bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Shared E-scooter Travels in Austin, TX
Authors: Jiao Junfeng , Bai Shunhua
Published: February 2020

This paper investigated the travel patterns of 1.7 million shared E-scooter trips from April 2018 to February 2019 in Austin, TX. There were more than 6000 active E-scooters in operation each month, generating over 150,000 trips and covered approximately 117,000 miles. During this period, the average travel distance and operation time of E-scooter trips were 0.77 miles and 7.55 min, respectively. We further identified two E-scooter usage hotspots in the city (Downtown Austin and the University of Texas campus). The spatial analysis showed that more trips originated from Downtown Austin than were completed, while the opposite was true for the UT campus. We also investigated the relationship between the number of E-scooter trips and the surrounding environments. The results show that areas with higher population density and more residents with higher education were correlated with more E-scooter trips. A shorter distance to the city center, the presence of transit stations, better street connectivity, and more compact land use were also associated with increased E scooter usage in Austin, TX. Surprisingly, the proportion of young residents within a neighborhood was negatively correlated with E-scooter usage.
Traffic Impact Area Detection and Spatiotemporal Influence Assessment for Disaster Reduction Based on Social Media: A Case Study of the 2018 Beijing Rainstorm
Authors: Yang Tengfei , Xie Jibo , Li Guoqing , Mou Naixia , Chen Cuiju , Zhao Jing , Liu Zhan , Lin Zhenyu
Published: February 2020

The abnormal change in the global climate has increased the chance of urban rainstorm disasters, which greatly threatens people’s daily lives, especially public travel. Timely and effective disaster data sources and analysis methods are essential for disaster reduction. With the popularity of mobile devices and the development of network facilities, social media has attracted widespread attention as a new source of disaster data. The characteristics of rich disaster information, near real-time transmission channels, and low-cost data production have been favored by many researchers. These researchers have used different methods to study disaster reduction based on the different dimensions of information contained in social media, including time, location and content. However, current research is not sufficient and rarely combines specific road condition information with public emotional information to detect traffic impact areas and assess the spatiotemporal influence of these areas. Thus, in this paper, we used various methods, including natural language processing and deep learning, to extract the fine-grained road condition information and public emotional information contained in social media text to comprehensively detect and analyze traffic impact areas during a rainstorm disaster. Furthermore, we proposed a model to evaluate the spatiotemporal influence of these detected traffic impact areas. The heavy rainstorm event in Beijing, China, in 2018 was selected as a case study to verify the validity of the disaster reduction method proposed in this paper.
Visualization, Spatiotemporal Patterns, and Directional Analysis of Urban Activities Using Geolocation Data Extracted from LBSN
Authors: Rizwan Muhammad , Wan Wanggen , Gwiazdzinski Luc
Published: February 2020

Location-based social networks (LBSNs) have rapidly prevailed in China with the increase in smart devices use, which has provided a wide range of opportunities to analyze urban behavior in terms of the use of LBSNs. In a LBSN, users socialize by sharing their location (also referred to as “geolocation”) in the form of a tweet (also referred to as a “check-in”), which contains information in the form of, but is not limited to, text, audio, video, etc., which records the visited place, movement patterns, and activities performed (e.g., eating, living, working, or leisure). Understanding the user’s activities and behavior in space and time using LBSN datasets can be achieved by archiving the daily activities, movement patterns, and social media behavior patterns, thus representing the user’s daily routine. The current research observing and analyzing urban activities behavior was often supported by the volunteered sharing of geolocation and the activity performed in space and time. The objective of this research was to observe the spatiotemporal and directional trends and the distribution differences of urban activities at the city and district levels using LBSN data. The density was estimated, and the spatiotemporal trend of activities was observed, using kernel density estimation (KDE); for spatial regression analysis, geographically weighted regression (GWR) analysis was used to observe the relationship between different activities in the study area. Finally, for the directional analysis, to observe the principle orientation and direction, and the spatiotemporal movement and extension trends, a standard deviational ellipse (SDE) analysis was used. The results of the study show that women were more inclined to use social media compared with men. However, the activities of male users were different during weekdays and weekends compared to those of female users. The results of the directional analysis at the district level reflect the change in the trajectory and spatiotemporal dynamics of activities. The directional analysis at the district level reveals its fine spatial structure in comparison to the whole city level. Therefore, LBSN can be considered as a supplementary and reliable source of social media big data for observing urban activities and behavior within a city in space and time.
Leveraging Container Technologies in a GIScience Project: A Perspective from Open Reproducible Research
Authors: Zaragozí Benito M. , Trilles Sergio , Navarro-Carrión José T.
Published: February 2020

Scientific reproducibility is essential for the advancement of science. It allows the results of previous studies to be reproduced, validates their conclusions and develops new contributions based on previous research. Nowadays, more and more authors consider that the ultimate product of academic research is the scientific manuscript, together with all the necessary elements (i.e., code and data) so that others can reproduce the results. However, there are numerous difficulties for some studies to be reproduced easily (i.e., biased results, the pressure to publish, and proprietary data). In this context, we explain our experience in an attempt to improve the reproducibility of a GIScience project. According to our project needs, we evaluated a list of practices, standards and tools that may facilitate open and reproducible research in the geospatial domain, contextualising them on Peng’s reproducibility spectrum. Among these resources, we focused on containerisation technologies and performed a shallow review to reflect on the level of adoption of these technologies in combination with OSGeo software. Finally, containerisation technologies proved to enhance the reproducibility and we used UML diagrams to describe representative work-flows deployed in our GIScience project.
Adaptation to Hypoxia: A Chimera?
Authors: Samaja Michele , Milano Giuseppina
Published: February 2020

“The Chimera was, according to Greek mythology, a monstrous fire-breathing hybrid creature of Lycia in Asia Minor, composed of the parts of more than one animal [...]
An Engineered Gene Nanovehicle Developed for Smart Gene Therapy to Selectively Inhibit Smooth Muscle Cells: An In Vitro Study
Authors: Cheng Ling-Yi , Wang Yu-Chi , Chen Ming-Hong , Tung Fu-I , Chiu Kuan-Ming , Liu Tse-Ying
Published: February 2020

In-stent restenosis is a serious concern for patients treated through the stenting procedure, although this can be solved using drug-eluting stents and/or drug-eluting balloon catheters. However, the chemical agents released from the drug-eluting layer for inhibiting smooth muscle cell (SMC) migration are inevitably associated with damage to vascular endothelial cell (ECs). The present in vitro study used a distinct strategy, in which a smart gene (phEGR1-PKCδ, an engineered plasmid consists of an SMC-specific promoter (human early growth response 1, hEGR1 promoter) ligated with a gene encoding apoptosis-inducing protein (protein kinase C-delta, PKCδ) was incorporated into a novel gene vehicle (Au cluster-incorporated polyethylenimine/carboxymethyl hexanoyl chitosan, PEI-Au/CHC) to form the PEI-Au/CHC/phEGR1-PKCδ complex, which was proposed for the selective inhibition of SMC proliferation. It was found that the cell viability of SMCs receiving the PEI-Au/CHC/phEGR1-PKCδ complex under simulated inflammation conditions was significantly lower than that of the ECs receiving the same treatment. In addition, the PEI-Au/CHC/phEGR1-PKCδ complex did not demonstrate an inhibitory effect on EC proliferation and migration under simulated inflammation conditions. Finally, the PEI-Au/CHC/phEGR1-PKCδ complexes coated onto a balloon catheter used in percutaneous transluminal coronary angioplasty (PTCA) could be transferred to both the ECs and the SMC layer of Sprague Dawley (SD) rat aortas ex vivo. These preliminary in vitro results suggest that the newly developed approach proposed in the present study might be a potential treatment for reducing the incidence rate of in-stent restenosis and late thrombosis in the future.
Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS
Authors: Palazzo Claudia , Abbrescia Pasqua , Valente Onofrio , Nicchia Grazia Paola , Banitalebi Shervin , Amiry-Moghaddam Mahmood , Trojano Maria , Frigeri Antonio
Published: February 2020

Translational readthrough (TRT) of aquaporin-4 (AQP4) has remarkably expanded the importance of this new post-transcriptional mechanism, as well as the regulation potential of AQP4. The TRT isoform of AQP4, named AQP4ex, is central for both AQP4 polarization and water channel activity in the central nervous system (CNS). Here we evaluate the relevance of the TRT mechanism by analyzing whether AQP4ex is also expressed in peripheral tissues and whether the expression of AQP4ex is necessary for its polarized expression as it occurs in perivascular astrocyte processes. To this purpose, AQP4ex null mice were used, and analysis was performed by immunolocalization and immunoblot. The results demonstrate that AQP4ex is expressed in kidney, stomach, trachea and skeletal muscle with the same localization pattern as the canonical AQP4 isoforms. AQP4ex protein levels vary from 6% to about 13% of the total AQP4 protein levels in peripheral tissues. Immunogold electron microscopy experiments demonstrated the localization of AQP4ex at the astrocytic endfeet, and experiments conducted on AQP4ex null mice CNS confirmed that the expression of AQP4ex is necessary for anchoring of the perivascular AQP4. Without the readthrough isoform, AQP4 assemblies are mis-localized, being uniformly distributed on the astrocyte processes facing the neuropile. No alteration of AQP4 polarization was found in AQP4ex null kidney, stomach, trachea or skeletal muscle, suggesting that AQP4ex does not have a role for proper membrane localization of AQP4 in peripheral tissues. We conclude that a dual role for AQP4ex is limited to the CNS.
Endothelial Nitric Oxide Mediates the Anti-Atherosclerotic Action of Torenia concolor Lindley var. Formosama Yamazaki
Authors: Cheng Li-Ching , Guo Bei-Chia , Chen Chia-Hui , Chang Chi-Jen , Yeh Ta-Sen , Lee Tzong-Shyuan
Published: February 2020

Torenia concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using an in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286), and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration, and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor), and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (an NOS inhibitor). Moreover, chronic treatment with TCEE attenuated hyperlipidemia, systemic and aortic inflammatory response, and the atherosclerotic lesions in apolipoprotein E-deficient mice. Collectively, our findings suggest that TCEE may confer protection from atherosclerosis by preventing endothelial dysfunction.
Strategy of Hepatic Metabolic Defects Induced by beclin1 Heterozygosity in Adult Zebrafish
Authors: Mawed Suzan Attia , He Yan , Zhang Jin , Mei Jie
Published: February 2020

Hepatic disorders have been increasing in recent years because of high carbohydrate diets. Hepatocytes depend mainly on the basal autophagy to maintain hepatic glucose/lipid homeostasis in mammals. However, the regulatory mechanisms of autophagy in hepatic energy metabolism are still unknown in fish species. Accordingly, mutant zebrafish lines of autophagy-related genes beclin1 and atg7 were generated by CRISPR/Cas9 gene-editing technology. Interestingly, unlike atg7+/−, male beclin1+/− zebrafish displayed liver defects in the morphology and histology, including abnormal hepatocyte proliferation, hemorrhagic and inflammatory phenotypes. A significant decrease in hepatocyte glycogen and an increase in hepatocyte lipids were detected in the histological assay that coincidence with the hepatic gene expression. Meanwhile, loss of heterozygosity for beclin1 creates a suitable microenvironment for hepatic tumorigenesis via phosphorylation of Akt kinase, which in turn affects liver autophagy. The reduction in autophagy activity in male beclin1+/− liver leads to a disturbance in the glucose/lipid metabolism and negatively regulates apoptosis accompanied by the induction of cellular proliferation and acute inflammatory response. Our findings highlight an important role of beclin1 in zebrafish liver development and energy metabolism, suggesting the crucial role of autophagy in maintaining homeostasis of the nutrient metabolism in fish species.
Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment
Authors: De Martinis Massimo , Sirufo Maria Maddalena , Suppa Mariano , Di Silvestre Daniela , Ginaldi Lia
Published: February 2020

Allergies are rapidly worsening in recent decades, representing the most common immunological diseases. The mechanism of disorders such as asthma, rhinocongiuntivitis, urticaria, atopic dermatitis, food and drug allergies, and anaphylaxis still remain unclear and consequently treatments is mostly still symptomatic and aspecific while developments of new therapies are limited. A growing amount of data in the literature shows us how the prevalence of allergic diseases is different in both sexes and its changes over the course of life. Genes, hormones, environmental and immunological factors affect sex disparities associated with the development and control of allergic diseases, while they more rarely are considered and reported regarding their differences related to social, psychological, cultural, economic, and employment aspects. This review describes the available knowledge on the role of sex and gender in allergies in an attempt to improve the indispensable gender perspective whose potential is still underestimated while it represents a significant turning point in research and the clinic. It will offer insights to stimulate exploration of the many aspects still unknown in this relationship that could ameliorate the preventive, diagnostic, and therapeutic strategies in allergic diseases.
Overcoming Resistance to FLT3 Inhibitors in the Treatment of FLT3-Mutated AML
Authors: Lam Stephen S.Y. , Leung Anskar Y.H.
Published: February 2020

Acute myeloid leukaemia (AML) carrying internal tandem duplication (ITD) of Fms-Like Tyrosine kinase 3 (FLT3) gene is associated with high risk of relapse and poor clinical outcome upon treatment with conventional chemotherapy. FLT3 inhibitors have been approved for the treatment of this AML subtype but leukaemia relapse remains to be a major cause of treatment failure. Mechanisms of drug resistance have been proposed, including evolution of resistant leukaemic clones; adaptive cellular mechanisms and a protective leukaemic microenvironment. These models have provided important leads that may inform design of clinical trials. Clinically, FLT3 inhibitors in combination with conventional chemotherapy as induction treatment for fit patients; with low-intensity treatment as salvage treatment or induction for unfit patients as well as maintenance treatment with FLT3 inhibitors post HSCT hold promise to improve survival in this AML subtype.
Neurons, Glia, Extracellular Matrix and Neurovascular Unit: A Systems Biology Approach to the Complexity of Synaptic Plasticity in Health and Disease
Authors: De Luca Ciro , Colangelo Anna Maria , Virtuoso Assunta , Alberghina Lilia , Papa Michele
Published: February 2020

The synaptic cleft has been vastly investigated in the last decades, leading to a novel and fascinating model of the functional and structural modifications linked to synaptic transmission and brain processing. The classic neurocentric model encompassing the neuronal pre- and post-synaptic terminals partly explains the fine-tuned plastic modifications under both pathological and physiological circumstances. Recent experimental evidence has incontrovertibly added oligodendrocytes, astrocytes, and microglia as pivotal elements for synapse formation and remodeling (tripartite synapse) in both the developing and adult brain. Moreover, synaptic plasticity and its pathological counterpart (maladaptive plasticity) have shown a deep connection with other molecular elements of the extracellular matrix (ECM), once considered as a mere extracellular structural scaffold altogether with the cellular glue (i.e., glia). The ECM adds another level of complexity to the modern model of the synapse, particularly, for the long-term plasticity and circuit maintenance. This model, called tetrapartite synapse, can be further implemented by including the neurovascular unit (NVU) and the immune system. Although they were considered so far as tightly separated from the central nervous system (CNS) plasticity, at least in physiological conditions, recent evidence endorsed these elements as structural and paramount actors in synaptic plasticity. This scenario is, as far as speculations and evidence have shown, a consistent model for both adaptive and maladaptive plasticity. However, a comprehensive understanding of brain processes and circuitry complexity is still lacking. Here we propose that a better interpretation of the CNS complexity can be granted by a systems biology approach through the construction of predictive molecular models that enable to enlighten the regulatory logic of the complex molecular networks underlying brain function in health and disease, thus opening the way to more effective treatments.
Surface Functionalization with Polyethylene Glycol and Polyethyleneimine Improves the Performance of Graphene-Based Materials for Safe and Efficient Intracellular Delivery by Laser-Induced Photoporation
Authors: Liu Jing , Li Chengnan , Brans Toon , Harizaj Aranit , Van de Steene Shana , De Beer Thomas , De Smedt Stefaan , Szunerits Sabine , Boukherroub Rabah , Xiong Ranhua , Braeckmans Kevin
Published: February 2020

Nanoparticle mediated laser-induced photoporation is a physical cell membrane disruption approach to directly deliver extrinsic molecules into living cells, which is particularly promising in applications for both adherent and suspension cells. In this work, we explored surface modifications of graphene quantum dots (GQD) and reduced graphene oxide (rGO) with polyethylene glycol (PEG) and polyethyleneimine (PEI) to enhance colloidal stability while retaining photoporation functionality. After photoporation with FITC-dextran 10 kDa (FD10), the percentage of positive HeLa cells (81% for GQD-PEG, 74% for rGO-PEG and 90% for rGO-PEI) increased approximately two-fold compared to the bare nanomaterials. While for Jurkat suspension cells, the photoporation efficiency with polymer-modified graphene-based nanomaterial reached as high as 80%. Cell viability was >80% in all these cases. In addition, polymer functionalization proved to be beneficial for the delivery of larger macromolecules (FD70 and FD500) as well. Finally, we show that rGO is suitable for photoporation using a near-infrared laser to reach 80% FD10 positive HeLa cells at 80% cell viability. We conclude that modification of graphene-based nanoparticles with PEG and especially PEI provide better colloidal stability in cell medium, resulting in more uniform transfection and overall increased efficiency.
Acetate and Butyrate Improve β-cell Metabolism and Mitochondrial Respiration under Oxidative Stress
Authors: Hu Shuxian , Kuwabara Rei , de Haan Bart J. , Smink Alexandra M. , de Vos Paul
Published: February 2020

Islet dysfunction mediated by oxidative and mitochondrial stress contributes to the development of type 1 and 2 diabetes. Acetate and butyrate, produced by gut microbiota via fermentation, have been shown to protect against oxidative and mitochondrial stress in many cell types, but their effect on pancreatic β-cell metabolism has not been studied. Here, human islets and the mouse insulinoma cell line MIN6 were pre-incubated with 1, 2, and 4 mM of acetate or butyrate with and without exposure to the apoptosis inducer and metabolic stressor streptozotocin (STZ). Both short-chain fatty acids (SCFAs) enhanced the viability of islets and β-cells, but the beneficial effects were more pronounced in the presence of STZ. Both SCFAs prevented STZ-induced cell apoptosis, viability reduction, mitochondrial dysfunction, and the overproduction of reactive oxygen species (ROS) and nitric oxide (NO) at a concentration of 1 mM but not at higher concentrations. These rescue effects of SCFAs were accompanied by preventing reduction of the mitochondrial fusion genes MFN, MFN2, and OPA1. In addition, elevation of the fission genes DRP1 and FIS1 during STZ exposure was prevented. Acetate showed more efficiency in enhancing metabolism and inhibiting ROS, while butyrate had less effect but was stronger in inhibiting the SCFA receptor GPR41 and NO generation. Our data suggest that SCFAs play an essential role in supporting β-cell metabolism and promoting survival under stressful conditions. It therewith provides a novel mechanism by which enhanced dietary fiber intake contributes to the reduction of Western diseases such as diabetes.
The Hypoxic Proteome and Metabolome of Barley (Hordeum vulgare L.) with and without Phytoglobin Priming
Authors: Andrzejczak Olga A. , Havelund Jesper F. , Wang Wei-Qing , Kovalchuk Sergey , Hagensen Christina E. , Hasler-Sheetal Harald , Jensen Ole N. , Rogowska-Wrzesinska Adelina , Møller Ian Max , Hebelstrup Kim H.
Published: February 2020

Overexpression of phytoglobins (formerly plant hemoglobins) increases the survival rate of plant tissues under hypoxia stress by the following two known mechanisms: (1) scavenging of nitric oxide (NO) in the phytoglobin/NO cycle and (2) mimicking ethylene priming to hypoxia when NO scavenging activates transcription factors that are regulated by levels of NO and O2 in the N-end rule pathway. To map the cellular and metabolic effects of hypoxia in barley (Hordeum vulgare L., cv. Golden Promise), with or without priming to hypoxia, we studied the proteome and metabolome of wild type (WT) and hemoglobin overexpressing (HO) plants in normoxia and after 24 h hypoxia (WT24, HO24). The WT plants were more susceptible to hypoxia than HO plants. The chlorophyll a + b content was lowered by 50% and biomass by 30% in WT24 compared to WT, while HO plants were unaffected. We observed an increase in ROS production during hypoxia treatment in WT seedlings that was not observed in HO seedlings. We identified and quantified 9694 proteins out of which 1107 changed significantly in abundance. Many proteins, such as ion transporters, Ca2+-signal transduction, and proteins related to protein degradation were downregulated in HO plants during hypoxia, but not in WT plants. Changes in the levels of histones indicates that chromatin restructuring plays a role in the priming of hypoxia. We also identified and quantified 1470 metabolites, of which the abundance of >500 changed significantly. In summary the data confirm known mechanisms of hypoxia priming by ethylene priming and N-end rule activation; however, the data also indicate the existence of other mechanisms for hypoxia priming in plants.
In Silico Insights into Protein–Protein Interaction Disruptive Mutations in the PCSK9-LDLR Complex
Authors: Martin William R. , Lightstone Felice C. , Cheng Feixiong
Published: February 2020

Gain-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to reduced uptake of LDL (low density lipoprotein) cholesterol and, therefore, increased plasma LDL levels. However, the mechanism by which these mutants reduce LDL reuptake is not fully understood. Here, we have used molecular dynamics simulations, MM/PBSA (Molecular Mechanics/Poisson–Boltzmann Surface Area) binding affinity calculations, and residue interaction networks, to investigate the protein–protein interaction (PPI) disruptive effects of two of PCSK9′s gain-of-function mutations, Ser127Arg and Asp374Tyr on the PCSK9 and LDL receptor complex. In addition to these PPI disruptive mutants, a third, non-interface mutation (Arg496Trp) is included as a positive control. Our results indicate that Ser127Arg and Asp374Tyr confer significantly improved binding affinity, as well as different binding modes, when compared to the wild-type. These PPI disruptive mutations lie between the EGF(A) (epidermal growth factor precursor homology domain A) of the LDL receptor and the catalytic domain of PCSK9 (Asp374Tyr) and between the prodomain of PCSK9 and the β-propeller of the LDL receptor (Ser127Arg). The interactions involved in these two interfaces result in an LDL receptor that is sterically inhibited from entering its closed conformation. This could potentially implicate the prodomain as a target for small molecule inhibitors.
Roles of Splicing Factors in Hormone-Related Cancer Progression
Authors: Takeiwa Toshihiko , Mitobe Yuichi , Ikeda Kazuhiro , Horie-Inoue Kuniko , Inoue Satoshi
Published: February 2020

Splicing of mRNA precursor (pre-mRNA) is a mechanism to generate multiple mRNA isoforms from a single pre-mRNA, and it plays an essential role in a variety of biological phenomena and diseases such as cancers. Previous studies have demonstrated that cancer-specific splicing events are involved in various aspects of cancers such as proliferation, migration and response to hormones, suggesting that splicing-targeting therapy can be promising as a new strategy for cancer treatment. In this review, we focus on the splicing regulation by RNA-binding proteins including Drosophila behavior/human splicing (DBHS) family proteins, serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) in hormone-related cancers, such as breast and prostate cancers.
Dynamics and Endocytosis of Flot1 in Arabidopsis Require CPI1 Function
Authors: Cao Yangyang , He Qizouhong , Qi Zengxing , Zhang Yan , Lu Liang , Xue Jingyuan , Li Junling , Li Ruili
Published: February 2020

Membrane microdomains are nano-scale domains (10–200 nm) enriched in sterols and sphingolipids. They have many important biological functions, including vesicle transport, endocytosis, and pathogen invasion. A previous study reported that the membrane microdomain-associated protein Flotillin1 (Flot1) was involved in plant development in Arabidopsis thaliana; however, whether sterols affect the plant immunity conveyed by Flot1 is unknown. Here, we showed that the root length in sterol-deficient cyclopropylsterol isomerase 1 (cpi1-1) mutants expressing Flot1 was significantly shorter than in control seedlings. The cotyledon epidermal cells in cpi1-1 mutants expressing Flot1 were smaller than in controls. Moreover, variable-angle total internal reflection fluorescence microscopy (VA-TIRFM) and single-particle tracking (SPT) analysis demonstrated that the long-distance Flot1-GFP movement was decreased significantly in cpi1-1 mutants compared with the control seedlings. Meanwhile, the value of the diffusion coefficient Ĝ was dramatically decreased in cpi1-1 mutants after flagelin22 (flg22) treatment compared with the control seedlings, indicating that sterols affect the lateral mobility of Flot1-GFP within the plasma membrane. Importantly, using confocal microscopy, we determined that the endocytosis of Flot1-GFP was decreased in cpi1-1 mutants, which was confirmed by fluorescence cross spectroscopy (FCS) analysis. Hence, these results demonstrate that sterol composition plays a critical role in the plant defense responses of Flot1.
Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators
Authors: Forte Nicola , Fernández-Rilo Alba Clara , Palomba Letizia , Di Marzo Vincenzo , Cristino Luigia
Published: February 2020

The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota–gut–brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the “expanded endocannabinoid (eCB) system” or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.
Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes
Authors: Chapa-Dubocq Xavier R. , Rodríguez-Graciani Keishla M. , Guzmán-Hernández Roberto A. , Jang Sehwan , Brookes Paul S. , Javadov Sabzali
Published: February 2020

Mitochondrial respiratory chain supercomplexes (RCS), particularly, the respirasome, which contains complexes I, III, and IV, have been suggested to participate in facilitating electron transport, reducing the production of reactive oxygen species (ROS), and maintaining the structural integrity of individual electron transport chain (ETC) complexes. Disassembly of the RCS has been observed in Barth syndrome, neurodegenerative and cardiovascular diseases, diabetes mellitus, and aging. However, the physiological role of RCS in high energy-demanding tissues such as the heart remains unknown. This study elucidates the relationship between RCS assembly and cardiac function. Adult male Sprague Dawley rats underwent Langendorff retrograde perfusion in the presence and absence of ethanol, isopropanol, or rotenone (an ETC complex I inhibitor). We found that ethanol had no effects on cardiac function, whereas rotenone reduced heart contractility, which was not recovered when rotenone was excluded from the perfusion medium. Blue native polyacrylamide gel electrophoresis revealed significant reductions of respirasome levels in ethanol- or rotenone-treated groups compared to the control group. In addition, rotenone significantly increased while ethanol had no effect on mitochondrial ROS production. In isolated intact mitochondria in vitro, ethanol did not affect respirasome assembly; however, acetaldehyde, a byproduct of ethanol metabolism, induced dissociation of respirasome. Isopropanol, a secondary alcohol which was used as an alternative compound, had effects similar to ethanol on heart function, respirasome levels, and ROS production. In conclusion, ethanol and isopropanol reduced respirasome levels without any noticeable effect on cardiac parameters, and cardiac function is not susceptible to moderate reductions of RCS.
Low Doses of Methylmercury Induce the Proliferation of Thyroid Cells In Vitro Through Modulation of ERK Pathway
Authors: Maggisano Valentina , Bulotta Stefania , Celano Marilena , Maiuolo Jessica , Lepore Saverio Massimo , Abballe Luana , Iannone Michelangelo , Russo Diego
Published: February 2020

Exposure to environmental endocrine disruptors has been associated with an increased frequency of thyroid pathology. In this study, we evaluated the effects of various concentrations of methylmercury (MeHg) on immortalized, non-tumorigenic thyroid cells (Nthy-ori-3-1). Exposure to MeHg at 2.5 and 5 µM for 24 h caused a reduction in cell viability with a decrease of the cell population in sub-G0 phase, as detected by MTT and flow cytometry. Conversely, MeHg at the lower concentration of 0.1 µM increased the cell viability with a rise of G2/M phase. An immunoblot analysis showed higher expression levels of phospho-ERK and not of phospho-Akt. Further enhancement of the cell growth rate was observed after a prolonged exposure of the cells up to 18 days to MeHg 0.1 µM. The present findings demonstrate the toxicity of high concentrations of MeHg on thyroid cells, while showing that treatment with lower doses of Hg, as may occur after prolonged exposure to this environmental contaminant, exerts a promoting effect on thyroid cell proliferation, by acting on the ERK-mediated pro-oncogenic signal transduction pathway.
Innovation in the Era of IoT and Industry 5.0: Absolute Innovation Management (AIM) Framework
Authors: Aslam Farhan , Aimin Wang , Li Mingze , Ur Rehman Khaliq
Published: February 2020

In the modern business environment, characterized by rapid technological advancements and globalization, abetted by IoT and Industry 5.0 phenomenon, innovation is indispensable for competitive advantage and economic growth. However, many organizations are facing problems in its true implementation due to the absence of a practical innovation management framework, which has made the implementation of the concept elusive instead of persuasive. The present study has proposed a new innovation management framework labeled as “Absolute Innovation Management (AIM)” to make innovation more understandable, implementable, and part of the organization’s everyday routine by synergizing the innovation ecosystem, design thinking, and corporate strategy to achieve competitive advantage and economic growth. The current study used an integrative literature review methodology to develop the “Absolute Innovation Management” framework. The absolute innovation management framework links the innovation ecosystem with the corporate strategy of the firm by adopting innovation management as a strategy through design thinking. Thus, making innovation more user/human-centered that is desirable by the customer, viable for business and technically feasible, creating both entrepreneurial and customer value, and boosting corporate venturing and corporate entrepreneurship to achieve competitive advantage and economic growth while addressing the needs of IoT and Industry 5.0 era. In sum, it synergizes innovation, design thinking, and strategy to make businesses future-ready for IoT and industry 5.0 revolution. The present study is significant, as it not only make considerable contributions to the existing literature on innovation management by developing a new framework but also makes the concept more practical, implementable and part of an organization’s everyday routine.
Albumentations: Fast and Flexible Image Augmentations
Authors: Buslaev Alexander , Iglovikov Vladimir I. , Khvedchenya Eugene , Parinov Alex , Druzhinin Mikhail , Kalinin Alexandr A.
Published: February 2020

Data augmentation is a commonly used technique for increasing both the size and the diversity of labeled training sets by leveraging input transformations that preserve corresponding output labels. In computer vision, image augmentations have become a common implicit regularization technique to combat overfitting in deep learning models and are ubiquitously used to improve performance. While most deep learning frameworks implement basic image transformations, the list is typically limited to some variations of flipping, rotating, scaling, and cropping. Moreover, image processing speed varies in existing image augmentation libraries. We present Albumentations, a fast and flexible open source library for image augmentation with many various image transform operations available that is also an easy-to-use wrapper around other augmentation libraries. We discuss the design principles that drove the implementation of Albumentations and give an overview of the key features and distinct capabilities. Finally, we provide examples of image augmentations for different computer vision tasks and demonstrate that Albumentations is faster than other commonly used image augmentation tools on most image transform operations.
Constructive Alignment in Game Design for Learning Activities in Higher Education
Authors: Romero Margarida , Kalmpourtzis George
Published: February 2020

The Bologna process has led European universities to review quality assurance in Higher Education. Active learning, competency-based education as well as outcome-based teaching and learning have been encouraged as means to maintain quality assurance in Higher Education. The aims of this paper are (a) to introduce the context of European Higher Education quality assurance challenges and review existing initiatives in game design in Higher Education, and (b) analyze the game design process in the Game Based Learning course of the MSc SmartEdTech program through the prism of constructive alignment. The analysis of student deliverables, in the form of Game Design Documents, shows improvement on how students approach educational game design but also points out some aspects for improvement on the course structure. The study also considers opportunities and limits of game design for learning in Higher Education in the specific context of online education.
Salivary Redox Biomarkers in Selected Neurodegenerative Diseases
Authors: Maciejczyk Mateusz , Zalewska Anna , Gerreth Karolina
Published: February 2020

Neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are disorders, which cause irreversible and progressive deterioration of the central nervous system. The pathophysiology of NDDs is still not fully explained; nevertheless, oxidative stress is considered as a critical mediator of cerebral degeneration, brain inflammation, as well as neuronal apoptosis. Therefore, it is not surprising that redox biomarkers are increasingly used in the diagnosis of neurodegenerative diseases. As saliva is a very easy to obtain bioliquid, it seems promising to use this biomaterial in the diagnosis of NDDs. Saliva collection is easy, cheap, stress-free, and non-infectious, and it does not require the help of a specialised medical personnel. Additionally, the concentrations of many salivary redox biomarkers correlate with their content in blood serum as well as the degree of disease progression, which makes them non-invasive indicators of NDDs. This paper reviews the latest knowledge concerning the use of salivary redox biomarkers in the diagnosis and prognosis of selected neurodegenerative diseases.
The Benefits of emotion Regulation Interventions in Virtual Reality for the Improvement of Wellbeing in Adults and Older Adults: A Systematic Review
Authors: Montana Jessica Isbely , Matamala-Gomez Marta , Maisto Marta , Mavrodiev Petar Aleksandrov , Cavalera Cesare Massimo , Diana Barbara , Mantovani Fabrizia , Realdon Olivia
Published: February 2020

The impact of emotion regulation interventions on wellbeing has been extensively documented in literature, although only in recent years virtual reality (VR) technologies have been incorporated in the design of such interventions, in both clinical and non-clinical settings. A systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, was therefore carried out to explore the state of the art in emotion regulation interventions for wellbeing using virtual reality. The literature on this topic was queried, 414 papers were screened, and 11 studies were included, covering adults and older adults. Our findings offer an overview of the current use of VR technologies for the enhancement of emotion regulation (ER) and wellbeing. The results are promising and suggest that VR-based emotion regulation training can facilitate the promotion of wellbeing. An overview of VR-based training interventions is crucial for better understanding how to use these tools in the clinical settings. This review offers a critical debate on the structure of such intervention protocols. It also analyzes and highlights the crucial role played by the selection of the objective and subjective wellbeing assessment measures of said intervention protocols.
Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study
Authors: Picca Anna , Guerra Flora , Calvani Riccardo , Marini Federico , Biancolillo Alessandra , Landi Giovanni , Beli Raffaella , Landi Francesco , Bernabei Roberto , Bentivoglio Anna , Lo Monaco Maria , Bucci Cecilia , Marzetti Emanuele
Published: February 2020

Systemic inflammation and mitochondrial dysfunction are involved in neurodegeneration in Parkinson’s disease (PD). Extracellular vesicle (EV) trafficking may link inflammation and mitochondrial dysfunction. In the present study, circulating small EVs (sEVs) from 16 older adults with PD and 12 non-PD controls were purified and characterized. A panel of serum inflammatory biomolecules was measured by multiplex immunoassay. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers (adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), nicotinamide adenine dinucleotide reduced form (NADH):ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2)) were quantified in purified sEVs by immunoblotting. Relative to controls, PD participants showed a greater amount of circulating sEVs. Levels of CD9 and CD63 were lower in the sEV fraction of PD participants, whereas those of CD81 were similar between groups. Lower levels of ATP5A, NDUFS3, and SDHB were detected in sEVs from PD participants. No signal was retrieved for UQCRC2, MTCOI, or NDUFB8 in either participant group. To identify a molecular signature in circulating sEVs in relationship to systemic inflammation, a low level-fused (multi-platform) partial least squares discriminant analysis was applied. The model correctly classified 94.2% ± 6.1% PD participants and 66.7% ± 5.4% controls, and identified seven biomolecules as relevant (CD9, NDUFS3, C-reactive protein, fibroblast growth factor 21, interleukin 9, macrophage inflammatory protein 1β, and tumor necrosis factor alpha). In conclusion, a mitochondrial signature was identified in circulating sEVs from older adults with PD, in association with a specific inflammatory profile. In-depth characterization of sEV trafficking may allow identifying new biomarkers for PD and possible targets for personalized interventions.
Clinical Impact of Atypical Chest Pain and Diabetes Mellitus in Patients with Acute Myocardial Infarction from Prospective KAMIR-NIH Registry
Authors: Lee Jun-Won , Moon Jin Sil , Kang Dae Ryong , Lee Sang Jun , Son Jung-Woo , Youn Young Jin , Ahn Sung Gyun , Ahn Min-Soo , Kim Jang-Young , Yoo Byung-Su , Lee Seung-Hwan , Kim Ju Han , Jeong Myung Ho , Park Jong-Seon , Chae Shung Chull , Hur Seung Ho , Cho Myeng-Chan , Rha Seung Woon , Cha Kwang Soo , Chae Jei Keon , Choi Dong-Ju , Seong In Whan , Oh Seok Kyu , Hwang Jin Yong , Yoon Junghan
Published: February 2020

Atypical chest pain and diabetic autonomic neuropathy attract less clinical attention, leading to underdiagnosis and delayed treatment. To evaluate the long-term clinical impact of atypical chest pain and diabetes mellitus (DM), we categorized 11,159 patients with acute myocardial infarction (AMI) from the Korea AMI-National Institutes of Health between November 2011 and December 2015 into four groups (atypical DM, atypical non-DM, typical DM, and typical non-DM). The primary endpoint was defined as patient-oriented composite endpoint (POCE) at 2 years including all-cause death, any myocardial infarction (MI), and any revascularization. Patients with atypical chest pain showed higher 2-year mortality than those with typical chest pain in both DM (29.5% vs. 11.4%, p < 0.0001) and non-DM (20.4% vs. 6.3%, p < 0.0001) groups. The atypical DM group had the highest risks of POCE (hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.48–2.10), all-cause death (HR 2.23, 95% CI 1.80–2.76) and any MI (HR 2.34, 95% CI 1.51–3.64) in the adjusted model. In conclusion, atypical chest pain was significantly associated with mortality in patients with AMI. Among four groups, the atypical DM group showed the worst clinical outcomes at 2 years. Application of rapid rule in/out AMI protocols would be beneficial to improve clinical outcomes.