bluuebunny/crossref_metadata_2025 huggingface dataset:
Logic Analysis of How the Emergency Management Legal System Used to Deal with Public Emerging Infectious Diseases under Balancing of Competing Interests—The Case of COVID-19
Authors: Zhang Chao , Hong Lei , Ma Ning , Sun Guohui
Published: July 2021

Development of measures for mitigating public emerging infectious diseases is now a focal point for emergency management legal systems. COVID-19 prevention and containment policies can be considered under the core goal of social and individual interests. In this study we analyzed the complexity between individual and public interests as they conflict when implementing disease preventative measures on an epidemic scale. The analysis was used to explore this complex landscape of conflicting social, public, and legal interests to quantify the potential benefits of public acceptance. Here we use the large-scale COVID-19 epidemic backdrop to examine legal norms of the emergency management legal framework. We find that the implementation of emergency management legal system measures involves the resolution of both direct and indirect conflicts of interest among public groups, individual groups, and various subsets of each. When competing interests are not balanced, optimal policies cannot be achieved to serve and safeguard shared social and community stability, whereas effective social outcomes are obtainable through the development of targeted policies as defined within the emergency management legal system. A balanced legal framework in regards to emergency management legal norms can more effectively serve to mitigate and prevent the continued spread of emerging infectious diseases. Further developing innovative procedural mechanisms as a means to ensure emergency response intervention should take into account the weighted interest of the different social parties to determine priorities and aims to protect legitimate public interests.
Assessing Earthquake Impacts and Monitoring Resilience of Historic Areas: Methods for GIS Tools
Authors: Giovinazzi Sonia , Marchili Corinna , Di Pietro Antonio , Giordano Ludovica , Costanzo Antonio , La Porta Luigi , Pollino Maurizio , Rosato Vittorio , Lückerath Daniel , Milde Katharina , Ullrich Oliver
Published: July 2021

Historic areas (HAs) are highly vulnerable to natural hazards, including earthquakes, that can cause severe damage, if not total destruction. This paper proposes methods that can be implemented through a geographical information system to assess earthquake-induced physical damages and the resulting impacts on the functions of HAs and to monitor their resilience. For the assessment of damages, making reference to the universally recognised procedure of convoluting hazard, exposure, and vulnerability, this paper proposes (a) a framework for assessing hazard maps of both real and end-user defined earthquakes; (b) a classification of the exposed elements of the built environment; and (c) an index-based seismic vulnerability assessment method for heritage buildings. Moving towards the continuous monitoring of resilience, an index-based assessment method is proposed to quantify how the functions of HAs recover over time. The implementation of the proposed methods in an ad hoc customized WebGIS Decision Support System, referred to as ARCH DSS, is demonstrated in this paper with reference to the historic area of Camerino-San Severino (Italy). Our conclusions show how ARCH DSS can inform and contribute to increasing awareness of the vulnerabilities of HAs and of the severity of the potential impacts, thus supporting effective decision making on mitigation strategies, post-disaster response, and build back better.
Cloud and Snow Segmentation in Satellite Images Using an Encoder–Decoder Deep Convolutional Neural Networks
Authors: Zheng Kai , Li Jiansheng , Ding Lei , Yang Jianfeng , Zhang Xucheng , Zhang Xun
Published: July 2021

The segmentation of cloud and snow in satellite images is a key step for subsequent image analysis, interpretation, and other applications. In this paper, a cloud and snow segmentation method based on a deep convolutional neural network (DCNN) with enhanced encoder–decoder architecture—ED-CNN—is proposed. In this method, the atrous spatial pyramid pooling (ASPP) module is used to enhance the encoder, while the decoder is enhanced with the fusion of features from different stages of the encoder, which improves the segmentation accuracy. Comparative experiments show that the proposed method is superior to DeepLabV3+ with Xception and ResNet50. Additionally, a rough-labeled dataset containing 23,520 images and fine-labeled data consisting of 310 images from the TH-1 satellite are created, where we studied the relationship between the quality and quantity of labels and the performance of cloud and snow segmentation. Through experiments on the same network with different datasets, we found that the cloud and snow segmentation performance is related more closely to the quantity of labels rather than their quality. Namely, under the same labeling consumption, using rough-labeled images only performs better than rough-labeled images plus 10% fine-labeled images.
Bioluminescent Optogenetics: A Novel Experimental Therapy to Promote Axon Regeneration after Peripheral Nerve Injury
Authors: English Arthur W. , Berglund Ken , Carrasco Dario , Goebel Katharina , Gross Robert E. , Isaacson Robin , Mistretta Olivia C. , Wynans Carly
Published: July 2021

Functional recovery after peripheral nerve injury (PNI) is poor, mainly due to the slow and incomplete regeneration of injured axons. Experimental therapies that increase the excitability of the injured axons have proven remarkably successful in promoting regeneration, but their clinical applicability has been limited. Bioluminescent optogenetics (BL-OG) uses luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels that could be used to increase neuronal excitability if exposed to a suitable substrate. Excitatory luminopsins were expressed in motoneurons of transgenic mice and in wildtype mice transduced with adeno-associated viral vectors. Intraperitoneal administration of coelenterazine (CTZ), a known luciferase substrate, generated intense bioluminescence in peripheral axons. This bioluminescence increased motoneuron excitability. A single administration of CTZ immediately after sciatic nerve transection and repair markedly enhanced motor axon regeneration. Compound muscle action potentials were 3–4 times larger than controls by 4 weeks after injury. The results observed with transgenic mice were comparable to those of mice in which the luminopsin was expressed using viral vectors. Significantly more motoneurons had successfully reinnervated muscle targets four weeks after nerve injury in BL-OG treated mice than in controls. Bioluminescent optogenetics is a promising therapeutic approach to enhancing axon regeneration after PNI.
Less Carcinogenic Chlorinated Estrogens Applicable to Hormone Replacement Therapy
Authors: Okamoto Yoshinori , Jinno Hideto , Itoh Shinji , Shibutani Shinya
Published: July 2021

Human estrogens prescribed for hormone replacement therapy (HRT) are known to be potent carcinogens. To find safer estrogens, several chlorinated estrogens were synthesized and their carcinogenic potential were determined. A pellet containing either 2-chloro-17β-estradiol (2-ClE2) or 4-chloro-17β-estradiol (4-ClE2) was implanted subcutaneously for 52 weeks into August Copenhagen Irish (ACI) rats, a preferred animal model for human breast cancer. 17β-Estradiol (E2) frequently induced mammary tumors while both 2-ClE2 and 4-ClE2 did not. Their 17α-ethinyl forms, thought to be orally active estrogens, were also synthesized. Neither 2-chloro-17α-ethinylestradiol (2-ClEE2) nor 4-chloro-17α-ethinylestradiol (4-ClEE2) induced tumors. The less carcinogenic effects were supported by histological examination of mammary glands of ACI rats treated with the chlorinated estrogens. A chlorine atom positioned at the 2- or 4-position of E2 may prevent the metabolic activation, resulting in reducing the carcinogenicity. 2-ClE2 and 4-ClE2 administered subcutaneously and 2-ClEE2 and 4-ClEE2 given orally to ovariectomized rats all showed uterotrophic potency, albeit slightly weaker than that of E2. Our results indicate that less carcinogenic chlorinated estrogens retaining estrogenic potential could be safer alternatives to the carcinogenic estrogens now in use for HRT.
Effects of Extracellular Vesicles from Blood-Derived Products on Osteoarthritic Chondrocytes within an Inflammation Model
Authors: Otahal Alexander , Kramer Karina , Kuten-Pella Olga , Moser Lukas B. , Neubauer Markus , Lacza Zsombor , Nehrer Stefan , De Luna Andrea
Published: July 2021

Osteoarthritis (OA) is hallmarked by a progressive degradation of articular cartilage. One major driver of OA is inflammation, in which cytokines such as IL-6, TNF-α and IL-1β are secreted by activated chondrocytes, as well as synovial cells—including macrophages. Intra-articular injection of blood products—such as citrate-anticoagulated plasma (CPRP), hyperacute serum (hypACT), and extracellular vesicles (EVs) isolated from blood products—is gaining increasing importance in regenerative medicine for the treatment of OA. A co-culture system of primary OA chondrocytes and activated M1 macrophages was developed to model an OA joint in order to observe the effects of EVs in modulating the inflammatory environment. Primary OA chondrocytes were obtained from patients undergoing total knee replacement. Primary monocytes obtained from voluntary healthy donors and the monocytic cell line THP-1 were differentiated and activated into proinflammatory M1 macrophages. EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and Western blot. Gene expression analysis of chondrocytes by RT-qPCR revealed increased type II collagen expression, while cytokine profiling via ELISA showed lower TNF-α and IL-1β levels associated with EV treatment. In conclusion, the inflammation model provides an accessible tool to investigate the effects of blood products and EVs in the inflammatory context of OA.
EVOO Polyphenols Relieve Synergistically Autophagy Dysregulation in a Cellular Model of Alzheimer’s Disease
Authors: Leri Manuela , Bertolini Andrea , Stefani Massimo , Bucciantini Monica
Published: July 2021

(1) Background: Autophagy, the major cytoplasmic process of substrate turnover, declines with age, contributing to proteostasis decline, accumulation of harmful protein aggregates, damaged mitochondria and to ROS production. Accordingly, abnormalities in the autophagic flux may contribute to many different pathophysiological conditions associated with ageing, including neurodegeneration. Recent data have shown that extra-virgin olive oil (EVOO) polyphenols stimulate cell defenses against plaque-induced neurodegeneration, mainly, through autophagy induction. (2) Methods: We carried out a set of in vitro experiments on SH-SY5Y human neuroblastoma cells exposed to toxic Aβ1–42 oligomers to investigate the molecular mechanisms involved in autophagy activation by two olive oil polyphenols, oleuropein aglycone (OleA), arising from the hydrolysis of oleuropein (Ole), the main polyphenol found in olive leaves and drupes and its main metabolite, hydroxytyrosol (HT). (3) Results: Our data show that the mixture of the two polyphenols activates synergistically the autophagic flux preventing cell damage by Aβ1–42 oligomers., in terms of ROS production, and impairment of mitochondria. (4) Conclusion: Our results support the idea that EVOO polyphenols act synergistically in autophagy modulation against neurodegeneration. These data confirm and provide the rationale to consider these molecules, alone or in combination, as promising candidates to contrast ageing-associated neurodegeneration.
YB-1 Is Altered in Pregnancy-Associated Disorders and Affects Trophoblast in Vitro Properties via Alternation of Multiple Molecular Traits
Authors: Stojanovska Violeta , Shah Aneri , Woidacki Katja , Fischer Florence , Bauer Mario , Lindquist Jonathan A. , Mertens Peter R. , Zenclussen Ana C.
Published: July 2021

Cold shock Y-box binding protein-1 (YB-1) coordinates several molecular processes between the nucleus and the cytoplasm and plays a crucial role in cell function. Moreover, it is involved in cancer progression, invasion, and metastasis. As trophoblast cells share similar characteristics with cancer cells, we hypothesized that YB-1 might also be necessary for trophoblast functionality. In samples of patients with intrauterine growth restriction, YB-1 mRNA levels were decreased, while they were increased in preeclampsia and unchanged in spontaneous abortions when compared to normal pregnant controls. Studies with overexpression and downregulation of YB-1 were performed to assess the key trophoblast processes in two trophoblast cell lines HTR8/SVneo and JEG3. Overexpression of YB-1 or exposure of trophoblast cells to recombinant YB-1 caused enhanced proliferation, while knockdown of YB-1 lead to proliferative disadvantage in JEG3 or HTR8/SVneo cells. The invasion and migration properties were affected at different degrees among the trophoblast cell lines. Trophoblast expression of genes mediating migration, invasion, apoptosis, and inflammation was altered upon YB-1 downregulation. Moreover, IL-6 secretion was excessively increased in HTR8/SVneo. Ultimately, YB-1 directly binds to NF-κB enhancer mark in HTR8/SVneo cells. Our data show that YB-1 protein is important for trophoblast cell functioning and, when downregulated, leads to trophoblast disadvantage that at least in part is mediated by NF-κB.
Metformin as a Treatment Strategy for Sjögren’s Syndrome
Authors: Kim Joa , Kim Yun-Sung , Park Sung-Hwan
Published: July 2021

Sjögren’s syndrome (SS), a chronic inflammatory disease involving the salivary and lacrimal glands, presents symptoms of sicca as well as systemic manifestations such as fatigue and musculoskeletal pain. Only a few treatments have been successful in management of SS; thus treatment of the disease is challenging. Metformin is the first-line agent for type 2 diabetes and has anti-inflammatory potential. Its immunomodulatory capacity is exerted via activation of 5’ adenosine monophosphate-activated protein kinase (AMPK). Metformin inhibits mitochondrial respiratory chain complex I which leads to change in adenosine mono-phosphate (AMP) to adenosine tri-phosphate (ATP) ratio. This results in AMPK activation and causes inhibition of mammalian target of rapamycin (mTOR). mTOR plays an important role in T cell differentiation and mTOR deficient T cells differentiate into regulatory T cells. In this manner, metformin enhances immunoregulatory response in an individual. mTOR is responsible for B cell proliferation and germinal center (GC) differentiation. Thus, reduction of B cell differentiation into antibody-producing plasma cells occurs via downregulation of mTOR. Due to the lack of suggested treatment for SS, metformin has been considered as a treatment strategy and is expected to ameliorate salivary gland function.
Fibroblast Growth Factor Type 1 Ameliorates High-Glucose-Induced Oxidative Stress and Neuroinflammation in Retinal Pigment Epithelial Cells and a Streptozotocin-Induced Diabetic Rat Model
Authors: Huang Hsin-Wei , Yang Chung-May , Yang Chang-Hao
Published: July 2021

Diabetic retinopathy (DR) is a common complication of diabetes that causes severe visual impairment globally. The pathogenesis of DR is related to oxidative stress and chronic inflammation. The fibroblast growth factor type 1 (FGF-1) mitogen plays crucial roles in cell function, development, and metabolism. FGF-1 is involved in blood sugar regulation and exerts beneficial antioxidative and anti-inflammatory effects on various organ systems. This study investigated the antioxidative and anti-inflammatory neuroprotective effects of FGF-1 on high-glucose-induced retinal damage. The results revealed that FGF-1 treatment significantly reversed the harmful effects of oxidative stress and inflammatory mediators in retinal tissue in a streptozotocin-induced diabetic rat model. These protective effects were also observed in the in vitro model of retinal ARPE-19 cells exposed to a high-glucose condition. We demonstrated that FGF-1 attenuated p38 mitogen-activated protein kinase and nuclear factor-κB pathway activation under the high-glucose condition. Our results indicated that FGF-1 could effectively prevent retinal injury in diabetes. The findings of this study could be used to develop novel treatments for DR that aim to reduce the cascade of oxidative stress and inflammatory signals in neuroretinal tissue.
The Lrat−/− Rat: CRISPR/Cas9 Construction and Phenotyping of a New Animal Model for Retinitis Pigmentosa
Authors: Koster Céline , van den Hurk Koen , Lewallen Colby , Talib Mays , ten Brink Jacoline , Boon Camiel , Bergen Arthur
Published: July 2021

Purpose: We developed and phenotyped a pigmented knockout rat model for lecithin retinol acyltransferase (LRAT) using CRISPR/Cas9. The introduced mutation (c.12delA) is based on a patient group harboring a homologous homozygous frameshift mutation in the LRAT gene (c.12delC), causing a dysfunctional visual (retinoid) cycle. Methods: The introduced mutation was confirmed by DNA and RNA sequencing. The expression of Lrat was determined on both the RNA and protein level in wildtype and knockout animals using RT-PCR and immunohistochemistry. The retinal structure and function, as well as the visual behavior of the Lrat−/− and control rats, were characterized using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG) and vision-based behavioral assays. Results: Wildtype animals had high Lrat mRNA expression in multiple tissues, including the eye and liver. In contrast, hardly any expression was detected in Lrat−/− animals. LRAT protein was abundantly present in wildtype animals and absent in Lrat−/− animals. Lrat−/− animals showed progressively reduced ERG potentials compared to wildtype controls from two weeks of age onwards. Vison-based behavioral assays confirmed reduced vision. Structural abnormalities, such as overall retinal thinning, were observed in Lrat−/− animals. The retinal thickness in knockout rats was decreased to roughly 80% by four months of age. No functional or structural differences were observed between wildtype and heterozygote animals. Conclusions: Our Lrat−/− rat is a new animal model for retinal dystrophy, especially for the LRAT-subtype of early-onset retinal dystrophies. This model has advantages over the existing mouse models and the RCS rat strain and can be used for translational studies of retinal dystrophies.
Citric Acid-Mediated Abiotic Stress Tolerance in Plants
Authors: Tahjib-Ul-Arif Md. , Zahan Mst. Ishrat , Karim Md. Masudul , Imran Shahin , Hunter Charles T. , Islam Md. Saiful , Mia Md. Ashik , Hannan Md. Abdul , Rhaman Mohammad Saidur , Hossain Md. Afzal , Brestic Marian , Skalicky Milan , Murata Yoshiyuki
Published: July 2021

Several recent studies have shown that citric acid/citrate (CA) can confer abiotic stress tolerance to plants. Exogenous CA application leads to improved growth and yield in crop plants under various abiotic stress conditions. Improved physiological outcomes are associated with higher photosynthetic rates, reduced reactive oxygen species, and better osmoregulation. Application of CA also induces antioxidant defense systems, promotes increased chlorophyll content, and affects secondary metabolism to limit plant growth restrictions under stress. In particular, CA has a major impact on relieving heavy metal stress by promoting precipitation, chelation, and sequestration of metal ions. This review summarizes the mechanisms that mediate CA-regulated changes in plants, primarily CA’s involvement in the control of physiological and molecular processes in plants under abiotic stress conditions. We also review genetic engineering strategies for CA-mediated abiotic stress tolerance. Finally, we propose a model to explain how CA’s position in complex metabolic networks involving the biosynthesis of phytohormones, amino acids, signaling molecules, and other secondary metabolites could explain some of its abiotic stress-ameliorating properties. This review summarizes our current understanding of CA-mediated abiotic stress tolerance and highlights areas where additional research is needed.
In Search of Effective Anticancer Agents—Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers
Authors: Snoch Wojciech , Wnuk Dawid , Witko Tomasz , Staroń Jakub , Bojarski Andrzej J. , Jarek Ewelina , Plou Francisco J. , Guzik Maciej
Published: July 2021

Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. The manuscript brings the reader closer to methods of obtaining various SFAEs using combined biological, chemical and enzymatic methods. It presents how modification of SFAE’s hydrophobic chains can influence their cytotoxicity against human skin melanoma and prostate cancer cell lines. The compound’s cytotoxicity was determined by an MTT assay, which followed an assessment of SFAEs’ potential metastatic properties in concentrations below IC50 values. Despite relatively high IC50 values (63.3–1737.6 μM) of the newly synthesized SFAE, they can compete with other sugar esters already described in the literature. The chosen bioactives caused low polymerization of microtubules and the depolymerization of actin filaments in nontoxic levels, which suggest an apoptotic rather than metastatic process. Altogether, cancer cells showed no propensity for metastasis after treating them with SFAE. They confirmed that lactose-based compounds seem the most promising surfactants among tested sugar esters. This manuscript creates a benchmark for creation of novel anticancer agents based on 3-hydroxylated fatty acids of bacterial origin.
Overlapping Functions of the Paralogous Proteins AtPAP2 and AtPAP9 in Arabidopsis thaliana
Authors: Zhang Renshan , Guan Xiaoqian , Yang Meijing , Law Yee-Song , Voon Chia Pao , Yan Junran , Sun Feng , Lim Boon Leong
Published: July 2021

Arabidopsis thaliana purple acid phosphatase 2 (AtPAP2), which is anchored to the outer membranes of chloroplasts and mitochondria, affects carbon metabolism by modulating the import of some preproteins into chloroplasts and mitochondria. AtPAP9 bears a 72% amino acid sequence identity with AtPAP2, and both proteins carry a hydrophobic motif at their C-termini. Here, we show that AtPAP9 is a tail-anchored protein targeted to the outer membrane of chloroplasts. Yeast two-hybrid and bimolecular fluorescence complementation experiments demonstrated that both AtPAP9 and AtPAP2 bind to a small subunit of rubisco 1B (AtSSU1B) and a number of chloroplast proteins. Chloroplast import assays using [35S]-labeled AtSSU1B showed that like AtPAP2, AtPAP9 also plays a role in AtSSU1B import into chloroplasts. Based on these data, we propose that AtPAP9 and AtPAP2 perform overlapping roles in modulating the import of specific proteins into chloroplasts. Most plant genomes contain only one PAP-like sequence encoding a protein with a hydrophobic motif at the C-terminus. The presence of both AtPAP2 and AtPAP9 in the Arabidopsis genome may have arisen from genome duplication in Brassicaceae. Unlike AtPAP2 overexpression lines, the AtPAP9 overexpression lines did not exhibit early-bolting or high-seed-yield phenotypes. Their differential growth phenotypes could be due to the inability of AtPAP9 to be targeted to mitochondria, as the overexpression of AtPAP2 on mitochondria enhances the capacity of mitochondria to consume reducing equivalents.
Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice
Authors: Jayaprakash Petrilla , Isaev Dmytro , Shabbir Waheed , Lorke Dietrich E. , Sadek Bassem , Oz Murat
Published: July 2021

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.
Profiling Cancer-Associated Fibroblasts in Melanoma
Authors: Papaccio Federica , Kovacs Daniela , Bellei Barbara , Caputo Silvia , Migliano Emilia , Cota Carlo , Picardo Mauro
Published: July 2021

Solid tumors are complex systems characterized by dynamic interactions between neoplastic cells, non-tumoral cells, and extracellular components. Among all the stromal cells that populate tumor microenvironment, fibroblasts are the most abundant elements and are critically involved in disease progression. Cancer-associated fibroblasts (CAFs) have pleiotropic functions in tumor growth and extracellular matrix remodeling implicated in local invasion and distant metastasis. CAFs additionally participate in the inflammatory response of the tumor site by releasing a variety of chemokines and cytokines. It is becoming clear that understanding the dynamic, mutual melanoma–fibroblast relationship would enable treatment options to be amplified. To better characterize melanoma-associated fibroblasts, here we analyzed low-passage primary CAFs derived from advanced-stage primary skin melanomas, focusing on the immuno-phenotype. Furthermore, we assessed the expression of several CAF markers and the production of growth factors. To deepen the study of CAF–melanoma cell crosstalk, we employed CAF-derived supernatants and trans-well co-culture systems to evaluate the influences of CAFs on (i) the motogenic ability of melanoma cells, (ii) the chemotherapy-induced cytotoxicity, and (iii) the release of mediators active in modulating tumor growth and spread.
Fluorometric Quantification of Human Platelet Polyphosphate Using 4′,6-Diamidine-2-phenylindole Dihydrochloride: Applications in the Japanese Population
Authors: Watanabe Taisuke , Kitamura Yutaka , Aizawa Hachidai , Masuki Hideo , Tsujino Tetsuhiro , Sato Atsushi , Kawabata Hideo , Isobe Kazushige , Nakata Koh , Kawase Tomoyuki
Published: July 2021

Polyphosphate (polyP), a biopolymer of inorganic phosphate, is widely distributed in living organisms. In platelets, polyP is released upon activation and plays important roles in coagulation and tissue regeneration. However, the lack of a specific quantification method has delayed the in-depth study of polyP. The fluorescent dye 4′,6-diamidine-2-phenylindole dihydrochloride (DAPI) has recently received attention as a promising probe for the visualization and quantification of cellular polyP levels. In this study, we further optimized quantification conditions and applied this protocol in quantification of platelet polyP levels in a Japanese population. Blood samples were collected from non-smoking, healthy Japanese subjects (23 males, 23 females). Washed platelets were fixed and probed with DAPI for fluorometric determination. PolyP levels per platelet count were significantly higher in women than that in men. A moderate negative correlation between age and polyP levels was found in women. Responsiveness to CaCl2 stimulation was also significantly higher in women than that in men. Overall, our optimized protocol requires neither purification nor degradation steps, reducing both the time and bias for reproducible quantification. Thus, we suggest that despite its low specificity, this DAPI-based protocol would be useful in routine laboratory testing to quantify platelet polyP levels efficiently and economically.
Impact of One-Carbon Metabolism-Driving Epitranscriptome as a Therapeutic Target for Gastrointestinal Cancer
Authors: Takeda Yu , Chijimatsu Ryota , Vecchione Andrea , Arai Takahiro , Kitagawa Toru , Ofusa Ken , Yabumoto Masami , Hirotsu Takaaki , Eguchi Hidetoshi , Doki Yuichiro , Ishii Hideshi
Published: July 2021

One-carbon (1C) metabolism plays a key role in biological functions linked to the folate cycle. These include nucleotide synthesis; the methylation of DNA, RNA, and proteins in the methionine cycle; and transsulfuration to maintain the redox condition of cancer stem cells in the tumor microenvironment. Recent studies have indicated that small therapeutic compounds affect the mitochondrial folate cycle, epitranscriptome (RNA methylation), and reactive oxygen species reactions in cancer cells. The epitranscriptome controls cellular biochemical reactions, but is also a platform for cell-to-cell interaction and cell transformation. We present an update of recent advances in the study of 1C metabolism related to cancer and demonstrate the areas where further research is needed. We also discuss approaches to therapeutic drug discovery using animal models and propose further steps toward developing precision cancer medicine.
Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation
Authors: Gauthier Benoit R. , Comaills Valentine
Published: July 2021

The dynamic nature of the nuclear envelope (NE) is often underestimated. The NE protects, regulates, and organizes the eukaryote genome and adapts to epigenetic changes and to its environment. The NE morphology is characterized by a wide range of diversity and abnormality such as invagination and blebbing, and it is a diagnostic factor for pathologies such as cancer. Recently, the micronuclei, a small nucleus that contains a full chromosome or a fragment thereof, has gained much attention. The NE of micronuclei is prone to collapse, leading to DNA release into the cytoplasm with consequences ranging from the activation of the cGAS/STING pathway, an innate immune response, to the creation of chromosomal instability. The discovery of those mechanisms has revolutionized the understanding of some inflammation-related diseases and the origin of complex chromosomal rearrangements, as observed during the initiation of tumorigenesis. Herein, we will highlight the complexity of the NE biology and discuss the clinical symptoms observed in NE-related diseases. The interplay between innate immunity, genomic instability, and nuclear envelope leakage could be a major focus in future years to explain a wide range of diseases and could lead to new classes of therapeutics.
Study of the Expression and Function of Calcium-Sensing Receptor in Human Skeletal Muscle
Authors: Romagnoli Cecilia , Sharma Preeti , Zonefrati Roberto , Palmini Gaia , Lucattelli Elena , Ward Donald T. , Ellinger Isabella , Innocenti Marco , Brandi Maria Luisa
Published: July 2021

Skeletal muscle has an outstanding capacity for regeneration in response to injuries, but there are disorders in which this process is seriously impaired, such as sarcopenia. Pharmacological treatments to restore muscle trophism are not available, therefore, the identification of suitable therapeutic targets that could be useful for the treatment of skeletal reduced myogenesis is highly desirable. In this in vitro study, we explored the expression and function of the calcium-sensing receptor (CaSR) in human skeletal muscle tissues and their derived satellite cells. The results obtained from analyses with various techniques of gene and protein CaSR expression and of its secondary messengers in response to calcium (Ca2+) and CaSR drugs have demonstrated that this receptor is not present in human skeletal muscle tissues, neither in the established satellite cells, nor during in vitro myogenic differentiation. Taken together, our data suggest that, although CaSR is a very important drug target in physiology and pathology, this receptor probably does not have any physiological role in skeletal muscle in normal conditions.
Biological Activities Related to Plant Protection and Environmental Effects of Coumarin Derivatives: QSAR and Molecular Docking Studies
Authors: Rastija Vesna , Vrandečić Karolina , Ćosić Jasenka , Majić Ivana , Šarić Gabriella Kanižai , Agić Dejan , Karnaš Maja , Lončarić Melita , Molnar Maja
Published: July 2021

The aim was to study the inhibitory effects of coumarin derivatives on the plant pathogenic fungi, as well as beneficial bacteria and nematodes. The antifungal assay was performed on four cultures of phytopathogenic fungi by measuring the radial growth of the fungal colonies. Antibacterial activity was determined by the broth microdilution method performed on two beneficial soil organisms. Nematicidal activity was tested on two entomopathogenic nematodes. The quantitative structure-activity relationship (QSAR) model was generated by genetic algorithm, and toxicity was estimated by T.E.S.T. software. The mode of inhibition of enzymes related to the antifungal activity is elucidated by molecular docking. Coumarin derivatives were most effective against Macrophomina phaseolina and Sclerotinia sclerotiorum, but were not harmful against beneficial nematodes and bacteria. A predictive QSAR model was obtained for the activity against M. phaseolina (R2tr = 0.78; R2ext = 0.67; Q2loo = 0.67). A QSAR study showed that multiple electron-withdrawal groups, especially at position C-3, enhanced activities against M. phaseolina, while the hydrophobic benzoyl group at the pyrone ring, and –Br, –OH, –OCH3, at the benzene ring, may increase inhibition of S. sclerotiourum. Tested compounds possibly act inhibitory against plant wall-degrading enzymes, proteinase K. Coumarin derivatives are the potentially active ingredient of environmentally friendly plant-protection products.
Peripheral Arterial Stiffness in Acute Pulmonary Embolism and Pulmonary Hypertension at Short-Term Follow-Up
Authors: Papa Silvia , Miotti Cristiano , Manzi Giovanna , Scoccia Gianmarco , Luongo Federico , Toto Federica , Malerba Claudia , Cedrone Nadia , Canuti Elena Sofia , Caputo Annalisa , Manguso Giulia , Valentini Serena , Sciomer Susanna , Ciciarello Francesco , Benedetti Giulia , Fedele Francesco , Vizza Carmine Dario , Badagliacca Roberto
Published: July 2021

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and under-recognized complication of acute pulmonary embolism (PE). Forty consecutive patients with acute PE (Group 1), predominantly female (22, 55%) with a mean age of 69 ± 15 years, were matched for demographic data with 40 healthy subjects (Group 2), 40 systemic hypertension patients (Group 3) and 45 prevalent idiopathic pulmonary arterial hypertension (IPAH) patients (Group 4). The baseline evaluation included physical examination, NYHA/WHO functional class, right heart catheterization (RHC) limited to IPAH patients, echocardiographic assessment and systemic arterial stiffness measurement by cardio-ankle vascular index (CAVI). Patients with PE underwent an echocardiographic evaluation within 1 month from hospital discharge (median 27 days; IQR 21–30) to assess the echo-derived probability of PH. The CAVI values were significantly higher in the PE and IPAH groups compared with the others (Group 1 vs. Group 2, p < 0.001; Group 1 vs. Group 3, p < 0.001; Group 1 vs. Group 4, p = ns; Group 4 vs. Group 2, p < 0.001; Group 4 vs. Group 3, p < 0.001; Group 2 vs. Group 3, p = ns). The predicted probability of echocardiography-derived high-risk criteria of PH increases for any unit increase of CAVI (OR 9.0; C.I.3.9–20.5; p = 0.0001). The PE patients with CAVI ≥ 9.0 at the time of hospital discharge presented an increased probability of PH. This study highlights a possible positive predictive role of CAVI as an early marker for the development of CTEPH.
Sleep Disorders in Adults with Down Syndrome
Authors: Giménez Sandra , Altuna Miren , Blessing Esther , Osorio Ricardo M. , Fortea Juan
Published: July 2021

Sleep disorders, despite being very frequent in adults with Down syndrome (DS), are often overlooked due to a lack of awareness by families and physicians and the absence of specific clinical sleep guidelines. Untreated sleep disorders have a negative impact on physical and mental health, behavior, and cognitive performance. Growing evidence suggests that sleep disruption may also accelerate the progression to symptomatic Alzheimer’s disease (AD) in this population. It is therefore imperative to have a better understanding of the sleep disorders associated with DS in order to treat them, and in doing so, improve cognition and quality of life, and prevent related comorbidities. This paper reviews the current knowledge of the main sleep disorders in adults with DS, including evaluation and management. It highlights the existing gaps in knowledge and discusses future directions to achieve earlier diagnosis and better treatment of sleep disorders most frequently found in this population.
Ship Berthing Information Extraction System Using Three-Dimensional Light Detection and Ranging Data
Authors: Chen Chen , Li Ying
Published: July 2021

Safe and efficient berthing is essential to ensure maritime transportation and the safety of ships and ports. Three-dimensional (3D) light detection and ranging (LiDAR) can monitor and support ship berthing because it provides abundant target information and offers excellent advantages in measuring accuracy. Hence, a berthing information extraction system has been developed based on 3D LiDAR. Principal component analysis is used to calculate a ship’s heading and the normal vector, and the feature points of the bow and stern are determined. The segments passing through the points are obtained via region growing. The bow and stern are recognized by the similarity of the normal vector of the segments and ship’s heading according to the positions of the ship relative to the berth through visibility analysis. Qualitative and quantitative calculated analyses of the distance, velocity, and approach angle of the dynamic ship’s bow and stern relative to the dock are performed based on the feature points of 3D LiDAR data. A laser scanner, used as the detection unit, efficiently monitored the Ro–Ro ship Ocean Island berthing at Lushun Port in field experiments. On-site applications demonstrated the feasibility and effectiveness of the proposed method for the recognition of dynamic ship target and ensuring safe ship berthing.
Cockle as Second Intermediate Host of Trematode Parasites: Consequences for Sediment Bioturbation and Nutrient Fluxes across the Benthic Interface
Authors: Richard Anaïs , de Montaudouin Xavier , Rubiello Auriane , Maire Olivier
Published: July 2021

Trematode parasites are distributed worldwide and can severely impact host populations. However, their influence on ecosystem functioning through the alteration of host engineering behaviours remains largely unexplored. This study focuses on a common host parasite system in marine coastal environments, i.e., the trematode Himasthla elongata, infecting the edible cockle Cerastoderma edule as second intermediate host. A laboratory experiment was conducted to investigate the indirect effects of metacercarial infection on sediment bioturbation and biogeochemical fluxes at the sediment water interface. Our results revealed that, despite high parasite intensity, the sediment reworking and bioirrigation rates, as well as nutrient fluxes, were not impacted. This finding was unexpected since previous studies showed that metacercarial infection impairs the physiological condition of cockles and induces a mechanical obstruction of their feet, thus altering their burrowing capacity. There are several explanations for such contrasting results. Firstly, the alteration of cockle behavior could arise over a longer time period following parasite infection. Secondly, the modulation of cockle bioturbation by parasites could be more pronounced in older specimens burying deeper. Thirdly, the intensity of the deleterious impacts of metacercariae could strongly vary across parasite species. Lastly, metacercarial infection alters cockle fitness through an interaction with other biotic and abiotic environmental stressors.
Review on Perioperative and Oncological Outcomes of Robotic Gastrectomy for Cancer
Authors: Giuliani Giuseppe , Guerra Francesco , De Franco Lorenzo , Salvischiani Lucia , Benigni Roberto , Coratti Andrea
Published: July 2021

Background. Minimally invasive gastrectomy is currently considered a valid option to treat gastric cancer and is gaining increasing acceptance. Recent reports have suggested that the application of robots may confer some advantages over conventional laparoscopy, but the role of robotic surgery in clinical practice is still uncertain. We aimed to critically review the relevant evidence comparing robotic to standard laparoscopic surgery in performing radical gastrectomy. Methods. The Pubmed/Medline electronic databases were searched through February 2021. Paper conference and the English language was the only restriction applied to our search strategy. Results. According to the existing data, robotic gastrectomy seems to provide some benefits in terms of blood loss, rate of conversion, procedure-specific postoperative morbidity, and length of hospital stay. Robotic gastrectomy is also associated with a longer duration of surgery and a higher economic burden as compared to its laparoscopic counterpart. No significant differences have been disclosed in terms of long-term survivals, while the number of lymph nodes retrieved with robotic gastrectomy is generally higher than that of laparoscopy. Conclusions. The current literature suggests that robotic radical gastrectomy appears as competent as the conventional laparoscopic procedure and may provide some clinical advantages. However, due to the relative paucity of high-level evidence, it is not possible to draw definitive conclusions.
Long-Term Land Cover Changes in the Western Part of the Korean Demilitarized Zone
Authors: Kim Jae Hyun , Park Shinyeong , Kim Seung Ho , Lee Eun Ju
Published: July 2021

After the Korean War, human access to the Korean Demilitarized Zone (DMZ) was highly restricted. However, limited agricultural activity was allowed in the Civilian Control Zone (CCZ) surrounding the DMZ. In this study, land cover and vegetation changes in the western DMZ and CCZ from 1919 to 2017 were investigated. Coniferous forests were nearly completely destroyed during the war and were then converted to deciduous forests by ecological succession. Plains in the DMZ and CCZ areas showed different patterns of land cover changes. In the DMZ, pre-war rice paddies were gradually transformed into grasslands. These grasslands have not returned to forest, and this may be explained by wildfires set for military purposes or hydrological fluctuations in floodplains. Grasslands near the floodplains in the DMZ are highly valued for conservation as a rare land type. Most grasslands in the CCZ were converted back to rice paddies, consistent with their previous use. After the 1990s, ginseng cultivation in the CCZ increased. In addition, the landscape changes in the Korean DMZ and CCZ were affected by political circumstances between South and North Korea. Our results provide baseline information for the development of ecosystem management and conservation plans for the Korean DMZ and CCZ. Given the high biodiversity and ecological integrity of the Korean DMZ region, transboundary governance for conservation should be designed.
Phytochemical Investigation, Antimicrobial, Antioxidant and Anticancer Activities of Acer cappadocicum Gled
Authors: Kausar Farzana , Farooqi Muhammad-Awais , Farooqi Hafiz-Muhammad-Umer , Salih Abdul-Rahim-Chethikkattuveli , Khalil Atif-Ali-Khan , Kang Chul-woong , Mahmoud Mohamed H. , Batiha Gaber-El-Saber , Choi Kyung-hyun , Mumtaz Abdul-Samad
Published: July 2021

The appearance of novel microbial resistance, diverse cancer ailment and several other morbidities such as appetite loss, hair loss, anemia, cell damage, etc., are among most critical situation that keeps the phytochemical quest on. Thus, this study characterized the antimicrobial, antioxidant, and anticancer potentials of a rarely accessed Acer cappadocicum gled (AC) population thriving in a remote Palas Valley in northern Pakistan. Leaf extracts of the plant were prepared in organic solvents with different polarities through maceration. Extracts were subjected to antimicrobial, antioxidant, and anticancer activities using agar well, DPPH and cell viability assays. A. cappadocicum methanolic extract (ACM) significantly inhibited bacterial growth, followed by n-butanolic extract (ACB) with the second-highest bacterial inhibition. Similar activity was observed against mycelial growth inhibition in plant-fungal pathogen by ACM and ACB. However, human pathogenic fungi did not affect much by extracts. In antioxidant assessment, the chloroform extract (ACC) showed strong scavenging activity and in cytotoxic evaluation, extracts restricted growth proliferation in cancer cells. The inhibitory evidence of extracts, potent scavenging ability, and low cell viability of human-derived cell lines supports the antimicrobial, antioxidant and anticancerous potential of A. cappadocicum. It advances our quest for natural product research.
Description of the Fifth New Species of Russula subsect. Maculatinae from Pakistan Indicates Local Diversity Hotspot of Ectomycorrhizal Fungi in Southwestern Himalayas
Authors: Kiran Munazza , Caboň Miroslav , Senko Dušan , Khalid Abdul Nasir , Adamčík Slavomír
Published: July 2021

Russula subsect. Maculatinae is morphologically and phylogenetically well-defined lineage of ectomycorrhizal fungi associated with arctic, boreal, temperate and Mediterranean habitats of Northern Hemisphere. Based on phylogenetic distance among species, it seems that this group diversified relatively recently. Russula ayubiana sp. nov., described in this study, is the fifth in the group known from relatively small area of northern Pakistan situated in southwestern Himalayas. This is the highest known number of agaric lineage members from a single area in the world. This study uses available data about phylogeny, ecology, and climate to trace phylogenetic origin and ecological preferences of Maculatinae in southwestern Himalayas. Our results suggest that the area has been recently colonised by Maculatinae members migrating from various geographical areas and adapting to local conditions. We also discuss the perspectives and obstacles in research of biogeography and ecology, and we propose improvements that would facilitate the integration of ecological and biogeographical metadata from the future taxonomic studies of fungi in the region.