bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strain partitioning in highly oblique rift settings: Inferences from the southwestern margin of the Gulf of California (Baja California Sur, México)
Authors: Bonini Marco , Cerca Mariano , Moratti Giovanna , López‐Martínez Margarita , Corti Giacomo , Gracia‐Marroquín Diego 
Published: November 2019

AbstractThis study aims to analyze the modalities of strain accommodation within a highly oblique rift, taking the Gulf of California as a prototype. Rifting in the Gulf of California is accomplished by intra‐Gulf strike‐slip (transform) faults, and mostly dip‐slip displacement on the rift‐margin faults. We have collected fault‐slip data and samples for radiometric dating at selected sites in southeastern Baja California, which is host to the southwestern margin of the rift. We have identified three styles of faulting, particularly (1) WSW‐dipping normal faults, (2) E‐ENE‐dipping normal faults, and (3) steep NNE‐NE‐trending left‐lateral faults. The E‐ENE‐dipping normal faults define the western margin of the Gulf of California rift and are most likely coeval (late Miocene to recent) with both the ~NNE‐NE‐trending left‐lateral faults and some of the WSW‐dipping faults. Fault‐slip data have often been collected on potentially active Gulf of California rift‐margin faults, which invariably display dominant dip‐slip kinematics (generally with minor dextral component). Distribution of extension directions determined from stress inversion of brittle fault kinematic data indicates a peak of 080°–090°, which is strikingly similar to the orientations of T axes from earthquake focal mechanisms of both rift‐margin normal/faults and intra‐Gulf strike‐slip faults. These findings suggest that this stretching may have been occurring throughout the protracted rift history. Furthermore, highly oblique rifts do not show across‐rift variations in the orientation of local extension, which is instead typical of continental rifts with lower obliquity.
MicroRNA-148a/b-3p regulates angiogenesis by targeting neuropilin-1 in endothelial cells
Authors: Kim Hyejeong , Ko Yeongrim , Park Hyojin , Zhang Haiying , Jeong Yoonjeong , Kim Yeomyeong , Noh Minyoung , Park Songyi , Kim Young-Myeong , Kwon Young-Guen 
Published: November 2019

Abstract
MicroRNAs (miRs) are crucial regulators of vascular endothelial cell (EC) functions, including migration, proliferation, and survival. However, the role of most miRs in ECs remains unknown. Using RNA sequencing analysis, we found that miR-148a/b-3p expression was significantly downregulated during the differentiation of umbilical cord blood mononuclear cells into outgrowing ECs and that decreased miR-148a/b-3p levels were closely related to EC behavior. Overexpression of miR-148a/b-3p in ECs significantly reduced migration, filamentous actin remodeling, and angiogenic sprouting. Intriguingly, the effects of decreased miR-148a/b-3p levels were augmented by treatment with vascular endothelial growth factor (VEGF). Importantly, we found that miR-148a/b-3p directly regulated neuropilin-1 (NRP1) expression by binding to its 3′-untranslated region. In addition, because NRP1 is the coreceptor for VEGF receptor 2 (VEGFR2), overexpression of miR-148a/b-3p inhibited VEGF-induced activation of VEGFR2 and inhibited its downstream pathways, as indicated by changes to phosphorylated focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase. Collectively, our results demonstrate that miR-148a/b-3p is a direct transcriptional regulator of NRP1 that mediates antiangiogenic pathways. These data suggest that miR-148a/b-3p is a therapeutic candidate for overcoming EC dysfunction and angiogenic disorders, including ischemia, retinopathy, and tumor vascularization.
The roles of exosomal miRNAs and lncRNAs in lung diseases
Authors: Li Yang , Yin Zhengrong , Fan Jinshuo , Zhang Siyu , Yang Weibing 
Published: November 2019

AbstractAn increasing number of studies have reported that exosomes released from various cells can serve as mediators of information exchange between different cells. With further exploration of exosome content, a more accurate molecular mechanism involved in the process of cell-to-cell communication has been revealed; specifically, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are shuttled by exosomes. In addition, exosomal miRNAs and lncRNAs may play vital roles in the pathogenesis of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), lung cancer, and asthma. Consequently, exosomal miRNAs and lncRNAs show promise as diagnostic biomarkers and therapeutic targets in several lung diseases. This review will summarize recent knowledge about the roles of exosomal miRNAs and lncRNAs in lung diseases, which has shed light on the discovery of novel diagnostic methods and treatments for these disorders. Because there is almost no published literature about exosomal lncRNAs in COPD, asthma, interstitial lung disease, or tuberculosis, we summarize the roles of exosomal lncRNAs only in lung cancer in the second section. This may inspire some new ideas for researchers who are interested in whether lncRNAs shuttled by exosomes may play roles in other lung diseases.
A role for spinal cord hypoxia in neurodegeneration
Authors: Hernandez-Gerez Elena , Fleming Ian N. , Parson Simon H. 
Published: November 2019

AbstractThe vascular system of the spinal cord is particularly complex and vulnerable. Damage to the main vessels or alterations to the regulation of blood flow will result in a reduction or temporary cessation of blood supply. The resulting tissue hypoxia may be brief: acute, or long lasting: chronic. Damage to the vascular system of the spinal cord will develop after a traumatic event or as a result of pathology. Traumatic events such as road traffic accidents, serious falls and surgical procedures, including aortic cross-clamping, will lead to an immediate cessation of perfusion, the result of which may not be evident for several days, but may have long-term consequences including neurodegeneration. Pathological events such as arterial sclerosis, venous occlusion and spinal cord compression will result in a progressive reduction of blood flow, leading to chronic hypoxia. While in some situations the initial pathology is exclusively vascular, recent research in neurodegenerative disease has drawn attention to concomitant vascular anomalies in disorders, including amyotrophic lateral sclerosis, spinal muscular atrophy and muscular sclerosis. Understanding the role of, and tissue response to, chronic hypoxia is particularly important in these cases, where inherent neural damage exacerbates the vulnerability of the nervous system to stressors including hypoxia.
Renal clearable nanochelators for iron overload therapy
Authors: Kang Homan , Han Murui , Xue Jie , Baek Yoonji , Chang JuOae , Hu Shuang , Nam HaYoung , Jo Min Joo , El Fakhri Georges , Hutchens Michael P. , Choi Hak Soo , Kim Jonghan 
Published: November 2019

AbstractIron chelators have been widely used to remove excess toxic iron from patients with secondary iron overload. However, small molecule-based iron chelators can cause adverse side effects such as infection, gastrointestinal bleeding, kidney failure, and liver fibrosis. Here we report renal clearable nanochelators for iron overload disorders. First, after a singledose intravenous injection, the nanochelator shows favorable pharmacokinetic properties, such as kidney-specific biodistribution and rapid renal excretion (>80% injected dose in 4 h), compared to native deferoxamine (DFO). Second, subcutaneous (SC) administration of nanochelators improves pharmacodynamics, as evidenced by a 7-fold increase in efficiency of urinary iron excretion compared to intravenous injection. Third, daily SC injections of the nanochelator for 5 days to iron overload mice and rats decrease iron levels in serum and liver. Furthermore, the nanochelator significantly reduces kidney damage caused by iron overload without demonstrating DFO’s own nephrotoxicity. This renal clearable nanochelator provides enhanced efficacy and safety.
Towards a fully automated algorithm driven platform for biosystems design
Authors: HamediRad Mohammad , Chao Ran , Weisberg Scott , Lian Jiazhang , Sinha Saurabh , Zhao Huimin 
Published: November 2019

AbstractLarge-scale data acquisition and analysis are often required in the successful implementation of the design, build, test, and learn (DBTL) cycle in biosystems design. However, it has long been hindered by experimental cost, variability, biases, and missed insights from traditional analysis methods. Here, we report the application of an integrated robotic system coupled with machine learning algorithms to fully automate the DBTL process for biosystems design. As proof of concept, we have demonstrated its capacity by optimizing the lycopene biosynthetic pathway. This fully-automated robotic platform, BioAutomata, evaluates less than 1% of possible variants while outperforming random screening by 77%. A paired predictive model and Bayesian algorithm select experiments which are performed by Illinois Biological Foundry for Advanced Biomanufacturing (iBioFAB). BioAutomata excels with black-box optimization problems, where experiments are expensive and noisy and the success of the experiment is not dependent on extensive prior knowledge of biological mechanisms.
A network-based approach to uncover microRNA-mediated disease comorbidities and potential pathobiological implications
Authors: Jin Shuting , Zeng Xiangxiang , Fang Jiansong , Lin Jiawei , Chan Stephen Y. , Erzurum Serpil C. , Cheng Feixiong 
Published: November 2019

AbstractDisease–disease relationships (e.g., disease comorbidities) play crucial roles in pathobiological manifestations of diseases and personalized approaches to managing those conditions. In this study, we develop a network-based methodology, termed meta-path-based Disease Network (mpDisNet) capturing algorithm, to infer disease–disease relationships by assembling four biological networks: disease–miRNA, miRNA–gene, disease–gene, and the human protein–protein interactome. mpDisNet is a meta-path-based random walk to reconstruct the heterogeneous neighbors of a given node. mpDisNet uses a heterogeneous skip-gram model to solve the network representation of the nodes. We find that mpDisNet reveals high performance in inferring clinically reported disease–disease relationships, outperforming that of traditional gene/miRNA-overlap approaches. In addition, mpDisNet identifies network-based comorbidities for pulmonary diseases driven by underlying miRNA-mediated pathobiological pathways (i.e., hsa-let-7a- or hsa-let-7b-mediated airway epithelial apoptosis and pro-inflammatory cytokine pathways) as derived from the human interactome network analysis. The mpDisNet offers a powerful tool for network-based identification of disease–disease relationships with miRNA-mediated pathobiological pathways.
Mechanical Properties of Human Dura Mater in Tension – An Analysis at an Age Range of 2 to 94 Years
Authors: Zwirner Johann , Scholze Mario , Waddell John Neil , Ondruschka Benjamin , Hammer Niels 
Published: November 2019

AbstractRealistic human head models are of great interest in traumatic brain injury research and in the forensic pathology courtroom and teaching. Due to a lack of biomechanical data, the human dura mater is underrepresented in head models. This study provides tensile data of 73 fresh human cranial dura mater samples retrieved from an area between the anterior middle and the posterior middle meningeal artery. Tissues were adapted to their native water content using the osmotic stress technique. Tensile tests were conducted under quasi-static uniaxial testing conditions with simultaneous digital image correlation. Human temporal dura mater is mechanically highly variable with regards to its elastic modulus of 70 ± 44 MPa, tensile strength of 7 ± 4 MPa, and maximum strain of 11 ± 3 percent. Mechanical properties of the dura mater did not vary significantly between side nor sex and decreased with the age of the cadaver. Both elastic modulus and tensile strength appear to have constant mechanical parameters within the first 139 hours post mortem. The mechanical properties provided by this study can help to improve computational and physical human head models. These properties under quasi-static conditions do not require adjustments for side nor sex, whereas adjustments of tensile properties accompanied with normal aging may be of interest.
Virtual-source imaging and repeatability for complex near surface
Authors: Zhao Yang , Liu Tao , Tang Genyang , Zhang Houzhu , Sengupta Madhumita 
Published: November 2019

AbstractBased on seismic interferometry, the virtual source (VS) method is able to produce virtual gathers at buried receiver locations by crosscorrelating the direct-downgoing waves with corresponding reflected-upgoing waves from surface-source gathers. Theoretically, the VS records can improve seismic quality with less negative impact from overburdened complexities. However, shallow complex structures and weathering layers at near surface not only severely distort the wavepaths, but also introduce multiples, surface waves, scattering noise, and interference among different wave modes. These additional seismic responsescontaminate both direct-downgoing and reflected-upgoing wavefields. As a result, the VS gathers experience spurious events and unbalanced illuminations associated with distorted radiation patterns. Conventional stacking operator can produce significant artifacts for sources associated with ineffective-wavepath cancellation. We review three publications and summarize a comprehensive workflow to address these issues using data-driven offset stacking, wavelet-crosscorrelation filtering, and radiation-pattern correction. A data-driven offset stacking theme, with each individual source contribution is weighted by certain quality measures, is applied for available offsets. The wavelet crosscorrelation transforms time-offset data into local time-frequency and local time-frequency-wavenumber domains. Filters are designed for the power-spectrum in each domain. The radiation-pattern correction spatially alters the contaminated direct-wavefields using a zero-phase matched filter, such that the filtered wavefield is consistent with the model-based direct P-wavefields observed at buried receiver locations. Our proposed workflow produces significant improvement as demonstrated in the 13 time-lapse field surveys that included substantial repeatability problems across a 17-month survey gap.
Investigation of protein-protein interactions and hot spot region between PD-1 and PD-L1 by fragment molecular orbital method
Authors: Lim Hocheol , Chun Jungho , Jin Xuemei , Kim Jongwan , Yoon JeongHyeok , No Kyoung Tai 
Published: November 2019

AbstractInhibitors to interfere protein-protein interactions (PPI) between programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) block evasion of cancers from immune surveillance. Analyzing hot spot residues in PPI is important for small-molecule drug development. In order to find out hot spots on PPI interface in PD-1/PD-L1 complex, we analyzed PPI in PD-1/PD-L1 with a new analysis method, 3-dimensional scattered pair interactions energies (3D-SPIEs), which assorts significant interactions with fragment molecular orbital (FMO) method. By additionally analyzing PPI in PD-1/antibody and PD-L1/antibody complexes, and small-ligand interactions in PD-L1/peptide and PD-L1/small-molecule complexes, we narrowed down the hot spot region with 3D-SPIEs-based interaction map, which integrates PPI and small-ligand interactions. Based on the map, there are two hot spot regions in PPI of PD-1/PD-L1 and the first hot spot region is important for inhibitors. In particular, LY56, LE58, and LN66 in the first hot spot of PD-L1 are important for PD-L1-antibodies and small-inhibitors in common, while LM115 is important for small-inhibitors. Therefore, the 3D-SPIEs-based map would provide valuable information for designing new small-molecule inhibitors to inhibit PPI of PD-1/PD-L1 and the FMO/3D-SPIEs method provides an effectual tool to understand PPI and integrate PPI and small-ligand interactions at a quantum mechanical level.
Bovine pericardial extracellular matrix niche modulates human aortic endothelial cell phenotype and function
Authors: Shklover Jeny , McMasters James , Alfonso-Garcia Alba , Higuita Manuela Lopera , Panitch Alyssa , Marcu Laura , Griffiths Leigh 
Published: November 2019

AbstractXenogeneic biomaterials contain biologically relevant extracellular matrix (ECM) composition and organization, making them potentially ideal surgical grafts and tissue engineering scaffolds. Defining the effect of ECM niche (e.g., basement membrane vs. non-basement membrane) on repopulating cell phenotype and function has important implications for use of xenogeneic biomaterials, particularly in vascular applications. We aim to understand how serous (i.e., basement membrane) versus fibrous (i.e., non-basement membrane) ECM niche of antigen-removed bovine pericardium (AR-BP) scaffolds influence human aortic endothelial cell (hAEC) adhesion, growth, phenotype, inflammatory response and laminin production. At low and moderate seeding densities hAEC proliferation was significantly increased on the serous side. Similarly, ECM niche modulated cellular morphology, with serous side seeding resulting in a more rounded aspect ratio and intact endothelial layer formation. At moderate seeding densities, hAEC production of human laminin was enhanced following serous seeding. Finally, inflammatory marker and pro-inflammatory cytokine expression decreased following long-term cell growth regardless of seeding side. This work demonstrates that at low and moderate seeding densities AR-BP sidedness significantly impacts endothelial cell growth, morphology, human laminin production, and inflammatory state. These findings suggest that ECM niche has a role in modulating response of repopulating recipient cells toward AR-BP scaffolds for vascular applications.
The effects of mechanical tactile stimulation on corticospinal excitability and motor function depend on pin protrusion patterns
Authors: Kojima Sho , Miyaguchi Shota , Sasaki Ryoki , Tsuiki Shota , Saito Kei , Inukai Yasuto , Otsuru Naofumi , Onishi Hideaki 
Published: November 2019

AbstractSomatosensory stimulation modulates corticospinal excitability. Mechanical tactile stimulation (MS) activates cortical activity depending on tactile stimulation patterns. In this study, we examined whether the effects of mechanical tactile stimulation on corticospinal excitability and motor function depend on different pin protrusions patterns. This single-blind study included 18 healthy subjects. Two types of MS interventions were used: repetitive global stimulus (RGS) intervention was used to stimulate the finger by using 24 pins installed on a finger pad, and sequential stepwise displacement stimulus (SSDS) intervention was used to stimulate the finger by moving a row of 6 pins between the left and right sides on the finger pad. MS interventions were applied to the right index finger for 20 min (stim on/stim off, 1 s/5 s) at a frequency of 20 Hz. After RGS intervention, motor evoked potentials (MEPs) by transcranial magnetic stimulation were observed to be significantly smaller than pre-intervention MEPs; however, motor function using the grooved pegboard task remained unchanged. After SSDS intervention, MEPs were significantly larger and motor function significantly improved compared with pre-intervention values. Our results demonstrated that MS intervention can modulate corticospinal excitability and motor function and that the effects of MS intervention depend on MS intervention patterns.
γδT cells contribute to type 2 inflammatory profiles in eosinophilic chronic rhinosinusitis with nasal polyps
Authors: Li Xia , Wang Zhiyuan , Chang Lihong , Chen Xiaohong , Yang Luoying , Lai Xiaoping , Li Shuaixiang , Huang Jiancong , Huang Zizhen , Wu Xifu , Bellanti Joseph A , Zheng Song Guo , Zhang Gehua 
Published: November 2019

Abstract
Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS) is a condition linked with type 2 inflammation, poor treatment outcomes, and high recurrence tendency. Although γδT cells have been reported to induce type 2 immune responses and eosinophilic infiltration in several diseases, their role in ECRS has not been fully explored. We aimed to evaluate the association of γδT cells with the type 2 inflammatory profiles in ECRS. Nasal tissue samples obtained from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (51 eosinophilic and 48 non-eosinophilic), 50 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 58 control subjects were examined for γδT cells, inflammatory markers and eosinophils using HE, RT-qPCR, ELISA, immunofluorescence, and flow cytometry. In parallel, studies were also conducted in an ECRS murine model induced by anti-γδT cells neutralizing antibody administration. γδT cells expression was significantly increased in tissues from patients with ECRS compared with non-ECRS, CRSsNP and control subjects. Moreover, inflammatory markers including type 2 proinflammatory cytokines (IL-4, IL-5, IL-13), GATA3, eosinophil cationic protein (ECP), and eotaxin levels were also increased in nasal tissues of patients with ECRS, and Vγ1+ γδT cells mRNA expression was positively correlated with type 2 cytokines, GATA3, and ECP. In the ECRS murine model, anti-Vγ1+ γδT antibody treatment reduced the infiltration of eosinophils and expression of type 2 cytokines, GATA3, and ECP in nasal mucosae. In conclusion, the results of the present study suggest that γδT cells play a crucial role in the type 2 inflammatory profiles and nasal tissue eosinophilic infiltration in patients with ECRS.
A tangled tale of microRNA and cardiac fibrosis
Authors: Chandy Mark 
Published: November 2019

Abstract
Cardiac fibrosis is important for wound healing, regeneration and producing the extracellular matrix (ECM) that provides the scaffold for cells. In pathological situations, fibroblasts are activated and remodel the ECM. In volume 133, issue 17 of Clinical Science, Yang et al. discovered that the miR-214-3p/NLRC5 axis is important for fibroblast-to-myofibroblast transition (FMT) and ECM remodelling in a pressure overload model of fibrosis [Clin. Sci. (2019) 133(17), 1845–1856]. This discovery helps to explain the complicated regulation of cardiac fibrosis. It also underscores the need for more investigation into the mechanisms of cardiac fibrosis to develop better diagnostic modalities and therapeutic options in heart failure.