bluuebunny/crossref_metadata_2025 huggingface dataset:
Gametogenesis-Related Fluctuations in Ovothiol Levels in the Mantle of Mussels from Different Estuaries: Fighting Oxidative Stress for Spawning in Polluted Waters
Authors: Diaz de Cerio Oihane , Reina Lander , Squatrito Valeria , Etxebarria Nestor , Gonzalez-Gaya Belen , Cancio Ibon
Published: March 2020

Reactive oxygen species present a challenge for marine organisms releasing gametes into the water. Thiol-containing molecules protect cells against oxidative stress, and ovothiol (OSH), an antioxidant-reducing mercaptohistidine, has been described as especially relevant in the oocytes of marine invertebrates. Ovothiol synthase (ovoA), in charge of the first step in OSH synthesis, was sequenced in mussels, Mytilus galloprovincialis. Transcription levels of ovoA in mantle did not significantly change along the reproductive cycle. No alterations of ovoA transcription were observed after a laboratory copper (10 µg/L) exposure or in mussels captured in a highly polluted site. Conversely, the metabolomic analysis of the hydrophilic metabolite content in mantle clearly classified mussels according to their site of origin, especially at the most advanced stages of oogenesis. Quantification of OSH-A and -B and glutathione (GSH), revealed stable levels in mantle at early gametogenesis in the unpolluted sampling site, but a strong increase in female mantle previous to spawning in the polluted site. These increased concentrations under pollution suggest that OSH-A accumulates along oogenesis, independent of gene transcription regulation. The concerted accumulation of OSH-A and GSH suggests the building of a balanced cellular redox-system to scavenge ROS produced in the oocyte before and during fertilization.
In Search of High-Yielding and Single-Compound-Yielding Plants: New Sources of Pharmaceutically Important Saponins from the Primulaceae Family
Authors: Włodarczyk Maciej , Pasikowski Paweł , Osiewała Kinga , Frankiewicz Aleksandra , Dryś Andrzej , Gleńsk Michał
Published: March 2020

So far, only a few primrose species have been analyzed regarding their saponin composition and content. Moreover, the roots of only two of them are defined by the European Union (EU) Pharmacopoeia monograph and commercially utilized by the pharmaceutical industry. Thus, this study intended to find some new sources of main triterpene saponins from Primulae radix, namely primulasaponins I and II together with the closely related sakurasosaponin. Using isolated standards, UHPLC-ESI-HRMS served to assess over 155 Primulaceae members qualitatively and quantitatively. Nine examples of plants accumulating over 5% of primulasaponin I in their roots were found. Among them, in one case, it was found as the almost sole secondary metabolite with the concentration of 15–20% (Primula grandis L.). A reasonable content of primulasaponin II was found to be typical for Primula vulgaris Huds. and P. megaseifolia Boiss. & Bal. The sakurasosaponin level was found in seven species to exceed 5%. The finding of new, single and rich sources of the abovementioned biomolecules among species that were never analyzed phytochemically is important for future research and economic benefit. The chemotaxonomic significance of the occurrence of these three saponins in Primulaceae is discussed.
Rhizophagus irregularis and Rhizoctonia solani Differentially Elicit Systemic Transcriptional Expression of Polyphenol Biosynthetic Pathways Genes in Sunflower
Authors: Rashad Younes , Aseel Dalia , Hammad Saad , Elkelish Amr
Published: March 2020

Plant roots are exposed to penetration by different biotrophic and necrotrophic fungi. However, plant immune responses vary, depending on the root-penetrating fungus. Using qRT-PCR, changes over time in the systemic transcriptional expression of the polyphenol biosynthesis-related genes were investigated in sunflower plants in response to colonization with Rhizophagus irregularis and/or infection with Rhizoctonia solani. The results demonstrated that both fungi systemically induced the transcriptional expression of most of the addressed genes at varying degrees. However, the inducing effect differed according to the treatment type, plant organ, targeted gene, and time stage. The inducing effect of R. irregularis was more prevalent than R. solani in the early stages. In general, the dual treatment showed a superior inducing effect over the single treatments at most of the time. The hierarchical clustering analysis showed that cinnamate-4-hydroxylase was the master expressed gene along the studied time period. The cell wall lignification was the main plant-defensive-mechanism induced. In addition, accumulations of chlorogenic acid, flavonoids, and anthocyanins were also triggered. Moreover, colonization with R. irregularis improved the plant growth and reduced the disease severity. We can conclude that the proactive, rather than curative, colonization with R. irregularis is of great importance, owing to their protective and growth-promoting roles, even if no infection occurred.
Using a Convolutional Siamese Network for Image-Based Plant Species Identification with Small Datasets
Authors: Figueroa-Mata Geovanni , Mata-Montero Erick
Published: March 2020

The application of deep learning techniques may prove difficult when datasets are small. Recently, techniques such as one-shot learning, few-shot learning, and Siamese networks have been proposed to address this problem. In this paper, we propose the use a convolutional Siamese network (CSN) that learns a similarity metric that discriminates between plant species based on images of leaves. Once the CSN has learned the similarity function, its discriminatory power is generalized to classify not just new pictures of the species used during training but also entirely new species for which only a few images are available. This is achieved by exposing the network to pairs of similar and dissimilar observations and minimizing the Euclidean distance between similar pairs while simultaneously maximizing it between dissimilar pairs. We conducted experiments to study two different scenarios. In the first one, the CSN was trained and validated with datasets that comprise 5, 10, 15, 20, 25, and 30 pictures per species, extracted from the well-known Flavia dataset. Then, the trained model was tested with another dataset composed of 320 images (10 images per species) also from Flavia. The obtained accuracy was compared with the results of feeding the same training, validation, and testing datasets to a convolutional neural network (CNN) in order to determine if there is a threshold value t for dataset size that defines the intervals for which either the CSN or the CNN has better accuracy. In the second studied scenario, the accuracy of both the CSN and the CNN—both trained and validated with the same datasets extracted from Flavia—were compared when tested on a set of images of leaves of 20 Costa Rican tree species that are not represented in Flavia.
The Detection of Wound Infection by Ion Mobility Chemical Analysis
Authors: Daulton Emma , Wicaksono Alfian , Bechar Janak , Covington James A. , Hardwicke Joseph
Published: March 2020

Surgical site infection represents a large burden of care in the National Health Service. Current methods for diagnosis include a subjective clinical assessment and wound swab culture that may take several days to return a result. Both techniques are potentially unreliable and result in delays in using targeted antibiotics. Volatile organic compounds (VOCs) are produced by micro-organisms such as those present in an infected wound. This study describes the use of a device to differentiate VOCs produced by an infected wound vs. colonised wound. Malodourous wound dressings were collected from patients, these were a mix of post-operative wounds and vascular leg ulcers. Wound microbiology swabs were taken and antibiotics commenced as clinically appropriate. A control group of soiled, but not malodorous wound dressings were collected from patients who had a split skin graft (SSG) donor site. The analyser used was a G.A.S. GC-IMS. The results from the samples had a sensitivity of 100% and a specificity of 88%, with a positive predictive value of 90%. An area under the curve (AUC) of 91% demonstrates an excellent ability to discriminate those with an infected wound from those without. VOC detection using GC-IMS has the potential to serve as a diagnostic tool for the differentiation of infected and non-infected wounds and facilitate the treatment of wound infections that is cost effective, non-invasive, acceptable to patients, portable, and reliable.
Bloods—An Open Access Journal of Hematology
Authors: Lin Shu-Kun
Published: March 2020

MDPI has been publishing several medical journals, including the International Journal of Neonatal Screening [...]
Welcome to Bloods—An International Open Access Journal
Authors: Carbone Antonino
Published: March 2020

Hematologists, hematopathologists, cellular biologists, immunologists, and molecular biologists are invited to contribute to Bloods, a new international multidisciplinary journal for clinicians and experimental researchers of neoplastic and non-neoplastic blood diseases [...]
Pediatric Traumatic Brain Injury in the United States: Rural-Urban Disparities and Considerations
Authors: Yue John K. , Upadhyayula Pavan S. , Avalos Lauro N. , Cage Tene A.
Published: March 2020

Introduction: Traumatic brain injury (TBI) remains a primary cause of pediatric morbidity. The improved characterization of healthcare disparities for pediatric TBI in United States (U.S.) rural communities is needed to advance care. Methods: The PubMed database was queried using keywords ((“brain/head trauma” OR “brain/head injury”) AND “rural/underserved” AND “pediatric/child”). All qualifying articles focusing on rural pediatric TBI, including the subtopics epidemiology (N = 3), intervention/healthcare cost (N = 6), and prevention (N = 1), were reviewed. Results: Rural pediatric TBIs were more likely to have increased trauma and head injury severity, with higher-velocity mechanisms (e.g., motor vehicle collisions). Rural patients were at risk of delays in care due to protracted transport times, inclement weather, and mis-triage to non-trauma centers. They were also more likely than urban patients to be unnecessarily transferred to another hospital, incurring greater costs. In general, rural centers had decreased access to mental health and/or specialist care, while the average healthcare costs were greater. Prevention efforts, such as mandating bicycle helmet use through education by the police department, showed improved compliance in children aged 5–12 years. Conclusions: U.S. rural pediatric patients are at higher risk of dangerous injury mechanisms, trauma severity, and TBI severity compared to urban. The barriers to care include protracted transport times, transfer to less-resourced centers, increased healthcare costs, missing data, and decreased access to mental health and/or specialty care during hospitalization and follow-up. Preventative efforts can be successful and will require an improved multidisciplinary awareness and education.
Novel Characterizations of Mechanical Properties for a Copper/Single-Walled Carbon Nanotube Nanocomposite Synthesized by Laser Surface Implanting
Authors: Tu Jay F. , Rajule Nilesh , Mun Sang Don
Published: March 2020

In our previous studies, we have developed a wet process, denoted laser surface implanting (LSI), to synthesize a copper/single-walled carbon nanotube (Cu–SWCNT) metal nanocomposite as an implant onto the surface of a pure copper substrate. The nanostructure of this Cu–SWCNT composite was confirmed independently by several methods, including transmission electron microscope (TEM) images, which show discernable SWCNT clusters in nano sizes inside the copper matrix. The hardness was measured by micro-hardness tests to indicate over three times hardness over that of pure copper could be achieved. In this paper, we present several unique ways to further characterize the mechanical properties of the Cu-SWCNT nanocomposite. Nano-hardness tests are first performed to confirm that hardness improvement, about three times that of pure copper, is achieved, consistent with the micro-hardness test results. A new toughness measurement based on focus ion beam (FIB) bombardment was performed to demonstrate 2.5 times toughness improvement. Finally, a new compression test rig was designed to conduct plane strain compression test for an array of Cu-SWCNT implants. The results confirmed that the Cu-SWCNT nanocomposite exhibits a stress-strain behavior consistent with the results of the hardness and FIB tests.
Systematic Review of Patient-Reported Outcomes following Surgical Treatment of Lymphedema
Authors: Coriddi Michelle , Dayan Joseph , Sobti Nikhil , Nash David , Goldberg Johanna , Klassen Anne , Pusic Andrea , Mehrara Babak
Published: March 2020

Introduction: Analysis of quality of life (QOL) outcomes is an important aspect of lymphedema treatment since this disease can substantially impact QOL in affected individuals. There are a growing number of studies reporting patient-reported outcomes (PROMs) for patients with lymphedema. The purpose of this study was to conduct a systematic review of outcomes and utilization of PROMs following surgical treatment of lymphedema. Methods: A literature search of four databases was performed up to and including March, 2019. Studies included reported on QOL outcomes after physiologic procedures, defined as either lymphovenous bypass (LVB) or vascularized lymph node transplant (VLNT), to treat upper and/or lower extremity primary or secondary lymphedema. Results: In total, 850 studies were screened—of which, 32 studies were included in this review. Lymphovenous bypass was the surgical intervention in 16 studies, VLNT in 11 studies, and both in 5 studies. Of the 32 total studies, 16 used validated survey tools. The most commonly used PROM was the lymph quality of life measure for limb lymphedema (LYMQOL) (12 studies). In the remaining four studies, the upper limb lymphedema 27 scale (ULL27), the short form 36 questionnaire (SF-36), the lymphedema functioning, disability and health questionnaire (Lymph-ICF), and lymphedema life impact scale (LLIS) were each used once. QOL improvement following surgical treatment was noted in all studies. Conclusions: Physiologic surgical treatment of lymphedema results in improved QOL outcomes in most patients. The use of validated PROM tools is increasing but there is no current consensus on use. Future research to evaluate the psychometric properties of PROMs in lymphedema is needed to guide the development and use of lymphedema-specific tools.
Potential Mechanisms of Cancer-Related Hypercoagulability
Authors: Nasser Nicola J. , Fox Jana , Agbarya Abed
Published: March 2020

The association between cancer and thrombosis has been known for over a century and a half. However, the mechanisms that underlie this correlation are not fully characterized. Hypercoagulability in cancer patients can be classified into two main categories: Type I and Type II. Type I occurs when the balance of endogenous heparin production and degradation is disturbed, with increased degradation of endogenous heparin by tumor-secreted heparanase. Type II hypercoagulability includes all the other etiologies, with factors related to the patient, the tumor, and/or the treatment. Patients with poor performance status are at higher risk of venous thromboembolism (VTE). Tumors can result in VTE through direct pressure on blood vessels, resulting in stasis. Several medications for cancer are correlated with a high risk of thrombosis. These include hormonal therapy (e.g., tamoxifen), chemotherapy (e.g., cisplatin, thalidomide and asparaginase), molecular targeted therapy (e.g., lenvatinib, osimertinib), and anti-angiogenesis monoclonal antibodies (e.g., bevacizumab and ramucirumab).
Photo-Functionalized Magnetic Nanoparticles as a Nanocarrier of Photodynamic Anticancer Agent for Biomedical Theragnostics
Authors: Nam Ki Chang , Han Yong Soo , Lee Jong-Min , Kim Si Chan , Cho Guangsup , Park Bong Joo
Published: March 2020

Various theragnostic agents have been devised and developed as cancer treatments; however, existing agents are often limited by their specific functions and complexities. Here, we report multifunctional magnetite (Fe3O4) nanoparticles functionalized with chlorin e6 (Ce6) and folic acid (FA) using a simple fabrication process to be used as theragnostic agents in photodynamic therapy (PDT). The effectiveness of cellular uptake of Fe3O4-Ce6-FA nanoparticles (FCF NPs) and its visualization as well as the photodynamic anticancer activities were evaluated. The mechanism of cancer cell death by the FCF NPs was also verified with qualitative and quantitative methods. Results indicate that FCF NPs have good penetration efficacy, resulting in excellent in vitro fluorescence and magnetic resonance imaging in cancer cells. FCF NPs exhibited promising anticancer activity in an irradiation time- and FCF NPs-dose-dependent manner in various cancer cell lines, leading to apoptotic cell death via morphological changes in cell membrane, nuclear, and DNA damage, and via overexpression of apoptosis-related genes, such as ZFP36L1, CYR61, GADD45G, caspases-2, -3, -9, 10, and -14. This study suggests that FCF NPs may be safely used in cancer therapy via PDT and could be a versatile therapeutic tool and biocompatible theragnostic agent, which may be used in diagnostic imaging.
Development and Validation of a Clinically Relevant Workflow for MR-Guided Volumetric Arc Therapy in a Rabbit Model of Head and Neck Cancer
Authors: Rajab Bolookat Eftekhar , Malhotra Harish , Rich Laurie J. , Sexton Sandra , Curtin Leslie , Spernyak Joseph A. , Singh Anurag K. , Seshadri Mukund
Published: March 2020

There is increased interest in the use of magnetic resonance imaging (MRI) for guiding radiation therapy (RT) in the clinical setting. In this regard, preclinical studies can play an important role in understanding the added value of MRI in RT planning. In the present study, we developed and validated a clinically relevant integrated workflow for MRI-guided volumetric arc therapy (VMAT) in a VX2 rabbit neck tumor model of HNSCC. In addition to demonstrating safety and feasibility, we examined the therapeutic impact of MR-guided VMAT using a single high dose to obtain proof-of-concept and compared the response to conventional 2D-RT. Contrast-enhanced MRI (CE-MRI) provided excellent soft tissue contrast for accurate tumor segmentation for VMAT. Notably, MRI-guided RT enabled improved tumor targeting ability and minimal dose to organs at risk (OAR) compared to 2D-RT, which resulted in notable morbidity within a few weeks of RT. Our results highlight the value of integrating MRI into the workflow for VMAT for improved delineation of tumor anatomy and optimal treatment planning. The model combined with the multimodal imaging approach can serve as a valuable platform for the conduct of preclinical RT trials.
Testing of the Survivin Suppressant YM155 in a Large Panel of Drug-Resistant Neuroblastoma Cell Lines
Authors: Michaelis Martin , Voges Yvonne , Rothweiler Florian , Weipert Fabian , Zia-Ahmad Amara , Cinatl Jaroslav , von Deimling Andreas , Westermann Frank , Rödel Franz , Wass Mark N. , Cinatl Jindrich
Published: March 2020

The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). Seventy seven (77) cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.
Hydrogen Production on Cu-Ni Catalysts via the Oxy-Steam Reforming of Methanol
Authors: Mosinska Magdalena , Stępińska Natalia , Maniukiewicz Waldemar , Rogowski Jacek , Mierczynska-Vasilev Agnieszka , Vasilev Krasimir , Szynkowska Malgorzata I. , Mierczynski Pawel
Published: March 2020

In this work, bimetallic Cu-Ni catalysts supported on binary oxides containing ZnO, ZrO2, CeO2 and Al2O3 were investigated in hydrogen production via the oxidative steam reforming of methanol (OSRM). Their physicochemical properties were extensively studied using various methods such as BET, TPR-H2, TPD-NH3, XRD, SEM-EDS, ToF-SIMS and XPS. The reactivity measurements showed that the active phase and support composition played an important role in the activity of the catalyst in the OSRM. The most active system at higher temperatures was 30% Cu–10% Ni/CeO2·Al2O3, with high catalytic activity attributed to the Cu0.8Ni0.2 alloy formation. In addition, the reactivity results showed that the most active catalyst exhibited high acidity and was easily reduced. At low temperatures, the best catalytic properties were exhibited by 30% Cu–10% Ni/ZrO2·Al2O3. The reactivity and physicochemical properties of the studied catalysts confirmed the crucial role of alloy composition on their catalytic properties in the oxy-steam reforming of methanol. The obtained results validate the possibility of using Cu-Ni catalysts for hydrogen production.
Plasma-Deposited Ru-Based Thin Films for Photoelectrochemical Water Splitting
Authors: Jozwiak Lukasz , Balcerzak Jacek , Tyczkowski Jacek
Published: March 2020

Plasma-enhanced chemical vapor deposition (PECVD) was used to produce new Ru-based thin catalytic films. The surface molecular structure of the films was examined by X-ray photoelectron spectroscopy (XPS). To determine the electro- and photoelectrochemical properties, the oxygen evolution reaction (OER) process was investigated by linear sweep voltammetry (LSV) at pH = 13.6. It was found that Ru atoms were mainly in the metallic state (Ru0) in the as-deposited films, whereas after the electrochemical stabilization, higher oxidation states, mainly Ru+4 (RuO2), were formed. The stabilized films exhibited high catalytic activity in OER—for the electrochemical process, the onset and η10 overpotentials were approx. 220 and 350 mV, respectively, while for the photoelectrochemical process, the pure photocurrent density of about 160 mA/cm2 mg was achieved at 1.6 V (vs. reversible hydrogen electrode (RHE)). The plasma-deposited RuOX catalyst appears to be an interesting candidate for photoanode material for photoelectrochemical (PEC) water splitting.
Effect of Morphology on the Photoelectrochemical Activity of TiO2 Self-Organized Nanotube Arrays
Authors: Ennaceri Houda , Fischer Kristina , Hanus Kevin , Chemseddine Abdelkrim , Prager Andrea , Griebel Jan , Kühnert Mathias , Schulze Agnes , Abel Bernd
Published: March 2020

In the present work, highly ordered titanium dioxide (TiO2) nanotube anodes were grown using a rapid anodization process. The photoelectrochemical performances of these electrodes strongly depend on the anodization conditions. Parameters such as electrolyte composition, anodization potential and anodization time are shown to affect the geometrical parameters of TiO2 nanotubes. The optimal anodization parameters are determined by photocurrent measurements, linear sweep voltammetry and electrochemical impedance spectroscopy. The thickness of the tube wall and its homogeneity is shown to strongly depend on the anodization potential, and the formation mechanism is discussed. This study permits the optimization of the photocurrent density and contributes to further improvement of the photoelectrochemical water-splitting performance of TiO2 nanotube photoelectrodes.
Adipocytes in Breast Cancer, the Thick and the Thin
Authors: Rybinska Ilona , Agresti Roberto , Trapani Anna , Tagliabue Elda , Triulzi Tiziana
Published: March 2020

It is well established that breast cancer development and progression depend not only on tumor-cell intrinsic factors but also on its microenvironment and on the host characteristics. There is growing evidence that adipocytes play a role in breast cancer progression. This is supported by: (i) epidemiological studies reporting the association of obesity with a higher cancer risk and poor prognosis, (ii) recent studies demonstrating the existence of a cross-talk between breast cancer cells and adipocytes locally in the breast that leads to acquisition of an aggressive tumor phenotype, and (iii) evidence showing that cancer cachexia applies also to fat tissue and shares similarities with stromal-carcinoma metabolic synergy. This review summarizes the current knowledge on the epidemiological link between obesity and breast cancer and outlines the results of the tumor-adipocyte crosstalk. We also focus on systemic changes in body fat in patients with cachexia developed in the course of cancer. Moreover, we discuss and compare adipocyte alterations in the three pathological conditions and the mechanisms through which breast cancer progression is induced.
Administration of Steamed and Freeze-Dried Mature Silkworm Larval Powder Prevents Hepatic Fibrosis and Hepatocellular Carcinogenesis by Blocking TGF-β/STAT3 Signaling Cascades in Rats
Authors: Lee Da-Young , Yun Sun-Mi , Song Moon-Young , Ji Sang-Deok , Son Jong-Gon , Kim Eun-Hee
Published: March 2020

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide and the majority of HCC patients occur with a background of hepatic fibrosis and cirrhosis. We have previously reported the hepatoprotective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in a chronic ethanol-treated rat model. Here, we assessed the anti-fibrotic and anti-carcinogenic effects of SMSP on diethylnitrosamine (DEN)-treated rats. Wistar rats were intraperitoneally injected with DEN once a week for 12 or 16 weeks with or without SMSP administration (0.1 and 1 g/kg). SMSP administration significantly attenuated tumor foci formation and proliferation in the livers of the rats treated with DEN for 16 weeks. SMSP administration also inhibited hepatic fibrosis by decreasing the levels of collagen fiber and the expression of pro-collagen I and alpha-smooth muscle actin (α-SMA). Moreover, SMSP supplementation improved the major parameters of fibrosis such as transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and collagen type I (Col1A1) in the livers from the rats treated with DEN for 16 weeks. As s possible mechanisms, we investigated the effects of SMSP on the TGF-β and signal transducer and activator of transcription 3 (STAT3)-mediated signaling cascades, which are known to promote hepatic fibrosis. We found that SMSP treatment inhibited the activation of TGF-β and the phosphorylation of STAT3 pathway in DEN-treated rats. Moreover, SMSP administration suppressed the expressions of the target genes of TGF-β and STAT3 induced by DEN treatment. Our findings provide experimental evidences that SMSP administration has inhibitory effects of hepatic fibrosis and HCC induced by DEN In Vivo and could be a promising strategy for the prevention or treatment of hepatic fibrosis and hepatocellular carcinogenesis.
Motor Neuron Generation from iPSCs from Identical Twins Discordant for Amyotrophic Lateral Sclerosis
Authors: Seminary Emily R. , Santarriaga Stephanie , Wheeler Lynn , Mejaki Marie , Abrudan Jenica , Demos Wendy , Zimmermann Michael T. , Urrutia Raul A. , Fee Dominic , Barkhaus Paul E. , Ebert Allison D.
Published: March 2020

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder characterized by the loss of the upper and lower motor neurons. Approximately 10% of cases are caused by specific mutations in known genes, with the remaining cases having no known genetic link. As such, sporadic cases have been more difficult to model experimentally. Here, we describe the generation and differentiation of ALS induced pluripotent stem cells reprogrammed from discordant identical twins. Whole genome sequencing revealed no relevant mutations in known ALS-causing genes that differ between the twins. As protein aggregation is found in all ALS patients and is thought to contribute to motor neuron death, we sought to characterize the aggregation phenotype of the sporadic ALS induced pluripotent stem cells (iPSCs). Motor neurons from both twins had high levels of insoluble proteins that commonly aggregate in ALS that did not robustly change in response to exogenous glutamate. In contrast, established genetic ALS iPSC lines demonstrated insolubility in a protein- and genotype-dependent manner. Moreover, whereas the genetic ALS lines failed to induce autophagy after glutamate stress, motor neurons from both twins and independent controls did activate this protective pathway. Together, these data indicate that our unique model of sporadic ALS may provide key insights into disease pathology and highlight potential differences between sporadic and familial ALS.
Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats
Authors: Izquierdo-Altarejos Paula , Cabrera-Pastor Andrea , Gonzalez-King Hernan , Montoliu Carmina , Felipo Vicente
Published: March 2020

Minimal hepatic encephalopathy is associated with changes in the peripheral immune system which are transferred to the brain, leading to neuroinflammation and thus to cognitive and motor impairment. Mechanisms by which changes in the immune system induce cerebral alterations remain unclear. Extracellular vesicles (EVs) seem to play a role in this process in certain pathologies. The aim of this work was to assess whether EVs play a role in the induction of neuroinflammation in cerebellum and motor incoordination by chronic hyperammonemia. We characterized the differences in protein cargo of EVs from plasma of hyperammonemic and control rats by proteomics and Western blot. We assessed whether injection of EVs from hyperammonemic to normal rats induces changes in neuroinflammation in cerebellum and motor incoordination similar to those exhibited by hyperammonemic rats. We found that hyperammonemia increases EVs amount and alters their protein cargo. Differentially expressed proteins are mainly associated with immune system processes. Injected EVs enter Purkinje neurons and microglia. Injection of EVs from hyperammonemic, but not from control rats, induces motor incoordination, which is mediated by neuroinflammation, microglia and astrocytes activation and increased IL-1β, TNFα, its receptor TNFR1, NF-κB in microglia, glutaminase I, and GAT3 in cerebellum. Plasma EVs from hyperammonemic rats carry molecules necessary and sufficient to trigger neuroinflammation in cerebellum and the mechanisms leading to motor incoordination.
Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition
Authors: Zhitnyak Irina Y. , Rubtsova Svetlana N. , Litovka Nikita I. , Gloushankova Natalya A.
Published: March 2020

Epithelial-mesenchymal transition (EMT) plays an important role in development and also in initiation of metastasis during cancer. Disruption of cell-cell contacts during EMT allowing cells to detach from and migrate away from their neighbors remains poorly understood. Using immunofluorescent staining and live-cell imaging, we analyzed early events during EMT induced by epidermal growth factor (EGF) in IAR-20 normal epithelial cells. Control cells demonstrated stable adherens junctions (AJs) and robust contact paralysis, whereas addition of EGF caused rapid dynamic changes at the cell-cell boundaries: fragmentation of the circumferential actin bundle, assembly of actin network in lamellipodia, and retrograde flow. Simultaneously, an actin-binding protein EPLIN was phosphorylated, which may have decreased the stability of the circumferential actin bundle. Addition of EGF caused gradual replacement of linear E-cadherin–based AJs with dynamic and unstable punctate AJs, which, unlike linear AJs, colocalized with the mechanosensitive protein zyxin, confirming generation of centripetal force at the sites of cell-cell contacts during EMT. Our data show that early EMT promotes heightened dynamics at the cell-cell boundaries—replacement of stable AJs and actin structures with dynamic ones—which results in overall weakening of cell-cell adhesion, thus priming the cells for front-rear polarization and eventual migration.
HSP70 Multi-Functionality in Cancer
Authors: Albakova Zarema , Armeev Grigoriy A. , Kanevskiy Leonid M. , Kovalenko Elena I. , Sapozhnikov Alexander M.
Published: March 2020

The 70-kDa heat shock proteins (HSP70s) are abundantly present in cancer, providing malignant cells selective advantage by suppressing multiple apoptotic pathways, regulating necrosis, bypassing cellular senescence program, interfering with tumor immunity, promoting angiogenesis and supporting metastasis. This direct involvement of HSP70 in most of the cancer hallmarks explains the phenomenon of cancer “addiction” to HSP70, tightly linking tumor survival and growth to the HSP70 expression. HSP70 operates in different states through its catalytic cycle, suggesting that it can multi-function in malignant cells in any of these states. Clinically, tumor cells intensively release HSP70 in extracellular microenvironment, resulting in diverse outcomes for patient survival. Given its clinical significance, small molecule inhibitors were developed to target different sites of the HSP70 machinery. Furthermore, several HSP70-based immunotherapy approaches were assessed in clinical trials. This review will explore different roles of HSP70 on cancer progression and emphasize the importance of understanding the flexibility of HSP70 nature for future development of anti-cancer therapies.
In-Parallel Polar Monitoring of Chemiluminescence Emission Anisotropy at the Solid–Liquid Interface by an Optical Fiber Radial Array
Authors: Berneschi Simone , Trono Cosimo , Mirasoli Mara , Giannetti Ambra , Zangheri Martina , Guardigli Massimo , Tombelli Sara , Marchegiani Elisa , Baldini Francesco , Roda Aldo
Published: March 2020

Chemiluminescence (CL) detection is widely employed in biosensors and miniaturized analytical devices since it offers high detectability and flexible device design (there are no geometry requirements for the measurement cell, except the ability to collect the largest fraction of emitted photons). Although the emission anisotropy phenomenon for an emitting dipole bound to the interface between two media with different refractive index is well known for fluorescence, it is still poorly investigated for CL reactions, in which the excited-state reaction products can diffuse in solution before the photon emission event. In this paper, we propose a simple method for the real-time evaluation of the CL emission anisotropy based on a radial array of optical fibers, embedded in a poly(methyl methacrylate) semicylinder and coupled with a Charge-Coupled Device (CCD) camera through a suitable interface. The polar-time evolutions of the CL emission have been studied for catalyzing enzymes immobilized onto a solid surface (heterogeneous configuration) or free in solution (homogeneous configuration). Evidence of the anisotropy phenomenon is observed, indicating that the lifetime of the excited-state products of the enzyme-catalyzed reactions is shorter than the time required for their diffusion in solution at a distance at which the CL can be considered isotropic. These results open new perspectives in the development of CL-based miniaturized analytical devices.
The Abrasive Wear Resistance of Coatings Manufactured on High-Strength Low-Alloy (HSLA) Offshore Steel in Wet Welding Conditions
Authors: Tomków Jacek , Czupryński Artur , Fydrych Dariusz
Published: March 2020

Some marine and offshore structure elements exploited in the water cannot be brought to the surface of the water as this will generate high costs, and for this reason, they require in-situ repairs. One of the repair techniques used in underwater pad welding conditions is a wet welding method. This paper presents an investigation of the abrasive wear resistance of coatings made in wet welding conditions with the use of two grades of covered electrodes—an electrode for underwater welding and a commercial general use electrode. Both electrodes were also used for manufacturing coatings in the air, which has been also tested. The Vickers HV10 hardness measurements are performed to demonstrate the correlation in abrasive wear resistance and the hardness of each specimen. The microscopic testing was performed. For both filler materials, the coatings prepared in a water environment are characterized by higher resistance to metal–mineral abrasion than coatings prepared in an air environment—0.61 vs. 0.44 for commercial usage electrode and 0.67 vs. 0.60 for underwater welding. We also proved that in the water, the abrasive wear was greater for specimens welded by the general use electrode, which results in a higher hardness of the layer surface. In the air welding conditions, the layer welded by the electrode for use in the water was characterized by a lower hardness and higher resistance to metal–mineral abrasion. The microstructure of the prepared layers is different for both the environment and both electrodes, which results in abrasive wear resistance.
Pt–Ti Alloy Coatings Deposited by DC Magnetron Sputtering: A Potential Current Collector at High Temperature
Authors: Briois Pascal , Arab-Pour-Yazdi Mohammad , Martin Nicolas , Billard Alain
Published: March 2020

Metallic platinum–titanium coatings were deposited by co-sputtering of two metallic Pt and Ti targets in pure argon atmosphere. The titanium concentrations varied from 0 to 47 atomic percent and were adjusted as a function of the current applied to the titanium target. The structural and chemical features of these films were assessed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). All as-deposited coatings exhibit a perfect covering of the alumina pellets’ substrate surface. The coatings containing more than 4 at.% Ti are amorphous, whereas the others crystallize in the face-centered cubic (fcc) structure of platinum. After an annealing treatment under air for 2 h, all of the coatings adopt the fcc structure with a crystallization temperature depending on the titanium content. For titanium concentrations higher than 32 at.%, the TiO2 phase appears during the annealing treatment. For the smaller film thickness of Pt–Ti alloys (15 nm), the Ostwald ripening mechanism is observed by SEM increasing the annealing temperature regardless of the content of Ti. The film resistivity measured at room temperature is lower than 7 × 10−4 Ω·cm and increases with the temperature to achieve an insulating behavior (in air and reducing atmosphere Ar-H2 (90-10) at 1123 K the resistivity is ρ ≈ 10+36 Ω·cm). When the thickness of intermetallic Pt3Ti layer is higher than 50 nm, the coating is continuous and the resistivity is below 5 × 10−4 Ω·cm in air and in reducing atmosphere (Ar with 10% of H2) up to 1273 K.
Improving the Protectiveness of 3-Mercaptopropyl-Trimethoxysilane Coatings on Bronze by Addition of Oxidic Nano- and Microparticles
Authors: Monticelli Cecilia , Zanotto Federica , Grassi Vincenzo , Seyedi Mahla , Balbo Andrea
Published: March 2020

The protectiveness of coatings based on 3-mercaptopropyl-trimethoxysilane (PropS-SH) applied on bronze artworks was enhanced by investigating and tuning a variety of factors. In particular, the coating performances were optimized by proper additive choice among oxide nanoparticles (CeO2, La2O3, TiO2) and microparticles (fly ash (FA)), and by varying the aging time of the nanoparticle suspensions before coating application and the RT curing time of the coatings. Moreover, the possibility of conservation of the silane solution under refrigerated conditions was assessed. The aggressive environment was a tenfold concentrated synthetic acid rain (AR × 10). The techniques adopted comprised electrochemical tests (polarization curve recording and EIS tests) and SEM-Energy Dispersion Spectroscopy (EDS) observations. In the case of FA microparticles, never used before as additives in silane coatings, further tests were performed in FA suspensions in AR × 10 to clarify the contribution of these particles to PropS-SH coating protectiveness. The tests included pH measurements, elemental chemical analyses, and electrochemical tests on bare bronze. Improved performances of PropS-SH coatings were achieved by La2O3, CeO2, and FA addition, with La2O3 affording the best results during 20 days of immersion. The positive influence of FA was connected to its alkaline character and to the release of soluble silicates.
The Sealing Step in Aluminum Anodizing: A Focus on Sustainable Strategies for Enhancing Both Energy Efficiency and Corrosion Resistance
Authors: Ofoegbu Stanley Udochukwu , Fernandes Fábio A.O. , Pereira António B.
Published: March 2020

Increasing demands for environmental accountability and energy efficiency in industrial practice necessitates significant modification(s) of existing technologies and development of new ones to meet the stringent sustainability demands of the future. Generally, development of required new technologies and appropriate modifications of existing ones need to be premised on in-depth appreciation of existing technologies, their limitations, and desired ideal products or processes. In the light of these, published literature mostly in the past 30 years on the sealing process; the second highest energy consuming step in aluminum anodization and a step with significant environmental impacts has been critical reviewed in this systematic review. Emphasis have been placed on the need to reduce both the energy input in the anodization process and environmental implications. The implications of the nano-porous structure of the anodic oxide on mass transport and chemical reactivity of relevant species during the sealing process is highlighted with a focus on exploiting these peculiarities, in improving the quality of sealed products. In addition, perspective is provided on plausible approaches and important factors to be considered in developing sealing procedures that can minimize the energy input and environmental impact of the sealing step, and ensure a more sustainable aluminum anodization process/industry.
The Effect of Ion Irradiation Density on the Defect of Graphene: A Molecular Dynamics Study
Authors: Lin Jinfu , Wang Shulong , Liu Hongxia , Yin Kai , Wu Lei , Li Wei
Published: March 2020

This paper analyzes graphene irradiation effects using a molecular dynamic simulation software, large-scale atomic / molecular massively parallel simulator (LAMMPS). We propose a hypothesis for the effective range of incident ions based on simulation results of irradiation effects that were found using a suspended single-layer graphene. This explains the influence mechanism of irradiation density on the degree of material defects. This paper does key research on how copper substrate influences a single- and bi-layer graphene. The results show that for a single-layer graphene (SLG) the substrate increases the effective range of the incident ions. Within a certain range of the irradiation density, the substrate enhances the defect production on graphene in low-energy irradiation (<5 keV). However, due to the shielding effect of the substrate, the overall trend of graphene damage will be reduced. For the bi-layer graphene (BLG), the effect of the indirect action range is more obvious than that of the direct-action range. In the case of low irradiation density, the knock-on atoms of BLG are much less than suspended SLG.
Endometriosis in Menopause—Renewed Attention on a Controversial Disease
Authors: Secosan Cristina , Balulescu Ligia , Brasoveanu Simona , Balint Oana , Pirtea Paul , Dorin Grigoraș , Pirtea Laurentiu
Published: March 2020

Endometriosis, an estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial tissue, has been the topic of renewed research and debate in recent years. The paradigm shift from the belief that endometriosis only affects women of reproductive age has drawn attention to endometriosis in both premenarchal and postmenopausal patients. There is still scarce information in literature regarding postmenopausal endometriosis, the mostly studied and reported being the prevalence in postmenopausal women. Yet, other important issues also need to be addressed concerning diagnosis, pathophysiology, and management. We aimed at summarizing the currently available data in literature in order to provide a concise and precise update regarding information available on postmenopausal endometriosis.
Measuring Information Coupling between the Solar Wind and the Magnetosphere–Ionosphere System
Authors: Stumpo Mirko , Consolini Giuseppe , Alberti Tommaso , Quattrociocchi Virgilio
Published: March 2020

The interaction between the solar wind and the Earth’s magnetosphere–ionosphere system is very complex, being essentially the result of the interplay between an external driver, the solar wind, and internal processes to the magnetosphere–ionosphere system. In this framework, modelling the Earth’s magnetosphere–ionosphere response to the changes of the solar wind conditions requires a correct identification of the causality relations between the different parameters/quantities used to monitor this coupling. Nowadays, in the framework of complex dynamical systems, both linear statistical tools and Granger causality models drastically fail to detect causal relationships between time series. Conversely, information theory-based concepts can provide powerful model-free statistical quantities capable of disentangling the complex nature of the causal relationships. In this work, we discuss how to deal with the problem of measuring causal information in the solar wind–magnetosphere–ionosphere system. We show that a time delay of about 30–60 min is found between solar wind and magnetospheric and ionospheric overall dynamics as monitored by geomagnetic indices, with a great information transfer observed between the z component of the interplanetary magnetic field and geomagnetic indices, while a lower transfer is found when other solar wind parameters are considered. This suggests that the best candidate for modelling the geomagnetic response to solar wind changes is the interplanetary magnetic field component B z . A discussion of the relevance of our results in the framework of Space Weather is also provided.
Statistical Generalized Derivative Applied to the Profile Likelihood Estimation in a Mixture of Semiparametric Models
Authors: Hirose Yuichi , Liu Ivy
Published: March 2020

There is a difficulty in finding an estimate of the standard error (SE) of the profile likelihood estimator in the joint model of longitudinal and survival data. The difficulty is on the differentiation of an implicit function that appear in the profile likelihood estimation. We solve the difficulty by introducing the “statistical generalized derivative”. The derivative is used to show the asymptotic normality of the estimator with the SE expressed in terms of the profile likelihood score function.