bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Connectivity Analysis Under Semantic Vigilance and Enhanced Mental States
Authors: Al-Shargie Fares , Tariq Usman , Hassanin Omnia , Mir Hasan , Babiloni Fabio , Al-Nashash Hasan
Published: December 2019

In this paper, we present a method to quantify the coupling between brain regions under vigilance and enhanced mental states by utilizing partial directed coherence (PDC) and graph theory analysis (GTA). The vigilance state is induced using a modified version of stroop color-word task (SCWT) while the enhancement state is based on audio stimulation with a pure tone of 250 Hz. The audio stimulation was presented to the right and left ears simultaneously for one-hour while participants perform the SCWT. The quantification of mental states was performed by means of statistical analysis of indexes based on GTA, behavioral responses of time-on-task (TOT), and Brunel Mood Scale (BRMUS). The results show that PDC is very sensitive to vigilance decrement and shows that the brain connectivity network is significantly reduced with increasing TOT, p < 0.05. Meanwhile, during the enhanced state, the connectivity network maintains high connectivity as time passes and shows significant improvements compared to vigilance state. The audio stimulation enhances the connectivity network over the frontal and parietal regions and the right hemisphere. The increase in the connectivity network correlates with individual differences in the magnitude of the vigilance enhancement assessed by response time to stimuli. Our results provide evidence for enhancement of cognitive processing efficiency with audio stimulation. The BRMUS was used to evaluate the emotional states of vigilance task before and after using the audio stimulation. BRMUS factors, such as fatigue, depression, and anger, significantly decrease in the enhancement group compared to vigilance group. On the other hand, happy and calmness factors increased with audio stimulation, p < 0.05.
ACLY (ATP Citrate Lyase) Mediates Radioresistance in Head and Neck Squamous Cell Carcinomas and is a Novel Predictive Radiotherapy Biomarker
Authors: Göttgens Eva-Leonne , van den Heuvel Corina NAM , de Jong Monique C , Kaanders Johannes HAM , Leenders William PJ , Ansems Marleen , Bussink Johan , Span Paul N
Published: December 2019

Radiotherapy is an important treatment modality of head and neck squamous cell carcinomas (HNSCC). Multiple links have been described between the metabolic activity of tumors and their clinical outcome. Here we test the hypothesis that metabolic features determine radiosensitivity, explaining the relationship between metabolism and clinical outcome. Radiosensitivity of 14 human HNSCC cell lines was determined using colony forming assays and the expression profile of approximately 200 metabolic and cancer-related genes was generated using targeted RNA sequencing by single molecule molecular inversion probes. Results: Correlation between radiosensitivity data and expression profiles yielded 18 genes associated with radiosensitivity or radioresistance, of which adenosine triphosphate (ATP) citrate lyase (ACLY) was of particular interest. Pharmacological inhibition of ACLY caused an impairment of DNA damage repair, specifically homologous recombination, and lead to radiosensitization in HNSCC cell lines. Examination of a The Cancer Genome Atlas (TCGA) cohort of HNSCC patients revealed that high expression of ACLY was predictive for radiotherapy failure, as it was only associated with poor overall survival in patients who received radiotherapy (hazard ratio of 2.00, 95% CI: 1.12–3.55; p = 0.0184). These data were further validated in an independent cohort of HNSCC patients treated with chemoradiation. Furthermore, patients with poor locoregional control after radiotherapy have significantly higher nuclear ACLY protein levels. Together, we here show that ACLY affects DNA damage repair, and is a predictive factor for radiotherapy outcome in HNSCC.
The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma—Association with Clinical Outcome and Tumor Phenotypes
Authors: Betancourt Lazaro Hiram , Szasz A. Marcell , Kuras Magdalena , Rodriguez Murillo Jimmy , Sugihara Yutaka , Pla Indira , Horvath Zsolt , Pawłowski Krzysztof , Rezeli Melinda , Miharada Kenichi , Gil Jeovanis , Eriksson Jonatan , Appelqvist Roger , Miliotis Tasso , Baldetorp Bo , Ingvar Christian , Olsson Håkan , Lundgren Lotta , Horvatovich Peter , Welinder Charlotte , Wieslander Elisabet , Kwon Ho Jeong , Malm Johan , Nemeth Istvan Balazs , Jönsson Göran , Fenyö David , Sanchez Aniel , Marko-Varga György
Published: December 2019

In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter- and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.
A Triple Co-Delivery Liposomal Carrier That Enhances Apoptosis via an Intrinsic Pathway in Melanoma Cells
Authors: Filipczak Nina , Jaromin Anna , Piwoni Adriana , Mahmud Mohamed , Sarisozen Can , Torchilin Vladimir , Gubernator Jerzy
Published: December 2019

The effectiveness of existing anti-cancer therapies is based mainly on the stimulation of apoptosis of cancer cells. Most of the existing therapies are somewhat toxic to normal cells. Therefore, the quest for nontoxic, cancer-specific therapies remains. We have demonstrated the ability of liposomes containing anacardic acid, mitoxantrone and ammonium ascorbate to induce the mitochondrial pathway of apoptosis via reactive oxygen species (ROS) production by the killing of cancer cells in monolayer culture and shown its specificity towards melanoma cells. Liposomes were prepared by a lipid hydration, freeze-and-thaw (FAT) procedure and extrusion through polycarbonate filters, a remote loading method was used for dug encapsulation. Following characterization, hemolytic activity, cytotoxicity and apoptosis inducing effects of loaded nanoparticles were investigated. To identify the anticancer activity mechanism of these liposomes, ROS level and caspase 9 activity were measured by fluorescence and by chemiluminescence respectively. We have demonstrated that the developed liposomal formulations produced a high ROS level, enhanced apoptosis and cell death in melanoma cells, but not in normal cells. The proposed mechanism of the cytotoxic action of these liposomes involved specific generation of free radicals by the iron ions mechanism.
p53-Mediated Tumor Suppression: DNA-Damage Response and Alternative Mechanisms
Authors: Pitolli Consuelo , Wang Ying , Candi Eleonora , Shi Yufang , Melino Gerry , Amelio Ivano
Published: December 2019

The tumor suppressor p53 regulates different cellular pathways involved in cell survival, DNA repair, apoptosis, and senescence. However, according to an increasing number of studies, the p53-mediated canonical DNA damage response is dispensable for tumor suppression. p53 is involved in mechanisms regulating many other cellular processes, including metabolism, autophagy, and cell migration and invasion, and these pathways might crucially contribute to its tumor suppressor function. In this review we summarize the canonical and non-canonical functions of p53 in an attempt to provide an overview of the potentially crucial aspects related to its tumor suppressor activity.
Stabilization of Hypoxia-Inducible Factors and BNIP3 Promoter Methylation Contribute to Acquired Sorafenib Resistance in Human Hepatocarcinoma Cells
Authors: Méndez-Blanco Carolina , Fondevila Flavia , Fernández-Palanca Paula , García-Palomo Andrés , van Pelt Jos , Verslype Chris , González-Gallego Javier , Mauriz José
Published: December 2019

Despite sorafenib effectiveness against advanced hepatocarcinoma (HCC), long-term exposure to antiangiogenic drugs leads to hypoxic microenvironment, a key contributor to chemoresistance acquisition. We aimed to study the role of hypoxia in the development of sorafenib resistance in a human HCC in vitro model employing the HCC line HepG2 and two variants with acquired sorafenib resistance, HepG2S1 and HepG2S3, and CoCl2 as hypoximimetic. Resistant cells exhibited a faster proliferative rate and hypoxia adaptive mechanisms, linked to the increased protein levels and nuclear translocation of hypoxia-inducible factors (HIFs). HIF-1α and HIF-2α overexpression was detected even under normoxia through a deregulation of its degradation mechanisms. Proapoptotic markers expression and subG1 population decreased significantly in HepG2S1 and HepG2S3, suggesting evasion of sorafenib-mediated cell death. HIF-1α and HIF-2α knockdown diminished resistant cells viability, relating HIFs overexpression with its prosurvival ability. Additionally, epigenetic silencing of Bcl-2 interacting protein 3 (BNIP3) was observed in sorafenib resistant cells under hypoxia. Demethylation of BNIP3 promoter, but not histone acetylation, restored BNIP3 expression, driving resistant cells’ death. Altogether, our results highlight the involvement of HIFs overexpression and BNIP3 methylation-dependent knockdown in the development of sorafenib resistance in HCC. Targeting both prosurvival mechanisms could overcome chemoresistance and improve future therapeutic approaches.
Passive Solar Photocatalytic Treatment of Emerging Contaminants in Water: A Field Study
Authors: Heydari Gisoo , Langford Cooper H. , Achari Gopal
Published: December 2019

Global economic shifts towards utilization of solar energy provides opportunities for photocatalytic technologies that can harness this abundant source of energy for treatment of organic contaminants. The majority of studies in this area have been performed under artificial light, whereas in this paper, the efficacy of passive photocatalysis was studied under sunlight. Buoyant titanium dioxide (TiO2) coated glass spheres were used to treat 2, 4-dichlorophenoxy acetic acid (2, 4-D), methyl chlorophenoxy propionic acid (MCPP), and 3, 6-Dichloro-2-methoxy benzoic acid (Dicamba) in Killex®, a commercially available herbicide. Furthermore, photocatalytic degradation of sulfolane and a typical naphthenic acid (cyclopentane carboxylic acid—CPA) were also tested under ambient conditions. The results showed 99.8% degradation of 2, 4-D, 100% degradation of both MCPP and Dicamba in Killex® solution, and 97.4% degradation of sulfolane by capturing 3.18 MJ/m2 solar energy. Total organic carbon (TOC) was decreased by 88% and 64% in both solutions, respectively. TOC of the aqueous solution containing 20 ppm CPA was also decreased by 78.4% with 7.8 MJ/m2 energy. Despite the slow kinetics and the temporal variations of sunlight in northern latitudes, the results indicated that passive photocatalysis is a promising approach for treatment of contaminants under ambient conditions.
GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice
Authors: Yang Xuezhi , Li Susu , Zhao Yingjie , Li Siyu , Zhao Tianjiao , Tai Yu , Zhang Bingjie , Wang Xinwei , Wang Chun , Chen Jingyu , Wang Qingtong , Zhang Lingling , Xu Dexiang , Chang Yan , Wei Wei
Published: December 2019

Rheumatoid arthritis (RA) is characterized by the massive infiltration of various chronic inflammatory cells in synovia. In synovial fluid of patients with RA, M1 macrophages are dominant among all subtypes of macrophages, the mechanisms of macrophages polarization imbalance in RA has not been fully illuminated. The prostaglandin E2 (PGE2) augments M2 polarization in part via the cyclic adenosine monophosphate (cAMP)-cyclic AMP responsive element binding (CREB) signaling. However, previous study found constant stimulus of PGE2 on fibroblast-like synovial cells of adjuvant arthritis rats induced the decrease of cAMP, which is primarily caused by G protein-coupled receptor kinase 2 (GRK2)-induced EP4 over- desensitization. Whether GRK2 mediated-EP4 over-desensitization reduces the level of cAMP and inhibits M2 polarization in RA is unclear. Here we observed M1 macrophages were dominant in peritoneal macrophages (PMs), bone-marrow-derived macrophages (BMMs) and synovial macrophages of collagen-induced arthritis (CIA) mice. PGE2 stimulated M2 polarization via the EP4-cAMP-CREB in normal mice, while failed to promote M2 polarization in the PMs of CIA mice. Further, we found the EP4 over-desensitization stimulated by PGE2 induced abnormal PGE2-cAMP-CREB signaling as well as the imbalance of macrophage polarization. Targeted disruption of GRK2 in Raw264.7 (RAW) through GRK2 siRNA or CRISPR/Cas9 downregulated the M1 macrophage markers, upregulated the M2 macrophage markers and the EP4 membrane localization. The reduced M1/M2 ratio and increased p-CREB expression were observed in BMMs and PMs of GRK2+/− mice. This study highlighted a novel role of GRK2 in regulating macrophages function in RA and provided new idea for precision treatment of RA.
Exosome Biogenesis in the Protozoa Parasite Giardia lamblia: A Model of Reduced Interorganellar Crosstalk
Authors: Moyano Sofía , Musso Juliana , Feliziani Constanza , Zamponi Nahuel , Frontera Lorena Soledad , Ropolo Andrea Silvana , Lanfredi-Rangel Adriana , Lalle Marco , Touz María  C.
Published: December 2019

Extracellular vesicles (EVs) facilitate intercellular communication and are considered a promising therapeutic tool for the treatment of infectious diseases. These vesicles involve microvesicles (MVs) and exosomes and selectively transfer proteins, lipids, mRNAs, and microRNAs from one cell to another. While MVs are formed by extrusion of the plasma membrane, exosomes are a population of vesicles of endosomal origin that are stored inside the multivesicular bodies (MVBs) as intraluminal vesicles (ILVs) and are released when the MVBs fuse with the plasma membrane. Biogenesis of exosomes may be driven by the endosomal sorting complex required for transport (ESCRT) machinery or may be ESCRT independent, and it is still debated whether these are entirely separate pathways. In this manuscript, we report that the protozoan parasite, Giardia lamblia, although lacking a classical endo-lysosomal pathway, is able to produce and release exosome-like vesicles (ElV). By using a combination of biochemical and cell biology analyses, we found that the ElVs have the same size, shape, and protein and lipid composition as exosomes described for other eukaryotic cells. Moreover, we established that some endosome/lysosome peripheral vacuoles (PVs) contain ILV during the stationary phase. Our results indicate that ILV formation and ElV release depend on the ESCRT-associated AAA+-ATPase Vps4a, Rab11, and ceramide in this parasite. Interestingly, EIV biogenesis and release seems to occur in Giardia despite the fact that this parasite has lost most of the ESCRT machinery components during evolution and is unable to produce ceramide de novo. The differences in protozoa parasite EV composition, origin, and release may reveal functional and structural properties of EVs and, thus, may provide information on cell-to-cell communication and on survival mechanisms.
Surfaces and Interfaces for Renewable Energy
Authors: Manzano-Agugliaro Francisco , Fernández-García Aránzazu
Published: December 2019

Energy is a growing need in today’s world. Citizens and governments are increasingly aware of the sustainable use that must be made of natural resources and the great negative impact on the environment produced by conventional energies. Therefore, developments in energy systems based on renewable energies must be carried out in the very near future. To ensure their sustainability, they must be made of durable materials, and for this, the study of coatings is extremely important. This is also vital in systems based on solar energy, where the optical properties of the materials must be preserved as long as possible, and to this must be added the fact that they tend to be installed in very aggressive environments from the point of view of corrosion. Therefore, this special issue aims to contribute to the development of this challenge.
Corrosion Resistant TiTaN and TiTaAlN Thin Films Grown by Hybrid HiPIMS/DCMS Using Synchronized Pulsed Substrate Bias with No External Substrate Heating
Authors: Chipatecua Godoy Yuri , Tengstrand Olof , Olaya Florez Jairo , Petrov Ivan , Bustos Erika , Hultman Lars , Herrera-Gomez Alberto , Greene J.E. , Greczynski Grzegorz
Published: December 2019

Ti0.92Ta0.08N and Ti0.41Al0.51Ta0.08N thin films grown on stainless-steel substrates, with no external heating, by hybrid high-power impulse and dc magnetron sputtering (HiPIMS/DCMS), were investigated for corrosion resistance. The Ta target was operated in HiPIMS mode to supply pulsed Ta-ion fluxes, while two Ti (or Ti and Al) targets were operated in DCSM mode in order to provide a high deposition rate. Corrosion resistance was investigated using potentiodynamic polarization and electrochemical impedance spectroscopy employing a 3.5% NaCl solution at room temperature. The 300-nm-thick transition-metal nitride coatings exhibited good corrosion resistance due to film densification resulting from pulsed heavy Ta-ion irradiation during film growth. Corrosion protective efficiencies were above 99.8% for both Ti0.41Al0.51Ta0.08N and Ti0.92Ta0.08N, and pore resistance was apparently four orders of magnitude higher than for bare 304 stainless-steel substrates.
Beyond Platform Economy: A Comprehensive Model for Decentralized and Self-Organizing Markets on Internet-Scale
Authors: Radonjic-Simic Mirjana , Pfisterer Dennis
Published: December 2019

The platform economy denotes a subset of economic activities enabled by platforms such as Amazon, Alibaba, and Uber. Due to their tremendous success, more and more offerings concentrate around platforms increasing platforms’ positional-power, hence leading towards a de-facto centralization of previously decentralized online markets. Furthermore, platform models work well for individual products and services or predefined combinations of these. However, they fall short in supporting complex products (personalized combinations of individual products and services), the combination of which is required to fulfill a particular consumer need, consequently increasing transaction costs for consumers looking for such products. To address these issues, we envision a “post-platform economy”—an economy facilitated by decentralized and self-organized online structures named Distributed Market Spaces. This work proposes a comprehensive model to serve as a guiding framework for the analysis, design, and implementation of Distributed Market Spaces. The proposed model leverages the St. Gallen Media Reference Model by adjusting existing and adding new entities and elements. The resulting multidimensional and multi-view model defines how a reference Distributed Market Space (a) works on the strategic and operational levels, (b) enables market exchange for complex products, and (c) how its instances might unfold during different life stages. In a case study, we demonstrated the application of our model and evaluated its suitability of meeting the primary objectives it was designed for.
Crypsis Decreases with Elevation in a Lizard
Authors: Moreno-Rueda Gregorio , González-Granda Laureano G. , Reguera Senda , Zamora-Camacho Francisco J. , Melero Elena
Published: December 2019

Predation usually selects for visual crypsis, the colour matching between an animal and its background. Geographic co-variation between animal and background colourations is well known, but how crypsis varies along elevational gradients remains unknown. We predict that dorsal colouration in the lizard Psammodromus algirus should covary with the colour of bare soil—where this lizard is mainly found—along a 2200 m elevational gradient in Sierra Nevada (SE Spain). Moreover, we predict that crypsis should decrease with elevation for two reasons: (1) Predation pressure typically decreases with elevation, and (2) at high elevation, dorsal colouration is under conflicting selection for both crypsis and thermoregulation. By means of standardised photographies of the substratum and colourimetric measurements of lizard dorsal skin, we tested the colour matching between lizard dorsum and background. We found that, along the gradient, lizard dorsal colouration covaried with the colouration of bare soil, but not with other background elements where the lizard is rarely detected. Moreover, supporting our prediction, the degree of crypsis against bare soil decreased with elevation. Hence, our findings suggest local adaptation for crypsis in this lizard along an elevational gradient, but this local adaptation would be hindered at high elevations.
Design and Analysis of Refined Inspection of Field Conditions of Oilfield Pumping Wells Based on Rotorcraft UAV Technology
Authors: Zhou Yu , Wu Chunxue , Wu Qunhui , Eli Zelda Makati , Xiong Naixue , Zhang Sheng
Published: December 2019

The traditional oil well monitoring method relies on manual acquisition and various high-precision sensors. Using the indicator diagram to judge the working condition of the well is not only difficult to establish but also consumes huge manpower and financial resources. This paper proposes the use of computer vision in the detection of working conditions in oil extraction. Combined with the advantages of an unmanned aerial vehicle (UAV), UAV aerial photography images are used to realize real-time detection of on-site working conditions by real-time tracking of the working status of the head working and other related parts of the pumping unit. Considering the real-time performance of working condition detection, this paper proposes a framework that combines You only look once version 3 (YOLOv3) and a sort algorithm to complete multi-target tracking in the form of tracking by detection. The quality of the target detection in the framework is the key factor affecting the tracking effect. The experimental results show that a good detector makes the tracking speed achieve the real-time effect and provides help for the real-time detection of the working condition, which has a strong practical application.
Interspecific Differences in Canopy-Derived Water, Carbon, and Nitrogen in Upland Oak-Hickory Forest
Authors: Limpert Katy , Siegert Courtney
Published: December 2019

Oaks (Quercus) are a dominant forest species throughout much of the eastern United States. However, oak regeneration failure due to a myriad of issues (e.g., suppression of natural fire, excess nitrogen deposition, pressure from herbivore activity) is leading to a decline in oak dominance. This change may alter forest hydrology and nutrients through variation in species characteristics. Throughfall (TF) and stemflow (SF) quantity and chemistry were sampled during storm events under oak and non-oak (hickory, Carya) species to quantify differences in canopy-derived water and nutrients from an upland oak-hickory forest in Mississippi. Stemflow partitioning was 86% higher in hickory species compared to oak species (394.50 L m−2; p < 0.001). Across all species, dissolved organic carbon (DOC) was 1.5 times greater in throughfall (p = 0.024) and 8.7 times greater in stemflow (p < 0.001) compared to rainfall. White oak DOC concentrations (TF: 22.8 ± 5.5 mg L−1; SF: 75.1 ± 9.5 mg L−1) were greater compared to hickory species (TF: 21.0 ± 18.3 mg L−1; SF: 34.5 ± 21.0 mg L−1) (p = 0.048). Results show that while smoother-barked hickory species generate more stemflow volume, rougher-barked oak species generate stemflow that is more enriched in nutrients, which is a function of the canopy characteristics of each species. Within a single stand, this study demonstrates how variable water and nutrient fluxes may be and provide insights into species-level variability in oak-hickory forest types that may be undergoing compositional changes.
Dynamics and Vertical Distribution of Roots in European Beech Forests and Douglas Fir Plantations in Bulgaria
Authors: Lozanova Lyudmila , Zhiyanski Miglena , Vanguelova Elena , Doncheva Svetla , Marinov Martin P. , Lazarova Stela
Published: December 2019

Identifying patterns in roots spatial distribution and dynamics, and quantifying the root stocks, annual production and turnover rates at species level is essential for understanding plant ecological responses to local environmental factors and climate change. We studied selected root traits in four different stands, two European beech (Fagus sylvatica L.) forests and two Douglas fir (Pseudotsuga menziezii Mirb. Franco) plantations. Root system vertical distribution and dynamics were studied using sequential coring method and characterised into three root diameter size classes (0–2, 2–5 and 5–10 mm) sampled at three different soil depths (0–15, 15–30, 30–45 cm). Root annual production and turnover rates were analysed and quantified using Decision Matrix and Maximum-Minimum estimation approaches. The overall root mass (<10 mm diameter up to 0–45 cm soil depth) was higher in the beech forests than in the Douglas fir plantations. Some root traits, e.g., the overall root mass, the fine (0–2 mm) and small (2–5 mm) roots mass, differed significantly between the sampling plots rather than between the forest types. The root system revealed a tree species specific vertical distribution pattern. More than half of the fine and small roots biomass of the Douglas fir stands were allocated in the uppermost soil layer and decreased significantly with depths, while in the beech forests the biomass was more uniformly distributed and decreased gradually with increasing soil depth. Although both tree species belong to two different plant functional types and the stands were situated in two distantly located regions with different climatic and soil characteristics, we revealed similar trends in the root biomass and necromass dynamics, and close values for the annual production and turnover rates. The mean turnover rates for all studied stands obtained by sequential coring and Decision Matrix were 1.11 yr−1 and 0.76 yr−1 based on mean and maximum biomass data, respectively. They were similar to the averaged values suggested for Central and Northern European forests but higher compared to those reported from Southern Europe.
From the Laboratory to the Kitchen: New Alternatives to Healthier Bakery Products
Authors: Peris Miguel , Rubio-Arraez Susana , Castelló María Luisa , Ortolá María Dolores
Published: December 2019

Due to the growing interest in improving the nutritional profile of bakery products, we have dealt with the most recent and relevant contributions regarding potential replacements for carbohydrates, proteins, and fats. Focusing on the influence of carbohydrates on metabolism, their excess implies obesity, diabetes and tooth decay. However, they are technologically important, since they are responsible for the structure of many bakery products. Regarding of the lipid profile, saturated fats have a great impact on the appearance of cardiovascular disease. Fortunately, nature and the food industry offer alternatives to traditional oils/butters with large amounts of omega 3 and other components that can mitigate these problems. Other relevant aspects are related to allergies concerning egg proteins, gluten or even requirements for vegan consumers. Several studies have been performed in this line, replacing eggs with milk serum, different mucilages obtained from legumes or some gums, etc. In conclusion, many papers have been published showing the possibility of successfully replacing (both at technological and sensory levels) less healthy ingredients with others that are nutritionally better. The challenge now is to combine these better components in a given product, as well as to evaluate possible interactions among them.
iTRAQ-Based Protein Profiling Provides Insights into the Mechanism of Light-Induced Anthocyanin Biosynthesis in Chrysanthemum (Chrysanthemum × morifolium)
Authors: Hong Yan , Li Mengling , Dai Silan
Published: December 2019

The generation of chrysanthemum (Chrysanthemum × morifolium) flower color is mainly attributed to the accumulation of anthocyanins. Light is one of the key environmental factors that affect the anthocyanin biosynthesis, but the deep molecular mechanism remains elusive. In our previous study, a series of light-induced structural and regulatory genes involved in the anthocyanin biosynthetic pathway in the chrysanthemum were identified using RNA sequencing. In the present study, differentially expressed proteins that are in response to light with the capitulum development of the chrysanthemum ‘Purple Reagan’ were further identified using isobaric tags for relative and absolute quantification (iTRAQ) technique, and correlation between the proteomic and the transcriptomic libraries was analyzed. In general, 5106 raw proteins were assembled based on six proteomic libraries (three capitulum developmental stages × two light treatments). As many as 160 proteins were differentially expressed between the light and the dark libraries with 45 upregulated and 115 downregulated proteins in response to shading. Comparative analysis between the pathway enrichment and the gene expression patterns indicated that most of the proteins involved in the anthocyanin biosynthetic pathway were downregulated after shading, which was consistent with the expression patterns of corresponding encoding genes; while five light-harvesting chlorophyll a/b-binding proteins were initially downregulated after shading, and their expressions were enhanced with the capitulum development thereafter. As revealed by correlation analysis between the proteomic and the transcriptomic libraries, GDSL esterase APG might also play an important role in light signal transduction. Finally, a putative mechanism of light-induced anthocyanin biosynthesis in the chrysanthemum was proposed. This study will help us to clearly identify light-induced proteins associated with flower color in the chrysanthemum and to enrich the complex mechanism of anthocyanin biosynthesis for use in cultivar breeding.
Protein Misfolding during Pregnancy: New Approaches to Preeclampsia Diagnostics
Authors: Gerasimova Elizaveta M. , Fedotov Sergey A. , Kachkin Daniel V. , Vashukova Elena S. , Glotov Andrey S. , Chernoff Yury O. , Rubel Aleksandr A.
Published: December 2019

Preeclampsia (PE) is a multisystem heterogeneous complication of pregnancy remaining a leading cause of maternal and perinatal morbidity and mortality over the world. PE has a large spectrum of clinical features and symptoms, which make diagnosis challenging. Despite a long period of studying, PE etiology is still unclear and there are no reliable rapid tests for early diagnosis of this disease. During the last decade, it was shown that proteins misfolding and aggregation are associated with PE. Several proteins, including amyloid beta peptide, transthyretin, alpha-1 antitrypsin, albumin, IgG k-free light chains, and ceruloplasmin are dysregulated in PE, resulting in toxic deposition of amyloid-like aggregates in the placenta and body fluids. It is also possible that aggregated proteins induce defective trophoblast invasion, placental ischemia, ER stress, and promote PE manifestation. The fact that protein aggregation is an emerging biomarker of PE provides an opportunity to develop new diagnostic approaches based on amyloids special features, such as Congo red (CR) staining and thioflavin T (ThT) enhanced fluorescence.
The Role of IgA in the Pathogenesis of IgA Nephropathy
Authors: Perše Martina , Večerić-Haler Željka
Published: December 2019

Immunoglobulin A (IgA) is the most abundant antibody isotype produced in humans, predominantly present in the mucosal areas where its main functions are the neutralization of toxins, prevention of microbial invasion across the mucosal epithelial barrier, and simultaneous maintenance of a physiologically indispensable symbiotic relationship with commensal bacteria. The process of IgA biosynthesis, interaction with receptors, and clearance can be disrupted in certain pathologies, like IgA nephropathy, which is the most common form of glomerulonephritis worldwide. This review summarizes the latest findings in the complex characteristics of the molecular structure and biological functions of IgA antibodies, offering an in-depth overview of recent advances in the understanding of biochemical, immunologic, and genetic factors important in the pathogenesis of IgA nephropathy.
Transoral Robot-Assisted Surgery in Supraglottic and Oropharyngeal Squamous Cell Carcinoma: Laser Versus Monopolar Electrocautery
Authors: Benazzo Marco , Canzi Pietro , Mauramati Simone , Sovardi Fabio , Occhini Antonio , Maiorano Eugenia , Trisolini Giuseppe , Morbini Patrizia
Published: December 2019

Background: Monopolar electrocautery (EC) is the surgical cutting and haemostatic tool most commonly used for transoral robotic surgery (TORS). The aim of this study was to retrospectively compare EC efficacy in the treatment of patients affected by T1 or T2 oropharyngeal and supraglottic squamous cell carcinomas with the more recently introduced laser fibres. Methods: We considered all TORS patients admitted to our department from January 2010 to June 2019. The outcomes of patients treated with Thulium: yttrium aluminium garnet (YAG) laser (TY-TORS), CO2 laser (CO2-TORS) and EC (EC-TORS) were analysed in order to assess surgical performances, functional outcomes and postoperative complications. Results: Twenty patients satisfied the enrolling criteria, of which nine underwent laser-TORS, and the remaining 11 underwent EC-TORS. In all candidates, TORS procedures were completed without the need for microscopic/open conversion. Close or positive margins were significantly more frequent in EC-TORS (p = 0.028). A considerable difference was found in overall functional parameters: times of nasogastric tube and tracheostomy removal and time of hospital discharge were significantly shorter in laser-TORS (p = 0.04, p = 0.05, p = 0.04, respectively). Conclusions: Laser-TORS showed better results in comparison with EC-TORS in term of tumour resection margins and patient functional outcomes. Our findings can be justified with the greater tissue thermal damage caused by EC-TORS, despite prospective randomized trials and increased patient numbers being needed to confirm these preliminary conclusions.
A Model for Intact and Damage Stability Evaluation of CNG Ships during the Concept Design Stage
Authors: Mauro Francesco , Braidotti Luca , Trincas Giorgio
Published: December 2019

To face the design of a new ship concept, the evaluation of multiple feasible solutions concerning several aspects of naval architecture and marine engineering is necessary. Compressed natural gas technologies are in continuous development; therefore, there are no available databases for existing ships to use as a basis for the design process of a new unit. In this sense, the adoption of a modern multi-attribute decision-based method can help the designer for the study of a completely new ship prototype. A database of compressed natural gas ships was generated starting from a baseline hull, varying six hull-form parameters by means of the design of experiment technique. Between the attributes involved in the concept design process, stability is for sure one of the most relevant topics, both for intact and damaged cases. This work describes two approaches to identify the compliance of a ship with the intact stability regulations based on the ship main geometrical quantities. Moreover, a metamodel based on the maximum floodable length concept (damage stability) allows determining the main internal subdivision of the ship. The metamodel outcomes were compared with results from direct calculations on a ship external to the database, highlighting the adequate accuracy given by the developed methods.
Dynamics of the Coastal Zone
Authors: Postacchini Matteo , Romano Alessandro
Published: December 2019

The coastal zone hosts many human activities and interests, which have significantly increased in the last few decades [...]
Generalized Parabolic Marcinkiewicz Integral Operators Related to Surfaces of Revolution
Authors: Darweesh Amer , Ali Mohammed
Published: December 2019

In this work, the generalized parametric Marcinkiewicz integral operators with mixed homogeneity related to surfaces of revolution are studied. Under some weak conditions on the kernels, the boundedness of such operators from Triebel–Lizorkin spaces to L p spaces are established. Our results, with the help of an extrapolation argument, improve and extend some previous known results.
The Dirichlet Problem of the Constant Mean Curvature in Equation in Lorentz-Minkowski Space and in Euclidean Space
Authors: López Rafael
Published: December 2019

We investigate the differences and similarities of the Dirichlet problem of the mean curvature equation in the Euclidean space and in the Lorentz-Minkowski space. Although the solvability of the Dirichlet problem follows standards techniques of elliptic equations, we focus in showing how the spacelike condition in the Lorentz-Minkowski space allows dropping the hypothesis on the mean convexity, which is required in the Euclidean case.
Diethyl Blechnic Exhibits Anti-Inflammatory and Antioxidative Activity via the TLR4/MyD88 Signaling Pathway in LPS-Stimulated RAW264.7 Cells
Authors: He Jia , Han Shan , Li Xin-Xing , Wang Qin-Qin , Cui Yushun , Chen Yangling , Gao Hongwei , Huang Liting , Yang Shilin
Published: December 2019

Inflammation is a common pathogenesis in many diseases. Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has been considered to have good anti-inflammatory effects. In the present study, we investigated the anti-inflammatory effect of diethyl blechnic (DB), a novel compound isolated from Danshen, and its possible mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The results showed that DB can inhibit the LPS-induced pro-inflammatory cytokines release of prostaglandin E2 (PGE2) and mRNA expression of TNF-α, IL-6, and IL-1β. In addition, the results of the flow cytometry assay and the fluorometric intracellular ROS kit assay indicated that DB reduced the generation of ROS in LPS-stimualted RAW264.7 cells. DB reversed the LPS-induced loss of the mitochondrial membrane potential (MMP). Furthermore, DB suppressed the LPS-stimulated increased expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88) and phosphorylation of TAK1, PI3K, and AKT. DB promoted NF-E2-related factor 2 (Nrf2) into the nucleus, increased the expression of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) and reduced the expression of Keap1. In summary, DB may inhibit LPS-induced inflammation, which mainly occurs through TLR4/MyD88 and oxidative stress signaling pathways in RAW264.7 cells.
Novel Homo-Bivalent and Polyvalent Compounds Based on Ligustrazine and Heterocyclic Ring as Anticancer Agents
Authors: Wang Jiawen , Hong Ge , Li Guoliang , Wang Wenzhi , Liu Tianjun
Published: December 2019

Bivalent and polyvalent inhibitors can be used as antitumor agents. In this experiment, eight ligustrazine dimers and seven ligustrazine tetramers linked by alkane diamine with different lengths of carbon chain lengths were synthesized. After screening their antiproliferation activities against five cancer cell lines, most ligustrazine derivatives showed better cytotoxicity than the ligustrazine monomer. In particular, ligustrazine dimer 8e linked with decane-1,10-diamine exhibited the highest cytotoxicity in FaDu cells with an IC50 (50% inhibiting concentration) value of 1.36 nM. Further mechanism studies suggested that 8e could induce apoptosis of FaDu cells through the depolarization of mitochondrial membrane potential and S-phase cell cycle arrest. Inspired by these results, twenty-seven additional small molecule heterocyclic dimers linked with decane-1,10-diamine and nine cinnamic acid dimers bearing ether chain were synthesized and screened. Most monocyclic and bicyclic aromatic systems showed highly selective anti-proliferation activity to FaDu cells and low toxicity to normal MCF 10A cells. The structure-activity relationship revealed that the two terminal amide bonds and the alkyl linker with a chain length of 8–12 carbon were two important factors to maintain its antitumor activity. In addition, the ADMET calculation predicted that most of the potent compounds had good oral bioavailability.
Optical Polarization Sensitive Ultra-Fast Switching and Photo-Electrical Device
Authors: Belhassen Jérémy , Zalevsky Zeev , Karsenty Avi
Published: December 2019

Ultra-fast electrical switches activated with an optical-polarized light trigger, also called photo-polarized activated electrical switches, are presented. A set of new transistor circuits is switched by light from above, illuminating deep V-grooves, whose angle is sensitive to the polarization of the incident. Thus, this application may serve for encryption/decryption devices since the strongest electrical responsivity is only obtained for very specific spatial polarization directions of the illumination beam. When this V-groove is sufficiently narrow, the device mainly responds to one polarization and not to the other. In such a way, electrons are generated only for one specific polarization. While the nature of the data remains electronic, the modulation control is optic, creating a photo-induced current depending on the polarization direction. This coupled device acts as a polarization modulator as well as an intensity modulator. The article focuses on the integration of several devices in different configurations of circuitry: dual, triple, and multi-element. Case studies of several adjacent devices are presented with varying critical variables, such as the V-groove aperture dimensions. Analytical models and complementary numerical analyses are presented for the future smooth integration into Complementary Metal-Oxide-Semiconductor (CMOS) technology.
Eugenol Polysiloxane-Polycarbonate/Graphene Nanocomposite: Enhanced in Thermostability and Barrier Property
Authors: Pang Xiaoyan , Chen Mingde , Fu Junwei , Lin Zehua , Li Yuming , Wu Jianxin , Yan Jie , Chen Xunjun , Ge Jianfang
Published: December 2019

Graphene (GR) was used to blend with eugenol polysiloxane-polycarbonate (Si-PC) copolymer to prepare a Si-PC/GR nanocomposite via a solution blending method and the impact of graphene on the properties of Si-PC/GR nanocomposite was investigated. The morphology and structure of the Si-PC/GR nanocomposite were characterized. Combining morphology and property analysis, the result showed that when the graphene dispersed uniformly in the Si-PC matrix, the mechanical properties, thermostability and barrier property of Si-PC/GR nanocomposite were enhanced. Compared with Si-PC copolymer, the pyrolytic temperature of Si-PC/2.5%GR nanocomposite at 5% weight loss was 434.3 °C, which was 20.6 °C higher than Si-PC copolymer; and the oxygen barrier value of Si-PC/1.5%GR nanocomposite decreased to 160.2 cm3/m2 24 h 0.1 MPa, which was 53.2 less than pure Si-PC. The mechanical properties of Si-PC/GR nanocomposite were enhanced with an appropriate additive amount of graphene. The hydrophobicity also had been enhanced at the meantime.
Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 Induce the Expression of the REG3 Family in the Small Intestine of Mice via the Stimulation of Dendritic Cells and Type 3 Innate Lymphoid Cells
Authors: Kobayashi Kyosuke , Honme Yoshiko , Sashihara Toshihiro
Published: December 2019

Accumulating evidence clarifies that intestinal barrier function, for example, by the mucus layer, antimicrobial peptides, immune systems, and epithelial tight junctions, plays crucial roles in maintaining our health. We reported previously that yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 induced the gene expression of the regenerating family member 3 (REG3) family, which encodes antimicrobial peptides in the small intestine, although it was unclear how the yogurt activated the intestinal cells related to it. Here, we evaluated the cytokine production from the intestinal immune cells stimulated by these strains in vitro and in vivo to elucidate the mechanism for the induction of the REG3 family by the yogurt. The results showed that stimulation by both strains induced interleukin (IL)-23 production from bone marrow-derived dendritic cells (DCs) and IL-22 production from small intestinal lamina propria (LP) cells. In addition, oral administration of these strains to mice increased IL-23p19+ LPDCs and IL-22+ type 3 innate lymphoid cells and induced the expression of Reg3g in small intestinal tissue. Moreover, we showed that the activities for the induction of IL-23 by DCs were strain dependent on L. bulgaricus and S. thermophilus and that S. thermophilus 1131, which is the predominant species in the yogurt, exhibited relatively higher activity compared to the other strains of S. thermophilus. Our findings suggested that these yogurt starter strains, L. bulgaricus 2038 and S. thermophilus 1131, have the potential to maintain and improve intestinal barrier function by stimulating immune cells in the LP.
The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition
Authors: Moron Rocio , Galvez Julio , Colmenero Manuel , Anderson Per , Cabeza José , Rodriguez-Cabezas Maria Elena
Published: December 2019

Critically ill patients have an alteration in the microbiome in which it becomes a disease-promoting pathobiome. It is characterized by lower bacterial diversity, loss of commensal phyla, like Firmicutes and Bacteroidetes, and a domination of pathogens belonging to the Proteobacteria phylum. Although these alterations are multicausal, many of the treatments administered to these patients, like antibiotics, play a significant role. Critically ill patients also have a hyperpermeable gut barrier and dysregulation of the inflammatory response that favor the development of the pathobiome, translocation of pathogens, and facilitate the emergence of sepsis. In order to restore the homeostasis of the microbiome, several nutritional strategies have been evaluated with the aim to improve the management of critically ill patients. Importantly, enteral nutrition has proven to be more efficient in promoting the homeostasis of the gut microbiome compared to parenteral nutrition. Several nutritional therapies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, are currently being used, showing variable results, possibly due to the unevenness of clinical trial conditions and the fact that the beneficial effects of probiotics are specific to particular species or even strains. Thus, it is of great importance to better understand the mechanisms by which nutrition and supplement therapies can heal the microbiome in critically ill patients in order to finally implement them in clinical practice with optimal safety and efficacy.