bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Environmental Injustice on Children’s Health—Interaction between Air Pollution and Socioeconomic Status
Authors: Mathiarasan Sahana , Hüls Anke
Published: January 2021

Air pollution disproportionately affects marginalized populations of lower socioeconomic status. There is little literature on how socioeconomic status affects the risk of exposure to air pollution and associated health outcomes, particularly for children’s health. The objective of this article was to review the existing literature on air pollution and children’s health and discern how socioeconomic status affects this association. The concept of environmental injustice recognizes how underserved communities often suffer from higher air pollution concentrations in addition to other underlying risk factors for impaired health. This exposure then exerts larger effects on their health than it does in the average population, affecting the whole body, including the lungs and the brain. Children, whose organs and mind are still developing and who do not have the means of protecting themselves or creating change, are the most vulnerable to the detrimental effects of air pollution and environmental injustice. The adverse health effects of air pollution and environmental injustice can harm children well into adulthood and may even have transgenerational effects. There is an urgent need for action in order to ensure the health and safety of future generations, as social disparities are continuously increasing, due to social discrimination and climate change.
Explaining the Social Acceptance of Renewables through Location-Related Factors: An Application to the Portuguese Case
Authors: Pinto Lígia M. Costa , Sousa Sara , Valente Marieta
Published: January 2021

The public perception of renewable energy sources is generally positive, due to their role in air pollution and CO2 emission mitigation policies. However, there are local environmental detrimental effects, and empirical evidence is not consistent as to the support of local communities. In the present paper, we analyse the antecedents of public generic perceptions of renewables grounded on objective location-related factors. Personal location-related factors can originate in the involvement of individuals with renewable energy sources. Regional location-related factors concern the importance of the renewable energy source in the district of residence and in relation to other renewables. We implement a questionnaire on public perceptions of renewable energy sources by the general population in mainland Portugal and complement respondent-level responses with renewable energy district information. Regression analysis shows that these objective location-related factors, both personal and regional, help explain public perceptions of renewables and thus we find empirical support for the proposed approach. These results can inform and guide policymakers in tackling future social acceptance issues of renewable energy policies towards lower carbon emissions and less polluting energy production.
Amyotrophic Lateral Sclerosis Genes in Drosophila melanogaster
Authors: Layalle Sophie , They Laetitia , Ourghani Sarah , Raoul Cédric , Soustelle Laurent
Published: January 2021

Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disease characterized by the progressive degeneration of upper and lower motoneurons. Most ALS cases are sporadic but approximately 10% of ALS cases are due to inherited mutations in identified genes. ALS-causing mutations were identified in over 30 genes with superoxide dismutase-1 (SOD1), chromosome 9 open reading frame 72 (C9orf72), fused in sarcoma (FUS), and TAR DNA-binding protein (TARDBP, encoding TDP-43) being the most frequent. In the last few decades, Drosophila melanogaster emerged as a versatile model for studying neurodegenerative diseases, including ALS. In this review, we describe the different Drosophila ALS models that have been successfully used to decipher the cellular and molecular pathways associated with SOD1, C9orf72, FUS, and TDP-43. The study of the known fruit fly orthologs of these ALS-related genes yielded significant insights into cellular mechanisms and physiological functions. Moreover, genetic screening in tissue-specific gain-of-function mutants that mimic ALS-associated phenotypes identified disease-modifying genes. Here, we propose a comprehensive review on the Drosophila research focused on four ALS-linked genes that has revealed novel pathogenic mechanisms and identified potential therapeutic targets for future therapy.
Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice
Authors: Chen Yu-Jen , Lin Chiao-Wei , Peng Yu-Ju , Huang Chao-Wei , Chien Yi-Shan , Huang Tzu-Hsuan , Liao Pei-Xin , Yang Wen-Yuan , Wang Mei-Hui , Mersmann Harry J. , Wu Shinn-Chih , Chuang Tai-Yuan , Lin Yuan-Yu , Kuo Wen-Hung , Ding Shih-Torng
Published: January 2021

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing “healthy obese” by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [18F] fluorodeoxyglucose-PET/CT (18F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.
LytR-CpsA-Psr Glycopolymer Transferases: Essential Bricks in Gram-Positive Bacterial Cell Wall Assembly
Authors: Stefanović Cordula , Hager Fiona F. , Schäffer Christina
Published: January 2021

The cell walls of Gram-positive bacteria contain a variety of glycopolymers (CWGPs), a significant proportion of which are covalently linked to the peptidoglycan (PGN) scaffolding structure. Prominent CWGPs include wall teichoic acids of Staphylococcus aureus, streptococcal capsules, mycobacterial arabinogalactan, and rhamnose-containing polysaccharides of lactic acid bacteria. CWGPs serve important roles in bacterial cellular functions, morphology, and virulence. Despite evident differences in composition, structure and underlaying biosynthesis pathways, the final ligation step of CWGPs to the PGN backbone involves a conserved class of enzymes—the LytR-CpsA-Psr (LCP) transferases. Typically, the enzymes are present in multiple copies displaying partly functional redundancy and/or preference for a distinct CWGP type. LCP enzymes require a lipid-phosphate-linked glycan precursor substrate and catalyse, with a certain degree of promiscuity, CWGP transfer to PGN of different maturation stages, according to in vitro evidence. The prototype attachment mode is that to the C6-OH of N-acetylmuramic acid residues via installation of a phosphodiester bond. In some cases, attachment proceeds to N-acetylglucosamine residues of PGN—in the case of the Streptococcus agalactiae capsule, even without involvement of a phosphate bond. A novel aspect of LCP enzymes concerns a predicted role in protein glycosylation in Actinomyces oris. Available crystal structures provide further insight into the catalytic mechanism of this biologically important class of enzymes, which are gaining attention as new targets for antibacterial drug discovery to counteract the emergence of multidrug resistant bacteria.
Mutations in GDAP1 Influence Structure and Function of the Trans-Golgi Network
Authors: Binięda Katarzyna , Rzepnikowska Weronika , Kolakowski Damian , Kaminska Joanna , Szczepankiewicz Andrzej Antoni , Nieznańska Hanna , Kochański Andrzej , Kabzińska Dagmara
Published: January 2021

Charcot-Marie-Tooth disease (CMT) is a heritable neurodegenerative disease that displays great genetic heterogeneity. The genes and mutations that underlie this heterogeneity have been extensively characterized by molecular genetics. However, the molecular pathogenesis of the vast majority of CMT subtypes remains terra incognita. Any attempts to perform experimental therapy for CMT disease are limited by a lack of understanding of the pathogenesis at a molecular level. In this study, we aim to identify the molecular pathways that are disturbed by mutations in the gene encoding GDAP1 using both yeast and human cell, based models of CMT-GDAP1 disease. We found that some mutations in GDAP1 led to a reduced expression of the GDAP1 protein and resulted in a selective disruption of the Golgi apparatus. These structural alterations are accompanied by functional disturbances within the Golgi. We screened over 1500 drugs that are available on the market using our yeast-based CMT-GDAP1 model. Drugs were identified that had both positive and negative effects on cell phenotypes. To the best of our knowledge, this study is the first report of the Golgi apparatus playing a role in the pathology of CMT disorders. The drugs we identified, using our yeast-based CMT-GDAP1 model, may be further used in translational research.
The Role of Gut Microbiota in an Ischemic Stroke
Authors: Pluta Ryszard , Januszewski Sławomir , Czuczwar Stanisław J.
Published: January 2021

The intestinal microbiome, the largest reservoir of microorganisms in the human body, plays an important role in neurological development and aging as well as in brain disorders such as an ischemic stroke. Increasing knowledge about mediators and triggered pathways has contributed to a better understanding of the interaction between the gut-brain axis and the brain-gut axis. Intestinal bacteria produce neuroactive compounds and can modulate neuronal function, which affects behavior after an ischemic stroke. In addition, intestinal microorganisms affect host metabolism and immune status, which in turn affects the neuronal network in the ischemic brain. Here we discuss the latest results of animal and human research on two-way communication along the gut-brain axis in an ischemic stroke. Moreover, several reports have revealed the impact of an ischemic stroke on gut dysfunction and intestinal dysbiosis, highlighting the delicate play between the brain, intestines and microbiome after this acute brain injury. Despite our growing knowledge of intestinal microflora in shaping brain health, host metabolism, the immune system and disease progression, its therapeutic options in an ischemic stroke have not yet been fully utilized. This review shows the role of the gut microflora-brain axis in an ischemic stroke and assesses the potential role of intestinal microflora in the onset, progression and recovery post-stroke.
Quantitative Proteomics Reveals that GmENO2 Proteins Are Involved in Response to Phosphate Starvation in the Leaves of Glycine max L.
Authors: Cheng Ling , Min Wanling , Li Man , Zhou Lili , Hsu Chuan-Chih , Yang Xuelian , Jiang Xue , Ruan Zhijie , Zhong Yongjia , Wang Zhi-Yong , Wang Wenfei
Published: January 2021

Soybean (Glycine max L.) is a major crop providing important source for protein and oil for human life. Low phosphate (LP) availability is a critical limiting factor affecting soybean production. Soybean plants develop a series of strategies to adapt to phosphate (Pi) limitation condition. However, the underlying molecular mechanisms responsible for LP stress response remain largely unknown. Here, we performed a label-free quantification (LFQ) analysis of soybean leaves grown under low and high phosphate conditions. We identified 267 induced and 440 reduced differential proteins from phosphate-starved leaves. Almost a quarter of the LP decreased proteins are involved in translation processes, while the LP increased proteins are accumulated in chlorophyll biosynthetic and carbon metabolic processes. Among these induced proteins, an enolase protein, GmENO2a was found to be mostly induced protein. On the transcriptional level, GmENO2a and GmENO2b, but not GmENO2c or GmENO2d, were dramatically induced by phosphate starvation. Among 14 enolase genes, only GmENO2a and GmENO2b genes contain the P1BS motif in their promoter regions. Furthermore, GmENO2b was specifically induced in the GmPHR31 overexpressing soybean plants. Our findings provide molecular insights into how soybean plants tune basic carbon metabolic pathway to adapt to Pi deprivation through the ENO2 enzymes.
Amino Acid Composition in Various Types of Nucleic Acid-Binding Proteins
Authors: Bartas Martin , Červeň Jiří , Guziurová Simona , Slychko Kristyna , Pečinka Petr
Published: January 2021

Nucleic acid-binding proteins are traditionally divided into two categories: With the ability to bind DNA or RNA. In the light of new knowledge, such categorizing should be overcome because a large proportion of proteins can bind both DNA and RNA. Another even more important features of nucleic acid-binding proteins are so-called sequence or structure specificities. Proteins able to bind nucleic acids in a sequence-specific manner usually contain one or more of the well-defined structural motifs (zinc-fingers, leucine zipper, helix-turn-helix, or helix-loop-helix). In contrast, many proteins do not recognize nucleic acid sequence but rather local DNA or RNA structures (G-quadruplexes, i-motifs, triplexes, cruciforms, left-handed DNA/RNA form, and others). Finally, there are also proteins recognizing both sequence and local structural properties of nucleic acids (e.g., famous tumor suppressor p53). In this mini-review, we aim to summarize current knowledge about the amino acid composition of various types of nucleic acid-binding proteins with a special focus on significant enrichment and/or depletion in each category.
Characterization of Pathogenicity-Associated V2 Protein of Tobacco Curly Shoot Virus
Authors: Li Mingjun , Li Changchang , Jiang Kairong , Li Ke , Zhang Junlei , Sun Miao , Wu Gentu , Qing Ling
Published: January 2021

V2 proteins encoded by some whitefly-transmitted geminiviruses were reported to be functionally important proteins. However, the functions of the V2 protein of tobacco curly shoot virus (TbCSV), a monopartite begomovirus that causes leaf curl disease on tomato and tobacco in China, remains to be characterized. In our report, an Agrobacterium infiltration-mediated transient expression assay indicated that TbCSV V2 can suppress local and systemic RNA silencing and the deletion analyses demonstrated that the amino acid region 1–92 of V2, including the five predicted α-helices, are required for local RNA silencing suppression. Site-directed substitutions showed that the conserved basic and ring-structured amino acids in TbCSV V2 are critical for its suppressor activity. Potato virus X-mediated heteroexpression of TbCSV V2 in Nicotiana benthamiana induced hypersensitive response-like (HR-like) cell death and systemic necrosis in a manner independent of V2′s suppressor activity. Furthermore, TbCSV infectious clone mutant with untranslated V2 protein (TbCSV∆V2) could not induce visual symptoms, and coinfection with betasatellite (TbCSB) could obviously elevate the viral accumulation and symptom development. Interestingly, symptom recovery occurred at 15 days postinoculation (dpi) and onward in TbCSV∆V2/TbCSB-inoculated plants. The presented work contributes to understanding the RNA silencing suppression activity of TbCSV V2 and extends our knowledge of the multifunctional role of begomovirus-encoded V2 proteins during viral infections.
Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
Authors: Lee Jihyun , Jung Yujin , Jeong Seo won , Jeong Ga Hee , Moon Gue Tae , Kim Miri
Published: January 2021

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.
Endocrine Disrupting Chemicals: Current Understanding, New Testing Strategies and Future Research Needs
Authors: Street Maria E. , Audouze Karine , Legler Juliette , Sone Hideko , Palanza Paola
Published: January 2021

Endocrine disrupting chemicals (EDCs) are exogenous chemicals which can disrupt any action of the endocrine system, and are an important class of substances which play a role in the Developmental Origins of Health and Disease (DOHaD) [...]
The NFκB Antagonist CDGSH Iron-Sulfur Domain 2 Is a Promising Target for the Treatment of Neurodegenerative Diseases
Authors: Kung Woon-Man , Lin Muh-Shi
Published: January 2021

Proinflammatory response and mitochondrial dysfunction are related to the pathogenesis of neurodegenerative diseases (NDs). Nuclear factor κB (NFκB) activation has been shown to exaggerate proinflammation and mitochondrial dysfunction, which underlies NDs. CDGSH iron-sulfur domain 2 (CISD2) has been shown to be associated with peroxisome proliferator-activated receptor-β (PPAR-β) to compete for NFκB and antagonize the two aforementioned NFκB-provoked pathogeneses. Therefore, CISD2-based strategies hold promise in the treatment of NDs. CISD2 protein belongs to the human NEET protein family and is encoded by the CISD2 gene (located at 4q24 in humans). In CISD2, the [2Fe-2S] cluster, through coordinates of 3-cysteine-1-histidine on the CDGSH domain, acts as a homeostasis regulator under environmental stress through the transfer of electrons or iron-sulfur clusters. Here, we have summarized the features of CISD2 in genetics and clinics, briefly outlined the role of CISD2 as a key physiological regulator, and presented modalities to increase CISD2 activity, including biomedical engineering or pharmacological management. Strategies to increase CISD2 activity can be beneficial for the prevention of inflammation and mitochondrial dysfunction, and thus, they can be applied in the management of NDs.
Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts
Authors: Baszanowska Weronika , Misiura Magdalena , Oscilowska Ilona , Palka Jerzy , Miltyk Wojciech
Published: January 2021

The role of prolidase (PEPD) as a ligand of the epidermal growth factor receptor (EGFR) was studied in an experimental model of wound healing in cultured fibroblasts. The cells were treated with PEPD (1–100 nM) and analysis of cell viability, proliferation, migration, collagen biosynthesis, PEPD activity, and the expressions of EGFR, insulin-like growth factor 1 (IGF-1), and β1-integrin receptor including downstream signaling proteins were performed. It has been found that PEPD stimulated proliferation and migration of fibroblasts via activation of the EGFR-downstream PI3K/Akt/mTOR signaling pathway. Simultaneously, PEPD stimulated the expression of β1-integrin and IGF-1 receptors and proteins downstream to these receptors such as FAK, Grb2, and ERK1/2. Collagen biosynthesis was increased in control and “wounded” fibroblasts under PEPD treatment. The data suggest that PEPD-induced EGFR signaling may serve as a new attempt to therapy wound healing.
Steroidal Regulation of Oviductal microRNAs Is Associated with microRNA-Processing in Beef Cows
Authors: Gonella-Diaza Angela Maria , Lopes Everton , Ribeiro da Silva Kauê , Perecin Nociti Ricardo , Mamede Andrade Gabriella , Atuesta-Bustos Jorge Eduardo , Coelho da Silveira Juliano , Vieira Meirelles Flávio , Binelli Mario
Published: January 2021

Information on molecular mechanisms through which sex-steroids regulate oviductal function to support early embryo development is lacking. Here, we hypothesized that the periovulatory endocrine milieu affects the miRNA processing machinery and miRNA expression in bovine oviductal tissues. Growth of the preovulatory follicle was controlled to obtain cows that ovulated a small follicle (SF) and subsequently bore a small corpus luteum (CL; SF-SCL) or a large follicle (LF) and large CL (LF-LCL). These groups differed in the periovulatory plasmatic sex-steroid’s concentrations. Ampulla and isthmus samples were collected on day four of the estrous cycle. Abundance of DROSHA, DICER1, and AGO4 transcripts was greater in the ampulla than the isthmus. In the ampulla, transcription of these genes was greater for the SF-SCL group, while the opposite was observed in the isthmus. The expression of the 88 most abundant miRNAs and 14 miRNAs in the ampulla and 34 miRNAs in isthmus were differentially expressed between LF-LCL and SF-SCL groups. Integration of transcriptomic and miRNA data and molecular pathways enrichment showed that important pathways were inhibited in the SF-SCL group due to miRNA control. In conclusion, the endocrine milieu affects the miRNA expression in the bovine oviduct in a region-specific manner.
Characteristics and Cryopreservation of Semen of Sex-Reversed Females of Salmonid Fish
Authors: Judycka Sylwia , Nynca Joanna , Hliwa Piotr , Ciereszko Andrzej
Published: January 2021

Sex reversal has been used as a breeding strategy by salmonid fish to produce genetically and phenotypically single sex populations. Production of all-female fish has great importance for the creation of monosex female triploids of salmonid fish, which are valued for their sterility, lack of female maturation, and larger commercial size. Among salmonids, the majority of rainbow trout (Oncorhynchus mykiss) production is based on all-female production with a high proportion of all-female triploid production in Europe. The main aim of this review is to present the recent knowledge regarding sex-reversed females (SRFs) of salmonid fish. We discuss the methods of sex reversal as well as their effects on the morphology and histology of the reproductive tract. We focus on the characteristics of SRF semen as well as the factors determining semen quality. The lower quality of SRF sperm compared to that of normal males has resulted in the need for the artificial maturation of semen. Most importantly, methods of semen storage—both short-term and long-term (cryopreservation)—that can improve hatchery operations are presented with the special emphasis on recent progress in development of efficient cryopreservation procedures and use of cryopreserved semen in hatchery practice. Moreover, we also address the emerging knowledge concerning the proteomic investigations of salmonid sperm, focusing primarily on the proteomic comparison of normal male and SRF testicular semen and presenting changes in SRF rainbow trout sperm proteome after in vitro incubation in artificial seminal plasma.
The Immunopathological and Histological Landscape of COVID-19-Mediated Lung Injury
Authors: Zarrilli Giovanni , Angerilli Valentina , Businello Gianluca , Sbaraglia Marta , Traverso Giulia , Fortarezza Francesco , Rizzo Stefania , De Gaspari Monica , Basso Cristina , Calabrese Fiorella , Dei Tos Angelo , Fassan Matteo
Published: January 2021

A complete understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) physiopathology and related histopathologic lesions is necessary to improve treatment and outcome of coronavirus disease 2019 (COVID-19) patients. Many studies have focused on autopsy findings in COVID-19-related deaths to try and define any possible specific pattern. Histopathologic alterations are principally found within lungs and blood vessels, and these abnormalities also seem to have the highest clinical impact. Nevertheless, many of the morphological data collected so far are non-specific, fickle, and possibly associated with other co-existing factors. The aim of this minireview is to describe the main histopathological features related to COVID-19 and the mechanism known as “cytokine storm”.
The Protein Phosphatase PP2A Plays Multiple Roles in Plant Development by Regulation of Vesicle Traffic—Facts and Questions
Authors: Máthé Csaba , M-Hamvas Márta , Freytag Csongor , Garda Tamás
Published: January 2021

The protein phosphatase PP2A is essential for the control of integrated eukaryotic cell functioning. Several cellular and developmental events, e.g., plant growth regulator (PGR) mediated signaling pathways are regulated by reversible phosphorylation of vesicle traffic proteins. Reviewing present knowledge on the relevant role of PP2A is timely. We discuss three aspects: (1) PP2A regulates microtubule-mediated vesicle delivery during cell plate assembly. PP2A dephosphorylates members of the microtubule associated protein family MAP65, promoting their binding to microtubules. Regulation of phosphatase activity leads to changes in microtubule organization, which affects vesicle traffic towards cell plate and vesicle fusion to build the new cell wall between dividing cells. (2) PP2A-mediated inhibition of target of rapamycin complex (TORC) dependent signaling pathways contributes to autophagy and this has possible connections to the brassinosteroid signaling pathway. (3) Transcytosis of vesicles transporting PIN auxin efflux carriers. PP2A regulates vesicle localization and recycling of PINs related to GNOM (a GTP–GDP exchange factor) mediated pathways. The proper intracellular traffic of PINs is essential for auxin distribution in the plant body, thus in whole plant development. Overall, PP2A has essential roles in membrane interactions of plant cell and it is crucial for plant development and stress responses.
Isolation and Characterization of Equine Uterine Extracellular Vesicles: A Comparative Methodological Study
Authors: Almiñana Carmen , Rudolf Vegas Alba , Tekin Muhittin , Hassan Mubbashar , Uzbekov Rustem , Fröhlich Thomas , Bollwein Heinrich , Bauersachs Stefan
Published: January 2021

Extracellular vesicles (EVs) have been identified in the uterine fluid in different species and have been pointed as key players in the embryo-maternal dialogue, maternal recognition of pregnancy and establishment of pregnancy. However, little is known about the uterine EVs in the mare. Therefore, the present study aimed at characterizing EVs from uterine lavage of cyclic mares by comparing five EVs isolation methods and the combination of them: (1) ultracentrifugation (UC); (2) concentration of lavage volume by Centricon ultrafiltration (CE); (3) the use of CE with different washing steps (phosphate-buffered saline with or without trehalose); (4) size-exclusion chromatography with iZON-qEV columns, and (5) a combination of the methods with best results based on EVs yield, purity, and protein cargo profiles. Transmission electron microscopy and Western blotting confirmed the isolation of EVs by all methods but with quantitative and qualitative differences. Mass spectrometry provided differences in protein profiles between methods, number of identified proteins, and protein classes. Our results indicate that the combination of CE/trehalose/iZON/UC is an optimal method to isolate equine uterine EVs with good yield and purity that can be applied in future studies to determine the role of equine uterine EVs in embryo-maternal interactions.
Correlating Local Volumetric Tissue Strains with Global Lung Mechanics Measurements
Authors: Arora Hari , Mitchell Ria , Johnston Richard , Manolesos Marinos , Howells David , Sherwood Joseph , Bodey Andrew , Wanelik Kaz
Published: January 2021

The mechanics of breathing is a fascinating and vital process. The lung has complexities and subtle heterogeneities in structure across length scales that influence mechanics and function. This study establishes an experimental pipeline for capturing alveolar deformations during a respiratory cycle using synchrotron radiation micro-computed tomography (SR-micro-CT). Rodent lungs were mechanically ventilated and imaged at various time points during the respiratory cycle. Pressure-Volume (P-V) characteristics were recorded to capture any changes in overall lung mechanical behaviour during the experiment. A sequence of tomograms was collected from the lungs within the intact thoracic cavity. Digital volume correlation (DVC) was used to compute the three-dimensional strain field at the alveolar level from the time sequence of reconstructed tomograms. Regional differences in ventilation were highlighted during the respiratory cycle, relating the local strains within the lung tissue to the global ventilation measurements. Strains locally reached approximately 150% compared to the averaged regional deformations of approximately 80–100%. Redistribution of air within the lungs was observed during cycling. Regions which were relatively poorly ventilated (low deformations compared to its neighbouring region) were deforming more uniformly at later stages of the experiment (consistent with its neighbouring region). Such heterogenous phenomena are common in everyday breathing. In pathological lungs, some of these non-uniformities in deformation behaviour can become exaggerated, leading to poor function or further damage. The technique presented can help characterize the multiscale biomechanical nature of a given pathology to improve patient management strategies, considering both the local and global lung mechanics.
Surface Modification of Biodegradable Mg-Based Scaffolds for Human Mesenchymal Stem Cell Proliferation and Osteogenic Differentiation
Authors: Wang Si-Han , Lee Shiao-Pieng , Yang Chung-Wei , Lo Chun-Min
Published: January 2021

Magnesium alloys with coatings have the potential to be used for bone substitute alternatives since their mechanical properties are close to those of human bone. However, the surface modification of magnesium alloys to increase the surface biocompatibility and reduce the degradation rate remains a challenge. Here, FHA-Mg scaffolds were made of magnesium alloys and coated with fluorohydroxyapatite (FHA). Human mesenchymal stem cells (hMSCs) were cultured on FHA-Mg scaffolds and cell viability, proliferation, and osteogenic differentiation were investigated. The results showed that FHA-Mg scaffolds display a nano-scaled needle-like structure of aggregated crystallites on their surface. The average Mg2+ concentration in the conditioned media collected from FHA-Mg scaffolds (5.8–7.6 mM) is much lower than those collected from uncoated, Mg(OH)2-coated, and hydroxyapatite (HA)-coated samples (32.1, 17.7, and 21.1 mM, respectively). In addition, compared with hMSCs cultured on a culture dish, cells cultured on FHA-Mg scaffolds demonstrated better proliferation and comparable osteogenic differentiation. To eliminate the effect of osteogenic induction medium, hMSCs were cultured on FHA-Mg scaffolds in culture medium and an approximate 66% increase in osteogenic differentiation was observed three weeks later, indicating a significant effect of the nanostructured surface of FHA-Mg scaffolds on hMSC behaviors. With controllable Mg2+ release and favorable mechanical properties, porous FHA-Mg scaffolds have a great potential in cell-based bone regeneration.
Conformational Stability of Poly (N-Isopropylacrylamide) Anchored on the Surface of Gold Nanoparticles
Authors: Li Runmei , Cheng Cong , Wang Zhuorui , Gu Xuefan , Zhang Caixia , Wang Chen , Liang Xinyue , Hu Daodao
Published: January 2021

To verify the temperature sensitive failure of poly (N-isopropylacrylamide) (PNIPAM) anchored on the surface of gold nanoparticles (AuNPs), the UV-Vis spectra with temperature variations of the following aqueous solutions respectively containing AuNPs-PNIPAM, Au-PNIPAM/PNIPAM, PNIPAM, in different media (including salt, ethanol, HCl and cetyltrimethylammoniumbromide (CTAB)), were systematically determined. The results indicated that the UV-Vis spectrum of AuNPs-PNIPAM suspension hardly changed even above the Lower Critical Solution Temperature (LCST) of PNIPAM, but that of Au-PNIPAM/PNIPAM sharply increased only in absorbance intensity. A possible mechanism of the failed temperature sensitivity of PNIPAM anchored on the surface of AuNPs was proposed. Being different from free PNIPAM molecules, a strong interaction exists among PNIPAM molecules anchored on the surface of AuNPs, restraining the change in conformation of PNIPAM. The temperature sensitivity of Au-PNIPAM/PNIPAM originates from the free PNIPAM molecules rather than the anchored PNIPAM one. The changing electrostatic interaction could effectively regulate the aggregation behavior of AuNPs-PNIPAM and enhance its sensitivity to temperature.
Experimental Investigation into the Effect of Pyrolysis on Chemical Forms of Heavy Metals in Sewage Sludge Biochar (SSB), with Brief Ecological Risk Assessment
Authors: Li Binbin , Ding Songxiong , Fan Haihong , Ren Yu
Published: January 2021

Experimental investigations were carried out to study the effect of pyrolysis temperature on the characteristics, structure and total heavy metal contents of sewage sludge biochar (SSB). The changes in chemical forms of the heavy metals (Zn, Cu, Cr, Ni, Pb and Cd) caused by pyrolysis were analyzed, and the potential ecological risk of heavy metals in biochar (SSB) was evaluated. The conversion of sewage sludge into biochar by pyrolysis reduced the H/C and O/C ratios considerably, resulting in stronger carbonization and a higher degree of aromatic condensation in biochar. Measurement results showed that the pH and specific surface area of biochar increased as the pyrolysis temperature increased. It was found that elements Zn, Cu, Cr and Ni were enriched and confined in biochar SSB with increasing pyrolysis temperature from 300–700 °C; however, the residual rates of Pb and Cd in biochar SSB decreased significantly when the temperature was increased from 600 °C to 700 °C. Measurement with the BCR sequential extraction method revealed that the pyrolysis of sewage sludge at a suitable temperature transferred its bioavailable/degradable heavy metals into a more stable oxidizable/residual form in biochar SSB. Toxicity of heavy metals in biochar SSB could be reduced about four times if sewage sludge was pyrolyzed at a proper temperature; heavy metals confined in sludge SSB pyrolyzed at about 600 °C could be assessed as being low in ecological toxicity.
Material Model Development of Magnesium Alloy and Its Strength Evaluation
Authors: Huang Wenjia , Ma Ninshu , Ma Yunwu , Amaishi Toshiro , Takada Kenji , Hama Takayuki
Published: January 2021

A new material model of magnesium alloys, combining both Hill’48 yield function and Cazacu’06 yield function, was developed and programmed into LS-DYNA using user subroutine, in which both slip dominant and twinning/untwinning dominant hardening phenomena were included. First, a cyclic load test was performed, and its finite element analysis was carried out to verify the new material model. Then, the deformation behaviors of the magnesium crash box subjected to the compressive impact loading were investigated using the developed material model. Compared with the experimental results, the new material model accurately predicted the deformation characteristics of magnesium alloy parts. Additionally, the effect of the thickness distribution, initial deflection and contact friction coefficient in simulation models on deformation behaviors were investigated using this validated material model.
Microstructure and Mechanical Properties of Laser-Welded DP Steels Used in the Automotive Industry
Authors: He Hanbing , Forouzan Farnoosh , Volpp Joerg , Robertson Stephanie M. , Vuorinen Esa
Published: January 2021

The aim of this work was to investigate the microstructure and the mechanical properties of laser-welded joints combined of Dual Phase DP800 and DP1000 high strength thin steel sheets. Microstructural and hardness measurements as well as tensile and fatigue tests have been carried out. The welded joints (WJ) comprised of similar/dissimilar steels with similar/dissimilar thickness were consisted of different zones and exhibited similar microstructural characteristics. The trend of microhardness for all WJs was consistent, characterized by the highest value at hardening zone (HZ) and lowest at softening zone (SZ). The degree of softening was 20 and 8% for the DP1000 and DP800 WJ, respectively, and the size of SZ was wider in the WJ combinations of DP1000 than DP800. The tensile test fractures were located at the base material (BM) for all DP800 weldments, while the fractures occurred at the fusion zone (FZ) for the weldments with DP1000 and those with dissimilar sheet thicknesses. The DP800-DP1000 weldment presented similar yield strength (YS, 747 MPa) and ultimate tensile strength (UTS, 858 MPa) values but lower elongation (EI, 5.1%) in comparison with the DP800-DP800 weldment (YS 701 MPa, UTS 868 MPa, EI 7.9%), which showed similar strength properties as the BM of DP800. However, the EI of DP1000-DP1000 weldment was 1.9%, much lower in comparison with the BM of DP1000. The DP800-DP1000 weldment with dissimilar thicknesses showed the highest YS (955 MPa) and UTS (1075 MPa) values compared with the other weldments, but with the lowest EI (1.2%). The fatigue fractures occurred at the WJ for all types of weldments. The DP800-DP800 weldment had the highest fatigue limit (348 MPa) and DP800-DP1000 with dissimilar thicknesses had the lowest fatigue limit (<200 MPa). The fatigue crack initiated from the weld surface.
Acknowledgment to Reviewers of Mathematics in 2020
Authors:   Mathematics Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Mathematics maintains its standards for the high quality of its published papers [...]
Topsentinol L Trisulfate, a Marine Natural Product That Targets Basal-like and Claudin-Low Breast Cancers
Authors: El-Chaar Nader N. , Smith Thomas E. , Shrestha Gajendra , Piccolo Stephen R. , Harper Mary Kay , Van Wagoner Ryan M. , Lu Zhenyu , Venancio Ashlee R. , Ireland Chris M. , Bild Andrea H. , Moos Philip J.
Published: January 2021

Patients diagnosed with basal-like breast cancer suffer from poor prognosis and limited treatment options. There is an urgent need to identify new targets that can benefit patients with basal-like and claudin-low (BL-CL) breast cancers. We screened fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancers. We identified a previously unreported trisulfated sterol, i.e., topsentinol L trisulfate (TLT), which exhibited increased efficacy against BL-CL breast cancers relative to luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL cell lines revealed its ability to inhibit activation of AMP-activated protein kinase (AMPK) and checkpoint kinase 1 (CHK1) and to promote activation of p38. The importance of targeting AMPK and CHK1 in BL-CL cell lines was validated by treating a panel of breast cancer cell lines with known small molecule inhibitors of AMPK (dorsomorphin) and CHK1 (Ly2603618) and recording the increased effectiveness against BL-CL breast cancers as compared with luminal/HER2+ breast cancer. Finally, we generated a drug response gene-expression signature and projected it against a human tumor panel of 12 different cancer types to identify other cancer types sensitive to the compound. The TLT sensitivity gene-expression signature identified breast and bladder cancer as the most sensitive to TLT, while glioblastoma multiforme was the least sensitive.
Enhanced Recovery after Surgery (ERAS) for Hip and Knee Replacement—Why and How It Should Be Implemented Following the COVID-19 Pandemic
Authors: Wainwright Thomas W.
Published: January 2021

The COVID-19 pandemic has led to a reduction in hip and knee replacement surgery across healthcare systems. When regular operating returns, there will be a large volume of patients and an emphasis on a short hospital stay. Patients will be keen to return home, and capacity will need to maximised. Strategies to reduce the associated risks of surgery and to accelerate recovery will be needed, and so Enhanced Recovery after Surgery (ERAS) should be promoted as the model of care. ERAS protocols are proven to reduce hospital stay safely; however, ERAS pathways may require adaption to ensure both patient and staff safety. The risk of exposure to possible sources of COVID-19 should be limited, and so hospital visits should be minimised. The use of technology such as smartphone apps to provide pre-operative education, wearable activity trackers to assist with rehabilitation, and the use of telemedicine to complete outpatient appointments may be utilised. Also, units should be reminded that ERAS protocols are multi-modal, and every component is vital to minimise the surgical stress response. The focus should be on providing better and not just faster care. Units should learn from the past in order to expedite the implementation of or adaption of existing ERAS protocols. Strong leadership will be required, along with a supportive organisational culture, an inter-professional approach, and a recognised QI method should be used to contextualize improvement efforts.
Synthesis and Biological Evaluation of 99mTc(I) Tricarbonyl Complexes Dual-Targeted at Tumoral Mitochondria
Authors: Figueiredo Diogo , Fernandes Célia , Silva Francisco , Palma Elisa , Raposinho Paula , Belchior Ana , Vaz Pedro , Paulo António
Published: January 2021

For effective Auger therapy of cancer, the Auger-electron emitters must be delivered to the tumor cells in close proximity to a radiosensitive cellular target. Nuclear DNA is considered the most relevant target of Auger electrons to have augmented radiotoxic effects and significant cell death. However, there is a growing body of evidence that other targets, such as the mitochondria, could be relevant subcellular targets in Auger therapy. Thus, we developed dual-targeted 99mTc(I) tricarbonyl complexes containing a triphenylphosphonium (TPP) moiety to promote accumulation of 99mTc in the mitochondria, and a bombesin peptide to provide specificity towards the gastrin releasing peptide receptor (GRPr) overexpressed in prostate cancer cells. The designed dual-targeted complex, 99mTc-TPP-BBN, is efficiently internalized by human prostate cancer PC3 cells through a specific GRPr-mediated mechanism of uptake. Moreover, the radioconjugate provided an augmented accumulation of 99mTc in the mitochondria of the target tumor cells, most probably following its intracellular cleavage by cathepsin B. In addition, 99mTc-TPP-BBN showed an enhanced ability to reduce the survival of PC3 cells, in a dose-dependent manner.
Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia
Authors: Mitsunari Kensuke , Miyata Yasuyoshi , Matsuo Tomohiro , Mukae Yuta , Otsubo Asato , Harada Junki , Kondo Tsubasa , Matsuda Tsuyoshi , Ohba Kojiro , Sakai Hideki
Published: January 2021

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.
Characterization of Cross-Linked Enzyme Aggregates of the Y509E Mutant of a Glycoside Hydrolase Family 52 β-xylosidase from G. stearothermophilus
Authors: Romero Gabriela , Contreras Lellys M. , Aguirre Carolina , Wilkesman Jeff , Clemente-Jiménez Josefa María , Rodríguez-Vico Felipe , Las Heras-Vázquez Francisco Javier
Published: January 2021

Cross-linked enzyme aggregates (CLEAs) of the Y509E mutant of glycoside hydrolase family 52 β-xylosidase from Geobacillus stearothermophilus with dual activity of β-xylosidase and xylanase (XynB2Y509E) were prepared. Ammonium sulfate was used as the precipitant agent, and glutaraldehyde as cross-linking agent. The optimum conditions were found to be 90% ammonium sulfate, 12.5 mM glutaraldehyde, 3 h of cross-linking reaction at 25 °C, and pH 8.5. Under these (most effective) conditions, XynB2Y509E-CLEAs retained 92.3% of their original β-xylosidase activity. Biochemical characterization of both crude and immobilized enzymes demonstrated that the maximum pH and temperature after immobilization remained unchanged (pH 6.5 and 65 °C). Moreover, an improvement in pH stability and thermostability was also found after immobilization. Analysis of kinetic parameters shows that the Km value of XynB2Y509E-CLEAs obtained was slightly higher than that of free XynB2Y509E (1.2 versus 0.9 mM). Interestingly, the xylanase activity developed by the mutation was also conserved after the immobilization process.