bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Internet Addiction with Adolescents’ Lifestyle: A National School-Based Survey
Authors: Ying Ying Chan , Awaluddin S Maria , Kuang Kuay Lim , Siew Man Cheong , Baharudin Azli , Miaw Yn Ling , Sahril Norhafizah , Omar Mohd Azahadi , Ahmad Noor Ani , Ibrahim Normala
Published: December 2020

Internet addiction (IA) among adolescents is an issue of growing concern with adverse effects on adolescents’ health and social functioning. This study aims to determine the prevalence of IA among school-going adolescents in Malaysia and its associated factors—specifically, lifestyle factors. A nationwide cross-sectional school-based health survey was conducted in 2017 among 27,497 students from 212 randomly selected secondary schools. Information regarding sociodemography, lifestyle, and internet use was obtained using a self-administered questionnaire. IA was measured using the Malay Version of Internet Addiction Test (MVIAT). The prevalence of internet addiction was 29.0%. A multivariable logistic analysis revealed that inadequate fruit and vegetable intakes, consumed carbonated soft drinks at least once a day, consumed fast food at least three days/week, sedentary behavior, current E-cigarette users, and ever/current alcohol drinkers were lifestyle factors significantly associated with IA. Adolescents from urban schools, of higher school grade, and those whose parents are married but living apart were also found to have a greater risk for internet addiction. A positive association was found between IA with unhealthy dietary and lifestyle behaviors among adolescents. The modification of lifestyle factors needs to be considered while developing strategies and interventions for awareness-raising and prevention of IA among adolescents.
Assessing the Respiratory Effects of Air Pollution from Biomass Cookstoves on Pregnant Women in Rural India
Authors: Parikh Raj , Rao Sowmya R. , Kukde Rakesh , O'Connor George T. , Patel Archana , Hibberd Patricia L.
Published: December 2020

Background: In India, biomass fuel is burned in many homes under inefficient conditions, leading to a complex milieu of particulate matter and environmental toxins known as household air pollution (HAP). Pregnant women are particularly vulnerable as they and their fetus may suffer from adverse consequences of HAP. Fractional exhaled nitric oxide (FeNO) is a noninvasive, underutilized tool that can serve as a surrogate for airway inflammation. We evaluated the prevalence of respiratory illness, using pulmonary questionnaires and FeNO measurements, among pregnant women in rural India who utilize biomass fuel as a source of energy within their home. Methods: We prospectively studied 60 pregnant women in their 1st and 2nd trimester residing in villages near Nagpur, Central India. We measured FeNO levels in parts per billion (ppb), St. George’s Respiratory Questionnaire (SGRQ-C) scores, and the Modified Medical Research Council (mMRC) Dyspnea Scale. We evaluated the difference in the outcome distributions between women using biomass fuels and those using liquefied petroleum gas (LPG) using two-tailed t-tests. Results: Sixty-five subjects (32 in Biomass households; 28 in LPG households; 5 unable to complete) were enrolled in the study. Age, education level, and second-hand smoke exposure were comparable between both groups. FeNO levels were higher in the Biomass vs. LPG group (25.4 ppb vs. 8.6 ppb; p-value = 0.001). There was a difference in mean composite SGRQ-C score (27.1 Biomass vs. 10.8 LPG; p-value < 0.001) including three subtotal scores for Symptoms (47.0 Biomass vs. 20.2 LPG; p-value< 0.001), Activity (36.4 Biomass vs. 16.5 LPG; p-value < 0.001) and Impact (15.9 Biomass vs. 5.2 LPG; p-value < 0.001). The mMRC Dyspnea Scale was higher in the Biomass vs. LPG group as well (2.9 vs. 0.5; p < 0.001). Conclusion: Increased FeNO levels and higher dyspnea scores in biomass-fuel-exposed subjects confirm the adverse respiratory effects of this exposure during pregnancy. More so, FeNO may be a useful, noninvasive biomarker of inflammation that can help better understand the physiologic effects of biomass smoke on pregnant women. In the future, larger studies are needed to characterize the utility of FeNO in a population exposed to HAP.
Public Health Impact of Using Biosimilars, Is Automated Follow up Relevant?
Authors: Perpoil Antoine , Grimandi Gael , Birklé Stéphane , Simonet Jean-François , Chiffoleau Anne , Bocquet François
Published: December 2020

Biologic reference drugs and their copies, biosimilars, have a complex structure. Biosimilars need to demonstrate their biosimilarity during development but unpredictable variations can remain, such as micro-heterogeneity. The healthcare community may raise questions regarding the clinical outcomes induced by this micro-heterogeneity. Indeed, unwanted immune reactions may be induced for numerous reasons, including product variations. However, it is challenging to assess these unwanted immune reactions because of the multiplicity of causes and potential delays before any reaction. Moreover, safety assessments as part of preclinical studies and clinical trials may be of limited value with respect to immunogenicity assessments because they are performed on a standardised population during a limited period. Real-life data could therefore supplement the assessments of clinical trials by including data on the real-life use of biosimilars, such as switches. Furthermore, real-life data also include any economic incentives to prescribe or use biosimilars. This article raises the question of relevance of automating real life data processing regarding Biosimilars. The objective is to initiate a discussion about different approaches involving Machine Learning. So, the discussion is established regarding implementation of Neural Network model to ensure safety of biosimilars subject to economic incentives. Nevertheless, the application of Machine Learning in the healthcare field raises ethical, legal and technical issues that require further discussion.
Gender Differences and Quality of Life in Parkinson’s Disease
Authors: Crispino Pietro , Gino Miriam , Barbagelata Elena , Ciarambino Tiziana , Politi Cecilia , Ambrosino Immacolata , Ragusa Rosalia , Marranzano Marina , Biondi Antonio , Vacante Marco
Published: December 2020

Parkinson’s disease has been found to significantly affect health-related quality of life. The gender differences of the health-related quality of life of subjects with Parkinson’s disease have been observed in a number of studies. These differences have been reported in terms of the age at onset, clinical manifestations, and response to therapy. In general, women with Parkinson’s disease showed more positive disease outcomes with regard to emotion processing, non-motor symptoms, and cognitive functions, although women report more Parkinson’s disease-related clinical manifestations. Female gender predicted poor physical functioning and socioemotional health-related quality of life, while male gender predicted the cognitive domain of health-related quality of life. Some studies reported gender differences in the association between health-related quality of life and non-motor symptoms. Depression and fatigue were the main causes of poorer health-related quality of life in women, even in the early stages of Parkinson’s disease. The aim of this review was to collect the best available evidence on gender differences in the development of Parkinson’s disease symptoms and health-related quality of life.
Obstetric Violence in Spain (Part II): Interventionism and Medicalization during Birth
Authors: Mena-Tudela Desirée , Iglesias-Casás Susana , González-Chordá Víctor Manuel , Cervera-Gasch Águeda , Andreu-Pejó Laura , Valero-Chilleron María Jesús
Published: December 2020

Background: obstetric violence can partially be represented by the high number of interventions and medicalization rates during the birthing process. The objective of the present study was to determine the interventionism and medicalization levels during childbirth in Spain. Methods: a descriptive, retrospective, and cross-sectional study was conducted between January 2018 and June 2019. Results: the intervention percentages were 34.2% for Kristeller maneuver and 39.3% for episiotomy. Differences appeared in public, private, and mixed healthcare settings (p < 0.001). The mean satisfaction, with healthcare in the different settings, was estimated at 6.88 points (SD ± 2.146) in public healthcare, 4.76 points (SD ± 3.968) in private healthcare, and 8.03 points (SD ± 1.930) in mixed healthcare (p < 0.001). No statistically significant differences were found in Spanish autonomous communities. Conclusions: births in Spain seem to be highly intervened. In this study, a certain equity criterion was found concerning interventionism during childbirth in Spain. Healthcare influenced female intervention, satisfaction, and perception levels for obstetric violence; this evidences that female empowerment plays an important role.
Pathological Insight into 5-HT2B Receptor Activation in Fibrosing Interstitial Lung Diseases
Authors: Löfdahl Anna , Tornling Göran , Wigén Jenny , Larsson-Callerfelt Anna-Karin , Wenglén Christina , Westergren-Thorsson Gunilla
Published: December 2020

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 conditions, of which primarily idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, hypersensitivity pneumonitis, ILD associated with autoimmune diseases and sarcoidosis may present a progressive fibrosing (PF) phenotype. Despite different aetiology and histopathological patterns, the PF-ILDs have similarities regarding disease mechanisms with self-sustaining fibrosis, which suggests that the diseases may share common pathogenetic pathways. Previous studies show an enhanced activation of serotonergic signaling in pulmonary fibrosis, and the serotonin (5-HT)2 receptors have been implicated to have important roles in observed profibrotic actions. Our research findings in support by others, demonstrate antifibrotic effects with 5-HT2B receptor antagonists, alleviating several key events common for the fibrotic diseases such as myofibroblast differentiation and connective tissue deposition. In this review, we will address the potential role of 5-HT and in particular the 5-HT2B receptors in three PF-ILDs: ILD associated with systemic sclerosis (SSc-ILD), ILD associated with rheumatoid arthritis (RA-ILD) and IPF. Highlighting the converging pathways in these diseases discloses the 5-HT2B receptor as a potential disease target for PF-ILDs, which today have an urgent unmet need for therapeutic strategies.
Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence
Authors: Caponio Giusy Rita , Wang David Q.-H. , Di Ciaula Agostino , De Angelis Maria , Portincasa Piero
Published: December 2020

Hypercholesterolemia represents one key pathophysiological factor predisposing to increasing risk of developing cardiovascular disease worldwide. Controlling plasma cholesterol levels and other metabolic risk factors is of paramount importance to prevent the overall burden of disease emerging from cardiovascular-disease-related morbidity and mortality. Dietary cholesterol undergoes micellization and absorption in the small intestine, transport via blood, and uptake in the liver. An important amount of cholesterol originates from hepatic synthesis, and is secreted by the liver into bile together with bile acids (BA) and phospholipids, with all forming micelles and vesicles. In clinical medicine, dietary recommendations play a key role together with pharmacological interventions to counteract the adverse effects of chronic hypercholesterolemia. Bioactive compounds may also be part of initial dietary plans. Specifically, soybean contains proteins and peptides with biological activity on plasma cholesterol levels and this property makes soy proteins a functional food. Here, we discuss how soy proteins modulate lipid metabolism and reduce plasma cholesterol concentrations in humans, with potential outcomes in improving metabolic- and dyslipidemia-related conditions.
Essential (Mg, Fe, Zn and Cu) and Non-Essential (Cd and Pb) Elements in Predatory Insects (Vespa crabro and Vespa velutina): A Molecular Perspective
Authors: Andreani Giulia , Ferlizza Enea , Cabbri Riccardo , Fabbri Micaela , Bellei Elisa , Isani Gloria
Published: December 2020

The recent introduction of the Asian yellow-legged hornet, Vespa velutina, into Europe has raised concern regarding the threat to honeybees and the competition with the European hornet, Vespa crabro. The aim of this study was to investigated essential (Mg, Fe, Zn, Cu) and non-essential (Cd and Pb) elements in these two species. Element concentrations were determined in the whole body and separately in the head, thorax and abdomen using atomic absorption spectrometry (AAS). The changes in essential element concentration and speciation during metamorphosis were also studied using size exclusion chromatography followed by AAS and proteomic analysis. In both species, the essential elements were more concentrated in the abdomen due to the presence of fat bodies. Magnesium, Fe and Zn concentrations were significantly higher in V. crabro than in V. velutina and could have been related to the higher aerobic energy demand of the former species required to sustain foraging flight. Low concentrations of Cd and Pb were indicative of low environmental exposure. The concentration and speciation of essential elements, particularly Fe, varied among the developmental stages, indicating a modification of ligand preferences during metamorphosis. Overall, the results in the present study provide a better understanding of the hornet metal metabolism and a foundation for additional studies.
Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations
Authors: Carlier Jeremy , Diao Xingxing , Giorgetti Raffaele , Busardò Francesco P. , Huestis Marilyn A.
Published: December 2020

For more than ten years, new synthetic cathinones (SCs) mimicking the effects of controlled cocaine-like stimulants have flooded the illegal drug market, causing numerous intoxications and fatalities. There are often no data on the pharmacokinetics of these substances when they first emerge onto the market. However, the detection of SC metabolites is often critical in order to prove consumption in clinical and forensic settings. In this research, the metabolite profile of two pyrrolidinyl SCs, α-pyrrolidinohexaphenone (α-PHP) and 4′′-fluoro-α-pyrrolidinovalerophenone (4F-α-PVP), were characterized to identify optimal intake markers. Experiments were conducted using pooled human hepatocyte incubations followed by liquid chromatography–high-resolution tandem mass spectrometry and data-mining software. We suggest α-PHP dihydroxy-pyrrolidinyl, α-PHP hexanol, α-PHP 2′-keto-pyrrolidinyl-hexanol, and α-PHP 2′-keto-pyrrolidinyl as markers of α-PHP use, and 4F-α-PVP dihydroxy-pyrrolidinyl, 4F-α-PVP hexanol, 4F-α-PVP 2′-keto-pyrrolidinyl-hexanol, and 4F-α-PVP 2′-keto-pyrrolidinyl as markers of 4F-α-PVP use. These results represent the first data available on 4F-α-PVP metabolism. The metabolic fate of α-PHP was previously studied using human liver microsomes and urine samples from α-PHP users. We identified an additional major metabolite (α-PHP dihydroxy-pyrrolidinyl) that might be crucial for documenting exposure to α-PHP. Further experiments with suitable analytical standards, which are yet to be synthesized, and authentic specimens should be conducted to confirm these results.
Evaluation of the Physicochemical Properties, Pharmacokinetics, and In Vitro Anticancer Effects of Docetaxel and Osthol Encapsulated in Methoxy Poly(ethylene glycol)-b-Poly(caprolactone) Polymeric Micelles
Authors: Jo Min Jeong , Lee Yu Jin , Park Chun-Woong , Chung Youn Bok , Kim Jin-Seok , Lee Mi Kyeong , Shin Dae Hwan
Published: December 2020

Docetaxel (DTX), a taxane-based anticancer drug, and osthol (OTH), a coumarin-derivative compound, have shown anticancer effects against different types of cancers through various mechanisms. However, these drugs have low solubility in water and low oral bioavailability, and thus their clinical application is difficult. To overcome these problems, we encapsulated DTX and OTH in methoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) and conducted studies in vitro and in vivo. We selected a 1:4 ratio as the optimal ratio of DTX and OTH, through combination index analysis in A549 cancer cells, and prepared micelles to evaluate the encapsulation efficiency, drug loading, particle size, and zeta potential. The in vitro drug-release profile showed that DTX/OTH-loaded mPEG-b-PCL micelles could slowly release DTX and OTH. In the clonogenic assay, DTX/OTH-loaded mPEG-b-PCL micelles showed 3.7 times higher inhibitory effect than the DTX/OTH solution. Pharmacokinetic studies demonstrated that micelles in combination with DTX and OTH exhibited increased area under curve and decreased clearance values, as compared with single micelles.
Tissue-Resident Lymphocytes: Implications in Immunotherapy for Hepatocellular Carcinoma
Authors: Han Ji Won , Yoon Seung Kew
Published: December 2020

Hepatocellular carcinoma (HCC) is a hard-to-treat cancer. The recent introduction of immune checkpoint inhibitors (ICIs) provided viable options to treat HCC, but the response rate is currently not sufficient. Thus, a better understanding of ICI-responding cells within tumors is needed to improve outcomes of ICI treatment in HCC. Recently, tissue-resident memory T (TRM) cells were defined as a subset of the memory T cell population; this cell population is actively under investigation to elucidate its role in anti-tumor immunity. In addition, the role of other tissue-resident populations such as tissue resident regulatory T (Treg) cells, mucosal associated invariant T (MAIT) cells, γδ T cells, and invariant natural killer T (iNKT) cells in anti-tumor immunity is also actively being investigated. However, there is no study that summarizes recent studies and discusses future perspectives in terms of tissue resident lymphocytes in HCC. In this review, we summarize key features of tissue-resident lymphocytes and their role in the anti-tumor immunity. Additionally, we review recent studies regarding the characteristics of tissue-resident lymphocytes in HCC and their role in ICI treatment and other immunotherapeutic strategies.
Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice
Authors: Park Eunkuk , Lee Chang Gun , Lim Eunguk , Hwang Seokjin , Yun Seung Hee , Kim Jeonghyun , Jeong Hyesoo , Yong Yoonjoong , Yun Seong-Hoon , Choi Chun Whan , Jin Hyun-Seok , Jeong Seon-Yong
Published: December 2020

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.
Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment
Authors: Niland Stephan , Eble Johannes A.
Published: December 2020

The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs.
Research Trends in the Efficacy of Stem Cell Therapy for Hepatic Diseases Based on MicroRNA Profiling
Authors: Kweon Minyeoung , Kim Jae Yeon , Jun Ji Hye , Kim Gi Jin
Published: December 2020

Liver diseases, despite the organ’s high regenerative capacity, are caused by several environmental factors and persistent injuries. Their optimal treatment is a liver transplantation. However, this option is limited by donor shortages and immune response issues. Therefore, many researchers have been interested in identifying the therapeutic potential in treating irreversible liver damage based on stem cells and developing suitable therapeutic agents. Mesenchymal stem cells (MSCs), which are representative multipotent stem cells, are known to be highly potential stem cell therapy compared to other stem cells in the clinical trial worldwide. MSCs have therapeutic potentials for several hepatic diseases such as anti-fibrosis, proliferation of hepatocytes injured, anti-inflammation, autophagic mechanism, and inactivation of hepatic stellate cells. There are much data regarding clinical treatments, however, the data for examining the efficacy of stem cell treatment and the correlation between the stem cell engraftment and the efficacy in liver diseases is limited due to the lack of monitoring system for treatment effectiveness. Therefore, this paper introduces the characteristics of microRNAs (miRNAs) and liver disease-specific miRNA profiles, and the possibility of a biomarker that miRNA can monitor stem cell treatment efficacy by comparing miRNAs changed in liver diseases following stem cell treatment. Additionally, we also discuss the miRNA profiling in liver diseases when treated with stem cell therapy and suggest the candidate miRNAs that can be used as a biomarker that can monitor treatment efficacy in liver diseases based on MSCs therapy.
Model Amphipathic Peptide Coupled with Tacrine to Improve Its Antiproliferative Activity
Authors: Silva Sara , Alves Cláudia , Duarte Diana , Costa Ana , Sarmento Bruno , Almeida António J. , Gomes Paula , Vale Nuno
Published: December 2020

Drug repurposing and drug combination are two strategies that have been widely used to overcome the traditional development of new anticancer drugs. Several FDA-approved drugs for other indications have been tested and have demonstrated beneficial anticancer effects. In this connection, our research group recently reported that Tacrine, used to treat Alzheimer’s Disease, inhibits the growth of breast cancer MCF-7 cells both alone and in combination with a reference drug. In this view, we have now coupled Tacrine with the model amphipathic cell-penetrating peptide (CPP) MAP, to ascertain whether coupling of the CPP might enhance the drug’s antiproliferative properties. To this end, we synthesized MAP through solid-phase peptide synthesis, coupled it with Tacrine, and made a comparative evaluation of the parent drug, peptide, and the conjugate regarding their permeability across the blood-brain barrier (BBB), ability to inhibit acetylcholinesterase (AChE) in vitro, and antiproliferative activity on cancer cells. Both MAP and its Tacrine conjugate were highly toxic to MCF-7 and SH-SY5Y cells. In turn, BBB-permeability studies were inconclusive, and conjugation to the CPP led to a considerable loss of Tacrine function as an AChE inhibitor. Nonetheless, this work reinforces the potential of repurposing Tacrine for cancer and enhances the antiproliferative activity of this drug through its conjugation to a CPP.
Reprogramming and Differentiation of Cutaneous Squamous Cell Carcinoma Cells in Recessive Dystrophic Epidermolysis Bullosa
Authors: Rami Avina , Łaczmański Łukasz , Jacków-Nowicka Jagoda , Jacków Joanna
Published: December 2020

The early onset and rapid progression of cutaneous squamous cell carcinoma (cSCC) leads to high mortality rates in individuals with recessive dystrophic epidermolysis bullosa (RDEB). Currently, the molecular mechanisms underlying cSCC development in RDEB are not well understood and there are limited therapeutic options. RDEB-cSCC arises through the accumulation of genetic mutations; however, previous work analyzing gene expression profiles have not been able to explain its aggressive nature. Therefore, we generated a model to study RDEB-cSCC development using cellular reprograming and re-differentiation technology. We compared RDEB-cSCC to cSCC that were first reprogrammed into induced pluripotent stem cells (RDEB-cSCC-iPSC) and then differentiated back to keratinocytes (RDEB-cSCC-iKC). The RDEB-cSCC-iKC cell population had reduced proliferative capacities in vitro and in vivo, suggesting that reprogramming and re-differentiation leads to functional changes. Finally, we performed RNA-seq analysis for RDEB-cSCC, RDEB-cSCC-iPSC, and RDEB-cSCC-iKC and identified different gene expression signatures between these cell populations. Taken together, this cell culture model offers a valuable tool to study cSCC and provides a novel way to identify potential therapeutic targets for RDEB-cSCC.
Mitochondrial TSPO Deficiency Triggers Retrograde Signaling in MA-10 Mouse Tumor Leydig Cells
Authors: Fan Jinjiang , Papadopoulos Vassilios
Published: December 2020

The mitochondrial translocator protein (TSPO) has been shown to bind cholesterol with high affinity and is involved in mediating its availability for steroidogenesis. We recently reported that targeted Tspo gene deletion in MA-10 mouse tumor Leydig cells resulted in reduced cAMP-stimulated steroid formation and significant reduction in the mitochondrial membrane potential (ΔΨm) compared to control cells. We hypothesized that ΔΨm reduction in the absence of TSPO probably reflects the dysregulation and/or maintenance failure of some basic mitochondrial function(s). To explore the consequences of TSPO depletion via CRISPR-Cas9-mediated deletion (indel) mutation in MA-10 cells, we assessed the transcriptome changes in TSPO-mutant versus wild-type (Wt) cells using RNA-seq. Gene expression profiles were validated using real-time PCR. We report herein that there are significant changes in nuclear gene expression in Tspo mutant versus Wt cells. The identified transcriptome changes were mapped to several signaling pathways including the regulation of membrane potential, calcium signaling, extracellular matrix, and phagocytosis. This is a retrograde signaling pathway from the mitochondria to the nucleus and is probably the result of changes in expression of several transcription factors, including key members of the NF-κB pathway. In conclusion, TSPO regulates nuclear gene expression through intracellular signaling. This is the first evidence of a compensatory response to the loss of TSPO with transcriptome changes at the cellular level.
Insight into the bZIP Gene Family in Solanum tuberosum: Genome and Transcriptome Analysis to Understand the Roles of Gene Diversification in Spatiotemporal Gene Expression and Function
Authors: Herath Venura , Verchot Jeanmarie
Published: December 2020

The basic region-leucine zipper (bZIP) transcription factors (TFs) form homodimers and heterodimers via the coil–coil region. The bZIP dimerization network influences gene expression across plant development and in response to a range of environmental stresses. The recent release of the most comprehensive potato reference genome was used to identify 80 StbZIP genes and to characterize their gene structure, phylogenetic relationships, and gene expression profiles. The StbZIP genes have undergone 22 segmental and one tandem duplication events. Ka/Ks analysis suggested that most duplications experienced purifying selection. Amino acid sequence alignments and phylogenetic comparisons made with the Arabidopsis bZIP family were used to assign the StbZIP genes to functional groups based on the Arabidopsis orthologs. The patterns of introns and exons were conserved within the assigned functional groups which are supportive of the phylogeny and evidence of a common progenitor. Inspection of the leucine repeat heptads within the bZIP domains identified a pattern of attractive pairs favoring homodimerization, and repulsive pairs favoring heterodimerization. These patterns of attractive and repulsive heptads were similar within each functional group for Arabidopsis and S. tuberosum orthologs. High-throughput RNA-seq data indicated the most highly expressed and repressed genes that might play significant roles in tissue growth and development, abiotic stress response, and response to pathogens including Potato virus X. These data provide useful information for further functional analysis of the StbZIP gene family and their potential applications in crop improvement.
Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures
Authors: Baltazar-Lara Rosario , Ávila-Mendoza José , Martínez-Moreno Carlos G. , Carranza Martha , Pech-Pool Santiago , Vázquez-Martínez Olivia , Díaz-Muñoz Mauricio , Luna Maricela , Arámburo Carlos
Published: December 2020

It has been reported that growth hormone (GH) and insulin-like growth factor 1 (IGF-1) exert protective and regenerative actions in response to neural damage. It is also known that these peptides are expressed locally in nervous tissues. When the central nervous system (CNS) is exposed to hypoxia-ischemia (HI), both GH and IGF-1 are upregulated in several brain areas. In this study, we explored the neuroprotective effects of GH and IGF-1 administration as well as the involvement of these endogenously expressed hormones in embryonic chicken cerebellar cell cultures exposed to an acute HI injury. To induce neural damage, primary cultures were first incubated under hypoxic-ischemic (<5% O2, 1g/L glucose) conditions for 12 h (HI), and then incubated under normal oxygenation and glucose conditions (HI + Ox) for another 24 h. GH and IGF-1 were added either during or after HI, and their effect upon cell viability, apoptosis, or necrosis was evaluated. In comparison with normal controls (Nx, 100%), a significant decrease of cell viability (54.1 ± 2.1%) and substantial increases in caspase-3 activity (178.6 ± 8.7%) and LDH release (538.7 ± 87.8%) were observed in the HI + Ox group. On the other hand, both GH and IGF-1 treatments after injury (HI + Ox) significantly increased cell viability (77.2 ± 4.3% and 72.3 ± 3.9%, respectively) and decreased both caspase-3 activity (118.2 ± 3.8% and 127.5 ± 6.6%, respectively) and LDH release (180.3 ± 21.8% and 261.6 ± 33.9%, respectively). Incubation under HI + Ox conditions provoked an important increase in the local expression of GH (3.2-fold) and IGF-1 (2.5-fold) mRNAs. However, GH gene silencing with a specific small-interfering RNAs (siRNAs) decreased both GH and IGF-1 mRNA expression (1.7-fold and 0.9-fold, respectively) in the HI + Ox group, indicating that GH regulates IGF-1 expression under these incubation conditions. In addition, GH knockdown significantly reduced cell viability (35.9 ± 2.1%) and substantially increased necrosis, as determined by LDH release (1011 ± 276.6%). In contrast, treatments with GH and IGF-1 stimulated a partial recovery of cell viability (45.2 ± 3.7% and 53.7 ± 3.2%) and significantly diminished the release of LDH (320.1 ± 25.4% and 421.7 ± 62.2%), respectively. Our results show that GH, either exogenously administered and/or locally expressed, can act as a neuroprotective factor in response to hypoxic-ischemic injury, and that this effect may be mediated, at least partially, through IGF-1 expression.
Intranasal Administration of Rotenone Reduces GABAergic Inhibition in the Mouse Insular Cortex Leading to Impairment of LTD and Conditioned Taste Aversion Memory
Authors: Toyoda Hiroki , Katagiri Ayano , Kato Takafumi , Sato Hajime
Published: December 2020

The pesticide rotenone inhibits mitochondrial complex I and is thought to cause neurological disorders such as Parkinson’s disease and cognitive disorders. However, little is known about the effects of rotenone on conditioned taste aversion memory. In the present study, we investigated whether intranasal administration of rotenone affects conditioned taste aversion memory in mice. We also examined how the intranasal administration of rotenone modulates synaptic transmission and plasticity in layer V pyramidal neurons of the mouse insular cortex that is critical for conditioned taste aversion memory. We found that the intranasal administration of rotenone impaired conditioned taste aversion memory to bitter taste. Regarding its cellular mechanisms, long-term depression (LTD) but not long-term potentiation (LTP) was impaired in rotenone-treated mice. Furthermore, spontaneous inhibitory synaptic currents and tonic GABA currents were decreased in layer V pyramidal neurons of rotenone-treated mice compared to the control mice. The impaired LTD observed in pyramidal neurons of rotenone-treated mice was restored by a GABAA receptor agonist muscimol. These results suggest that intranasal administration of rotenone decreases GABAergic synaptic transmission in layer V pyramidal neurons of the mouse insular cortex, the result of which leads to impairment of LTD and conditioned taste aversion memory.
Cardiac Connexin-43 Hemichannels and Pannexin1 Channels: Provocative Antiarrhythmic Targets
Authors: Andelova Katarina , Egan Benova Tamara , Szeiffova Bacova Barbara , Sykora Matus , Prado Natalia Jorgelina , Diez Emiliano Raul , Hlivak Peter , Tribulova Narcis
Published: December 2020

Cardiac connexin-43 (Cx43) creates gap junction channels (GJCs) at intercellular contacts and hemi-channels (HCs) at the peri-junctional plasma membrane and sarcolemmal caveolae/rafts compartments. GJCs are fundamental for the direct cardiac cell-to-cell transmission of electrical and molecular signals which ensures synchronous myocardial contraction. The HCs and structurally similar pannexin1 (Panx1) channels are active in stressful conditions. These channels are essential for paracrine and autocrine communication through the release of ions and signaling molecules to the extracellular environment, or for uptake from it. The HCs and Panx1 channel-opening profoundly affects intracellular ionic homeostasis and redox status and facilitates via purinergic signaling pro-inflammatory and pro-fibrotic processes. These conditions promote cardiac arrhythmogenesis due to the impairment of the GJCs and selective ion channel function. Crosstalk between GJCs and HCs/Panx1 channels could be crucial in the development of arrhythmogenic substrates, including fibrosis. Despite the knowledge gap in the regulation of these channels, current evidence indicates that HCs and Panx1 channel activation can enhance the risk of cardiac arrhythmias. It is extremely challenging to target HCs and Panx1 channels by inhibitory agents to hamper development of cardiac rhythm disorders. Progress in this field may contribute to novel therapeutic approaches for patients prone to develop atrial or ventricular fibrillation.
Calcium Pyrophosphate Dihydrate Crystals Increase the Granulocyte/Monocyte Progenitor (GMP) and Enhance Granulocyte and Monocyte Differentiation In Vivo
Authors: Onai Nobuyuki , Ogasawara Chie
Published: December 2020

Calcium pyrophosphate dihydrate (CPPD) crystals are formed locally within the joints, leading to pseudogout. Although the mobilization of local granulocytes can be observed in joints where pseudogout has manifested, the mechanism of this activity remains poorly understood. In this study, CPPD crystals were administered to mice, and the dynamics of splenic and peripheral blood myeloid cells were analyzed. As a result, levels of both granulocytes and monocytes were found to increase following CPPD crystal administration in a concentration-dependent manner, with a concomitant decrease in lymphocytes in the peripheral blood. In contrast, the levels of other cells, such as dendritic cell subsets, T-cells, and B-cells, remained unchanged in the spleen, following CPPD crystal administration. Furthermore, an increase in granulocytes/monocyte progenitors (GMPs) and a decrease in megakaryocyte/erythrocyte progenitors (MEPs) were also observed in the bone marrow. In addition, CPPD administration induced production of IL-1β, which acts on hematopoietic stem cells and hematopoietic progenitors and promotes myeloid cell differentiation and expansion. These results suggest that CPPD crystals act as a “danger signal” to induce IL-1β production, resulting in changes in course of hematopoietic progenitor cell differentiation and in increased granulocyte/monocyte levels, and contributing to the development of gout.
Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases
Authors: Śledziński Paweł , Nowak-Terpiłowska Agnieszka , Zeyland Joanna
Published: December 2020

Recently, there has been a growing interest in the medical applications of Cannabis plants. They owe their unique properties to a group of secondary metabolites known as phytocannabinoids, which are specific for this genus. Phytocannabinoids, and cannabinoids generally, can interact with cannabinoid receptors being part of the endocannabinoid system present in animals. Over the years a growing body of scientific evidence has been gathered, suggesting that these compounds have therapeutic potential. In this article, we review the classification of cannabinoids, the molecular mechanisms of their interaction with animal cells as well as their potential application in the treatment of human diseases. Specifically, we focus on the research concerning the anticancer potential of cannabinoids in preclinical studies, their possible use in cancer treatment and palliative medicine, as well as their influence on the immune system. We also discuss their potential as therapeutic agents in infectious, autoimmune, and gastrointestinal inflammatory diseases. We postulate that the currently ongoing and future clinical trials should be accompanied by research focused on the cellular and molecular response to cannabinoids and Cannabis extracts, which will ultimately allow us to fully understand the mechanism, potency, and safety profile of cannabinoids as single agents and as complementary drugs.
Vision-Based Vibration Monitoring of Structures and Infrastructures: An Overview of Recent Applications
Authors: Zona Alessandro
Published: December 2020

Contactless structural monitoring has in recent years seen a growing number of applications in civil engineering. Indeed, the elimination of physical installations of sensors is very attractive, especially for structures that might not be easily or safely accessible, yet requiring the experimental evaluation of their conditions, for example following extreme events such as strong earthquakes, explosions, and floods. Among contactless technologies, vision-based monitoring is possibly the solution that has attracted most of the interest of civil engineers, given that the advantages of contactless monitoring can be potentially obtained thorough simple and low-cost consumer-grade instrumentations. The objective of this review article is to provide an introductory discussion of the latest applications of vision-based vibration monitoring of structures and infrastructures through an overview of the results achieved in full-scale field tests, as documented in the published technical literature. In this way, engineers new to vision-based monitoring and stakeholders interested in the possibilities of contactless monitoring in civil engineering could have an outline of up-to-date achievements to support a first evaluation of the feasibility and convenience for future monitoring tasks.
Study on the Influence of Temperature on the Temporal and Spatial Distribution Characteristics of Natural Cavitating Flow around a Vehicle
Authors: Sun Tiezhi , Zhang Jianyu , Zhang Xiaoshi , Jiang Yichen
Published: December 2020

Cavitation involves complex multiphase turbulence and has important research significance. In this study, the Schnerr–Sauer cavitation model was used to model cavitation, and the detached-eddy simulation (DES) method was used to calculate the unsteady natural cavitating flow. The predicted results are in good agreement with experimentally measured cavity evolution and pressure values, demonstrating the effectiveness of this numerical method. Low temperature causes changes in the properties of water. The density of water at 0° is 999.84 kg/m3 and the density of water at 25° is 997.04. Cavitation evolution and shedding are analyzed at temperatures of 0 °C and 25 °C. The results showed that lower temperature increased the frequency of cavitation and enhanced pressure pulsation. At the same time, low temperature also increases the frequency of cavity shedding and shortens the cycle. In addition, based on the Ω method, the difference between vortex dynamics at various temperatures was studied, and it was found that different cavity stages showed different vortex structure characteristics, and lower temperature would aggravate the change of wake vortex structure. At the same time, the analysis of the turbulence characteristics in the downstream of the cavity shows that the lower temperature reduces the velocity pulsation and reduces the turbulence integral scale. At the end of the model, large-scale pulsations are transformed into small-scale pulsations.
Implementation Science to Increase Adoption of Genomic Medicine: An Urgent Need
Authors: Bangash Hana , Kullo Iftikhar J.
Published: December 2020

Advances in genomics have the potential to improve human health [...]
Seasonal and Interannual Ground-Surface Displacement in Intact and Disturbed Tundra along the Dalton Highway on the North Slope, Alaska
Authors: Iwahana Go , Busey Robert , Saito Kazuyuki
Published: December 2020

Spatiotemporal variation in ground-surface displacement caused by ground freeze–thaw and thermokarst is critical information to understand changes in the permafrost ecosystem. Measurement of ground displacement, especially in the disturbed ground underlain by ice-rich permafrost, is important to estimate the rate of permafrost and carbon loss. We conducted high-precision global navigation satellite system (GNSS) positioning surveys to measure the surface displacements of tundra in northern Alaska, together with maximum thaw depth (TD) and surface moisture measurements from 2017 to 2019. The measurements were performed along two to three 60–200 m transects per site with 1–5 m intervals at the three areas. The average seasonal thaw settlement (STS) at intact tundra sites ranged 5.8–14.3 cm with a standard deviation range of 2.1–3.3 cm. At the disturbed locations, averages and variations in STS and the maximum thaw depth were largest in all observed years and among all sites. The largest seasonal and interannual subsidence (44 and 56 cm/year, respectively) were recorded at points near troughs of degraded ice-wedge polygons or thermokarst lakes. Weak or moderate correlation between STS and TD found at the intact sites became obscure as the thermokarst disturbance progressed, leading to higher uncertainty in the prediction of TD from STS.
Perceived Phonological Overlap in Second-Language Categories: The Acquisition of English /r/ and /l/ by Japanese Native Listeners
Authors: Tyler Michael D.
Published: December 2020

Japanese learners of English can acquire /r/ and /l/, but discrimination accuracy rarely reaches native speaker levels. How do L2 learners develop phonological categories to acquire a vocabulary when they cannot reliably tell them apart? This study aimed to test the possibility that learners establish new L2 categories but perceive phonological overlap between them when they perceive an L2 phone. That is, they perceive it to be an instance of more than one of their L2 phonological categories. If so, improvements in discrimination accuracy with L2 experience should correspond to a reduction in overlap. Japanese native speakers differing in English L2 immersion, and native English speakers, completed a forced category goodness rating task, where they rated the goodness of fit of an auditory stimulus to an English phonological category label. The auditory stimuli were 10 steps of a synthetic /r/–/l/ continuum, plus /w/ and /j/, and the category labels were L, R, W, and Y. Less experienced Japanese participants rated steps at the /l/-end of the continuum as equally good versions of /l/ and /r/, but steps at the /r/-end were rated as better versions of /r/ than /l/. For those with more than 2 years of immersion, there was a separation of goodness ratings at both ends of the continuum, but the separation was smaller than it was for the native English speakers. Thus, L2 listeners appear to perceive a phonological overlap between /r/ and /l/. Their performance on the task also accounted for their responses on /r/–/l/ identification and AXB discrimination tasks. As perceived phonological overlap appears to improve with immersion experience, assessing category overlap may be useful for tracking L2 phonological development.
A Variationist Study of Subject Pronoun Expression in Medellín, Colombia
Authors: Orozco Rafael , Hurtado Luz Marcela
Published: December 2020

This variationist study of subject pronoun expression (SPE) in Medellín, Colombia uses multivariate regressions to probe the effects of ten predictors on 4623 tokens from the Proyecto para el Estudio Sociolingüístico del Español de España y de América (PRESEEA) corpus. We implement analytical innovations by exploring transitivity and the lexical effect of the verb, which we analyze by testing infinitives and subject pronoun + verb collocations, respectively, as standalone, random-effect factors. Our results reveal the highest pronominal rate (28%) found in a mainland Spanish-speaking community. Additionally, we uncover that pronominal rates increase with age, a finding which appears to have cognitive implications. The internal conditioning contributes to pronombrista studies by showing the effects of discourse type and transitivity. Narratives and opinion statements favor overt subjects, but statements indicating routine activities favor null subjects. Whereas unergative verbs promote overt subjects, reflexive verbs favor null subjects. The lexical effect of the verb reveals opposing tendencies between verbs in the same category as well as within different collocations of the same verb, providing more definitive answers than the semantically guided approaches used for the last four decades and showing that verb groupings do not constitute functional categories with regard to SPE. Overall, this study contributes to expand our baseline knowledge of SPE in mainland Latin American communities and opens interesting research avenues.