell walls and free in voids is fundamental to develop consolidating and drying technologies. Herein, a lacquer-wooden ware and a boat-coffin dating 4th century BC were selected as representative artifacts to study. Wood anatomy results indicated that they belonged to Idesia sp. and Machilus sp., respectively. They exhibited a typical spongy texture, as revealed by SEM observations, and their water contents had increased significantly. Solid state NMR, Py-GC/MS, imaging FTIR microscopy and 2D-XRD results demonstrated that the deterioration resulted from the partial cleavages of both polysaccharide backbones and cellulose hydrogen-bonding networks, almost complete elimination of acetyl side chains of hemicellulose, the partial depletion of β-O-4 interlinks, as well as oxidation and demethylation/demethoxylation of lignin. These further caused the disoriented arrangement of crystalline cellulose, and the decrease in cellulose crystallite dimensions and crystallinity. In consequence, mesopores and macropores formed, and the number of moisture-adsorbed sites and their accessibility increased. Moreover, results on free water deduced by the changes of pore structure and the maximum monolayer water capacity achieved by the GAB model indicated that water in waterlogged archeological wooden artifacts was mainly free water in mesopores.
Catalogue of Notomastus M. Sars, 1851 (Annelida, Capitellidae) and the description of a new species from the Gulf of California
Authors: GARCÍA-GARZA MARÍA ELENA , DE LEÓN-GONZÁLEZ JESÚS ANGEL , TOVAR-HERNÁNDEZ MARÍA ANA 
Published: April 2019

Capitellids are burrowing, earthworm-like polychaetes. The taxonomy within the group presents significant difficulties, due in part to their relative simplicity. In this study, a catalogue of the capitellid genus Notomastus M. Sars, 1851, is presented and a new species is described from the Southern Gulf of California: Notomastus mazatlanensis sp. nov. The catalogue provides original names and synonymies for 43 species; type locality and location of type materials; records and remarks on systematics and distribution. Type material of 35 species were examined, 31 from which were photographed to illustrate the catalogue. Notomastus mazatlanensis sp. nov. is established based on the presence of finger-like branchiae emerging from the epithelium near to the notopodia. Branchiae are composed by 3–4 filaments, and the first chaetiger is uniramous. A taxonomic key for species distributed in the Gulf of California is presented. [Species name is register in ZooBank under urn: lsid: zoobank.org: pub:CC8A9E5A-7810-4272-A23C-DCB054E5B4EB]
Statistical Projection of the North Atlantic Storm Tracks
Authors: Parding Kajsa M. , Benestad Rasmus , Mezghani Abdelkader , Erlandsen Helene B. 
Published: April 2019

AbstractA method for empirical–statistical downscaling was adapted to project seasonal cyclone density over the North Atlantic Ocean. To this aim, the seasonal mean cyclone density was derived from instantaneous values of the 6-h mean sea level pressure (SLP) reanalysis fields. The cyclone density was then combined with seasonal mean reanalysis and global climate model projections of SLP or 500-hPa geopotential height to obtain future projections of the North Atlantic storm tracks. The empirical–statistical approach is computationally efficient because it makes use of seasonally aggregated cyclone statistics and allows the future cyclone density to be estimated from the full ensemble of available CMIP5 models rather than from a smaller subset. However, the projected cyclone density in the future differs considerably depending on the choice of predictor, SLP, or 500-hPa geopotential height. This discrepancy suggests that the relationship between the cyclone density and SLP, 500-hPa geopotential height, or both is nonstationary; that is, that the statistical model depends on the calibration period. A stationarity test based on 6-hourly HadGEM2-ES data indicated that the 500-hPa geopotential height was not a robust predictor of cyclone density.
Impacts of High-Resolution Urban Canopy Parameters within the WRF Model on Dynamical and Thermal Fields over Guangzhou, China
Authors: Shen Chong , Chen Xiaoyang , Dai Wei , Li Xiaohui , Wu Jie , Fan Qi , Wang Xuemei , Zhu Liye , Chan Pakwai , Hang Jian , Fan Shaojia , Li Weibiao 
Published: April 2019

AbstractOn urban scales, the detailed characteristics of land-use information and building properties are vital to improving the meteorological model. The WRF Model with high-spatial-resolution urban fraction (UF) and urban morphology (UM) is used to study the impacts of these urban canopy parameters (UCPs) on dynamical and thermal meteorological fields in two representative seasons in Guangzhou. The results of two seasons are similar and as follows. 1) The impacts of updated UF and UM are obvious on wind speed but minor on temperature and humidity. In the urban environment, the results with updated UF and UM are more consistent with observations compared with the default UCPs, which means the performance of the model has been improved. 2) The dynamical factors associated with wind speed are analyzed. Turbulent kinetic energy (TKE) is significantly affected by UM but little by UF. And both UF and UM are found to influence friction velocity U*. The UM and greater UF attained larger U*. 3) In addition, the thermal fields are analyzed. The UM and increased UF induce higher surface skin temperature (TSK) and ground heat flux in the daytime, indicating that more heat is transported from the surface to the soil. At night, more heat is transported from the soil to the surface, producing higher TSK. For sensible heat flux (HFX), greater UF induces larger HFX during the daytime. But the effects of UM are complex, which makes HFX decrease during the daytime and increase at night. Finally, larger UF attains lower latent heat in the daytime.
The protective role of carnosic acid in ischemic/reperfusion injury through regulation of autophagy under T2DM
Authors: Hu Min , Li Tianyu , Bo Zixiang , Xiang Feixiang 
Published: April 2019

Ischemic heart disease (IHD) is the most common cardiovascular disease and is the main cause of death and disability worldwide. Myocardial ischemia/reperfusion (MI/R) injury has been linked to IHD-induced cardiomyocytes apoptosis and tissue damage. Recently, it has been reported that carnosic acid (CA) may function as a potent antioxidant in liver ischemia/reperfusion (I/R). However, whether it regulates I/R in the heart remains unclear. Here, we elucidated the emerging role of CA in MI/R under diabetic myocardial conditions. Diabetes mellitus (DM) was induced in mice by consumption of a high-fat diet for 16 weeks. To create the I/R in mice, the left anterior descending coronary artery was occluded for 30 min, and then occlusion was released to reperfuse the heart for 3 or 24 h. In diabetic myocardial ischemia/reperfusion (DMI/R) mice, pre-treatment with CA suppressed the overgeneration of reactive oxygen species (ROS) and production of cytokine. Importantly, the activation of autophagy was significantly increased by CA treatment, as assessed by p62 degradation and LC3-II/LC3-I conversion, as well as by phosphorylation of AMPKα, Akt, and mTOR. Interestingly, all of the protective effects of CA were impeded by the treatment with chloroquine, which is an autophagy inhibitor. These studies suggest that CA prevents DMI/R injury via regulation of autophagy. In conclusion, our findings indicate that CA has potential as a novel therapeutic to prevent DMI/R injury. Impact statement We have provided, for the first time, evidence that carnosic acid (CA) attenuates ischemia–reperfusion injury of diabetic myocardium, i.e. diabetic myocardial ischemia/reperfusion (DMI/R) injury, via enhancement of autophagy. A greater understanding of the target molecule in CA-enhanced autophagy is necessary for the development of potential chemotherapy for DMI/R injury.