bluuebunny/crossref_metadata_2025 huggingface dataset:
A Noisy SAR Image Fusion Method Based on NLM and GAN
Authors: Fang Jing , Ma Xiaole , Wang Jingjing , Qin Kai , Hu Shaohai , Zhao Yuefeng
Published: March 2021

The unavoidable noise often present in synthetic aperture radar (SAR) images, such as speckle noise, negatively impacts the subsequent processing of SAR images. Further, it is not easy to find an appropriate application for SAR images, given that the human visual system is sensitive to color and SAR images are gray. As a result, a noisy SAR image fusion method based on nonlocal matching and generative adversarial networks is presented in this paper. A nonlocal matching method is applied to processing source images into similar block groups in the pre-processing step. Then, adversarial networks are employed to generate a final noise-free fused SAR image block, where the generator aims to generate a noise-free SAR image block with color information, and the discriminator tries to increase the spatial resolution of the generated image block. This step ensures that the fused image block contains high resolution and color information at the same time. Finally, a fused image can be obtained by aggregating all the image blocks. By extensive comparative experiments on the SEN1–2 datasets and source images, it can be found that the proposed method not only has better fusion results but is also robust to image noise, indicating the superiority of the proposed noisy SAR image fusion method over the state-of-the-art methods.
Modulation Methods for Direct and Indirect Matrix Converters: A Review
Authors: Varajão Diogo , Araújo Rui Esteves
Published: March 2021

Matrix converters (MCs) allow the implementation of single-stage AC/AC power conversion systems (PCS) with inherent bidirectional power flow capability. By avoiding the typical DC-link capacitor, MCs have the potential to achieve higher power density with a more reliable operation and less maintenance when compared with conventional two-stage AC/DC/AC PCS. For these reasons, matrix converters have been receiving significant attention from the academic sector but have not yet been implemented on a large industrial scale. This article reviews the Direct Matrix Converter (DMC) and the Indirect Matrix Converter (IMC) along with the respective actual and most important modulation methods. Simulation results are provided to validate the theoretical analysis and to get a deep insight about the implementation of space vector modulation (SVM) and respective switching pattern generator.
An FPGA-Based Four-Channel 128k-Point FFT Processor Suitable for Spaceborne SAR
Authors: Li Yongrui , Chen He , Xie Yizhuang
Published: March 2021

Spaceborne synthetic aperture radar (SAR) plays an important role in many fields of national defense and the national economy, and the Fast Fourier Transform (FFT) processor is an important part of the spaceborne real-time SAR imaging system. How to meet the increasing demand for ultra-large-scale data processing and to reduce the scale of the hardware platform while ensuring real-time processing is a major problem for real-time processing of on-orbit SAR. To solve this problem, in this study, we propose a 128k-point fixed-point FFT processor based on Field-Programmable Gate Array (FPGA) with a four-channel Single-path Delay Feedback (SDF) structure. First, we combine the radix-23 and mixed-radix algorithms to propose a four-channel processor structure, to achieve high efficiency hardware resources and high real-time performance. Secondly, we adopt the SDF structure combined with the radix-23 algorithm to achieve efficient use of storage resources. Third, we propose a word length adjustment strategy to ensure the accuracy of calculations. The experimental results show that the relative error between the processor and the MATLAB calculation result is maintained at about 10−4, which has good calculation accuracy.
Modulated High Power and Narrow Pulse Width Laser Drive Circuit for Lidar System
Authors: Chen Zhiwen , Yan Yingying , Shu Jun , Liu Kefu , Qiu Jian
Published: March 2021

This manuscript introduces a laser drive circuit for a light detection and ranging (Lidar) system. A Lidar system usually requires its drive circuit to provide laser pulses with nanosecond pulse width, >100 W peak power and high repetition frequency. However, the existing research results show difficulties in meeting these requirements. In order to reduce the pulse width and increase the peak power of laser pulses, special circuit design and component selection are used to optimize the parasitic parameters of the drive circuit, and GaN devices are used to increase the switching speed. The characteristics of laser pulses are tested under different input voltage, pulse per second and switch conducting time. Meanwhile, the reasons for the changes in these characteristics are analyzed and explained. In order to meet the requirements of the Lidar system to detect targets at different distances, a modulation method to change the peak power of the laser pulse is proposed. In our experiment, ideally, the peak power of the laser pulse reaches 135 W, and the pulse width is less than 2 ns at a pulse per second rate of 400 kHz.
Management of the Torch Structure with the New Methodological Approaches to Regulation Based on Neural Network Algorithms
Authors: Osintsev Konstantin , Aliukov Sergei , Prikhodko Yuri
Published: March 2021

A method for evaluating the thermophysical characteristics of the torch is developed. Mathematically the temperature at the end of the zone of active combustion based on continuous distribution functions of particles of solid fuels, in particular coal dust. The particles have different average sizes, which are usually grouped and expressed as a fraction of the total mass of the fuel. The authors suggest taking into account the sequential nature of the entry into the chemical reactions of combustion of particles of different masses. In addition, for the application of the developed methodology, it is necessary to divide the furnace volume into zones and sections. In particular, the initial section of the torch, the zone of intense burning and the zone of afterburning. In this case, taking into account all the thermophysical characteristics of the torch, it is possible to make a thermal balance of the zone of intense burning. Then determines the rate of expiration of the fuel-air mixture, the time of combustion of particles of different masses and the temperature at the end of the zone of intensive combustion. The temperature of the torch, the speed of flame propagation, and the degree of particle burnout must be controlled. The authors propose an algorithm for controlling the thermophysical properties of the torch based on neural network algorithms. The system collects data for a certain time, transmits the information to the server. The data is processed and a forecast is made using neural network algorithms regarding the combustion modes. This allows to increase the reliability and efficiency of the combustion process. The authors present experimental data and compare them with the data of the analytical calculation. In addition, data for certain modes are given, taking into account the system’s operation based on neural network algorithms.
Sweet Dreams (Are Made of This): A Review and Perspectives on Aspartic Acid Production
Authors: Appleton Holly , Rosentrater Kurt A.
Published: March 2021

Aspartic acid, or “aspartate,” is a non-essential, four carbon amino acid produced and used by the body in two enantiomeric forms: L-aspartic acid and D-aspartic acid. The L-configuration of amino acids is the dominant form used in protein synthesis; thus, L-aspartic acid is by far the more common configuration. However, D-aspartic acid is one of only two known D-amino acids biosynthesized by eukaryotes. While L-aspartic acid is used in protein biosynthesis and neurotransmission, D-aspartic acid is associated with neurogenesis and the endocrine system. Aspartic acid production and use has been growing in recent years. The purpose of this article is to discuss various perspectives on aspartic acid, including its industrial utility, global markets, production and manufacturing, optimization, challenges, and future outlook. As such, this review will provide a thorough background on this key biochemical.
Enhancing the Nutritional Properties of Bread by Incorporating Mushroom Bioactive Compounds: The Manipulation of the Pre-Dictive Glycaemic Response and the Phenolic Properties
Authors: Lu Xikun , Brennan Margaret A. , Guan Wenqiang , Zhang Jie , Yuan Li , Brennan Charles S.
Published: March 2021

Wheat bread supplemented with mushroom powder from three different species of mushrooms was investigated in terms of starch characteristics (content, gelatinisation, and digestibility) and antioxidant capacities. The decrease in total starch contents, and increase in phenolic contents of the breads, were associated with increased mushroom powder contents. Mushroom inclusion reduced the rate of reducing sugar released over 120 min in an in vitro digestion compared to the control sample, implying a lower area under the curve (AUC) value with the inclusion of mushroom powder and a potentially lower predicted glycaemic response of the bread. Mushroom powder incorporation also enhanced the DPPH radical scavenging assay and oxygen radical absorbance capacity (ORAC) compared to control bread. The action of the addition of different mushroom powders on the bread crust and crumb microstructure properties was also studied. Mushroom powder altered the internal microstructure of the bread crust and crumb by affecting the interactions between starch and the other components of the bread. Overall, this shows that mushroom powder could be added to bread to deliver health benefits to consumers.
The Potential of Exploiting Economical Solar Dryer in Food Preservation: Storability, Physicochemical Properties, and Antioxidant Capacity of Solar-Dried Tomato (Solanum lycopersicum) Fruits
Authors: Al Maiman Salah A. , Albadr Nawal A. , Almusallam Ibrahim A. , Al-Saád Mohammed Jawad , Alsuliam Sarah , Osman Magdi A. , Hassan Amro B.
Published: March 2021

This study investigated the effect of solar drying on storability and physiochemical and antioxidant capacities of dried tomatoes. Sliced fruit was dried at 45 ± 2 °C for 24 h under a solar tunnel dryer and stored at ambient temperature for 90 and 180 days. Solar drying treatments significantly (p < 0.05) reduced the bacterial and mold load, and eliminated Staphylococcus aureus, S. saprophyticus, and Escherichia coli in all samples. Solar drying treatment reduced the water activity of the dried tomato’s to 0.31 that remained at the same level during storage period 180 days. Storage of dried tomato slices resulted in the decrease of both color and vitamin C content while it increased the total carotenoid, lycopene, phenolic compound content, and antioxidant activity. Furthermore, the principle component analysis (PCA) revealed that solar drying of tomato slices enhanced its physicochemical properties, antioxidant capacity particularly after storage for 90 and 180 days. Interestingly, the solar drying process enhanced tomato slices storage and physicochemical characteristics, that resulted in extending the shelf life by up to 6 months, indicating the great potential application of low-tech solar in food industry and could become an emerging effective post-harvest preservative method for seasonal perishable vegetable and fruit, particularly in developing countries.
The 1930s Horror Adventure Film on Location in Jamaica: ‘Jungle Gods’, ‘Voodoo Drums’ and ‘Mumbo Jumbo’ in the ‘Secret Places of Paradise Island’
Authors: Martens Emiel
Published: March 2021

In this article, I consider the representation of African-Caribbean religions in the early horror adventure film from a postcolonial perspective. I do so by zooming in on Ouanga (1935), Obeah (1935), and Devil’s Daughter (1939), three low-budget horror productions filmed on location in Jamaica during the 1930s (and the only films shot on the island throughout that decade). First, I discuss the emergence of depictions of African-Caribbean religious practices of voodoo and obeah in popular Euro-American literature, and show how the zombie figure entered Euro-American empire cinema in the 1930s as a colonial expression of tropical savagery and jungle terror. Then, combining historical newspaper research with content analyses of these films, I present my exploration into the three low-budget horror films in two parts. The first part contains a discussion of Ouanga, the first sound film ever made in Jamaica and allegedly the first zombie film ever shot on location in the Caribbean. In this early horror adventure, which was made in the final year of the U.S. occupation of Haiti, zombies were portrayed as products of evil supernatural powers to be oppressed by colonial rule. In the second part, I review Obeah and The Devil’s Daughter, two horror adventure movies that merely portrayed African-Caribbean religion as primitive superstition. While Obeah was disturbingly set on a tropical island in the South Seas infested by voodoo practices and native cannibals, The Devil’s Daughter was authorized by the British Board of Censors to show black populations in Jamaica and elsewhere in the colonial world that African-Caribbean religions were both fraudulent and dangerous. Taking into account both the production and content of these movies, I show that these 1930s horror adventure films shot on location in Jamaica were rooted in a long colonial tradition of demonizing and terrorizing African-Caribbean religions—a tradition that lasts until today.
MicroRNA Interference in Hepatic Host-Pathogen Interactions
Authors: Morishita Asahiro , Oura Kyoko , Tadokoro Tomoko , Fujita Koji , Tani Joji , Masaki Tsutomu
Published: March 2021

The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host–pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens.
Molecular Determinants of Seminal Plasma on Sperm Biology and Fertility
Authors: Álvarez-Rodríguez Manuel , Martinez-Pastor Felipe
Published: March 2021

Seminal plasma has gained attention in the last decades, developing from being a mere vehicle for spermatozoa delivery to the female to having a pivotal role in fertility and offspring well-being [...]
Changes in Serum MicroRNAs after Anti-IL-5 Biological Treatment of Severe Asthma
Authors: Rial Manuel J. , Cañas José A. , Rodrigo-Muñoz José M. , Valverde-Monge Marcela , Sastre Beatriz , Sastre Joaquín , del Pozo Victoria
Published: March 2021

There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment (p < 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the biosynthesis/degradation of glucans (p < 0.05). However, it did not correlate with an improvement in lung function. MiRNA-338-3p could be used as a biomarker of early response to reslizumab and mepolizumab in severe eosinophilic asthmatic patients. In fact, this miRNA could be involved in airway remodeling, targeting genes related to MAPK and TGF-β signaling pathways.
Defining Phenotype, Tropism, and Retinal Gene Therapy Using Adeno-Associated Viral Vectors (AAVs) in New-Born Brown Norway Rats with a Spontaneous Mutation in Crb1
Authors: Boon Nanda , Alves C. Henrique , Mulder Aat A. , Andriessen Charlotte A. , Buck Thilo M. , Quinn Peter M. J. , Vos Rogier M. , Koster Abraham J. , Jost Carolina R. , Wijnholds Jan
Published: March 2021

Mutations in the Crumbs homologue 1 (CRB1) gene cause inherited retinal dystrophies, such as early-onset retinitis pigmentosa and Leber congenital amaurosis. A Brown Norway rat strain was reported with a spontaneous insertion-deletion (indel) mutation in exon 6 of Crb1. It has been reported that these Crb1 mutant rats show vascular abnormalities associated with retinal telangiectasia and possess an early-onset retinal degenerative phenotype with outer limiting membrane breaks and focal loss of retinal lamination at 2 months of age. Here, we further characterized the morphological phenotype of new-born and adult Crb1 mutant rats in comparison with age-matched Brown Norway rats without a mutation in Crb1. A significantly decreased retinal function and visual acuity was observed in Crb1 mutant rats at 1 and 3 months of age, respectively. Moreover, in control rats, the subcellular localization of canonical CRB1 was observed at the subapical region in Müller glial cells while CRB2 was observed at the subapical region in both photoreceptors and Müller glial cells by immuno-electron microscopy. CRB1 localization was lost in the Crb1 mutant rats, whereas CRB2 was still observed. In addition, we determined the tropism of subretinal or intravitreally administered AAV5-, AAV9- or AAV6-variant ShH10Y445F vectors in new-born control and Crb1 mutant rat retinas. We showed that subretinal injection of AAV5 and AAV9 at postnatal days 5 (P5) or 8 (P8) predominantly infected the retinal pigment epithelium (RPE) and photoreceptor cells; while intravitreal injection of ShH10Y445F at P5 or P8 resulted in efficient infection of mainly Müller glial cells. Using knowledge of the subcellular localization of CRB1 and the ability of ShH10Y445F to infect Müller glial cells, canonical hCRB1 and hCRB2 AAV-mediated gene therapy were explored in new-born Crb1 mutant rats. Enhanced retinal function after gene therapy delivery in the Crb1 rat was not observed. No timely rescue of the retinal phenotype was observed using retinal function and visual acuity, suggesting the need for earlier onset of expression of recombinant hCRB proteins in Müller glial cells to rescue the severe retinal phenotype in Crb1 mutant rats.
The Pro-Apoptotic Effect of Silica Nanoparticles Depends on Their Size and Dose, as Well as the Type of Glioblastoma Cells
Authors: Krętowski Rafał , Kusaczuk Magdalena , Naumowicz Monika , Cechowska-Pasko Marzanna
Published: March 2021

Despite intensive investigations, nanoparticle-induced cellular damage is an important problem that has not been fully elucidated yet. Here, we report that silica nanoparticles (SiNPs) demonstrated anticancer influence on glioblastoma cells by the induction of apoptosis or necrosis. These effects are highly cell type-specific, as well as dependent on the size and dose of applied nanoparticles. Exposure of LN-18 and LBC3 cells to different sizes of SiNPs—7 nm, 5–15 nm, or 10–20 nm—at dosages, ranging from 12.5 to 1000 µg/mL, for 24 and 48 h reduced the viability of these cells. Treatment of LN-18 and LBC3 cells with 7 nm or 10–20 nm SiNPs at doses ≥50 µg/mL caused a strong induction of apoptosis, which is connected with an increase of intracellular reactive oxygen species (ROS) production. The 5–15 nm SiNPs exhibited distinct behavior comparing to silica nanoparticles of other studied sizes. In contrast to LBC3, in LN-18 cells exposed to 5–15 nm SiNPs we did not observe any effect on apoptosis. These nanoparticles exerted only strong necrosis, which was connected with a reduction in ROS generation. This suggests that SiNPs can trigger different cellular/molecular effects, depending on the exposure conditions, the size and dose of nanoparticles, and cell type of glioblastoma.
Metabolomics in Severe Aortic Stenosis Reveals Intermediates of Nitric Oxide Synthesis as Most Distinctive Markers
Authors: van Driel Beau Olivier van , Schuldt Maike , Algül Sila , Levin Evgeni , Güclü Ahmet , Germans Tjeerd , Rossum Albert C. van , Pei Jiayi , Harakalova Magdalena , Baas Annette , Jans Judith J. M. , van der Velden Jolanda
Published: March 2021

Background: Calcific aortic valve disease (CAVD) is a rapidly growing global health problem with an estimated 12.6 million cases globally in 2017 and a 112% increase of deaths since 1990 due to aging and population growth. CAVD may develop into aortic stenosis (AS) by progressive narrowing of the aortic valve. AS is underdiagnosed, and if treatment by aortic valve replacement (AVR) is delayed, this leads to poor recovery of cardiac function, absence of symptomatic improvement and marked increase of mortality. Considering the current limitations to define the stage of AS-induced cardiac remodeling, there is need for a novel method to aid in the diagnosis of AS and timing of intervention, which may be found in metabolomics profiling of patients. Methods: Serum samples of nine healthy controls and 10 AS patients before and after AVR were analyzed by untargeted mass spectrometry. Multivariate modeling was performed to determine a metabolic profile of 30 serum metabolites which distinguishes AS patients from controls. Human cardiac microvascular endothelial cells (CMECs) were incubated with serum of the AS patients and then stained for ICAM-1 with Western Blot to analyze the effect of AS patient serum on endothelial cell activation. Results: The top 30 metabolic profile strongly distinguishes AS patients from healthy controls and includes 17 metabolites related to nitric oxide metabolism and 12 metabolites related to inflammation, in line with the known pathomechanism for calcific aortic valve disease. Nine metabolites correlate strongly with left ventricular mass, of which three show reversal back to control values after AVR. Western blot analysis of CMECs incubated with AS patient sera shows a significant reduction (14%) in ICAM-1 in AS samples taken after AVR compared to AS patient sera before AVR. Conclusion: Our study defined a top 30 metabolic profile with biological and clinical relevance, which may be used as blood biomarker to identify AS patients in need of cardiac surgery. Future studies are warranted in patients with mild-to-moderate AS to determine if these metabolites reflect disease severity and can be used to identify AS patients in need of cardiac surgery.
Sacubitril/Valsartan Improves Diastolic Function But Not Skeletal Muscle Function in a Rat Model of HFpEF
Authors: Schauer Antje , Adams Volker , Augstein Antje , Jannasch Anett , Draskowski Runa , Kirchhoff Virginia , Goto Keita , Mittag Jeniffer , Galli Roberta , Männel Anita , Barthel Peggy , Linke Axel , Winzer Ephraim B.
Published: March 2021

The angiotensin receptor/neprilysin inhibitor Sacubitril/Valsartan (Sac/Val) has been shown to be beneficial in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, the impact of Sac/Val in patients presenting with heart failure with preserved ejection fraction (HFpEF) is not yet clearly resolved. The present study aimed to reveal the influence of the drug on the functionality of the myocardium, the skeletal muscle, and the vasculature in a rat model of HFpEF. Female obese ZSF-1 rats received Sac/Val as a daily oral gavage for 12 weeks. Left ventricle (LV) function was assessed every four weeks using echocardiography. Prior to organ removal, invasive hemodynamic measurements were performed in both ventricles. Vascular function of the carotid artery and skeletal muscle function were monitored. Sac/Val treatment reduced E/é ratios, left ventricular end diastolic pressure (LVEDP) and myocardial stiffness as well as myocardial fibrosis and heart weight compared to the obese control group. Sac/Val slightly improved endothelial function in the carotid artery but had no impact on skeletal muscle function. Our results demonstrate striking effects of Sac/Val on the myocardial structure and function in a rat model of HFpEF. While vasodilation was slightly improved, functionality of the skeletal muscle remained unaffected.
Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression
Authors: Kim Bonglee , Park Ji-Eon , Im Eunji , Cho Yongmin , Lee Jinjoo , Lee Hyo-Jung , Sim Deok-Yong , Park Woon-Yi , Shim Bum-Sang , Kim Sung-Hoon
Published: March 2021

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.
Function Trumps Form in Two Sugar Symporters, LacY and vSGLT
Authors: Abramson Jeff , Wright Ernest M.
Published: March 2021

Active transport of sugars into bacteria occurs through symporters driven by ion gradients. LacY is the most well-studied proton sugar symporter, whereas vSGLT is the most characterized sodium sugar symporter. These are members of the major facilitator (MFS) and the amino acid-Polyamine organocation (APS) transporter superfamilies. While there is no structural homology between these transporters, they operate by a similar mechanism. They are nano-machines driven by their respective ion electrochemical potential gradients across the membrane. LacY has 12 transmembrane helices (TMs) organized in two 6-TM bundles, each containing two 3-helix TM repeats. vSGLT has a core structure of 10 TM helices organized in two inverted repeats (TM 1–5 and TM 6–10). In each case, a single sugar is bound in a central cavity and sugar selectivity is determined by hydrogen- and hydrophobic- bonding with side chains in the binding site. In vSGLT, the sodium-binding site is formed through coordination with carbonyl- and hydroxyl-oxygens from neighboring side chains, whereas in LacY the proton (H3O+) site is thought to be a single glutamate residue (Glu325). The remaining challenge for both transporters is to determine how ion electrochemical potential gradients drive uphill sugar transport.
Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma
Authors: Armando Federico , Fayyad Adnan , Arms Stefanie , Barthel Yvonne , Schaudien Dirk , Rohn Karl , Gambini Matteo , Lombardo Mara Sophie , Beineke Andreas , Baumgärtner Wolfgang , Puff Christina
Published: March 2021

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.
The Major Ciliary Isoforms of RPGR Build Different Interaction Complexes with INPP5E and RPGRIP1L
Authors: Vössing Christine , Atigbire Paul , Eilers Jannis , Markus Fenja , Stieger Knut , Song Fei , Neidhardt John
Published: March 2021

X-linked retinitis pigmentosa (XLRP) is frequently caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. A complex splicing process acts on the RPGR gene resulting in three major isoforms: RPGRex1-19, RPGRORF15 and RPGRskip14/15. We characterized the widely expressed, alternatively spliced transcript RPGRskip14/15 lacking exons 14 and 15. Using the CRISPR/eSpCas9 system, we generated HEK293T cell lines exclusively expressing the RPGRskip14/15 transcript from the endogenous RPGR gene. RPGRex1-19 and RPGRORF15 were knocked out. Immunocytochemistry demonstrated that the RPGRskip14/15 protein localizes along primary cilia, resembling the expression pattern of RPGRex1-19. The number of cilia-carrying cells was not affected by the absence of the RPGRex1-19 and RPGRORF15 isoforms. Co-immunoprecipitation assays demonstrated that both RPGRex1-19 and RPGRskip14/15 interact with PDE6D, further supporting that RPGRskip14/15 is associated with the protein networks along the primary cilium. Interestingly, interaction complexes with INPP5E or RPGRIP1L were only detectable with isoform RPGRex1-19, but not with RPGRskip14/15, demonstrating distinct functional properties of the major RPGR isoforms in spite of their similar subcellular localization. Our findings lead to the conclusion that protein binding sites within RPGR are mediated through alternative splicing. A tissue-specific expression ratio between RPGRskip14/15 and RPGRex1-19 seems required to regulate the ciliary concentration of RPGR interaction partners.
Ex Vivo and In Vivo Analyses of Novel 3D-Printed Bone Substitute Scaffolds Incorporating Biphasic Calcium Phosphate Granules for Bone Regeneration
Authors: Oberdiek Franciska , Vargas Carlos Ivan , Rider Patrick , Batinic Milijana , Görke Oliver , Radenković Milena , Najman Stevo , Baena Jose Manuel , Jung Ole , Barbeck Mike
Published: March 2021

(1) Background: The aim of this study was examining the ex vivo and in vivo properties of a composite made from polycaprolactone (PCL) and biphasic calcium phosphate (BCP) (synprint, ScientiFY GmbH) fabricated via fused deposition modelling (FDM); (2) Methods: Scaffolds were tested ex vivo for their mechanical properties using porous and solid designs. Subcutaneous implantation model analyzed the biocompatibility of PCL + BCP and PCL scaffolds. Calvaria implantation model analyzed the osteoconductive properties of PCL and PCL + BCP scaffolds compared to BCP as control group. Established histological, histopathological and histomorphometrical methods were performed to evaluate new bone formation.; (3) Results Mechanical testing demonstrated no significant differences between PCL and PCL + BCP for both designs. Similar biocompatibility was observed subcutaneously for PCL and PCL + BCP scaffolds. In the calvaria model, new bone formation was observed for all groups with largest new bone formation in the BCP group, followed by the PCL + BCP group, and the PCL group. This finding was influenced by the initial volume of biomaterial implanted and remaining volume after 90 days. All materials showed osteoconductive properties and PCL + BCP tailored the tissue responses towards higher cellular biodegradability. Moreover, this material combination led to a reduced swelling in PCL + BCP; (4) Conclusions: Altogether, the results show that the newly developed composite is biocompatible and leads to successful osteoconductive bone regeneration. The new biomaterial combines the structural stability provided by PCL with bioactive characteristics of BCP-based BSM. 3D-printed BSM provides an integration behavior in accordance with the concept of guided bone regeneration (GBR) by directing new bone growth for proper function and restoration.
Poly(ADP-Ribose) Polymerase 1 Promotes Inflammation and Fibrosis in a Mouse Model of Chronic Pancreatitis
Authors: El-Hamoly Tarek , Hajnády Zoltán , Nagy-Pénzes Máté , Bakondi Edina , Regdon Zsolt , Demény Máté A. , Kovács Katalin , Hegedűs Csaba , Abd El-Rahman Sahar S. , Szabó Éva , Maléth József , Hegyi Péter , Virág László
Published: March 2021

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by ductal obstructions, tissue fibrosis, atrophy and exocrine and endocrine pancreatic insufficiency. However, our understanding is very limited concerning the disease’s progression from a single acute inflammation, via recurrent acute pancreatitis (AP) and early CP, to the late stage CP. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor enzyme activated mostly by oxidative DNA damage. As a co-activator of inflammatory transcription factors, PARP1 is a central mediator of the inflammatory response and it has also been implicated in acute pancreatitis. Here, we set out to investigate whether PARP1 contributed to the pathogenesis of CP. We found that the clinically used PARP inhibitor olaparib (OLA) had protective effects in a murine model of CP induced by multiple cerulein injections. OLA reduced pancreas atrophy and expression of the inflammatory mediators TNFα and interleukin-6 (IL-6), both in the pancreas and in the lungs. Moreover, there was significantly less fibrosis (Masson’s trichrome staining) in the pancreatic sections of OLA-treated mice compared to the cerulein-only group. mRNA expression of the fibrosis markers TGFβ, smooth muscle actin (SMA), and collagen-1 were markedly reduced by OLA. CP was also induced in PARP1 knockout (KO) mice and their wild-type (WT) counterparts. Inflammation and fibrosis markers showed lower expression in the KO compared to the WT mice. Moreover, reduced granulocyte infiltration (tissue myeloperoxidase activity) and a lower elevation of serum amylase and lipase activity could also be detected in the KO mice. Furthermore, primary acinar cells isolated from KO mice were also protected from cerulein-induced toxicity compared to WT cells. In summary, our data suggest that PARP inhibitors may be promising candidates for repurposing to treat not only acute but chronic pancreatitis as well.
Candidates for Intra-Articular Administration Therapeutics and Therapies of Osteoarthritis
Authors: Toyoda Eriko , Maehara Miki , Watanabe Masahiko , Sato Masato
Published: March 2021

Osteoarthritis (OA) of the knee is a disease that significantly decreases the quality of life due to joint deformation and pain caused by degeneration of articular cartilage. Since the degeneration of cartilage is irreversible, intervention from an early stage and control throughout life is important for OA treatment. For the treatment of early OA, the development of a disease-modifying osteoarthritis drug (DMOAD) for intra-articular (IA) injection, which is attracting attention as a point-of-care therapy, is desired. In recent years, the molecular mechanisms involved in OA progression have been clarified while new types of drug development methods based on gene sequences have been established. In addition to conventional chemical compounds and protein therapeutics, the development of DMOAD from the new modalities such as gene therapy and oligonucleotide therapeutics is accelerating. In this review, we have summarized the current status and challenges of DMOAD for IA injection, especially for protein therapeutics, gene therapy, and oligonucleotide therapeutics.
Pressure and Chemical Unfolding of an α-Helical Bundle Protein: The GH2 Domain of the Protein Adaptor GIPC1
Authors: Dubois Cécile , Planelles-Herrero Vicente J. , Tillatte-Tripodi Camille , Delbecq Stéphane , Mammri Léa , Sirkia Elena M. , Ropars Virginie , Roumestand Christian , Barthe Philippe
Published: March 2021

When combined with NMR spectroscopy, high hydrostatic pressure is an alternative perturbation method used to destabilize globular proteins that has proven to be particularly well suited for exploring the unfolding energy landscape of small single-domain proteins. To date, investigations of the unfolding landscape of all-β or mixed-α/β protein scaffolds are well documented, whereas such data are lacking for all-α protein domains. Here we report the NMR study of the unfolding pathways of GIPC1-GH2, a small α-helical bundle domain made of four antiparallel α-helices. High-pressure perturbation was combined with NMR spectroscopy to unravel the unfolding landscape at three different temperatures. The results were compared to those obtained from classical chemical denaturation. Whatever the perturbation used, the loss of secondary and tertiary contacts within the protein scaffold is almost simultaneous. The unfolding transition appeared very cooperative when using high pressure at high temperature, as was the case for chemical denaturation, whereas it was found more progressive at low temperature, suggesting the existence of a complex folding pathway.
High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea
Authors: Boneberg Raphael , Pardun Anita , Hannemann Lena , Hildebrandt Olaf , Koehler Ulrich , Kinscherf Ralf , Hildebrandt Wulf
Published: March 2021

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with “hypoxic stress” (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.
Dual Detection of the Chytrid Fungi Batrachochytrium spp. with an Enhanced Environmental DNA Approach
Authors: Lastra González David , Baláž Vojtech , Vojar Jiří , Chajma Petr
Published: March 2021

Environmental DNA (eDNA) is becoming an indispensable tool in biodiversity monitoring, including the monitoring of invasive species and pathogens. Aquatic chytrid fungi Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal) are major threats to amphibians. However, the use of eDNA for detecting these pathogens has not yet become widespread, due to technological and economic obstacles. Using the enhanced eDNA approach (a simple and cheap sampling protocol) and the universally accepted qPCR assay, we confirmed the presence of Bsal and Bd in previously identified sites in Spain, including four sites that were new for Bsal. The new approach was successfully tested in laboratory conditions using manufactured gene fragments (gBlocks) of the targeted DNA sequence. A comparison of storage methods showed that samples kept in ethanol had the best DNA yield. Our results showed that the number of DNA copies in the Internal Transcribed Spacer region was 120 copies per Bsal cell. Eradication of emerging diseases requires quick and cost-effective solutions. We therefore performed cost-efficiency analyses of standard animal swabbing, a previous eDNA approach, and our own approach. The procedure presented here was evaluated as the most cost-efficient. Our findings will help to disseminate information about efforts to prevent the spread of chytrid fungi.
The Promise of Patient-Derived Preclinical Models to Accelerate the Implementation of Personalised Medicine for Children with Neuroblastoma
Authors: Tucker Elizabeth R. , George Sally , Angelini Paola , Bruna Alejandra , Chesler Louis
Published: March 2021

Patient-derived preclinical models are now a core component of cancer research and have the ability to drastically improve the predictive power of preclinical therapeutic studies. However, their development and maintenance can be challenging, time consuming, and expensive. For neuroblastoma, a developmental malignancy of the neural crest, it is possible to establish patient-derived models as xenografts in mice and zebrafish, and as spheroids and organoids in vitro. These varied approaches have contributed to comprehensive packages of preclinical evidence in support of new therapeutics for neuroblastoma. We discuss here the ethical and technical considerations for the creation of patient-derived models of neuroblastoma and how their use can be optimized for the study of tumour evolution and preclinical therapies. We also discuss how neuroblastoma patient-derived models might become avatars for personalised medicine for children with this devastating disease.
Construction of a Landscape Ecological Network for a Large-Scale Energy and Chemical Industrial Base: A Case Study of Ningdong, China
Authors: Yu Haochen , Huang Jiu , Ji Chuning , Li Zi’ao
Published: March 2021

A large-scale energy and chemical industry base is an important step in the promotion of the integrated and coordinated development of coal and its downstream coal-based industry. A number of large-scale energy and chemical industrial bases have been built in the Yellow River Basin that rely on its rich coal resources. However, the ecological environment is fragile in this region. Once the eco-environment is destroyed, the wildlife would lose its habitat. Therefore, this area has attracted wide attention regarding the development of the coal-based industry while also protecting the ecological environment. An ecological network could improve landscape connectivity and provide ideas for ecological restoration. This study took the Ningdong Energy and Chemical Industrial Base as a case study. Morphological spatial pattern analysis was applied to extract core patches. The connectivity of the core patches was evaluated, and then the ecological source patches were recognized. The minimum cumulative resistance model, hydrologic analysis and circuit theory were used to simulate the ecological network. Then, ecological corridors and ecological nodes were classified. The results were as follows: (1) The vegetation fractional coverage has recently been significantly improved. The area of core patches was 22,433.30 ha. In addition, 18 patches were extracted as source patches, with a total area of 9455.88 ha; (2) Fifty-eight potential ecological corridors were simulated. In addition, it was difficult to form a natural ecological corridor because of the area’s great resistance. Moreover, the connectivity was poor between the east and west; (3) A total of 52 potential ecological nodes were simulated and classified. The high-importance nodes were concentrated in the western grassland and Gobi Desert. This analysis indicated that restoration would be conducive to the ecological landscape in this area. Furthermore, five nodes with high importance but low vegetation fractional coverage should be given priority in later construction. In summary, optimizing the ecological network to achieve ecological restoration was suggested in the study area. The severe eco-environmental challenges urgently need more appropriate policy guidance in the large energy and chemical bases. Thus, the ecological restoration and ecological network construction should be combined, the effectiveness of ecological restoration could be effectively achieved, and the cost could also be reduced.
Exploitation of Marine-Derived Robust Biological Molecules to Manage Inflammatory Bowel Disease
Authors: Bilal Muhammad , Nunes Leonardo Vieira , Duarte Marco Thúlio Saviatto , Ferreira Luiz Fernando Romanholo , Soriano Renato Nery , Iqbal Hafiz M. N.
Published: March 2021

Naturally occurring biological entities with extractable and tunable structural and functional characteristics, along with therapeutic attributes, are of supreme interest for strengthening the twenty-first-century biomedical settings. Irrespective of ongoing technological and clinical advancement, traditional medicinal practices to address and manage inflammatory bowel disease (IBD) are inefficient and the effect of the administered therapeutic cues is limited. The reasonable immune response or invasion should also be circumvented for successful clinical translation of engineered cues as highly efficient and robust bioactive entities. In this context, research is underway worldwide, and researchers have redirected or regained their interests in valorizing the naturally occurring biological entities/resources, for example, algal biome so-called “treasure of untouched or underexploited sources”. Algal biome from the marine environment is an immense source of excellence that has also been demonstrated as a source of bioactive compounds with unique chemical, structural, and functional features. Moreover, the molecular modeling and synthesis of new drugs based on marine-derived therapeutic and biological cues can show greater efficacy and specificity for the therapeutics. Herein, an effort has been made to cover the existing literature gap on the exploitation of naturally occurring biological entities/resources to address and efficiently manage IBD. Following a brief background study, a focus was given to design characteristics, performance evaluation of engineered cues, and point-of-care IBD therapeutics of diverse bioactive compounds from the algal biome. Noteworthy potentialities of marine-derived biologically active compounds have also been spotlighted to underlying the impact role of bio-active elements with the related pathways. The current review is also focused on the applied standpoint and clinical translation of marine-derived bioactive compounds. Furthermore, a detailed overview of clinical applications and future perspectives are also given in this review.