bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals
Authors: Bhattacharjee Shamee , Dashwood Roderick H.
Published: September 2020

Epigenetics has provided a new dimension to our understanding of nuclear factor erythroid 2–related factor 2/Kelch-like ECH-associated protein 1 (human NRF2/KEAP1 and murine Nrf2/Keap1) signaling. Unlike the genetic changes affecting DNA sequence, the reversible nature of epigenetic alterations provides an attractive avenue for cancer interception. Thus, targeting epigenetic mechanisms in the corresponding signaling networks represents an enticing strategy for therapeutic intervention with dietary phytochemicals acting at transcriptional, post-transcriptional, and post-translational levels. This regulation involves the interplay of histone modifications and DNA methylation states in the human NFE2L2/KEAP1 and murine Nfe2l2/Keap1 genes, acetylation of lysine residues in NRF2 and Nrf2, interaction with bromodomain and extraterminal domain (BET) acetyl “reader” proteins, and non-coding RNAs such as microRNA (miRNA) and long non-coding RNA (lncRNA). Phytochemicals documented to modulate NRF2 signaling act by reversing hypermethylated states in the CpG islands of NFE2L2 or Nfe2l2, via the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), through the induction of ten-eleven translocation (TET) enzymes, or by inducing miRNA to target the 3′-UTR of the corresponding mRNA transcripts. To date, fewer than twenty phytochemicals have been reported as NRF2 epigenetic modifiers, including curcumin, sulforaphane, resveratrol, reserpine, and ursolic acid. This opens avenues for exploring additional dietary phytochemicals that regulate the human epigenome, and the potential for novel strategies to target NRF2 signaling with a view to beneficial interception of cancer and other chronic diseases.
Anti-Osteoporotic Effects of Antioxidant Peptides PIISVYWK and FSVVPSPK from Mytilus edulis on Ovariectomized Mice
Authors: Oh Yunok , Ahn Chang-Bum , Cho Won Ho , Yoon Na Young , Je Jae-Young
Published: September 2020

Numerous amounts of evidence suggest that bioactive peptides with diverse physiological activities can be nutraceuticals or potential drug candidates. In this study, blue mussel-derived antioxidant peptides PIISVYWK and FSVVPSPK were subjected to evaluate their osteogenic effect in mouse bone marrow mesenchymal stem cells (mBMMSCs) followed by an in vivo anti-osteoporotic effect. Treatment of PIISVYWK and FSVVPSPK on mBMMSCs stimulated alkaline phosphatase activity and calcification. Western blot results revealed that PIISVYWK and FSVVPSPK increased the expression of bone morphogenetic protein-2/4 (BMP-2/4) followed by upregulating p-Smad1/5, type I collagen, and transcription factors including Runx2 and osterix in mBMMSCs. Two peptides also activated the phosphorylation of MAPKs (p-p38, p-ERK, and p-JNK). Treatment of MAPK inhibitors significantly inhibited the BMP signaling pathway, indicating that PIISVYWK and FSVVPSPK stimulated osteoblast differentiation of mBMMSCs through the MAPK-dependent BMP signaling pathway. The anti-osteoporotic effect of PIISVYWK and FSVVPSPK in ovariectomized (OVX) mice was investigated. Treatment of PIISVYWK and FSVVPSPK for ten weeks showed a notable anti-osteoporotic effect in OVX mice via increasing bone mineral density and other bone parameters compared to OVX mice without peptides. Serum analysis also showed that treatment of PIISVYWK and FSVVPSPK completely reduced osteocalcin and ALP (alkAline phosphatase) activity. Taken together, these results suggest that PIISVYWK and FSVVPSPK could be health-promoting functional food ingredients against osteoporosis.
Regulatory Functions of L-Carnitine, Acetyl, and Propionyl L-Carnitine in a PCOS Mouse Model: Focus on Antioxidant/Antiglycative Molecular Pathways in the Ovarian Microenvironment
Authors: Di Emidio Giovanna , Rea Francesco , Placidi Martina , Rossi Giulia , Cocciolone Domenica , Virmani Ashraf , Macchiarelli Guido , Palmerini Maria Grazia , D’Alessandro Anna Maria , Artini Paolo Giovanni , Tatone Carla
Published: September 2020

Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with female infertility. Based on energy and antioxidant regulatory functions of carnitines, we investigated whether acyl-L-carnitines improve PCOS phenotype in a mouse model induced by dehydroepiandrosterone (DHEA). CD1 mice received DHEA for 20 days along with two different carnitine formulations: one containing L-carnitine (LC) and acetyl-L-carnitine (ALC), and the other one containing also propionyl-L-carnitine (PLC). We evaluated estrous cyclicity, testosterone level, ovarian follicle health, ovulation rate and oocyte quality, collagen deposition, lipid droplets, and 17ß-HSD IV (17 beta-hydroxysteroid dehydrogenase type IV) expression. Moreover, we analyzed protein expression of SIRT1, SIRT3, SOD2 (superoxide dismutase 2), mitochondrial transcriptional factor A (mtTFA), RAGE (receptor for AGEs), GLO2 (glyoxalase 2) and ovarian accumulation of MG-AGEs (advanced glycation end-products formed by methylglyoxal). Both carnitine formulations ameliorated ovarian PCOS phenotype and positively modulated antioxidant molecular pathways in the ovarian microenvironment. Addition of PLC to LC-ALC formulation mitigated intraovarian MG-AGE accumulation and increased mtTFA expression. In conclusion, our study supports the hypothesis that oral administration of acyl-L-carnitines alleviates ovarian dysfunctions associated with this syndrome and that co-administration of PLC provides better activity. Molecular mechanisms underlying these effects include anti-oxidant/glycative activity and potentiation of mitochondria.
Soluble Cyanobacterial Carotenoprotein as a Robust Antioxidant Nanocarrier and Delivery Module
Authors: Maksimov Eugene G. , Zamaraev Alexey V. , Parshina Evgenia Yu. , Slonimskiy Yury B. , Slastnikova Tatiana A. , Abdrakhmanov Alibek A. , Babaev Pavel A. , Efimova Svetlana S. , Ostroumova Olga S. , Stepanov Alexey V. , Slutskaya Ekaterina A. , Ryabova Anastasia V. , Friedrich Thomas , Sluchanko Nikolai N.
Published: September 2020

To counteract oxidative stress, antioxidants including carotenoids are highly promising, yet their exploitation is drastically limited by the poor bioavailability and fast photodestruction, whereas current delivery systems are far from being efficient. Here we demonstrate that the recently discovered nanometer-sized water-soluble carotenoprotein from Anabaena sp. PCC 7120 (termed AnaCTDH) transiently interacts with liposomes to efficiently extract carotenoids via carotenoid-mediated homodimerization, yielding violet–purple protein samples. We characterize the spectroscopic properties of the obtained pigment–protein complexes and the thermodynamics of liposome–protein carotenoid transfer and demonstrate the delivery of carotenoid echinenone from AnaCTDH into liposomes with an efficiency of up to 70 ± 3%. Most importantly, we show efficient carotenoid delivery to membranes of mammalian cells, which provides protection from reactive oxygen species (ROS). Incubation of neuroblastoma cell line Tet21N in the presence of 1 μM AnaCTDH binding echinenone decreased antimycin A ROS production by 25% (p < 0.05). The described carotenoprotein may be considered as part of modular systems for the targeted antioxidant delivery.
S-Nitrosoglutathione Reverts Dietary Sucrose-Induced Insulin Resistance
Authors: Sousa-Lima Inês , Fernandes Ana B. , Patarrão Rita S. , Kim Young-Bum , Macedo M. Paula
Published: September 2020

The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase in insulin sensitivity from the fast to the postprandial status. Hepatic regulation of glucose metabolism is crucial and has been shown to be modulated by glutathione (GSH) and nitric oxide (NO). However, knowledge of the metabolic action of GSH and NO in glucose homeostasis remains incomplete. The current study was designed to test the hypothesis that treatment with S-nitrosoglutathione is sufficient to revert insulin resistance induced by a high-sucrose diet. Male Wistar rats were divided in a control or high-sucrose group. Insulin sensitivity was determined: (i) in the fast state; (ii) after a standardized test meal; (iii) after GSH + NO; and after (iv) S-nitrosoglutathione (GSNO) administration. The fasting glucose level was not different between the control and high-sucrose group. In the liver, the high-sucrose model shows increased NO and unchanged GSH levels. In control animals, insulin sensitivity increased after a meal or administration of GSH+NO/GSNO, but this was abrogated by sucrose feeding. GSNO was able to revert insulin resistance induced by sucrose feeding, in a dose-dependent manner, suggesting that they have an insulin-sensitizing effect in vivo. These effects are associated with an increased insulin receptor and Akt phosphorylation in muscle cells. Our findings demonstrate that GSNO promotes insulin sensitivity in a sucrose-induced insulin-resistant animal model and further implicates that this antioxidant molecule may act as a potential pharmacological tool for the treatment of insulin resistance in obesity and type 2 diabetes.
Berry Phenolic and Volatile Extracts Inhibit Pro-Inflammatory Cytokine Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB Signaling Pathway
Authors: Gu Inah , Brownmiller Cindi , Stebbins Nathan B. , Mauromoustakos Andy , Howard Luke , Lee Sun-Ok
Published: September 2020

Berries are a rich source of phytochemicals, especially phenolics well known for protective activity against many chronic diseases. Berries also contain a complex mixture of volatile compounds that are responsible for the unique aromas of berries. However, there is very limited information on the composition and potential health benefits of berry volatiles. In this study, we isolated phenolic and volatile fractions from six common berries and characterized them by HPLC/HPLC-MS and GC/GC-MS, respectively. Berry phenolic and volatile fractions were evaluated for an anti-inflammatory effect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by measuring levels of pro-inflammatory cytokines and the nuclear factor-kappa B (NF-κB) signaling pathway. Results showed that LPS-induced excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which were inhibited by berry phenolic and volatile extracts. Moreover, berry phenolic and volatile extracts reduced the nuclear translocation of NF-κB by blocking the phosphorylation of p65 and degradation of IκBα. These findings showed that berry volatiles from six berries had comparable anti-inflammatory effects to berry phenolics through the suppression of pro-inflammatory mediators and cytokines expression via NF-κB down-regulation, despite being present in the fruit at a lower concentration.
Detecting Relative Amplitude of IR Signals with Active Sensors and Its Application to a Positioning System
Authors: Aparicio-Esteve Elena , Hernández Álvaro , Ureña Jesús , Villadangos José Manuel , Lluva Sergio , Pérez-Rubio María Carmen
Published: September 2020

Nowadays, there is an increasing interest in smart systems, e.g., smart metering or smart spaces, for which active sensing plays an important role. In such systems, the sample or environment to be measured is irradiated with a signal (acoustic, infrared, radio-frequency…) and some of their features are determined from the transmitted or reflected part of the original signal. In this work, infrared (IR) signals are emitted from different sources (four in this case) and received by a unique quadrature angular diversity aperture (QADA) sensor. A code division multiple access (CDMA) technique is used to deal with the simultaneous transmission of all the signals and their separation (depending on the source) at the receiver’s processing stage. Furthermore, the use of correlation techniques allows the receiver to determine the amount of energy received from each transmitter, by quantifying the main correlation peaks. This technique can be used in any system requiring active sensing; in the particular case of the IR positioning system presented here, the relative amplitudes of those peaks are used to determine the central incidence point of the light from each emitter on the QADA. The proposal tackles the typical phenomena, such as distortions caused by the transducer impulse response, the near-far effect in CDMA-based systems, multipath transmissions, the correlation degradation from non-coherent demodulations, etc. Finally, for each emitter, the angle of incidence on the QADA receiver is estimated, assuming that it is on a horizontal plane, although with any rotation on the vertical axis Z. With the estimated angles and the known positions of the LED emitters, the position (x, y, z) of the receiver is determined. The system is validated at different positions in a volume of 3 × 3 × 3.4 m3 obtaining average errors of 7.1, 5.4, and 47.3 cm in the X, Y and Z axes, respectively.
Improving Machine Learning Identification of Unsafe Driver Behavior by Means of Sensor Fusion
Authors: Lattanzi Emanuele , Castellucci Giacomo , Freschi Valerio
Published: September 2020

Most road accidents occur due to human fatigue, inattention, or drowsiness. Recently, machine learning technology has been successfully applied to identifying driving styles and recognizing unsafe behaviors starting from in-vehicle sensors signals such as vehicle and engine speed, throttle position, and engine load. In this work, we investigated the fusion of different external sensors, such as a gyroscope and a magnetometer, with in-vehicle sensors, to increase machine learning identification of unsafe driver behavior. Starting from those signals, we computed a set of features capable to accurately describe the behavior of the driver. A support vector machine and an artificial neural network were then trained and tested using several features calculated over more than 200 km of travel. The ground truth used to evaluate classification performances was obtained by means of an objective methodology based on the relationship between speed, and lateral and longitudinal acceleration of the vehicle. The classification results showed an average accuracy of about 88% using the SVM classifier and of about 90% using the neural network demonstrating the potential capability of the proposed methodology to identify unsafe driver behaviors.
The Pheromone-Based Harmony Search Algorithm for the Asymmetric Traveling Salesman Problem
Authors: Szwarc Krzysztof , Boryczka Urszula
Published: September 2020

This paper presents a modification of the Harmony Search algorithm (HS) adjusted to an effective solving of instances of the Asymmetric Traveling Salesman Problem. The improvement of the technique spans the application of a pheromone, which, by serving the role of long-term memory, enables the improvement of the quality of determined results, especially for tasks characterized by a significant number of vertices. The publication includes the results of tests that suggest the achievement of effectiveness improvement through the modification of the HS and recommendations concerning the proper configuration of the algorithm.
Precision Analysis and Error Compensation of a Telescope Truss Structure Based on Robotics
Authors: Wang Rui , Wang Fuguo , Cao Yuyan , Wang Honghao , Sun Xueqian , Liu Fuhe
Published: September 2020

We propose a new secondary mirror support structure assisted by multi-robotics to improve the observation performance of vehicle-mobile telescope systems. A mathematical model of the displacement at the end of the robotic and the variation of telescope pitch angle is established, then the posture of the robotic is optimized by the Jacobian matrix iteration inverse kinematic problem method. Based on the new support structure, a high-order sensitivity matrix is proposed to establish the mapping relationship between the robotic misalignment and the Zernike coefficient, with the accuracy verified via the Monte Carlo method. The method of adjusting the secondary mirror to compensate the aberration caused by the primary mirror is proposed, and the relationship between the primary mirror surface error and the system error is established under different pitch angles before and after compensation. The experiment and simulation results showed that the adjustment calculated by the high-order sensitivity matrix method can effectively compensate for the misalignment caused by the robotics and the primary mirror surface error to a certain degree. After multiple iterations, the root mean square of the wavefront aberration was better than λ/15. This conclusion provides an engineering application reference value for the secondary mirror support and aberration correction technology of the vehicle telescope system.
Traditional Herbal Medicine Mediated Regulations during Head and Neck Carcinogenesis
Authors: Lan Xiang-Yun , Chung Tzu-Ting , Huang Chien-Ling , Lee Yi-Jang , Li Wan-Chun
Published: September 2020

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. It is well recognized that environmental challenges such as smoking, viral infection and alcohol consumption are key factors underlying HNSCC pathogenesis. Other than major clinical interventions (e.g., surgical resection, chemical and radiotherapy) that have been routinely practiced over years, adjuvant anticancer agents from Traditional Herbal Medicine (THM) are proposed, either alone or together with conventional therapies, to be experimentally effective for improving treatment efficacy in different cancers including HNSCCs. At a cellular and molecular basis, THM extracts could modulate different malignant indices via distinct signaling pathways and provide better control in HNSCC malignancy and its clinical complications such as radiotherapy-induced xerostomia/oral mucositis. In this article, we aim to systemically review the impacts of THM in regulating HNSCC tumorous identities and its potential perspective for clinical use.
Curcumin Inhibits the Primary Nucleation of Amyloid-Beta Peptide: A Molecular Dynamics Study
Authors: Doytchinova Irini , Atanasova Mariyana , Salamanova Evdokiya , Ivanov Stefan , Dimitrov Ivan
Published: September 2020

The amyloid plaques are a key hallmark of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Amyloidogenesis is a complex long-lasting multiphase process starting with the formation of nuclei of amyloid peptides: a process assigned as a primary nucleation. Curcumin (CU) is a well-known inhibitor of the aggregation of amyloid-beta (Aβ) peptides. Even more, CU is able to disintegrate preformed Aβ firbils and amyloid plaques. Here, we simulate by molecular dynamics the primary nucleation process of 12 Aβ peptides and investigate the effects of CU on the process. We found that CU molecules intercalate among the Aβ chains and bind tightly to them by hydrogen bonds, hydrophobic, π–π, and cation–π interactions. In the presence of CU, the Aβ peptides form a primary nucleus of a bigger size. The peptide chains in the nucleus become less flexible and more disordered, and the number of non-native contacts and hydrogen bonds between them decreases. For comparison, the effects of the weaker Aβ inhibitor ferulic acid (FA) on the primary nucleation are also examined. Our study is in good agreement with the observation that taken regularly, CU is able to prevent or at least delay the onset of neurodegenerative disorders.
Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes
Authors: Park Eun Jung , Dusabimana Theodomir , Je Jihyun , Jeong Kyuho , Yun Seung Pil , Kim Hye Jung , Kim Hwajin , Park Sang Won
Published: September 2020

Glutathione (GSH) is an endogenous antioxidant found in plants, animals, fungi, and some microorganisms that protects cells by neutralizing hydrogen peroxide. Honokiol, an active ingredient of Magnolia officinalis, is known for antioxidant, anti-inflammatory, and anti-bacterial properties. We investigated the protective mechanism of honokiol through regulating cellular GSH in renal proximal tubules against acute kidney injury (AKI). First, we measured cellular GSH levels and correlated them with the expression of GSH biosynthetic enzymes after honokiol treatment in human kidney-2 (HK-2) cells. Second, we used pharmacological inhibitors or siRNA-mediated gene silencing approach to determine the signaling pathway induced by honokiol. Third, the protective effect of honokiol via de novo GSH biosynthesis was investigated in renal ischemia-reperfusion (IR) mice. Honokiol significantly increased cellular GSH levels by upregulating the subunits of glutamate-cysteine ligase (Gcl)—Gclc and Gclm. These increases were mediated by activation of nuclear factor erythroid 2-related factor 2, via PI3K/Akt and protein kinase C signaling. Consistently, honokiol treatment reduced the plasma creatinine, tubular cell death, neutrophil infiltration and lipid peroxidation in IR mice and the effect was correlated with upregulation of Gclc and Gclm. Conclusively, honokiol may benefit to patients with AKI by increasing antioxidant GSH via transcriptional activation of the biosynthetic enzymes.
Can Pallidal Deep Brain Stimulation Rescue Borderline Dystonia? Possible Coexistence of Functional (Psychogenic) and Organic Components
Authors: Morigaki Ryoma , Miyamoto Ryosuke , Mure Hideo , Fujita Koji , Matsuda Taku , Yamamoto Yoko , Nakataki Masahito , Okahisa Tetsuya , Matsumoto Yuki , Miyake Kazuhisa , Yamamoto Nobuaki , Kaji Ryuji , Takagi Yasushi , Goto Satoshi
Published: September 2020

The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery.
Prospective Study Using Plasma Apolipoprotein A2-Isoforms to Screen for High-Risk Status of Pancreatic Cancer
Authors: Sato Yu , Kobayashi Takashi , Nishiumi Shin , Okada Akihiko , Fujita Tsuyoshi , Sanuki Tsuyoshi , Kobayashi Masao , Asahara Masakyo , Adachi Masayasu , Sakai Arata , Shiomi Hideyuki , Masuda Atsuhiro , Yoshida Masaru , Takeuchi Keiko , Kodama Yuzo , Kutsumi Hiromu , Nagashima Kengo , Honda Kazufumi
Published: September 2020

Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) has been identified as a minimally invasive biomarker for detecting pancreatic cancer (PC) and high-risk (HR) individuals for PC. To establish an efficient enrichment strategy for HR, we carried out a plasma apoA2-ATQ/AT level-based prospective screening study among the general population. The subjects for the screening study were recruited at six medical check-up facilities in Japan between October 2015 and January 2017. We evaluated the positive predictive value (PPV) of the plasma apoA2-ATQ/AT level of ≤35 μg/mL for detecting PC and HR. Furthermore, we prospectively confirmed its diagnostic accuracy with another post-diagnosis population in a cross-sectional study. We enrolled 5120 subjects in experimental screening, with 84 subjects (1.3%) showing positive results for apoA2-ATQ/AT. Pancreatic abnormalities were recognized in 26 of the 84 subjects from imaging examinations. Pancreatic abnormalities detected included 1 PC and 15 HR abnormalities, such as cystic lesions including intraductal papillary mucinous neoplasm. The PPV of apoA2-ATQ/AT for detecting PC and HR was 33.3%. Moreover, a combination study with another cross-sectional study revealed that the area under the curve for apoA2-ATQ/AT to distinguish PC from healthy controls was 0.903. ApoA2-ATQ/AT has the potential to enrich PC and HR by increasing the diagnostic probability before imaging examinations.
N-Terminal Acetyltransferases Are Cancer-Essential Genes Prevalently Upregulated in Tumours
Authors: Koufaris Costas , Kirmizis Antonis
Published: September 2020

N-terminal acetylation (Nt-Ac) is an abundant eukaryotic protein modification, deposited in humans by one of seven N-terminal acetyltransferase (NAT) complexes composed of a catalytic and potentially auxiliary subunits. The involvement of NATs in cancers is being increasingly recognised, but a systematic cross-tumour assessment is currently lacking. To address this limitation, we conducted here a multi-omic data interrogation for NATs. We found that tumour genomic alterations of NATs or of their protein substrates are generally rare events, with some tumour-specific exceptions. In contrast, altered gene expression of NATs in cancers and their association with patient survival constitute a widespread cancer phenomenon. Examination of dependency screens revealed that (i), besides NAA60 and NAA80 and the NatA paralogues NAA11 and NAA16, the other ten NAT genes were within the top 80th percentile of the most dependent genes (ii); NATs act through distinct biological processes. NAA40 (NatD) emerged as a NAT with particularly interesting cancer biology and therapeutic potential, especially in liver cancer where a novel oncogenic role was supported by its increased expression in multiple studies and its association with patient survival. In conclusion, this study generated insights and data that will be of great assistance in guiding further research into the function and therapeutic potential of NATs in cancer.
Spirulina-in Silico-Mutations and Their Comparative Analyses in the Metabolomics Scale by Using Proteome-Based Flux Balance Analysis
Authors: Lertampaiporn Supatcha , Senachak Jittisak , Taenkaew Wassana , Khannapho Chiraphan , Hongsthong Apiradee
Published: September 2020

This study used an in silico metabolic engineering strategy for modifying the metabolic capabilities of Spirulina under specific conditions as an approach to modifying culture conditions in order to generate the intended outputs. In metabolic models, the basic metabolic fluxes in steady-state metabolic networks have generally been controlled by stoichiometric reactions; however, this approach does not consider the regulatory mechanism of the proteins responsible for the metabolic reactions. The protein regulatory network plays a critical role in the response to stresses, including environmental stress, encountered by an organism. Thus, the integration of the response mechanism of Spirulina to growth temperature stresses was investigated via simulation of a proteome-based GSMM, in which the boundaries were established by using protein expression levels obtained from quantitative proteomic analysis. The proteome-based flux balance analysis (FBA) under an optimal growth temperature (35 °C), a low growth temperature (22 °C) and a high growth temperature (40 °C) showed biomass yields that closely fit the experimental data obtained in previous research. Moreover, the response mechanism was analyzed by the integration of the proteome and protein–protein interaction (PPI) network, and those data were used to support in silico knockout/overexpression of selected proteins involved in the PPI network. The Spirulina, wild-type, proteome fluxes under different growth temperatures and those of mutants were compared, and the proteins/enzymes catalyzing the different flux levels were mapped onto their designated pathways for biological interpretation.
Nano-Enhanced Cancer Immunotherapy: Immunology Encounters Nanotechnology
Authors: Bockamp Ernesto , Rosigkeit Sebastian , Siegl Dominik , Schuppan Detlef
Published: September 2020

Cancer immunotherapy utilizes the immune system to fight cancer and has already moved from the laboratory to clinical application. However, and despite excellent therapeutic outcomes in some hematological and solid cancers, the regular clinical use of cancer immunotherapies reveals major limitations. These include the lack of effective immune therapy options for some cancer types, unresponsiveness to treatment by many patients, evolving therapy resistance, the inaccessible and immunosuppressive nature of the tumor microenvironment (TME), and the risk of potentially life-threatening immune toxicities. Given the potential of nanotechnology to deliver, enhance, and fine-tune cancer immunotherapeutic agents, the combination of cancer immunotherapy with nanotechnology can overcome some of these limitations. In this review, we summarize innovative reports and novel strategies that successfully combine nanotechnology and cancer immunotherapy. We also provide insight into how nanoparticular combination therapies can be used to improve therapy responsiveness, to reduce unwanted toxicity, and to overcome adverse effects of the TME.
General Conceptual Framework of Future Wearables in Healthcare: Unified, Unique, Ubiquitous, and Unobtrusive (U4) for Customized Quantified Output
Authors: Haghi Mostafa , Deserno Thomas M.
Published: September 2020

We concentrate on the importance and future conceptual development of wearable devices as the major means of personalized healthcare. We discuss and address the role of wearables in the new era of healthcare in proactive medicine. This work addresses the behavioral, environmental, physiological, and psychological parameters as the most effective domains in personalized healthcare, and the wearables are categorized according to the range of measurements. The importance of multi-parameter, multi-domain monitoring and the respective interactions are further discussed and the generation of wearables based on the number of monitoring area(s) is consequently formulated.
Stress in Caregivers and Children with a Developmental Disorder Who Receive Rehabilitation
Authors: Kim Sung Hyun , Sung In Young , Ko Eun Jae , Park Jieun , Heo Nayoung
Published: September 2020

This study aimed to evaluate the stress levels of caregivers and children with developmental disorders who were receiving rehabilitation treatment. The relationships between stress levels and factors such as early rehabilitation and home rehabilitation were quantified. Methods: This study was conducted in children with development disorders, aged from 1.5 years to 18 years, who were undergoing rehabilitation. The Korean version of the Child Behavior Checklist (K-CBCL) and the Adult Self-Report (K-ASR) were used to evaluate stress levels in children and caregivers, respectively. Results: Questionnaires were provided to 150 caregivers who agreed to participate. However, only 76 copies of the K-CBCL and 75 copies of the K-ASR were collected. The mean K-CBCL and K-ASR t scores were in the normal range. The K-CBCL score correlated positively with the K-ASR score (p value < 0.5). K-CBCL externalizing problems score correlated positively with the age at the start of rehabilitation, and the K-CBCL and K-ASR externalizing problems scores correlated negatively with home treatment delivered by caregivers. Conclusions: Stress levels of children and caregivers were closely related. Home rehabilitation provided by caregivers reduced stress in both caregivers and children. Early rehabilitation did not impart additional psychological burden on caregivers or children.
Novel Topical Application of a Postbiotic, LactoSporin®, in Mild to Moderate Acne: A Randomized, Comparative Clinical Study to Evaluate its Efficacy, Tolerability and Safety
Authors: Majeed Muhammed , Majeed Shaheen , Nagabhushanam Kalyanam , Mundkur Lakshmi , Rajalakshmi H. , Shah Kalpesh , Beede Kirankumar
Published: September 2020

Acne vulgaris is a common skin disorder of pilosebaceous units. The therapy for mild-to-moderate acne includes topical antibiotics, benzoyl peroxide and retinoids. In this open-label, randomized monocentric study, we compared the efficacy of LactoSporin® 2% w/w cream with benzoyl peroxide in 64 male and female subjects with mild-to-moderate acne for three weeks. The efficacy parameters were evaluated based on the dermatologist visual assessment and instrumental measurements using Sebumeter® MPA580, Antera 3DTM and VISIA CR 2.2 and subject self-assessment questionnaires. Adverse events were recorded throughout the study period. In order to understand the mechanism of action and properties of LactoSporin, the pH stability, thermostability, antimicrobial activity and 5-alpha reductase activity were evaluated in vitro. A significant improvement was observed in the dermatological assessment of closed comedones (p < 0.0001), open comedones (p = 0.0069) and papules count (p < 0.0001) in comparison to the baseline in both LactoSporin and benzoyl peroxide groups. The antera analysis showed significant improvement in redness (p < 0.0001) and elevation (p < 0.0001) (small and medium) in both the treatment groups. The sebumeter analysis showed a significant decrease in sebaceous secretion (p < 0.0001) for LactoSporin, which resulted in reduced oiliness, pimples, acne spots and redness around the acne spot. The product was found to be safe without any irritancy. LactoSporin was stable at an acidic pH and temperature range of 70 to 90 °C, with antimicrobial activity against various pathogenic bacteria, including Cutibacterium acnes. It was also a potent inhibitor of 5-alpha reductase activity. Thus, it can be concluded that the efficacy of LactoSporin is equivalent to benzoyl peroxide in the treatment of mild-to-moderate acne lesions and better than benzoyl peroxide for reducing the sebaceous secretion and oily, greasy nature of the skin, implying its efficacy in other sebohorriec conditions.
Viable Materials with a Giant Magnetocaloric Effect
Authors: Zarkevich Nikolai A. , Zverev Vladimir I.
Published: September 2020

This review of the current state of magnetocalorics is focused on materials exhibiting a giant magnetocaloric response near room temperature. To be economically viable for industrial applications and mass production, materials should have desired useful properties at a reasonable cost and should be safe for humans and the environment during manufacturing, handling, operational use, and after disposal. The discovery of novel materials is followed by a gradual improvement of properties by compositional adjustment and thermal or mechanical treatment. Consequently, with time, good materials become inferior to the best. There are several known classes of inexpensive materials with a giant magnetocaloric effect, and the search continues.
Pug-Headedness Anomaly in a Wild and Isolated Population of Native Mediterranean Trout Salmo trutta L., 1758 Complex (Osteichthyes: Salmonidae)
Authors: Palmas Francesco , Righi Tommaso , Musu Alessio , Frongia Cheoma , Podda Cinzia , Serra Melissa , Splendiani Andrea , Caputo Barucchi Vincenzo , Sabatini Andrea
Published: September 2020

Skeletal anomalies are commonplace among farmed fish. The pug-headedness anomaly is an osteological condition that results in the deformation of the maxilla, pre-maxilla, and infraorbital bones. Here, we report the first record of pug-headedness in an isolated population of the critically endangered native Mediterranean trout Salmo trutta L., 1758 complex from Sardinia, Italy. Fin clips were collected for the molecular analyses (D-loop, LDH-C1* locus. and 11 microsatellites). A jaw index (JI) was used to classify jaw deformities. Ratios between the values of morphometric measurements of the head and body length were calculated and plotted against values of body length to identify the ratios that best discriminated between malformed and normal trout. Haplotypes belonging to the AD lineage and the genotype LDH-C1*100/100 were observed in all samples, suggesting high genetic integrity of the population. The analysis of 11 microsatellites revealed that observed heterozygosity was similar to the expected one, suggesting the absence of inbreeding or outbreeding depression. The frequency of occurrence of pug-headedness was 12.5% (two out of 16). One specimen had a strongly blunted forehead and an abnormally short upper jaw, while another had a slightly anomaly asymmetrical jaw. Although sample size was limited, variation in environmental factors during larval development seemed to be the most likely factors to trigger the deformities.
Assessing the Diversity of the Form of Age-Specific Changes in Adult Mortality from Captive Mammalian Populations
Authors: Ronget Victor , Lemaître Jean-François , Tidière Morgane , Gaillard Jean-Michel
Published: September 2020

Actuarial senescence (i.e., the age-specific increase in mortality rate) is pervasive across mammalian species, but our current understanding of the diversity of forms that actuarial senescence displays across species remains limited. Although several mathematical models have been proposed to model actuarial senescence, there is still no consensus on which model to use, especially when comparing mortality patterns among species. To fill this knowledge gap, we fitted and compared different forms of increase using models commonly used in senescence studies (i.e., Gompertz, Weibull, and logistic) across 61 species of mammalian captive populations using the Bayesian Survival Trajectory Analysis (BaSTA) approach. For as much as 79% of the species, a Gompertz increase of mortality with age was the most parsimonious model that satisfactorily described the shape of age-specific mortality changes in adults. This highlights that the form of the increase in mortality is mostly consistent across mammalian species and follows the Gompertz rule with some rare exceptions. The implications of that result are twofold. First, the Gompertz rate of mortality increase should be used in cross-species comparative analyses of mammals, as already done in some studies. Second, although the Gompertz model accurately describes actuarial senescence in most mammals, there are notable exceptions, and the factors causing this deviation from an exponential mortality increase during the adult stage warrant further investigation.
Efficient Decision Approaches for Asset-Based Dynamic Weapon Target Assignment by a Receding Horizon and Marginal Return Heuristic
Authors: Zhang Kai , Zhou Deyun , Yang Zhen , Zhao Yiyang , Kong Weiren
Published: September 2020

The weapon-target assignment problem is a crucial decision support in a Command and Control system. As a typical operational scenario, the major asset-based dynamic weapon target assignment (A-DWTA) models and solving algorithms are challenging to reflect the actual requirement of decision maker. Deriving from the “shoot–look–shoot” principle, an “observe–orient–decide–act” loop model for A-DWTA (OODA/A-DWTA) is established. Focus on the decide phase of the OODA/A-DWTA loop, a novel A-DWTA model, which is based on the receding horizon decomposition strategy (A-DWTA/RH), is established. To solve the A-DWTA/RH efficiently, a heuristic algorithm based on statistical marginal return (HA-SMR) is designed, which proposes a reverse hierarchical idea of “asset value-target selected-weapon decision.” Experimental results show that HA-SMR solving A-DWTA/RH has advantages of real-time and robustness. The obtained decision plan can fulfill the operational mission in the fewer stages and the “radical-conservative” degree can be adjusted adaptively by parameters.
Investigation of the Spray Development Process of Gasoline-Biodiesel Blended Fuel Sprays in a Constant Volume Chamber
Authors: Kim Kihyun , Lim Ocktaeck
Published: September 2020

This study investigated gasoline–biodiesel blended fuel (GB) subjected to a fuel spray development process on macroscopic and microscopic scales. The four tested fuels were neat gasoline and gasoline containing biodiesel (5%, 20%, and 40% by volume) at three different ratios. The initial spray near the nozzle revealed that the spray penetration and spray tip velocity both decreased with decreasing biodiesel blending ratio. In addition, the different spray tip velocities at the start of spraying result in different atomization regimes between the fuels. The GB fuels with a low biodiesel blending ratio were disadvantaged in terms of spray atomization due to their lower spray penetration and tip velocity. The macroscopic spray penetration changes were similar to those observed in the microscopic spray. The fuel with the lower biodiesel blending ratio had a larger spray cone angle, indicating increased radial spray dispersion.
Performance of a Woodchip Bioreactor for the Treatment of Nitrate-Laden Agricultural Drainage Water in Northeastern Germany
Authors: Gosch Lennart , Liu Haojie , Lennartz Bernd
Published: September 2020

Reactive barriers, such as denitrifying bioreactors, have been identified as a clean-up option for nutrient-laden agriculture runoff. Here we tested a 20 m long, 3.75 m wide and 2.2 m deep woodchip bioreactor receiving tile drainage water from a 5.2 ha field site, aiming at testing the hydraulic functioning of a dual-inlet system and quantifying its impact on nutrient loads (nitrogen, reactive phosphorus, organic carbon) in a region with a drainage season taking place in the hydrological winter (November to April). The hydraulic conditions in the dual-inlet bioreactor system developed differently than expected; asymmetric flow rates led to long average hydraulic retention times and a highly dispersed residence time distribution, which was revealed by a bromide tracer test. With a nitrate load reduction of 51 to 90% over three drainage seasons, the woodchip bioreactor proved at the same time to be very effective under the winter conditions of northeastern Germany. The bioreactor turned from an orthophosphate source in the first year of operation into an orthophosphate sink in the second and third year, which was not expected because of anoxic conditions (favorable for denitrification) prevailing within the woodchips. Besides an efficient nutrient retention, the woodchip bioreactor contributed to the total organic carbon load of receiving waters, which impairs the overall positive role of bioreactors within intensively agriculturally used landscapes. We consider this promising low-maintenance biotechnology particularly suitable for single drainage pipes with high discharge and high nitrate concentrations.
Urbanization and Decline of Old Growth Windbreak Trees on Private Homesteads: A Case Study in Ryukyu Island Villages, Japan
Authors: Chen Bixia
Published: September 2020

Urban trees are under unprecedented pressure and competition worldwide with other land uses. Homestead windbreaks in urban areas are an important part of urban forests because of their proximity to settlements. To aid in the conservation of old-growth homestead trees in the urban setting on Ryukyu Archipelago, Japan, this article surveys the dimensions and spatial distribution of century-old trees planted as windbreaks along homestead borderlines on Ishigaki Island in the Ryukyu Archipelago and the historical change caused by urban sprawl. The homesteads studied in this article do not match the scale of a traditional Western context and usually consist of an area of less than 200 square meters on Okinawa. A combined approach consisting of field surveys and the study of aerial photos was applied to identify changes in spatial distribution of tree lines surrounding the houses in 1945, 1972 and the present. We measured the dimensions of 1659 Fukugi trees with a minimum diameter at breast height (DBH) of 5 cm. The mean tree height, mean DBH and mean estimated tree age were 7.3 m, 26.9 cm and 107.5 years, respectively. Homestead trees are not only useful as windbreaks, timber sources and musical instruments, but have also been historically resilient in the face of strong typhoons and catastrophic tsunamis in the region. Over 60% of the surveyed trees were planted on the east and north sides of homesteads as protection from typhoons and monsoonal winds in the winter. In addition to G. subelliptica, other tree species, namely Podocarpus macrophyllus and Diospyros egbert-walkeri, have been commonly used as homestead windbreaks. However, homestead windbreaks in highly urbanized regions are generally declining and have experienced fragmentation, lower tree density and shorter tree height than those in rural areas. Because of the small number of trees older than 200 years, we assume that high urbanization has jeopardized old-growth trees. The demand for settlement land dramatically increases as the population increases and household-size decreases, creating more households. Therefore, a conservation project involving multiple stakeholders must be developed to conserve old-growth trees in urban settings.
Estimation of Genetic Parameters and Selection of Superior Genotypes in a 12-Year-Old Clonal Norway Spruce Field Trial after Phenotypic Assessment Using a UAV
Authors: Liziniewicz Mateusz , Ene Liviu Theodor , Malm Johan , Lindberg Jens , Helmersson Andreas , Karlsson Bo
Published: September 2020

Height is a key trait in the indices applied when selecting genotypes for use in both tree breeding populations and production populations in seed orchards. Thus, measurement of tree height is an important activity in the Swedish Norway spruce breeding program. However, traditional measurement techniques are time-consuming, expensive, and often involve work in bad weather, so automatization of the data acquisition would be beneficial. Possibilities for such automatization have been opened by advances in unmanned aerial vehicle (UAV) technology. Therefore, to test its applicability in breeding programs, images acquired by a consumer-level UAV (DJI Phantom 4 Pro V2.0) system were used to predict the height and breast height diameter of Norway spruce trees in a 12-year-old genetic field trial established with 2.0 × 2.0 m initial spacing. The tree heights were also measured in the field using an ultrasonic system. Three additive regression models with different numbers of predictor variables were used to estimate heights of individual trees. On stand level, the average height estimate derived from UAV data was 2% higher than the field-measured average. The estimation of family means was very accurate, but the genotype-level accuracy, which is crucial for selection in the Norway spruce breeding program, was not high enough. There was just ca. 60% matching of genotypes in groups selected using actual and estimated heights. In addition, heritability values calculated from the predicted values were underestimated and overestimated for height and diameter, respectively, with deviations from measurement-based estimates ranging between −19% and +12%. However, the use of more sophisticated UAV and camera equipment could significantly improve the results and enable automatic individual tree detection.