bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Mobile Health and the Impact on Health-Related Quality of Life: Perceptions of Older Adults with Cognitive Impairment
Authors: Christiansen Line , Lindberg Catharina , Sanmartin Berglund Johan , Anderberg Peter , Skär Lisa
Published: April 2020

Digital health technologies such as mobile health (mHealth) are considered to have the potential to support the needs of older adults with cognitive impairment. However, the evidence for improving health with the use of mHealth applications is of limited quality. Few studies have reported on the consequences of technology use concerning the older adults’ quality of life. The purpose of this study was to describe perceptions of mHealth and its impact on health-related quality of life (HRQoL) among older adults with cognitive impairment. The study was conducted using a qualitative design with a phenomenographic approach. A total of 18 older participants with cognitive impairment were interviewed. The interviews were analyzed in order to apply phenomenography in a home-care context. The results showed variations in the older adults’ perceptions that were comprised within three categories of description; Require technology literacy, Maintain social interaction, and Facilitate independent living. In conclusion, the development and design of mHealth technologies need to be tailored based on older adults´ needs in order to be understood and perceived as useful in a home-care context. For mHealth to support HRQoL, healthcare should be provided in a way that encourages various forms of communication and interaction.
Benefits of Exercise on Influenza or Pneumonia in Older Adults: A Systematic Review
Authors: Song Yang , Ren Feng , Sun Dong , Wang Meizi , Baker Julien S. , István Bíró , Gu Yaodong
Published: April 2020

A coronavirus pandemic has recently become one of the greatest threats the world is facing. Older adults are under a high risk of infection because of weaker immune systems. Therefore, the purpose of this review is to summarize the recent scientific evidence that outlines the effects of exercise on influenza or pneumonia in older adults. An electronic literature search was conducted using the WEB OF SCIENCE, SCIENCEDIRECT and GOOGLE SCHOLAR databases using the following keywords, “Exercise,” “Older adult,” “Influenza,” and “Pneumonia.” Any randomized control trials, cross-sectional and observational studies that related to this topic were all included. Twenty studies met the eligibility criteria for this review. Thirteen randomized control trials investigated the effects of exercise on the immune responses to influenza or pneumonia vaccination: seven trials employed moderate aerobic exercise, three employed resistance exercise, and the remaining three used Asian martial arts or special home-based exercises. Five cross-sectional and two observational studies examined the associations between exercise/physical condition and influenza/pneumonia. Most of the current studies suggested that prolonged moderate aerobic exercise may help to reduce the risk of influenza-related infection and improve the immune responses to influenza or pneumonia vaccination in older adults. In addition, training in traditional Asian martial arts was also found to be beneficial. Future research should focus on the different effects of moderate and vigorous exercise on influenza-related diseases.
Inducible Polarized Secretion of Exosomes in T and B Lymphocytes
Authors: Calvo Victor , Izquierdo Manuel
Published: April 2020

Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to the plasma membrane. However, inducible exosome secretion controlled by cell surface receptors is restricted to very few cell types and a limited number of cell surface receptors. Among these, exosome secretion is induced in T lymphocytes and B lymphocytes when stimulated at the immune synapse (IS) via T-cell receptors (TCR) and B-cell receptors (BCR), respectively. IS formation by T and B lymphocytes constitutes a crucial event involved in antigen-specific, cellular, and humoral immune responses. Upon IS formation by T and B lymphocytes with antigen-presenting cells (APC), the convergence of MVB towards the microtubule organization center (MTOC), and MTOC polarization to the IS, are involved in polarized exosome secretion at the synaptic cleft. This specialized mechanism provides the immune system with a finely-tuned strategy to increase the specificity and efficiency of crucial secretory effector functions of B and T lymphocytes. As inducible exosome secretion by antigen-receptors is a critical and unique feature of the immune system this review considers the study of the traffic events leading to polarized exosome secretion at the IS and some of their biological consequences.
Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities
Authors: Opazo-Ríos Lucas , Mas Sebastián , Marín-Royo Gema , Mezzano Sergio , Gómez-Guerrero Carmen , Moreno Juan Antonio , Egido Jesús
Published: April 2020

Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Serum lipid abnormalities and renal ectopic lipid accumulation have been associated with the development of kidney diseases, in particular diabetic nephropathy. Chronic hyperinsulinemia, often seen in type 2 diabetes, plays a crucial role in blood and liver lipid metabolism abnormalities, thus resulting in increased non-esterified fatty acids (NEFA). Excessive lipid accumulation alters cellular homeostasis and activates lipogenic and glycogenic cell-signaling pathways. Recent evidences indicate that both quantity and quality of lipids are involved in renal damage associated to lipotoxicity by activating inflammation, oxidative stress, mitochondrial dysfunction, and cell-death. The pathological effects of lipotoxicity have been observed in renal cells, thus promoting podocyte injury, tubular damage, mesangial proliferation, endothelial activation, and formation of macrophage-derived foam cells. Therefore, this review examines the recent preclinical and clinical research about the potentially harmful effects of lipids in the kidney, metabolic markers associated with these mechanisms, major signaling pathways affected, the causes of excessive lipid accumulation, and the types of lipids involved, as well as offers a comprehensive update of therapeutic strategies targeting lipotoxicity.
Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets
Authors: Gandoy-Fieiras Nerea , Gonzalez-Juanatey Jose Ramon , Eiras Sonia
Published: April 2020

The main energy substrate of adult cardiomyocytes for their contractility are the fatty acids. Its metabolism generates high ATP levels at the expense of high oxygen consumption in the mitochondria. Under low oxygen supply, they can get energy from other substrates, mainly glucose, lactate, ketone bodies, etc., but the mitochondrial dysfunction, in pathological conditions, reduces the oxidative metabolism. In consequence, fatty acids are stored into epicardial fat and its accumulation provokes inflammation, insulin resistance, and oxidative stress, which enhance the myocardium dysfunction. Some therapies focused on improvement the fatty acids entry into mitochondria have failed to demonstrate benefits on cardiovascular disorders. Oppositely, those therapies with effects on epicardial fat volume and inflammation might improve the oxidative metabolism of myocardium and might reduce the cardiovascular disease progression. This review aims at explain (a) the energy substrate adaptation of myocardium in physiological conditions, (b) the reduction of oxidative metabolism in pathological conditions and consequences on epicardial fat accumulation and insulin resistance, and (c) the reduction of cardiovascular outcomes after regulation by some therapies.
Promising Perspectives for Detection, Identification, and Quantification of Plant Pathogenic Fungi and Oomycetes through Targeting Mitochondrial DNA
Authors: Kulik Tomasz , Bilska Katarzyna , Żelechowski Maciej
Published: April 2020

Fungi and oomycetes encompass many pathogens affecting crops worldwide. Their effective control requires screening pathogens across the local and international trade networks along with the monitoring of pathogen inocula in the field. Fundamentals to all of these concerns are their efficient detection, identification, and quantification. The use of molecular markers showed the best promise in the field of plant pathogen diagnostics. However, despite the unquestionable benefits of DNA-based methods, two significant limitations are associated with their use. The first limitation concerns the insufficient level of sensitivity due to the very low and uneven distribution of pathogens in plant material. The second limitation pertains to the inability of widely used diagnostic assays to detect cryptic species. Targeting mtDNA appears to provide a solution to these challenges. Its high copy number in microbial cells makes mtDNA an attractive target for developing highly sensitive assays. In addition, previous studies on different pathogen taxa indicated that mitogenome sequence variation could improve cryptic species delimitation accuracy. This review sheds light on the potential application of mtDNA for pathogen diagnostics. This paper covers a brief description of qPCR and DNA barcoding as two major strategies enabling the diagnostics of plant pathogenic fungi and oomycetes. Both strategies are discussed along with the potential use of mtDNA, including their strengths and weaknesses.
Multifaceted Role of PRDM Proteins in Human Cancer
Authors: Casamassimi Amelia , Rienzo Monica , Di Zazzo Erika , Sorrentino Anna , Fiore Donatella , Proto Maria Chiara , Moncharmont Bruno , Gazzerro Patrizia , Bifulco Maurizio , Abbondanza Ciro
Published: April 2020

The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.
The Role of Taste Receptor mTAS1R3 in Chemical Communication of Gametes
Authors: Frolikova Michaela , Otcenaskova Tereza , Valasková Eliska , Postlerova Pavla , Stopkova Romana , Stopka Pavel , Komrskova Katerina
Published: April 2020

Fertilization is a multiple step process leading to the fusion of female and male gametes and the formation of a zygote. Besides direct gamete membrane interaction via binding receptors localized on both oocyte and sperm surface, fertilization also involves gamete communication via chemical molecules triggering various signaling pathways. This work focuses on a mouse taste receptor, mTAS1R3, encoded by the Tas1r3 gene, as a potential receptor mediating chemical communication between gametes using the C57BL/6J lab mouse strain. In order to specify the role of mTAS1R3, we aimed to characterize its precise localization in testis and sperm using super resolution microscopy. The testis cryo-section, acrosome-intact sperm released from cauda epididymis and sperm which underwent the acrosome reaction (AR) were evaluated. The mTAS1R3 receptor was detected in late spermatids where the acrosome was being formed and in the acrosomal cap of acrosome intact sperm. AR is triggered in mice during sperm maturation in the female reproductive tract and by passing through the egg surroundings such as cumulus oophorus cells. This AR onset is independent of the extracellular matrix of the oocyte called zona pellucida. After AR, the relocation of mTAS1R3 to the equatorial segment was observed and the receptor remained exposed to the outer surroundings of the female reproductive tract, where its physiological ligand, the amino acid L-glutamate, naturally occurs. Therefore, we targeted the possible interaction in vitro between the mTAS1R3 and L-glutamate as a part of chemical communication between sperm and egg and used an anti-mTAS1R3-specific antibody to block it. We detected that the acrosome reacted spermatozoa showed a chemotactic response in the presence of L-glutamate during and after the AR, and it is likely that mTAS1R3 acted as its mediator.
The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance
Authors: Cheng Kuang-Ting , Wu Chih-Lung , Yip Bak-Sau , Chih Ya-Han , Peng Kuang-Li , Hsu Su-Ya , Yu Hui-Yuan , Cheng Jya-Wei
Published: April 2020

In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.
Hypoxia, Inflammation and Necrosis as Determinants of Glioblastoma Cancer Stem Cells Progression
Authors: Papale Marco , Buccarelli Mariachiara , Mollinari Cristiana , Russo Matteo A. , Pallini Roberto , Ricci-Vitiani Lucia , Tafani Marco
Published: April 2020

Tumor hypoxic microenvironment causes hypoxia inducible factor 1 alpha (HIF-1α) activation and necrosis with alarmins release. Importantly, HIF-1α also controls the expression of alarmin receptors in tumor cells that can bind to and be activated by alarmins. Human tumor tissues possess 1–2% of cancer stem cells (CSCs) residing in hypoxic niches and responsible for the metastatic potential of tumors. Our hypothesis is that hypoxic CSCs express alarmin receptors that can bind alarmins released during necrosis, an event favoring CSCs migration. To investigate this aspect, glioblastoma stem-like cell (GSC) lines were kept under hypoxia to determine the expression of hypoxic markers as well as receptor for advanced glycation end products (RAGE). The presence of necrotic extracts increased migration, invasion and cellular adhesion. Importantly, HIF-1α inhibition by digoxin or acriflavine prevented the response of GSCs to hypoxia alone or plus necrotic extracts. In vivo, GSCs injected in one brain hemisphere of NOD/SCID mice were induced to migrate to the other one in which a necrotic extract was previously injected. In conclusion, our results show that hypoxia is important not only for GSCs maintenance but also for guiding their response to external necrosis. Inhibition of hypoxic pathway may therefore represent a target for preventing brain invasion by glioblastoma stem cells (GSCs).
Cerebrospinal Fluid Neurofilament Light Chain Is Associated with Kynurenine Pathway Metabolite Changes in Multiple Sclerosis
Authors: Rajda Cecilia , Galla Zsolt , Polyák Helga , Maróti Zoltán , Babarczy Kristóf , Pukoli Dániel , Vécsei László
Published: April 2020

Neurofilament light (NFL) has proved to be a good prognostic factor in multiple sclerosis (MS), as its level is proportionally elevated with extended neuraxonal damage. The involvement of the kynurenine pathway in neuroinflammation has been proved. The precursor of this pathway is the essential amino acid tryptophan, which is catabolized 95% towards kynurenine metabolites. Quinolinic acid (QUIN) within the brain is only produced in activated microglia and macrophages, leading to axonal degeneration via the activation of N-Methyl-D-aspartate receptors. Neopterin is a biomarker for inflammation produced by macrophages. The association of these biomarkers has not previously been investigated. Our aim was to assess whether there is an association of the neurodegenerative biomarker NFL with the markers of neuroinflammation, e.g., kynurenine metabolites and neopterin, in the cerebrospinal fluid (CSF). CSF samples of patients with MS (pwMS; n = 37) and age-matched controls (n = 22) were compared for NFL levels by ELISA, while the kynurenine pathway metabolites tryptophan and neopterin were detected with mass spectrometry. Spearman’s correlation showed that NFL is an independent predictor of neurological disability in the MS group. Significant correlations were found between NFL, neopterin, and QUIN, and between kynurenine and neopterin. Receiver operating characteristic (ROC) curve analysis was used to plot the top three best predictors of MS-related disability that yielded the best specificity and sensitivity. Normalized NFL (AUC: 0.923), QUIN (AUC: 0.803), and neopterin (AUC: 0.843) were the best independent predictors of neurological disability in pwMS. The CSF NFL and CSF QUIN, together with neopterin, were elevated in the CSF of pwMS compared to controls. The combination of the neurodegenerative biomarkers together with biomarkers of neuroinflammation could provide additional information on the underlying pathomechanism of disease activity, which is essential for the identification of patients at risk of developing cumulative disabilities.
Transcriptional Profiling of the Probiotic Escherichia coli Nissle 1917 Strain under Simulated Microgravity
Authors: Yim Jaewoo , Cho Sung Won , Kim Beomhee , Park Sungwoo , Han Yong Hee , Seo Sang Woo
Published: April 2020

Long-term space missions affect the gut microbiome of astronauts, especially the viability of some pathogens. Probiotics may be an effective solution for the management of gut microbiomes, but there is a lack of studies regarding the physiology of probiotics in microgravity. Here, we investigated the effects of microgravity on the probiotic Escherichia coli Nissle 1917 (EcN) by comparing transcriptomic data during exponential and stationary growth phases under simulated microgravity and normal gravity. Microgravity conditions affected several physiological features of EcN, including its growth profile, biofilm formation, stress responses, metal ion transport/utilization, and response to carbon starvation. We found that some changes, such as decreased adhesion ability and acid resistance, may be disadvantageous to EcN relative to gut pathogens under microgravity, indicating the need to develop probiotics optimized for space flight.
HPV Infection Significantly Accelerates Glycogen Metabolism in Cervical Cells with Large Nuclei: Raman Microscopic Study with Subcellular Resolution
Authors: Sitarz Katarzyna , Czamara Krzysztof , Bialecka Joanna , Klimek Malgorzata , Zawilinska Barbara , Szostek Slawa , Kaczor Agnieszka
Published: April 2020

Using Raman microscopy, we investigated epithelial cervical cells collected from 96 women with squamous cell carcinoma (SCC) or belonging to groups I, IIa, IIID-1 and IIID-2 according to Munich III classification (IIID-1 and IIID-2 corresponding to Bethesda LSIL and HSIL groups, respectively). All women were tested for human papillomavirus (HPV) infection using PCR. Subcellular resolution of Raman microscopy enabled to understand phenotypic differences in a heterogeneous population of cervical cells in the following groups: I/HPV−, IIa/HPV−, IIa/HPV−, LSIL/HPV−, LSIL/HPV+, HSIL/HPV−, HSIL/HPV+ and cancer cells (SCC/HPV+). We showed for the first time that the glycogen content in the cytoplasm decreased with the nucleus size of cervical cells in all studied groups apart from the cancer group. For the subpopulation of large-nucleus cells HPV infection resulted in considerable glycogen depletion compared to HPV negative cells in IIa, LSIL (for both statistical significance, ca. 45%) and HSIL (trend, 37%) groups. We hypothesize that accelerated glycogenolysis in large-nucleus cells may be associated with the increased protein metabolism for HPV positive cells. Our work underlines unique capabilities of Raman microscopy in single cell studies and demonstrate potential of Raman-based methods in HPV diagnostics.
Immediate or Delayed Transplantation of a Vein Conduit Filled with Nasal Olfactory Stem Cells Improves Locomotion and Axogenesis in Rats after a Peroneal Nerve Loss of Substance
Authors: Bonnet Maxime , Guiraudie-Capraz Gaëlle , Marqueste Tanguy , Garcia Stéphane , Jaloux Charlotte , Decherchi Patrick , Féron François
Published: April 2020

Over the recent years, several methods have been experienced to repair injured peripheral nerves. Among investigated strategies, the use of natural or synthetic conduits was validated for clinical application. In this study, we assessed the therapeutic potential of vein guides, transplanted immediately or two weeks after a peroneal nerve injury and filled with olfactory ecto-mesenchymal stem cells (OEMSC). Rats were randomly allocated to five groups. A3 mm peroneal nerve loss was bridged, acutely or chronically, with a 1 cm long femoral vein and with/without OEMSCs. These four groups were compared to unoperated rats (Control group). OEMSCs were purified from male olfactory mucosae and grafted into female hosts. Three months after surgery, nerve repair was analyzed by measuring locomotor function, mechanical muscle properties, muscle mass, axon number, and myelination. We observed that stem cells significantly (i) increased locomotor recovery, (ii) partially maintained the contractile phenotype of the target muscle, and (iii) augmented the number of growing axons. OEMSCs remained in the nerve and did not migrate in other organs. These results open the way for a phase I/IIa clinical trial based on the autologous engraftment of OEMSCs in patients with a nerve injury, especially those with neglected wounds.
Atopic Dermatitis: Identification and Management of Complicating Factors
Authors: Tamagawa-Mineoka Risa , Katoh Norito
Published: April 2020

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, associated with impaired skin barrier function and an atopic background. Various complicating factors, such as irritants, aeroallergens, food, microbial organisms, contact allergens, sweat, and scratching can induce the development of AD symptoms. Irritants, including soap/shampoo and clothes, can cause itching and eczematous lesions. In addition, young children with AD tend to become sensitized to eggs, milk, or peanuts, while older children and adults more often become sensitized to environmental allergens, such as house dust mites (HDM), animal dander, or pollen. Serum-specific IgE levels and skin prick test reactions to food tend to show high negative predictive values and low specificity and positive predictive values for diagnosing food allergy. On the other hand, AD adult patients tend to have severe skin symptoms and exhibit high HDM-specific IgE levels. Microbial organisms, e.g., Staphylococcus aureus and Malassezia furfur, might contribute to the pathogenetic mechanisms of AD. While sweat plays a major role in maintaining skin homeostasis, it can become an aggravating factor in patients with AD. Furthermore, scratching often exacerbates eczematous lesions. Several patient-specific complicating factors are seen in most cases. The identification and management of complicating factors are important for controlling AD.
Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling
Authors: Kim Sang Jin , Shin Min Jea , Kim Dae Won , Yeo Hyeon Ji , Yeo Eun Ji , Choi Yeon Joo , Sohn Eun Jeong , Han Kyu Hyung , Park Jinseu , Lee Keun Wook , Park Jong Kook , Cho Yong-Jun , Kim Duk-Soo , Eum Won Sik , Choi Soo Young
Published: April 2020

Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on H2O2-induced HT-22 cell death and in an animal ischemia model were investigated. Transduced Tat-BLVRA markedly inhibited cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibited the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passed through the blood-brain barrier (BBB) and significantly prevented hippocampal cell death in an ischemic model. These results suggest that Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia.
Modes of Communication between T Cells and Relevance for Immune Responses
Authors: Uhl Lion F. K. , Gérard Audrey
Published: April 2020

T cells are essential mediators of the adaptive immune system, which constantly patrol the body in search for invading pathogens. During an infection, T cells that recognise the pathogen are recruited, expand and differentiate into subtypes tailored to the infection. In addition, they differentiate into subsets required for short and long-term control of the pathogen, i.e., effector or memory. T cells have a remarkable degree of plasticity and heterogeneity in their response, however, their overall response to a given infection is consistent and robust. Much research has focused on how individual T cells are activated and programmed. However, in order to achieve a critical level of population-wide reproducibility and robustness, neighbouring cells and surrounding tissues have to provide or amplify relevant signals to tune the overall response accordingly. The characteristics of the immune response—stochastic on the individual cell level, robust on the global level—necessitate coordinated responses on a system-wide level, which facilitates the control of pathogens, while maintaining self-tolerance. This global coordination can only be achieved by constant cellular communication between responding cells, and faults in this intercellular crosstalk can potentially lead to immunopathology or autoimmunity. In this review, we will discuss how T cells mount a global, collective response, by describing the modes of T cell-T cell (T-T) communication they use and highlighting their physiological relevance in programming and controlling the T cell response.
Nuclear Functions of the Tyrosine Kinase Src
Authors: Bagnato Giulia , Leopizzi Martina , Urciuoli Enrica , Peruzzi Barbara
Published: April 2020

Src is the representative member of the Src-family kinases (SFKs), a group of tyrosine kinases involved in several cellular processes. Its main function has been for long confined to the plasma membrane/cytoplasm compartment, being a myristoylated protein anchored to the cell membrane and functioning downstream to receptors, most of them lacking intrinsic kinase activity. In the last decades, new roles for some SFKs have been described in the nuclear compartment, suggesting that these proteins can also be involved in directly regulating gene transcription or nucleoskeleton architecture. In this review, we focused on those nuclear functions specifically attributable to Src, by considering its function as both tyrosine kinase and adapting molecule. In particular, we addressed the Src involvement in physiological as well as in pathological conditions, especially in tumors.
Construction of a Lectin–Glycan Interaction Network from Enterohemorrhagic Escherichia coli Strains by Multi-omics Analysis
Authors: Cho Seung-Hak , Lee Kang Mo , Kim Cheorl-Ho , Kim Sung Soon
Published: April 2020

Enterohemorrhagic Escherichia coli (EHEC) causes hemorrhagic colitis and hemolytic uremic syndrome. EHEC infection begins with bacterial adherence to the host intestine via lectin-like adhesins that bind to the intestinal wall. However, EHEC-related lectin–glycan interactions (LGIs) remain unknown. Here, we conducted a genome-wide investigation of putative adhesins to construct an LGI network. We performed microarray-based transcriptomic and proteomic analyses with E. coli EDL933. Using PSORTb-based analysis, potential outer-membrane-embedded adhesins were predicted from the annotated genes of 318 strains. Predicted proteins were classified using TMHMM v2.0, SignalP v5.0, and LipoP v1.0. Functional and protein–protein interaction analyses were performed using InterProScan and String databases, respectively. Structural information of lectin candidate proteins was predicted using Iterative Threading ASSEmbly Refinement (I-TASSER) and Spatial Epitope Prediction of Protein Antigens (SEPPA) tools based on 3D structure and B-cell epitopes. Pathway analysis returned 42,227 Gene Ontology terms; we then selected 2585 lectin candidate proteins by multi-omics analysis and performed homology modeling and B-cell epitope analysis. We predicted a total of 24,400 outer-membrane-embedded proteins from the genome of 318 strains and integrated multi-omics information into the genomic information of the proteins. Our integrated multi-omics data will provide a useful resource for the construction of LGI networks of E. coli.
Understanding the Action of RARγ Agonists on Human Osteochondroma Explants
Authors: Garcia Sonia A. , Tian Hongying , Imamura-Kawasawa Yuka , Fisher Aidan , Cellini Ashley , Codd Casey , Herzenberg John E. , Abzug Joshua M. , Ng Vincent , Iwamoto Masahiro , Enomoto-Iwamoto Motomi
Published: April 2020

Osteochondromas are cartilage-capped growths located proximate to the physis that can cause skeletal deformities, pain, limited motion, and neurovascular impingement. Previous studies have demonstrated retinoic acid receptor gamma (RARγ) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RARγ agonists can target on established osteochondromas. The purpose of this study was to examine the action of RARγ agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RARγ agonists or vehicles. Gene expression analysis confirmed the up-regulation of RARγ target genes in the explants treated with NRX 204647 and Palovarotene and revealed strong inhibition of cartilage matrix and increased extracellular matrix proteases gene expression. In addition, immunohistochemical staining for the neoepitope of protease-cleaved aggrecan indicated that RARγ agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RARγ agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RARγ agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RARγ agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.
Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy
Authors: Chen Huai-An , Ma Yunn-Hwa , Hsu Tzu-Yuan , Chen Jyh-Ping
Published: April 2020

Recombinant tissue plasminogen activator (rtPA) is the only thrombolytic agent that has been approved by the FDA for treatment of ischemic stroke. However, a high dose intravenous infusion is required to maintain effective drug concentration, owing to the short half-life of the thrombolytic drug, whereas a momentous limitation is the risk of bleeding. We envision a dual targeted strategy for rtPA delivery will be feasible to minimize the required dose of rtPA for treatment. For this purpose, rtPA and fibrin-avid peptide were co-immobilized to poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (PMNP) to prepare peptide/rtPA conjugated PMNPs (pPMNP-rtPA). During preparation, PMNP was first surface modified with avidin, which could interact with biotin. This is followed by binding PMNP-avidin with biotin-PEG-rtPA (or biotin-PEG-peptide), which was prepared beforehand by binding rtPA (or peptide) to biotin-PEG-maleimide while using click chemistry between maleimide and the single –SH group in rtPA (or peptide). The physicochemical property characterization indicated the successful preparation of the magnetic nanoparticles with full retention of rtPA fibrinolysis activity, while biological response studies underlined the high biocompatibility of all magnetic nanoparticles from cytotoxicity and hemolysis assays in vitro. The magnetic guidance and fibrin binding effects were also confirmed, which led to a higher thrombolysis rate in vitro using PMNP-rtPA or pPMNP-rtPA when compared to free rtPA after static or dynamic incubation with blood clots. Using pressure-dependent clot lysis model in a flow system, dual targeted pPMNP-rtPA could reduce the clot lysis time for reperfusion by 40% when compared to free rtPA at the same drug dosage. From in vivo targeted thrombolysis in a rat embolic model, pPMNP-rtPA was used at 20% of free rtPA dosage to restore the iliac blood flow in vascular thrombus that was created by injecting a blood clot to the hind limb area.
Checkpoint Kinase 1 (CHK1) Inhibition Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Proton Irradiation via Rad51 Downregulation
Authors: Choi Changhoon , Cho Won Kyung , Park Sohee , Shin Sung-Won , Park Won , Kim Haeyoung , Choi Doo Ho
Published: April 2020

Due to a superior dose conformity to the target, proton beam therapy (PBT) continues to rise in popularity. Recently, considerable efforts have been directed toward discovering treatment options for use in combination with PBT. This study aimed to investigate the targeting of checkpoint kinase 1 (CHK1), a critical player regulating the G2/M checkpoint, as a promising strategy to potentiate PBT in human triple-negative breast cancer (TNBC) cells. Protons induced cell-cycle arrest at the G2/M checkpoint more readily in response to increased CHK1 activation than X-rays. A clonogenic survival assay revealed that CHK1 inhibition using PF-477736 or small interfering RNA (siRNA) enhanced the sensitivity toward protons to a greater extent than toward X-rays. Western blotting demonstrated that PF-477736 treatment in the background of proton irradiation increased the pro-apoptotic signaling, which was further supported by flow cytometry using annexin V. Immunofluorescence revealed that proton-induced DNA double-strand breaks (DSBs) were further enhanced by PF-477736, which was linked to the downregulation of Rad51, essential for the homologous recombination repair of DSBs. Direct inactivation of Rad51 resulted in enhanced proton sensitization. Collectively, these data suggest that targeting CHK1 may be a promising approach for improving PBT efficacy in the treatment of TNBC.
Transgenic Breeding Approaches for Improving Abiotic Stress Tolerance: Recent Progress and Future Perspectives
Authors: Anwar Ali , Kim Ju-Kon
Published: April 2020

The recent rapid climate changes and increasing global population have led to an increased incidence of abiotic stress and decreased crop productivity. Environmental stresses, such as temperature, drought, nutrient deficiency, salinity, and heavy metal stresses, are major challenges for agriculture, and they lead to a significant reduction in crop growth and productivity. Abiotic stress is a very complex phenomenon, involving a variety of physiological and biochemical changes in plant cells. Plants exposed to abiotic stress exhibit enhanced levels of ROS (reactive oxygen species), which are highly reactive and toxic and affect the biosynthesis of chlorophyll, photosynthetic capacity, and carbohydrate, protein, lipid, and antioxidant enzyme activities. Transgenic breeding offers a suitable alternative to conventional breeding to achieve plant genetic improvements. Over the last two decades, genetic engineering/transgenic breeding techniques demonstrated remarkable developments in manipulations of the genes for the induction of desired characteristics into transgenic plants. Transgenic approaches provide us with access to identify the candidate genes, miRNAs, and transcription factors (TFs) that are involved in specific plant processes, thus enabling an integrated knowledge of the molecular and physiological mechanisms influencing the plant tolerance and productivity. The accuracy and precision of this phenomenon assures great success in the future of plant improvements. Hence, transgenic breeding has proven to be a promising tool for abiotic stress improvement in crops. This review focuses on the potential and successful applications, recent progress, and future perspectives of transgenic breeding for improving abiotic stress tolerance and productivity in plants.
Comprehensive Analysis of Autophagy-Related Genes in Sweet Orange (Citrus sinensis) Highlights Their Roles in Response to Abiotic Stresses
Authors: Fu Xing-Zheng , Zhou Xue , Xu Yuan-Yuan , Hui Qiu-Ling , Chun Chang-Pin , Ling Li-Li , Peng Liang-Zhi
Published: April 2020

Autophagy is a highly conserved intracellular degradation pathway that breaks down damaged macromolecules and/or organelles. It is involved in plant development and senescence, as well as in biotic and abiotic stresses. However, the autophagy process and related genes are largely unknown in citrus. In this study, we identified 35 autophagy-related genes (CsATGs—autophagy-related genes (ATGs) of Citrus sinensis, Cs) in a genome-wide manner from sweet orange (Citrus sinensis). Bioinformatic analysis showed that these CsATGs were highly similar to Arabidopsis ATGs in both sequence and phylogeny. All the CsATGs were randomly distributed on nine known (28 genes) and one unknown (7 genes) chromosomes. Ten CsATGs were predicted to be segmental duplications. Expression patterns suggested that most of the CsATG were significantly up- or down-regulated in response to drought; cold; heat; salt; mannitol; and excess manganese, copper, and cadmium stresses. In addition, two ATG18 members, CsATG18a and CsATG18b, were cloned from sweet orange and ectopically expressed in Arabidopsis. The CsATG18a and CsATG18b transgenic plants showed enhanced tolerance to osmotic stress, salt, as well as drought (CsATG18a) or cold (CsATG18b), compared to wild-type plants. These results highlight the essential roles of CsATG genes in abiotic stresses.
Systematic Review of Platelet-Rich Plasma Use in Androgenetic Alopecia Compared with Minoxidil®, Finasteride®, and Adult Stem Cell-Based Therapy
Authors: Gentile Pietro , Garcovich Simone
Published: April 2020

The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®.
Applying the ETL Process to Blockchain Data. Prospect and Findings
Authors: Galici Roberta , Ordile Laura , Marchesi Michele , Pinna Andrea , Tonelli Roberto
Published: April 2020

We present a novel strategy, based on the Extract, Transform and Load (ETL) process, to collect data from a blockchain, elaborate and make it available for further analysis. The study aims to satisfy the need for increasingly efficient data extraction strategies and effective representation methods for blockchain data. For this reason, we conceived a system to make scalable the process of blockchain data extraction and clustering, and to provide a SQL database which preserves the distinction between transaction and addresses. The proposed system satisfies the need to cluster addresses in entities, and the need to store the extracted data in a conventional database, making possible the data analysis by querying the database. In general, ETL processes allow the automation of the operation of data selection, data collection and data conditioning from a data warehouse, and produce output data in the best format for subsequent processing or for business. We focus on the Bitcoin blockchain transactions, which we organized in a relational database to distinguish between the input section and the output section of each transaction. We describe the implementation of address clustering algorithms specific for the Bitcoin blockchain and the process to collect and transform data and to load them in the database. To balance the input data rate with the elaboration time, we manage blockchain data according to the lambda architecture. To evaluate our process, we first analyzed the performances in terms of scalability, and then we checked its usability by analyzing loaded data. Finally, we present the results of a toy analysis, which provides some findings about blockchain data, focusing on a comparison between the statistics of the last year of transactions, and previous results of historical blockchain data found in the literature. The ETL process we realized to analyze blockchain data is proven to be able to perform a reliable and scalable data acquisition process, whose result makes stored data available for further analysis and business.
The Effect of Increasing Topsoil Disturbance on Surface-Active Invertebrate Composition and Abundance under Grazing and Cropping Regimes on Vertisols in North-West New South Wales, Australia
Authors: Nkem Johnson N. , Lobry de Bruyn Lisa , King Kathleen
Published: April 2020

Agricultural intensification practices involve varying degrees of disturbance to the soil ecosystem. This study evaluated six agricultural management regimes with increasing levels of topsoil disturbance, on the composition and abundance of surface-active invertebrates on Vertisols at a sub-catchment scale. Two grazing (native and introduced pastures), and four cropping (combining short and long fallow, with zero and conventional tillage) management regimes were examined. Surface-active invertebrates were collected seasonally with pitfall traps over 2 years (8 seasons), and identified to order, while ants (Formicidae) that comprised 47% of total invertebrates collected, were identified to genera. Season had a significant effect on ant abundance and number of genera recorded with higher abundance and twice the number of genera in summer than all other seasons. Ants, particularly Iridomyrmex, were mainly active in summer, while other invertebrates especially Coleoptera, were more active in winter. Surface-active invertebrates were 30% more abundant in grazing than cropping land use types. Native pasture, with little surface soil disturbance, recorded the highest number of invertebrates, mainly ants, compared to other agricultural management regimes. Coleoptera and Dermaptera were higher in abundance under conventional tillage compared with those agricultural management regimes that disturb the topsoil less. Optimizing surface-active invertebrate activity on Vertisols for most taxa will require reducing topsoil disturbance. However, the research findings also suggest that the impact of agricultural management regimes on invertebrate activity was difficult to predict with any certainty as the three main ant genera, and most abundant invertebrate collected, did not respond in a consistent manner.
Behavioral and Electrophysiological Responses of the Fringed Larder Beetle Dermestes frischii to the Smell of a Cadaver at Different Decomposition Stages
Authors: Martin Clément , Minchilli Damien , Francis Frédéric , Verheggen François
Published: April 2020

A cadaver is colonized by a wide diversity of necrophagous insects. It is well documented that Dipterans are attracted by the volatile organic compounds (VOCs) released by a corpse during the first minutes following death. Coleopterans are known to be attracted by highly decomposed cadavers, but have received less attention regarding the olfaction-based mechanisms underlying these interactions. In the present study, we impregnated gauzes with VOCs collected from each decomposition stage of dead rats: fresh, bloated, active, and advanced decay. We collected the VOCs released by the gauze and confirmed what was previously know from the literature: the decomposition stages are associated with contrasting chemical profiles. We exposed Dermestes frischii Kugelann (Coleoptera: Dermestidae) male and female antennae to the same gauzes and found that stronger electrical responses were recorded when using the smell of the advanced decay stage. Finally, we performed two choices behavioral assays. Females showed no preference for the four decomposition stages, while males were attracted by the smell associated with active and advanced decay stages. These results suggest that specific VOCs released by a decaying body guide necrophagous coleopterans to their feeding site. Whether D. frischii males release pheromones to attract females remains to be tested.