bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowing, Being and Co-Constructing an Age-Friendly Tāmaki Makaurau Auckland
Authors: Blakey Judy , Clews Janet
Published: December 2020

A third of Aotearoa New Zealand’s increasingly ageing population resides in Tāmaki Makaurau Auckland. This most populous cosmopolitan urban area in the country is also home to the largest Polynesian population of any global city. Sprawling across a North Island isthmus inclusive of Hauraki Gulf islands, 70% of the city region is rural, whilst almost 90% of the ethnically diverse residents live in urban areas. Members of Auckland Council’s Seniors Advisory Panel (SAP) advocated for, and in 2018 secured unanimous support from the governing body to resource an Age-friendly City (AFC) Project. This case study inquiry applied bricolage methodology to provide diverse contextual perspectives of this unique Polynesian setting, prior to exploring interview narratives of three SAP members who served two consecutive terms (six years) as AFC advocates. Weaving insights gleaned from their interview transcripts responding to relational leadership prompts about their age-friendly advocacy with the findings from the council’s AFC Community Engagement report highlighted the achievements and challenges of the evolving AFC Project. Service-learning recommendations include co-developing: (1) A sustainable co-governance framework for an independent steering group that embodies the values and principles of Te Tiriti o Waitangi to enable empowered active ageing for all residents; (2) A succession plan that enables the timely transfer of knowledge and skills to empower incoming SAP members.
A 3-year Longitudinal Study of Pocket Money, Eating Behavior, Weight Status: The Childhood Obesity Study in China Mega-Cities
Authors: Ma Lu , Fang Zeping , Gao Liwang , Zhao Yaling , Xue Hong , Li Ke , Wang Youfa
Published: December 2020

The associations between children’s pocket money and their eating behaviors and weight status have not been examined using longitudinal data in China. Examined child and parental factors associated with children’s pocket money, and longitudinal effects of pocket money on children’s eating behaviors and weight status. Data were collected in 2015, 2016, and 2017 from 3261 school-age children and their parents in mega-cities across China (Beijing, Shanghai, Nanjing, Xi’an, Chengdu). Children’s weight, height, and waist circumference were measured; pocket money and eating behaviors were self-reported. Mixed effect models were used. Older children received more pocket money than younger children (incident rate ratio (IRR) = 1.21, 95% confidence interval (CI): 1.15, 1.26). Fathers gave their children more pocket money than mothers did (IRR = 1.22, 95% CI: 1.16, 1.30). Children with fathers having ≥ college education received more pocket money than the others did (IRR = 1.20, 95% CI: 1.04, 1.40). Some nutrition-related parenting behaviors and attitude were also associated with children’s pocket money. Compared with children receiving no weekly pocket money, those having 1–10 or 10–30 or >30-yuan weekly pocket money were 12.0–136% more likely to consume unhealthy foods and were 66–132% more likely to be overweight or obese. Some child and parental factors were associated with children’s pocket money, which increased risks of having unhealthy eating behaviors and being overweight and obese.
Long-Term Ambient Air Pollutant Exposure and Risk of Recurrent Headache in Children: A 12-Year Cohort Study
Authors: Hong Syuan-Yu , Wan Lei , Lin Hui-Ju , Lin Cheng-Li , Wei Chang-Ching
Published: December 2020

Although studies have suggested environmental factors to be triggers of headache, the contribution of long-term air pollution exposure to recurrent headaches is poorly understood. Hence, we executed this nationwide cohort study to investigate associations between levels of ambient air pollutants and risks of recurrent headaches in children in Taiwan from 2000 to 2012. We used data from the Taiwan National Health Insurance Research Database and linked them to the Taiwan Air Quality Monitoring Database. Overall, 218,008 children aged < 18 were identified from 1 January 2000, and then followed until they were diagnosed by a physician for ≥3 times with recurrent headaches or until 31 December 2012. We categorized the annual average concentration of each air pollutant (fine particulate matter, total hydrocarbon, methane, sulfur dioxide, and nitrogen dioxide) into quartiles (Q1–Q4). We measured the incidence rate, hazard ratios (HRs), and the corresponding 95% confidence intervals for recurrent headaches. stratified by the quartiles. A total of 28,037 children (12.9%) were identified with recurrent headaches. The incidence rate and adjusted HR for recurrent headaches increased with higher-level exposure of air pollutants, except sulfur dioxide. We herein demonstrate that long-term ambient air pollutant exposure might be a risk factor for childhood recurrent headaches.
Research on Pricing and Service Level Strategies of Dual Channel Reverse Supply Chain Considering Consumer Preference in Multi-Regional Situations
Authors: Kang Yao , Chen Juhong , Wu Di
Published: December 2020

Facing the increasingly serious waste electrical and electronic equipment (WEEE) recycling problem, recycling enterprises actively introduce online recycling channels, build dual channel reverse supply chains (DRSC), and use high-level recycling price and service levels to enhance consumers’ recycling enthusiasm and recycling amount. Nevertheless, in China, where the imbalance of regional development is widespread, the recycling center, third-party recycler (TPR), and third-party platform (TPP) are faced with the choices of pricing and service level when facing multi-regional consumers. This paper mainly answers the following questions: (1) When the recycling center and TPP introduce online recycling channels in multi-regional situations, how should they set online recycling price, transfer price, and service level? (2) When consumer preference for online channels changes in a certain region, how should recycling enterprises adjust their optimal pricing and service level decisions for different regions to maximize their own profits? How do the profits of recycling enterprises change? In order to solve the above problems, in this paper, we propose three pricing and service level decision models for the recycling center with online channels, namely, keeping prices unchanged, unifying all prices, and maximizing its own profits. By using the Stackelberg game to solve the model, we get the optimal pricing, service level decisions, as well as the maximum profits of the recycling center, TPP, and TPR when consumer preference changes. By analyzing the results of the model, we find that the change of consumer preference for online channels in a certain region will affect the decision and profits of multi-regional recycling enterprises. Specifically, consumer preference for online channels in a certain region will not only lead to an increase in the profits of the recycling center and TPP and a decrease in the profit of local TPRs, but also an increase in the profit of TPRs in other regions. In addition, at the beginning of introducing online channels, the recycling center can adopt two strategies to avoid conflicts among channels: keeping offline transfer prices unchanged and unifying all transfer prices, but the former promotes its economic profits more significantly.
Multi-Criteria Evaluation (MCE) Method for the Management of Woodland Plantations in Floodplain Areas
Authors: Tzioutzios Christos , Kastridis Aristeidis
Published: December 2020

The potential of woodland and floodplain woodland plantations in a wide area, of high flood risk, along the Spey River (Scotland) is investigated, to mitigate the floods’ catastrophic impact. The spatial analysis required various datasets to be overlaid, to define the suitable sites for woodland and floodplain woodland establishment. These datasets that concern the topography, the physical and technical characteristics (existing woodland, road system, urban and rural areas, river system and open water areas, railway) and the protected sites of the study area were obtained and merged using Geographical Information System (GIS) techniques. The most suitable and unsuitable areas within the region were identified, using multi-criteria evaluation methods (Boolean approach). In total, 13 constraints were created by expressing true/false statements for each factor, and were combined together using spatial analysis tools. The results revealed the high potential of woodland and floodplain woodland plantations to prevent floods, with 59.2% of the total study area (177.5 km2) determined to be appropriate for such practices’ application. The River Dulnain tributary demonstrated the highest potential for floodplain woodland planting, followed by Rivers Avon and Fiddich, and the southwestern and northeastern Spey River parts. The methodology proposed is simple and provides rapid and accurate results at low cost, while the datasets can be easily accessed and are available in convenient type/format. This useful methodology for researchers and authorities could be applied successfully to similar watersheds, contributing significantly to flood risk mitigation and the enhancement of the flood-preventative measures’ planning efficiency.
Spatial Dimensions of Female Political Participation: Regional Perspective of Women’s Descriptive Representation in Czech Local Councils, 1994–2018
Authors: Maškarinec Pavel
Published: December 2020

This paper focusses on the analysis of female political participation in the decision-making processes at the local level. We analyse women’s descriptive representation in Czechia on a very detailed spatial structure and an extended yearly time series (1994–2018). The main goal of the paper is to examine the spatial dimension of the disparities in female representation in local elections at the level of all Czech municipalities. To achieve this goal, global and local spatial autocorrelation methods were used. The observed spatial patterns of women’s descriptive representation in Czech local councils proved to be very stable. Furthermore, an analysis of the spatio-temporal (in)stability of women’s representation across different elections demonstrated that despite the divergent spatial autocorrelation of women’s descriptive representation across Czechia’s territory, there were no substantial changes in the clustering of women’s representation between elections, except for an identified overall decline in the homogeneity of the clusters. This suggests the existence of considerable spatio-temporal stability of women’s representation between local elections in the different municipalities. Thus, women’s descriptive representation attained in a municipality in a specific election reproduces at a similar level in the following elections rather than diffusing to surrounding municipalities in the form of a contagion effect.
An Adaptive Cutoff Frequency Selection Approach for Fast Fourier Transform Method and Its Application into Short-Term Traffic Flow Forecasting
Authors: Wang Runjie , Shi Wenzhong , Liu Xianglei , Li Zhiyuan
Published: December 2020

Historical measurements are usually used to build assimilation models in sequential data assimilation (S-DA) systems. However, they are always disturbed by local noises. Simultaneously, the accuracy of assimilation model construction and assimilation forecasting results will be affected. The fast Fourier transform (FFT) method can be used to acquire de-noised historical traffic flow measurements to reduce the influence of local noises on constructed assimilation models and improve the accuracy of assimilation results. In the practical signal de-noising applications, the FFT method is commonly used to de-noise the noisy signal with known noise frequency. However, knowing the noise frequency is difficult. Thus, a proper cutoff frequency should be chosen to separate high-frequency information caused by noises from the low-frequency part of useful signals under the unknown noise frequency. If the cutoff frequency is too high, too much noisy information will be treated as useful information. Conversely, if the cutoff frequency is too low, part of the useful information will be lost. To solve this problem, this paper proposes an adaptive cutoff frequency selection (A-CFS) method based on cross-validation. The proposed method can determine a proper cutoff frequency and ensure the quality of de-noised outputs for a given dataset using the FFT method without noise frequency information. Experimental results of real-world traffic flow data measurements in a sub-area of a highway near Birmingham, England, demonstrate the superior performance of the proposed A-CFS method in noisy information separation using the FFT method. The differences between true and predicted traffic flow values are evaluated using the mean absolute error (MAE), root mean square error (RMSE), and mean absolute percentage (MAPE) values. Compared to the results of the two commonly used de-noising methods, i.e., discrete wavelet transform (DWT) and ensemble empirical mode decomposition (EEMD) methods, the short-term traffic flow forecasting results of the proposed A-CFS method are much more reliable. In terms of the MAE value, the average relative improvements of the assimilation model built using the proposed method are 19.26%, 3.47%, and 4.25%, compared to the model built using raw data, DWT method, and EEMD method, respectively; the corresponding average relative improvements in RMSE are 19.05%, 5.36%, and 3.02%, respectively; lastly, the corresponding average relative improvements in MAPE are 18.88%, 2.83%, and 2.28%, respectively. The test results show that the proposed method is effective in separating noises from historical measurements and can improve the accuracy of assimilation model construction and assimilation forecasting results.
Fluorescence-Based Nanoparticle Tracking Analysis and Flow Cytometry for Characterization of Endothelial Extracellular Vesicle Release
Authors: Oesterreicher Johannes , Pultar Marianne , Schneider Jaana , Mühleder Severin , Zipperle Johannes , Grillari Johannes , Holnthoner Wolfgang
Published: December 2020

As extracellular vesicles (EVs) have become a prominent topic in life sciences, a growing number of studies are published on a regular basis addressing their biological relevance and possible applications. Nevertheless, the fundamental question of the true vesicular nature as well as possible influences on the EV secretion behavior have often been not adequately addressed. Furthermore, research regarding endothelial cell-derived EVs (EndoEVs) often focused on the large vesicular fractions comprising of microvesicles (MV) and apoptotic bodies. In this study we aimed to further extend the current knowledge of the influence of pre-isolation conditions, such as cell density and conditioning time, on EndoEV release from human umbilical vein endothelial cells (HUVECs). We combined fluorescence nanoparticle tracking analysis (NTA) and the established fluorescence-triggered flow cytometry (FT-FC) protocol to allow vesicle-specific detection and characterization of size and surface markers. We found significant effects of cell density and conditioning time on both abundance and size distribution of EndoEVs. Additionally, we present detailed information regarding the surface marker display on EVs from different fractions and size ranges. Our data provide crucial relevance for future projects aiming to elucidate EV secretion behavior of endothelial cells. Moreover, we show that the influence of different conditioning parameters on the nature of EndoEVs has to be considered.
Toxicology and Analysis of Psychoactive Tryptamines
Authors: Malaca Sara , Lo Faro Alfredo Fabrizio , Tamborra Alice , Pichini Simona , Busardò Francesco Paolo , Huestis Marilyn A.
Published: December 2020

Our understanding of tryptamines is poor due to the lack of data globally. Tryptamines currently are not part of typical toxicology testing regimens and their contribution to drug overdoses may be underestimated. Although their prevalence was low, it is increasing. There are few published data on the many new compounds, their mechanisms of action, onset and duration of action, toxicity, signs and symptoms of intoxication and analytical methods to identify tryptamines and their metabolites. We review the published literature and worldwide databases to describe the newest tryptamines, their toxicology, chemical structures and reported overdose cases. Tryptamines are 5-HT2A receptor agonists that produce altered perceptions of reality. Currently, the most prevalent tryptamines are 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT), 5-methoxy-N,N- diallyltryptamine (5-MeO-DALT) and dimethyltryptamine (DMT). From 2015 to 2020, 22 new analytical methods were developed to identify/quantify tryptamines and metabolites in biological samples, primarily by liquid chromatography tandem mass spectrometry. The morbidity accompanying tryptamine intake is considerable and it is critical for clinicians and laboratorians to be informed of the latest data on this public health threat.
Guanosine-Mediated Anxiolytic-Like Effect: Interplay with Adenosine A1 and A2A Receptors
Authors: Frinchi Monica , Verdi Vincenzo , Plescia Fulvio , Ciruela Francisco , Grillo Maria , Garozzo Roberta , Condorelli Daniele F. , Di Iorio Patrizia , Caciagli Francesco , Ciccarelli Renata , Belluardo Natale , Di Liberto Valentina , Mudò Giuseppa
Published: December 2020

Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or A1R (CPA, CCPA) or A2AR (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, whereas when administered alone, each compound was ineffective as compared to the control group. Interestingly, the pretreatment with nonselective antagonist caffeine or selective A1R (DPCPX) or A2AR (ZM241385) antagonists did not modify the GUO-induced anxiolytic-like effect. Finally, binding assay performed in hippocampal membranes showed that [3H]GUO binding became saturable at 100–300 nM, suggesting the existence of a putative GUO binding site. In competition experiments, ADO showed a potency order similar to GUO in displacing [3H]GUO binding, whereas AR selective agonists, CPA and CGS21680, partially displaced [3H]GUO binding, but the sum of the two effects was able to displace [3H]GUO binding to the same extent of ADO alone. Overall, our results strengthen previous data supporting GUO-mediated anxiolytic-like effects, add new evidence that these effects are blocked by A1R and A2AR agonists and pave, although they do not elucidate the mechanism of GUO and ADO receptor interaction, for a better characterization of GUO binding sites in ARs.
Nucleosome Positioning around Transcription Start Site Correlates with Gene Expression Only for Active Chromatin State in Drosophila Interphase Chromosomes
Authors: Levitsky Victor G. , Zykova Tatyana Yu. , Moshkin Yuri M. , Zhimulev Igor F.
Published: December 2020

We analyzed the whole-genome experimental maps of nucleosomes in Drosophila melanogaster and classified genes by the expression level in S2 cells (RPKM value, reads per kilobase million) as well as the number of tissues in which a gene was expressed (breadth of expression, BoE). Chromatin in 5′-regions of genes we classified on four states according to the hidden Markov model (4HMM). Only the Aquamarine chromatin state we considered as Active, while the rest three states we defined as Non-Active. Surprisingly, about 20/40% of genes with 5′-regions mapped to Active/Non-Active chromatin possessed the minimal/at least modest RPKM and BoE. We found that regardless of RPKM/BoE the genes of Active chromatin possessed the regular nucleosome arrangement in 5′-regions, while genes of Non-Active chromatin did not show respective specificity. Only for genes of Active chromatin the RPKM/BoE positively correlates with the number of nucleosome sites upstream/around TSS and negatively with that downstream TSS. We propose that for genes of Active chromatin, regardless of RPKM value and BoE the nucleosome arrangement in 5′-regions potentiates transcription, while for genes of Non-Active chromatin, the transcription machinery does not require the substantial support from nucleosome arrangement to influence gene expression.
Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll-Like Receptor 4 Pathway in LPS-Induced RAW 264.7 Cells
Authors: Kwon Mijin , Lee Jaehoon , Park Sangkyu , Kwon Oh-Hee , Seo Jeongmin , Roh Sangho
Published: December 2020

Inflammation is a biological response of the immune system to defend the body from negative stimulation. However, the excessive inflammatory response can damage host tissues and pose serious threats. Exopolysaccharide (EPS), one of the postbiotics, is secreted from lactic acid bacteria. Although many studies have described the beneficial effects of EPS, such as its anti-inflammatory and anti-oxidant effects, its underlying mechanisms have remained to be poorly understood. Thus, we identified that EPS obtained from Lactobacillus plantarum L-14 was a homogeneous polysaccharide primarily comprised of glucose. To examine these anti-inflammatory effects, an inflammatory response was induced by lipopolysaccharide (LPS) administration to mouse macrophage RAW 264.7 cells that were pretreated with EPS. The anti-inflammatory effects of EPS were identified by analyzing the changes within inflammatory markers at the molecular level. We demonstrate here that EPS suppressed proinflammatory mediators, such as cyclooxygenase-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β, and downregulated the expression of an inducible nitric oxide synthase known to lead to oxidative stress. It was also confirmed that EPS had anti-inflammatory effects by blocking the interaction of LPS with Toll-like receptor 4 (TLR4), as demonstrated by using the known TLR4 inhibitor TAK-242. In addition, we found that EPS itself could suppress the expression of TLR4. Consequently, our data suggest that EPS can be a potential target for the development of natural product-derived medicine for treating inflammatory diseases related to TLR4.
Effects of Sphingosine-1-Phosphate on Cell Viability, Differentiation, and Gene Expression of Adipocytes
Authors: Wu Xiyuan , Sakharkar Meena Kishore , Wabitsch Martin , Yang Jian
Published: December 2020

Sphingosine-1-phosphate (S1P) is a highly potent sphingolipid metabolite, which controls numerous physiological and pathological process via its extracellular and intracellular functions. The breast is mainly composed of epithelial cells (mammary gland) and adipocytes (stroma). Adipocytes play an important role in regulating the normal functions of the breast. Compared to the vast amount studies on breast epithelial cells, the functions of S1P in breast adipocytes are much less known. Thus, in the current study, we used human preadipocyte cell lines SGBS and mouse preadipocyte cell line 3T3-L1 as in vitro models to evaluate the effects of S1P on cell viability, differentiation, and gene expression in adipocytes. Our results showed that S1P increased cell viability in SGBS and 3T3-L1 preadipocytes but moderately reduced cell viability in differentiated SGBS and 3T3-L1 adipocytes. S1P was also shown to inhibit adipogenic differentiation of SGBS and 3T3-L1 at concentration higher than 1000 nM. Transcriptome analyses showed that S1P was more influential on gene expression in differentiated adipocytes. Furthermore, our network analysis in mature adipocytes showed that the upregulated DEGs (differentially expressed genes) were related to regulation of lipolysis, PPAR (peroxisome proliferator-activated receptor) signaling, alcoholism, and toll-like receptor signaling, whereas the downregulated DEGs were overrepresented in cytokine-cytokine receptor interaction, focal adhesion, starch and sucrose metabolism, and nuclear receptors pathways. Together previous studies on the functions of S1P in breast epithelial cells, the current study implicated that S1P may play a critical role in modulating the bidirectional regulation of adipocyte-extracellular matrix-epithelial cell axis and maintaining the normal physiological functions of the breast.
miR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions
Authors: Beer Lucian , Kalinina Polina , Köcher Martin , Laggner Maria , Jeitler Markus , Abbas Zadeh Salman , Copic Dragan , Tschachler Erwin , Mildner Michael
Published: December 2020

The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA–miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1β and INFγ synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.
Self-Assembly of pH-Labile Polymer Nanoparticles for Paclitaxel Prodrug Delivery: Formulation, Characterization, and Evaluation
Authors: Levit Shani L. , Gade Narendar Reddy , Roper Thomas D. , Yang Hu , Tang Christina
Published: December 2020

The efficacy of paclitaxel (PTX) is limited due to its poor solubility, poor bioavailability, and acquired drug resistance mechanisms. Designing paclitaxel prodrugs can improve its anticancer activity and enable formulation of nanoparticles. Overall, the aim of this work is to improve the potency of paclitaxel with prodrug synthesis, nanoparticle formation, and synergistic formulation with lapatinib. Specifically, we improve potency of paclitaxel by conjugating it to α-tocopherol (vitamin E) to produce a hydrophobic prodrug (Pro); this increase in potency is indicated by the 8-fold decrease in half maximal inhibitory concentration (IC50) concentration in ovarian cancer cell line, OVCA-432, used as a model system. The efficacy of the paclitaxel prodrug was further enhanced by encapsulation into pH-labile nanoparticles using Flash NanoPrecipitation (FNP), a rapid, polymer directed self-assembly method. There was an 1100-fold decrease in IC50 concentration upon formulating the prodrug into nanoparticles. Notably, the prodrug formulations were 5-fold more potent than paclitaxel nanoparticles. Finally, the cytotoxic effects were further enhanced by co-encapsulating the prodrug with lapatinib (LAP). Formulating the drug combination resulted in synergistic interactions as indicated by the combination index (CI) of 0.51. Overall, these results demonstrate this prodrug combined with nanoparticle formulation and combination therapy is a promising approach for enhancing paclitaxel potency.
Secretory Peptides as Bullets: Effector Peptides from Pathogens against Antimicrobial Peptides from Soybean
Authors: Ku Yee-Shan , Cheng Sau-Shan , Gerhardt Aisha , Cheung Ming-Yan , Contador Carolina A. , Poon Lok-Yiu Winnie , Lam Hon-Ming
Published: December 2020

Soybean is an important crop as both human food and animal feed. However, the yield of soybean is heavily impacted by biotic stresses including insect attack and pathogen infection. Insect bites usually make the plants vulnerable to pathogen infection, which causes diseases. Fungi, oomycetes, bacteria, viruses, and nematodes are major soybean pathogens. The infection by pathogens and the defenses mounted by soybean are an interactive and dynamic process. Using fungi, oomycetes, and bacteria as examples, we will discuss the recognition of pathogens by soybean at the molecular level. In this review, we will discuss both the secretory peptides for soybean plant infection and those for pathogen inhibition. Pathogenic secretory peptides and peptides secreted by soybean and its associated microbes will be included. We will also explore the possible use of externally applied antimicrobial peptides identical to those secreted by soybean and its associated microbes as biopesticides.
Policing Cancer: Vitamin D Arrests the Cell Cycle
Authors: Bhoora Sachin , Punchoo Rivak
Published: December 2020

Vitamin D is a steroid hormone crucial for bone mineral metabolism. In addition, vitamin D has pleiotropic actions in the body, including anti-cancer actions. These anti-cancer properties observed within in vitro studies frequently report the reduction of cell proliferation by interruption of the cell cycle by the direct alteration of cell cycle regulators which induce cell cycle arrest. The most recurrent reported mode of cell cycle arrest by vitamin D is at the G1/G0 phase of the cell cycle. This arrest is mediated by p21 and p27 upregulation, which results in suppression of cyclin D and E activity which leads to G1/G0 arrest. In addition, vitamin D treatments within in vitro cell lines have observed a reduced C-MYC expression and increased retinoblastoma protein levels that also result in G1/G0 arrest. In contrast, G2/M arrest is reported rarely within in vitro studies, and the mechanisms of this arrest are poorly described. Although the relationship of epigenetics on vitamin D metabolism is acknowledged, studies exploring a direct relationship to cell cycle perturbation is limited. In this review, we examine in vitro evidence of vitamin D and vitamin D metabolites directly influencing cell cycle regulators and inducing cell cycle arrest in cancer cell lines.
Intravitreal Injection of Liposomes Loaded with a Histone Deacetylase Inhibitor Promotes Retinal Ganglion Cell Survival in a Mouse Model of Optic Nerve Crush
Authors: Sung Mi Sun , Moon Myeong Ju , Thomas Reju George , Kim So Young , Lee Jun Sung , Jeong Yong Yeon , Park In-Kyu , Park Sang Woo
Published: December 2020

Various neuroprotective agents have been studied for the treatment of retinal ganglion cell (RGC) diseases, but issues concerning the side effects of systemically administered drugs and the short retention time of intravitreally injected drugs limit their clinical applications. The current study aimed to evaluate the neuroprotective effects of intravitreally injected trichostatin A (TSA)-loaded liposomes in a mouse model of optic nerve crush (ONC) and determine whether TSA-loaded liposomes have therapeutic potential in RGC diseases. The histone deacetylase inhibitor, TSA, was incorporated into polyethylene glycolylated liposomes. C57BL/6J mice were treated with an intravitreal injection of TSA-loaded liposomes and liposomes loaded with a lipophilic fluorescent dye for tracking, immediately after ONC injury. The expression of macroglial and microglial cell markers (glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1), RGC survival, and apoptosis were assessed. We found that the liposomes reached the inner retina. Their fluorescence was detected for up to 10 days after the intravitreal injection, with peak intensity at 3 days postinjection. Intravitreally administered TSA-loaded liposomes significantly decreased reactive gliosis and RGC apoptosis and increased RGC survival in a mouse model of ONC. Our results suggest that TSA-loaded liposomes may help in the treatment of various RGC diseases.
The Roles of Sodium-Independent Inorganic Phosphate Transporters in Inorganic Phosphate Homeostasis and in Cancer and Other Diseases
Authors: Lacerda-Abreu Marco Antonio , Russo-Abrahão Thais , Meyer-Fernandes Jose Roberto
Published: December 2020

Inorganic phosphate (Pi) is an essential nutrient for the maintenance of cells. In healthy mammals, extracellular Pi is maintained within a narrow concentration range of 0.70 to 1.55 mM. Mammalian cells depend on Na+/Pi cotransporters for Pi absorption, which have been well studied. However, a new type of sodium-independent Pi transporter has been identified. This transporter assists in the absorption of Pi by intestinal cells and renal proximal tubule cells and in the reabsorption of Pi by osteoclasts and capillaries of the blood–brain barrier (BBB). Hyperphosphatemia is a risk factor for mineral deposition, the development of diseases such as osteoarthritis, and vascular calcifications (VCs). Na+-independent Pi transporters have been identified and biochemically characterized in vascular smooth muscle cells (VSMCs), chondrocytes, and matrix vesicles, and their involvement in mineral deposition in the extracellular microenvironment has been suggested. According to the growth rate hypothesis, cancer cells require more phosphate than healthy cells due to their rapid growth rates. Recently, it was demonstrated that breast cancer cells (MDA-MB-231) respond to high Pi concentration (2 mM) by decreasing Na+-dependent Pi transport activity concomitant with an increase in Na+-independent (H+-dependent) Pi transport. This Pi H+-dependent transport has a fundamental role in the proliferation and migratory capacity of MDA-MB-231 cells. The purpose of this review is to discuss experimental findings regarding Na+-independent inorganic phosphate transporters and summarize their roles in Pi homeostasis, cancers and other diseases, such as osteoarthritis, and in processes such as VC.
Dihydrotanshinone, a Natural Diterpenoid, Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor
Authors: Fresta Claudia Giuseppina , Caruso Giuseppe , Fidilio Annamaria , Platania Chiara Bianca Maria , Musso Nicolò , Caraci Filippo , Drago Filippo , Bucolo Claudio
Published: December 2020

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.
Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines
Authors: Haque Inamul , Kawsar Hameem I. , Motes Hannah , Sharma Mukut , Banerjee Snigdha , Banerjee Sushanta K. , Godwin Andrew K. , Huang Chao H.
Published: December 2020

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood. Recently, increasing numbers of microRNAs (miRNAs) are implicated in EGFR-TKI resistance, indicating that miRNAs may serve as novel targets and may hold promise as predictive biomarkers for anti-EGFR therapy. MicroRNA-506 (miR-506) has been identified as a tumor suppressor in many cancers, including lung cancer; however, the role of miR-506 in lung cancer chemoresistance has not yet been addressed. Here we report that miR-506-3p expression was markedly reduced in erlotinib-resistant (ER) cells. We identified Sonic Hedgehog (SHH) as a novel target of miR-506-3p, aberrantly activated in ER cells. The ectopic overexpression of miR-506-3p in ER cells downregulates SHH signaling, increases E-cadherin expression, and inhibits the expression of vimentin, thus counteracting the epithelial–mesenchymal transition (EMT)-mediated chemoresistance. Our results advanced our understanding of the molecular mechanisms underlying EGFR-TKI resistance and indicated that the miR-506/SHH axis might represent a novel therapeutic target for future EGFR mutated lung cancer treatment.
New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams
Authors: Vázquez-Ucha Juan C. , Arca-Suárez Jorge , Bou Germán , Beceiro Alejandro
Published: December 2020

Carbapenem resistance is a major global health problem that seriously compromises the treatment of infections caused by nosocomial pathogens. Resistance to carbapenems mainly occurs via the production of carbapenemases, such as VIM, IMP, NDM, KPC and OXA, among others. Preclinical and clinical trials are currently underway to test a new generation of promising inhibitors, together with the recently approved avibactam, relebactam and vaborbactam. This review summarizes the main, most promising carbapenemase inhibitors synthesized to date, as well as their spectrum of activity and current stage of development. We particularly focus on β-lactam/β-lactamase inhibitor combinations that could potentially be used to treat infections caused by carbapenemase-producer pathogens of critical priority. The emergence of these new combinations represents a step forward in the fight against antimicrobial resistance, especially in regard to metallo-β-lactamases and carbapenem-hydrolysing class D β-lactamases, not currently inhibited by any clinically approved inhibitor.
The Contribution of Endothelial Dysfunction in Systemic Injury Subsequent to SARS-Cov-2 Infection
Authors: Maiuolo Jessica , Mollace Rocco , Gliozzi Micaela , Musolino Vincenzo , Carresi Cristina , Paone Sara , Scicchitano Miriam , Macrì Roberta , Nucera Saverio , Bosco Francesca , Scarano Federica , Zito Maria Caterina , Ruga Stefano , Tavernese Annamaria , Mollace Vincenzo
Published: December 2020

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease, leading to irreversible tissue damage and death of people with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.
The Role of β-Arrestins in Regulating Stem Cell Phenotypes in Normal and Tumorigenic Cells
Authors: Kallifatidis Georgios , Mamouni Kenza , Lokeshwar Bal
Published: December 2020

β-Arrestins (ARRBs) are ubiquitously expressed scaffold proteins that mediate inactivation of G-protein-coupled receptor signaling, and in certain circumstances, G-protein independent pathways. Intriguingly, the two known ARRBs, β-arrestin1 (ARRB1) and β-Arrestin2 (ARRB2), seem to have opposing functions in regulating signaling cascades in several models in health and disease. Recent evidence suggests that ARRBs are implicated in regulating stem cell maintenance; however, their role, although crucial, is complex, and there is no universal model for ARRB-mediated regulation of stem cell characteristics. For the first time, this review compiles information on the function of ARRBs in stem cell biology and will discuss the role of ARRBs in regulating cell signaling pathways implicated in stem cell maintenance in normal and malignant stem cell populations. Although promising targets for cancer therapy, the ubiquitous nature of ARRBs and the plethora of functions in normal cell biology brings challenges for treatment selectivity. However, recent studies show promising evidence for specifically targeting ARRBs in myeloproliferative neoplasms.
A Celecoxib Derivative Eradicates Antibiotic-Resistant Staphylococcus aureus and Biofilms by Targeting YidC2 Translocase
Authors: Tzeng Shiou-Ru , Huang Yi-Wei , Zhang Yao-Qing , Yang Ching-Yi , Chien Han-Sheng , Chen Yi-Ru , Yu Sung-Liang , Chen Ching S. , Chiu Hao-Chieh
Published: December 2020

The treatment of Staphylococcus aureus infections is impeded by the prevalence of MRSA and the formation of persisters and biofilms. Previously, we identified two celecoxib derivatives, Cpd36 and Cpd46, to eradicate MRSA and other staphylococci. Through whole-genome resequencing, we obtained several lines of evidence that these compounds might act by targeting the membrane protein translocase YidC2. Our data showed that ectopic expression of YidC2 in S. aureus decreased the bacterial susceptibility to Cpd36 and Cpd46, and that the YidC2-mediated tolerance to environmental stresses was suppressed by both compounds. Moreover, the membrane translocation of ATP synthase subunit c, a substrate of YidC2, was blocked by Cpd46, leading to a reduction in bacterial ATP production. Furthermore, we found that the thermal stability of bacterial YidC2 was enhanced, and introducing point mutations into the substrate-interacting cavity of YidC2 had a dramatic effect on Cpd36 binding via surface plasmon resonance assays. Finally, we demonstrated that these YidC2 inhibitors could effectively eradicate MRSA persisters and biofilms. Our findings highlight the potential of impeding YidC2-mediated translocation of membrane proteins as a new strategy for the treatment of bacterial infections.
Characterization and Transcriptome Analysis of Exosomal and Nonexosomal RNAs in Bovine Adipocytes
Authors: Yue Binglin , Yang Haiyan , Wu Jiyao , Wang Jian , Ru Wenxiu , Cheng Jie , Huang Yongzheng , Lei Chuzhao , Lan Xianyong , Chen Hong
Published: December 2020

Exosomes are endosome-derived extracellular vesicles that allow intercellular communication. However, the biological significance of adipocyte exosomal RNAs remains unclear. To determine the role of RNAs from bovine adipocytes and exosomes in bovine adipogenesis, exosomal and nonexosomal RNAs were extracted from three bovine primary white adipocyte samples and then profiles were generated using DNBSEQ/BGISEQ-500 technology. The RNAome of adipocytes consisted of 12,082 mRNAs, 8589 lncRNAs, and 378 miRNAs for a higher complexity that that detected in exosomes, with 1083 mRNAs, 105 lncRNAs, and 48 miRNAs. Exosomal miRNA-mRNA and lncRNA–miRNA–mRNA networks were constructed and enrichment analysis was performed to predict functional roles and regulatory mechanisms. Our study provides the first characterization of RNAs from bovine adipocyte and exosomes. The findings reveal that some RNAs are specifically packaged in adipocyte-derived exosomes, potentially enabling crosstalk between adipocytes and/or other cells that is mediated by exosomes. Our results greatly expand our understanding of exosomal RNAs from bovine adipocytes, and provide a reference for future functional investigations of adipocyte exosomal RNAs under normal physiological conditions.