bluuebunny/crossref_metadata_2025 huggingface dataset:
Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study
Authors: Lin Yen-Chung , Wang Jhih-Cheng , Wu Mai-Szu , Lin Yuh-Feng , Chen Chang-Rong , Chen Chang-Yu , Chen Kuan-Chou , Peng Chiung-Chi
Published: June 2020

Dysregulation of fatty acid oxidation and accumulation of fatty acids can cause kidney injury. Nifedipine modulates lipogenesis-related transcriptional factor SREBP-1/2 in proximal tubular cells by inhibiting the Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) pathway in vitro. However, the mechanisms by which nifedipine (NF) modulates lipotoxicity in vivo are unclear. Here, we examined the effect of NF in a doxorubicin (DR)-induced kidney injury rat model. Twenty-four Sprague–Dawley rats were divided into control, DR, DR+NF, and high-fat diet (HFD) groups. The DR, DR+NF, and HFD groups showed hypertension and proteinuria. Western blotting and immunohistochemical analysis showed that NF significantly induced TNF-α, CD36, SREBP-1/2, and acetyl-CoA carboxylase expression and renal fibrosis, and reduced fatty acid synthase and AMPK compared to other groups (p < 0.05). Additionally, 18 patients with chronic kidney disease (CKD) who received renal transplants were enrolled to examine their graft fibrosis and lipid contents via transient elastography. Low-density lipoprotein levels in patients with CKD strongly correlated with lipid contents and fibrosis in grafted kidneys (p < 0.05). Thus, NF may initiate lipogenesis through the SREBP-1/2/AMPK pathway and lipid uptake by CD36 upregulation and aggravate renal fibrosis in vivo. Higher low-density lipoprotein levels may correlate with renal fibrosis and lipid accumulation in grafted kidneys of patients with CKD.
Femto- to Millisecond Time-Resolved Photodynamics of a Double-Functionalized Push–Pull Organic Linker: Potential Candidate for Optoelectronically Active MOFs
Authors: Gutiérrez Mario , Duplouy-Armani Lucie , Angiolini Lorenzo , Pintado-Sierra Mercedes , Sánchez Félix , Douhal Abderrazzak
Published: June 2020

The design of improved organic linkers for the further engineering of smarter metal–organic framework (MOF) materials has become a paramount task for a wide number of material scientists. In this report, a luminescent double-functionalized push–pull (electron donor–acceptor) archetype organic molecule, dimethyl 4-amino-8-cyanonaphthalene-2,6-dicarboxylate (Me2CANADC), has been synthesized and characterized. The optical steady-state properties of Me2CANADC are strongly influenced by the surrounding environment as a direct consequence of its strong charge transfer (CT) character. The relaxation from its first electronically excited singlet state follows a double pathway: (1) on one side deactivating from its local excited (LE) state in the sub-picosecond or picosecond time domain, and (2) on the other side undergoing an ultrafast intramolecular charge transfer (ICT) reaction that is slowing down in viscous solvents. The deactivation to the ground state of these species with CT character is the origin of the Me2CANADC luminescence, and they present solvent-dependent lifetime values ranging from 8 to 18 ns. The slow photodynamics of Me2CANADC unveils the coexistence of a non-emissive triplet excited state and the formation of a long-lived charge separated state (2 µs). These observations highlight the promising optical properties of Me2CANADC linker, opening a window for the design of new functional MOFs with huge potential to be applied in the fields of luminescent sensing and optoelectronics.
Machine-Learned Association of Next-Generation Sequencing-Derived Variants in Thermosensitive Ion Channels Genes with Human Thermal Pain Sensitivity Phenotypes
Authors: Lötsch Jörn , Kringel Dario , Geisslinger Gerd , Oertel Bruno G. , Resch Eduard , Malkusch Sebastian
Published: June 2020

Genetic association studies have shown their usefulness in assessing the role of ion channels in human thermal pain perception. We used machine learning to construct a complex phenotype from pain thresholds to thermal stimuli and associate it with the genetic information derived from the next-generation sequencing (NGS) of 15 ion channel genes which are involved in thermal perception, including ASIC1, ASIC2, ASIC3, ASIC4, TRPA1, TRPC1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM8, TRPV1, TRPV2, TRPV3, and TRPV4. Phenotypic information was complete in 82 subjects and NGS genotypes were available in 67 subjects. A network of artificial neurons, implemented as emergent self-organizing maps, discovered two clusters characterized by high or low pain thresholds for heat and cold pain. A total of 1071 variants were discovered in the 15 ion channel genes. After feature selection, 80 genetic variants were retained for an association analysis based on machine learning. The measured performance of machine learning-mediated phenotype assignment based on this genetic information resulted in an area under the receiver operating characteristic curve of 77.2%, justifying a phenotype classification based on the genetic information. A further item categorization finally resulted in 38 genetic variants that contributed most to the phenotype assignment. Most of them (10) belonged to the TRPV3 gene, followed by TRPM3 (6). Therefore, the analysis successfully identified the particular importance of TRPV3 and TRPM3 for an average pain phenotype defined by the sensitivity to moderate thermal stimuli.
ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke
Authors: Li Li , Li Rongwen , Zacharek Alex , Wang Fengjie , Landschoot-Ward Julie , Chopp Michael , Chen Jieli , Cui Xu
Published: June 2020

ATP-binding cassette transporter A1 (ABCA1) plays an important role in the regulation of apolipoprotein E (ApoE) and the biogenesis of high-density lipoprotein (HDL) cholesterol in the mammalian brain. Cholesterol is a major source for myelination. Here, we investigate whether ABCA1/ApoE/HDL contribute to myelin repair and oligodendrogenesis in the ischemic brain after stroke. Specific brain ABCA1-deficient (ABCA1-B/-B) and ABCA1-floxed (ABCA1fl/fl) control mice were subjected to permanent distal middle-cerebral-artery occlusion (dMCAo) and were intracerebrally administered (1) artificial mouse cerebrospinal fluid (CSF) as vehicle control, (2) human plasma HDL3, and (3) recombined human ApoE2 starting 24 h after dMCAo for 14 days. All stroke mice were sacrificed 21 days after dMCAo. The ABCA1-B/-B–dMCAo mice exhibit significantly reduced myelination and oligodendrogenesis in the ischemic brain as well as decreased functional outcome 21 days after stroke compared with ABCA1fl/fl mice; administration of human ApoE2 or HDL3 in the ischemic brain significantly attenuates the deficits in myelination and oligodendrogenesis in ABCA1-B/-B–dMCAo mice ( p < 0.05, n = 9/group). In vitro, ABCA1-B/-B reduces ApoE expression and decreases primary oligodendrocyte progenitor cell (OPC) migration and oligodendrocyte maturation; HDL3 and ApoE2 treatment significantly reverses ABCA1-B/-B-induced reduction in OPC migration and oligodendrocyte maturation. Our data indicate that the ABCA1/ApoE/HDL signaling pathway contributes to myelination and oligodendrogenesis in the ischemic brain after stroke.
S(+)-(2E)-N-(2-Hydroxypropyl)-3-Phenylprop-2-Enamide (KM-568): A Novel Cinnamamide Derivative with Anticonvulsant Activity in Animal Models of Seizures and Epilepsy
Authors: Gunia-Krzyżak Agnieszka , Żesławska Ewa , Słoczyńska Karolina , Żelaszczyk Dorota , Sowa Aleksandra , Koczurkiewicz-Adamczyk Paulina , Popiół Justyna , Nitek Wojciech , Pękala Elżbieta , Marona Henryk
Published: June 2020

Epilepsy is one of the most frequent neurological disorders affecting about 1% of the world’s human population. Despite availability of multiple treatment options including antiseizure drugs, it is estimated that about 30% of seizures still remain resistant to pharmacotherapy. Searching for new antiseizure and antiepileptic agents constitutes an important issue within modern medicinal chemistry. Cinnamamide derivatives were identified in preclinical as well as clinical studies as important drug candidates for the treatment of epilepsy. The cinnamamide derivative presented here: S(+)-(2E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (S(+)-N-(2-hydroxypropyl)cinnamamide, compound KM-568) showed anticonvulsant activity in several models of epilepsy and seizures in mice and rats. It was active in a genetic animal model of epilepsy (Frings audiogenic seizure-susceptible mouse model, ED50 = 13.21 mg/kg, i.p.), acute seizures induced electrically (maximal electroshock test ED50 = 44.46 mg/kg mice i.p., ED50 = 86.6 mg/kg mice p.o., ED50 = 27.58 mg/kg rats i.p., ED50 = 30.81 mg/kg rats p.o., 6-Hz psychomotor seizure model 32 mA ED50 = 71.55 mg/kg mice i.p., 44 mA ED50 = 114.4 mg/kg mice i.p.), chronic seizures induced electrically (corneal kindled mouse model ED50 = 79.17 mg/kg i.p., hippocampal kindled rat model ED50 = 24.21 mg/kg i.p., lamotrigine-resistant amygdala kindled seizure model in rats ED50 = 58.59 mg/kg i.p.), acute seizures induced chemically (subcutaneous metrazol seizure threshold test ED50 = 104.29 mg/kg mice i.p., ED50 = 107.27 mg/kg mice p.o., ED50 = 41.72 mg/kg rats i.p., seizures induced by picrotoxin in mice ED50 = 94.11 mg/kg i.p.) and the pilocarpine-induced status epilepticus model in rats (ED50 = 279.45 mg/kg i.p., ED97 = 498.2 mg/kg i.p.). The chemical structure of the compound including configuration of the chiral center was confirmed by NMR spectroscopy, LC/MS spectroscopy, elemental analysis, and crystallography. Compound KM-568 was identified as a moderately stable derivative in an in vitro mouse liver microsome system. According to the Ames microplate format mutagenicity assay performed, KM-568 was not a base substitution or frameshift mutagen. Cytotoxicity evaluation in two cell lines (HepG2 and H9c2) proved the safety of the compound in concentrations up to 100 µM. Based on the results of anticonvulsant activity and safety profile, S(+)-(2E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide could be proposed as a new lead compound for further preclinical studies on novel treatment options for epilepsy.
SSADH Variants Increase Susceptibility of U87 Cells to Mitochondrial Pro-Oxidant Insult
Authors: Menduti Giovanna , Vitaliti Alessandra , Capo Concetta Rosa , Lettieri-Barbato Daniele , Aquilano Katia , Malaspina Patrizia , Rossi Luisa
Published: June 2020

Succinate semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme, encoded by ALDH5A1, mainly involved in γ-aminobutyric acid (GABA) catabolism and energy supply of neuronal cells, possibly contributing to antioxidant defense. This study aimed to further investigate the antioxidant role of SSADH, and to verify if common SNPs of ALDH5A1 may affect SSADH activity, stability, and mitochondrial function. In this study, we used U87 glioblastoma cells as they represent a glial cell line. These cells were transiently transfected with a cDNA construct simultaneously harboring three SNPs encoding for a triple mutant (TM) SSADH protein (p.G36R/p.H180Y/p.P182L) or with wild type (WT) cDNA. SSADH activity and protein level were measured. Cell viability, lipid peroxidation, mitochondrial morphology, membrane potential (ΔΨ), and protein markers of mitochondrial stress were evaluated upon Paraquat treatment, in TM and WT transfected cells. TM transfected cells show lower SSADH protein content and activity, fragmented mitochondria, higher levels of peroxidized lipids, and altered ΔΨ than WT transfected cells. Upon Paraquat treatment, TM cells show higher cell death, lipid peroxidation, 4-HNE protein adducts, and lower ΔΨ, than WT transfected cells. These results reinforce the hypothesis that SSADH contributes to cellular antioxidant defense; furthermore, common SNPs may produce unstable, less active SSADH, which could per se negatively affect mitochondrial function and, under oxidative stress conditions, fail to protect mitochondria.
Prediction of the Secretome and the Surfaceome: A Strategy to Decipher the Crosstalk between Adipose Tissue and Muscle during Fetal Growth
Authors: Bonnet Muriel , Kaspric Nicolas , Vonnahme Kimberly , Viala Didier , Chambon Christophe , Picard Brigitte
Published: June 2020

Crosstalk between adipose and muscular tissues is hypothesized to regulate the number of muscular and adipose cells during fetal growth, with post-natal consequences on lean and fat masses. Such crosstalk largely remains, however, to be described. We hypothesized that a characterization of the proteomes of adipose and muscular tissues from bovine fetuses may enhance the understanding of the crosstalk between these tissues through the prediction of their secretomes and surfaceomes. Proteomic experiments have identified 751 and 514 proteins in fetal adipose tissue and muscle. These are mainly involved in the regulation of cell proliferation or differentiation, but also in pathways such as apoptosis, Wnt signalling, or cytokine-mediated signalling. Of the identified proteins, 51 adipokines, 11 myokines, and 37 adipomyokines were predicted, together with 26 adipose and 13 muscular cell surface proteins. Analysis of protein–protein interactions suggested 13 links between secreted and cell surface proteins that may contribute to the adipose–muscular crosstalk. Of these, an interaction between the adipokine plasminogen and the muscular cell surface alpha-enolase may regulate the fetal myogenesis. The in silico secretome and surfaceome analyzed herein exemplify a powerful strategy to enhance the elucidation of the crosstalk between cell types or tissues.
ESR Method in Monitoring of Nanoparticle Endocytosis in Cancer Cells
Authors: Krzyminiewski Ryszard , Dobosz Bernadeta , Krist Bart , Schroeder Grzegorz , Kurczewska Joanna , Bluyssen Hans A.R.
Published: June 2020

Magnetic nanoparticles are extensively studied for their use in diagnostics and medical therapy. The behavior of nanoparticles after adding them to cell culture is an essential factor (i.e., whether they attach to a cell membrane or penetrate the membrane and enter into the cell). The present studies aimed to demonstrate the application of electron spin resonance (ESR) as a suitable technique for monitoring of nanoparticles entering into cells during the endocytosis process. The model nanoparticles were composed of magnetite iron (II, III) oxide core functionalized with organic unit containing nitroxide radical 4-hydroxy-TEMPO (TEMPOL). The research studies included breast cancer cells, as well as model yeast and human microvascular endothelial cells. The results confirmed that the ESR method is suitable for studying the endocytosis process of nanoparticles in the selected cells. It also allows for direct monitoring of radical cellular processes.
Therapeutic Functions of Stem Cells from Oral Cavity: An Update
Authors: Yang Ji Won , Shin Ye Young , Seo Yoojin , Kim Hyung-Sik
Published: June 2020

Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit the characteristics of mesenchymal stem cells (MSCs). Dental MSCs can be applied for the replacement of dental and oral tissues against various tissue-damaging conditions including dental caries, periodontitis, and oral cancers, as well as for systemic regulation of excessive inflammation in immune disorders, such as autoimmune diseases and hypersensitivity. Therefore, in this review, we summarized and updated the types of dental stem cells and their functions to exert therapeutic efficacy against diseases.
Classroom Attendance Systems Based on Bluetooth Low Energy Indoor Positioning Technology for Smart Campus
Authors: Puckdeevongs Apiruk , Tripathi N. K. , Witayangkurn Apichon , Saengudomlert Poompat
Published: June 2020

Student attendance during classroom hours is important, because it impacts the academic performance of students. Consequently, several universities impose a minimum attendance percentage criterion for students to be allowed to attend examinations; therefore, recording student attendance is a vital task. Conventional methods for recording student attendance in the classroom, such as roll-call and sign-in, are an inefficient use of instruction time and only increase teachers’ workloads. In this study, we propose a Bluetooth Low Energy-based student positioning framework for automatically recording student attendance in classrooms. The proposed architecture consists of two components, an indoor positioning framework within the classroom and student attendance registration. Experimental studies using our method show that the Received Signal Strength Indicator fingerprinting technique that is used in indoor scenarios can achieve satisfactory positioning accuracy, even in a classroom environment with typically high signal interference. We intentionally focused on designing a basic system with simple indoor devices based on ubiquitous Bluetooth technology and integrating an attendance system with computational techniques in order to minimize operational costs and complications. The proposed system is tested and demonstrated to be usable in a real classroom environment at Rangsit University, Thailand.
Suitability and Profitability of a Cereal Aphid for the Parasitoid Aphidius platensis in the Context of Conservation Biological Control of Myzus persicae in Orchards
Authors: Alvarez-Baca Jeniffer K. , Alfaro-Tapia Armando , Lavandero Blas , Le Lann Cécile , Van Baaren Joan
Published: June 2020

The use of cover crops can promote the abundance and early arrival of populations of natural enemies. Cereal cover crops between orchards rows could encourage the early arrival of the parasitoid Aphidius platensis, as they offer alternative winter hosts (e.g., Rhopalosiphum padi), enhancing the control of Myzus persicae in spring. However, the preference for and suitability of the alternative host must be addressed beforehand. To evaluate the potential of this strategy, we assessed host preference using behavioural choice tests, as well as no-choice tests measuring fitness traits, when developing on both host species. One source field for each aphid population from the above hosts was chosen. There was a clear choice for R. padi compared to M persicae, independently of the source, probably due to more defensive behaviours of M. persicae (i.e., kicks and escapes). Nevertheless, both aphid species were suitable for parasitoids’ development. The female progeny developed on R. padi were larger in size, irrespective of their origin. According to our results, in peach orchards with cereals sown between peach trees during the autumn, where we expect when R. padi populations will no longer be available during spring, A. platensis should be able to switch to M. persicae.
Distinctive Pathophysiology Underlying Constipation in Parkinson’s Disease: Implications for Cognitive Inefficiency
Authors: Tucker Rosalind M. , Ryan Suzanne , Hayee Bu’ Hussain , Bjarnason Ingvar , Augustin Aisha D. , Umamahesan Chianna , Taylor David , Weller Clive , Dobbs Sylvia M , Dobbs R John , Charlett André
Published: June 2020

Depression is associated with constipation within and outside Parkinson’s disease (PD). Since inefficient cognitive-processing (bradyphrenia) features in PD and an enterokinetic agent improved cognitive performance in healthy individuals, bradyphrenia may be associated with constipation. We aim to define the archetypical bowel function of PD, and its association with cognition, mood, and motor features within and outside PD. We assessed colonic transit time (oral radio-opaque markers over 6 days), bowel function and psychometric questionnaires and measures of PD facets, including bradyphrenia, in 58 participants with diagnosed PD, and 71 without (controls). The best abdominal X-ray (day 7) predictors of PD status were total retained marker count and transverse colon segmental delay. However, Rome functional constipation status complemented segmental delay better, giving good specificity (85%) but low sensitivity (56%). Transverse colon marker count appeared to be age-associated only in PD. In PD, those correctly classified by bowel dysfunction had higher depression scores (p = 0.02) and longer cognitive-processing times than the misclassified (p = 0.05). Controls misclassified as PD by bowel dysfunction had higher depression and anxiety scores than the correctly classified (p = 0.002 and 0.003, respectively), but not slower cognitive processing. Measures of motor features were independent of sub-classification by bowel function in PD and in controls. In conclusion, constipation in PD has distinct localized pathophysiology, and is associated with bradyphrenia.
COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection
Authors: Lechowicz Kacper , Drożdżal Sylwester , Machaj Filip , Rosik Jakub , Szostak Bartosz , Zegan-Barańska Małgorzata , Biernawska Jowita , Dabrowski Wojciech , Rotter Iwona , Kotfis Katarzyna
Published: June 2020

In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients’ quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.
Ursodeoxycholic Acid Halts Pathological Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy
Authors: Thounaojam Menaka C. , Jadeja Ravirajsinh N. , Rajpurohit Shubhra , Gutsaeva Diana R. , Stansfield Brian K. , Martin Pamela M. , Bartoli Manuela
Published: June 2020

Retinopathy of prematurity (ROP) is the leading cause of blindness in infants. We have investigated the efficacy of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine and glycine conjugated derivatives tauroursodeoxycholic acid (TUDCA) and glycoursodeoxycholic acid (GUDCA) in preventing retinal neovascularization (RNV) in an experimental model of ROP. Seven-day-old mice pups (P7) were subjected to oxygen-induced retinopathy (OIR) and were treated with bile acids for various durations. Analysis of retinal vascular growth and distribution revealed that UDCA treatment (50 mg/kg, P7–P17) of OIR mice decreased the extension of neovascular and avascular areas, whereas treatments with TUDCA and GUDCA showed no changes. UDCA also prevented reactive gliosis, preserved ganglion cell survival, and ameliorated OIR-induced blood retinal barrier dysfunction. These effects were associated with decreased levels of oxidative stress markers, inflammatory cytokines, and normalization of the VEGF–STAT3 signaling axis. Furthermore, in vitro tube formation and permeability assays confirmed UDCA inhibitory activity toward VEGF-induced pro-angiogenic and pro-permeability effects on human retinal microvascular endothelial cells. Collectively, our results suggest that UDCA could represent a new effective therapy for ROP.
The Impact of Marijuana on the Cardiovascular System: A Review of the Most Common Cardiovascular Events Associated with Marijuana Use
Authors: Latif Zara , Garg Nadish
Published: June 2020

With the expanded legalization of marijuana, its medical and recreational use have sharply increased over the past decade. A wide array of new forms of cannabis is available on the market today, and the potencies are ten times those of forms previously tested, meaning that the true impact of marijuana on the cardiovascular system remains unclear. Cannabis mainly exerts its effects via the sympathetic and parasympathetic nervous systems, with different doses affecting different cannabinoids receptors. Studies have shown that marijuana plays a role in thrombosis, inflammation, and atherosclerosis. Case reports have linked marijuana use to myocardial infarction, cardiac arrythmias, cardiomyopathies, stroke, and arteritis. Most patients are young, healthy men with no cardiovascular risk factors; however, the patient population is expected to change to include older individuals in the future. The widespread public perception of safety accompanying marijuana use has contributed to its increased use among the elderly, who are the most at risk population for acute cardiovascular events. In this review, we aim to provide a basic understanding of the physiological effects of marijuana on the cardiovascular system and to review the current literature regarding cardiovascular diseases linked to marijuana use in adults.
Number of Regularly Prescribed Drugs and Intrapatient Tacrolimus Trough Levels Variability in Stable Kidney Transplant Recipients
Authors: Giza Piotr , Ficek Rafał , Dwulit Tomasz , Chudek Jerzy , Woźniak Iwona , Więcek Andrzej , Kolonko Aureliusz
Published: June 2020

High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant time of 6.0 ± 3.1 years. The coefficient of variation (CV) as a measure of IPV was calculated in each individual patient. Data concerning the type and number of currently prescribed medications were collected. The participants were divided into four groups, based on the number of regularly prescribed drugs (≤3, 4–6, 7–9, ≥10 drugs, respectively). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (interquartile range, 0.08–0.14), group 2: 0.14 (0.01–0.17), group 3: 0.17 (0.14–0.23), group 4: 0.17 (0.15–0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503, p < 0.001] independently influenced the tacrolimus IPV. Concomitant steroid or diuretics use increased IPV only in Advagraf-treated KTRs, whereas proton-pump inhibitor or statin use increased IPV in the Prograf group but not in the Advagraf group. A large number of concomitant medications significantly increases the tacrolimus IPV in stable KTRs.
Genotypic and Phenotypic Resistance to Clarithromycin in Helicobacter pylori Strains
Authors: Gong Eun Jeong , Ahn Ji Yong , Kim Jung Mogg , Lee Sun Mi , Na Hee Kyong , Lee Jeong Hoon , Jung Kee Wook , Choi Kee Don , Kim Do Hoon , Song Ho June , Lee Gin Hyug , Kim So Won , Jung Hwoon-Yong
Published: June 2020

Background: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori. The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance. Methods: A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695. Results: Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype. Conclusions: All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population.
Underwater Image Enhancement and Mosaicking System Based on A-KAZE Feature Matching
Authors: Abaspur Kazerouni Iman , Dooly Gerard , Toal Daniel
Published: June 2020

Feature extraction and matching is a key component in image stitching and a critical step in advancing image reconstructions, machine vision and robotic perception algorithms. This paper presents a fast and robust underwater image mosaicking system based on (2D)2PCA and A-KAZE key-points extraction and optimal seam-line methods. The system utilizes image enhancement as a preprocessing step to improve quality and allow for greater keyframe extraction and matching performance, leading to better quality mosaicking. The application focus of this paper is underwater imaging and it demonstrates the suitability of the developed system in advanced underwater reconstructions. The results show that the proposed method can address the problems of noise, mismatching and quality issues which are typically found in underwater image datasets. The results demonstrate the proposed method as scale-invariant and show improvements in terms of processing speed and system robustness over other methods found in the literature.
Representational Difference Analysis of Transcripts Involved in Jervine Biosynthesis
Authors: Szeliga Magdalena , Ciura Joanna , Tyrka Mirosław
Published: June 2020

Veratrum-type steroidal alkaloids (VSA) are the major bioactive ingredients that strongly determine the pharmacological activities of Veratrum nigrum. Biosynthesis of VSA at the molecular and genetic levels is not well understood. Next-generation sequencing of representational difference analysis (RDA) products after elicitation and precursor feeding was applied to identify candidate genes involved in VSA biosynthesis. A total of 12,048 contigs with a median length of 280 bases were received in three RDA libraries obtained after application of methyl jasmonate, squalene and cholesterol. The comparative analysis of annotated sequences was effective in identifying candidate genes. GABAT2 transaminase and hydroxylases active at C-22, C-26, C-11, and C-16 positions in late stages of jervine biosynthesis were selected. Moreover, genes coding pyrroline-5-carboxylate reductase and enzymes from the short-chain dehydrogenases/reductases family (SDR) associated with the reduction reactions of the VSA biosynthesis process were proposed. The data collected contribute to better understanding of jervine biosynthesis and may accelerate implementation of biotechnological methods of VSA biosynthesis.
Patient and Operator Centered Outcomes in Implant Dentistry: Comparison between Fully Digital and Conventional Workflow for Single Crown and Three-Unit Fixed-Bridge
Authors: De Angelis Paolo , Manicone Paolo Francesco , De Angelis Silvio , Grippaudo Cristina , Gasparini Giulio , Liguori Margherita Giorgia , Camodeca Francesca , Piccirillo Giovan Battista , Desantis Viviana , D’Amato Giuseppe , D’Addona Antonio
Published: June 2020

Background: Scientific information about the effects of implant therapy following a precise workflow and patient and operators’ preferences should be considered to choose which implant treatment protocol to use, and to achieve patient’s satisfaction and functional results. The aim of this study was to analyze implant rehabilitations with a fully digital workflow and compare this approach with a conventional one. Methods: This study comprises 64 patients treated with a fully digital approach and 58 patients treated using a conventional protocol. Patient and operator centered outcomes were assessed through two visual analogue scale (VAS) questionnaires. Results: The VAS questionnaire demonstrated better results for the digital workflow concerning anxiety, convenience, taste, nausea sensation, pain and breathing difficulties (p < 0.0001). The VAS questionnaire administered to the operators showed better scores for the digital approach in relation to anxiety, convenience, difficulties of the impression procedure and the workflow (p < 0.0001). A significant reduced mean time for the digital workflow as well as a reduced number of required visits were recorded. Conclusion: The analysis of a fully digital and a conventional protocol showed better results according to patient and operators’ preferences when a fully digital approach was used.
Zinc Oxide and Zinc Oxide Nanoparticles Impact on In Vitro Germination and Seedling Growth in Allium cepa L.
Authors: Tymoszuk Alicja , Wojnarowicz Jacek
Published: June 2020

Zinc oxide nanoparticles (ZnO NPs) are ones of the most commonly manufactured nanomaterials worldwide. They can be used as a zinc fertilizer in agriculture to enhance yielding and to control the occurrence of diseases thanks to its broad antifungal and antibacterial action. The aim of this study was to investigate and compare the effects of ZnO submicron particles (ZnO SMPs) and ZnO NPs on the process of in vitro seed germination and seedling growth in onion (Allium cepa L. ‘Sochaczewska’), and to indicate the potential use of these compounds in onion production. In the experiment, disinfected seeds were inoculated on the modified Murashige and Skoog (MS) medium and poured with ZnO SMP or ZnO NP water suspension, at the concentrations of 50, 100, 200, 400, 800, 1600, and 3200 mg∙L−1. During three successive weeks, the germinating seeds were counted. Germination started most often on the second or third day of in vitro culture. The highest share of germination was recorded for seeds treated with 800 mg∙L−1 ZnO SMPs and ZnO NPs (52% and 56%, respectively). After the application of ZnO SMPs and ZnO NPs at the highest tested concentration (3200 mg∙L−1), the share of germinating seeds was only 19% and 11%, respectively. Interestingly, seedlings obtained from control seeds and seeds treated with ZnO SMPs and ZnO NPs did not differ statistically in terms of length, fresh weight, and dry weight of leaves, and roots. Both ZnO SMPs and ZnO NPs, in the concentration range from 50 to 1600 mg∙L−1, can be used to stimulate the germination process of onion seeds, without negative effects on the further growth and development of seedlings. There were no differences found between the action of ZnO NPs and ZnO SMPs, which suggested that the most important factor influencing seed germination was in fact the concentration of zinc ions, not the particle size.
Representations of Generalized Self-Shrunken Sequences
Authors: Cardell Sara D. , Climent Joan-Josep , Fúster-Sabater Amparo , Requena Verónica
Published: June 2020

Output sequences of the cryptographic pseudo-random number generator, known as the generalized self-shrinking generator, are obtained self-decimating Pseudo-Noise (PN)-sequences with shifted versions of themselves. In this paper, we present three different representations of this family of sequences. Two of them, the p and G-representations, are based on the parameters p and G corresponding to shifts and binary vectors, respectively, used to compute the shifted versions of the original PN-sequence. In addition, such sequences can be also computed as the binary sum of diagonals of the Sierpinski’s triangle. This is called the B-representation. Characteristics and generalities of the three representations are analyzed in detail. Under such representations, we determine some properties of these cryptographic sequences. Furthermore, these sequences form a family that has a group structure with the bit-wise XOR operation.
An Extension of Fuzzy Competition Graph and Its Uses in Manufacturing Industries
Authors: Pramanik Tarasankar , Muhiuddin G. , Alanazi Abdulaziz M. , Pal Madhumangal
Published: June 2020

Competition graph is a graph which constitutes from a directed graph (digraph) with an edge between two vertices if they have some common preys in the digraph. Moreover, Fuzzy competition graph (briefly, FCG) is the higher extension of the crisp competition graph by assigning fuzzy value to each vertex and edge. Also, Interval-valued FCG (briefly, IVFCG) is another higher extension of fuzzy competition graph by taking each fuzzy value as a sub-interval of the interval [ 0 , 1 ] . This graph arises in many real world systems; one of them is discussed as follows: Each and every species in nature basically needs ecological balance to survive. The existing species depends on one another for food. If there happens any extinction of any species, there must be a crisis of food among those species which depend on that extinct species. The height of food crisis among those species varies according to their ecological status, environment and encompassing atmosphere. So, the prey to prey relationship among the species cannot be assessed exactly. Therefore, the assessment of competition of species is vague or shadowy. Motivated from this idea, in this paper IVFCG is introduced and several properties of IVFCG and its two variants interval-valued fuzzy k-competition graphs (briefly, IVFKCG) and interval-valued fuzzy m-step competition graphs (briefly, IVFMCG) are presented. The work is helpful to assess the strength of competition among competitors in the field of competitive network system. Furthermore, homomorphic and isomorphic properties of IVFCG are also discussed. Finally, an appropriate application of IVFCG in the competition among the production companies in market is presented to highlight the relevance of IVFCG.
Endomorphism Spectra of Double Fan Graphs
Authors: Tong Mengdi , Hou Hailong
Published: June 2020

There are six different classes of endomorphisms for a graph. The sets of these endomorphisms always form a chain under the inclusion of sets. For a more systematic treatment of different endomorphisms, Böttcher and Knauer proposed the concepts of the endomorphism type and the endomorphism spectrum of a graph in 1992. In this paper, we studied endomorphism types and endomorphism spectra of double fan graphs.
Algae Metabolites in Cosmeceutical: An Overview of Current Applications and Challenges
Authors: Thiyagarasaiyar Krishnapriya , Goh Bey-Hing , Jeon You-Jin , Yow Yoon-Yen
Published: June 2020

Cosmetics are widely used by people around the world to protect the skin from external stimuli. Consumer preference towards natural cosmetic products has increased as the synthetic cosmetic products caused adverse side effects and resulted in low absorption rate due to the chemicals’ larger molecular size. The cosmetic industry uses the term “cosmeceutical”, referring to a cosmetic product that is claimed to have medicinal or drug-like benefits. Marine algae have gained tremendous attention in cosmeceuticals. They are one of the richest marine resources considered safe and possessed negligible cytotoxicity effects on humans. Marine algae are rich in bioactive substances that have shown to exhibit strong benefits to the skin, particularly in overcoming rashes, pigmentation, aging, and cancer. The current review provides a detailed survey of the literature on cosmeceutical potentials and applications of algae as skin whitening, anti-aging, anticancer, antioxidant, anti-inflammation, and antimicrobial agents. The biological functions of algae and the underlying mechanisms of all these activities are included in this review. In addition, the challenges of using algae in cosmeceutical applications, such as the effectiveness of different extraction methods and processing, quality assurance, and regulations concerning extracts of algae in this sector were also discussed.
Bile Acid Sequestrant, Sevelamer Ameliorates Hepatic Fibrosis with Reduced Overload of Endogenous Lipopolysaccharide in Experimental Nonalcoholic Steatohepatitis
Authors: Tsuji Yuki , Kaji Kosuke , Kitade Mitsuteru , Kaya Daisuke , Kitagawa Koh , Ozutsumi Takahiro , Fujinaga Yukihisa , Takaya Hiroaki , Kawaratani Hideto , Namisaki Tadashi , Moriya Kei , Akahane Takemi , Yoshiji Hitoshi
Published: June 2020

Despite the use of various pharmacotherapeutic strategies, fibrosis due to nonalcoholic steatohepatitis (NASH) remains an unsatisfied clinical issue. We investigated the effect of sevelamer, a hydrophilic bile acid sequestrant, on hepatic fibrosis in a murine NASH model. Male C57BL/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat (CDHF) diet for 12 weeks with or without orally administered sevelamer hydrochloride (2% per diet weight). Histological and biochemical analyses revealed that sevelamer prevented hepatic steatosis, macrophage infiltration, and pericellular fibrosis in CDHF-fed mice. Sevelamer reduced the portal levels of total bile acid and inhibited both hepatic and intestinal farnesoid X receptor activation. Gut microbiome analysis demonstrated that sevelamer improved a lower α-diversity and prevented decreases in Lactobacillaceae and Clostridiaceae as well as increases in Desulfovibrionaceae and Enterobacteriaceae in the CDHF-fed mice. Additionally, sevelamer bound to lipopolysaccharide (LPS) in the intestinal lumen and promoted its fecal excretion. Consequently, the sevelamer treatment restored the tight intestinal junction proteins and reduced the portal LPS levels, leading to the suppression of hepatic toll-like receptor 4 signaling pathway. Furthermore, sevelamer inhibited the LPS-mediated induction of fibrogenic activity in human hepatic stellate cells in vitro. Collectively, sevelamer inhibited the development of murine steatohepatitis by reducing hepatic LPS overload.
Frequency of Toxoplasma gondii and Risk Factors Associated with the Infection in Stray Dogs and Cats of Panama
Authors: Fábrega Lorena , Restrepo Carlos M. , Torres Alicia , Smith Diorene , Chan Patricia , Pérez Dimas , Cumbrera Alberto , Caballero E. Zuleima
Published: June 2020

Stray animals such as dogs and cats have an important role in maintaining the transmission cycles and dissemination of Toxoplasma gondii. Therefore, the objective of this study was to evaluate the frequency of T. gondii in stray dogs and cats in six different regions of Panama and determine risk factors associated with the dynamics of infection in each of the studied regions. Data were obtained using serological tests for the detection of anti-T. gondii IgG and IgM antibodies. The results of this study revealed an overall infection frequency of 23.73%. The infection frequencies found in dog and cat populations were 25.70% and 21.93% respectively, showing no statistically significant difference. Risk factor correlations suggested different infection dynamics depending on the region analyzed. The San Miguelito, North and West regions were more associated with positive cases in dogs with an age range greater than 13 months. Conversely, the Metro, Central and East regions were more associated with negative cases in cats with age ranging between 0 and 5 months. Infection of the parasite in stray animals can be influenced by intrinsic characteristics of each region, which can potentiate different risk factors associated with the different routes of transmission.
Comparative Genomics of Beggiatoa leptomitoformis Strains D-401 and D-402T with Contrasting Physiology But Extremely High Level of Genomic Identity
Authors: Rudenko Tatyana S. , Tarlachkov Sergey V. , Shatskiy Nikolay D. , Grabovich Margarita Yu.
Published: June 2020

Representatives of filamentous colorless sulfur-oxidizing bacteria often dominate in sulfide biotopes, preventing the diffusion of toxic sulfide into the water column. One of the most intriguing groups is a recently described Beggiatoa leptomitoformis including strains D-401 and D-402T. Both strains have identical genes encoding enzymes which are involved in the oxidation of hydrogen sulfide and thiosulfate. Surprisingly, the B. leptomitoformis strain D-401 is not capable to grow lithotrophically in the presence of reduced sulfur compounds and to accumulate elemental sulfur inside the cells, in contrast to the D-402T strain. In general, genomes of D-401 and D-402T have an extremely high level of identity and only differ in 1 single-letter substitution, 4 single-letter indels, and 16 long inserts. Among long inserts, 14 are transposons. It was shown that in the D-401 strain, a gene coding for a sulfur globule protein was disrupted by one of the mentioned transposons. Based on comparative genomics, RT-qPCR, and HPLC-MS/MS, we can conclude that this gene plays a crucial role in the formation of the sulfur globules inside the cells, and the disruption of its function prevents lithotrophic growth of B. leptomitoformis in the presence of reduced sulfur compounds.
Authigenic Carbonates in the Water–Biota–Bottom Sediments’ System of Small Lakes (South of Western Siberia)
Authors: Ovdina Ekaterina , Strakhovenko Vera , Solotchina Emilia
Published: June 2020

We studied 46 small, drainless lakes in various landscape types: The sub-taiga (Vasyugan plain), forest–steppe (Baraba lowland), and steppe and subzone of ribbon forests (Kulunda plain). Sampling of lake components (sediments, water, and biota) was performed. The materials were analyzed via a combination of modern analytical methods (atomic absorption spectroscopy, X-ray fluorescence, scanning electron microscopy and X-ray diffractometry). It was found that in the south of Western Siberia, lakes with a bicarbonate-sodium water composition are widespread against the background of general landscape zoning. This composition contributes to the abundant growth of biota in the lakes, which leads to the processes of authigenic carbonate formation from calcite–dolomite series and aragonite on geochemical barriers, i.e., drifting biota–water, submerged biota–water, and water–bottom sediments against a background of terrigenous demolition and organic matter accumulation. The article shows the differences in the composition and structure of low-temperature carbonate minerals formed on various geochemical barriers. It was found that low-magnesium calcite and aragonite are the most common authigenic carbonates in small lakes in the south of Western Siberia and are formed on all three geochemical barriers in lakes. High-magnesium calcites and Ca-excess dolomites are formed only at the water–bottom sediment barrier in lakes with HCO3–Na and Cl–HCO3–Na water composition at pH > 9 and with a total dissolved solids > 3 g·L−1 (in some lakes of HCO3-Na composition with a TDS < 3 g·L−1 and pH > 9).