bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactoferrin Functionalized Biomaterials: Tools for Prevention of Implant-Associated Infections
Authors: Pall Emoke , Roman Alexandra
Published: August 2020

Tissue engineering is one of the most important biotechnologies in the biomedical field. It requires the application of the principles of scientific engineering in order to design and build natural or synthetic biomaterials feasible for the maintenance of tissues and organs. Depending on the specific applications, the selection of the proper material remains a significant clinical concern. Implant-associated infection is one of the most severe complications in orthopedic implant surgeries. The treatment of these infections is difficult because the surface of the implant serves not only as a substrate for the formation of the biofilm, but also for the selection of multidrug-resistant bacterial strains. Therefore, a promising new approach for prevention of implant-related infection involves development of new implantable, non-antibiotic-based biomaterials. This review provides a brief overview of antimicrobial peptide-based biomaterials—especially those coated with lactoferrin.
Advanced Glycation End Product Accumulation in Subjects with Open-Angle Glaucoma with and without Exfoliation
Authors: Shirakami Tomoki , Yamanaka Mikihiro , Fujihara Jo , Matsuoka Yotaro , Gohto Yuko , Obana Akira , Tanito Masaki
Published: August 2020

Advanced glycation end products (AGEs), which are the products of a non-enzymatic reaction between reducing sugars and other macromolecules, are critical in aging, as well as metabolic and degenerative diseases. To assess the involvement of AGEs in glaucoma, skin autofluorescence (sAF) level, which is a measurement of AGEs’ accumulation, was compared among Japanese patients with glaucoma (316 with primary open-angle glaucoma (PG) and 127 exfoliation syndrome and glaucoma (EG)) and controls (133 nonglaucomatous controls) (mean age 71.6 ± 12.8 years, 254 men and 322 women). The sAF values were estimated from the middle fingertip using a 365 nm light-emitting diode for excitation and detection at 440 nm emission light. The estimated AGE values (arbitrary unit) were 0.56 ± 0.15, 0.56 ± 0.11, and 0.61 ± 0.11 in the control, PG, and EG groups, respectively (p < 0.0001, analysis of variance); and were significantly higher in the EG group than the control (p = 0.0007) and PG (p < 0.0001) groups. After adjustment for various demographic parameters by multivariate analyses, male sex (standard β = 0.23), EG (0.19), and diabetes (0.09) were associated with higher AGE levels; PG (−0.18) and smoking (−0.19) were associated with lower AGE levels. Age, visual acuity, intraocular pressure, glaucoma medications, lens status, and systemic hypertension were not associated with AGEs. The high AGE level in EG suggested that specific oxidation and glycation mechanisms underlie the glaucoma pathogenesis associated with pseudoexfoliation syndrome.
Theoretical Study of the Iron Complexes with Aminoguanidine: Investigating Secondary Antioxidant Activity
Authors: García-Díez Guillermo , Mora-Diez Nelaine
Published: August 2020

A thorough analysis of the thermodynamic stability of various complexes of aminoguanidine (AG) with Fe(III) at a physiological pH is presented. Moreover, the secondary antioxidant activity of AG is studied with respect to its kinetic role in the Fe(III) reduction to Fe(II) when reacting with the superoxide radical anion or ascorbate. Calculations are performed at the M05(SMD)/6-311+G(d,p) level of theory. Solvent effects (water) are taken into account in both geometry optimizations and frequency calculations employing the SMD solvation method. Even though the results of this study show that AG can form an extensive number of stable complexes with Fe(III), none of these can reduce the rate constant of the initial step of the Haber–Weiss cycle when the reducing agent is O2•−. However, when the reductant is the ascorbate anion, AG is capable of reducing the rate constant of this reaction significantly, to the point of inhibiting the production of •OH radicals. In fact, the most stable complex of Fe(III) with AG, having a ∆Gf° of −37.9 kcal/mol, can reduce the rate constant of this reaction by 7.9 × 105 times. Thus, AG possesses secondary antioxidant activity relative to the Fe(III)/Fe(II) reduction with ascorbate, but not with O2•−. Similar results have also been found for AG relative to the Cu(II)/Cu(I) reduction, in agreement with experimental results.
BKCa Channels as Targets for Cardioprotection
Authors: Szteyn Kalina , Singh Harpreet
Published: August 2020

The large-conductance calcium- and voltage-activated K+ channel (BKCa) are encoded by the Kcnma1 gene. They are ubiquitously expressed in neuronal, smooth muscle, astrocytes, and neuroendocrine cells where they are known to play an important role in physiological and pathological processes. They are usually localized to the plasma membrane of the majority of the cells with an exception of adult cardiomyocytes, where BKCa is known to localize to mitochondria. BKCa channels couple calcium and voltage responses in the cell, which places them as unique targets for a rapid physiological response. The expression and activity of BKCa have been linked to several cardiovascular, muscular, and neurological defects, making them a key therapeutic target. Specifically in the heart muscle, pharmacological and genetic activation of BKCa channels protect the heart from ischemia-reperfusion injury and also facilitate cardioprotection rendered by ischemic preconditioning. The mechanism involved in cardioprotection is assigned to the modulation of mitochondrial functions, such as regulation of mitochondrial calcium, reactive oxygen species, and membrane potential. Here, we review the progress made on BKCa channels and cardioprotection and explore their potential roles as therapeutic targets for preventing acute myocardial infarction.
Self-Assembled Three-Dimensional Microporous rGO/PNT/Fe3O4 Hydrogel Sorbent for Magnetic Preconcentration of Multi-Residue Insecticides
Authors: Wang Sheng , Li Xiuqin , Li Ming , Li Xianjiang , Li Xiaomin , Li Shuangqing , Zhang Qinghe , Li Hongmei
Published: August 2020

The purpose of this work was to develop a highly selective, sensitive, and reliable method for multi-residual analysis. A three-dimensional microporous reduced graphene oxide/polypyrrole nanotube/magnetite hydrogel (3D-rGOPFH) composite was synthesized and utilized as a magnetic solid-phase extraction (MSPE) sorbent to preconcentrate thirteen insecticides, including five organophosphorus (isocarbophos, quinalphos, phorate, chlorpyrifos, and phosalone), two carbamates (pirimor and carbaryl), two triazoles (myclobutanil and diniconazole), two pyrethroids (lambda-cyhalothrin and bifenthrin), and two organochlorines (2, 4′-DDT and mirex), from vegetables, followed by gas chromatography-tandem mass spectrometry. This method exhibited several major advantages, including simultaneous enrichment of different types of insecticides, no matrix effect, high sensitivity, and ease of operation. This is ascribed to the beneficial effects of 3D-rGOPFH, including the large specific surface (237 m2 g−1), multiple adsorption interactions (hydrogen bonding, electrostatic, π–π stacking and hydrophobic interaction force), appropriate pore size distribution (1–10 nm), and the good paramagnetic property. Under the optimal conditions, the analytical figures of merit were obtained as: linear dynamic range of 0.1–100 ng g−1 with determination coefficients of 0.9975–0.9998; limit of detections of 0.006–0.03 ng g−1; and the intra-day and inter-day relative standard deviations were 2.8–7.1% and 3.5–8.8%, respectively. Recoveries were within the range of 79.2 to 109.4% for tomato, cucumber, and pakchoi samples at the fortification levels of 5, 25, and 50 ng g−1. This effective and robust method can be applied for determining multi-classes of insecticide residues in vegetables.
An eLORETA Longitudinal Analysis of Resting State EEG Rhythms in Alzheimer’s Disease
Authors: Dattola Serena , La Foresta Fabio
Published: August 2020

Alzheimer’s disease (AD) is a degenerative brain disorder which is the most common cause of dementia. As there is no cure for AD, an early diagnosis is essential to slow down the progression of the disease with a proper pharmacological treatment. Electroencephalography (EEG) represents a valid tool for studying AD. EEG signals of AD patients are characterized by a “slowing”, meaning the power increases in low frequencies (delta and theta) and decreases in higher frequency (alpha and beta), compared to normal elderly. The purpose of our study is the computation of the power current density in eight patients, who were diagnosed with MCI at time T0 and mild AD at time T1 (four months later), starting from the brain active source reconstruction. The novelty is that we employed the eLORETA algorithm, unlike the previous studies which used the old version of the algorithm named LORETA. It is also the first longitudinal study which considers such a short time period to explore the evolution of the disease. Five patients out of eight showed an increasing power in delta and theta bands. Seven patients exhibited a lower activation in alpha 1 and beta 2 bands. Finally, six patients revealed a decreased power in alpha 2 and beta 1 bands. These findings are consistent with those reported in literature. On the other hand, the discrepancy of some outcome could be related to a not yet severe stage of the disease. In our opinion, this study could represent a good starting point for more detailed future investigation.
An Autonomous Attack Guidance Method with High Aiming Precision for UCAV Based on Adaptive Fuzzy Control under Model Predictive Control Framework
Authors: Yang Zhen , Sun Zhixiao , Piao Haiyin , Zhao Yiyang , Zhou Deyun , Kong Weiren , Zhang Kai
Published: August 2020

With its superior performance, the unmanned combat air vehicle (UCAV) will gradually become an important combat force in the future beyond-visual-range (BVR) air combat. For the problem of UCAV using the BVR air-to-air missile (AAM) to intercept the highly maneuvering aerial target, an autonomous attack guidance method with high aiming precision is proposed. In BVR air combat, the best launching conditions can be formed through the attack guidance and aiming of fighters, which can give full play to the combat effectiveness of BVR AAMs to the greatest extent. The mode of manned fighters aiming by manual control of pilots is inefficient and obviously not suitable for the autonomous UCAV. Existing attack guidance control methods have some defects such as low precision, poor timeliness, and too much reliance on manual experience when intercepting highly maneuvering targets. To address this problem, aiming error angle is calculated based on the motion model of UCAV and the aiming model of BVR attack fire control in this study, then target motion prediction information is introduced based on the designed model predictive control (MPC) framework, and the adaptive fuzzy guidance controller is designed to generate control variable. To reduce the predicted aiming error angle, the algorithm iteratively optimizes and updates the actual guidance control variable online. The simulation results show that the proposed method is very effective for solving the autonomous attack guidance problem, which has the characteristics of adaptivity, high timeliness, and high aiming precision.
Measurements of Acoustical Parameters in the Ancient Open-Air Theatre of Tyndaris (Sicily, Italy)
Authors: Astolfi Arianna , Bo Elena , Aletta Francesco , Shtrepi Louena
Published: August 2020

The emerging field of archaeoacoustics is attracting increasing research attention from scholars of different disciplines: the investigation of the acoustic features of ancient open-air theatres is possibly one of its main themes. In this paper, the outcomes of a measurement campaign of acoustical parameters in accordance with ISO 3382-1 in the ancient theatre of Tyndaris (Sicily) are presented and compared with datasets from other sites. Two sound sources were used (firecrackers and dodecahedron) and their differences were analysed. A very good reproducibility has been shown between the two measurement chains, with differences on average of 0.01 s for reverberation time T20, and less than 0.3 dB for Clarity C50 and C80 and for sound strength. In general, results show that the reverberation time and strength of sound values are relatively low when compared with other theatres because of the lack of the original architectural element of the scaenae frons. When combining this effect with the obvious condition of an unroofed space, issues emerge in terms of applicability of the protocols recommended in the ISO standard. This raises the question of whether different room acoustics parameters should be used to characterise open-air ancient theatres.
Mechanical Properties and Freeze–Thaw Durability of Basalt Fiber Reactive Powder Concrete
Authors: Li Wenjun , Liu Hanbing , Zhu Bing , Lyu Xiang , Gao Xin , Liang Chunyu
Published: August 2020

Basalt fiber has a great advantage on the mechanical properties and durability of reactive powder concrete (RPC) because of its superior mechanical properties and chemical corrosion resistance. In this paper, basalt fiber was adopted to modified RPC, and plain reactive powder concrete (PRPC), basalt fiber reactive powder concrete (BFRPC) and steel fiber reactive powder concrete (SFRPC) were prepared. The mechanical properties and freeze–thaw durability of BFRPC with different basalt fiber contents were tested and compared with PRPC and SFRPC to investigate the effects of basalt fiber contents and fiber type on the mechanical properties and freeze–thaw durability of RPC. Besides, the mass loss rate and compressive strength loss rate of RPC under two freeze–thaw conditions (fresh-water freeze–thaw and chloride-salt freeze–thaw) were tested to evaluate the effects of freeze–thaw conditions on the freeze–thaw durability of RPC. The experiment results showed that the mechanical properties and freeze–thaw resistance of RPC increased as the basalt fiber content increase. Compared with the fresh-water freeze–thaw cycle, the damage of the chloride-salt freeze–thaw cycle on RPC was great. Based on the freeze–thaw experiment results, it was found that SFRPC was sensitive to the corrosion of chloride salts and compared with the steel fiber, the improvement of basalt fiber on the freeze–thaw resistance of RPC was great.
Foxn1 Control of Skin Function
Authors: Gawronska-Kozak Barbara
Published: August 2020

The forkhead box N1 (Foxn1) transcription factor regulates biological processes of the thymus and skin. Loss-of-function mutations in Foxn1 cause the nude phenotype in humans, mice, and rats, which is characterized by hairless skin and a lack of thymus. This review focuses on the role of Foxn1 in skin biology, including epidermal, dermal, and dermal white adipose tissue (dWAT) skin components. In particular, the role of Foxn1 in the scar-forming skin wound healing process is discussed, underscoring that Foxn1 inactivity in nude mice is permissive for scar-less cutaneous wound resolution.
Enhancement of the Purcell Effect by the Wire Metamaterials Formed by the Hexagonal Unit Cells
Authors: Gric Tatjana , Rafailov Edik
Published: August 2020

The dependence of the Purcell factor on nanowire metamaterial geometry was analyzed. Calculations made about the Purcell factor in realistic composites, operating at an optical spectral range, are provided. We applied a metamaterial, aiming to mitigate the negative effects of absorption in metals on the Purcell effect in nanowire structures. A nanowire metamaterial was treated as an anisotropic composite in the long-wavelength limit. We investigated the mode patterns of the surface waves, propagating at the boundary separating such a structure and a dielectric material, along with the position of the peak in the local density of states, for the various filling factors of the periodic structure. By calculating the frequency dependence of the Purcell factor, we showed an increase in the peak value in comparison with the conventional plasmonic structure in the (1–100 THz) frequency range. Moreover, an optimal set of the parameters, needed to obtain the two topological transitions in the frequency range under investigation, is proposed.
Analysis of Madrid Metro Network: From Structural to HJ-Biplot Perspective
Authors: Frutos Bernal E. , Martín del Rey A. , Galindo Villardón P.
Published: August 2020

With the growth of cities, urban traffic has increased and traffic congestion has become a serious problem. Due to their characteristics, metro systems are one of the most used public transportation networks in big cities. So, optimization and planning of metro networks are challenges which governments must focus on. The objective of this study was to analyze Madrid metro network using graph theory. Through complex network theory, the main structural and topological properties of the network as well as robustness characteristics were obtained. Furthermore, to inspect these results, multivariate analysis techniques were employed, specifically HJ-Biplot. This analysis tool allowed us to explore relationships between centrality measures and to classify stations according to their centrality. Therefore, it is a multidisciplinary study that includes network analysis and multivariate analysis. The study found that closeness and eccentricity were strongly negatively correlated. In addition, the most central stations were those located in the city center, that is, there is a relationship between centrality and geographic location. In terms of robustness, a highly agglomerated community structure was found.
Constructing a Smart Home for Future Elders toward All-around Happiness: Taking Connectivity as the Core Element
Authors: Liu Yuqi , Tamura Ryoichi , Song Yao
Published: August 2020

Smart homes, as one of the most prosperous industries of the Internet of Things, have tremendous potential in helping the elderly aging in place and dealing with the global aging society challenges. This study takes the needs of future elderly in China as a starting point and proposes that the core requirement of the aging group is “connectivity”, smart homes for older adults should assist them with connectivity establishment both physically and psychologically to improve their quality of life and help them live an independent, safe, and happy life in their older stage. The article defines the types of elderly connectivity needs as two main types and eight sub-connectivity, and further puts forward thirty smart home subsystems and their implementation elements. Moreover, the research applies the Kano model and questionnaire survey to provide the empirical proof of those thirty smart home subsystems based on the analysis of 371 questionnaire responses. Last but not least, we construct a five-layer architecture and abstract four principles on the connectivity building of a smart home for future Chinese elders. The research explores the possibility of building a wide range of connectivity and all-around happiness smart home environment for future elderly, which provides significant insights and an important reference for both the smart home industry and the pension industry.
Adaptive Trajectory Tracking Safety Control of Air Cushion Vehicle with Unknown Input Effective Parameters
Authors: Fu Mingyu , Dong Lijing , Xu Yujie , Wang Chenglong
Published: August 2020

This paper studies the trajectory tracking control problem of an Air Cushion Vehicle (ACV) with yaw rate error constraint, input effective parameters, model uncertainties and external wind disturbance. Firstly, based on the four-degree of freedom (DOF) vector mathematical mode of ACV, the radial basis function neural network (RBFNN) is adopted to provide the estimation of model uncertainties and external wind disturbance. Then, an adaptive Nussbaum gain-based approach is incorporated with the backstepping control scheme to handle the unknown input efficient parameters. To avoid the complicated derivative of the virtual control laws, the command filter and auxiliary systems are introduced in backstepping. Furthermore, combing a barrier Lyapunov function (BLF) with backstepping technique, a novel trajectory tracking safety controller is designed to ensure all signals of the closed-loop system are uniformly ultimately bounded, while the yaw rate error is within the pre-set safe range. Finally, the simulation results show the effectiveness of the controller scheme.
Quantifying the Changing Nature of the Winter Season Precipitation Phase from 1849 to 2017 in Downtown Toronto (Canada)
Authors: Hewer Micah J. , Gough William A.
Published: August 2020

One hundred and sixty–nine years of weather station data were analyzed to quantify the changing nature of the winter season precipitation phase in the downtown area of Toronto (Canada). The precipitation variables examined were rainfall, snowfall water equivalent, total precipitation, rain days, snow days, and precipitation days. From these precipitation variables, three precipitation phase metrics were constructed for further analysis: the fraction of total precipitation that fell as snow, the fraction of precipitation days that recorded snow, and finally, the precipitation phase index (PPI) derived from comparing the rainfall to the snowfall water equivalent. Snowfall and snow days were decreasing at the most significant rate over this time period, and although rain days were increasing, total precipitation and precipitation days were also decreasing at a statistically significant rate. All three precipitation phase metrics suggest that winters are becoming less snowy in Toronto’s urban center. We also looked at trends and changes in average winter season temperatures to explore correlations between warming temperatures and changes in the winter season precipitation phase. Of the three precipitation phase metrics considered, the ratio of snow days to precipitation days recorded the strongest time series trend and the strongest correlation with warming temperatures.
A Hydrodynamical Atmosphere/Ocean Coupled Modeling System for Multiple Tropical Cyclones
Authors: Alaka Ghassan J. , Sheinin Dmitry , Thomas Biju , Gramer Lew , Zhang Zhan , Liu Bin , Kim Hyun-Sook , Mehra Avichal
Published: August 2020

The goal of this paper is to introduce a new multi-storm atmosphere/ocean coupling scheme that was implemented and tested in the Basin-Scale Hurricane Weather Research and Forecasting (HWRF-B) model. HWRF-B, an experimental model developed at the National Oceanic and Atmospheric Administration (NOAA) and supported by the Hurricane Forecast Improvement Program, is configured with multiple storm-following nested domains to produce high-resolution predictions for several tropical cyclones (TCs) within the same forecast integration. The new coupling scheme parallelizes atmosphere/ocean interactions for each nested domain in HWRF-B, and it may be applied to any atmosphere/ocean coupled system. TC forecasts from this new hydrodynamical modeling system were produced in the North Atlantic and eastern North Pacific from 2017–2019. The performance of HWRF-B was evaluated, including forecasts of TC track, intensity, structure (e.g., surface wind radii), and intensity change, and simulated sea-surface temperatures were compared with satellite observations. Median forecast skill scores showed significant improvement over the operational HWRF at most forecast lead times for track, intensity, and structure. Sea-surface temperatures cooled by 1–8 °C for the five HWRF-B case studies, demonstrating the utility of the model to study the impact of the ocean on TC intensity forecasting. These results show the value of a multi-storm modeling system and provide confidence that the multi-storm coupling scheme was implemented correctly. Future TC models within NOAA, especially the Unified Forecast System’s Hurricane Analysis and Forecast System, would benefit from the multi-storm coupling scheme whose utility and performance are demonstrated in HWRF-B here.
Typhoon Quantitative Rainfall Prediction from Big Data Analytics by Using the Apache Hadoop Spark Parallel Computing Framework
Authors: Wei Chih-Chiang , Chou Tzu-Hao
Published: August 2020

Situated in the main tracks of typhoons in the Northwestern Pacific Ocean, Taiwan frequently encounters disasters from heavy rainfall during typhoons. Accurate and timely typhoon rainfall prediction is an imperative topic that must be addressed. The purpose of this study was to develop a Hadoop Spark distribute framework based on big-data technology, to accelerate the computation of typhoon rainfall prediction models. This study used deep neural networks (DNNs) and multiple linear regressions (MLRs) in machine learning, to establish rainfall prediction models and evaluate rainfall prediction accuracy. The Hadoop Spark distributed cluster-computing framework was the big-data technology used. The Hadoop Spark framework consisted of the Hadoop Distributed File System, MapReduce framework, and Spark, which was used as a new-generation technology to improve the efficiency of the distributed computing. The research area was Northern Taiwan, which contains four surface observation stations as the experimental sites. This study collected 271 typhoon events (from 1961 to 2017). The following results were obtained: (1) in machine-learning computation, prediction errors increased with prediction duration in the DNN and MLR models; and (2) the system of Hadoop Spark framework was faster than the standalone systems (single I7 central processing unit (CPU) and single E3 CPU). When complex computation is required in a model (e.g., DNN model parameter calibration), the big-data-based Hadoop Spark framework can be used to establish highly efficient computation environments. In summary, this study successfully used the big-data Hadoop Spark framework with machine learning, to develop rainfall prediction models with effectively improved computing efficiency. Therefore, the proposed system can solve problems regarding real-time typhoon rainfall prediction with high timeliness and accuracy.
An Updated Synoptic Climatology of Lake Erie and Lake Ontario Heavy Lake-Effect Snow Events
Authors: Wiley Jake , Mercer Andrew
Published: August 2020

Lake-effect snow (LES) storms pose numerous hazards, including extreme snowfall and blizzard conditions, and insight into the large-scale precursor conditions associated with LES can aid local forecasters and potentially allow risks to be mitigated. In this study, a synoptic climatology of severe LES events over Lakes Erie and Ontario was created using an updated methodology based on previous studies with similar research objectives. Principal component analysis (PCA) coupled with cluster analysis (CA) was performed on a case set of LES events from a study domain encompassing both lakes, grouping LES events with similar spatial characteristics into the primary composite structures for LES. Synoptic scale composites were constructed for each cluster using the North American Regional Reanalysis (NARR). Additionally, one case from each cluster was simulated using the Weather Research and Forecast (WRF) model to analyze mesoscale conditions associated with each of the clusters. Three synoptic setups were identified that consisted of discrepancies, mostly in the surface fields, from a common pattern previously identified as being conducive to LES, which features a dipole and upper-level low pressure anomaly located near the Hudson Bay. Mesoscale conditions associated with each composite support differing LES impacts constrained to individual lakes or a combination of both.
Protoplast Isolation and Shoot Regeneration from Protoplast-Derived Callus of Petunia hybrida Cv. Mirage Rose
Authors: Kang Hyun Hee , Naing Aung Htay , Kim Chang Kil
Published: August 2020

Despite the increasing use of protoplasts in plant biotechnology research, shoot regeneration from protoplasts remains challenging. In this study, we investigated the factors involved in protoplast isolation, callus induction, and shoot regeneration in Petunia hybrida cv. Mirage Rose. The following conditions were found to be most optimal for protoplast yield and viability: 0.6 M mannitol, 2.0% cellulase, and 6 h digestion time. A plating density of 10 × 104 protoplasts/mL under osmoticum condition (0.58 M mannitol) showed high microcolony viability in liquid culture. The Kao and Michayluk medium was found to be appropriate for callus proliferation from microcalli under a 16-h light photoperiod. Calli cultured in Murashige and Skoog medium containing 1.0 mg/L 6-benzylaminopurine and 0.2 mg/L 3-indole butyric acid showed the highest shoot regeneration frequency and number of shoots obtained per explant. Random amplification of polymorphic DNA analysis showed that the protoplast-derived shoots exhibited the same banding patterns as those of donor plants. Collectively, these findings can contribute to solving problems encountered in protoplast isolation and shoot regeneration in other petunia cultivars and related species. As the protocol developed by us is highly reproducible, it can be applied in biotechnology research on P. hybrida cv. Mirage Rose.
The Dawn of the Age of Multi-Parent MAGIC Populations in Plant Breeding: Novel Powerful Next-Generation Resources for Genetic Analysis and Selection of Recombinant Elite Material
Authors: Arrones Andrea , Vilanova Santiago , Plazas Mariola , Mangino Giulio , Pascual Laura , Díez María José , Prohens Jaime , Gramazio Pietro
Published: August 2020

The compelling need to increase global agricultural production requires new breeding approaches that facilitate exploiting the diversity available in the plant genetic resources. Multi-parent advanced generation inter-cross (MAGIC) populations are large sets of recombinant inbred lines (RILs) that are a genetic mosaic of multiple founder parents. MAGIC populations display emerging features over experimental bi-parental and germplasm populations in combining significant levels of genetic recombination, a lack of genetic structure, and high genetic and phenotypic diversity. The development of MAGIC populations can be performed using “funnel” or “diallel” cross-designs, which are of great relevance choosing appropriate parents and defining optimal population sizes. Significant advances in specific software development are facilitating the genetic analysis of the complex genetic constitutions of MAGIC populations. Despite the complexity and the resources required in their development, due to their potential and interest for breeding, the number of MAGIC populations available and under development is continuously growing, with 45 MAGIC populations in different crops being reported here. Though cereals are by far the crop group where more MAGIC populations have been developed, MAGIC populations have also started to become available in other crop groups. The results obtained so far demonstrate that MAGIC populations are a very powerful tool for the dissection of complex traits, as well as a resource for the selection of recombinant elite breeding material and cultivars. In addition, some new MAGIC approaches that can make significant contributions to breeding, such as the development of inter-specific MAGIC populations, the development of MAGIC-like populations in crops where pure lines are not available, and the establishment of strategies for the straightforward incorporation of MAGIC materials in breeding pipelines, have barely been explored. The evidence that is already available indicates that MAGIC populations will play a major role in the coming years in allowing for impressive gains in plant breeding for developing new generations of dramatically improved cultivars.
Polyphenol Profile and Biological Activity Comparisons of Different Parts of Astragalus macrocephalus subsp. finitimus from Turkey
Authors: Sarikurkcu Cengiz , Zengin Gokhan
Published: August 2020

The members of the genus Astragalus have great interest as traditional drugs in several folk systems including Turkey. In this sense, the present paper was aimed to explore the biological properties and chemical profiles of different parts (aerial parts, leaves, flowers, stems, and roots) of A. macrocephalus subsp. finitimus. Antioxidant (radical quenching, reducing power, and metal chelating) and enzyme inhibitory (α-amylase and tyrosinase) effects were investigated for biological properties. Regarding chemical profiles, individual phenolic compounds were detected by LC-MS, as well as total amounts. The leaves extract exhibited the strongest antioxidant abilities when compared with other parts. However, flowers extract had the best metal chelating ability. Hyperoside, apigenin, p-coumaric, and ferulic acids were identified as main compounds in the tested parts. Regarding enzyme inhibitory properties, tyrosinase inhibitory effects varied from IC50: 1.02 to 1.41 mg/mL. In addition, the best amylase inhibition effect was observed by leaves (3.36 mg/mL), followed by aerial parts, roots, stems, and flowers. As a result, from multivariate analysis, the tested parts were classified in three cluster. Summing up the results, it can be concluded that A. macrocephalus subsp. finitimus could be a precious source of natural bioactive agents in pharmaceutical, nutraceutical, and cosmeceutical applications.
Proteomic and Bioinformatic Profiling of Transporters in Higher Plant Mitochondria
Authors: Møller Ian , Rao R. , Jiang Yuexu , Thelen Jay , Xu Dong
Published: August 2020

To function as a metabolic hub, plant mitochondria have to exchange a wide variety of metabolic intermediates as well as inorganic ions with the cytosol. As identified by proteomic profiling or as predicted by MU-LOC, a newly developed bioinformatics tool, Arabidopsis thaliana mitochondria contain 128 or 143 different transporters, respectively. The largest group is the mitochondrial carrier family, which consists of symporters and antiporters catalyzing secondary active transport of organic acids, amino acids, and nucleotides across the inner mitochondrial membrane. An impressive 97% (58 out of 60) of all the known mitochondrial carrier family members in Arabidopsis have been experimentally identified in isolated mitochondria. In addition to many other secondary transporters, Arabidopsis mitochondria contain the ATP synthase transporters, the mitochondria protein translocase complexes (responsible for protein uptake across the outer and inner membrane), ATP-binding cassette (ABC) transporters, and a number of transporters and channels responsible for allowing water and inorganic ions to move across the inner membrane driven by their transmembrane electrochemical gradient. A few mitochondrial transporters are tissue-specific, development-specific, or stress-response specific, but this is a relatively unexplored area in proteomics that merits much more attention.
The Non-Fibrillating N-Terminal of α-Synuclein Binds and Co-Fibrillates with Heparin
Authors: Skaanning Line K. , Santoro Angelo , Skamris Thomas , Martinsen Jacob Hertz , D’Ursi Anna Maria , Bucciarelli Saskia , Vestergaard Bente , Bugge Katrine , Langkilde Annette Eva , Kragelund Birthe B.
Published: August 2020

The intrinsically disordered protein α-synuclein (aSN) is, in its fibrillated state, the main component of Lewy bodies—hallmarks of Parkinson’s disease. Additional Lewy body components include glycosaminoglycans, including heparan sulfate proteoglycans. In humans, heparan sulfate has, in an age-dependent manner, shown increased levels of sulfation. Heparin, a highly sulfated glycosaminoglycan, is a relevant mimic for mature heparan sulfate and has been shown to influence aSN fibrillation. Here, we decompose the underlying properties of the interaction between heparin and aSN and the effect of heparin on fibrillation. Via the isolation of the first 61 residues of aSN, which lacked intrinsic fibrillation propensity, fibrillation could be induced by heparin, and access to the initial steps in fibrillation was possible. Here, structural changes with shifts from disorder via type I β-turns to β-sheets were revealed, correlating with an increase in the aSN1–61/heparin molar ratio. Fluorescence microscopy revealed that heparin and aSN1–61 co-exist in the final fibrils. We conclude that heparin can induce the fibrillation of aSN1–61, through binding to the N-terminal with an affinity that is higher in the truncated form of aSN. It does so by specifically modulating the structure of aSN via the formation of type I β-turn structures likely critical for triggering aSN fibrillation.
Enhancement of Migration and Invasion of Gastric Cancer Cells by IQGAP3
Authors: Jinawath Natini , Shiao Meng-Shin , Chanpanitkitchote Pichaya , Svasti Jisnuson , Furukawa Yoichi , Nakamura Yusuke
Published: August 2020

Although gastric cancer is one of the most common causes of cancer death in the world, mechanisms underlying this type of tumor have not been fully understood. In this study, we found that IQGAP3, a member of the IQGAP gene family, was significantly up-regulated in human gastric cancer starting from the early stages of tumor progression. Overexpression of IQGAP3 in 293T and NIH3T3 cells, which have no endogenous IQGAP3 expression, resulted in morphological change with multiple dendritic-like protrusions and enhanced migration. Overexpression of IQGAP3 also led to reduced cell–cell adhesion in 293T cells, likely as a result of its interactions with e-cadherin or β-catenin proteins. Additionally, IQGAP3 accumulated along the leading edge of migrating cells and at the cleavage furrow of dividing cells. In contrast, suppression of IQGAP3 by short-interfering RNA (siRNA) markedly reduced invasion and anchorage-independent growth of MKN1 and TMK-1 gastric cancer cells. We further confirmed that IQGAP3 interacted with Rho family GTPases, and had an important role in cytokinesis. Taken together, we demonstrated that IQGAP3 plays critical roles in migration and invasion of human gastric cancer cells, and regulates cytoskeletal remodeling, cell migration and adhesion. These findings may open a new avenue for the diagnosis and treatment of gastric cancer.
Consecutive Treatment with Brain-Derived Neurotrophic Factor and Electrical Stimulation Has a Protective Effect on Primary Auditory Neurons
Authors: Scheper Verena , Seidel-Effenberg Ira , Lenarz Thomas , Stöver Timo , Paasche Gerrit
Published: August 2020

Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded. After one month of treatment, the tissue was harvested and the SGN density was assessed. The results show that consecutive treatment with BDNF and ES was as successful as the simultaneous combined treatment in terms of enhanced SGN density compared to the untreated contralateral side but not in regard to the numbers of protected cells.
Ruptured Thoracolumbar Perimedullary Arteriovenous Fistula during Pregnancy Complicated by Cerebral Subarachnoid Hemorrhage and Brainstem Hematoma: A Case Report
Authors: Sroubek Jan , Janouskova Ladislava , Klener Jan
Published: August 2020

Intradural spinal arteriovenous fistulas (sAVF) are spinal vascular lesions that usually manifest due to myelopathy or local symptoms caused by venous congestion and ischemia. In addition, perimedullary arteriovenous fistulas (PMAVF) in particular may rupture and cause subarachnoid or intramedullary hemorrhage along with relevant symptoms. Subarachnoid hemorrhage (SAH) can propagate into cranial space with clinically dominant symptoms and signs of typical aneurysmal intracranial SAH. The standard workup for cerebral SAH, after excluding an intracranial source of hemorrhage, is usually limited to a cervical spine MRI; therefore, thoracolumbar sources of hemorrhage can be missed, or their diagnosis may be delayed. Here we present a case of a pregnant patient who presented with cerebral SAH. The source of hemorrhage was not initially identified, leading to a presumptive diagnosis of benign pretruncal non-aneurysmal SAH. The correct diagnosis of spinal thoracolumbar PMAVF was revealed 2.5 months later due to the progression of local symptoms. While the diagnosis was being refined and endovascular treatment was being planned (but delayed due to pregnancy), there was a recurrence of intraconal hemorrhage followed by brainstem hemorrhage. This led to significant clinical deterioration. The PMAVF was then treated microsurgically and the patient experienced partial recovery.
Support Vector Machine-Based Schizophrenia Classification Using Morphological Information from Amygdaloid and Hippocampal Subregions
Authors: Guo Yingying , Qiu Jianfeng , Lu Weizhao
Published: August 2020

Structural changes in the hippocampus and amygdala have been demonstrated in schizophrenia patients. However, whether morphological information from these subcortical regions could be used by machine learning algorithms for schizophrenia classification were unknown. The aim of this study was to use volume of the amygdaloid and hippocampal subregions for schizophrenia classification. The dataset consisted of 57 patients with schizophrenia and 69 healthy controls. The volume of 26 hippocampal and 20 amygdaloid subregions were extracted from T1 structural MRI images. Sequential backward elimination (SBE) algorithm was used for feature selection, and a linear support vector machine (SVM) classifier was configured to explore the feasibility of hippocampal and amygdaloid subregions in the classification of schizophrenia. The proposed SBE-SVM model achieved a classification accuracy of 81.75% on 57 patients and 69 healthy controls, with a sensitivity of 84.21% and a specificity of 81.16%. AUC was 0.8241 (p < 0.001 tested with 1000-times permutation). The results demonstrated evidence of hippocampal and amygdaloid structural changes in schizophrenia patients, and also suggested that morphological features from the amygdaloid and hippocampal subregions could be used by machine learning algorithms for the classification of schizophrenia.
Renal Contributions in the Pathophysiology and Neuropathological Substrates Shared by Chronic Kidney Disease and Alzheimer’s Disease
Authors: Stanciu Gabriela Dumitrita , Ababei Daniela Carmen , Bild Veronica , Bild Walther , Paduraru Luminita , Gutu Mihai Marius , Tamba Bogdan-Ionel
Published: August 2020

Chronic kidney disease and Alzheimer’s disease are chronic conditions highly prevalent in elderly communities and societies, and a diagnosis of them is devastating and life changing. Demanding therapies and changes, such as non-compliance, cognitive impairment, and non-cognitive anomalies, may lead to supplementary symptoms and subsequent worsening of well-being and quality of life, impacting the socio-economic status of both patient and family. In recent decades, additional hypotheses have attempted to clarify the connection between these two diseases, multifactorial in their nature, but even so, the mechanisms behind this link are still elusive. In this paper, we sought to highlight the current understanding of the mechanisms for cognitive decline in patients with these concurrent pathologies and provide insight into the relationship between markers related to these disease entities and whether the potential biomarkers for renal function may be used for the diagnosis of Alzheimer’s disease. Exploring detailed knowledge of etiologies, heterogeneity of risk factors, and neuropathological processes associated with these conditions opens opportunities for the development of new therapies and biomarkers to delay or slow their progression and validation of whether the setting of chronic kidney disease could be a potential determinant for cognitive damage in Alzheimer’s disease.
SP8 Promotes an Aggressive Phenotype in Hepatoblastoma via FGF8 Activation
Authors: Wagner Alexandra , Schwarzmayr Thomas , Häberle Beate , Vokuhl Christian , Schmid Irene , Kaller Markus , Hermeking Heiko , von Schweinitz Dietrich , Kappler Roland
Published: August 2020

Hepatoblastoma (HB) is the most common malignant liver tumor in childhood and it generally has a good prognosis. However, if associated with aggressive metastatic disease, outcome is still poor. The molecular mechanisms leading to metastatic spread in HB patients are still unknown. By combining RNA-sequencing and a genome-wide methylome analysis, we identified the transcription factor SP8 and the growth factor FGF8 among the most strongly upregulated genes in metastatic HB cases, with a concomitant robust demethylation of the respective promoter regions. Of note, high expression of both candidates was associated with the aggressive C2 subtype of the 16-gene signature and poor survival. Chromatin immunoprecipitation revealed a direct transcriptional regulation of FGF8 through binding of SP8 to the FGF8 promoter. Gain- and loss-of-function experiments proved promoting effects of SP8 on motility, self-renewal, migration, and the invasive potential of HB cells. Moreover, stable overexpression of SP8 in Hep3B cells resulted in the acquisition of a mesenchymal phenotype and a strong upregulation of epithelial-mesenchymal transition-associated genes. Using KRAB-mediated CRISPR-dCas9 interference directed against FGF8, we could show that FGF8 is essential for the SP8-mediated aggressive tumor behavior. Treatment of HB cell lines with the pan SP family inhibitor mithramycin A resulted in a significant inhibition of their clonogenic growth. In summary, we identified SP8 and FGF8 as key players in aggressive traits of HB and propose SP8 inhibiting drugs as a new effective treatment strategy especially for metastatic tumors.
Lymphatic Valves and Lymph Flow in Cancer-Related Lymphedema
Authors: Iyer Drishya , Jannaway Melanie , Yang Ying , P. Scallan Joshua
Published: August 2020

Lymphedema is a complex disease caused by the accumulation of fluid in the tissues resulting from a dysfunctional or damaged lymphatic vasculature. In developed countries, lymphedema most commonly occurs as a result of cancer treatment. Initially, impaired lymph flow causes edema, but over time this results in inflammation, fibrotic and fatty tissue deposition, limited mobility, and bacterial infections that can lead to sepsis. While chronically impaired lymph flow is generally believed to be the instigating factor, little is known about what pathophysiological changes occur in the lymphatic vessels to inhibit lymph flow. Lymphatic vessels not only regulate lymph flow through a variety of physiologic mechanisms, but also respond to lymph flow itself. One of the fascinating ways that lymphatic vessels respond to flow is by growing bicuspid valves that close to prevent the backward movement of lymph. However, lymphatic valves have not been investigated in cancer-related lymphedema patients, even though the mutations that cause congenital lymphedema regulate genes involved in valve development. Here, we review current knowledge of the regulation of lymphatic function and development by lymph flow, including newly identified genetic regulators of lymphatic valves, and provide evidence for lymphatic valve involvement in cancer-related lymphedema.