bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Cultivar, Nitrogen Supply and Soil Type on Radiation Use Efficiency and Harvest Index in Spring Wheat
Authors: Wang Xizi , Christensen Svend , Svensgaard Jesper , Jensen Signe M. , Liu Fulai
Published: September 2020

There is an urgent need among plant breeders for a deeper understanding of the links between wheat genotypes and their ability to utilize light for biomass production and their efficiency at converting the biomass into grain yield. This field trail was conducted to investigate the variations in radiation use efficiency (RUE) and harvest index (HI) of four spring wheat cultivars grown on two soil types with two nitrogen (N) fertilization levels. Grain yield (GY) was significantly higher with 200 kg N ha−1 than 100 kg N ha−1 and on clay soil than on sandy soil, and a similar trend was observed for shoot dry matter (DM) at maturity. RUE and HI was neither affected by cultivar nor N-fertilization, but was affected by soil type, with a significantly higher RUE and HI on clay than on sandy soil. The differences of water holding capacity between the two soil types was suggested to be a major factor influencing RUE and HI as exemplified by the principal component analysis. Thus, to achieve a high RUE and/or HI, sustaining a good soil water status during the critical growth stages of wheat crops is essential, especially on sandy soils with a low water holding capacity.
Modulatory Effects of Interspecific and Gourd Rootstocks on Crop Performance, Physicochemical Quality, Bioactive Components and Postharvest Performance of Diploid and Triploid Watermelon Scions
Authors: Kyriacou Marios C. , Soteriou Georgios A. , Rouphael Youssef
Published: September 2020

Vegetable grafting has become entrenched as a sustainable tool for addressing biotic and abiotic stresses of vegetable crops, including watermelon. The concerted action of scion–rootstock genotypes in shaping crop performance, fruit quality and postharvest behavior of watermelon is critical. In this respect, scions of different ploidy grafted on interspecific and gourd rootstocks were assessed. Yield traits were strongly influenced by rootstock, as opposed to fruit morphometric characteristics. Interspecific rootstock supported stable yield across seasons with a 20.5% increase over gourd, and induced thicker rind and higher pulp firmness by 30.1% over gourd, which constitute advantageous traits for shelf-life. Interspecific rootstock also increased lycopene content, which was further influenced by scion genotype irrespective of ploidy. Triploid cultivars attained higher firmness but lower sugars than diploid, which renders the former particularly prone to loss of sensory quality during postharvest depletion of sugars. Although total and reducing sugars decreased during storage, sucrose increased, which in conjunction with the postharvest accumulation of lycopene sheds new light on the postharvest physiology of watermelon. The marginal rootstock effect on sugars renders interspecific rootstock superior to gourd on account of higher yield, firmness and lycopene content. The present work constitutes a contribution toward understanding rootstock–scion relations and how they mediate crop performance, fruit quality and postharvest behavior of watermelon.
Unconventional Yeasts Are Tolerant to Common Antifungals, and Aureobasidium pullulans Has Low Baseline Sensitivity to Captan, Cyprodinil, and Difenoconazole
Authors: Magoye Electine , Hilber-Bodmer Maja , Pfister Melanie , Freimoser Florian M.
Published: September 2020

Many yeasts have demonstrated intrinsic insensitivity to certain antifungal agents. Unlike the fungicide resistance of medically relevant yeasts, which is highly undesirable, intrinsic insensitivity to fungicides in antagonistic yeasts intended for use as biocontrol agents may be of great value. Understanding how frequently tolerance exists in naturally occurring yeasts and their underlying molecular mechanisms is important for exploring the potential of biocontrol yeasts and fungicide combinations for plant protection. Here, yeasts were isolated from various environmental samples in the presence of different fungicides (or without fungicide as a control) and identified by sequencing the internal transcribed spacer (ITS) region or through matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Among 376 isolates, 47 taxa were identified, and Aureobasidium pullulans was the most frequently isolated yeast. The baseline sensitivity of this yeast was established for 30 isolates from different environmental samples in vitro to captan, cyprodinil, and difenoconazole. For these isolates, the baseline minimum inhibitory concentration (MIC50) values for all the fungicides were higher than the concentrations used for the control of plant pathogenic fungi. For some isolates, there was no growth inhibition at concentrations as high as 300 µg/mL for captan and 128 µg/mL for cyprodinil. This information provides insight into the presence of resistance among naturally occurring yeasts and allows the choice of strains for further mechanistic analyses and the assessment of A. pullulans for novel applications in combination with chemical agents and as part of integrated plant-protection strategies.
Intradialytic Cardiovascular Exercise Training Alters Redox Status, Reduces Inflammation and Improves Physical Performance in Patients with Chronic Kidney Disease
Authors: Sovatzidis Apostolos , Chatzinikolaou Athanasios , Fatouros Ioannis G. , Panagoutsos Stylianos , Draganidis Dimitrios , Nikolaidou Eirini , Avloniti Alexandra , Michailidis Yiannis , Mantzouridis Ioannis , Batrakoulis Alexios , Pasadakis Ploumis , Vargemezis Vassilis
Published: September 2020

Redox status (RS) perturbations and inflammation are fundamental features of chronic kidney disease (CKD) that are substantially exacerbated in end-stage renal disease (ESRD). This study aimed at investigating the efficacy of a 6-month intradialytic exercise training program on RS, inflammation and physical performance in patients with ESRD. Twenty hemodialysis (HD) patients (17 males, three females) were randomly assigned to either an intradialytic training (bedside cycling) group (TR; n = 10) or a control group (CON; n = 10) for 6 months. Anthropometrics [body mass and height, body mass index (BMI), body composition], physical performance (VO2peak), functional capacity [North Staffordshire Royal Infirmary (NSRI) walk test, sit-to-stand test (STS-60)], quality of life (short form-36 (SF-36) as well as RS [thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG, total antioxidant capacity (TAC), catalase activity (CAT)] and high-sensitivity C-reactive protein (hs-CRP) were assessed at baseline and after the 6-month intervention. Peak oxygen consumption (VO2peak) increased by 15% only in TR (p < 0.01). Performance in NSRI, STS-60 and SF-36 improved by 4–13% only in TR (p < 0.01). Exercise training reduced TBARS (by 28%), PC (by 31%) and hs-CRP (by 15%), and elevated GSH (by 52%), GSH/GSSG (by 51%), TAC (by 59%) and CAT (by 15%) (p < 0.01). These findings suggest that engagement in chronic intradialytic cardiovascular exercise alters RS, reduces inflammation and improves performance in patients with ESRD.
Towards an App to Estimate Patient-Specific Perioperative Femur Fracture Risk
Authors: Esposito L. , Minutolo V. , Gargiulo P. , Jonsson H. , Gislason M. K. , Fraldi M.
Published: September 2020

Total Hip Arthroplasty has been one of the most successful surgical procedure in terms of patient outcomes and satisfaction. However, due to increase in life expectancy and the related incidence of age-dependent bone diseases, a growing number of cases of intra-operative fractures lead to revision surgery with high rates of morbidity and mortality. Surgeons choose the type of the implant, either cemented or cementless prosthesis, on the basis of the age, the quality of the bone and the general medical conditions of the patients. Generally, no quantitative measures are available to assess the intra-operative fracture risk. Consequently, the decision-making process is mainly based on surgical operators’ expertise and qualitative information obtained from imaging. Motivated by this scenario, we here propose a mechanical-supported strategy to assist surgeons in their decisions, by giving intelligible maps of the risk fracture which take into account the interplay between the actual mechanical strength distribution inside the bone tissue and its response to the forces exerted by the implant. In the presented study, we produce charts and patient-specific synthetic “traffic-light” indicators of fracture risk, by making use of ad hoc analytical solutions to predict the stress levels in the bone by means of Computed Tomography-based mechanical and geometrical parameters of the patient. We felt that if implemented in a friendly software or proposed as an app, the strategy could constitute a practical tool to help the medical decision-making process, in particular with respect to the choice of adopting cemented or cementless implant.
Genuine Reversible Data Hiding Technique for H.264 Bitstream Using Multi-Dimensional Histogram Shifting Technology on QDCT Coefficients
Authors: Kang Jinwoo , Kim Hyunjung , Kang Sang-ug
Published: September 2020

Video has become the most important medium for communication among people. Video has become the most important medium for communication among people. Therefore, reversible data hiding technologies for video have been developed so that information can be hidden in the video without damaging the original video in order to be used in the copyright protection and distribution field of video. This paper proposes a practical and genuine reversible data hiding method by using a multi-dimensional histogram shifting scheme on QDCT coefficients in the H.264/AVC bitstream. The proposed method defines the vacant histogram bins as a set of n-dimensional vectors and finds the optimal vector space, which gives the best performance, in a 4 × 4 QDCT block. In addition, the secret message is mapped to the optimal vector space, which is equivalent to embedding the information into the QDCT block. The simulation results show that the data hiding efficiency is the highest among the compared five existing methods. In addition, the image distortion and maximum payload capacity are measured quite high.
Chemical Characterization of Oleaster, Olea europaea var. sylvestris (Mill.) Lehr., Oils from Different Locations of Northeast Portugal
Authors: Rodrigues Nuno , Pinho Teresa , Casal Susana , Peres António M. , Baptista Paula , Pereira José Alberto
Published: September 2020

Oleaster (Olea europaea var. sylvestris), or the wild olive tree, has great interest as a source of genetic material for olive breeding programs. Nevertheless, information about its oil composition is scarce. In the present work, the characterization of oleaster fruit morphology and oil chemical composition from three different tree populations in Northeastern Portugal (Moncorvo, Alijó and Vila Nova de Foz Côa) was performed. The three studied populations presented some morphological differences in the fruits, but similar oil chemical composition. Oleic acid (68.9–70.6%) was the most abundant fatty acid. High variability was observed in total tocopherol content, ranging between 263 and 503 mg/kg. Additionally, high amounts of total sterols were found, from 1742 to 2198 mg/kg of oil. A rich composition in phenols was found with 14 phenolic compounds identified. The evaluated parameters for oleander oils allowed discriminating the oils according to the geographical origin and were consistent with those commonly found in olive oil, showing that they are particularly rich in antioxidants and can be exploited in breeding programs to increase the amounts of bioactive compounds in cultivated oils.
Assessment of Implicit and Explicit Measures of Mental Workload in Working Situations: Implications for Industry 4.0
Authors: Mingardi Michele , Pluchino Patrik , Bacchin Davide , Rossato Chiara , Gamberini Luciano
Published: September 2020

Nowadays, in the context of Industry 4.0, advanced working environments aim at achieving a high degree of human–machine collaboration. This phenomenon occurs, on the one hand, through the correct interpretation of operators’ data by machines that can adapt their functioning to support workers, and on the other hand, by ensuring the transparency of the actions of the system itself. This study used an ad hoc system that allowed the co-registration of a set of participants’ implicit and explicit (I/E) data in two experimental conditions that varied in the level of mental workload (MWL). Findings showed that the majority of the considered I/E measures were able to discriminate the different task-related mental demands and some implicit measures were capable of predicting task performance in both tasks. Moreover, self-reported measures showed that participants were aware of such differences in MWL. Finally, the paradigm’s ecology highlights that task and environmental features may affect the reliability of the various I/E measures. Thus, these factors have to be considered in the design and development of advanced adaptive systems within the industrial context.
Removal of Lead from Water Solution by Reusable Magnetic Adsorbent Incorporating Selective Lead-Binding Peptide
Authors: Xu Yue , Yoo Ik-Keun
Published: September 2020

As a reusable adsorbent to remove lead from water, a peptide-based magnetic adsorbent incorporating lead-binding peptide was constructed. First, a 7-mer lead-binding peptide (TNTLSNN) was covalently bonded onto the surface of a magnetic bead. Compared to the adsorption capacity of a bare magnetic bead (4.0 mg lead/g bead), the peptide-linked bead exhibited a capacity more than eight times higher than that of a bare bead (34.1 mg lead/g bead). The regenerated peptide bead, by desorbing the lead from the bead with EDTA, could be repeatedly used (tested over six cycles) for the following round of lead adsorption without any significant loss of adsorption capacity. The selective removal of lead in the presence of other interfering metals was demonstrated with the individual or the combinatory use of four metal ions, namely Pb(II), Ni(II), Co(II), and Cu(II), where the amount of adsorbed Pb(II) was remarkably higher than those of the other metal ions. The adsorption isotherm followed the Langmuir model well, with the maximum adsorption loading (qmax) of 70.4 mg lead/g bead.
Reinforcement-Learning-Based Virtual Energy Storage System Operation Strategy for Wind Power Forecast Uncertainty Management
Authors: Oh Eunsung
Published: September 2020

Uncertainties related to wind power generation (WPG) restrict its usage. Energy storage systems (ESSs) are key elements employed in managing this uncertainty. This study proposes a reinforcement learning (RL)-based virtual ESS (VESS) operation strategy for WPG forecast uncertainty management. The VESS logically shares a physical ESS to multiple units, while VESS operation reduces the cost barrier of the ESS. In this study, the VESS operation model is suggested considering not only its own operation but also the operation of other units, and the VESS operation problem is formulated as a decision-making problem. To solve this problem, a policy-learning strategy is proposed based on an expected state-action-reward-state-action (SARSA) approach that is robust to variations in uncertainty. Moreover, multi-dimensional clustering is performed according to the WPG forecast data of multiple units to enhance performance. Simulation results using real datasets recorded by the National Renewable Energy Laboratory project of U.S. demonstrate that the proposed strategy provides a near-optimal performance with a less than 2%-point gap with the optimal solution. In addition, the performance of the VESS operation is enhanced by multi-user diversity gain in comparison with individual ESS operation.
The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers
Authors: Bartlett Allison , Gullickson Robert G. , Singh Rajan , Ro Seungil , Omaye Stanley T.
Published: September 2020

The objective of this review is to provide recent evidence for the oral–gut axis connection and to discuss gastrointestinal (GI) immune response, inflammatory bowel disease (IBD) pathogenesis, and potential salivary biomarkers for determining GI health. IBD affects an estimated 1.3% of the US adult population. While genetic predisposition and environment play a role, abnormal immune activity and microbiota dysbiosis within the gastrointestinal tract are also linked in IBD pathogenesis. It has been inferred that a reduced overall richness of bacterial species as well as colonization of opportunistic bacteria induce systemic inflammation in the GI tract. Currently, there is supporting evidence that both oral and gut microbiota may be related to the development of IBD. Despite this, there are currently no curative therapies for IBD, and diagnosis requires samples of blood, stool, and invasive diagnostic imaging techniques. Considering the relative ease of collection, emerging evidence of association with non-oral diseases may imply that saliva microbiome research may have the potential for gut diagnostic or prognostic value. This review demonstrates a link between saliva and intestinal profiles in IBD patients, suggesting that saliva sampling has the potential to serve as a non-invasive biomarker for gut diseases such as IBD in the oral–gut axis.
Radiomics-Based Prediction of Overall Survival in Lung Cancer Using Different Volumes-Of-Interest
Authors: D’Amico Natascha Claudia , Sicilia Rosa , Cordelli Ermanno , Tronchin Lorenzo , Greco Carlo , Fiore Michele , Carnevale Alessia , Iannello Giulio , Ramella Sara , Soda Paolo
Published: September 2020

Lung cancer accounts for the largest amount of deaths worldwide with respect to the other oncological pathologies. To guarantee the most effective cure to patients for such aggressive tumours, radiomics is increasing as a novel and promising research field that aims at extracting knowledge from data in terms of quantitative measures that are computed from diagnostic images, with prognostic and predictive ends. This knowledge could be used to optimize current treatments and to maximize their efficacy. To this end, we hereby study the use of such quantitative biomarkers computed from CT images of patients affected by Non-Small Cell Lung Cancer to predict Overall Survival. The main contributions of this work are two: first, we consider different volumes of interest for the same patient to find out whether the volume surrounding the visible lesions can provide useful information; second, we introduce 3D Local Binary Patterns, which are texture measures scarcely explored in radiomics. As further validation, we show that the proposed signature outperforms not only the features automatically computed by a deep learning-based approach, but also another signature at the state-of-the-art using other handcrafted features.
The Application of Artificial Intelligence in Prostate Cancer Management—What Improvements Can Be Expected? A Systematic Review
Authors: Thenault Ronan , Kaulanjan Kevin , Darde Thomas , Rioux-Leclercq Nathalie , Bensalah Karim , Mermier Marie , Khene Zine-eddine , Peyronnet Benoit , Shariat Shahrokh , Pradère Benjamin , Mathieu Romain
Published: September 2020

Artificial Intelligence (AI) is progressively remodeling our daily life. A large amount of information from “big data” now enables machines to perform predictions and improve our healthcare system. AI has the potential to reshape prostate cancer (PCa) management thanks to growing applications in the field. The purpose of this review is to provide a global overview of AI in PCa for urologists, pathologists, radiotherapists, and oncologists to consider future changes in their daily practice. A systematic review was performed, based on PubMed MEDLINE, Google Scholar, and DBLP databases for original studies published in English from January 2009 to January 2019 relevant to PCa, AI, Machine Learning, Artificial Neural Networks, Convolutional Neural Networks, and Natural-Language Processing. Only articles with full text accessible were considered. A total of 1008 articles were reviewed, and 48 articles were included. AI has potential applications in all fields of PCa management: analysis of genetic predispositions, diagnosis in imaging, and pathology to detect PCa or to differentiate between significant and non-significant PCa. AI also applies to PCa treatment, whether surgical intervention or radiotherapy, skills training, or assessment, to improve treatment modalities and outcome prediction. AI in PCa management has the potential to provide a useful role by predicting PCa more accurately, using a multiomic approach and risk-stratifying patients to provide personalized medicine.
Explosive Strength Modeling in Children: Trends According to Growth and Prediction Equation
Authors: Carnevale Pellino Vittoria , Giuriato Matteo , Ceccarelli Gabriele , Codella Roberto , Vandoni Matteo , Lovecchio Nicola , Nevill Alan M.
Published: September 2020

Lower limb explosive strength has been widely used to evaluate physical fitness and general health in children. A plethora of studies have scoped the practicality of the standing broad jump (SBJ), though without accounting for body dimensions, which are tremendously affected by growth. This study aimed at modeling SBJ-specific allometric equations, underlying an objectively predictive approach while controlling for maturity offset (MO). A total of 7317 children (8–11 years) were tested for their SBJs; demographics and anthropometrics data were also collected. The multiplicative model with allometric body size components, MO, and categorial differences were implemented with SBJ performance. The log-multiplicative model suggested that the optimal body shape associated with SBJs is ectomorphic (H = −0.435; M = 1.152). Likewise, age, sex, and age–sex interactions were revealed to be significant (p < 0.001). Our results confirmed the efficacy of the allometric approach to identify the most appropriate body size and shape in children. Males, as they mature, did not significantly augment their performances, whereas females did, outperforming their peers. The model successfully fit the equation for SBJ performance, adjusted for age, sex, and MO. Predictive equations modeled on developmental factors are needed to interpret appropriately the performances that are used to evaluate physical fitness.
An Asian Summer Monsoon-Related Relative Humidity Record from Tree-Ring δ18O in Gansu Province, North China
Authors: Wang Yan , Liu Yu , Li Qiang , Song Huiming , Sun Changfeng , Fang Congxi
Published: September 2020

The monsoon fringe region in North China (NC) is also an ecologically fragile zone. Improving our comprehension of the paleoclimate variations and their driving mechanisms in this region has great significance for environmental protection and agricultural economic development. In order to provide more reliable data for future climate forecasting and reduce the effects of climatic disasters in NC, we established a 328-year stable oxygen isotope (δ18O) chronology based on four Pinus tabulaeformis Carr. from Mt. Hasi, Gansu Province, and found that the tree-ring δ18O inherited the signals of summer (July–August) monsoonal precipitation δ18O (δ18OP). Correlation function analysis indicated that the tree-ring δ18O series responded significantly to the observed local relative humidity from July to August (RHJA) with r = −0.65 (n = 55, p < 0.001). Based on the clear physiological mechanism, we reconstructed the RHJA variations from 1685 to 2012 using a transfer function. Our reconstruction was very stable and had strong spatial representativeness, it was significantly positively correlated with Asian summer monsoon (ASM) indices, indicating that our reconstruction reflected the variations of ASM to a large extent. The RHJA series successfully captured the weakening of the ASM since the 1930s. There was a close connection between the reconstructed sequence and the East Pacific sea surface temperature (SST). Further analyses revealed that El Niño–Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) may play important roles in the summer monsoon precipitation in NC.
Predicting Suitable Habitats of the African Cherry (Prunus africana) under Climate Change in Tanzania
Authors: Giliba Richard A. , Yengoh Genesis Tambang
Published: September 2020

Prunus africana is a fast-growing, evergreen canopy tree with several medicinal, household, and agroforestry uses, as well as ecological value for over 22 countries in sub-Saharan Africa. This species is under immense pressure from human activity, compounding its vulnerability to the effects of climate change. Predicting suitable habitats for P. africana under changing climate is essential for conservation monitoring and planning. This study intends to predict the impact of climate change on the suitable habitats for the vulnerable P. africana in Tanzania. We used maximum entropy modeling to predict future habitat distribution based on the representative concentration pathways scenario 4.5 and 8.5 for the mid-century 2050 and late-century 2070. Species occurrence records and environmental variables were used as a dependent variable and predictor variables respectively. The model performance was excellent with the area under curve (AUC) and true skill statistics (TSS) values of 0.96 and 0.85 respectively. The mean annual temperature (51.7%) and terrain ruggedness. index (31.6%) are the most important variables in predicting the current and future habitat distribution for P. africana. Our results show a decrease in suitable habitats for P. africana under all future representative concentration pathways scenario when compared with current distributions. These results have policy implications for over 22 countries of sub-Saharan Africa that are facing problems associated with the sustainability of this species. Institutional, policy, and conservation management approaches are proposed to support sustainable practices in favor of P. africana.
Biomimetic Nanocarriers for Cancer Target Therapy
Authors: Guido Clara , Maiorano Gabriele , Cortese Barbara , D’Amone Stefania , Palamà Ilaria Elena
Published: September 2020

Nanotechnology offers innovative tools for the design of biomimetic nanocarriers for targeted cancer therapy. These nano-systems present several advantages such as cargo’s protection and modulation of its release, inclusion of stimuli-responsive elements, and enhanced tumoral accumulation. All together, these nano-systems suffer low therapeutic efficacy in vivo because organisms can recognize and remove foreign nanomaterials. To overcome this important issue, different modifications on nanoparticle surfaces were exploited in order to reach the desired therapeutic efficacy eliciting, also, the response of immune system against cancer cells. For this reason, more recently, a new strategy involving cell membrane-covered nanoparticles for biomedical application has been attracting increasing attention. Membranes from red blood cells, platelets, leukocytes, tumor, and stem cells, have been exploited as biomimetic coatings of nanoparticles for evading clearance or stimulated immune system by maintaining in the same way their targeting capability. In this review, the use of different cell sources as coating of biomimetic nanocarriers for cancer therapy is discussed.
Synthesis and Inhibitory Studies of Phosphonic Acid Analogues of Homophenylalanine and Phenylalanine towards Alanyl Aminopeptidases
Authors: Wanat Weronika , Talma Michał , Dziuk Błażej , Kafarski Paweł
Published: September 2020

A library of novel phosphonic acid analogues of homophenylalanine and phenylalanine, containing fluorine and bromine atoms in the phenyl ring, have been synthesized. Their inhibitory properties against two important alanine aminopeptidases, of human (hAPN, CD13) and porcine (pAPN) origin, were evaluated. Enzymatic studies and comparison with literature data indicated the higher inhibitory potential of the homophenylalanine over phenylalanine derivatives towards both enzymes. Their inhibition constants were in the submicromolar range for hAPN and the micromolar range for pAPN, with 1-amino-3-(3-fluorophenyl) propylphosphonic acid (compound 15c) being one of the best low-molecular inhibitors of both enzymes. To the best of our knowledge, P1 homophenylalanine analogues are the most active inhibitors of the APN among phosphonic and phosphinic derivatives described in the literature. Therefore, they constitute interesting building blocks for the further design of chemically more complex inhibitors. Based on molecular modeling simulations and SAR (structure-activity relationship) analysis, the optimal architecture of enzyme-inhibitor complexes for hAPN and pAPN were determined.
Promising Opportunities for Treating Neurodegenerative Diseases with Mesenchymal Stem Cell-Derived Exosomes
Authors: Guy Reut , Offen Daniel
Published: September 2020

Neurodegenerative disease refers to any pathological condition in which there is a progressive decline in neuronal function resulting from brain atrophy. Despite the immense efforts invested over recent decades in developing treatments for neurodegenerative diseases, effective therapy for these conditions is still an unmet need. One of the promising options for promoting brain recovery and regeneration is mesenchymal stem cell (MSC) transplantation. The therapeutic effect of MSCs is thought to be mediated by their secretome, and specifically, by their exosomes. Research shows that MSC-derived exosomes retain some of the characteristics of their parent MSCs, such as immune system modulation, regulation of neurite outgrowth, promotion of angiogenesis, and the ability to repair damaged tissue. Here, we summarize the functional outcomes observed in animal models of neurodegenerative diseases following MSC-derived exosome treatment. We will examine the proposed mechanisms of action through which MSC-derived exosomes mediate their therapeutic effects and review advanced studies that attempt to enhance the improvement achieved using MSC-derived exosome treatment, with a view towards future clinical use.
Lighting Conditions Influence the Dynamics of Protease Synthesis and Proteasomal Activity in the White Rot Fungus Cerrena unicolor
Authors: Pawlik Anna , Jaszek Magdalena , Swatek Anita , Ruminowicz-Stefaniuk Marta , Ciołek Beata , Mazur Andrzej , Janusz Grzegorz
Published: September 2020

Recent transcriptomic and biochemical studies have revealed that light influences the global gene expression profile and metabolism of the white-rot fungus Cerrena unicolor. Here, we aimed to reveal the involvement of proteases and ubiquitin-mediated proteolysis by the 26S proteasome in the response of this fungus to white, red, blue and green lighting conditions and darkness. The changes in the expression profile of C. unicolor genes putatively engaged in proteolysis were found to be unique and specific to the applied wavelength of light. It was also demonstrated that the activity of proteases in the culture fluid and mycelium measured using natural and synthetic substrates was regulated by light and was substrate-dependent. A clear influence of light on protein turnover and the qualitative and quantitative changes in the hydrolytic degradation of proteins catalyzed by various types of proteases was shown. The analysis of activity associated with the 26S proteasome showed a key role of ATP-dependent proteolysis in the initial stages of adaptation of fungal cells to the stress factors. It was suggested that the light-sensing pathways in C. unicolor are cross-linked with stress signaling and secretion of proteases presumably serving as regulatory molecules.
Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH
Authors: Hsu Mei-Ju , Karkossa Isabel , Schäfer Ingo , Christ Madlen , Kühne Hagen , Schubert Kristin , Rolle-Kampczyk Ulrike E. , Kalkhof Stefan , Nickel Sandra , Seibel Peter , von Bergen Martin , Christ Bruno
Published: September 2020

Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were analyzed one week thereafter. Combined metabolomic and proteomic data were applied to weighted gene correlation network analysis (WGCNA) and subsequent identification of key drivers. Livers were analyzed histologically and biochemically. The mechanisms of MSC action on hepatocyte lipid accumulation were studied in co-cultures of hepatocytes and MSCs by quantitative image analysis and immunocytochemistry. WGCNA and key driver analysis revealed that NASH caused the impairment of central carbon; amino acid; and lipid metabolism associated with mitochondrial and peroxisomal dysfunction; which was reversed by MSC treatment. MSC improved hepatic lipid metabolism and tissue homeostasis. In co-cultures of hepatocytes and MSCs; the decrease of lipid load was associated with the transfer of mitochondria from the MSCs to the hepatocytes via tunneling nanotubes (TNTs). Hence; MSCs may ameliorate lipid load and tissue perturbance by the donation of mitochondria to the hepatocytes. Thereby; they may provide oxidative capacity for lipid breakdown and thus promote recovery from NASH-induced metabolic impairment and tissue injury.
Simvastatin Impairs Glucose Homeostasis in Mice Depending on PGC-1α Skeletal Muscle Expression
Authors: Panajatovic Miljenko Valentin , Singh François , Krähenbühl Stephan , Bouitbir Jamal
Published: September 2020

Several studies showed an increased risk for diabetes with statin treatment. PGC-1α is an important regulator of muscle energy metabolism and mitochondrial biogenesis. Since statins impair skeletal muscle PGC-1α expression and reduced PGC-1α expression has been observed in diabetic patients, we investigated the possibility that skeletal muscle PGC1α expression influences the effect of simvastatin on muscle glucose metabolism. Mice with muscle PGC-1α knockout (KO) or PGC-1α overexpression (OE), and wild-type (WT) mice were investigated. Mice were treated orally for 3 weeks with simvastatin (5 mg/kg/day) and investigated by intraperitoneal glucose tolerance (iGTT), in vivo skeletal muscle glucose uptake, muscle glycogen content, and Glut4 and hexokinase mRNA and protein expression. Simvastatin impaired glucose metabolism in WT mice, as manifested by increased glucose blood concentrations during the iGTT, decreased skeletal muscle glucose uptake and glycogen stores. KO mice showed impaired glucose homeostasis with increased blood glucose concentrations during the iGTT already without simvastatin treatment and simvastatin induced a decrease in skeletal muscle glucose uptake. In OE mice, simvastatin treatment increased blood glucose and insulin concentrations during the iGTT, and increased skeletal muscle glucose uptake, glycogen stores, and Glut4 and hexokinase protein expression. In conclusion, simvastatin impaired skeletal muscle insulin sensitivity in WT mice, while KO mice exhibited impaired skeletal muscle insulin sensitivity already in the absence of simvastatin. In OE mice, simvastatin augmented muscular glucose uptake but impaired whole-body insulin sensitivity. Thus, simvastatin affected glucose homeostasis depending on PGC-1α expression.
Polygenic Markers in Patients Diagnosed of Autosomal Dominant Hypercholesterolemia in Catalonia: Distribution of Weighted LDL-c-Raising SNP Scores and Refinement of Variant Selection
Authors: Martín-Campos Jesús , Ruiz-Nogales Sheila , Ibarretxe Daiana , Ortega Emilio , Sánchez-Pujol Elisabet , Royuela-Juncadella Meritxell , Vila Àlex , Guerrero Carolina , Zamora Alberto , Soler i Ferrer Cristina , Arroyo Juan , Carreras Gemma , Martínez-Figueroa Susana , Roig Rosa , Plana Núria , Blanco-Vaca Francisco ,   Xarxa d’Unitats de Lípids i Arteriosclerosi (XULA)
Published: September 2020

Familial hypercholesterolemia (FH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes. A pathological variant has not been identified in 30–70% of clinically diagnosed FH patients, and a burden of LDL cholesterol (LDL-c)-raising alleles has been hypothesized as a potential cause of hypercholesterolemia in these patients. Our aim was to study the distribution of weighted LDL-c-raising single-nucleotide polymorphism (SNP) scores (weighted gene scores or wGS) in a population recruited in a clinical setting in Catalonia. The study included 670 consecutive patients with a clinical diagnosis of FH and a prior genetic study involving 250 mutation-positive (FH/M+) and 420 mutation-negative (FH/M−) patients. Three wGSs based on LDL-c-raising variants were calculated to evaluate their distribution among FH patients and compared with 503 European samples from the 1000 Genomes Project. The FH/M− patients had significantly higher wGSs than the FH/M+ and control populations, with sensitivities ranging from 42% to 47%. A wGS based only on the SNPs significantly associated with FH (wGS8) showed a higher area under the receiver operating characteristic curve, and higher diagnostic specificity and sensitivity, with 46.4% of the subjects in the top quartile. wGS8 would allow for the assignment of a genetic cause to 66.4% of the patients if those with polygenic FH are added to the 37.3% of patients with monogenic FH. Our data indicate that a score based on 8 SNPs and the75th percentile cutoff point may identify patients with polygenic FH in Catalonia, although with limited diagnostic sensitivity and specificity.
Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?
Authors: Clavreul Anne , Menei Philippe
Published: September 2020

The glioma microenvironment is a critical regulator of tumor progression. It contains different cellular components such as blood vessels, immune cells, and neuroglial cells. It also contains non-cellular components, such as the extracellular matrix, extracellular vesicles, and cytokines, and has certain physicochemical properties, such as low pH, hypoxia, elevated interstitial pressure, and impaired perfusion. This review focuses on a particular type of cells recently identified in the glioma microenvironment: glioma-associated stromal cells (GASCs). This is just one of a number of names given to these mesenchymal stromal-like cells, which have phenotypic and functional properties similar to those of mesenchymal stem cells and cancer-associated fibroblasts. Their close proximity to blood vessels may provide a permissive environment, facilitating angiogenesis, invasion, and tumor growth. Additional studies are required to characterize these cells further and to analyze their role in tumor resistance and recurrence.
Structure Prediction of a Thermostable SR74 α-Amylase from Geobacillus stearothermophilus Expressed in CTG-Clade Yeast Meyerozyma guilliermondii Strain SO
Authors: Lim Si Jie , Muhd Noor Noor Dina , Salleh Abu Bakar , Oslan Siti Nurbaya
Published: September 2020

α-amylase which catalyzes the hydrolysis of α-1,4-glycosidic bonds in starch have frequently been cloned into various microbial workhorses to yield a higher recombinant titer. A thermostable SR74 α-amylase from Geobacillus stearothermophilus was found to have a huge potential in detergent industries due to its thermostability properties. The gene was cloned into a CTG-clade yeast Meyerozyma guilliermondii strain SO. However, the CUG ambiguity present in the strain SO has possibly altered the amino acid residues in SR74 amylase wild type (WT) encoded by CUG the codon from the leucine to serine. From the multiple sequence alignment, six mutations were found in recombinant SR74 α-amylase (rc). Their effects on SR74 α-amylase structure and function remain unknown. Herein, we predicted the structures of the SR74 amylases (WT and rc) using the template 6ag0.1.A (PDB ID: 6ag0). We sought to decipher the possible effects of CUG ambiguity in strain SO via in silico analysis. They are structurally identical, and the metal triad (CaI–CaIII) might contribute to the thermostability while CaIV was attributed to substrate specificity. Since the pairwise root mean square deviation (RMSD) between the WT and rc SR74 α-amylase was lower than the template, we suggest that the biochemical properties of rc SR74 α-amylase were better deduced from its WT, especially its thermostability.
Biodiesel Production from Low-Quality Oils Using Heterogeneous Cesium Salts of Vanadium-Substituted Polyoxometalate Acid Catalyst
Authors: Xie Wenlei , Gao Chunli , Wang Hongyan
Published: September 2020

This research aims at developing an efficient and reusable catalyst to improve biodiesel production processes. To achieve this, a vanadium-substituted polyoxometalate (POM) acid, namely H6PV3MoW8O40, was firstly prepared, and then the heterogenzation of the homogeneous Keggin-type heteropoly acids was performed by the partial proton substitution by monovalent large cesium cations with the formation of solid Cs2H4PV3MoW8O40 catalysts. Several techniques, such as X-ray diffractometer, Fourier transform infrared, coupled plasma–atomic emission spectrometry, Diffuse reflectance ultraviolet–visible spectrum, thermal gravimetric analysis and N2 adsorption–desorption techniques, were employed to characterize the as-prepared solid catalyst. The solid acid catalyst had the capacity to catalyze both the transesterification of soybean oil and esterification of free fatty acids (FFAs) simultaneously, providing an efficient production process for the production of biodiesel from low-quality oils. Under the operational conditions of a methanol/oil molar ratio of 30:1, a catalyst dosage of 5 wt.%, a reaction temperature of 140 °C, and a reaction duration of 8 h, an oil conversion of 92.2% was attained with the total FFA transformation to biodiesel. Furthermore, the catalyst could be reutilized for several cycles with no significant drop in its activity, thus having great potential for application with a bright perspective in the production of biodiesel, especially from low-quality oil feedstocks.
Glycine–Nitrate Combustion Synthesis of Cu-Based Nanoparticles for NP9EO Degradation Applications
Authors: Cheng Hsu-Hui , Chen Shiao-Shing , Liu Hui-Ming , Jang Liang-Wei , Chang Shu-Yuan
Published: September 2020

Copper-based nanoparticles were synthesized using the glycine–nitrate process (GNP) by using copper nitrate trihydrate [Cu(NO3)2·3H2O] as the main starting material, and glycine [C2H5NO2] as the complexing and incendiary agent. The as-prepared powders were characterized through X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy analysis. Using Cu(NO3)2·3H2O as the oxidizer (N) and glycine as fuel (G), we obtained CuO, mixed-valence copper oxides (CuO + Cu2O, G/N = 0.3–0.5), and metallic Cu (G/N = 0.7). The XRD and BET results indicated that increasing the glycine concentration (G/N = 0.7) and reducing the particle surface area increased the yield of metallic Cu. The effects of varying reaction parameters, such as catalyst activity, catalyst dosage, and H2O2 concentration on nonylphenol-9-polyethoxylate (NP9EO) degradation, were assessed. With a copper-based catalyst in a heterogeneous system, the NP9EO and total organic carbon removal efficiencies were 83.1% and 70.6%, respectively, under optimum operating conditions (pH, 6.0; catalyst dosage, 0.3 g/L; H2O2 concentration, 0.05 mM). The results suggest that the removal efficiency increased with an increase in H2O2 concentration but decreased when the H2O2 concentration exceeded 0.05 mM. Furthermore, the trend of photocatalytic activity was as follows: G/N = 0.5 > G/N = 0.7 > G/N = 0.3. The G/N = 0.5 catalysts showed the highest photocatalytic activity and resulted in 94.6% NP9EO degradation in 600 min.
Increased Uptake of Silica Nanoparticles in Inflamed Macrophages but Not upon Co-Exposure to Micron-Sized Particles
Authors: Susnik Eva , Taladriz-Blanco Patricia , Drasler Barbara , Balog Sandor , Petri-Fink Alke , Rothen-Rutishauser Barbara
Published: September 2020

Silica nanoparticles (NPs) are widely used in various industrial and biomedical applications. Little is known about the cellular uptake of co-exposed silica particles, as can be expected in our daily life. In addition, an inflamed microenvironment might affect a NP’s uptake and a cell’s physiological response. Herein, prestimulated mouse J774A.1 macrophages with bacterial lipopolysaccharide were post-exposed to micron- and nanosized silica particles, either alone or together, i.e., simultaneously or sequentially, for different time points. The results indicated a morphological change and increased expression of tumor necrosis factor alpha in lipopolysaccharide prestimulated cells, suggesting a M1-polarization phenotype. Confocal laser scanning microscopy revealed the intracellular accumulation and uptake of both particle types for all exposure conditions. A flow cytometry analysis showed an increased particle uptake in lipopolysaccharide prestimulated macrophages. However, no differences were observed in particle uptakes between single- and co-exposure conditions. We did not observe any colocalization between the two silica (SiO2) particles. However, there was a positive colocalization between lysosomes and nanosized silica but only a few colocalized events with micro-sized silica particles. This suggests differential intracellular localizations of silica particles in macrophages and a possible activation of distinct endocytic pathways. The results demonstrate that the cellular uptake of NPs is modulated in inflamed macrophages but not in the presence of micron-sized particles.
Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?
Authors: Jans David A. , Wagstaff Kylie M.
Published: September 2020

The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its apparent exciting potential as an antiviral. It was identified in a high-throughput chemical screen as inhibiting recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins. Excitingly, cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Phase III human clinical trials have been completed for DENV, with >50 trials currently in progress worldwide for SARS-CoV-2. This mini-review discusses the case for ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.