bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendritic Spines in Alzheimer’s Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure
Authors: Pelucchi Silvia , Stringhi Ramona , Marcello Elena
Published: January 2020

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by Aβ-driven synaptic dysfunction in the early phases of pathogenesis. In the synaptic context, the actin cytoskeleton is a crucial element to maintain the dendritic spine architecture and to orchestrate the spine’s morphology remodeling driven by synaptic activity. Indeed, spine shape and synaptic strength are strictly correlated and precisely governed during plasticity phenomena in order to convert short-term alterations of synaptic strength into long-lasting changes that are embedded in stable structural modification. These functional and structural modifications are considered the biological basis of learning and memory processes. In this review we discussed the existing evidence regarding the role of the spine actin cytoskeleton in AD synaptic failure. We revised the physiological function of the actin cytoskeleton in the spine shaping and the contribution of actin dynamics in the endocytosis mechanism. The internalization process is implicated in different aspects of AD since it controls both glutamate receptor membrane levels and amyloid generation. The detailed understanding of the mechanisms controlling the actin cytoskeleton in a unique biological context as the dendritic spine could pave the way to the development of innovative synapse-tailored therapeutic interventions and to the identification of novel biomarkers to monitor synaptic loss in AD.
Phenylthiourea Binding to Human Tyrosinase-Related Protein 1
Authors: Lai Xuelei , Wichers Harry J. , Soler-López Montserrat , Dijkstra Bauke W.
Published: January 2020

Tyrosinase-related protein 1 (TYRP1) is one of the three human melanogenic enzymes involved in the biosynthesis of melanin, a pigment responsible for the color of the skin, hair, and eyes. It shares high sequence identity with tyrosinase, but has two zinc ions in its active site rather than two copper ions as in tyrosinase. Typical tyrosinase inhibitors do not directly coordinate to the zinc ions of TYRP1. Here, we show, from an X-ray crystal structure determination, that phenylthiourea, a highly potent tyrosinase inhibitor, does neither coordinate the active site zinc ions, but binds differently from other structurally characterized TYRP1-inhibitor complexes. Its aromatic ring is directed outwards from the active site, apparently as a result from the absence of polar oxygen substituents that can take the position of water molecules bound in the active site. The compound binds via hydrophobic interactions, thereby blocking substrate access to the active site.
Dormancy-Associated MADS-Box (DAM) Genes Influence Chilling Requirement of Sweet Cherries and Co-Regulate Flower Development with SOC1 Gene
Authors: Wang Jiyuan , Gao Zhen , Li Hui , Jiu Songtao , Qu Yueting , Wang Lei , Ma Chao , Xu Wenping , Wang Shiping , Zhang Caixi
Published: January 2020

Floral bud dormancy release of fruit tree species is greatly influenced by climate change. The lack of chilling accumulation often results in the occurrence of abnormal flower and low yields of sweet cherries (Prunus avium L.) in warm regions. To investigate the regulation of dormancy in sweet cherries, six DAM genes with homology to peach DAM, designated PavDAM1-6, have been identified and characterized. Phylogenetic analysis indicate that these genes are similar to DAMs in peach, apple and pear. The expression patterns of the PavDAMs in the low-chill cultivar ‘Royal Lee’ were different from that in the high-chill cultivar ‘Hongdeng’. ‘Royal Lee’ exhibits lower transcriptional level of PavDAM1 compared to ‘Hongdeng’, especially at the stage of chilling accumulation, and transcriptional levels of PavDAM4/5 were high in both cultivars during the endodormancy. Ectopic expression of PavDAM1 and PavDAM5 in Arabidopsis resulted in plants with abnormal flower and seed development, especially the PavDAM5. Higher transcriptional levels of SOC1 were observed in transgenic PavDAM1/5 lines, and ectopic expression of PavSOC1 had the similar floral phenotype. Further, protein interaction analysis demonstrated that PavDAM1/5 could interact with PavSOC1 in vivo and in vitro, which will help clarify the molecular mechanism of the flower development in sweet cherry or other fruit trees.
Potential Use of Biotherapeutic Bacteria to Target Colorectal Cancer-Associated Taxa
Authors: Lawrence Garreth W. , Begley Máire , Cotter Paul D. , Guinane Caitriona M.
Published: January 2020

The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review. By extension, such taxa represent potential therapeutic targets. In particular, the emerging human pathogen Fusobacterium nucleatum represents an important agent in CRC development and its control within the gastrointestinal tract is desirable. This paper reviews the principal bacterial pathogens that have been associated with CRC to date and discusses the in vitro and human studies that have shown the potential use of biotherapeutic strains as a means of targeting CRC-associated bacteria.
The Pentose Phosphate Pathway and Its Involvement in Cisplatin Resistance
Authors: Giacomini Isabella , Ragazzi Eugenio , Pasut Gianfranco , Montopoli Monica
Published: January 2020

Cisplatin is the first-line treatment for different types of solid tumors, such as ovarian, testicular, bladder, cervical, head and neck, lung, and esophageal cancers. The main problem related to its clinical use is the onset of drug resistance. In the last decades, among the studied molecular mechanisms of cisplatin resistance, metabolic reprogramming has emerged as a possible one. This review focuses on the pentose phosphate pathway (PPP) playing a pivotal role in maintaining the high cell proliferation rate and representing an advantage for cancer cells. In particular, the oxidative branch of PPP plays a role in oxidative stress and seems to be involved in cisplatin resistance. In light of these considerations, it has been demonstrated that overexpression and higher enzymatic activity of different enzymes of both oxidative and non-oxidative branches (such as glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and transketolase) increase cisplatin resistance, and their silencing or combined treatment with cisplatin could restore cisplatin sensitivity. Moreover, drug delivery systems loaded with both PPP inhibitors and cisplatin give the possibility of reaching cancer cells selectively. In conclusion, targeting PPP is becoming a strategy to overcome cisplatin resistance; however, further studies are required to better understand the mechanisms.
The Nootropic Drug Α-Glyceryl-Phosphoryl-Ethanolamine Exerts Neuroprotective Effects in Human Hippocampal Cells
Authors: Daniele Simona , Mangano Giorgina , Durando Lucia , Ragni Lorella , Martini Claudia
Published: January 2020

Brain aging involves changes in the lipid membrane composition that lead to a decrease in membrane excitability and neurotransmitter release. These membrane modifications have been identified as contributing factors in age-related memory decline. In this sense, precursors of phospholipids (PLs) can restore the physiological composition of cellular membranes and produce valuable therapeutic effects in brain aging. Among promising drugs, alpha-glycerylphosphorylethanolamine (GPE) has demonstrated protective effects in amyloid-injured astrocytes and in an aging model of human neural stem cells. However, the compound properties on mature neuronal cells remain unexplored. Herein, GPE was tested in human hippocampal neurons, which are involved in learning and memory, and characterized by a functional cholinergic transmission, thus representing a valuable cellular model to explore the beneficial properties of GPE. GPE induced the release of the main membrane phospholipids and of the acetylcholine neurotransmitter. Moreover, the compound reduced lipid peroxidation and enhanced membrane fluidity of human brain cells. GPE counteracted the DNA damage and viability decrease observed in in vitro aged neurons. Among GPE treatment effects, the autophagy was found positively upregulated. Overall, these results confirm the beneficial effects of GPE treatment and suggest the compound as a promising drug to preserve hippocampal neurons and virtually memory performances.
Development and Evaluation of Antimicrobial and Modulatory Activity of Inclusion Complex of Euterpe oleracea Mart Oil and β-Cyclodextrin or HP-β-Cyclodextrin
Authors: de Almeida Magalhães Thalita Sévia Soares , de Oliveira Macedo Pollyana Cristina , Kawashima Pacheco Stephany Yumi , Silva Sofia Santos da , Barbosa Euzébio Guimarães , Pereira Rayanne Rocha , Costa Roseane Maria Ribeiro , Silva Junior José Otávio Carréra , da Silva Ferreira Marília Andreza , de Almeida José Cezário , Rolim Neto Pedro José , Converti Attilio , Neves de Lima Ádley Antonini
Published: January 2020

The development of inclusion complexes is used to encapsulate nonpolar compounds and improve their physicochemical characteristics. This study aims to develop complexes made up of Euterpe oleracea Mart oil (EOO) and β-cyclodextrin (β-CD) or hydroxypropyl-β-cyclodextrin (HP-β-CD) by either kneading (KND) or slurry (SL). Complexes were analyzed by molecular modeling, Fourier-transform infrared spectroscopy, scanning electron microscopy, powder X-ray diffraction, thermogravimetry analysis and differential scanning calorimetry. The antibacterial activity was expressed as Minimum Inhibitory Concentration (MIC), and the antibiotic resistance modulatory activity as subinhibitory concentration (MIC/8) against Escherichia coli, Streptomyces aureus, Pseudomonas aeruginosa and Enterococcus faecalis. Inclusion complexes with β-CD and HP-β-CD were confirmed, and efficiency was proven by an interaction energy between oleic acid and β-CD of −41.28 ± 0.57 kJ/mol. MIC values revealed higher antibacterial activity of complexes compared to the isolated oil. The modulatory response of EOO and EOO-β-CD prepared by KND as well as of EOO-β-CD and EOO-HP-β-CD prepared by SL showed a synergistic effect with ampicillin against E. coli, whereas it was not significant with the other drugs tested, maintaining the biological response of antibiotics. The antimicrobial response exhibited by the complexes is of great significance because it subsidizes studies for the development of new pharmaceutical forms.
Bioinformatics for Renal and Urinary Proteomics: Call for Aggrandization
Authors: Paul Piby , Antonydhason Vimala , Gopal Judy , Haga Steve W. , Hasan Nazim , Oh Jae-Wook
Published: January 2020

The clinical sampling of urine is noninvasive and unrestricted, whereby huge volumes can be easily obtained. This makes urine a valuable resource for the diagnoses of diseases. Urinary and renal proteomics have resulted in considerable progress in kidney-based disease diagnosis through biomarker discovery and treatment. This review summarizes the bioinformatics tools available for this area of proteomics and the milestones reached using these tools in clinical research. The scant research publications and the even more limited bioinformatic tool options available for urinary and renal proteomics are highlighted in this review. The need for more attention and input from bioinformaticians is highlighted, so that progressive achievements and releases can be made. With just a handful of existing tools for renal and urinary proteomic research available, this review identifies a gap worth targeting by protein chemists and bioinformaticians. The probable causes for the lack of enthusiasm in this area are also speculated upon in this review. This is the first review that consolidates the bioinformatics applications specifically for renal and urinary proteomics.
Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death
Authors: Arnold Maria , Méndez-Carmona Natalia , Gulac Patrik , Wyss Rahel K , Rutishauser Nina , Segiser Adrian , Carrel Thierry , Longnus Sarah
Published: January 2020

Donation after circulatory death (DCD) could improve donor heart availability; however, warm ischemia-reperfusion injury raises concerns about graft quality. Mechanical postconditioning (MPC) may limit injury, but mechanisms remain incompletely characterized. Therefore, we investigated the roles of glucose metabolism and key signaling molecules in MPC using an isolated rat heart model of DCD. Hearts underwent 20 min perfusion, 30 min global ischemia, and 60 minu reperfusion with or without MPC (two cycles: 30 s reperfusion—30 s ischemia). Despite identical perfusion conditions, MPC either significantly decreased (low recovery = LoR; 32 ± 5%; p < 0.05), or increased (high recovery = HiR; 59 ± 7%; p < 0.05) the recovery of left ventricular work compared with no MPC (47 ± 9%). Glucose uptake and glycolysis were increased in HiR vs. LoR hearts (p < 0.05), but glucose oxidation was unchanged. Furthermore, in HiR vs. LoR hearts, phosphorylation of raptor, a downstream target of AMPK, increased (p < 0.05), cytochrome c release (p < 0.05) decreased, and TNFα content tended to decrease. Increased glucose uptake and glycolysis, lower mitochondrial damage, and a trend towards decreased pro-inflammatory cytokines occurred specifically in HiR vs. LoR MPC hearts, which may result from greater AMPK activation. Thus, we identify endogenous cellular mechanisms that occur specifically with cardioprotective MPC, which could be elicited in the development of effective reperfusion strategies for DCD cardiac grafts.
Magnetic Composite Submicron Carriers with Structure-Dependent MRI Contrast
Authors: Kozlova Anastasiia A. , German Sergey V. , Atkin Vsevolod S. , Zyev Victor V. , Astle Maxwell A. , Bratashov Daniil N. , Svenskaya Yulia I. , Gorin Dmitry A.
Published: January 2020

Magnetic contrast agents are widely used in magnetic resonance imaging in order to significantly change the signals from the regions of interest in comparison with the surrounding tissue. Despite a high variety of single-mode T1 or T2 contrast agents, there is a need for dual-mode contrast from the one agent. Here, we report on the synthesis of magnetic submicron carriers, containing Fe3O4 nanoparticles in their structure. We show the ability to control magnetic resonance contrast by changing not only the number of magnetite nanoparticles in one carrier or the concentration of magnetite in the suspension but also the structure of the core–shell itself. The obtained data open up the prospects for dual-mode T1/T2 magnetic contrast formation, as well as provides the basis for future investigations in this direction.
The Bed Nucleus of the Stria Terminalis as a Brain Correlate of Psychological Inflexibility in Fibromyalgia
Authors: Feliu-Soler Albert , Martínez-Zalacaín Ignacio , Pérez-Aranda Adrián , Borràs Xavier , Andrés-Rodríguez Laura , Sanabria-Mazo Juan P. , Fayed Nicolás , Stephan-Otto Christian , Núñez Christian , Soriano-Mas Carles , Luciano Juan V.
Published: January 2020

This study explored the brain structural correlates of psychological flexibility (PF) as measured with the Psychological Inflexibility in Pain Scale (PIPS) in patients with fibromyalgia (FM). Structural magnetic resonance imaging data from 47 FM patients were used to identify Gray Matter Volume (GMV) alterations related to PIPS scores. Brain GMV clusters related to PIPS were then correlated with clinical and cognitive variables to further explore how emerged brain clusters were intertwined with FM symptomatology. Longitudinal changes in PIPS-related brain clusters values were assessed by studying pre–post data from 30 patients (15 allocated to a mindfulness-based stress reduction (MBSR) program and 15 to treatment-as-usual). Changes in PIPS-related brain clusters were also explored in participants showing greater/lower longitudinal changes in PIPS scores. PIPS scores were positively associated with GMV in a bilateral cluster in the ventral part of the bed nucleus of the stria terminalis (BNST). Significant associations between BNST cluster with functional impairment, depressive symptomatology, perceived stress and the nonjudging mindfulness facet were observed. Participants reporting greater pre–post increases in PIPS scores showed greater increases in BNST cluster values. These findings contribute to the understanding on the neurobiological bases of PF in FM and encourage further explorations of the role of the BNST in chronic pain.
Saharan Dust Events in the Dust Belt -Canary Islands- and the Observed Association with in-Hospital Mortality of Patients with Heart Failure
Authors: Dominguez-Rodriguez Alberto , Baez-Ferrer Néstor , Rodríguez Sergio , Avanzas Pablo , Abreu-Gonzalez Pedro , Terradellas Enric , Cuevas Emilio , Basart Sara , Werner Ernest
Published: January 2020

Recent studies have found increases in the cardiovascular mortality rates during poor air quality events due to outbreaks of desert dust. In Tenerife, we collected (2014–2017) data in 829 patients admitted with a heart failure diagnosis in the Emergency Department of the University Hospital of the Canaries. In this region, concentrations of PM10 and PM2.5 are usually low (~20 and 10 µg/m3), but they increase to 360 and 115 μg/m3, respectively, during Saharan dust events. By using statistical tools (including multivariable logistic regressions), we compared in-hospital mortality of patients with heart failure and exposure to PM10 and PM2.5 during dust and no-dust events. We found that 86% of in-hospital heart failure mortality cases occurred during Saharan dust episodes that resulted in PM10 > 50 µg/m3 (interquartile range: 71–96 µg/m3). A multivariate analysis showed that, after adjusting for other covariates, exposure to Saharan dust events associated with PM10 > 50 µg/m3 was an independent predictor of heart failure in-hospital mortality (OR = 2.79, 95% CI (1.066–7.332), p = 0.03). In conclusion, this study demonstrates that exposure to high Saharan dust concentrations is independently associated with in-hospital mortality in patients with heart failure.
Saliva Diagnosis as a Disease Predictor
Authors: McGeer Patrick L , Lee Moonhee , Kennedy Krista , McGeer Edith G
Published: January 2020

Background: Saliva, the most readily available body fluid, is the product of genes which are in constant activity throughout life. Measurement of saliva can predict the onset of some diseases years before their accumulation in vulnerable tissues causes clinical signs to appear. The purpose of this study was is to demonstrate current applications of saliva analysis and to predict and prevent disease progression. Methods: We measured levels of Abeta42, C-reactive proteins (CRPs), and tumornecrosis factors (TNFs) in saliva from both healthy and fatal diseased cases such as cancer, Alzheimer’s disease (AD), and coronary heart disease by ELISA-mediated techniques. We also immunostained human tissue sections with antibodies specific to these proteins to demonstrate the data are comparable. Results: We found all the proteins expressed constantly in saliva from healthy controls but increased in diseased cases. This was accompanied by data from immunohistochemistry. It was also found that these proteins wereexpressed in high amounts in some healthy controls, which reflects high risk for the onset of diseases such as AD and heart diseases.Conclusions: It is concluded that measuring changes in essential gene products in saliva can predict onset of fatal diseases and open the door to effective protection measures, thus preventing premature death.
Gestational Exercise and Maternal and Child Health: Effects until Delivery and at Post-Natal Follow-up
Authors: Perales María , Valenzuela Pedro L. , Barakat Ruben , Cordero Yaiza , Peláez Mireia , López Carmen , Ruilope Luis M. , Santos-Lozano Alejandro , Lucia Alejandro
Published: January 2020

We studied the influence of pregnancy exercise on maternal/offspring cardiometabolic health until delivery and at follow-up. We pooled data from two randomized controlled trials from our group that were performed following the same methodology (one unpublished). We also collected follow-up data de novo from the participants of both trials and their offspring. In total, 1348 women with uncomplicated, singleton gestations were assigned to an intervention (n = 688, performing a supervised, moderate-intensity exercise program (three sessions/week)) or control group (n = 660). Maternal outcomes were excessive gestational weight gain (EGWG), gestational hypertension/diabetes and, at follow-up, return to pre-pregnancy weight within six months, hypertension, overweight/obesity, and other cardiometabolic conditions. Offspring outcomes were macrosomia and low-birthweight and, at follow-up, overweight/obesity, low-weight, and cardiometabolic conditions. Adherence to the intervention, which proved safe, was > 95%. Pregnancy exercise reduced the risk of EGWG, gestational hypertension, and diabetes (adjusted odds ratio (OR) and 95% confidence interval: 0.60 (0.46–0.79), 0.39 (0.23–0.67), and 0.48 (0.28–0.84)), and it was associated with a greater likelihood of returning to pre-pregnancy weight (2.37 (1.26–4.54)) and a lower risk of maternal cardiometabolic conditions (0.27 (0.08–0.95)) at the end of follow-up (median 6.1 years (interquartile range 1.8)). Pregnancy exercise also reduced the risk of macrosomia (0.36 (0.20–0.63)) and of childhood overweight/obesity during the first year (0.20 (0.06–0.63)). Our findings suggest that pregnancy exercise might protect maternal/offspring health.
Outcomes After Transjugular Intrahepatic Portosystemic Shunt in Cirrhotic Patients 70 Years and Older
Authors: Adlakha Natasha , Russo Mark W.
Published: January 2020

Transjugular intrahepatic portosystemic shunt (TIPS) is effective at treating ascites and variceal bleeding but may be associated with increased morbidity and mortality in older patients. Our aim was to report outcomes in patients 70 years and older who underwent TIPS because data are limited in this population. We performed a retrospective review of patients who underwent TIPS at our institution over 10 years. We matched those 70 years and older to those 50–59 years old by year of TIPS and the Model for End-Stage Liver Diseae-Sodium (MELD-Na). Thirty-day readmissions were higher in the elderly group (n = 50) compared to the younger group (n = 50), n = 17 (34%) and n = 6 (12%) (p = 0.02), respectively. Readmissions for post-TIPS hepatic encephalopathy (HE) in the older and younger groups were n = 14 (28%) and n = 5 (10%) (p = 0.04), respectively. Thirty-day mortality was higher in the older group compared to the younger group, but the difference was not statistically significant, 24% and 12%, respectively (p = 0.19). TIPS can be performed safely in patients 70 years and older, but the overall readmissions, and specifically for HE, were significantly higher in older patients. Patients 70 years and older should be followed closely after TIPS, and early introduction of treatment for encephalopathy should be considered.
Extending Complex Conjugate Control to Nonlinear Wave Energy Converters
Authors: Wilson David G. , Robinett Rush D. , Bacelli Giorgio , Abdelkhalik Ossama , Coe Ryan G.
Published: January 2020

This paper extends the concept of Complex Conjugate Control (CCC) of linear wave energy converters (WECs) to nonlinear WECs by designing optimal limit cycles with Hamiltonian Surface Shaping and Power Flow Control (HSSPFC). It will be shown that CCC for a regular wave is equivalent to a power factor of one in electrical power networks, equivalent to mechanical resonance in a mass-spring-damper (MSD) system, and equivalent to a linear limit cycle constrained to a Hamiltonian surface defined in HSSPFC. Specifically, the optimal linear limit cycle is defined as a second-order center in the phase plane projection of the constant energy orbit across the Hamiltonian surface. This concept of CCC described by a linear limit cycle constrained to a Hamiltonian surface will be extended to nonlinear limit cycles constrained to a Hamiltonian surface for maximum energy harvesting by the nonlinear WEC. The case studies presented confirm increased energy harvesting which utilizes nonlinear geometry realization for reactive power generation.
The Squeaky Yeast Gets Greased: The Roles of Host Lipids in the Clearance of Pathogenic Fungi
Authors: Guzman Gaelen , Niekamp Patrick , Tafesse Fikadu Geta
Published: January 2020

Fungal infections remain a global health threat with high morbidity and mortality. The human immune system must, therefore, perpetually defend against invasive fungal infections. Phagocytosis is critical for the clearance of fungal pathogens, as this cellular process allows select immune cells to internalize and destroy invading fungal cells. While much is known about the protein players that enable phagocytosis, the various roles that lipids play during this fundamental innate immune process are still being illuminated. In this review, we describe recent discoveries that shed new light on the mechanisms by which host lipids enable the phagocytic uptake and clearance of fungal pathogens.
Synthesis and Antimicrobial Evaluation of Side-Chain Derivatives based on Eurotiumide A
Authors: Nakayama Atsushi , Sato Hideo , Nakamura Tenta , Hamada Mai , Nagano Shuji , Kameyama Shuhei , Furue Yui , Hayashi Naoki , Kamoshida Go , Karanjit Sangita , Oda Masataka , Namba Kosuke
Published: January 2020

Side-chain derivatives of eurotiumide A, a dihydroisochroman-type natural product, have been synthesized and their antimicrobial activities described. Sixteen derivatives were synthesized from a key intermediate of the total synthesis of eurotiumide A, and their antimicrobial activities against two Gram-positive bacteria, methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), and a Gram-negative bacterium, Porphyromonas gingivalis, were evaluated. The results showed that derivatives having an iodine atom on their aromatic ring instead of the prenyl moiety displayed better antimicrobial activity than eurotiumide A against MSSA and P. gingivalis. Moreover, we discovered that a derivative with an isopentyl side chain, which is a hydrogenated product of eurotiumide A, is the strongest antimicrobial agent against all three strains, including MRSA.
Overexpression of KLF17 Predicts a Favorable Prognosis in Patients with Oral Squamous Cell Carcinoma: A Retrospective Study
Authors: Lee Yi-Ju , Chan Lung , Yeh Chung-Min , Lee Chien-Hsun , Sung Wen-Wei
Published: January 2020

Background and Objectives: Patients with oral squamous cell carcinoma (OSCC), a common malignancy in Asian countries, have a poor prognosis. We investigated the role of Krüppel-like factor 17 (KLF17) and its prognostic significance in OSCC. Materials and Methods: KLF17 expression was measured by immunohistochemical staining of specimens from 283 patients with OSCC. We analyzed correlations between KLF17 expression and clinicopathologic features and between KLF17 expression and overall survival. The prognostic value of KLF17 was tested using Kaplan–Meier analysis and Cox proportional hazard models. Results: Among the 283 patients, high KLF17 expression was significantly associated with an early OSCC stage and low T-value (p = 0.033 and p = 0.036, respectively). The five-year survival rates were better in patients with high KLF17 expression than with low expression (66.5% and 49.6%, respectively). The prognostic role of KLF17 was further confirmed through multivariate analysis (hazard ratio 1.506, 95% confidence interval 1.034–2.191, p = 0.033). The prognostic value was more significant in patients with a history of betel quid chewing or with a low T-value. Conclusions: High KLF17 expression can serve as a marker for a favorable prognosis in patients with OSCC. The prognostic role of KLF17 is more significant in patients with a history of betel quid chewing or a low T-value.
Mathematical Modeling of the Effect of Water Splitting on Ion Transfer in the Depleted Diffusion Layer Near an Ion-Exchange Membrane
Authors: Nikonenko Victor , Urtenov Mahamet , Mareev Semyon , Pourcelly Gérald
Published: January 2020

Water splitting (WS) and electroconvection (EC) are the main phenomena affecting ion transfer through ion-exchange membranes in intensive current regimes of electrodialysis. While EC enhances ion transport, WS, in most cases, is an undesirable effect reducing current efficiency and causing precipitation of sparingly soluble compounds. A mathematical description of the transfer of salt ions and H+ (OH−) ions generated in WS is presented. The model is based on the Nernst–Planck and Poisson equations; it takes into account deviation from local electroneutrality in the depleted diffusion boundary layer (DBL). The current transported by water ions is given as a parameter. Numerical and semi-analytical solutions are developed. The analytical solution is found by dividing the depleted DBL into three zones: the electroneutral region, the extended space charge region (SCR), and the quasi-equilibrium zone near the membrane surface. There is an excellent agreement between two solutions when calculating the concentration of all four ions, electric field, and potential drop across the depleted DBL. The treatment of experimental partial current–voltage curves shows that under the same current density, the surface space charge density at the anion-exchange membrane is lower than that at the cation-exchange membrane. This explains the negative effect of WS, which partially suppresses EC and reduces salt ion transfer. The restrictions of the analytical solution, namely, the local chemical equilibrium assumption, are discussed.
Near Solidus Forming (NSF): Semi-Solid Steel Forming at High Solid Content to Obtain As-Forged Properties
Authors: Lozares Jokin , Plata Gorka , Hurtado Iñaki , Sánchez Andrea , Loizaga Iñigo
Published: January 2020

Near solidus forming (NSF) of steels is a novel process under the umbrella of semi-solid forming technologies midway between classical hot forging and semi-solid technologies. This article presents the work done at Mondragon Unibertsitatea to develop this technology and demonstrates the great potential of the NSF process. The study proves the capability of the process to reduce raw material consumption by 20%, reduce forming loads from 2100 t to 300 t, and reduce forming steps from three to one, to obtain as-forged mechanical properties, as well as the excellent repeatability of the process. The work demonstrates that manufacturing commercial steel components in a single step using several off-the-shelf alloys is possible thanks to the flowing pattern of the material, which enables near-net shaping. In the first part of the article, a general overview of the semi-automated near solidus forming cell, together with a description of the NSF manufacturing trials, is provided, followed by the presentation and discussion of the results for the selected steel alloys.
A Quantitative Study of the Secondary Acoustic Radiation Force on Biological Cells during Acoustophoresis
Authors: Saeidi Davood , Saghafian Mohsen , Haghjooy Javanmard Shaghayegh , Wiklund Martin
Published: January 2020

We investigate cell-particle secondary acoustic radiation forces in a plain ultrasonic standing wave field inside a microfluidic channel. The effect of secondary acoustic radiation forces on biological cells is measured in a location between a pressure node and a pressure anti-node and the result is compared with theory by considering both compressibility and density dependent effects. The secondary acoustic force between motile red blood cells (RBCs) and MCF-7 cells and fixed 20 µm silica beads is investigated in a half-wavelength wide microchannel actuated at 2 MHz ultrasonic frequency. Our study shows that the secondary acoustic force between cells in acoustofluidic devices could play an important role for cell separation, sorting, and trapping purposes. Our results also demonstrate the possibility to isolate individual cells at trapping positions provided by silica beads immobilized and adhered to the microchannel bottom. We conclude that during certain experimental conditions, the secondary acoustic force acting on biological cells can dominate over the primary acoustic radiation force, which could open up for new microscale acoustofluidic methods.
Effects of Light Pollution on the Early Life Stages of the Most Abundant Northern Red Sea Coral
Authors: Tamir Raz , Eyal Gal , Cohen Itay , Loya Yossi
Published: January 2020

The growth in human population along coastal areas is exposing marine environments to increasing anthropogenic light sources. Despite the potential effects of this modern phenomenon, very few studies have examined its implications for corals. Here, we present a long-term study of coral early life stages under light pollution conditions at night. Coral larvae were collected from Stylophora pistillata colonies, and then settled and grown under experimental conditions of two different common city lighting methods (fluorescent or LED). Effects of the artificial lighting on the coral settlement success, survivorship, growth rate, photosynthetic efficiency, and calcification rate were examined over a period of one year. The control exhibited ~30% higher settlement success compared to the two light treatments, while under the light treatments corals showed higher survivorship, growth, and calcification rates. In addition, an indication of damage to the photosynthetic system was found in the light-polluted corals, which was reflected in their photosynthesis efficiency parameters: i.e., lower maximum light utilization coefficient (α), lower maximum potential photosynthetic rate (Pmax), and lower photosynthetic maximal quantum yield (Fv/Fm). Our findings provide evidence of the potential adverse effects of artificial lighting methods on the natural environment of coral reefs. We conclude that the use of the LED lighting method has high interference potential for the early life stages of corals.
Evaluation of A Phylogenetic Pipeline to Examine Transmission Networks in A Canadian HIV Cohort
Authors: Mak Lauren , Perera Deshan , Lang Raynell , Kossinna Pathum , He Jingni , Gill M. John , Long Quan , van Marle Guido
Published: January 2020

Modern computational methods using patient Human Immunodeficiency Virus type 1 (HIV-1) genetic sequences can model population-wide viral transmission dynamics. Accurate transmission inferences can play a critical role in the characterization of high-risk transmission clusters important for enhanced epidemiological control. We evaluated a phylogenetics-based analysis pipeline to infer person-to-person (P2P) infection dates and transmission relationships using 139 patient HIV-1 polymerase Sanger sequences curated by the Southern Alberta HIV Clinic. Parameter combinations tailored to HIV-1 transmissions were tuned with respect to inference accuracy. Inference accuracy was assessed using clinically confirmed P2P transmission patient data. The most accurate parameter settings correctly inferred 48.56% of the P2P relationships (95% confidence interval 63.89–33.33%), slightly lower than next-generation-sequencing methods. The infection date was correctly inferred 43.02% (95% confidence interval 49.89–35.63%). Several novel unsuspected transmission clusters of up to twelve patients were identified. An accuracy trade-off between inferring transmission relationships and infection dates was observed. Using clinically confirmed P2P transmission data as benchmark, our phylogenetic methods identified sufficient P2P transmission relationships using readily available low-resolution Sanger sequences. These approaches may give valuable information about HIV infection dynamics within a population and may be easily deployed to guide public health interventions, without a need for next generation sequencing technology.
Computational Modeling of the Human Microbiome
Authors: Chowdhury Shomeek , Fong Stephen S.
Published: January 2020

The impact of microorganisms on human health has long been acknowledged and studied, but recent advances in research methodologies have enabled a new systems-level perspective on the collections of microorganisms associated with humans, the human microbiome. Large-scale collaborative efforts such as the NIH Human Microbiome Project have sought to kick-start research on the human microbiome by providing foundational information on microbial composition based upon specific sites across the human body. Here, we focus on the four main anatomical sites of the human microbiome: gut, oral, skin, and vaginal, and provide information on site-specific background, experimental data, and computational modeling. Each of the site-specific microbiomes has unique organisms and phenomena associated with them; there are also high-level commonalities. By providing an overview of different human microbiome sites, we hope to provide a perspective where detailed, site-specific research is needed to understand causal phenomena that impact human health, but there is equally a need for more generalized methodology improvements that would benefit all human microbiome research.
Adhesion of Campylobacter jejuni Is Increased in Association with Foodborne Bacteria
Authors: Klančnik Anja , Gobin Ivana , Jeršek Barbara , Smole Možina Sonja , Vučković Darinka , Tušek Žnidarič Magda , Abram Maja
Published: January 2020

The aim of this study was to evaluate Campylobacter jejuni NTCT 11168 adhesion to abiotic and biotic surfaces when grown in co-culture with Escherichia coli ATCC 11229 and/or Listeria monocytogenes 4b. Adhesion of C. jejuni to polystyrene and to Caco-2 cells and Acanthamoeba castellanii was lower for at least 3 log CFU/mL compared to E. coli and L. monocytogenes. Electron micrographs of ultrathin sections revealed interactions of C. jejuni with host cells. In co-culture with E. coli and L. monocytogenes, adhesion of C. jejuni to all tested surfaces was significantly increased for more than 1 log CFU/mL. There was 10% higher aggregation for C. jejuni than for other pathogens, and high co-aggregation of co-cultures of C. jejuni with E. coli and L. monocytogenes. These data show that C. jejuni in co-cultures with E. coli and L. monocytogenes present significantly higher risk than C. jejuni as mono-cultures, which need to be taken into account in risk evaluation. C. jejuni adhesion is a prerequisite for their colonization, biofilm formation, and further contamination of the environment. C. jejuni survival under adverse conditions as a factor in their pathogenicity and depends on their adhesion to different surfaces, not only as individual strains, but also in co-cultures with other bacteria like E. coli and L. monocytogenes.
Transmission of Vancomycin-Resistant Enterococci in the Hospital Setting: Uncovering the Patient–Environment Interplay
Authors: Correa-Martinez Carlos L. , Tönnies Hauke , Froböse Neele J. , Mellmann Alexander , Kampmeier Stefanie
Published: January 2020

Vancomycin-resistant enterococci (VRE) are relevant nosocomial pathogens with an increasing incidence in the last decades. Their transmission is optimal in the hospital setting, as it offers two potential, large reservoirs that are closely related: susceptible patients and their environment. Here we investigate the role of the hospital environment in the nosocomial transmission of VRE by establishing concrete links between contaminated surfaces and colonized/infected patients in outbreak and non-outbreak settings. Environmental and patient VRE isolates were collected between 2013 and 2019 and analyzed by whole-genome sequencing (WGS), subsequent multilocus sequence typing (MLST), and core genome (cg) MLST. Pairs of isolates differing in <3 alleles were rated as closely related, making a transmission likely. Fifty-three environmental VRE isolates were analyzed. MLST sequence types (ST) ST203 (50.0%), ST192 (21.3%), ST117 (17.3%), ST721 (8.8%), ST80 (2%), and ST1489 (0.7%) were detected, carrying the resistance determinants vanA (72.7%), vanB (24%), or both (3.3%). Of the 53 environmental isolates, 51 were found to form five clusters with genetically related patient isolates (n = 97 isolates). WGS confirms the role of the environment in the transmission dynamics of VRE in both the outbreak and non-outbreak settings, highlighting the importance of prevention and control of VRE spread.
Novel Approach to Modeling the Seismic Waves in the Areas with Complex Fractured Geological Structures
Authors: Khokhlov Nikolay , Stognii Polina
Published: January 2020

This paper presents a novel approach to modeling the propagation of seismic waves in a medium containing subvertical fractured inhomogeneities, typical for mineralization zones. The developed method allows us to perform calculations on a structural computational grid, which avoids the construction of unstructured grids. For the calculations, the grid-characteristic method is used. We also present a comparison of the proposed method with the one described at earlier works and discuss the areas of its practical application. As an example, the numerical results for a cluster of subvertical fractures are given. A new approach for modeling fractures makes it quite easy to incorporate fractured objects into the seismic models and perform calculations without using algorithms on unstructured and curved grids.
Timing of Paleozoic Exhumation and Deformation of the High-Pressure Vestgӧtabreen Complex at the Motalafjella Nunatak, Svalbard
Authors: Barnes Christopher J. , Walczak Katarzyna , Janots Emilie , Schneider David , Majka Jarosław
Published: January 2020

The Vestgӧtabreen Complex exposed in the Southwestern Caledonian Basement Province of Svalbard comprises two Caledonian high-pressure units. In situ white mica 40Ar/39Ar and monazite Th-U-total Pb geochronology has resolved the timing of the tectonic evolution of the complex. Cooling of the Upper Unit during exhumation occurred at 476 ± 2 Ma, shortly after eclogite-facies metamorphism. The two units were juxtaposed at 454 ± 6 Ma. This was followed by subaerial exposure and deposition of Bullbreen Group sediments. A 430–400 Ma late Caledonian phase of thrusting associated with major sinistral shearing throughout Svalbard deformed both the complex and the overlying sediments. This phase of thrusting is prominently recorded in the Lower Unit, and is associated with a pervasive greenschist-facies metamorphic overprint of high-pressure lithologies. A c. 365–344 Ma geochronological record may represent an Ellesmerian tectonothermal overprint. Altogether, the geochronological evolution of the Vestgӧtabreen Complex, with previous petrological and structural studies, suggests that it may be a correlative to the high-pressure Tsäkkok Lens in the Scandinavian Caledonides. It is suggested that the Vestgӧtabreen Complex escaped to the periphery of the orogen along the sinistral strike-slip shear zones prior to, or during the initial stages of continental collision between Baltica and Laurentia.
Quantitative Microstructural Analysis and X-ray Computed Tomography of Ores and Rocks—Comparison of Results
Authors: Popov Oleg , Talovina Irina , Lieberwirth Holger , Duriagina Asiia
Published: January 2020

Profound knowledge of the structure and texture of rocks and ores as well as the behavior of the materials under external loads is essential to further improvements in size reduction processes, particularly in terms of liberation size. New analytical methods such as computer tomography (CT) were adopted to improve the understanding of material characteristics in rocks and ores relevant to mineral processing, particular the crushing and grinding and the modelling/simulation thereof. Results obtained on the texture and structure of identical samples of rather different rocks and ores (copper ore, granodiorite, kimberlite) are compared by CT with quantitative results from traditional optical microscopy obtained by quantitative microstructural analysis (QMA). While the two approaches show a good agreement of the results in many areas, the measurements with the two different methods also exhibit remarkable differences in other areas, which are discussed further. In conclusion, both methods have their specific advantages starting from sample preparation to the accuracy of information obtained concerning certain parameters of mode and fabric. While sample preparation is faster with CT and information on special distribution of metal minerals is more reliable, the information on mode, grain size and clustering seem to be more precise with QMA. Based on the results, it can be concluded that both methods are comparable in many areas, but in in the field of spatial distribution, they are merely complementary.
Photocatalytic and Gas Sensitive Multiwalled Carbon Nanotube/TiO2-ZnO and ZnO-TiO2 Composites Prepared by Atomic Layer Deposition
Authors: Bakos László Péter , Justh Nóra , Moura da Silva Bezerra da Costa Ulisses Carlo , László Krisztina , Lábár János László , Igricz Tamás , Varga-Josepovits Katalin , Pasierb Pawel , Färm Elina , Ritala Mikko , Leskelä Markku , Szilágyi Imre Miklós
Published: January 2020

TiO2 and ZnO single and multilayers were deposited on hydroxyl functionalized multi-walled carbon nanotubes using atomic layer deposition. The bare carbon nanotubes and the resulting heterostructures were characterized by TG/DTA, Raman, XRD, SEM-EDX, XPS, TEM-EELS-SAED and low temperature nitrogen adsorption techniques, and their photocatalytic and gas sensing activities were also studied. The carbon nanotubes (CNTs) were uniformly covered with anatase TiO2 and wurtzite ZnO layers and with their combinations. In the photocatalytic degradation of methyl orange, the most beneficial structures are those where ZnO is the external layer, both in the case of single and double oxide layer covered CNTs (CNT-ZnO and CNT-TiO2-ZnO). The samples with multilayer oxides (CNT-ZnO-TiO2 and CNT-TiO2-ZnO) have lower catalytic activity due to their larger average densities, and consequently lower surface areas, compared to single oxide layer coated CNTs (CNT-ZnO and CNT-TiO2). In contrast, in gas sensing it is advantageous to have TiO2 as the outer layer. Since ZnO has higher conductivity, its gas sensing signals are lower when reacting with NH3 gas. The double oxide layer samples have higher resistivity, and hence a larger gas sensing response than their single oxide layer counterparts.