bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer’s Disease
Authors: Sharma Chanchal , Kim Sehwan , Nam Youngpyo , Jung Un Ju , Kim Sang Ryong
Published: May 2021

Alzheimer’s disease (AD) is the most frequent cause of age-related neurodegeneration and cognitive impairment, and there are currently no broadly effective therapies. The underlying pathogenesis is complex, but a growing body of evidence implicates mitochondrial dysfunction as a common pathomechanism involved in many of the hallmark features of the AD brain, such as formation of amyloid-beta (Aβ) aggregates (amyloid plaques), neurofibrillary tangles, cholinergic system dysfunction, impaired synaptic transmission and plasticity, oxidative stress, and neuroinflammation, that lead to neurodegeneration and cognitive dysfunction. Indeed, mitochondrial dysfunction concomitant with progressive accumulation of mitochondrial Aβ is an early event in AD pathogenesis. Healthy mitochondria are critical for providing sufficient energy to maintain endogenous neuroprotective and reparative mechanisms, while disturbances in mitochondrial function, motility, fission, and fusion lead to neuronal malfunction and degeneration associated with excess free radical production and reduced intracellular calcium buffering. In addition, mitochondrial dysfunction can contribute to amyloid-β precursor protein (APP) expression and misprocessing to produce pathogenic fragments (e.g., Aβ1-40). Given this background, we present an overview of the importance of mitochondria for maintenance of neuronal function and how mitochondrial dysfunction acts as a driver of cognitive impairment in AD. Additionally, we provide a brief summary of possible treatments targeting mitochondrial dysfunction as therapeutic approaches for AD.
Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging
Authors: Kim Jong-Won , Lee Kyung-Kwan , Park Kyoung-Woo , Kim Moonil , Lee Chang-Soo
Published: May 2021

Bone homeostasis plays a major role in supporting and protecting various organs as well as a body structure by maintaining the balance of activities of the osteoblasts and osteoclasts. Unbalanced differentiation and functions of these cells result in various skeletal diseases, such as osteoporosis, osteopetrosis, and Paget’s disease. Although various synthetic nanomaterials have been developed for bone imaging and therapy through the chemical conjugation, they are associated with serious drawbacks, including heterogeneity and random orientation, in turn resulting in low efficiency. Here, we report the synthesis of bone-targeting ferritin nanoparticles for bone imaging. Ferritin, which is a globular protein composed of 24 subunits, was employed as a carrier molecule. Bone-targeting peptides that have been reported to specifically bind to osteoblast and hydroxyapatite were genetically fused to the N-terminus of the heavy subunit of human ferritin in such a way that the peptides faced outwards. Ferritin nanoparticles with fused bone-targeting peptides were also conjugated with fluorescent dyes to assess their binding ability using osteoblast imaging and a hydroxyapatite binding assay; the results showed their specific binding with osteoblasts and hydroxyapatite. Using in vivo analysis, a specific fluorescent signal from the lower limb was observed, demonstrating a highly selective affinity of the modified nanoparticles for the bone tissue. These promising results indicate a specific binding ability of the nanoscale targeting system to the bone tissue, which might potentially be used for bone disease therapy in future clinical applications.
Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos
Authors: Basnet Ram Manohar , Zizioli Daniela , Muscò Alessia , Finazzi Dario , Sigala Sandra , Rossini Elisa , Tobia Chiara , Guerra Jessica , Presta Marco , Memo Maurizio
Published: May 2021

In this study, we report the effects of caffeine on angiogenesis in zebrafish embryos both during normal development and after exposure to Fibroblast Growth Factor 2 (FGF2). As markers of angiogenesis, we measured the length and width of intersegmental vessels (ISVs), performed whole-mount in situ hybridization with fli1 and cadh5 vascular markers, and counted the number of interconnecting vessels (ICVs) in sub-intestinal venous plexus (SIVP). In addition, we measured angiogenesis after performing zebrafish yolk membrane (ZFYM) assay with microinjection of fibroblast growth factor 2 (FGF2) and perivitelline tumor xenograft assay with microinjection of tumorigenic FGF2-overexpressing endothelial (FGF2-T-MAE) cells. The results showed that caffeine treatment causes a shortening and thinning of ISVs along with a decreased expression of the vascular marker genes and a decrease in the number of ICVs in the SIVP. Caffeine was also able to block angiogenesis induced by exogenous FGF2 or FGF2-producing cells. Overall, our results are suggestive of the inhibitory effect of caffeine in both direct and indirect angiogenesis.
Polycystin-1 Enhances Stemmness Potential of Umbilical Cord Blood-Derived Mesenchymal Stem Cells
Authors: Jung Se-Hwa , You Ji-Eun , Choi Soon-Won , Kang Kyung-Sun , Cho Je-Yeol , Lyu Jungmook , Kim Pyung-Hwan
Published: May 2021

Polycystic Kidney Disease (PKD) is a disorder that affects the kidneys and other organs, and its major forms are encoded by polycystin-1 (PC1) and polycystin-2 (PC2), as PKD1 and PKD2. It is located sandwiched inside and outside cell membranes and interacts with other cells. This protein is most active in kidney cells before birth, and PC1 and PC2 work together to help regulate cell proliferation, cell migration, and interactions with other cells. The molecular relationship and the function between PKD1 and cancer is well known, such as increased or decreased cell proliferation and promoting or suppressing cell migration depending on the cancer cell type specifically. However, its function in stem cells has not been revealed. Therefore, in this study, we investigated the biological function of PC1 and umbilical cord blood-derived mesenchymal stem cell (UCB-MSC). Furthermore, we assessed how it affects cell migration, proliferation, and the viability of cells when expressed in the PKD1 gene. In addition, we confirmed in an ex vivo artificial tooth model generated by the three-dimension printing technique that the ability to differentiate into osteocytes improved according to the expression level of the stemness markers when PKD1 was expressed. This study is the first report to examine the biological function of PKD1 in UCB-MSC. This gene may be capable of enhancing differentiation ability and maintaining long-term stemness for the therapeutic use of stem cells.
Vitamin D and Beta-Glucans Synergically Stimulate Human Macrophage Activity
Authors: Bergandi Loredana , Apprato Giulia , Silvagno Francesca
Published: May 2021

Vitamin D and beta-glucans are both immunostimulants. Vitamin D exerts its beneficial effects on many components of the immune system. In macrophages, the hormone modulates both phagocytic activity and cytokine production; therefore, it plays an important role in mediating the innate immune response to infection. The immunomodulatory properties of beta-glucans are attributed to the ability of these fungal cell wall polysaccharides to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes and macrophages. The intracellular signaling pathways activated by beta-glucans lead to enhanced phagocytosis and cytokine response. In this study we investigated the possible potentiation of immunomodulatory properties of the combined treatment with vitamin D and beta-glucans. The effects of 100 nM 1,25-dihydroxyvitamin D3 or 100 µg/mL beta-glucans were evaluated in human macrophages in terms of cytokine production, intracellular vesicle acidification and changes in energy metabolism, three hallmarks of macrophage antimicrobial activation. We found that all the analyzed parameters were enhanced by the co-treatment compared to the response to single molecules. The results of this study support the validity of a novel therapeutic approach that could boost the immune response, taking advantage of the synergy between two natural compounds.
Assessment of Betulinic Acid Cytotoxicity and Mitochondrial Metabolism Impairment in a Human Melanoma Cell Line
Authors: Coricovac Dorina , Dehelean Cristina Adriana , Pinzaru Iulia , Mioc Alexandra , Aburel Oana-Maria , Macasoi Ioana , Draghici George Andrei , Petean Crina , Soica Codruta , Boruga Madalina , Vlaicu Brigitha , Muntean Mirela Danina
Published: May 2021

Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 μM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.
Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response
Authors: Geindreau Mannon , Ghiringhelli François , Bruchard Mélanie
Published: May 2021

During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.
NFAT5-Mediated Signalling Pathways in Viral Infection and Cardiovascular Dysfunction
Authors: Zhao Guangze , Aghakeshmiri Sana , Chen Yankuan T. , Zhang Huifang M. , Yip Fione , Yang Decheng
Published: May 2021

The nuclear factor of activated T cells 5 (NFAT5) is well known for its sensitivity to cellular osmolarity changes, such as in the kidney medulla. Accumulated evidence indicates that NFAT5 is also a sensitive factor to stress signals caused by non-hypertonic stimuli such as heat shock, biomechanical stretch stress, ischaemia, infection, etc. These osmolality-related and -unrelated stimuli can induce NFAT5 upregulation, activation and nuclear accumulation, leading to its protective role against various detrimental effects. However, dysregulation of NFAT5 expression may cause pathological conditions in different tissues, leading to a variety of diseases. These protective or pathogenic effects of NFAT5 are dictated by the regulation of its target gene expression and activation of its signalling pathways. Recent studies have found a number of kinases that participate in the phosphorylation/activation of NFAT5 and related signal proteins. Thus, this review will focus on the NFAT5-mediated signal transduction pathways. As for the stimuli that upregulate NFAT5, in addition to the stresses caused by hyperosmotic and non-hyperosmotic environments, other factors such as miRNA, long non-coding RNA, epigenetic modification and viral infection also play an important role in regulating NFAT5 expression; thus, the discussion in this regard is another focus of this review. As the heart, unlike the kidneys, is not normally exposed to hypertonic environments, studies on NFAT5-mediated cardiovascular diseases are just emerging and rapidly progressing. Therefore, we have also added a review on the progress made in this field of research.
Role of Hypoxia in the Control of the Cell Cycle
Authors: Druker Jimena , Wilson James W. , Child Fraser , Shakir Dilem , Fasanya Temitope , Rocha Sonia
Published: May 2021

The cell cycle is an important cellular process whereby the cell attempts to replicate its genome in an error-free manner. As such, mechanisms must exist for the cell cycle to respond to stress signals such as those elicited by hypoxia or reduced oxygen availability. This review focuses on the role of transcriptional and post-transcriptional mechanisms initiated in hypoxia that interface with cell cycle control. In addition, we discuss how the cell cycle can alter the hypoxia response. Overall, the cellular response to hypoxia and the cell cycle are linked through a variety of mechanisms, allowing cells to respond to hypoxia in a manner that ensures survival and minimal errors throughout cell division.
TAS-116, a Well-Tolerated Hsp90 Inhibitor, Prevents the Activation of the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells
Authors: Ranta-aho Sofia , Piippo Niina , Korhonen Eveliina , Kaarniranta Kai , Hytti Maria , Kauppinen Anu
Published: May 2021

Chronic inflammation has been associated with several chronic diseases, such as age-related macular degeneration (AMD). The NLRP3 inflammasome is a central proinflammatory signaling complex that triggers caspase-1 activation leading to the maturation of IL-1β. We have previously shown that the inhibition of the chaperone protein, Hsp90, prevents NLRP3 activation in human retinal pigment epithelial (RPE) cells; these are cells which play a central role in the pathogenesis of AMD. In that study, we used a well-known Hsp90 inhibitor geldanamycin, but it cannot be used as a therapy due to its adverse effects, including ocular toxicity. Here, we have tested the effects of a novel Hsp90 inhibitor, TAS-116, on NLRP3 activation using geldanamycin as a reference compound. Using our existing protocol, inflammasome activation was induced in IL-1α-primed ARPE-19 cells with the proteasome and autophagy inhibitors MG-132 and bafilomycin A1, respectively. Intracellular caspase-1 activity was determined using a commercial caspase-1 activity kit and the FLICA assay. The levels of IL-1β were measured from cell culture medium samples by ELISA. Cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) measurements. Our findings show that TAS-116 could prevent the activation of caspase-1, subsequently reducing the release of mature IL-1β. TAS-116 has a better in vitro therapeutic index than geldanamycin. In summary, TAS-116 appears to be a well-tolerated Hsp90 inhibitor, with the capability to prevent the activation of the NLRP3 inflammasome in human RPE cells.
Inhibition of Lipid Accumulation and Cyclooxygenase-2 Expression in Differentiating 3T3-L1 Preadipocytes by Pazopanib, a Multikinase Inhibitor
Authors: Yadav Anil Kumar , Jang Byeong-Churl
Published: May 2021

Pazopanib is a multikinase inhibitor with anti-tumor activity. As of now, the anti-obesity effect and mode of action of pazopanib are unknown. In this study, we investigated the effects of pazopanib on lipid accumulation, lipolysis, and expression of inflammatory cyclooxygenase (COX)-2 in differentiating and differentiated 3T3-L1 cells, a murine preadipocyte. Of note, pazopanib at 10 µM markedly decreased lipid accumulation and triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. Furthermore, pazopanib inhibited not only expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and perilipin A but also phosphorylation of signal transducer and activator of transcription (STAT)-3 during 3T3-L1 preadipocyte differentiation. In addition, pazopanib treatment increased phosphorylation of cAMP-activated protein kinase (AMPK) and its downstream effector ACC during 3T3-L1 preadipocyte differentiation. However, in differentiated 3T3-L1 adipocytes, pazopanib treatment did not stimulate glycerol release and hormone-sensitive lipase (HSL) phosphorylation, hallmarks of lipolysis. Moreover, pazopanib could inhibit tumor necrosis factor (TNF)-α-induced expression of COX-2 in both 3T3-L1 preadipocytes and differentiated cells. In summary, this is the first report that pazopanib has strong anti-adipogenic and anti-inflammatory effects in 3T3-L1 cells, which are mediated through regulation of the expression and phosphorylation of C/EBP-α, PPAR-γ, STAT-3, ACC, perilipin A, AMPK, and COX-2.
AtWAKL10, a Cell Wall Associated Receptor-Like Kinase, Negatively Regulates Leaf Senescence in Arabidopsis thaliana
Authors: Li Lu , Li Kui , Ali Akhtar , Guo Yongfeng
Published: May 2021

Receptor-like kinases (RLKs) constitute a large group of cell surface receptors that play crucial roles in multiple biological processes. However, the function of most RLKs in plants has not been extensively explored, and much less for the class of cell wall associated kinases (WAKs) and WAK-like kinases (WAKLs). In this study, analyses of developmental expression patterns uncovered a putative role of AtWAKL10 in modulating leaf senescence, which was further investigated at physiological and molecular levels. The expression level of AtWAKL10 increased with the developmental progression and was rapidly upregulated in senescing leaf tissues. The promoter of AtWAKL10 contains various defense and hormone responsive elements, and its expression could be significantly induced by exogenous ABA, JA and SA. Moreover, the loss-of-function atwakl10 mutant showed earlier senescence along the course of natural development and accelerated leaf senescence under darkness and hormonal stresses, while plants overexpressing AtWAKL10 showed an opposite trend. Additionally, some defense and senescence related WRKY transcription factors could bind to the promoter of AtWAKL10. In addition, deletion and overexpression of AtWAKL10 caused several specific transcriptional alterations, including genes involved in cell extension, cell wall modification, defense response and senescence related WRKYs, which may be implicated in regulatory mechanisms adopted by AtWAKL10 in controlling leaf senescence. Taken together, these results revealed that AtWAKL10 negatively regulated leaf senescence.
Death Processes in Bovine Theca and Granulosa Cells Modelled and Analysed Using a Systems Biology Approach
Authors: McEvoy Malgorzata J. , Sinderewicz Emilia , Creedon Leo , McAfee Marion , Jonczyk Agnieszka W. , Piotrowska-Tomala Katarzyna K. , Skarzynski Dariusz J.
Published: May 2021

In this paper, newly discovered mechanisms of atresia and cell death processes in bovine ovarian follicles are investigated. For this purpose the mRNA expression of receptor interacting protein kinases 1 and 3 (RIPK1 and RIPK3) of the granulosa and theca cells derived from healthy and atretic follicles are studied. The follicles were assigned as either healthy or atretic based on the estradiol to progesterone ratio. A statistically significant difference was recorded for the mRNA expression of a RIPK1 and RIPK3 between granulosa cells from healthy and atretic follicles. To further investigate this result a systems biology approach was used. The genes playing roles in necroptosis, apoptosis and atresia were chosen and a network was created based on human genes annotated by the IMEx database in Cytoscape to identify hubs and bottle-necks. Moreover, correlation networks were built in the Cluepedia plug-in. The networks were created separately for terms describing apoptosis and programmed cell death. We demonstrate that necroptosis (RIPK—dependent cell death pathway) is an alternative mechanism responsible for death of bovine granulosa and theca cells. We conclude that both apoptosis and necroptosis occur in the granulosa cells of dominant follicles undergoing luteinisation and in the theca cells from newly selected follicles.
BiFC Method Based on Intraorganellar Protein Crowding Detects Oleate-Dependent Peroxisomal Targeting of Pichia pastoris Malate Dehydrogenase
Authors: Farré Jean-Claude , Li Paul , Subramani Suresh
Published: May 2021

The maintenance of intracellular NAD+/NADH homeostasis across multiple, subcellular compartments requires the presence of NADH-shuttling proteins, which circumvent the lack of permeability of organelle membranes to these cofactors. Very little is known regarding these proteins in the methylotrophic yeast, Pichia pastoris. During the study of the subcellular locations of these shuttling proteins, which often have dual subcellular locations, it became necessary to develop new ways to detect the weak peroxisomal locations of some of these proteins. We have developed a novel variation of the traditional Bimolecular Fluorescence Complementation (BiFC), called divergent BiFC, to detect intraorganellar colocalization of two noninteracting proteins based on their proximity-based protein crowding within a small subcellular compartment, rather than on the traditional protein–protein interactions expected for BiFC. This method is used to demonstrate the partially peroxisomal location of one such P. pastoris NADH-shuttling protein, malate dehydrogenase B, only when cells are grown in oleate, but not when grown in methanol or glucose. We discuss the mode of NADH shuttling in P. pastoris and the physiological basis of the medium-dependent compartmentalization of PpMdhB.
Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy
Authors: Ellwood Rebecca A. , Piasecki Mathew , Szewczyk Nathaniel J.
Published: May 2021

The nematode worm Caenorhabditis elegans has been used extensively to enhance our understanding of the human neuromuscular disorder Duchenne Muscular Dystrophy (DMD). With new arising clinically relevant models, technologies and treatments, there is a need to reconcile the literature and collate the key findings associated with this model.
Preventive Applications of Polyphenols in Dentistry—A Review
Authors: Flemming Jasmin , Meyer-Probst Clara Theres , Speer Karl , Kölling-Speer Isabelle , Hannig Christian , Hannig Matthias
Published: May 2021

Polyphenols are natural substances that have been shown to provide various health benefits. Antioxidant, anti-inflammatory, and anti-carcinogenic effects have been described. At the same time, they inhibit the actions of bacteria, viruses, and fungi. Thus, studies have also examined their effects within the oral cavity. This review provides an overview on the different polyphenols, and their structure and interactions with the tooth surface and the pellicle. In particular, the effects of various tea polyphenols on bioadhesion and erosion have been reviewed. The current research confirms that polyphenols can reduce the growth of cariogenic bacteria. Furthermore, they can decrease the adherence of bacteria to the tooth surface and improve the erosion-protective properties of the acquired enamel pellicle. Tea polyphenols, especially, have the potential to contribute to an oral health-related diet. However, in vitro studies have mainly been conducted. In situ studies and clinical studies need to be extended and supplemented in order to significantly contribute to additive prevention measures in caries prophylaxis.
Syndrome of Undifferentiated Recurrent Fever (SURF): An Emerging Group of Autoinflammatory Recurrent Fevers
Authors: Papa Riccardo , Penco Federica , Volpi Stefano , Sutera Diana , Caorsi Roberta , Gattorno Marco
Published: May 2021

Syndrome of undifferentiated recurrent fever (SURF) is a heterogeneous group of autoinflammatory diseases (AID) characterized by self-limiting episodes of systemic inflammation without a confirmed molecular diagnosis, not fulfilling the criteria for periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. In this review, we focused on the studies enrolling patients suspected of AID and genotyped them with next generation sequencing technologies in order to describe the clinical manifestations and treatment response of published cohorts of patients with SURF. We also propose a preliminary set of indications for the clinical suspicion of SURF that could help in everyday clinical practice.
Correlation between Liver Stiffness by Two-Dimensional Shear Wave Elastography and Waist Circumference in Japanese Local Citizens with Abdominal Obesity
Authors: Miyoshi Tomoki , Hamaguchi Masahide , Kitagawa Noriyuki , Hashimoto Yoshitaka , Fukui Michiaki
Published: May 2021

Background: Various factors other than fibrosis could affect liver stiffness (LS), measured by two-dimensional shear wave elastography (2D-SWE). We aimed to clarify the factors affecting LS in local citizens. Methods: We performed a cross-sectional study among local citizens of a health checkup program. Abdominal obesity was defined as waist circumference ≥85 cm for men and ≥90 cm for women. We evaluated the correlation between LS by 2D-SWE (Aplio 500) and waist circumference with linear regression analyses. We selected the following items as variables in the multivariate analysis: waist circumference, sex, hypertension, diabetes, diagnostic components of metabolic syndrome, γ−glutamyl transpeptidase, total bilirubin, NAFLD fibrosis score, and an indicator of a fatty liver, evaluated ultrasonographically. Results: Overall, 345 individuals were included; 318 (181 men and 137 women; age, 63.4 years; waist circumference, 84.0 cm; LS, 5.79 kPa) were analyzed, 128 of whom had abdominal obesity and significantly higher LS than non-abdominally obese individuals. In the multivariate analysis, waist circumference was positively, independently, and significantly correlated with LS only in abdominally obese individuals. Conclusions: Liver stiffness by 2D-SWE could increase with increases in waist circumference in local citizens with abdominal obesity. Physicians should pay attention when assessing the LS of abdominally obese individuals.
Heterologous Expression, Engineering and Characterization of a Novel Laccase of Agrocybe pediades with Promising Properties as Biocatalyst
Authors: Aza Pablo , Molpeceres Gonzalo , Ruiz-Dueñas Francisco Javier , Camarero Susana
Published: May 2021

Agaricomycetes fungi responsible for decay of wood and other lignocellulosic substrates constitute a valuable source of lignin-degrading enzymes. Among these enzymes, laccases (multi-copper oxidases) present remarkable biotechnological potential as environmentally friendly biocatalysts able to oxidize a wide range of aromatic compounds using oxygen as the only requirement. Laccases from saprotrophic Agaricales species have been much less studied than laccases from Polyporales, despite the fact that the former fungi are excellent sources of laccases. Here, the gene of a novel laccase of Agrocybe pediades, that is secreted by the fungus during lignocellulose degradation, was synthesised de novo and expressed in Saccharomyces cerevisiae using an improved signal peptide previously obtained and enzyme directed evolution. The characterization of the new laccase variants provided new insights on the contribution of different amino acid residues to modulate laccase production, catalytic activity or optimal pH. The selected double-mutated variant also showed interesting properties as a biocatalyst, such as the ability to oxidise a wide range of substrates, including high-redox potential mediators and recalcitrant organic dyes, improved activity at neutral pH and high tolerance to inhibitors. Finally, we demonstrate the existence of three N-glycosylation sites in the laccase and their distinct effect on the secretion or catalytic activity of the enzyme.
New Insights Regarding Diagnosis and Medication for Schizophrenia Based on Neuronal Synapse–Microglia Interaction
Authors: Izuo Naotaka , Nitta Atsumi
Published: May 2021

Schizophrenia is a common psychiatric disorder that usually develops during adolescence and young adulthood. Since genetic and environmental factors are involved in the disease, the molecular status of the pathology of schizophrenia differs across patients. Recent genetic studies have focused on the association between schizophrenia and the immune system, especially microglia–synapse interactions. Microglia physiologically eliminate unnecessary synapses during the developmental period. The overactivation of synaptic pruning by microglia is involved in the pathology of brain disease. This paper focuses on the synaptic pruning function and its molecular machinery and introduces the hypothesis that excessive synaptic pruning plays a role in the development of schizophrenia. Finally, we suggest a strategy for diagnosis and medication based on modulation of the interaction between microglia and synapses. This review provides updated information on the involvement of the immune system in schizophrenia and proposes novel insights regarding diagnostic and therapeutic strategies for this disease.
Free Myocutaneous Flap Assessment in a Rat Model: Verification of a Wireless Bioelectrical Impedance Assessment (BIA) System for Vascular Compromise Following Microsurgery
Authors: Huang Yao-Kuang , Wong Min Yi , Wu Chi-Rung , Cheng Yung-Ze , Lin Bor-Shyh
Published: May 2021

Background: Microvascular tissue transfer is a common reconstructive procedure. We designed a bioelectrical impedance assessment (BIA) system for quantitative analysis of tissue status. This study attempts to verify it through the animal model. Methods: The flaps of the rat model were monitored by the BIA system. Results: The BIA variation of the free flap in the rat after the vascular compromise was recorded. The non-vascular ligation limbs of the same rat served as a control group. The bio-impedance in the experimental group was larger than the control group. The bio-impedances of both the thigh/feet flaps in the experimental group were increased over time. In the thigh, the difference in bio-impedance from the control group was first detected at 10 kHz at the 3rd and last at 1 kHz at the 6th h, after vascular compromise. The same finding was observed in the feet. Compared with the control group, the bio-impedance ratio (1 kHz/20 kHz) of the experimental group decreased with time, while their variation tendencies in the thigh and feet were similar. Conclusions: The flap may be monitored by the BIA for vascular status.
Evaluation of Market with Accommodation Facilities Considering Risk Influence—Case Study Slovakia
Authors: Csikosova Adriana , Culkova Katarina , Weiss Erik , Janoskova Maria
Published: May 2021

Tourism currently contributes significantly to the national economy. When investing in the accommodation facility on the real-estate market, the tourism sector also represents a certain risk due to a high level of seasonality. This paper investigates the risks related to prices, income and occupancy of accommodation facilities for selected regions in Slovakia. The value of accommodation facilities is estimated using discounted cash flow, probabilistic distribution of rental prices and occupancy of accommodation facilities in selected Slovak regions. The results provide information for potential and profitable investments in exposed regions in tourism. The information can be used in the field of risk management to avoid or reduce the risk of risk investments. Although the resulting values were calculated only for some selected regions, the proposed procedure can be used for any region and compared with the current values.
A Comparison and Interpretation of Machine Learning Algorithm for the Prediction of Online Purchase Conversion
Authors: Lee Jungwon , Jung Okkyung , Lee Yunhye , Kim Ohsung , Park Cheol
Published: May 2021

Machine learning technology is recently being applied to various fields. However, in the field of online consumer conversion, research is limited despite the high possibility of machine learning application due to the availability of big data. In this context, we investigate the following three research questions. First, what is the suitable machine learning model for predicting online consumer behavior? Second, what is the good data sampling method for predicting online con-sumer behavior? Third, can we interpret machine learning’s online consumer behavior prediction results? We analyze 374,749 online consumer behavior data from Google Merchandise Store, an online shopping mall, and explore research questions. As a result of the empirical analysis, the performance of the ensemble model eXtreme Gradient Boosting model is most suitable for pre-dicting purchase conversion of online consumers, and oversampling is the best method to mitigate data imbalance bias. In addition, by applying explainable artificial intelligence methods to the context of retargeting advertisements, we investigate which consumers are effective in retargeting advertisements. This study theoretically contributes to the marketing and machine learning lit-erature by exploring and answering the problems that arise when applying machine learning models to predicting online consumer conversion. It also contributes to the online advertising literature by exploring consumer characteristics that are effective for retargeting advertisements.
Personnel aspect of the introduction of digital technologies in agriculture
Authors: Dulzon S.
Published: May 2021

The article attempts to analyze the use of digital technologies in agriculture from the point of view of the personnel aspect. Many experts point to the low cost of labor and the level of qualification of workers engaged in agricultural production as the main factors hindering their implementation. Therefore, on the path of digitalization of the agro-industrial complex, more attention should be paid to personnel policy issues, in particular, to the ongoing qualitative changes in the labor force used in the industry (in its professionalism, competence and motivation).
Modern mechanisms of social and professional rehabilitation and adaptation of disabled people in the labor market
Authors: Novikov V. , Zelikov N. , Gorokhov S.
Published: May 2021

The main goal of social and vocational rehabilitation and adaptation is to provide a person with a disability with the opportunity to get or keep a suitable job and thereby promote their social integration, achieve material independence or increase their income and self-sufficiency. Professional rehabilitation helps to improve the social status and security of not only the disabled person, but also his family. Professional rehabilitation with subsequent employment of disabled people is also beneficial for the whole society. The funds invested in the professional rehabilitation of disabled people will be returned to the state in the form of tax revenues as a result of the employment of disabled people. This article presents the main mechanisms, measures, stages, as well as the main types and content of services for social and professional rehabilitation and adaptation of disabled people.
STUDY ON SERUM FGF-23 CONCENTRATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Nguyen Huu Vu Quang , Vo Tam
Published: May 2021

Objective: To determine the serum FGF-23 levels in patients with chronic kidney disease (CKD) receiving conservative treatment and hemodialysis.

Method: Cross-sectional study, describing serum FGF-23 concentration and some other biochemical parameters of 149 patients with chronic kidney disease at Hue Central Hospital, compared with a control group of 64 people who were not affected by CKD.

Results: The concentration of FGF-23 in the control group, conservative treatment and hemodialysis group were 32.53 ± 9.803 pg/ml, 333.01 ± 243.02717 pg/ml, 717.66 ± 357.360 pg/ml, respectively, there were statistically significant differences (p < 0.05). The concentration of FGF-23, PTH, total Calcium, phosphorus, Calcium x phosphorus accumulation increased with increasing renal failure (p < 0.05). The concentration of Vitamin D and calcium ion decrease when renal failure level increases (p < 0.05). FGF-23 had a better predictive value of the increasing total blood calcium level than PTH. FGF-23, PTH levels were all predictive of increasing blood phosphorus level, but FGF-23 was more valuable. Concentrations of FGF-23 and PTH had predictive values of the increasing Calcium x phosphorus accumulation, but FGF-23 was more valuable. The concentration of FGF-23 had predictive value of the increasing PTH concentration with the area under the curve by 0.765 (p < 0.05).

Conclusion: The concentration of FGF-23 significantly increased in patients with chronic kidney disease, and is worth predicting changes in factors related to mineral metabolism such as Calcium, Phosphorus, PTH

Key words: hronic kidney disease, Fibroblast growth factor 23, Parathyroid hormone, Renal osteodystrophy, Calcium phosphate product
PHILOSOPHY OF MECHANISMS FOR STATE IMPACT IN MARKET ENVIRONMENT: EXPERIENCE OF UKRAINE
Authors: Korzhenko Volodymyr , Kovalenko Nataliia , Kozyrieva Nataliia
Published: May 2021

The problem of providing a proportional development of all the spheres of social being through public administration impact is growing in intensity in Ukraine, beginning from the mid-1990s i.e. in the period of the market environment emergence and inculcation, institutionalization of market relations and creation of market infrastructure. At that time, the idea of public administration mechanisms comes itno being and acquires the relevant content. Gradually comes the awareness of the fact that the state is able to affect in a variety of ways the socio-economic processes in a transformational society.

The present research makes an attempt at summarizing some ideas that relate to application of mechanisms of state impact in a dynamically changing society. Essential differences between the mechanisms of public administration and state mechanisms of governance have been identified for further discussion by scientific community.
ТЕОРЕТИЧНІ АСПЕКТИ ДЕРЖАВНОГО РЕГУЛЮВАННЯ МАЛОГО ТА СЕРЕДНЬОГО ПІДПРИЄМНИЦТВА
Authors: Kucheriava K.Y.  , Orel Yu.L.
Published: May 2021

Стаття присвячена теоретичному осмисленню понять “державне регулювання малогота середнього підприємництва” і “механізм державного регулювання малого та середньогопідприємництва”. Здійснено огляд національного сектору підприємництва, проаналізованодинаміку основних показників суб’єктів господарювання та визначено особливості їх розви-тку. Надано визначення поняття “державне регулювання малого та середнього підприємни-цтва”. Проаналізовано підходи до визначення поняття “механізм державного регулюваннямалого та середнього підприємництва”, надано його авторське розуміння.
ГАРАНТУВАННЯ ПРОДОВОЛЬЧОЇ БЕЗПЕКИ ЯК ОДИН З ПРІОРИТЕТНИХ НАЦІОНАЛЬНИХ ІНТЕРЕСІВ
Authors: Grybko O.V.
Published: May 2021

Розглянуто стан гарантування продовольчої безпеки в Україні на основі даних ООН.Проаналізовано європейський досвід побудови системи продовольчої безпеки, наведенонизку пропозицій щодо застосування досвіду ЄС в царині продовольчої безпеки для України.
ПЕРЕОСМИСЛЕННЯ РОЛІ УРЯДУ В ЕКОНОМІЦІ 21 СТОЛІТТЯ: АНАЛІЗ НА ОСНОВІ ТРАДИЦІЙНИХ ДЕРЖАВНИХ ПРОГРАМ
Authors: Kud A.A.
Published: May 2021

Стаття пропонує авторський погляд на нову роль держави в економіці 21 століття, щовикликано нездатністю колишніх і нинішніх моделей взаємодії держави і ринку долати регу-лярні “провали ринку” і “провали держави”. Мета статті – теоретично обґрунтувати підхід доподальшого переосмислення нової сучасної ролі держави, використовуючи прийом пере-гляду традиційних державних програм в сфері соціального забезпечення. В основу стат-ті покладено припущення, що навіть в умовах почастішання “провалів ринку” роль і межідержавного регулювання не будуть незмінними, при цьому визнається, що приватні ринкибезперервно розвиваються і відносно швидко змінюються, що дозволяє їм задовольнятизапити все більшого числа людей. В результаті огляду сучасної літератури і ґрунтуючись наекономічній теорії Річарда Талера про “поведінкові підштовхування”, автор критично пере-глядає можливість заміни частини державних соціальних програм на програми з альтерна-тивних джерел. Автор приходить до висновків, що державу потрібно все більше розглядатияк суб’єкт із більшим ступенем автономії, ніж є сьогодні, та який виконує задані функції, а та-кож дотримується доступних йому фінансових ресурсів. Не дотримуючись якоїсь теоретич-ної моделі майбутньої держави, варто зазначити, що найближчим часом набагато більшогозначення матимуть інші інструменти, окрім податків і державних бюджетних видатків, – на-самперед інструменти регулювання. І це значно ближче до тієї ролі, що належала державідо 20 століття, але якість цієї ролі буде зовсім іншою. Проте регулювання буде спрямованона допомогу громадянам і гарантію їх права без нав’язування своїх послуг, а не на пряме до-бування ренти деякими привілейованими групами підприємців або корумпованими політика-ми. Проте на цей час нема упевнених прогнозів, яка роль держави стане успішною не лишез ідеологічного, політичного та соціально-економічного погляду, але й з погляду безпеки.
МЕТОДИЧНІ ПІДХОДИ ДО УПРАВЛІНСЬКОГО ПРОЦЕСУ В ОРГАНАХ ПУБЛІЧНОЇ ВЛАДИ НА ОСНОВІ АУТСОРСИНГУ
Authors: Kalinin M.V.
Published: May 2021

Здійснено спробу визначити методичні засади використання аутсорсингу в органахпублічної влади. Систематизовано уявлення про сутність аутсорсингу, що дозволило ви-значити його як стратегію управління, яка передбачає виведення окремих видів діяльності,що раніше виконувалися органами публічної влади, за рамки їх функціонування шляхомукладення контрактів на виконання робіт (надання послуг) із зовнішніми виконавцями наконкурсній основі. Виокремлено ознаки аутсорсингу в органах публічної влади. Дослідженорізновиди аутсорсингу, що використовуються в органах публічної влади. Визначено тенден-ції використання аутсорсингу в органах публічної влади.
СУЧАСНІ ТЕНДЕНЦІЇ ФУНКЦІОНУВАННЯ РЕГІОНАЛЬНОГО РИНКУ ПРАЦІ
Authors: Kramareva O.S.  , Nadtochii A.O.
Published: May 2021

Проаналізовано діяльність в основних сферах виробництва України та її регіонів засічень – червень 2020 р., визначено основні негативні тенденції в них: стрімке скороченняобсягів виробництва промислової та сільськогосподарської продукції, будівництва, та обся-гів капітальних інвестицій. Виявлено сучасні тенденції функціонування регіонального ринкупраці за трьома його основними індикаторами: попиту, пропозиції робочої сили та заробітнійплаті. Визначено, що попит на робочу силу значно скоротився, пропозиція суттєво збіль-шилася, середня зарплата має тенденцію до зростання, а реальна зарплата зменшується.
МОЖЛИВОСТІ ТА ВИКЛИКИ ПРИ ВИКОРИСТАННІ БРАУНФІЛДІВ
Authors: Dovbnia O.B.
Published: May 2021

Проаналізовано передумови виникнення браунфілдів та їх визначення, запропонованокласифікація промпідприємств на групи за характером використання. Розглянуто прикладінвестиційного наміру підприємства щодо перетворення браунфілду. Визначено алгоритмвнесення змін до генерального плану міста із визначенням термінів виконання, проаналізо-вано законодавство, яке регламентує діяльність браунфілдів. Запропоновано кроки щодополіпшення процедури виявлення браунфілдів та їх паспортизації з метою залучення інвес-тицій.
ФОРМУВАННЯ ПОЗИТИВНОГО ІМІДЖУ УКРАЇНИ У СВІТІ
Authors: Kalinkina N.V.  , Gerasimenko A.G.
Published: May 2021

У статті досліджено питання іміджу держави у контексті здійснення демократичних пе-ретворень в Україні. Доведено, що імідж держави на міжнародній арені є одним з основнихфакторів формування міжнародних відносин країни. Здійснено аналіз формування та ре-алізації зовнішньої іміджевої політики України у світі. Доведено, що позитивне сприйняттядержави всередині країни та у світі є запорукою успіху глобальних політичних, соціальних таекономічних рухів, які і є реформами.
УПРАВЛІННЯ БРЕНДИНГОМ ЗАКЛАДІВ ВИЩОЇ ОСВІТИ УКРАЇНИ В КОНТЕКСТІ ІНТЕГРАЦІЇ У СВІТОВИЙ ОСВІТНІЙ ПРОСТІР
Authors: Kolisnichenko N.M.
Published: May 2021

Досліджено основи управління брендингом закладів вищої освіти України в контекстіінтеграції у світовий освітній простір. Уточнено понятійно-категорійний апарат: категорії“бренд”, “брендинг” у вищій освіті. Обґрунтовано процеси в управлінні брендингом у системівищої освіти: формалізація, комерціалізація (перехід на ринкові механізми), промоційність(просування), професіоналізація брендингової діяльності закладів. Визначено три тенденціїбрендингу, що представлені на сьогодні в університетах світу. Розглянуто три рівні форму-вання відповідної “цінності” бренда закладу вищої освіти.
СТАНОВЛЕННЯ ТА РОЗВИТОК СИСТЕМИ ТЕХНІЧНОГО РЕГУЛЮВАННЯ В ЄВРОПЕЙСЬКОМУ СОЮЗІ
Authors: Myrna N.V.  , Sokolova V.V.
Published: May 2021

У статті проаналізовано становлення та розвиток системи технічного регулювання наприкладі Європейського Союзу. Розглянуто історичні етапі побудови та становлення систе-ми технічного регулювання в Європі. Окремо визначено вплив системи технічного регулю-вання на розвиток та створення внутрішнього ринку ЄС. Виокремлено чотири етапи побудо-ви сучасної системи технічного регулювання в ЄС.
АНАЛІЗ ГІБРИДНИХ ОПЕРАЦІЙ ТА УПРАВЛІНСЬКІ РІШЕННЯ ЩОДО ПРОТИДІЇ ТАКИМ З’ЯВИЩАМ – ІНОЗЕМНИЙ ДОСВІД
Authors: Hranovskyi М.V.
Published: May 2021

У сучасному світі спостерігається тенденція до значного зростання кількості гібриднихконфліктів, які стають все більш витонченими й непередбачуваними. Стаття присвячена те-оретичним і практичним аспектам таких з’явищ, як гібридна війна, гібридний конфлікт абоагресія, що впливають на безпеку міжнародного середовища, а також діям органів держав-ної влади щодо протидії таким загрозам, зокрема, у країнах ЄС. Під час аналізу зазначеногопитання було здійснено спробу надати відповідь на такі запитання: “У чому виражаєтьсясуть гібридних дій? Як відбувається їх еволюція? Який є характер сьогоднішньої гібридноїагресії?” Аргументи, викладені у статті, підтверджують необхідність подальшого проведен-ня досліджень гібридних дій, які порушили цілісність державних кордонів багатьох країн,у тому числі й України, та продовжують становити реальну загрозу безпеці в Європі та світі.Сучасна практика гібридних операцій з боку агресора демонструє кардинальну зміну такти-ки та засобів, які використовує держава-гравець світового рівня проти супротивника, який єслабким і нездатним захищати цілісність власної території.
Публічна політика як предмет практичної діяльності суб’єктів публічної влади
Authors: Bakumenko V. D.  , Popov S. A.  , Voshko I. V.
Published: May 2021

Публічну політику досліджено, як предмет практичної діяльності публічного управління та адміністрування. Структуровано та охарактеризовано політичну сферу суспільства, в межах якої розглянуто владне і громадське політичні середовища. Проаналізовано поняття «політика», «публічна політика», «публічна влада», «публічне адміністрування» і прикметник «публічний». З’ясовано їх місце, роль і сутність у політичному процесі, уточнено поняття «публічна політика». Побудовано й охарактеризовано моделі політичної діяльності публічної влади, сформульовано поняття «політична діяльність публічної влади».
Концептуальні підходи до сутності організаційно-правового механізму гендерної політики в Україні
Authors: Bezborodova O. L.
Published: May 2021

Проаналізовано специфіку класифікації механізмів гендерної політики в Україні. Досліджено концептуальні підходи до сутності організаційно-правового механізму гендерної політики в Україні, інституційний та функціонально-структурні підходи до організаційно-правового механізму гендерної політики в Україні. Розглянуто організаційно-правовий механізм гендерної політики в Україні та запропоновано власне його визначення. Окреслено проблеми та питання подальших наукових досліджень.