bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Calibration for the General Cable-Driven Serial Manipulator with Multi-Segment Cables
Authors: Lou Ya’nan , Lin Haoyu , Quan Pengkun , Wei Dongbo , Di Shichun
Published: February 2021

This paper focuses on the kinematic calibration problem for the general cable-driven serial manipulator (CDSM) with multi-segment cables to improve its motion control accuracy. Firstly, to fully describe the calibration parameters of cables, links, joint positions, and the transmission system, this paper proposes a new cable routing description method named cable-routing configuration struct (CRCS), which provides a complete set of parameters to be calibrated for the proposed self-calibration algorithm. Then, a self-calibration algorithm for CDSM with motor incremental encoders is proposed, which can calibrate the robot at one time only using sufficient measured motor and joint positions. Its premise, the initial cable length, needs to be calibrated. Finally, the parameters of a three-DOF (degree of freedom) six-cable CDSM were described using the CRCS description method, and a comparative experiment was carried out on the same motion controller using the parameters before and after calibration. The experiment results of trajectory tracking error showed that the calibration parameters obtained by the proposed calibration algorithm can significantly improve the motion control accuracy of the three-DOF six-cable CDSM. This verified the correctness and effectiveness of the proposed calibration algorithm.
An Automated Method for Biometric Handwritten Signature Authentication Employing Neural Networks
Authors: Kurowski Mariusz , Sroczyński Andrzej , Bogdanis Georgis , Czyżewski Andrzej
Published: February 2021

Handwriting biometrics applications in e-Security and e-Health are addressed in the course of the conducted research. An automated analysis method for the dynamic electronic representation of handwritten signature authentication was researched. The developed algorithms are based on the dynamic analysis of electronically handwritten signatures employing neural networks. The signatures were acquired with the use of the designed electronic pen described in the paper. The triplet loss method was used to train a neural network suitable for writer-invariant signature verification. For each signature, the same neural network calculates a fixed-length latent space representation. The hand-corrected dataset containing 10,622 signatures was used in order to train and evaluate the proposed neural network. After learning, the network was tested and evaluated based on a comparison with the results found in the literature. The use of the triplet loss algorithm to teach the neural network to generate embeddings has proven to give good results in aggregating similar signatures and separating them from signatures representing different people.
npTrack: A n-Position Single Axis Solar Tracker Model for Optimized Energy Collection
Authors: de Sá Campos Manoel Henriques , Tiba Chigueru
Published: February 2021

The single axis solar tracker based on flat panels is used in large solar plants and in distribution-level photovoltaic systems. In order to achieve this, the solar tracking systems generally need to work by tracking the sun’s position with dozens, maybe hundreds of movements along the day with a maximal known tracking error within the specifications. A novel model is proposed along this work based on the control of the angle deviation within a (polar) single axis configuration. This way an optimization of the harnessing of solar energy can be achieved with as few panel displacements as possible in order to decrease the wear in the mechanical parts of the equipment and the energy consumed by it. This tracking approach was implemented with as few as seven positions along the day and got an estimated theoretical value of 99.27% of the total collected energy in a continuous tracking system. Regarding an annual average basis, it would be about 96.5% of a dual axis system according to the proposed model. The novelty of the model is related to a tradeoff between the gain with the simplicity of a single axis n-position tracking and the solar energy loss associated.
Meeting Challenges in Forestry: Improving Performance and Competitiveness
Authors: Lundmark Robert , Lundgren Tommy , Olofsson Elias , Zhou Wenchao
Published: February 2021

Improving the efficiency of the forestry sector will have an important impact on our possibility to attain long-term sustainability and mitigate climate change. In this study, attainable, and sustainable, efficiency improvements in the harvesting of forest products are analyzed using Data Envelopment Analysis (DEA). The price impacts of the efficient harvesting volumes are evaluated in a second step using a spatial forest sector model. The results indicate that the harvested volumes of forest products, both for the industry and energy sectors, can be significantly increased if a more efficient forest management is adopted. This supply-side effect will also result in general price decreases for sawlogs, pulpwood, fuelwood and harvesting residues. However, in certain counties, and for specific forest products, the estimated decreasing price effect from a more efficient forest management cannot fully offset the increasing price effect of the energy sector expanding its use of forest products. More forest biomass enters the market, which is needed in the transition towards a bioeconomy, and the increased availability of forest biomass will restrict the price effect making investments in the bioeconomy more likely to be profitable.
Environmental Drivers and Age Trends in Site Productivity for Oak in Southern Poland
Authors: Tymińska-Czabańska Luiza , Socha Jarosław , Maj Marek , Cywicka Dominika , Hoang Duong Xo Viet
Published: February 2021

Site productivity provides critical information for forest management practices and is a fundamental measure in forestry. It is determined using site index (SI) models, which are developed using two primary groups of methods, namely, phytocentric (plant-based) or geocentric (earth-based). Geocentric methods allow for direct site growth modelling, in which the SI is predicted using multiple environmental indicators. However, changes in non-static site factors—particularly nitrogen deposition and rising CO2 concentration—lead to an increase in site productivity, which may be visible as an age trend in the SI. In this study, we developed a geocentric SI model for oak. For the development of the SI model, we used data from 150 sample plots, representing a wide range of local topographic and site conditions. A generalized additive model was used to model site productivity. We found that the oak SI depended predominantly on physicochemical soil properties—mainly nitrogen, carbon, sand, and clay content. Additionally, the oak SI value was found to be slightly shaped by the topography, especially by altitude above sea level, and topographic position. We also detected a significant relationship between the SI and the age of oak stands, indicating the long-term increasing site productivity for oak, most likely caused by nitrogen deposition and changes in climatic conditions. The developed geocentric site productivity model for oak explained 77.2% of the SI variation.
Digital Regulation of Intellectual Capital for Open Innovation: Industries’ Expert Assessments of Tacit Knowledge for Controlling and Networking Outcome
Authors: Pokrovskaia Nadezhda N. , Korableva Olga N. , Cappelli Lucio , Fedorov Denis A.
Published: February 2021

Digital regulation implies the quantified measuring and the network infrastructure allowing managers to control the processes of value creation. Digital regulation needs to take into account tacit elements of the value creation process, including unconscious competency, creativity, and intuitive anticipation, to assure the resulting network’s innovation growth. Digital society in developing countries is built on the ground of fact change of the economy and social relations, of transition towards an emerging market within the global offline network of interactions and online activities through Internet; the innovative growth imposes the evolution of managerial behavior and attitudes. The main objective of the paper is to obtain indications on the perception of intellectual capital by corporate managers. The exploratory study was carried out in Russian companies operating in different sectors, with the use of the open-ended approach, including focused interviews and group discussion among experts, middle and senior managers from marketing or corporate governance background. The data were complemented by documentary analysis of descriptions of internal processes of the implementation of digital tools of accounting, which includes the human resources control applied for the remote work during the pandemic. Networking helps to coordinate functions between team members at remote work and between teams and administrators. The interviews demonstrated the administrative tendency to under-estimate the non-formalized factors of innovation activity, such as awareness of corporate strategy, creativity, motivation, and affective and behavioral components of communication of the persons involved in the enrichment of intellectual capital. The results show fuzzy boundaries between the intellectual capital components that are difficult to control. This difficulty provokes the preference for the use of “traditional” quantitative indicators that had been implemented at the stage of the financial digitalization, instead of developing new parameters or measuring approaches. The networking emerges synergetic effect if the administrators refuse their monopoly on the uncertainty zones and are oriented to construct the trustful atmosphere of personal responsibility within the network.
Two Expansin Genes, AtEXPA4 and AtEXPB5, Are Redundantly Required for Pollen Tube Growth and AtEXPA4 Is Involved in Primary Root Elongation in Arabidopsis thaliana
Authors: Liu Weimiao , Xu Liai , Lin Hui , Cao Jiashu
Published: February 2021

The growth of plant cells is inseparable from relaxation and expansion of cell walls. Expansins are a class of cell wall binding proteins, which play important roles in the relaxation of cell walls. Although there are many members in expansin gene family, the functions of most expansin genes in plant growth and development are still poorly understood. In this study, the functions of two expansin genes, AtEXPA4 and AtEXPB5 were characterized in Arabidopsis thaliana. AtEXPA4 and AtEXPB5 displayed consistent expression patterns in mature pollen grains and pollen tubes, but AtEXPA4 also showed a high expression level in primary roots. Two single mutants, atexpa4 and atexpb5, showed normal reproductive development, whereas atexpa4atexpb5 double mutant was defective in pollen tube growth. Moreover, AtEXPA4 overexpression enhanced primary root elongation, on the contrary, knocking out AtEXPA4 made the growth of primary root slower. Our results indicated that AtEXPA4 and AtEXPB5 were redundantly involved in pollen tube growth and AtEXPA4 was required for primary root elongation.
Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus
Authors: Iacobas Dumitru , Wen Jing , Iacobas Sanda , Schwartz Noa , Putterman Chaim
Published: February 2021

Cognitive dysfunction and mood changes are prevalent and especially taxing issues for patients with systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the cortices of MRL/+, MRL/lpr (that manifest lupus-like phenotype) and MRL/lpr-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK/Fn14 on cortical gene expression in lupus. We found that the TWEAK/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the Phosphoinositide 3-kinase (PI3K)-AKT pathway in the MRL/lpr lupus strain compared with the MRL/+ control and Fn14ko mice was particularly prominent and, therefore, promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models.
Common Myelin Regulatory Factor Gene Variants Predisposing to Excellence in Sports
Authors: Pepłońska Beata , Piestrzynska-Kajtoch Agata , Humińska-Lisowska Kinga , Adamczyk Jakub Grzegorz , Siewierski Marcin , Gurgul Artur , Fornal Agnieszka , Michałowska-Sawczyn Monika , Żekanowski Cezary , Cięszczyk Paweł , Berdyński Mariusz
Published: February 2021

In all sport disciplines, excellent coordination of movements is crucial for achieving mastery. The ability to learn new motor skills quickly and effectively is dependent on efficient myelination which varies between individuals. It has been suggested that these differences may play a role in athletic performance. The process of myelination is under transcriptional control by Myelin Regulatory Factor (MYRF) as well as other transcription factors (SOX10 and OLIG2). We analyze a panel of 28 single nucleotide polymorphisms (SNPs) located within the frequencies of common variants of MYRF, SOX10 and OLIG2 genes in professional athletes compared to non-athletes. No significant differences were detected after correction for multiple testing by false discovery rate (FDR) for any of the models tested. However, some deviations from the expected distribution was found for seven SNPs (rs174528, rs139884, rs149435516 and rs2238001, rs7943728, rs61747222, and rs198459). The MYRF alleles rs7943728 and rs61747222 showed a correlation with the level of sport achievement among the athletes. Even though the athletes did not differ from the non-athlete controls in the distribution of most SNPs analyzed, some interesting differences of several variants were noted. Presented results indicate that genetic variants of MYRF and SOX10 could be genetic factors weakly predisposing for successful athletic performance.
Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA): An Unconventional Mitochondrial Disorder
Authors: Indrieri Alessia , Franco Brunella
Published: February 2021

Mitochondrial disorders, although heterogeneous, are traditionally described as conditions characterized by encephalomyopathy, hypotonia, and progressive postnatal organ failure. Here, we provide a systematic review of Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), a rare, unconventional mitochondrial disorder which presents as a developmental disease; its main clinical features include microphthalmia with different degrees of severity, linear skin lesions, and central nervous system malformations. The molecular basis of this disorder has been elusive for several years. Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11, which are all endowed with defined roles in the mitochondrial respiratory chain. A peculiar feature of this condition is its inheritance pattern: X-linked dominant male-lethal. Only female or XX male individuals can be observed, implying that nullisomy for these genes is incompatible with normal embryonic development in mammals. All three genes undergo X-inactivation that, according to our hypothesis, may contribute to the extreme variable expressivity observed in this condition. We propose that mitochondrial dysfunction should be considered as an underlying cause in developmental disorders. Moreover, LSDMCA should be taken into consideration by clinicians when dealing with patients with microphthalmia with or without associated skin phenotypes.
Mass Balance of Austre Grønfjordbreen, Svalbard, 2006–2020, Estimated by Glaciological, Geodetic and Modeling Aproaches
Authors: Elagina Nelly , Kutuzov Stanislav , Rets Ekaterina , Smirnov Andrei , Chernov Robert , Lavrentiev Ivan , Mavlyudov Bulat
Published: February 2021

Glacier mass balance measurements, reconstructions and modeling are the precondition for assessing glacier sensitivity to regional climatic fluctuations. This paper presents new glaciological and geodetic mass balance data of Austre Grønfjordbreen located in the western part of Nordenskiöld Land in Central Spitsbergen. The average annual mass balance from 2014 to 2019 was −1.59 m w.e. The geodetic mass balance from 2008 to 2017 was −1.34 m w.e. The mass balance was also reconstructed by the temperature-index model from 2006 to 2020 and by spatially-distributed energy-balance models for 2011–2015 and 2019. We found a cumulative mass balance of −21.62 m w.e. over 2006–2020. The calculated mass-balance sensitivity to temperature was −1.04 m w.e. °C−1, which corresponds to the highest glacier mass balance sensitivity among Svalbard glaciers. Sensitivity to precipitation change was 0.10 m w.e. for a 10% increase in precipitation throughout the balance year. Comparing the results of the current study with other glacier mass balance assessments in Svalbard, we found that Austre Grønfjordbreen loses mass most rapidly due to its location, which is mostly influenced by the warm West Spitsbergen Current, small area and low elevation range.
Rill Erosion in Unpaved and Rock-Paved Roads after Wildfire in a Mediterranean Forest
Authors: Lucas-Borja Manuel Esteban , Zema Demetrio Antonio
Published: February 2021

Forest roads are often subject to intense runoff and erosion, and the rates can be increased by other disturbance factors, such as wildfires. Since scarce literature exists on the effects of wildfires on rill erosion of forest roads, this study presents the first results of a wider research, evaluating rill erosion in four different types of roads on a forest in Hellìn (Castilla-La Mancha, Central-Eastern Spain): unpaved roads made of native materials (soil found at the study site) and rock-paved roads, both built in unburned areas as well as unpaved and rock-paved roads, in fire-affected areas. In general, the unpaved roads are more subject to rill erosion compared to the rock-paved roads. In particular, the road of burned areas shows an erodibility that is higher by more than 200% compared to the unpaved and unburned roads, and even by about 400% compared to rock-paved roads (in both burned and unburned areas). A modeling approach based on distance linear models and distance-based redundancy analysis has identified the slope of road surface and upstream hillslope as well as the percent bare soil over the road surface as important input variables to predict rill erosion in future modeling experiences. All these variables may be easily measured by quick field surveys. Although the analytical approach of this study is limited to the geometric characteristics of erosion features, the results and the methods developed are useful to support the activity of land managers to better understand the magnitude of road erosion and to develop efficient measures for its control and mitigation.
Tectonic Setting of the Kenya Rift in the Nakuru Area, Based on Geophysical Prospecting
Authors: Conti Paolo , Pistis Marco , Bernardinetti Stefano , Barbagli Alessio , Zirulia Andrea , Serri Lisa , Colonna Tommaso , Guastaldi Enrico , Ghiglieri Giorgio
Published: February 2021

In this paper, we present results of tectonic and geophysical investigations in the Kenya Rift valley, in the Nakuru area. We compiled a detailed geological map of the area based on published earlier works, well data and satellite imagery. The map was then integrated with original fieldwork and cross sections were constructed. In key areas, we then performed geophysical survey using Electrical Resistivity Tomography (ERT), Hybrid Source Audio MagnetoTelluric (HSAMT), and single station passive seismic measurements (HVSR). In the study area, a volcano-sedimentary succession of the Neogene-Quaternary age characterized by basalts, trachytes, pyroclastic rocks, and tephra with intercalated lacustrine and fluvial deposits crops out. Faulting linked with rift development is evident and occurs throughout the area crosscutting all rock units. We show a rotation of the extension in this portion of the Kenya rift with the NE–SW extension direction of a Neogene-Middle Pleistocene age, followed by the E–W extension direction of an Upper Pleistocene-Present age. Geophysical investigations allowed to outline main lithostratigraphic units and tectonic features at depth and were also useful to infer main cataclasites and fractured rock bodies, the primary paths for water flow in rocks. These investigations are integrated in a larger EU H2020 Programme aimed to produce a geological and hydrogeological model of the area to develop a sustainable water management system.
Biotechnologically-Produced Myconoside and Calceolarioside E Induce Nrf2 Expression in Neutrophils
Authors: Amirova Kristiana M. , Dimitrova Petya A. , Marchev Andrey S. , Krustanova Slaveya V. , Simova Svetlana D. , Alipieva Kalina I. , Georgiev Milen I.
Published: February 2021

The pathological manifestation of various diseases can be suppressed by the activation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a transcriptional regulator of the cellular redox balance. Haberlea rhodopensis Friv. is a resurrection plant species endemic for Bulgaria, containing biologically active phenylethanoid glycosides that might possess antioxidant or redox activity. This study aimed to analyze the metabolic profile of in vitro cultured H. rhodopensis and to identify molecules that increase Nrf2 expression in bone marrow neutrophils. Fractions B, D, and E containing myconoside, or myconoside and calceolarioside E in ratios 1:0.6 and 0.25:1 were found to be the most active ones. Fraction B (200 µg/mL) improved neutrophil survival and strongly increased the Nrf2 intracellular level, while D and E, as well as, myconoside and calceolarioside E at the same ratios had a superior effect. Calceolarioside E (32 µg/mL) had stronger activity than myconoside, the effect of which was very similar to that of 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me), used as a positive control. These data indicate that both molecules, used alone or in combination have stimulatory activity on the endogenous Nrf2 level, indicating their therapeutic potential to regulate the cellular redox homeostasis oxidative stress-associated pathologies.
Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators
Authors: Grundmann Manuel , Bender Eckhard , Schamberger Jens , Eitner Frank
Published: February 2021

The physiological function of free fatty acids (FFAs) has long been regarded as indirect in terms of their activities as educts and products in metabolic pathways. The observation that FFAs can also act as signaling molecules at FFA receptors (FFARs), a family of G protein-coupled receptors (GPCRs), has changed the understanding of the interplay of metabolites and host responses. Free fatty acids of different chain lengths and saturation statuses activate FFARs as endogenous agonists via binding at the orthosteric receptor site. After FFAR deorphanization, researchers from the pharmaceutical industry as well as academia have identified several ligands targeting allosteric sites of FFARs with the aim of developing drugs to treat various diseases such as metabolic, (auto)inflammatory, infectious, endocrinological, cardiovascular, and renal disorders. GPCRs are the largest group of transmembrane proteins and constitute the most successful drug targets in medical history. To leverage the rich biology of this target class, the drug industry seeks alternative approaches to address GPCR signaling. Allosteric GPCR ligands are recognized as attractive modalities because of their auspicious pharmacological profiles compared to orthosteric ligands. While the majority of marketed GPCR drugs interact exclusively with the orthosteric binding site, allosteric mechanisms in GPCR biology stay medically underexploited, with only several allosteric ligands currently approved. This review summarizes the current knowledge on the biology of FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41), FFAR4 (GPR120), and GPR84, including structural aspects of FFAR1, and discusses the molecular pharmacology of FFAR allosteric ligands as well as the opportunities and challenges in research from the perspective of drug discovery.
Adipose Tissue Gene Expression of Entire Male, Immunocastrated and Surgically Castrated Pigs
Authors: Poklukar Klavdija , Čandek-Potokar Marjeta , Vrecl Milka , Batorek-Lukač Nina , Fazarinc Gregor , Kress Kevin , Stefanski Volker , Škrlep Martin
Published: February 2021

Differences in adipose tissue deposition and properties between pig male sex categories, i.e., entire males (EM), immunocastrates (IC) and surgical castrates (SC) are relatively well-characterized, whereas the underlying molecular mechanisms are still not fully understood. To gain knowledge about the genetic regulation of the differences in adipose tissue deposition, two different approaches were used: RNA-sequencing and candidate gene expression by quantitative PCR. A total of 83 differentially expressed genes were identified between EM and IC, 15 between IC and SC and 48 between EM and SC by RNA-sequencing of the subcutaneous adipose tissue. Comparing EM with IC or SC, upregulated genes related to extracellular matrix dynamics and adipogenesis, and downregulated genes involved in the control of lipid and carbohydrate metabolism were detected. Differential gene expression generally indicated high similarity between IC and SC as opposed to EM, except for several heat shock protein genes that were upregulated in EM and IC compared with SC. The candidate gene expression approach showed that genes involved in lipogenesis were downregulated in EM compared with IC pigs, further confirming RNA-sequencing results.
Detection of Coronaviruses Using RNA Toehold Switch Sensors
Authors: Park Soan , Lee Jeong Wook
Published: February 2021

A rapid, sensitive and simple point-of-care (POC) nucleic acid diagnostic test is needed to prevent spread of infectious diseases. Paper-based toehold reaction, a recently emerged colorimetric POC nucleic acid diagnostic test, has been widely used for pathogen detection and microbiome profiling. Here, we introduce an amplification method called reverse transcription loop-mediated amplification (RT-LAMP) prior to the toehold reaction and modify it to enable more sensitive and faster colorimetric detection of RNA viruses. We show that incorporating the modified RT-LAMP to the toehold reaction detects as few as 120 copies of coronavirus RNA in 70 min. Cross-reactivity test against other coronaviruses indicates this toehold reaction with the modified RT-LAMP is highly specific to the target RNA. Overall, the paper-based toehold switch sensors with the modified RT-LAMP allow fast, sensitive, specific and colorimetric coronavirus detection.
Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles
Authors: Rio-Aige Karla , Azagra-Boronat Ignasi , Massot-Cladera Malén , Selma-Royo Marta , Parra-Llorca Anna , González Sonia , García-Mantrana Izaskun , Castell Margarida , Rodríguez-Lagunas María J. , Collado María Carmen , Pérez Cano Francisco José
Published: February 2021

Mothers confer natural passive immunization to their infants through the transplacental pathway during the gestation period. The objective of the present study was to establish at birth the maternal and cord plasma concentration and relationship of immunoglobulins (Igs), cytokines (CKs), and adipokines. In addition, the impact of the maternal microbiota and diet was explored. The plasma profile of these components was different between mothers and babies, with the levels of many CKs, IgM, IgG2a, IgE, IgA, and leptin significantly higher in mothers than in the cord sample. Moreover, the total Igs, all IgG subtypes, IgE, and the Th1/Th2 ratio positively correlated in the mother–infant pair. Maternal dietary components such as monounsaturated fatty acids-polyunsaturated fatty acids and fiber were positively associated with some immune factors such as IgA in cord samples. The microbiota composition clustering also influenced the plasma profile of some factors (i.e., many CKs, some Ig, and adiponectin). In conclusion, we have established the concentration of these immunomodulatory factors in the maternal–neonatal pair at birth, some positive associations, and the influence of maternal diet and the microbiota composition, suggesting that the immune status during pregnancy, in terms of CKs and Igs levels, can influence the immune status of the infant at birth.
The Roles of Post-Translational Modifications on mTOR Signaling
Authors: Yin Shasha , Liu Liu , Gan Wenjian
Published: February 2021

The mechanistic target of rapamycin (mTOR) is a master regulator of cell growth, proliferation, and metabolism by integrating various environmental inputs including growth factors, nutrients, and energy, among others. mTOR signaling has been demonstrated to control almost all fundamental cellular processes, such as nucleotide, protein and lipid synthesis, autophagy, and apoptosis. Over the past fifteen years, mapping the network of the mTOR pathway has dramatically advanced our understanding of its upstream and downstream signaling. Dysregulation of the mTOR pathway is frequently associated with a variety of human diseases, such as cancers, metabolic diseases, and cardiovascular and neurodegenerative disorders. Besides genetic alterations, aberrancies in post-translational modifications (PTMs) of the mTOR components are the major causes of the aberrant mTOR signaling in a number of pathologies. In this review, we summarize current understanding of PTMs-mediated regulation of mTOR signaling, and also update the progress on targeting the mTOR pathway and PTM-related enzymes for treatment of human diseases.
Oxidative Stress, Plant Natural Antioxidants, and Obesity
Authors: Pérez-Torres Israel , Castrejón-Téllez Vicente , Soto María Elena , Rubio-Ruiz María Esther , Manzano-Pech Linaloe , Guarner-Lans Verónica
Published: February 2021

Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite. This review discusses the participation of oxidative stress in obesity and the important groups of compounds found in plants with antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, and isoflavones), and curcuminoids (b) carotenoids, (c) capsaicinoids and casinoids, (d) isothiocyanates, (e) catechins, and (f) vitamins. Examples are analyzed, such as resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, and garlic. The antioxidant activities of these compounds depend on their activities as reactive oxygen species (ROS) scavengers and on their capacity to prevent the activation of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), and reduce the expression of target genes, including those participating in inflammation. We conclude that natural compounds have therapeutic potential for diseases mediated by oxidative stress, particularly obesity. Controlled and well-designed clinical trials are still necessary to better know the effects of these compounds.
Adipocyte-Derived Extracellular Vesicles: State of the Art
Authors: Rome Sophie , Blandin Alexia , Le Lay Soazig
Published: February 2021

White adipose tissue (WAT) is involved in long-term energy storage and represents 10–15% of total body weight in healthy humans. WAT secretes many peptides (adipokines), hormones and steroids involved in its homeostatic role, especially in carbohydrate–lipid metabolism regulation. Recently, adipocyte-derived extracellular vesicles (AdEVs) have been highlighted as important actors of intercellular communication that participate in metabolic responses to control energy flux and immune response. In this review, we focus on the role of AdEVs in the cross-talks between the different cellular types composing WAT with regard to their contribution to WAT homeostasis and metabolic complications development. We also discuss the AdEV cargoes (proteins, lipids, RNAs) which may explain AdEV’s biological effects and demonstrate that, in terms of proteins, AdEV has a very specific signature. Finally, we list and suggest potential therapeutic strategies to modulate AdEV release and composition in order to reduce their deleterious effects during the development of metabolic complications associated with obesity.
Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment
Authors: Mroweh Mariam , Roth Gaël , Decaens Thomas , Marche Patrice N. , Lerat Hervé , Macek Jílková Zuzana
Published: February 2021

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide, and its incidence is rising. HCC develops almost exclusively on the background of chronic liver inflammation, which can be caused by chronic alcohol consumption, viral hepatitis, or an unhealthy diet. The key role of chronic inflammation in the process of hepatocarcinogenesis, including in the deregulation of innate and adaptive immune responses, has been demonstrated. The inhibition of Akt (also known as Protein Kinase B) directly affects cancer cells, but this therapeutic strategy also exhibits indirect anti-tumor activity mediated by the modulation of the tumor microenvironment, as demonstrated by using Akt inhibitors AZD5363, MK-2206, or ARQ 092. Moreover, the isoforms of Akt converge and diverge in their designated roles, but the currently available Akt inhibitors fail to display an isoform specificity. Thus, selective Akt inhibition needs to be better explored in the context of HCC and its possible combination with immunotherapy. This review presents a compact overview of the current knowledge concerning the role of Akt in HCC and the effect of Akt inhibition on the HCC and liver tumor microenvironment.
Axonal Organelles as Molecular Platforms for Axon Growth and Regeneration after Injury
Authors: Petrova Veselina , Nieuwenhuis Bart , Fawcett James W. , Eva Richard
Published: February 2021

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.
Nanopore Sequencing Resolves Elusive Long Tandem-Repeat Regions in Mitochondrial Genomes
Authors: Kinkar Liina , Gasser Robin , Webster Bonnie , Rollinson David , Littlewood D. , Chang Bill , Stroehlein Andreas , Korhonen Pasi , Young Neil
Published: February 2021

Long non-coding, tandem-repetitive regions in mitochondrial (mt) genomes of many metazoans have been notoriously difficult to characterise accurately using conventional sequencing methods. Here, we show how the use of a third-generation (long-read) sequencing and informatic approach can overcome this problem. We employed Oxford Nanopore technology to sequence genomic DNAs from a pool of adult worms of the carcinogenic parasite, Schistosoma haematobium, and used an informatic workflow to define the complete mt non-coding region(s). Using long-read data of high coverage, we defined six dominant mt genomes of 33.4 kb to 22.6 kb. Although no variation was detected in the order or lengths of the protein-coding genes, there was marked length (18.5 kb to 7.6 kb) and structural variation in the non-coding region, raising questions about the evolution and function of what might be a control region that regulates mt transcription and/or replication. The discovery here of the largest tandem-repetitive, non-coding region (18.5 kb) in a metazoan organism also raises a question about the completeness of some of the mt genomes of animals reported to date, and stimulates further explorations using a Nanopore-informatic workflow.
Convergence: Lactosylceramide-Centric Signaling Pathways Induce Inflammation, Oxidative Stress, and Other Phenotypic Outcomes
Authors: Chatterjee Subroto , Balram Amrita , Li Wendy
Published: February 2021

Lactosylceramide (LacCer), also known as CD17/CDw17, is a member of a large family of small molecular weight compounds known as glycosphingolipids. It plays a pivotal role in the biosynthesis of glycosphingolipids, primarily by way of serving as a precursor to the majority of its higher homolog sub-families such as gangliosides, sulfatides, fucosylated-glycosphingolipids and complex neutral glycosphingolipids—some of which confer “second-messenger” and receptor functions. LacCer is an integral component of the “lipid rafts,” serving as a conduit to transduce external stimuli into multiple phenotypes, which may contribute to mortality and morbidity in man and in mouse models of human disease. LacCer is synthesized by the action of LacCer synthase (β-1,4 galactosyltransferase), which transfers galactose from uridine diphosphate galactose (UDP-galactose) to glucosylceramide (GlcCer). The convergence of multiple physiologically relevant external stimuli/agonists—platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), stress, cigarette smoke/nicotine, tumor necrosis factor-α (TNF-α), and in particular, oxidized low-density lipoprotein (ox-LDL)—on β-1,4 galactosyltransferase results in its phosphorylation or activation, via a “turn-key” reaction, generating LacCer. This newly synthesized LacCer activates NADPH (nicotinamide adenine dihydrogen phosphate) oxidase to generate reactive oxygen species (ROS) and a highly “oxidative stress” environment, which trigger a cascade of signaling molecules and pathways and initiate diverse phenotypes like inflammation and atherosclerosis. For instance, LacCer activates an enzyme, cytosolic phospholipase A2 (cPLA2), which cleaves arachidonic acid from phosphatidylcholine. In turn, arachidonic acid serves as a precursor to eicosanoids and prostaglandin, which transduce a cascade of reactions leading to inflammation—a major phenotype underscoring the initiation and progression of several debilitating diseases such as atherosclerosis and cancer. Our aim here is to present an updated account of studies made in the field of LacCer metabolism and signaling using multiple animal models of human disease, human tissue, and cell-based studies. These advancements have led us to propose that previously unrelated phenotypes converge in a LacCer-centric manner. This LacCer synthase/LacCer-induced “oxidative stress” environment contributes to inflammation, atherosclerosis, skin conditions, hair greying, cardiovascular disease, and diabetes due to mitochondrial dysfunction. Thus, targeting LacCer synthase may well be the answer to remedy these pathologies.
Current Understandings on Magnesium Deficiency and Future Outlooks for Sustainable Agriculture
Authors: Chaudhry Ahmad Hassan , Nayab Shafa , Hussain Syed Bilal , Ali Muqarrab , Pan Zhiyong
Published: February 2021

The productivity of agricultural produce is fairly dependent on the availability of nutrients and efficient use. Magnesium (Mg2+) is an essential macronutrient of living cells and is the second most prevalent free divalent cation in plants. Mg2+ plays a role in several physiological processes that support plant growth and development. However, it has been largely forgotten in fertilization management strategies to increase crop production, which leads to severe reductions in plant growth and yield. In this review, we discuss how the Mg2+ shortage induces several responses in plants at different levels: morphological, physiological, biochemical and molecular. Additionally, the Mg2+ uptake and transport mechanisms in different cellular organelles and the role of Mg2+ transporters in regulating Mg2+ homeostasis are also discussed. Overall, in this review, we critically summarize the available information about the responses of Mg deficiency on plant growth and development, which would facilitate plant scientists to create Mg2+-deficiency-resilient crops through agronomic and genetic biofortification.
Coumarins from Seseli devenyense Simonk.: Isolation by Liquid–Liquid Chromatography and Potential Anxiolytic Activity Using an In Vivo Zebrafish Larvae Model
Authors: Widelski Jarosław , Luca Simon Vlad , Skiba Adrianna , Maciąg Monika , Budzyńska Barbara , Marcourt Laurence , Wolfender Jean-Luc , Skalicka-Woźniak Krystyna
Published: February 2021

Different types of anxiety disorders have become the number one mental health issue in developed countries. The search for new, safer and effective drug-like molecules among naturally derived substances faces two difficulties: an efficient method of isolation compounds with a high-purity and high-throughput animal model for activity assay. Thus, the aim of the present study was to isolate by liquid–liquid chromatography high-purity rare coumarins from the fruits of Seseli devenyense Simonk. and evaluate their anxiolytic effect (defined as reversed thimotaxis) using a 5-days post-fertilization (dpf) Danio rerio larvae model. Liquid–liquid chromatography enabled the isolation of one simple hydroxycoumarin (devenyol) and four pyranocoumarins (cis-khellactone, d-laserpitin, isolaserpitin and octanoyllomatin). The anxiolytic effect was defined as a decrease in the time spent in the boundaries of the living space (also described as reversed thigmotaxis). Our results show that all isolated courmarins exerted a significant influence on the anxiety behavior (anxiolytic activity) in the zebrafish larvae model. According to our knowledge, this is the first report of anxiolytic activity of pyranocoumarins and devenyol.
Whole Exome Sequencing Identifies APCDD1 and HDAC5 Genes as Potentially Cancer Predisposing in Familial Colorectal Cancer
Authors: Skopelitou Diamanto , Miao Beiping , Srivastava Aayushi , Kumar Abhishek , Kuświk Magdalena , Dymerska Dagmara , Paramasivam Nagarajan , Schlesner Matthias , Lubinski Jan , Hemminki Kari , Försti Asta , Bandapalli Obul
Published: February 2021

Germline mutations in predisposition genes account for only 20% of all familial colorectal cancers (CRC) and the remaining genetic burden may be due to rare high- to moderate-penetrance germline variants that are not explored. With the aim of identifying such potential cancer-predisposing variants, we performed whole exome sequencing on three CRC cases and three unaffected members of a Polish family and identified two novel heterozygous variants: a coding variant in APC downregulated 1 gene (APCDD1, p.R299H) and a non-coding variant in the 5′ untranslated region (UTR) of histone deacetylase 5 gene (HDAC5). Sanger sequencing confirmed the variants segregating with the disease and Taqman assays revealed 8 additional APCDD1 variants in a cohort of 1705 familial CRC patients and no further HDAC5 variants. Proliferation assays indicated an insignificant proliferative impact for the APCDD1 variant. Luciferase reporter assays using the HDAC5 variant resulted in an enhanced promoter activity. Targeting of transcription factor binding sites of SNAI-2 and TCF4 interrupted by the HDAC5 variant showed a significant impact of TCF4 on promoter activity of mutated HDAC5. Our findings contribute not only to the identification of unrecognized genetic causes of familial CRC but also underline the importance of 5’UTR variants affecting transcriptional regulation and the pathogenesis of complex disorders.
B Cells with a Senescent-Associated Secretory Phenotype Accumulate in the Adipose Tissue of Individuals with Obesity
Authors: Frasca Daniela , Romero Maria , Diaz Alain , Garcia Denisse , Thaller Seth , Blomberg Bonnie B.
Published: February 2021

Senescent cells accumulate in the adipose tissue (AT) of individuals with obesity and secrete multiple factors that constitute the senescence-associated secretory phenotype (SASP). This paper aimed at the identification of B cells with a SASP phenotype in the AT, as compared to the peripheral blood, of individuals with obesity. Our results show increased expression of SASP markers in AT versus blood B cells, a phenotype associated with a hyper-metabolic profile necessary to support the increased immune activation of AT-derived B cells as compared to blood-derived B cells. This hyper-metabolic profile is needed for the secretion of the pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) that fuel local and systemic inflammation.
Increased Serum Levels of Brain-Derived Neurotrophic Factor Contribute to Inflammatory Responses in Patients with Rheumatoid Arthritis
Authors: Lai Ning-Sheng , Yu Hui-Chun , Huang Tseng Hsien-Yu , Hsu Chia-Wen , Huang Hsien-Bin , Lu Ming-Chi
Published: February 2021

The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF) in the inflammatory responses in patients with rheumatoid arthritis (RA). Serum levels of BDNF and the precursor form of BDNF (proBDNF) from 625 RA patients and 40 controls were analyzed using enzyme-linked immunosorbent assay. Effects of BDNF on the mitogen-activated protein kinase pathway were analyzed by Western blotting. Microarray analysis was conducted to search BDNF regulated gene expression in Jurkat cells, and the differentially expressed genes were validated using T cells from patients with RA and controls. Serum BDNF levels were significantly elevated in patients with RA compared with the controls. Low serum BDNF levels were found in RA patients with anxiety or receiving biologics treatment. BDNF (20 ng/mL) enhanced the phosphorylation of ERK, JNK, and c-Jun, but suppressed the phosphorylation of p38, whereas BDNF (200 ng/mL) enhanced the phosphorylation of ERK and p38. After validation, the expression of CAMK2A, MASP2, GNG13, and MUC5AC, regulated by BDNF and one of its receptors, NGFR, was increased in RA T cells. BDNF increased the IL-2, IL-17, and IFN-γ expression in Jurkat cells and IL-2 and IFN-γ secretion in activated peripheral blood mononuclear cells.
Topic Modeling and Sentiment Analysis of Online Review for Airlines
Authors: Kwon Hye-Jin , Ban Hyun-Jeong , Jun Jae-Kyoon , Kim Hak-Seon
Published: February 2021

The purpose of this study is to conduct topic modeling and sentiment analysis on the posts of Skytrax (airlinequality.com), where there are many interests and participation of the people who have used or are willing to use it for airlines. The purpose of people gathering at Skytrax is to make better choices using the actual experiences of other customers who have experienced airlines. Online reviews written by customers with experience using airlines in Asia were collected. The data collected were online reviews from 27 airlines, with more than 14,000 reviews. Topic modeling and sentiment analysis were used with the collected data to figure out what kinds of important words are in the online reviews. As a result of the topic modeling, ‘seat’, ‘service’, and ‘meal’ were significant issues in the flight through frequency analysis. Additionally, the result revealed that delay was the main issue, which can affect customer dissatisfaction while ‘staff service’ can make customers satisfied through sentiment analysis as the result shows the ‘staff service’ with meal and food in the topic modeling.