bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferability of Cardiopulmonary Parameters between Treadmill and Cycle Ergometer Testing in Male Triathletes—Prediction Formulae
Authors: Wiecha Szczepan , Price Szymon , Cieśliński Igor , Kasiak Przemysław Seweryn , Tota Łukasz , Ambroży Tadeusz , Śliż Daniel
Published: February 2022

Cardiopulmonary exercise testing (CPET) on a treadmill (TE) or cycle ergometry (CE) is a common method in sports diagnostics to assess athletes’ aerobic fitness and prescribe training. In a triathlon, the gold standard is performing both CE and TE CPET. The purpose of this research was to create models using CPET results from one modality to predict results for the other modality. A total of 152 male triathletes (age = 38.20 ± 9.53 year; BMI = 23.97 ± 2.10 kg·m−2) underwent CPET on TE and CE, preceded by body composition (BC) analysis. Speed, power, heart rate (HR), oxygen uptake (VO2), respiratory exchange ratio (RER), ventilation (VE), respiratory frequency (fR), blood lactate concentration (LA) (at the anaerobic threshold (AT)), respiratory compensation point (RCP), and maximum exertion were measured. Random forests (RF) were used to find the variables with the highest importance, which were selected for multiple linear regression (MLR) models. Based on R2 and RF variable selection, MLR equations in full, simplified, and the most simplified forms were created for VO2AT, HRAT, VO2RCP, HRRCP, VO2max, and HRmax for CE (R2 = 0.46–0.78) and TE (R2 = 0.59–0.80). By inputting only HR and power/speed into the RF, MLR models for practical HR calculation on TE and CE (both R2 = 0.41–0.75) were created. BC had a significant impact on the majority of CPET parameters. CPET parameters can be accurately predicted between CE and TE testing. Maximal parameters are more predictable than submaximal. Only HR and speed/power from one testing modality could be used to predict HR for another. Created equations, combined with BC analysis, could be used as a method of choice in comprehensive sports diagnostics.
Analyzing the Influencing Factors and Workload Variation of Takeover Behavior in Semi-Autonomous Vehicles
Authors: Zhang Hui , Zhang Yijun , Xiao Yiying , Wu Chaozhong
Published: February 2022

There are many factors that will influence the workload of drivers during autonomous driving. To examine the correlation between different factors and the workload of drivers, the influence of different factors on the workload variations is investigated from subjective and objective viewpoints. Thirty-seven drivers were recruited to participant the semi-autonomous driving experiments, and the drivers were required to complete different NDRTs (Non-Driving-Related Tasks): mistake finding, chatting, texting, and monitoring when the vehicle is in autonomous mode. Then, we introduced collision warning to signal there is risk ahead, and the warning signal was triggered at different TB (Time Budget)s before the risk, at which time the driver had to take over the driving task. During driving, the NASA-TLX-scale data were obtained to analyze the variation of the driver’s subjective workload. The driver’s pupil-diameter data acquired by the eye tracker from 100 s before the TOR (Take-Over Request) to 19 s after the takeover were obtained as well. The sliding time window was set to process the pupil-diameter data, and the 119-s normalized average pupil-diameter data under different NDRTs were fitted and modeled to analyze the variation of the driver’s objective workload. The results show that the total subjective workload score under the influence of different factors is as follows: obstacle-avoidance scene > lane-keeping scene; TB = 7 s and TB = 3 s have no significant difference; and mistake finding > chatting > texting > monitoring. The results of pupil-diameter data under different factors are as follows: obstacle-avoidance scene > lane-keeping scene; TB = 7 s > TB = 3 s; and monitoring type (chatting and monitoring) > texting type (mistake finding and texting). The research results can provide a reference for takeover safety prediction modeling based on workload.
Stigma towards Mental Disorders among Nursing Students and Professionals: A Bibliometric Analysis
Authors: Martínez-Martínez Concepción , Esteve-Claramunt Francisca , Prieto-Callejero Blanca , Ramos-Pichardo Juan Diego
Published: February 2022

Stigma is one of the main barriers to prevention, treatment and recovery from mental illness. However, bibliometric studies in this area are still scarce. Therefore, our aim was to quantify and analyze the scientific literature on the stigma of nursing students and professionals towards mental disorders. To this purpose, bibliometric indicators of scientific production, impact and collaboration were used. Among our results, it stands out that only 14.3% of the total number of studies analyzed measure the efficacy of the interventions carried out to reduce stigma. Furthermore, with exceptions such as Happell B and Byrne L, collaborations between authors and institutions are limited. “Service user involvement” appeared as a prominent keyword in 2018, coinciding with the increase in publications on the effectiveness of interventions. Interventions based on the involvement of people with psychiatric diagnoses in the design of nursing curricula seem to become a promising line of research. More studies measuring the efficacy of such interventions are needed. Knowledge of the lines of research that are being developed and of the researchers and institutions involved can contribute to creating synergy between the different researchers and to continue adding projects to the existing ones, thus contributing to the generation of more robust results that show the most indicated interventions to reduce the still present stigma and improve care for people with psychiatric diagnoses.
Detraining Effects of COVID-19 Pandemic on Physical Fitness, Cytokines, C-Reactive Protein and Immunocytes in Men of Various Age Groups
Authors: Heo Seung-Jae , Park Sang-Kyun , Jee Yong-Seok
Published: February 2022

Background and Objectives: Since the start of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus II, levels of physical inactivity have become more severe and widespread than ever before. Physical inactivity is known to have a negative effect on the human body, but the extent to which reduced physical fitness has effected immune function before and after the current pandemic has not yet been uncovered. The aim of this study was to investigate the detraining effects of the COVID-19 confinement period on physical fitness, immunocytes, inflammatory cytokines, and proteins in various age groups. The participants of this study included sixty-four male adults who did not exercise during the pandemic, although they had exercised regularly before. Materials and Methods: Participants were classified by age group, which included the 20s group (20s’G, n = 14), 30s group (30s’G, n = 12), 40s group (40s’G, n = 12), 50s group (50s’G, n = 12), and 60s group (60s’G, n = 14). Results: Regarding body composition, muscle mass significantly decreased, whereas fat mass, fat percentage, and waist/hip ratio significantly increased in most groups. Cardiopulmonary endurance and strength significantly decreased in all groups, while muscle endurance and flexibility decreased in some groups compared to the pre-COVID-19 pandemic. This study confirmed the immunocytopenia and enhanced inflammation due to physical inactivity during the COVID-19 pandemic, and a greater detrimental decrease mainly after the age of 50. Conclusion: This study confirmed a decrease in physical fitness after the start of the COVID-19 pandemic, characterized by an increase in fat mass and a decrease in muscle mass, thereby increasing cytokines and reducing immunocytes in the body. While social distancing is important during the pandemic, maintaining physical fitness should also be a top priority.
Changes in Active Behaviours, Physical Activity, Sedentary Time, and Physical Fitness in Chilean Parents during the COVID-19 Pandemic: A Retrospective Study
Authors: Hernández-Jaña Sam , Escobar-Gómez Danica , Cristi-Montero Carlos , Castro-Piñero José , Rodríguez-Rodríguez Fernando
Published: February 2022

Strategies to reduce the spread of coronavirus disease 2019 (COVID-19) have caused different behavioural modifications in all populations. Therefore, this study aimed to determine changes in active commuting, moderate-to-vigorous physical activity (MVPA), physical fitness, and sedentary time during the COVID-19 pandemic in Chilean parents. Eighty-six fathers (41.30 ± 6.82 years) and 294 mothers (40.68 ± 6.92 years) of children from different schools from Valparaíso, Chile, participated. Inclusion criteria were adults with schoolchildren who were resident in Chile during the research period. Convenience sampling was used as a non-probabilistic sampling technique. Respondents completed a self-reported online survey about active commuting, MVPA, self-perceived physical fitness, and sedentary time July–September 2020 during the first pandemic period. Comparisons between before and during the pandemic were performed using t-tests and covariance analysis (ANCOVA), establishing a significance level at p < 0.05. Most participants stayed at home during the pandemic, whereas active and passive commuting significantly decreased in both fathers and mothers (p < 0.001). MVPA and physical fitness scores reduced considerably (p < 0.05), while sedentary time significantly increased (p < 0.05), independent of the sex of parents and children’s school type. Differences by age groups and the number of children were more heterogeneous, as younger parents showed a larger decrease in MVPA (p < 0.05) and physical fitness score (p < 0.05). Additionally, parents with one child showed a larger decrease in sedentary time (p < 0.05) than those with two or more children. The COVID-19 pandemic significantly affected healthy behaviours. Hence, health policies should promote more strategies to mitigate the long-term health effects of the pandemic on Chilean parents.
Prevalence, Risk Factors and Impacts Related to Mould-Affected Housing: An Australian Integrative Review
Authors: Coulburn Lisa , Miller Wendy
Published: February 2022

In response to an Australian governmental inquiry into biotoxin-related illness, the purpose of this integrative review is to bring together the current state of evidence on the prevalence, risk factors and impacts related to mould-affected housing in an Australian context, in order to inform building, housing and health research, practice and policy. The robust integrative review methodology simultaneously sought quantitative and qualitative studies and grey literature from multiple disciplines, identifying only 45 studies directly relating to Australian housing and indoor mould. Twenty-one studies highlight negative health impacts relating to indoor residential mould, with asthma, respiratory, allergy conditions and emerging health concerns for chronic multiple-symptom presentation. The majority of studies reported risk factors for indoor mould including poor housing conditions, poor-quality rental accommodation, socioeconomic circumstance, age-related housing issues and concerns for surface/interstitial condensation and building defects in newer housing. Risks for indoor mould in both older and newer housing raise concerns for the extent of the problem of indoor mould in Australia. Understanding the national prevalence of housing risks and “root cause” associated with indoor mould is not conclusive from the limited existing evidence. Synthesis of this evidence reveals a lack of coverage on: (1) national and geographical representation, (2) climatical coverage, (3) housing typologies, (4) housing defects, (5) maintenance, (6) impact from urbanisation, and (7) occupant’s behaviour. This integrative review was key in identifying emerging housing and health concerns, highlighting gaps in data and implications to be addressed by researchers, practice and policy and acts as a comprehensive holistic review process that can be applied to other countries.
Development of a Nutrition Environment Assessment Tool for Latino Ethnic Stores
Authors: Baier Jenny L. , Palmer Shelly M. , Winham Donna M. , Shelley Mack C.
Published: February 2022

The objectives were to: (1) adapt the Nutrition Environment Measures Survey for Stores (NEMS-S) to better culturally fit small Latino grocery stores (tiendas) in Iowa; (2) assess the newly adapted Latino NEMS-S for inter-rater and test-retest reliability; and (3) compare Latino and original NEMS-S summary scores. This pilot instrument, containing culturally appropriate foods from the original NEMS-S and 2015 US Dietary Guidelines for Americans, underwent two rounds of formative evaluation. The new instrument and scoring protocol were applied to a random sample of 42 of 81 possible tiendas in Iowa. Cohen’s kappa was used to assess inter-rater and test-retest reliability for availability and quality of indicator food items (total scores and food category sub scores). There were no differences in summary scores for inter-rater or test-retest reliability using paired t-tests. Inter-rater agreement was high (range 0.82–1.00; p < 0.001). Tiendas averaged 42.0 ± 7.5 of 57 possible points on the Latino NEMS-S, but only 12.0 ± 4.6 of 54 points on the original NEMS-S (p < 0.001). The Latino NEMS-S is a reliable tool for assessing the food environment within Iowa tiendas. Culturally specific instruments can describe diverse food environments more accurately and guide public health nutrition interventions within communities.
FC-RRT*: An Improved Path Planning Algorithm for UAV in 3D Complex Environment
Authors: Guo Yicong , Liu Xiaoxiong , Liu Xuhang , Yang Yue , Zhang Weiguo
Published: February 2022

In complex environments, path planning is the key for unmanned aerial vehicles (UAVs) to perform military missions autonomously. This paper proposes a novel algorithm called flight cost-based Rapidly-exploring Random Tree star (FC-RRT*) extending the standard Rapidly-exploring Random Tree star (RRT*) to deal with the safety requirements and flight constraints of UAVs in a complex 3D environment. First, a flight cost function that includes threat strength and path length was designed to comprehensively evaluate the connection between two path nodes. Second, in order to solve the UAV path planning problem from the front-end, the flight cost function and flight constraints were used to inspire the expansion of new nodes. Third, the designed cost function was used to guide the update of the parent node to allow the algorithm to consider both the threat and the length of the path when generating the path. The simulation and comparison results show that FC-RRT* effectively overcomes the shortcomings of standard RRT*. FC-RRT* is able to plan an optimal path that significantly improves path safety as well as maintains has the shortest distance while satisfying flight constraints in the complex environment. This paper has application value in UAV 3D global path planning.
Towards a Sensitivity Analysis in Seismic Risk with Probabilistic Building Exposure Models: An Application in Valparaíso, Chile Using Ancillary Open-Source Data and Parametric Ground Motions
Authors: Gómez Zapata Juan Camilo , Zafrir Raquel , Pittore Massimiliano , Merino Yvonne
Published: February 2022

Efforts have been made in the past to enhance building exposure models on a regional scale with increasing spatial resolutions by integrating different data sources. This work follows a similar path and focuses on the downscaling of the existing SARA exposure model that was proposed for the residential building stock of the communes of Valparaíso and Viña del Mar (Chile). Although this model allowed great progress in harmonising building classes and characterising their differential physical vulnerabilities, it is now outdated, and in any case, it is spatially aggregated over large administrative units. Hence, to more accurately consider the impact of future earthquakes on these cities, it is necessary to employ more reliable exposure models. For such a purpose, we propose updating this existing model through a Bayesian approach by integrating ancillary data that has been made increasingly available from Volunteering Geo-Information (VGI) activities. Its spatial representation is also optimised in higher resolution aggregation units that avoid the inconvenience of having incomplete building-by-building footprints. A worst-case earthquake scenario is presented to calculate direct economic losses and highlight the degree of uncertainty imposed by exposure models in comparison with other parameters used to generate the seismic ground motions within a sensitivity analysis. This example study shows the great potential of using increasingly available VGI to update worldwide building exposure models as well as its importance in scenario-based seismic risk assessment.
Lipid Droplet Accumulation Promotes RPE Dysfunction
Authors: Yako Tomohiro , Otsu Wataru , Nakamura Shinsuke , Shimazawa Masamitsu , Hara Hideaki
Published: February 2022

Non-exudative age-related macular degeneration (AMD) is an irreversibly progressive retinal degenerative disease characterized by dysfunction and loss of retinal pigment epithelium (RPE). It has been suggested that impaired phagocytosis of the RPE is involved in the progression of non-exudative AMD, but the mechanism is not fully clear. In this study, we investigated the effect of lipid droplet accumulation on RPE function. Compared to young mice, the expression of lipid droplet-associated proteins increased in the RPE-choroidal complex, and lipid droplet in the RPE was observed in aged pigmented mice (12-month-old). Repeated treatment of the photoreceptor outer segment against ARPE-19 resulted in lipid droplets in ARPE-19 cells in vitro. Oleic acid treatment for ARPE-19 cells to form intracellular lipid droplet reduced the POS uptake into the ARPE-19 cells without causing a decrease in cell viability. The suppression of the POS uptake by lipid droplet formation improved by inhibiting lipid droplet formation using triacsin C. Moreover, the amount of intracellular reactive oxygen species was suppressed by the triacsin C treatment. These results indicate that lipid droplet is involved in the RPE dysfunction, and inhibiting lipid droplet formation may be a target for preventing and treating non-exudative AMD.
Overexpression of a Malus baccata MYB Transcription Factor Gene MbMYB4 Increases Cold and Drought Tolerance in Arabidopsis thaliana
Authors: Yao Chunya , Li Xingguo , Li Yingmei , Yang Guohui , Liu Wanda , Shao Bangtao , Zhong Jiliang , Huang Pengfei , Han Deguo
Published: February 2022

In the natural environment, plants often face unfavorable factors such as drought, cold, and freezing, which affect their growth and yield. The MYB (v-myb avian myeloblastosis viral oncogene homolog) transcription factor family is widely involved in plant responses to biotic and abiotic stresses. In this study, Malus baccata (L.) Borkh was used as the research material, and a gene MbMYB4 of the MYB family was cloned from it. The open reading frame (ORF) of MbMYB4 was found to be 762 bp, encoding 253 amino acids; sequence alignment results and predictions of the protein structure indicated that the MbMYB4 protein contained the conserved MYB domain. Subcellular localization showed that MbMYB4 was localized in the nucleus. In addition, the use of quantitative real-time PCR (qPCR) technology found that the expression of MbMYB4 was enriched in the young leaf and root, and it was highly affected by cold and drought treatments in M. baccata seedlings. When MbMYB4 was introduced into Arabidopsis thaliana, it greatly increased the cold and drought tolerance in the transgenic plant. Under cold and drought stresses, the proline and chlorophyll content, and peroxidase (POD) and catalase (CAT) activities of transgenic A. thaliana increased significantly, and the content of malondialdehyde (MDA) and the relative conductivity decreased significantly, indicating that the plasma membrane damage of transgenic A. thaliana was lesser. Therefore, the overexpression of the MbMYB4 gene in A. thaliana can enhance the tolerance of transgenic plants to cold and drought stresses.
Reversible Redox Processes in Polymer of Unmetalated Salen-Type Ligand: Combined Electrochemical in Situ Studies and Direct Comparison with Corresponding Nickel Metallopolymer
Authors: Polozhentseva Julia , Novozhilova Maria , Karushev Mikhail
Published: February 2022

Most non-metalized Salen-type ligands form passivation thin films on electrode surfaces upon electrochemical oxidation. In contrast, the H2(3-MeOSalen) forms electroactive polymer films similarly to the corresponding nickel complex. There are no details of electrochemistry, doping mechanism and charge transfer pathways in the polymers of pristine Salen-type ligands. We studied a previously uncharacterized electrochemically active polymer of a Salen-type ligand H2(3-MeOSalen) by a combination of cyclic voltammetry, in situ ultraviolet–visible (UV–VIS) spectroelectrochemistry, in situ electrochemical quartz crystal microbalance and Fourier Transform infrared spectroscopy (FTIR) spectroscopy. By directly comparing it with the polymer of a Salen-type nickel complex poly-Ni(3-MeOSalen) we elucidate the effect of the central metal atom on the structure and charge transport properties of the electrochemically doped polymer films. We have shown that the mechanism of charge transfer in the polymeric ligand poly-H2(3-MeOSalen) are markedly different from the corresponding polymeric nickel complex. Due to deviation from planarity of N2O2 sphere for the ligand H2(3-MeOSalen), the main pathway of electron transfer in the polymer film poly-H2(3-MeOSalen) is between π-stacked structures (the π-electronic systems of phenyl rings are packed face-to-face) and C-C bonded phenyl rings. The main way of electron transfer in the polymer film poly-Ni(3-MeOSalen) is along the polymer chain, while redox processes are ligand-based.
Broad Spectrum Anti-Bacterial Activity and Non-Selective Toxicity of Gum Arabic Silver Nanoparticles
Authors: Fadaka Adewale O. , Meyer Samantha , Ahmed Omnia , Geerts Greta , Madiehe Madimabe A. , Meyer Mervin , Sibuyi Nicole R. S.
Published: February 2022

Silver nanoparticles (AgNPs) are the most commercialized nanomaterials and presumed to be biocompatible based on the biological effects of the bulk material. However, their physico-chemical properties differ significantly to the bulk materials and are associated with unique biological properties. The study investigated the antimicrobial and cytotoxicity effects of AgNPs synthesized using gum arabic (GA), sodium borohydride (NaBH4), and their combination as reducing agents. The AgNPs were characterized using ultraviolet-visible spectrophotometry (UV-Vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FT-IR). The anti-bacterial activity was assessed using agar well diffusion and microdilution assays, and the cytotoxicity effects on Caco-2, HT-29 and KMST-6 cells using MTT assay. The GA-synthesized AgNPs (GA-AgNPs) demonstrated higher bactericidal activity against all bacteria, and non-selective cytotoxicity towards normal and cancer cells. AgNPs reduced by NaBH4 (C-AgNPs) and the combination of GA and NaBH4 (GAC-AgNPs) had insignificant anti-bacterial activity and cytotoxicity at ≥50 µg/mL. The study showed that despite the notion that AgNPs are safe and biocompatible, their toxicity cannot be overruled and that their toxicity can be channeled by using biocompatible polymers, thereby providing a therapeutic window at concentrations that are least harmful to mammalian cells but toxic to bacteria.
Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host–Pathogen Response to Infection
Authors: López-Agudelo Víctor A. , Baena Andres , Barrera Vianey , Cabarcas Felipe , Alzate Juan F. , Beste Dany J. V. , Ríos-Estepa Rigoberto , Barrera Luis F.
Published: February 2022

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), leading to pulmonary and extrapulmonary TB, whereby Mtb is disseminated to many other organs and tissues. Dissemination occurs early during the disease, and bacteria can be found first in the lymph nodes adjacent to the lungs and then later in the extrapulmonary organs, including the spleen. The early global gene expression response of human tissue macrophages and intracellular clinical isolates of Mtb has been poorly studied. Using dual RNA-seq, we have explored the mRNA profiles of two closely related clinical strains of the Latin American and Mediterranean (LAM) family of Mtb in infected human splenic macrophages (hSMs). This work shows that these pathogens mediate a distinct host response despite their genetic similarity. Using a genome-scale host–pathogen metabolic reconstruction to analyze the data further, we highlight that the infecting Mtb strain also determines the metabolic response of both the host and pathogen. Thus, macrophage ontogeny and the genetic-derived program of Mtb direct the host–pathogen interaction.
The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes
Authors: Luchian Ionut , Goriuc Ancuta , Sandu Darius , Covasa Mihai
Published: February 2022

Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ranks sixth in terms of global spread, affecting about 11% of the population. Metalloproteinases (MMPs) are extracellular matrix (ECM) macromolecules that are important in cellular development and morphogenesis, and they are capable of activating growth factors in their proximity, cell surface receptors, and adhesion molecules. MMPs are part of a major family of zinc-dependent endopeptidases, and their activity is modulated and regulated by certain inhibitors known as tissue metalloproteinase inhibitors (TIMPs). Because type I collagen is the major component of the periodontal extracellular matrix, special attention has been paid to the role of collagenases, especially MMP-8 and MMP-13 and gelatinases, MMP-2 and MMP-9, in periodontal diseases. In fact, MMP-8 (or collagenase 2) is currently one of the most promising biomarkers for periodontitis in oral fluids. Among them, salivary MMP-9 has been shown to be a more sensitive marker for periodontal inflammation during orthodontic treatment, which opens new perspectives in reducing periodontal hazards during such treatments. Both MMP-8 and MMP-9 are extremely valuable diagnostic tools in treating periodontitis, and future studies and healthcare policies should focus on implementing more accessible methods of chairside testing in order to reduce the prevalence of this disease.
Tumor-Associated Macrophages/Microglia in Glioblastoma Oncolytic Virotherapy: A Double-Edged Sword
Authors: Blitz Sarah E. , Kappel Ari D. , Gessler Florian A. , Klinger Neil V. , Arnaout Omar , Lu Yi , Peruzzi Pier Paolo , Smith Timothy R. , Chiocca Ennio A. , Friedman Gregory K. , Bernstock Joshua D.
Published: February 2022

Oncolytic virotherapy is a rapidly progressing field that uses oncolytic viruses (OVs) to selectively infect malignant cells and cause an antitumor response through direct oncolysis and stimulation of the immune system. Despite demonstrated pre-clinical efficacy of OVs in many cancer types and some favorable clinical results in glioblastoma (GBM) trials, durable increases in overall survival have remained elusive. Recent evidence has emerged that tumor-associated macrophage/microglia (TAM) involvement is likely an important factor contributing to OV treatment failure. It is prudent to note that the relationship between TAMs and OV therapy failures is complex. Canonically activated TAMs (i.e., M1) drive an antitumor response while also inhibiting OV replication and spread. Meanwhile, M2 activated TAMs facilitate an immunosuppressive microenvironment thereby indirectly promoting tumor growth. In this focused review, we discuss the complicated interplay between TAMs and OV therapies in GBM. We review past studies that aimed to maximize effectiveness through immune system modulation—both immunostimulatory and immunosuppressant—and suggest future directions to maximize OV efficacy.
Characterization of Endogenous Levels of Brassinosteroids and Related Genes in Grapevines
Authors: Parada Francisca , Oklestkova Jana , Arce-Johnson Patricio
Published: February 2022

Agronomic breeding practices for grapevines (Vitis vinifera L.) include the application of growth regulators in the field. Brassinosteroids (BRs) are a family of sterol-derived plant hormones that regulate several physiological processes and responses to biotic and abiotic stress. In grapevine berries, the production of biologically active BRs, castasterone and 6-deoxocastasterone, has been reported. In this work, key BR genes were identified, and their expression profiles were determined in grapevine. Bioinformatic homology analyses of the Arabidopsis genome found 14 genes associated with biosynthetic, perception and signaling pathways, suggesting a partial conservation of these pathways between the two species. The tissue- and development-specific expression profiles of these genes were determined by qRT-PCR in nine different grapevine tissues. Using UHPLC-MS/MS, 10 different BR compounds were pinpointed and quantified in 20 different tissues, each presenting specific accumulation patterns. Although, in general, the expression profile of the biosynthesis pathway genes of BRs did not directly correlate with the accumulation of metabolites, this could reflect the complexity of the BR biosynthesis pathway and its regulation. The development of this work thus generates a contribution to our knowledge about the presence, and diversity of BRs in grapevines.
New Strategies for the Treatment of Neuropsychiatric Disorders Based on Reelin Dysfunction
Authors: Tsuneura Yumi , Nakai Tsuyoshi , Mizoguchi Hiroyuki , Yamada Kiyofumi
Published: February 2022

Reelin is an extracellular matrix protein that is mainly produced in Cajal-Retzius cells and controls neuronal migration, which is important for the proper formation of cortical layers in the developmental stage of the brain. In the adult brain, Reelin plays a crucial role in the regulation of N-methyl-D-aspartate receptor-dependent synaptic function, and its expression decreases postnatally. Clinical studies showed reductions in Reelin protein and mRNA expression levels in patients with psychiatric disorders; however, the causal relationship remains unclear. Reelin-deficient mice exhibit an abnormal neuronal morphology and behavior, while Reelin supplementation ameliorates learning deficits, synaptic dysfunctions, and spine loss in animal models with Reelin deficiency. These findings suggest that the neuronal deficits and brain dysfunctions associated with the down-regulated expression of Reelin are attenuated by enhancements in its expression and functions in the brain. In this review, we summarize findings on the role of Reelin in neuropsychiatric disorders and discuss potential therapeutic approaches for neuropsychiatric disorders associated with Reelin dysfunctions.
Melatonin as the Cornerstone of Neuroimmunoendocrinology
Authors: Kvetnoy Igor , Ivanov Dmitry , Mironova Ekaterina , Evsyukova Inna , Nasyrov Ruslan , Kvetnaia Tatiana , Polyakova Victoria
Published: February 2022

Much attention has been recently drawn to studying melatonin – a hormone whose synthesis was first found in the epiphysis (pineal gland). This interest can be due to discovering the role of melatonin in numerous physiological processes. It was the discovery of melatonin synthesis in endocrine organs (pineal gland), neural structures (Purkinje cells in the cerebellum, retinal photoreceptors), and immunocompetent cells (T lymphocytes, NK cells, mast cells) that triggered the evolution of new approaches to the unifield signal regulation of homeostasis, which, at the turn of the 21st century, lead to the creation of a new integral biomedical discipline — neuroimmunoendocrinology. While numerous hormones have been verified over the last decade outside the “classical” locations of their formation, melatonin occupies an exclusive position with regard to the diversity of locations where it is synthesized and secreted. This review provides an overview and discussion of the major data regarding the role of melatonin in various physiological and pathological processes, which affords grounds for considering melatonin as the “cornerstone” on which neuroimmunoendocrinology has been built as an integral concept of homeostasis regulation.
Identification of a Negative Regulator for Salt Tolerance at Seedling Stage via a Genome-Wide Association Study of Thai Rice Populations
Authors: Kojonna Thammaporn , Suttiyut Thiti , Khunpolwattana Nopphakhun , Pongpanich Monnat , Suriya-arunroj Duangjai , Comai Luca , Buaboocha Teerapong , Chadchawan Supachitra
Published: February 2022

Salt stress is a major limiting factor in crop production and yield in many regions of the world. The objective of this study was to identify the genes responsible for salt tolerance in Thai rice populations. We performed a genome-wide association study with growth traits, relative water content, and cell membrane stability at the seedling stage, and predicted 25 putative genes. Eleven of them were located within previously reported salt-tolerant QTLs (ST-QTLs). OsCRN, located outside the ST-QTLs, was selected for gene characterization using the Arabidopsis mutant line with T-DNA insertion in the orthologous gene. Mutations in the AtCRN gene led to the enhancement of salt tolerance by increasing the ability to maintain photosynthetic pigment content and relative water content, while the complemented lines with ectopic expression of OsCRN showed more susceptibility to salt stress detected by photosynthesis performance. Moreover, the salt-tolerant rice varieties showed lower expression of this gene than the susceptible rice varieties under salt stress conditions. The study concludes that by acting as a negative regulator, OsCRN plays an important role in salt tolerance in rice.
The Anxiolytic Drug Buspirone Prevents Rotenone-Induced Toxicity in a Mouse Model of Parkinson’s Disease
Authors: Thomas Broome Sarah , Castorina Alessandro
Published: February 2022

A pharmacological and genetic blockade of the dopamine D3 receptor (D3R) has shown to be neuroprotective in models of Parkinson’s disease (PD). The anxiolytic drug buspirone, a serotonin receptor 1A agonist, also functions as a potent D3R antagonist. To test if buspirone elicited neuroprotective activities, C57BL/6 mice were subjected to rotenone treatment (10mg/kg i.p for 21 days) to induce PD-like pathology and were co-treated with increasing dosages of buspirone (1, 3, or 10 mg/kg i.p.) to determine if the drug could prevent rotenone-induced damage to the central nervous system (CNS). We found that high dosages of buspirone prevented the behavioural deficits caused by rotenone in the open field test. Molecular and histological analyses confirmed that 10 mg/kg of buspirone prevented the degeneration of TH-positive neurons. Buspirone attenuated the induction of interleukin-1β and interleukin-6 expression by rotenone, and this was paralleled by the upregulation of arginase-1, brain-derived neurotrophic factor (BDNF), and activity-dependent neuroprotective protein (ADNP) in the midbrain, striatum, prefrontal cortex, amygdala, and hippocampus. Buspirone treatment also improved mitochondrial function and antioxidant activities. Lastly, the drug prevented the disruptions in the expression of two neuroprotective peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). These results pinpoint the neuroprotective efficacy of buspirone against rotenone toxicity, suggesting its potential use as a therapeutic agent in neurodegenerative and neuroinflammatory diseases, such as PD.
A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics
Authors: Lamptey Richard N. L. , Chaulagain Bivek , Trivedi Riddhi , Gothwal Avinash , Layek Buddhadev , Singh Jagdish
Published: February 2022

Neurodegenerative disorders are primarily characterized by neuron loss. The most common neurodegenerative disorders include Alzheimer’s and Parkinson’s disease. Although there are several medicines currently approved for managing neurodegenerative disorders, a large majority of them only help with associated symptoms. This lack of pathogenesis-targeting therapies is primarily due to the restrictive effects of the blood–brain barrier (BBB), which keeps close to 99% of all “foreign substances” out of the brain. Since their discovery, nanoparticles have been successfully used for targeted delivery into many organs, including the brain. This review briefly describes the pathophysiology of Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis, and their current management approaches. We then highlight the major challenges of brain-drug delivery, followed by the role of nanotherapeutics for the diagnosis and treatment of various neurological disorders.
Evolutionary Analysis of Dipeptidyl Peptidase I
Authors: Varda Nina , Novinec Marko
Published: February 2022

Human dipeptidyl peptidase I (DPPI) belongs to the family of papain-like cysteine peptidases. Its distinctive features are the unique exclusion domain which enables the eponymous activity and homotetramerization of DPPI, and its dependence on chloride ions for enzymatic activity. The oligomeric state of DPPI is unique in this family of predominantly monomeric peptidases. However, a distant DPPI ortholog from Plasmodium falciparum has been shown to be monomeric, indicating that the oligomeric state of DPPI varies between lineages. The aim of this work was to study the evolution of DPPI, with particular attention to the structural features that determine its characteristic enzymatic activity and preferences, and to reconstruct the evolution of its oligomerization. We analyzed fifty-seven selected sequences of DPPI and confirmed its presence in three lineages, namely, Amorphea (including animals and Amoebozoa), Alveolates and the metamonad Giardia. The amino acid residues that bind the chloride ion are highly conserved in all species, indicating that the dependence on chloride ions for activity is an evolutionarily conserved feature of DPPI. The number of N-glycosylation sites is significantly increased in animals, particularly vertebrates. Analysis of homology models and subunit contacts suggests that oligomerization is likely restricted to DPPIs in the Amorphea group.
A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine
Authors: Yun Un-Jung , Bae Su-Jin , Song Yu-Rim , Kim Young-Woo
Published: February 2022

Liver cancer has relatively few early symptoms and is usually diagnosed in the advanced stage. Sorafenib is the only first-line anticancer drug approved by the Food and Drug Administration (FDA) for advanced HCC; however, its use is limited due to resistance. Therefore, the development of new drugs is essential to achieving customized treatment. Many studies have suggested that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) is associated with metastasis and cancer formation and progression in various cancers. In the present study, YAP was overexpressed in various patient-derived hepatocarcinoma (HCC) tissues. In addition, this study examined whether evodiamine (which has anticancer effects) can inhibit YAP and, if so, modulate HCC. Evodiamine significantly reduced both the YAP level and cell growth of HCC in a dose-dependent manner. Biochemical analysis indicated mitochondria dysfunction-mediated apoptosis to be the cause of the reduction in HCC cell growth by evodiamine. YAP was overexpressed in metastatic HCC tissues as well when compared to primary HCC tissues. Migration and invasion analysis showed that evodiamine has anti-metastatic ability on Hep3B and Huh-7 cells and reduces the level of vimentin, an EMT marker. In conclusion, YAP is a critical target in HCC therapy, and evodiamine can be an effective HCC anticancer drug by reducing the YAP level.
Metabolic Reprogramming in Response to Alterations of Mitochondrial DNA and Mitochondrial Dysfunction in Gastric Adenocarcinoma
Authors: Chang Tzu-Ching , Lee Hui-Ting , Pan Siao-Cian , Cho Shih-Han , Cheng Chieh , Ou Liang-Hung , Lin Chia-I , Lin Chen-Sung , Wei Yau-Huei
Published: February 2022

We used gastric cancer cell line AGS and clinical samples to investigate the roles of mitochondrial DNA (mtDNA) alterations and mitochondrial respiratory dysfunction in gastric adenocarcinoma (GAC). A total of 131 clinical samples, including 17 normal gastric mucosa (N-GM) from overweight patients who had received sleeve gastrectomy and 57 paired non-cancerous gastric mucosae (NC-GM) and GAC from GAC patients who had undergone partial/subtotal/total gastrectomy, were recruited to examine the copy number and D310 sequences of mtDNA. The gastric cancer cell line AGS was used with knockdown (KD) mitochondrial transcription factor A (TFAM) to achieve mitochondrial dysfunction through a decrease of mtDNA copy number. Parental (PT), null-target (NT), and TFAM-KD-(A/B/C) represented the parental, control, and TFAM knocked-down AGS cells, respectively. These cells were used to compare the parameters reflecting mitochondrial biogenesis, glycolysis, and cell migration activity. The median mtDNA copy numbers of 17 N-GM, 57 NC-GM, and 57 GAC were 0.058, 0.055, and 0.045, respectively. The trend of decrease was significant (p = 0.030). In addition, GAC had a lower mean mtDNA copy number of 0.055 as compared with the paired NC-GM of 0.078 (p < 0.001). The mean mtDNA copy number ratio (mtDNA copy number of GAC/mtDNA copy number of paired NC-GM) was 0.891. A total of 35 (61.4%) GAC samples had an mtDNA copy number ratio ≤0.804 (p = 0.017) and 27 (47.4%) harbored a D310 mutation (p = 0.047), and these patients had shorter survival time and poorer prognosis. After effective knockdown of TFAM, TFAM-KD-B/C cells expressed higher levels of hexokinase II (HK-II) and v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT, but lower levels of phosphorylated pyruvate dehydrogenase (p-PDH) than did the NT/PT AGS cells. Except for a higher level of p-PDH, the expression levels of these proteins remained unchanged in TFAM-KD-A, which had a mild knockdown of TFAM. Compared to those of NT, TFAM-KD-C had not only a lower mtDNA copy number (p = 0.050), but also lower oxygen consumption rates (OCR), including basal respiration (OCRBR), ATP-coupled respiration (OCRATP), reserve capacity (OCRRC), and proton leak (OCRPL)(all with p = 0.050). In contrast, TFAM-KD-C expressed a higher extracellular acidification rate (ECAR)/OCRBR ratio (p = 0.050) and a faster wound healing migration at 6, 12, and 18 h, respectively (all with p = 0.050). Beyond a threshold, the decrease in mtDNA copy number, the mtDNA D310 mutation, and mitochondrial dysfunction were involved in the carcinogenesis and progression of GACs. Activation of PDH might be considered as compensation for the mitochondrial dysfunction in response to glucose metabolic reprogramming or to adjust mitochondrial plasticity in GAC.
T-Cell-Specific CerS4 Depletion Prolonged Inflammation and Enhanced Tumor Burden in the AOM/DSS-Induced CAC Model
Authors: El-Hindi Khadija , Brachtendorf Sebastian , Hartel Jennifer Christina , Oertel Stephanie , Birod Kerstin , Merz Nadine , Trautmann Sandra , Thomas Dominique , Weigert Andreas , Schäufele Tim J. , Scholich Klaus , Schiffmann Susanne , Ulshöfer Thomas , Utermöhlen Olaf , Grösch Sabine
Published: February 2022

To better understand the role of sphingolipids in the multifactorial process of inflammatory bowel disease (IBD), we elucidated the role of CerS4 in colitis and colitis-associated cancer (CAC). For this, we utilized the azoxymethane/dextran sodium sulphate (AOM/DSS)-induced colitis model in global CerS4 knockout (CerS4 KO), intestinal epithelial (CerS4 Vil/Cre), or T-cell restricted knockout (CerS4 LCK/Cre) mice. CerS4 KO mice were highly sensitive to the toxic effect of AOM/DSS, leading to a high mortality rate. CerS4 Vil/Cre mice had smaller tumors than WT mice. In contrast, CerS4 LCK/Cre mice frequently suffered from pancolitis and developed more colon tumors. In vitro, CerS4-depleted CD8+ T-cells isolated from the thymi of CerS4 LCK/Cre mice showed impaired proliferation and prolonged cytokine production after stimulation in comparison with T-cells from WT mice. Depletion of CerS4 in human Jurkat T-cells led to a constitutively activated T-cell receptor and NF-κB signaling pathway. In conclusion, the deficiency of CerS4 in T-cells led to an enduring active status of these cells and prevents the resolution of inflammation, leading to a higher tumor burden in the CAC mouse model. In contrast, CerS4 deficiency in epithelial cells resulted in smaller colon tumors and seemed to be beneficial. The higher tumor incidence in CerS4 LCK/Cre mice and the toxic effect of AOM/DSS in CerS4 KO mice exhibited the importance of CerS4 in other tissues and revealed the complexity of general targeting CerS4.
Structural and Functional Differences between Homologous Bacterial Ribonucleases
Authors: Ulyanova Vera , Nadyrova Alsu , Dudkina Elena , Kuznetsova Aleksandra , Ahmetgalieva Albina , Faizullin Dzhigangir , Surchenko Yulia , Novopashina Darya , Zuev Yuriy , Kuznetsov Nikita , Ilinskaya Olga
Published: February 2022

Small cationic guanyl-preferring ribonucleases (RNases) produced by the Bacillus species share a similar protein tertiary structure with a high degree of amino acid sequence conservation. However, they form dimers that differ in conformation and stability. Here, we have addressed the issues (1) whether the homologous RNases also have distinctions in catalytic activity towards different RNA substrates and interactions with the inhibitor protein barstar, and (2) whether these differences correlate with structural features of the proteins. Circular dichroism and dynamic light scattering assays revealed distinctions in the structures of homologous RNases. The activity levels of the RNases towards natural RNA substrates, as measured spectrometrically by acid-soluble hydrolysis products, were similar and decreased in the row high-polymeric RNA >>> transport RNA > double-stranded RNA. However, stopped flow kinetic studies on model RNA substrates containing the guanosine residue in a hairpin stem or a loop showed that the cleavage rates of these enzymes were different. Moreover, homologous RNases were inhibited by the barstar with diverse efficiency. Therefore, minor changes in structure elements of homologous proteins have a potential to significantly effect molecule stability and functional activities, such as catalysis or ligand binding.