bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of Long Non-Coding RNAs in Age-Related Macular Degeneration
Authors: Blasiak Janusz , Hyttinen Juha M. T. , Szczepanska Joanna , Pawlowska Elzbieta , Kaarniranta Kai
Published: August 2021

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population with poorly known pathogenesis and lack of effective treatment. Age and family history are the strongest AMD risk factors, and several loci were identified to contribute to AMD. Recently, also the epigenetic profile was associated with AMD, and some long non-coding RNAs (lncRNAs) were shown to involve in AMD pathogenesis. The Vax2os1/2 (ventral anterior homeobox 2 opposite strand isoform 1) lncRNAs may modulate the balance between pro- and anti-angiogenic factors in the eye contributing to wet AMD. The stress-induced dedifferentiation of retinal pigment epithelium cells can be inhibited by the ZNF503-AS1 (zinc finger protein 503 antisense RNA 2) and LINC00167 lncRNAs. Overexpression of the PWRN2 (Prader-Willi region non-protein-coding RNA 2) lncRNA aggravated RPE cells apoptosis and mitochondrial impairment induced by oxidative stress. Several other lncRNAs were reported to exert protective or detrimental effects in AMD. However, many studies are limited to an association between lncRNA and AMD in patients or model systems with bioinformatics. Therefore, further works on lncRNAs in AMD are rational, and they should be enriched with mechanistic and clinical studies to validate conclusions obtained in high-throughput in vitro research.
Mesenchymal Stem Cell-Conditioned Media Regulate Steroidogenesis and Inhibit Androgen Secretion in a PCOS Cell Model via BMP-2
Authors: Chugh Rishi Man , Park Hang-soo , Esfandyari Sahar , Elsharoud Amro , Ulin Mara , Al-Hendy Ayman
Published: August 2021

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Previous studies have demonstrated the therapeutic efficacy of human bone marrow mesenchymal stem cells (BM-hMSCs) for PCOS; however, the regulatory mechanism remains unknown. Bone morphogenetic proteins (BMPs) secreted by BM-hMSCs may underlie the therapeutic effect of these cells on PCOS, based on the ability of BMPs to modulate androgen production and alter steroidogenesis pathway enzymes. In this study, we analyze the effect of BMP-2 on androgen production and steroidogenic pathway enzymes in H295R cells as a human PCOS in vitro cell model. In H295R cells, BMP-2 significantly suppressed cell proliferation, androgen production, and expression of androgen-synthesizing genes, as well as inflammatory gene expression. Furthermore, H295R cells treated with the BM-hMSCs secretome in the presence of neutralizing BMP-2 antibody or with BMP-2 gene knockdown showed augmented expression of androgen-producing genes. Taken together, these results indicate that BMP-2 is a key player mediating the favorable effects of the BM-hMSCs secretome in a human PCOS cell model. BMP-2 overexpression could increase the efficacy of BM-hMSC-based therapy, serving as a novel stem cell therapy for patients with intractable PCOS.
Extracellular Matrix Biomarkers in Colorectal Cancer
Authors: Kim Min-Seob , Ha Se-Eun , Wu Moxin , Zogg Hannah , Ronkon Charles F. , Lee Moon-Young , Ro Seungil
Published: August 2021

The cellular microenvironment composition and changes therein play an extremely important role in cancer development. Changes in the extracellular matrix (ECM), which constitutes a majority of the tumor stroma, significantly contribute to the development of the tumor microenvironment. These alterations within the ECM and formation of the tumor microenvironment ultimately lead to tumor development, invasion, and metastasis. The ECM is composed of various molecules such as collagen, elastin, laminin, fibronectin, and the MMPs that cleave these protein fibers and play a central role in tissue remodeling. When healthy cells undergo an insult like DNA damage and become cancerous, if the ECM does not support these neoplastic cells, further development, invasion, and metastasis fail to occur. Therefore, ECM-related cancer research is indispensable, and ECM components can be useful biomarkers as well as therapeutic targets. Colorectal cancer specifically, is also affected by the ECM and many studies have been conducted to unravel the complex association between the two. Here we summarize the importance of several ECM components in colorectal cancer as well as their potential roles as biomarkers.
Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide
Authors: Merz Tamara , McCook Oscar , Denoix Nicole , Radermacher Peter , Waller Christiane , Kapapa Thomas
Published: August 2021

This paper explored the potential mediating role of hydrogen sulfide (H2S) and the oxytocin (OT) systems in hemorrhagic shock (HS) and/or traumatic brain injury (TBI). Morbidity and mortality after trauma mainly depend on the presence of HS and/or TBI. Rapid “repayment of the O2 debt” and prevention of brain tissue hypoxia are cornerstones of the management of both HS and TBI. Restoring tissue perfusion, however, generates an ischemia/reperfusion (I/R) injury due to the formation of reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, pre-existing-medical-conditions (PEMC’s) can aggravate the occurrence and severity of complications after trauma. In addition to the “classic” chronic diseases (of cardiovascular or metabolic origin), there is growing awareness of psychological PEMC’s, e.g., early life stress (ELS) increases the predisposition to develop post-traumatic-stress-disorder (PTSD) and trauma patients with TBI show a significantly higher incidence of PTSD than patients without TBI. In fact, ELS is known to contribute to the developmental origins of cardiovascular disease. The neurotransmitter H2S is not only essential for the neuroendocrine stress response, but is also a promising therapeutic target in the prevention of chronic diseases induced by ELS. The neuroendocrine hormone OT has fundamental importance for brain development and social behavior, and, thus, is implicated in resilience or vulnerability to traumatic events. OT and H2S have been shown to interact in physical and psychological trauma and could, thus, be therapeutic targets to mitigate the acute post-traumatic effects of chronic PEMC’s. OT and H2S both share anti-inflammatory, anti-oxidant, and vasoactive properties; through the reperfusion injury salvage kinase (RISK) pathway, where their signaling mechanisms converge, they act via the regulation of nitric oxide (NO).
Compromised Biomechanical Properties, Cell–Cell Adhesion and Nanotubes Communication in Cardiac Fibroblasts Carrying the Lamin A/C D192G Mutation
Authors: Lachaize Veronique , Peña Brisa , Ciubotaru Catalin , Cojoc Dan , Chen Suet Nee , Taylor Matthew R. G. , Mestroni Luisa , Sbaizero Orfeo
Published: August 2021

Clinical effects induced by arrhythmogenic cardiomyopathy (ACM) originate from a large spectrum of genetic variations, including the missense mutation of the lamin A/C gene (LMNA), LMNA D192G. The aim of our study was to investigate the biophysical and biomechanical impact of the LMNA D192G mutation on neonatal rat ventricular fibroblasts (NRVF). The main findings in mutated NRVFs were: (i) cytoskeleton disorganization (actin and intermediate filaments); (ii) decreased elasticity of NRVFs; (iii) altered cell–cell adhesion properties, that highlighted a strong effect on cellular communication, in particular on tunneling nanotubes (TNTs). In mutant-expressing fibroblasts, these nanotubes were weakened with altered mechanical properties as shown by atomic force microscopy (AFM) and optical tweezers. These outcomes complement prior investigations on LMNA mutant cardiomyocytes and suggest that the LMNA D192G mutation impacts the biomechanical properties of both cardiomyocytes and cardiac fibroblasts. These observations could explain how this mutation influences cardiac biomechanical pathology and the severity of ACM in LMNA-cardiomyopathy.
Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art
Authors: de Castro María José , del Toro Mireia , Giugliani Roberto , Couce María Luz
Published: August 2021

The need for long-lasting and transformative therapies for mucopolysaccharidoses (MPS) cannot be understated. Currently, many forms of MPS lack a specific treatment and in other cases available therapies, such as enzyme replacement therapy (ERT), do not reach important areas such as the central nervous system (CNS). The advent of newborn screening procedures represents a major step forward in early identification and treatment of individuals with MPS. However, the treatment of brain disease in neuronopathic MPS has been a major challenge to date, mainly because the blood brain barrier (BBB) prevents penetration of the brain by large molecules, including enzymes. Over the last years several novel experimental therapies for neuronopathic MPS have been investigated. Gene therapy and gene editing constitute potentially curative treatments. However, despite recent progress in the field, several considerations should be taken into account. This review focuses on the state of the art of in vivo and ex vivo gene therapy-based approaches targeting the CNS in neuronopathic MPS, discusses clinical trials conducted to date, and provides a vision for the future implications of these therapies for the medical community. Recent advances in the field, as well as limitations relating to efficacy, potential toxicity, and immunogenicity, are also discussed.
Promising Nanoparticle-Based Heat Transfer Fluids—Environmental and Techno-Economic Analysis Compared to Conventional Fluids
Authors: Czaplicka Natalia , Grzegórska Anna , Wajs Jan , Sobczak Joanna , Rogala Andrzej
Published: August 2021

Providing optimal operating conditions is one of the major challenges for effective heating or cooling systems. Moreover, proper adjustment of the heat transfer fluid is also important from the viewpoint of the correct operation, maintenance, and cost efficiency of these systems. Therefore, in this paper, a detailed review of recent work on the subject of conventional and novel heat transfer fluid applications is presented. Particular attention is paid to the novel nanoparticle-based materials used as heat transfer fluids. In-depth comparison of environmental, technical, and economic characteristics is discussed. Thermophysical properties including thermal conductivity, specific heat, density, viscosity, and Prandtl number are compared. Furthermore, the possible benefits and limitations of various transfer fluids in the fields of application are taken into account.
Increasing Angiogenesis Factors in Hypoxic Diabetic Wound Conditions by siRNA Delivery: Additive Effect of LbL-Gold Nanocarriers and Desloratadine-Induced Lysosomal Escape
Authors: Shaabani Elnaz , Sharifiaghdam Maryam , Lammens Joris , De Keersmaecker Herlinde , Vervaet Chris , De Beer Thomas , Motevaseli Elahe , Ghahremani Mohammad Hossein , Mansouri Parvin , De Smedt Stefaan , Raemdonck Koen , Faridi-Majidi Reza , Braeckmans Kevin , Fraire Juan C.
Published: August 2021

Impaired wound healing in people with diabetes has multifactorial causes, with insufficient neovascularization being one of the most important. Hypoxia-inducible factor-1 (HIF-1) plays a central role in the hypoxia-induced response by activating angiogenesis factors. As its activity is under precise regulatory control of prolyl-hydroxylase domain 2 (PHD-2), downregulation of PHD-2 by small interfering RNA (siRNA) could stabilize HIF-1α and, therefore, upregulate the expression of pro-angiogenic factors as well. Intracellular delivery of siRNA can be achieved with nanocarriers that must fulfill several requirements, including high stability, low toxicity, and high transfection efficiency. Here, we designed and compared the performance of layer-by-layer self-assembled siRNA-loaded gold nanoparticles with two different outer layers—Chitosan (AuNP@CS) and Poly L-arginine (AuNP@PLA). Although both formulations have exactly the same core, we find that a PLA outer layer improves the endosomal escape of siRNA, and therefore, transfection efficiency, after endocytic uptake in NIH-3T3 cells. Furthermore, we found that endosomal escape of AuNP@PLA could be improved further when cells were additionally treated with desloratadine, thus outperforming commercial reagents such as Lipofectamine® and jetPRIME®. AuNP@PLA in combination with desloratadine was proven to induce PHD-2 silencing in fibroblasts, allowing upregulation of pro-angiogenic pathways. This finding in an in vitro context constitutes a first step towards improving diabetic wound healing with siRNA therapy.
SARS-CoV-2 Impairs Dendritic Cells and Regulates DC-SIGN Gene Expression in Tissues
Authors: Cai Guoshuai , Du Mulong , Bossé Yohan , Albrecht Helmut , Qin Fei , Luo Xizhi , Androulakis Xiao Michelle , Cheng Chao , Nagarkatti Mitzi , Nagarkatti Prakash , Christiani David C. , Whitfield Michael L. , Amos Christopher I. , Xiao Feifei
Published: August 2021

The current spreading coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three host receptors (ACE2, DC-SIGN and L-SIGN) of SARS coronaviruses and dendritic cells (DCs) status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of COVID-19 patients and healthy controls. In COVID-19 patients, DC-SIGN gene expression was interestingly decreased in lung DCs but increased in blood DCs. Within DCs, conventional DCs (cDCs) were depleted while plasmacytoid DCs (pDCs) were augmented in the lungs of mild COVID-19. In severe cases, we identified augmented types of immature DCs (CD22+ or ANXA1+ DCs) with MHCII downregulation. In this study, our observation indicates that DCs in severe cases stimulate innate immune responses but fail to specifically present SARS-CoV-2. It provides insights into the profound modulation of DC function in severe COVID-19.
Kisspeptin Neurons and Estrogen–Estrogen Receptor α Signaling: Unraveling the Mystery of Steroid Feedback System Regulating Mammalian Reproduction
Authors: Uenoyama Yoshihisa , Inoue Naoko , Nakamura Sho , Tsukamura Hiroko
Published: August 2021

Estrogen produced by ovarian follicles plays a key role in the central mechanisms controlling reproduction via regulation of gonadotropin-releasing hormone (GnRH) release by its negative and positive feedback actions in female mammals. It has been well accepted that estrogen receptor α (ERα) mediates both estrogen feedback actions, but precise targets had remained as a mystery for decades. Ever since the discovery of kisspeptin neurons as afferent ERα-expressing neurons to govern GnRH neurons, the mechanisms mediating estrogen feedback are gradually being unraveled. The present article overviews the role of kisspeptin neurons in the arcuate nucleus (ARC), which are considered to drive pulsatile GnRH/gonadotropin release and folliculogenesis, in mediating the estrogen negative feedback action, and the role of kisspeptin neurons located in the anteroventral periventricular nucleus-periventricular nucleus (AVPV-PeN), which are thought to drive GnRH/luteinizing hormone (LH) surge and consequent ovulation, in mediating the estrogen positive feedback action. This implication has been confirmed by the studies showing that estrogen-bound ERα down- and up-regulates kisspeptin gene (Kiss1) expression in the ARC and AVPV-PeN kisspeptin neurons, respectively. The article also provides the molecular and epigenetic mechanisms regulating Kiss1 expression in kisspeptin neurons by estrogen. Further, afferent ERα-expressing neurons that may regulate kisspeptin release are discussed.
H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating
Authors: Farrugia Audrey , Rollet Kevin , Sinniger Jérome , Brun Susana , Spenle Caroline , Ludes Bertrand , Taleb Omar , Mensah-Nyagan Ayikoe Guy
Published: August 2021

Long QT syndrome is one of the most common hereditary channelopathies inducing fatal arrhythmias and sudden cardiac death. We identified in a sudden arrhythmic death syndrome case a C-term KCNH2 mutation (c.3457C > T; p.His1153Tyr) classified as variant of unknown significance and functional impact. Heterologous expression in HEK293 cells combined with western-blot, flow-cytometry, immunocytochemical and microscope analyses shows no modification of channel trafficking to the cell membrane. Electrophysiological studies reveal that the mutation causes a loss of HERG channel function through an alteration of channel biophysical properties that reduces the current density leading to LQT2. These results provide the first functional evidence for H1153Y-KCNH2 mutation-induced abnormal channel properties. They concur with previous biophysical and clinical presentations of a survived patient with another variant that is G1036D. Therefore, the present report importantly highlights the potential severity of variants that may have useful implications for treatment, surveillance, and follow-up of LQT2 patients.
Dimer Interface in Natural Variant NK1 Is Dispensable for HGF-Dependent Met Receptor Activation
Authors: Tahira Yumiko , Sakai Katsuya , Sato Hiroki , Imamura Ryu , Matsumoto Kunio
Published: August 2021

NK1, a splicing variant of hepatocyte growth factor (HGF), binds to and activates Met receptor by forming an NK1 dimer and 2:2 complex with Met. Although the structural mechanism underlying Met activation by HGF remains incompletely resolved, it has been proposed that the NK1 dimer structure participates in this activation. We investigated the NK1 dimer interface’s role in Met activation by HGF. Because N127, V140, and K144 are closely involved in the head-to-tail NK1 dimer formation, mutant NK1 proteins with replacement of these residues by alanine were prepared. In Met tyrosine phosphorylation assays, N127-NK1, V140-NK1, and K144-NK1 showed 8.3%, 23.8%, and 52.2% activity, respectively, compared with wild-type NK1. Although wild-type NK1 promoted cell migration and scattering, N127-NK1, V140-NK1, and K144-NK1 hardly or marginally promoted them, indicating loss of activity of these mutant NK1 proteins to activate Met. In contrast, mutant HGFs (N127-HGF, V140-HGF, and K144-HGF) with the same amino acid replacements as in NK1 induced Met tyrosine phosphorylation and biological responses at levels comparable to those of wild-type HGF. These results indicate that the structural basis responsible for NK1-dependent Met dimer formation and activation differs from, or is at least distinguishable from, the structural basis responsible for HGF-dependent Met activation.
The Amino Acid-mTORC1 Pathway Mediates APEC TW-XM-Induced Inflammation in bEnd.3 Cells
Authors: Zhang Dong , Xu Shu , Wang Yiting , Bin Peng , Zhu Guoqiang
Published: August 2021

The blood–brain barrier (BBB) is key to establishing and maintaining homeostasis in the central nervous system (CNS); meningitis bacterial infection can disrupt the integrity of BBB by inducing an inflammatory response. The changes in the cerebral uptake of amino acids may contribute to inflammatory response during infection and were accompanied by high expression of amino acid transporters leading to increased amino acid uptake. However, it is unclear whether amino acid uptake is changed and how to affect inflammatory responses in mouse brain microvascular endothelial (bEnd.3) cells in response to Avian Pathogenic Escherichia coli TW-XM (APEC XM) infection. Here, we firstly found that APEC XM infection could induce serine (Ser) and glutamate (Glu) transport from extracellular into intracellular in bEnd.3 cells. Meanwhile, we also shown that the expression sodium-dependent neutral amino acid transporter 2 (SNAT2) for Ser and excitatory amino acid transporter 4 (EAAT4) for Glu was also significantly elevated during infection. Then, in amino acid deficiency or supplementation medium, we found that Ser or Glu transport were involving in increasing SNAT2 or EAAT4 expression, mTORC1 (mechanistic target of rapamycin complex 1) activation and inflammation, respectively. Of note, Ser or Glu transport were inhibited after SNAT2 silencing or EAAT4 silencing, resulting in inhibition of mTORC1 pathway activation, and inflammation compared with the APEC XM infection group. Moreover, pEGFP-SNAT2 overexpression and pEGFP-EAAT4 overexpression in bEnd.3 cells all could promote amino acid uptake, activation of the mTORC1 pathway and inflammation during infection. We further found mTORC1 silencing could inhibit inflammation, the expression of SNAT2 and EAAT4, and amino acid uptake. Taken together, our results demonstrated that APEC TW-XM infection can induce Ser or Glu uptake depending on amino acid transporters transportation, and then activate amino acid-mTORC1 pathway to induce inflammation in bEnd.3 cells.
Advanced Diagnostic System and Introduction of Newborn Screening of Adrenoleukodystrophy and Peroxisomal Disorders in Japan
Authors: Shimozawa Nobuyuki , Takashima Shigeo , Kawai Hiroki , Kubota Kazuo , Sasai Hideo , Orii Kenji , Ogawa Megumi , Ohnishi Hidenori
Published: August 2021

We established a diagnostic system for adrenoleukodystrophy (ALD) and peroxisomal disorders (PD) over 35 years ago in Japan, and have diagnosed 237 families with ALD and more than 100 cases of PD other than ALD using biochemical and molecular analyses. In particular, since the only treatment for the cerebral form of ALD is hematopoietic stem cell transplantation at an early stage of onset, we have developed a protocol for the rapid diagnosis of ALD that can provide the measurements of the levels of very-long-chain fatty acids in the serum and genetic analysis within a few days. In addition, to improve the prognosis of patients with ALD, we are working on the detection of pre-symptomatic patients by familial analysis from the proband, and the introduction of newborn screening. In this review, we introduce the diagnostic and newborn screening approaches for ALD and PD in Japan.
DebtG: A Graph Model for Debt Relationship
Authors: Cui Huanqing
Published: August 2021

Debt is common in daily transactions, but it may bring great harm to individuals, enterprises, and society and even lead to a debt crisis. This paper proposes a weighted directed multi-arc graph model DebtG of debts among a large number of entities, including individuals, enterprises, banks, and governments, etc. Both vertices and arcs of DebtG have attributes. In further, it defines three basic debt structures: debt path, debt tree, and debt circuit, and it presents algorithms to detect them and basic methods to solve debt clearing problems using these structures. Because the data collection and computation need a third-party platform, this paper also presents the profit analysis of the platform. It carries out a case analysis using the real-life data of enterprises in Huangdao Zone. Finally, it points out four key problems that should be addressed in the future.
Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19
Authors: Schwartz David A. , Bugatti Mattia , Santoro Amerigo , Facchetti Fabio
Published: August 2021

A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together—chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.
The Combination of a Biocontrol Agent Trichoderma asperellum SC012 and Hymexazol Reduces the Effective Fungicide Dose to Control Fusarium Wilt in Cowpea
Authors: Zhang Chongyuan , Wang Weiwei , Xue Ming , Liu Zhen , Zhang Qinman , Hou Jumei , Xing Mengyu , Wang Rui , Liu Tong
Published: August 2021

The use of synthetic fungicide needs to be gradually reduced because of its adverse effect on human health and the environment. An integrated approach combining fungicides with biological control agents (BCAs) can be used to reduce the fungicide doses, thereby minimizing the risks associated with chemical fungicides. In this study, the combined application of a BCA Trichoderma and a fungicide hymexazol was used to manage the cowpea wilt disease caused by Fusarium oxysporum. The Trichoderma SC012 strain, which is resistant to hymexazol, was screened out and identified as T. asperellum. T. asperellum SC012 showed hyperparasitism to F. oxysporum and could penetrate and encircle the hyphae of pathogen on a medium amended or not with hymexazol. When combined with hymexazol, the population density in the rhizosphere soil of cowpea showed no significant difference compared with the treatment Trichoderma used alone. When the concentration of T. asperellum SC012 or hymexazol was halved, their combined application could control cowpea wilt disease more effectively than their individual use. The findings showed that the combination of Trichoderma and hymexazol could reduce the use of chemical fungicide, which is eco-friendly and may be an important part of integrated control of Fusarium wilt in cowpea.
Adapting an Ergosterol Extraction Method with Marine Yeasts for the Quantification of Oceanic Fungal Biomass
Authors: Salazar Alekseyeva Katherine , Mähnert Barbara , Berthiller Franz , Breyer Eva , Herndl Gerhard J. , Baltar Federico
Published: August 2021

Ergosterol has traditionally been used as a proxy to estimate fungal biomass as it is almost exclusively found in fungal lipid membranes. Ergosterol determination has been mostly used for fungal samples from terrestrial, freshwater, salt marsh- and mangrove-dominated environments or to describe fungal degradation of plant matter. In the open ocean, however, the expected concentrations of ergosterol are orders of magnitude lower than in terrestrial or macrophyte-dominated coastal systems. Consequently, the fungal biomass in the open ocean remains largely unknown. Recent evidence based on microscopy and -omics techniques suggests, however, that fungi contribute substantially to the microbial biomass in the oceanic water column, highlighting the need to accurately determine fungal biomass in the open ocean. We performed ergosterol extractions of an oceanic fungal isolate (Rhodotorula sphaerocarpa) with biomass concentrations varying over nine orders of magnitude. While after the initial chloroform-methanol extraction ~87% of the ergosterol was recovered, a second extraction recovered an additional ~10%. Testing this extraction method on samples collected from the open Atlantic Ocean, we successfully determined ergosterol concentrations as low as 0.12 pM. Thus, this highly sensitive method is well suited for measuring fungal biomass from open ocean waters, including deep-sea environments.
Are Foreign Banks Disadvantaged Vis-À-Vis Domestic Banks in China?
Authors: Liu Li Xian , Jiang Fuming , Sathye Milind , Liu Hongbo
Published: August 2021

Do foreign banks enjoy a competitive edge in the Chinese banking market or are they disadvantaged vis-à-vis domestic banks? This is the question that the present paper seeks to answer. The issue is important since on the one hand, these banks face the challenges the liability of foreignness brings, but at the same time, they have bank-specific advantages. We examine this issue in light of the literature of the liability of foreignness. In our path-breaking study, we found that due to the cost of foreignness, foreign banks’ performance was not as good as that of the local banks. Furthermore, despite the same amount of location- and bank-specific advantages, they performed badly as compared to their local counterparts. It was found that the cost of location-based disadvantages outweighed the cost of bank-specific disadvantages for foreign banks, and recent policy changes may help them overcome some of the cost of foreignness.
Using K-Means Cluster Analysis and Decision Trees to Highlight Significant Factors Leading to Homelessness
Authors: Yoder Clark Andrea , Blumenfeld Nicole , Lal Eric , Darbari Shikar , Northwood Shiyang , Wadpey Ashkan
Published: August 2021

Homelessness has been a persistent social concern in the United States. A combination of political and economic events since the 1960s has driven increases in poverty that, by 1991, had surpassed 1928 depression era levels in some accounts. This paper explores how the emerging field of behavioral economics can use machine learning and data science methods to explore preventative responses to homelessness. In this study, machine learning data mining strategies, specifically K-means cluster analysis and later, decision trees, were used to understand how environmental factors and resultant behaviors can contribute to the experience of homelessness. Prevention of the first homeless event is especially important as studies show that if a person has experienced homelessness once, they are 2.6 times more likely to have another homeless episode. Study findings demonstrate that when someone is at risk for not being able to pay utility bills at the same time as they experience challenges with two or more of the other social determinants of health, the individual is statistically significantly more likely to have their first homeless event. Additionally, for men over 50 who are not in the workforce, have a health hardship, and experience two or more other social determinants of health hardships at the same time, the individual has a high statistically significant probability of experiencing homelessness for the first time.
Is Happiness Linked to Subjective Life Expectancy? A Study of Chilean Senior Citizens
Authors: Gimenez Gregorio , Gil-Lacruz Ana Isabel , Gil-Lacruz Marta
Published: August 2021

The main goal of this research is to determine the link between happiness and individual subjective life expectancy (SLE) among Chilean senior citizens. We use data from the 2015 edition of the Chilean Social Protection Survey. Our sample consists of 1298 seniors: 700 aged 65–74, 421 aged 75–84, and 177 aged 85 and older. We provide a novel methodological approach that allows us to measure the relative contribution of happiness to SLE, by combining the Shapley–Owen–Shorrocks decomposition with contrasts of marginal linear predictions of the equality of the means by groups. Results reveal that happiness is the most important determinant of seniors’ SLE, and the effect is stronger the older the people are. Addressing varying levels of happiness is important because both happiness and unhappiness have a significant impact. In an ageing population, social agents should consider that these variables (happiness and SLE) are related to engagement in healthy lifestyles. If prevention programs integrated this interaction, welfare systems could save scarce resources. Therefore, governments should foster happiness to support active ageing.
Construction of an Explicit Solution of a Time-Fractional Multidimensional Differential Equation
Authors: Sultanov Murat A. , Durdiev Durdimurod K. , Rahmonov Askar A.
Published: August 2021

In this work, an explicit solution of the initial-boundary value problem for a multidimensional time-fractional differential equation is constructed. The possibility of obtaining this equation from an integro-differential wave equation with a Mittag–Leffler–type memory kernel is shown. An explicit solution to the problem under consideration is obtained using the Laplace and Fourier transforms, the properties of the Fox H-functions and the convolution theorem.
Fixed Point Theorems for Nonexpansive Mappings under Binary Relations
Authors: Alam Aftab , George Reny , Imdad Mohammad , Hasanuzzaman Md
Published: August 2021

In the present article, we establish relation-theoretic fixed point theorems in a Banach space, satisfying the Opial condition, using the R-Krasnoselskii sequence. We observe that graphical versions (Fixed Point Theory Appl. 2015:49 (2015) 6 pp.) and order-theoretic versions (Fixed Point Theory Appl. 2015:110 (2015) 7 pp.) of such results can be extended to a transitive binary relation.
Precursor-Directed Biosynthesis Mediated Amplification of Minor Aza Phenylpropanoid Piperazines in an Australian Marine Fish-Gut-Derived Fungus, Chrysosporium sp. CMB-F214
Authors: Elbanna Ahmed H. , Agampodi Dewa Amila , Khalil Zeinab G. , Capon Robert J.
Published: August 2021

Chemical analysis of an M1 agar plate cultivation of a marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214, revealed the known chrysosporazines A–D (11–14) in addition to a suite of very minor aza analogues 1–6. A microbioreactor (MATRIX) cultivation profiling analysis failed to deliver cultivation conditions that significantly improved the yields of 1–6; however, it did reveal that M2 agar cultivation produced the new natural product 15. A precursor-directed biosynthesis strategy adopting supplementation of a CMB-F214 M1 solid agar culture with sodium nicotinate enhanced production of otherwise inaccessible azachrysposorazines A1 (1), A2 (2), B1 (3), C1 (4), C2 (5) and D1 (6), in addition to four new chrysosporazines; chrysosporazines N–P (7–9) and spirochrysosporazine A (10). Structures inclusive of absolute configurations were assigned to 1–15 based on detailed spectroscopic and chemical analyses, and biosynthetic considerations. Non-cytotoxic to human carcinoma cells, azachrysosporazies 1–5 were capable of reversing doxorubicin resistance in P-glycoprotein (P-gp)-overexpressing human colon carcinoma cells (SW620 Ad300), with optimum activity exhibited by the C-2′ substituted analogues 3–5.
Interactions of Globular and Ribbon [γ4E]GID with α4β2 Neuronal Nicotinic Acetylcholine Receptor
Authors: Wu Xiaosa , Craik David J. , Kaas Quentin
Published: August 2021

The α4β2 nAChR is implicated in a range of diseases and disorders including nicotine addiction, epilepsy and Parkinson’s and Alzheimer’s diseases. Designing α4β2 nAChR selective inhibitors could help define the role of the α4β2 nAChR in such disease states. In this study, we aimed to modify globular and ribbon α-conotoxin GID to selectively target the α4β2 nAChR through competitive inhibition of the α4(+)β2(−) or α4(+)α4(−) interfaces. The binding modes of the globular α-conotoxin [γ4E]GID with rat α3β2, α4β2 and α7 nAChRs were deduced using computational methods and were validated using published experimental data. The binding mode of globular [γ4E]GID at α4β2 nAChR can explain the experimental mutagenesis data, suggesting that it could be used to design GID variants. The predicted mutational energy results showed that globular [γ4E]GID is optimal for binding to α4β2 nAChR and its activity could not likely be further improved through amino-acid substitutions. The binding mode of ribbon GID with the (α4)3(β2)2 nAChR was deduced using the information from the cryo-electron structure of (α4)3(β2)2 nAChR and the binding mode of ribbon AuIB. The program FoldX predicted the mutational energies of ribbon [γ4E]GID at the α4(+)α4(−) interface, and several ribbon[γ4E]GID mutants were suggested to have desirable properties to inhibit (α4)3(β2)2 nAChR.
New Antiproliferative Compounds against Glioma Cells from the Marine-Sourced Fungus Penicillium sp. ZZ1750
Authors: Yong Kuo , Kaleem Sidra , Wu Bin , Zhang Zhizhen
Published: August 2021

Seven novel compounds, namely peniresorcinosides A–E (1–5), penidifarnesylin A (6), and penipyridinone A (7), together with the 11 known ones 8–17, were isolated from a culture of the marine-associated fungus Penicillium sp. ZZ1750 in rice medium. The structures of the new compounds were established based on their high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, extensive nuclear magnetic resonance (NMR) spectroscopic analyses, chemical degradation, Mosher’s method, 13C-NMR calculations, electronic circular dichroism (ECD) calculations, and single crystal X-ray diffraction. Peniresorcinosides A (1) and B (2) are rare glycosylated alkylresorcinols and exhibited potent antiglioma activity, with IC50 values of 4.0 and 5.6 µM for U87MG cells and 14.1 and 9.8 µM for U251 cells, respectively.
The Urosepsis—A Literature Review
Authors: Guliciuc Mădălin , Maier Adrian Cornel , Maier Ioana Maria , Kraft Alin , Cucuruzac Roxana Ramona , Marinescu Monica , Şerban Cristina , Rebegea Laura , Constantin Georgiana Bianca , Firescu Dorel
Published: August 2021

Urosepsis is a very serious condition with a high mortality rate. The immune response is in the center of pathophysiology. The therapeutic management of these patients includes surgical treatment of the source of infection, antibiotic therapy and life support. The management of this pathology is multidisciplinary and requires good collaboration between the urology, intensive care, imaging and laboratory medicine departments. An imbalance of pro and anti-inflammatory cytokines produced during sepsis plays an important role in pathogenesis. The study of cytokines in sepsis has important implications for understanding pathophysiology and for development of other therapeutic solutions. If not treated adequately, urosepsis may lead to serious septic complications and organ sequelae, even to a lethal outcome.
Escherichia coli Specific Virulence-Gene Markers Analysis for Quality Control of Ovine Cheese in Slovakia
Authors: Bujňáková Dobroslava , Karahutová Lívia , Kmeť Vladimír
Published: August 2021

Shiga toxin-producing and extra-intestinal pathogenic Escherichia coli (E. coli) have the potential to spread through faecal waste, resulting in contamination of food and causing foodborne disease outbreaks. With the aim of characterizing unpasteurized ovine cheese in Slovakia, a total of 92 E. coli strains were examined for eleven representative virulence genes typical for (extra-)intestinal pathogenic E. coli and phylogenetic grouping. Phylogenetic groups B1 (36%) and A (32%) were the most dominant, followed by groups C (14%) and D (13%), while the lowest incidence was recorded for F (4%), and E (1%), and 43 (47%) samples carried at least one virulent gene, i.e., potential pathogens. Isolates present in groups E, F and D showed higher presence of virulence genes (100%, 75%, and 67%), versus 55%, 39%, and 28% in commensal B1, C, and A, respectively. Occurrence of papC and fyuA (both 24%) was highest, followed by tsh, iss, stx2, cnf1, kpsII, cvaC, stx1, iutA and eaeA. Nine E. coli strains (almost 10% of all tested and around 21% of our virulence-gene-associated isolates) harboured stx1, stx2 or eae. Ovine cheeses in Slovakia are highly contaminated with E. coli including potentially pathogenic strains capable of causing intestinal and/or extra-intestinal diseases, and thus may pose a threat to public health while unpasteurized.
Novel Microdialysis Technique Reveals a Dramatic Shift in Metabolite Secretion during the Early Stages of the Interaction between the Ectomycorrhizal Fungus Pisolithus microcarpus and Its Host Eucalyptus grandis
Authors: Plett Krista L. , Buckley Scott , Plett Jonathan M. , Anderson Ian C. , Lundberg-Felten Judith , Jämtgård Sandra
Published: August 2021

The colonisation of tree roots by ectomycorrhizal (ECM) fungi is the result of numerous signalling exchanges between organisms, many of which occur before physical contact. However, information is lacking about these exchanges and the compounds that are secreted by each organism before contact. This is in part due to a lack of low disturbance sampling methods with sufficient temporal and spatial resolution to capture these exchanges. Using a novel in situ microdialysis approach, we sampled metabolites released from Eucalyptus grandis and Pisolithus microcarpus independently and during indirect contact over a 48-h time-course using UPLC-MS. A total of 560 and 1530 molecular features (MFs; ESI- and ESI+ respectively) were identified with significant differential abundance from control treatments. We observed that indirect contact between organisms altered the secretion of MFs to produce a distinct metabolomic profile compared to either organism independently. Many of these MFs were produced within the first hour of contact and included several phenylpropanoids, fatty acids and organic acids. These findings show that the secreted metabolome, particularly of the ECM fungus, can rapidly shift during the early stages of pre-symbiotic contact and highlight the importance of observing these early interactions in greater detail. We present microdialysis as a useful tool for examining plant–fungal signalling with high temporal resolution and with minimal experimental disturbance.
Experimental and Modelling Analysis of the Hyperthermia Properties of Iron Oxide Nanocubes
Authors: Ferrero Riccardo , Barrera Gabriele , Celegato Federica , Vicentini Marta , Sözeri Hüseyin , Yıldız Nuray , Atila Dinçer Ceren , Coïsson Marco , Manzin Alessandra , Tiberto Paola
Published: August 2021

The ability of magnetic nanoparticles (MNPs) to transform electromagnetic energy into heat is widely exploited in well-known thermal cancer therapies, such as magnetic hyperthermia, which proves useful in enhancing the radio- and chemo-sensitivity of human tumor cells. Since the heat release is ruled by the complex magnetic behavior of MNPs, a careful investigation is needed to understand the role of their intrinsic (composition, size and shape) and collective (aggregation state) properties. Here, the influence of geometrical parameters and aggregation on the specific loss power (SLP) is analyzed through in-depth structural, morphological, magnetic and thermometric characterizations supported by micromagnetic and heat transfer simulations. To this aim, different samples of cubic Fe3O4 NPs with an average size between 15 nm and 160 nm are prepared via hydrothermal route. For the analyzed samples, the magnetic behavior and heating properties result to be basically determined by the magnetic single- or multi-domain configuration and by the competition between magnetocrystalline and shape anisotropies. This is clarified by micromagnetic simulations, which enable us to also elucidate the role of magnetostatic interactions associated with locally strong aggregation.
Systematic Analysis on the Effect of Sintering Temperature for Optimized Performance of Li0.15Ni0.45Zn0.4O2-Gd0.2Ce0.8O2-Li2CO3-Na2CO3-K2CO3 Based 3D Printed Single-Layer Ceramic Fuel Cell
Authors: Asghar Muhammad Imran , Mäkinen Pyry , Virtanen Sini , Maitre Anna , Borghei Maryam , Lund Peter D.
Published: August 2021

Single-layer ceramic fuel cells consisting of Li0.15Ni0.45Zn0.4O2, Gd0.2Ce0.8O2 and a eutectic mixture of Li2CO3, Na2CO3 and K2CO3, were fabricated through extrusion-based 3D printing. The sintering temperature of the printed cells was varied from 700 °C to 1000 °C to identify the optimal thermal treatment to maximize the cell performance. It was found that the 3D printed single-layer cell sintered at 900 °C produced the highest power density (230 mW/cm2) at 550 °C, which is quite close to the performance (240 mW/cm2) of the single-layer cell fabricated through a conventional pressing method. The best printed cell still had high ohmic (0.46 Ω·cm2) and polarization losses (0.32 Ω·cm2) based on EIS measurements conducted in an open-circuit condition. The XRD spectra showed the characteristic peaks of the crystalline structures in the composite material. HR-TEM, SEM and EDS measurements revealed the morphological information of the composite materials and the distribution of the elements, respectively. The BET surface area of the single-layer cells was found to decrease from 2.93 m2/g to 0.18 m2/g as the sintering temperature increased from 700 °C to 1000 °C. The printed cell sintered at 900 °C had a BET surface area of 0.34 m2/g. The fabrication of single-layer ceramic cells through up-scalable 3D technology could facilitate the scaling up and commercialization of this promising fuel cell technology.
Self-Supported Defect-Rich Au-Based Nanostructures as Robust Bifunctional Catalysts for the Methanol Oxidation Reaction and Oxygen Reduction Reaction in an Alkaline Medium
Authors: Tao Yuanyuan , Liang Xiu , Xu Guanchen , Li Dongwei , Li Yong , Zhang Na , Chen Yingzhou , Jiang Xifeng , Gong Hongyu
Published: August 2021

Recently, alkaline direct methanol fuel cells have made great progress with the development of alkaline electrocatalysis, and a wide variety of catalysts have been explored for methanol oxidation reaction (MOR)and oxygen reduction reaction (ORR). However, the slow kinetics of the MOR and ORR remain a great challenge. In this paper, self-supported defect-rich AuCu was obtained by a convenient one-pot strategy. Self-supported AuCu presented a branched, porous nanostructure. The nanobranch consisted of several 13 nm skeletons, which connected in the kink of the structure. Different growth directions co-existed at the kink, and the twin boundaries and dislocations as defects were observed. When the Au-based nanostructure functioned as an electrocatalyst, it showed robust MOR and ORR performance. For the MOR, the forward peak current was 2.68 times greater than that of Au/C; for the ORR, the activity was close to that of Pt/C and significantly better than that of Au/C. In addition, it possessed superior electrochemical stability for MOR and ORR. Finally, an in-depth exploration of the impact of surface defects and electrochemical Cu removal on MOR and ORR activity was carried out to explain the MOR and ORR’s catalytic performance.