bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Educational Technology on Teacher Stress and Anxiety: A Literature Review
Authors: Fernández-Batanero José-María , Román-Graván Pedro , Reyes-Rebollo Miguel-María , Montenegro-Rueda Marta
Published: January 2021

Educational technology has become an increasingly important element for improving the teaching and learning process of students. To achieve these goals, it is essential that teachers have the skills they need to be able to introduce technology into their teaching practice. However, this is often overwhelming and stressful for many of them. The aim of this review was to find out how research on teacher stress and anxiety associated with the use of educational technology was proceeding. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through the following bibliographic databases: PubMed, Web of Science, and Scopus. Sixteen articles were found from the review. The main findings show that teachers present high levels of anxiety or stress due to their use of educational technology in the classroom. Among the conclusions, the need for research on different strategies to prevent the emergence of these anxiety and stress symptoms in teachers stands out.
Within-Person Variation of Affective Well-Being during and after Exercise: Does the Person–Exercise Fit Matter?
Authors: Schmid Julia , Gut Vanessa , Schorno Nina , Yanagida Takuya , Conzelmann Achim
Published: January 2021

Affective well-being is positively linked to regular exercise. Therefore, it is important to identify the factors that influence intra-individual variability of affective well-being. This study investigated (1) whether affective responses vary within an individual and (2) how affective responses are associated with a motive–incentive fit and a skill–task fit. A total of 107 adults (66% females, Mage = 41.79 years old, 58% doing no exercise) took part in three exercise sessions in a random order. Each session lasted 30 min with a break of 10 min between. The sessions were similarly structured but covered diverse activity incentives (e.g., figure vs. social contact vs. aesthetic movements). Intraclass correlation coefficients showed a very high within-person variation of affective valence and enjoyment across the exercise sessions. The results of multi-level regression analyses revealed that associations between perceived competence, considered to be an indicator of the skill–task fit, and affective well-being were moderate to high, whereas those between motive–incentive fit and affective well-being were low to moderate.
A Serial-Mediation Model to Link Entrepreneurship Education and Green Entrepreneurial Behavior: Application of Resource-Based View and Flow Theory
Authors: Hameed Irfan , Zaman Umer , Waris Idrees , Shafique Owais
Published: January 2021

Eco-conscious behaviors have become a global imperative for entrepreneurs, as the consumer demand for products and services has become increasingly green. Hence, the purpose of this study is to identify the role of entrepreneurship education in environmental sustainability as measured by the launch of green ventures. This study also aims at extending the literature of resource-based view and flow theory by highlighting their application into the green venturing context. Data were collected from 420 Pakistani students having studied an entrepreneurship course in their university life by using the convenience sampling technique. The covariance based structural equation modeling (CB-SEM) was used to test the hypothesized relationships, and it was identified that entrepreneurship education evokes commitment to the environment, subsequently leading towards university green entrepreneurial support, environmental motivation, and green entrepreneurial behavior. University green entrepreneurial support also significantly influences green venturing; however, environmental motivation does not affect green entrepreneurial behavior. The findings of this study can be useful for policymakers in higher educational institutions, regulatory bodies, and diverse-government agencies dealing with UN sustainable development goals.
“Enticing” but Not Necessarily a “Space Designed for Me”: Experiences of Urban Park Use by Older Adults with Disability
Authors: Perry Meredith , Cotes Lucy , Horton Benjamin , Kunac Rebecca , Snell Isaac , Taylor Blake , Wright Abbey , Devan Hemakumar
Published: January 2021

Urban parks are spaces that can enhance older adults’ physical, social and psychological wellbeing. As the prevalence of older adults with disability increases, it is important that urban parks are accessible to this population so that they too might gain health benefits. There is limited literature investigating the experiences of urban parks by older adults with disability. This qualitative study, set in a region of New Zealand, explored the experiences, including accessibility, of urban parks by 17 older adults (55 years and older) with self-reported disabilities. Three focus groups (n = 4, 5 and 4 people) and four individual interviews were undertaken. Data were analyzed using the General Inductive Approach. Two primary themes of “Enticing” and “Park use considerations” are presented. Urban parks and green spaces are perceived to provide an environment for older adults with a disability to improve their physical, psychosocial and spiritual health, and social connectedness. Parks that are not age, ability or culture diverse are uninviting and exclusive. Meaningful collaboration between park designers, city councils and people with disability is required to maximize the public health benefits of parks and make parks inviting and accessible for users of all ages, cultures and abilities. Park co-design with people with disability may provide one means of improving accessibility and park usability and thus park participation by older adults with disability.
Evaluation of China’s High-Speed Rail Station Development and Nearby Human Activity Based on Nighttime Light Images
Authors: Du Zhenyu , Wu Wei , Liu Yongxue , Zhi Weifeng , Lu Wanyun
Published: January 2021

High-speed rail (HSR) represents China’s advancing productivity; however, quite a few HSR stations face problems due to inappropriate planning and limited passenger flow. To optimize future planning on HSR lines and stations and facilitate efficient operation, we used brightness as a representative of station development and nearby human activity, analyzing its spatial and temporal distribution, classification categories, and influencing factors of 980 stations using nighttime light images from 2012 to 2019. The following conclusions were drawn: (1) There are 41 stations with high brightness between 80 and 320 nW·cm−2·sr−1, which are concentrated in provincial capitals, large cities, and at line ends. The overall number of these stations increases by 57% in the past eight years. (2) Stations with high brightness but minimal changes that opened in 2013–2019 are mainly concentrated in provincial capitals and large- or medium-sized cities, and those with high brightness and significant changes are mostly new stations nearby. More than 70% of stations that started HSR operation before or in 2012 have high brightness. (3) Brightness positively correlates with the number of daily trains, and it changes faster at stations with more daily trains. It changes most within 0–1 year after HSR operation opening and exhibits a relatively slow but long-term increase over the next 2–6 years.
Assessing the Effects of Land Use on Surface Water Quality in the Lower uMfolozi Floodplain System, South Africa
Authors: Dlamini Mandla , Chirima George , Jovanovic Nebo , Adam Elhadi
Published: January 2021

This study investigated the impacts of cultivation on water and soil quality in the lower uMfolozi floodplain system in KwaZulu-Natal province, South Africa. We did this by assessing seasonal variations in purposefully selected water and soil properties in these two land-use systems. The observed values were statistically analysed by performing Student’s paired t-tests to determine seasonal trends in these variables. Results revealed significant seasonal differences in chloride and sodium concentrations and electrical conductivity (EC) and the sodium adsorption ratio (SAR) with cultivated sites exhibiting higher values. Most of the analyzed chemical parameters were within acceptable limits specified by the South African agricultural-water-quality (SAWQ) water quality guidelines for irrigation except for sodium adsorption ratio (SAR), chloride, sodium and EC. EC, pH and nitrate content which were higher than the specified SAWQ limits in cultivated sites. Quantities of glyphosate, ametryn and imidacloprid could not be measured because they were below detectable limits. The study concludes that most water quality parameters met SAWQ’s standards. These results argue for concerted efforts to systematically monitor water and soil quality characteristics in this environment to enhance sustainability by providing timely information for management purposes.
Experiences of Parental Suicide-Bereavement: A Longitudinal Qualitative Analysis over Two Years
Authors: Entilli Lorenza , Ross Victoria , De Leo Diego , Cipolletta Sabrina , Kõlves Kairi
Published: January 2021

Limited research exists on the experiences of parents bereaved by suicide. Our earlier qualitative analysis examined the experiences of parents’ suicide bereavement at 6 and 12 months after their loss. The current study aimed to extend the analysis over 24 months, outlining the key themes of parents’ suicide bereavement experience. In the frames of a longitudinal study of suicide bereavement in Queensland, Australia, parents were interviewed at 6, 12, and 24 months after their loss. Thematic analysis was used to further explore new themes and three key themes identified in earlier analyses: searching for answers and sense-making, coping strategies and support, and finding meaning and purpose. Results at 24 months revealed a clearer differentiation between strategies adopted by mothers and fathers. Anger and blame had changed towards feelings of depression. A polarization was observed between parents still oscillating in brooding rumination and those who have shifted towards sense-making. The former more frequently reported depression symptoms, and the latter reported a more positive attitude towards life and acceptance of their loss. Consistent with the dual-process model, parents managed to reach acceptance after oscillating between sense-making and meaning making. Findings provide insights how suicide loss affects parents, with implications for postvention.
Analysis of Differences in the Spatial Distribution among Terrestrial Mammals Using Geodetector—A Case Study of China
Authors: Chi Yao , Qian Tianlu , Sheng Caiying , Xi Changbai , Wang Jiechen
Published: January 2021

The survival and distribution of animals cannot be separated from a certain environment. How patterns in mammalian species depend on the environment remain unclear. This study incorporating spatial data on climate, precipitation, topography, and vegetation quantitatively analyzed the influence of specific geographical factors on the spatial distribution of terrestrial mammalian richness using the Geodetector model. We used the spatial analysis method of geographical information systems (GIS), separating the mammalian distribution of 621 species into 10 by 10 km grids to measure spatial richness. Our results showed that there were significant spatial differences in terrestrial mammalian richness in China. There was a low richness in the east and west, but high richness in the south. Individual factor detection results showed that annual precipitation (AP) and the minimum temperature of the coldest month (MTCM) were the dominant factors affecting the spatial pattern of mammal richness in China. Patterns in the distribution of species richness had distinct characteristics for different mammalian orders and were influenced by different environmental factors. The richness distribution of most orders was mainly affected by MTCM and AP. Interactive detection results showed that interacting factors in pairs play much bigger roles in the spatial distribution of species richness than individual factors. The synergistic effect of elevation with AP and MTCM best explained the distribution differences of species richness. We found that the Geodetector model is a valuable tool, hoping to be more widely used in biogeography.
Post-Translational Modifications of Nitrate Reductases Autoregulates Nitric Oxide Biosynthesis in Arabidopsis
Authors: Costa-Broseta Álvaro , Castillo MariCruz , León José
Published: January 2021

Nitric oxide (NO) is a regulator of growth, development, and stress responses in living organisms. Plant nitrate reductases (NR) catalyze the reduction of nitrate to nitrite or, alternatively, to NO. In plants, NO action and its targets remain incompletely understood, and the way NO regulates its own homeostasis remains to be elucidated. A significant transcriptome overlapping between NO-deficient mutant and NO-treated wild type plants suggests that NO could negatively regulate its biosynthesis. A significant increase in NO content was detected in transgenic plants overexpressing NR1 and NR2 proteins. In turn, NR protein and activity as well as NO content, decreased in wild-type plants exposed to a pulse of NO gas. Tag-aided immunopurification procedures followed by tandem mass spectrometry allowed identifying NO-triggered post-translational modifications (PTMs) and ubiquitylation sites in NRs. Nitration of tyrosine residues and S-nitrosation of cysteine residues affected key amino acids involved in binding the essential FAD and molybdenum cofactors. NO-related PTMs were accompanied by ubiquitylation of lysine residues flanking the nitration and S-nitrosation sites. NO-induced PTMs of NRs potentially inhibit their activities and promote their proteasome-mediated degradation. This auto-regulatory feedback loop may control nitrate assimilation to ammonium and nitrite-derived production of NO under complex environmental conditions.
Candidate Effectors from Botryosphaeria dothidea Suppress Plant Immunity and Contribute to Virulence
Authors: Zhang Chuan-Jie , Wang Shi-Xing , Liang Yan-Na , Wen Sheng-Hui , Dong Bao-Zhu , Ding Zheng , Guo Li-Yun , Zhu Xiao-Qiong
Published: January 2021

Fungal effectors play important roles in host–pathogen interactions. Botryosphaeria dothidea is an ascomycetous fungus that is responsible for the diseases of hundreds of woody plant species, including apple ring rot, which seriously affects apples worldwide. However, little is known about the effectors of B. dothidea. In this study, we analyzed the B. dothidea genome and predicted 320 candidate effector genes, 124 of which were successfully amplified and cloned. We investigated the effects of these genes on plant cell death in Nicotiana benthamiana while using a transient expression system. Twenty-four hours after initial inoculation with Agrobacterium tumefaciens cells carrying candidate effectors, the infiltrated leaves were challenged with A. tumefaciens cells carrying the BAX gene. In total, 116 candidate effectors completely inhibited, while one partially inhibited, the programmed cell death (PCD) of N. benthamiana induced by BAX, whereas seven candidate effectors had no effect. We then further tested seven candidate effectors able to suppress BAX-triggered PCD (BT-PCD) and found that they all completely inhibited PCD triggered by the elicitors INF1, MKK1, and NPK1. This result suggests that these effectors were activated in order to suppress pathogen-associated molecular pattern-triggered immunity. The signal peptides of these candidate effectors exhibited secretory activity in yeast (pSUC2 vector). Moreover, the respective deletion of Bdo_11198 and Bdo_12090 significantly reduced the virulence of B. dothidea. These results suggest that these effectors play important roles in the interaction of B. dothidea with its hosts.
Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation
Authors: Cappiello Floriana , Carnicelli Veronica , Casciaro Bruno , Mangoni Maria Luisa
Published: January 2021

Persistent infections, such as those provoked by the Gram-negative bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) patients, can induce inflammation with lung tissue damage and progressive alteration of respiratory function. Therefore, compounds having both antimicrobial and immunomodulatory activities are certainly of great advantage in fighting infectious diseases and chronic inflammation. We recently demonstrated the potent antipseudomonal efficacy of the antimicrobial peptide (AMP) Esc(1-21) and its diastereomer Esc(1-21)-1c, namely Esc peptides. Here, we confirmed this antimicrobial activity by reporting on the peptides’ ability to kill P. aeruginosa once internalized into alveolar epithelial cells. Furthermore, by means of enzyme-linked immunosorbent assay and Western blot analyses, we investigated the peptides’ ability to detoxify the bacterial lipopolysaccharide (LPS) by studying their effects on the secretion of the pro-inflammatory cytokine IL-6 as well as on the expression of cyclooxygenase-2 from macrophages activated by P. aeruginosa LPS. In addition, by a modified scratch assay we showed that both AMPs are able to stimulate the closure of a gap produced in alveolar epithelial cells when cell migration is inhibited by concentrations of Pseudomonas LPS that mimic lung infection conditions, suggesting a peptide-induced airway wound repair. Overall, these results have highlighted the two Esc peptides as valuable candidates for the development of new multifunctional therapeutics for treatment of chronic infectious disease and inflammation, as found in CF patients.
Genetics and Pathogenetic Role of Inflammasomes in Philadelphia Negative Chronic Myeloproliferative Neoplasms: A Narrative Review
Authors: Di Battista Valeria , Bochicchio Maria Teresa , Giordano Giulio , Napolitano Mariasanta , Lucchesi Alessandro
Published: January 2021

The last decade has been very important for the quantity of preclinical information obtained regarding chronic myeloproliferative neoplasms (MPNs) and the following will be dedicated to the translational implications of the new biological acquisitions. The overcoming of the mechanistic model of clonal evolution and the entry of chronic inflammation and dysimmunity into the new model are the elements on which to base a part of future therapeutic strategies. The innate immune system plays a major role in this context. Protagonists of the initiation and regulation of many pathological aspects, from cytokine storms to fibrosis, the NLRP3 and AIM2 inflammasomes guide and condition the natural history of the disease. For this reason, MPNs share many biological and clinical aspects with non-neoplastic diseases, such as autoimmune disorders. Finally, cardiovascular risk and disturbances in iron metabolism and myelopoiesis are also closely linked to the role of inflammasomes. Although targeted therapies are already being tested, an increase in knowledge on the subject is desirable and potentially translates into better care for patients with MPNs.
Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle
Authors: Rajavel Abirami , Schmitt Armin Otto , Gültas Mehmet
Published: January 2021

African Animal Trypanosomiasis (AAT) is transmitted by the tsetse fly which carries pathogenic trypanosomes in its saliva, thus causing debilitating infection to livestock health. As the disease advances, a multistage progression process is observed based on the progressive clinical signs displayed in the host’s body. Investigation of genes expressed with regular monotonic patterns (known as Monotonically Expressed Genes (MEGs)) and of their master regulators can provide important clue for the understanding of the molecular mechanisms underlying the AAT disease. For this purpose, we analysed MEGs for three tissues (liver, spleen and lymph node) of two cattle breeds, namely trypanosusceptible Boran and trypanotolerant N’Dama. Our analysis revealed cattle breed-specific master regulators which are highly related to distinguish the genetic programs in both cattle breeds. Especially the master regulators MYC and DBP found in this study, seem to influence the immune responses strongly, thereby susceptibility and trypanotolerance of Boran and N’Dama respectively. Furthermore, our pathway analysis also bolsters the crucial roles of these master regulators. Taken together, our findings provide novel insights into breed-specific master regulators which orchestrate the regulatory cascades influencing the level of trypanotolerance in cattle breeds and thus could be promising drug targets for future therapeutic interventions.
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes
Authors: Amaral Lorena M. , Sandrim Valeria C. , Kutcher Matthew E. , Spradley Frank T. , Cavalli Ricardo C. , Tanus-Santos Jose E. , Palei Ana C.
Published: January 2021

Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE). Total DNA was extracted from plasma using the QIAamp DNA blood mini kit and quantified using Quant-iT™ PicoGreen® dsDNA fluorescent detection kit. We found higher total cfDNA levels in GH and PE (197.0 and 174.2 ng/mL, respectively) than in HP (140.5 ng/mL; both p < 0.0001). Interestingly, total cfDNA levels were elevated in both male and female-bearing pregnancies diagnosed with either HDP, and in more severe versus less severe HDP cases, as classified according to responsiveness to antihypertensive therapy. In addition, total cfDNA was independently associated with HDP, and a cutoff concentration of 160 ng/mL provided appropriate sensitivity and specificity values for diagnosing GH and PE compared to HP (70–85%, both p < 0.0001). Moreover, high total cfDNA was associated with adverse clinical outcomes (high blood pressure, low platelet count, preterm delivery, fetal growth restriction) and high prohypertensive factors (sFLT-1, sEndoglin, MMP-2). These findings represent a step towards to the establishment of cfDNA as a diagnostic tool and the need to understand its role in HDP.
Ectopic Expression of CrPIP2;3, a Plasma Membrane Intrinsic Protein Gene from the Halophyte Canavalia rosea, Enhances Drought and Salt-Alkali Stress Tolerance in Arabidopsis
Authors: Zheng Jiexuan , Lin Ruoyi , Pu Lin , Wang Zhengfeng , Mei Qiming , Zhang Mei , Jian Shuguang
Published: January 2021

Aquaporins are channel proteins that facilitate the transmembrane transport of water and other small neutral molecules, thereby playing vital roles in maintaining water and nutrition homeostasis in the life activities of all organisms. Canavalia rosea, a seashore and mangrove-accompanied halophyte with strong adaptability to adversity in tropical and subtropical regions, is a good model for studying the molecular mechanisms underlying extreme saline-alkaline and drought stress tolerance in leguminous plants. In this study, a PIP2 gene (CrPIP2;3) was cloned from C. rosea, and its expression patterns and physiological roles in yeast and Arabidopsis thaliana heterologous expression systems under high salt-alkali and high osmotic stress conditions were examined. The expression of CrPIP2;3 at the transcriptional level in C. rosea was affected by high salinity and alkali, high osmotic stress, and abscisic acid treatment. In yeast, the expression of CrPIP2;3 enhanced salt/osmotic and oxidative sensitivity under high salt/osmotic and H2O2 stress. The overexpression of CrPIP2;3 in A. thaliana could enhance the survival and recovery of transgenic plants under drought stress, and the seed germination and seedling growth of the CrPIP2;3 OX (over-expression) lines showed slightly stronger tolerance to high salt/alkali than the wild-type. The transgenic plants also showed a higher response level to high-salinity and dehydration than the wild-type, mostly based on the up-regulated expression of salt/dehydration marker genes in A. thaliana plants. The reactive oxygen species (ROS) staining results indicated that the transgenic lines did not possess stronger ROS scavenging ability and stress tolerance than the wild-type under multiple stresses. The results confirmed that CrPIP2;3 is involved in the response of C. rosea to salt and drought, and primarily acts by mediating water homeostasis rather than by acting as an ROS transporter, thereby influencing physiological processes under various abiotic stresses in plants.
The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification
Authors: Wells Carrow I. , Al-Ali Hassan , Andrews David M. , Asquith Christopher R. M. , Axtman Alison D. , Dikic Ivan , Ebner Daniel , Ettmayer Peter , Fischer Christian , Frederiksen Mathias , Futrell Robert E. , Gray Nathanael S. , Hatch Stephanie B. , Knapp Stefan , Lücking Ulrich , Michaelides Michael , Mills Caitlin E. , Müller Susanne , Owen Dafydd , Picado Alfredo , Saikatendu Kumar S. , Schröder Martin , Stolz Alexandra , Tellechea Mariana , Turunen Brandon J. , Vilar Santiago , Wang Jinhua , Zuercher William J. , Willson Timothy M. , Drewry David H.
Published: January 2021

We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Molecular Analysis of 14-3-3 Genes in Citrus sinensis and Their Responses to Different Stresses
Authors: Lyu Shiheng , Chen Guixin , Pan Dongming , Chen Jianjun , She Wenqin
Published: January 2021

14-3-3 proteins (14-3-3s) are among the most important phosphorylated molecules playing crucial roles in regulating plant development and defense responses to environmental constraints. No report thus far has documented the gene family of 14-3-3s in Citrus sinensis and their roles in response to stresses. In this study, nine 14-3-3 genes, designated as CitGF14s (CitGF14a through CitGF14i) were identified from the latest C. sinensis genome. Phylogenetic analysis classified them into ε-like and non-ε groups, which were supported by gene structure analysis. The nine CitGF14s were located on five chromosomes, and none had duplication. Publicly available RNA-Seq raw data and microarray databases were mined for 14-3-3 expression profiles in different organs of citrus and in response to biotic and abiotic stresses. RT-qPCR was used for further examining spatial expression patterns of CitGF14s in citrus and their temporal expressions in one-year-old C. sinensis “Xuegan” plants after being exposed to different biotic and abiotic stresses. The nine CitGF14s were expressed in eight different organs with some isoforms displayed tissue-specific expression patterns. Six of the CitGF14s positively responded to citrus canker infection (Xanthomonas axonopodis pv. citri). The CitGF14s showed expressional divergence after phytohormone application and abiotic stress treatments, suggesting that 14-3-3 proteins are ubiquitous regulators in C. sinensis. Using the yeast two-hybrid assay, CitGF14a, b, c, d, g, and h were found to interact with CitGF14i proteins to form a heterodimer, while CitGF14i interacted with itself to form a homodimer. Further analysis of CitGF14s co-expression and potential interactors established a 14-3-3s protein interaction network. The established network identified 14-3-3 genes and several candidate clients which may play an important role in developmental regulation and stress responses in this important fruit crop. This is the first study of 14-3-3s in citrus, and the established network may help further investigation of the roles of 14-3-3s in response to abiotic and biotic constraints.
A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism
Authors: Cros-Brunsó Laia , Camacho-Rodríguez Laura , Martínez-González Ángel , Llévenes Pablo , Salaices Mercedes , García-Redondo Ana Belen , Blanco-Rivero Javier
Published: January 2021

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT. In segments from the superior mesenteric artery, the application of an electrical field stimulation (EFS) induced a vasoconstrictor response, which was lower in arteries from HT animals. The alpha-adrenoceptor antagonist phentolamine diminished EFS-induced vasoconstriction to a lower extent in HT arteries, while the purinergic receptor antagonist suramin reduced contractile response to EFS only in segments from CT. In line with this, noradrenaline release, tyrosine hydroxylase expression and activation and dopamine β hydroxylase expression were diminished in HT. The unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in segments from HT rats. NO release was enhanced in HT, probably due to an enhancement in neuronal NOS activity, in which a hyperactivation of both PKC and PI3K-AKT signaling pathways might play a relevant role. In conclusion, perivascular mesenteric innervation might contribute to reduce the vascular resistance observed in hyperthyroidism.
Effect of Sulfonamides and Their Structurally Related Derivatives on the Activity of ι-Carbonic Anhydrase from Burkholderia territorii
Authors: De Luca Viviana , Petreni Andrea , Nocentini Alessio , Scaloni Andrea , Supuran Claudiu T. , Capasso Clemente
Published: January 2021

Carbonic anhydrases (CAs) are essential metalloenzymes in nature, catalyzing the carbon dioxide reversible hydration into bicarbonate and proton. In humans, breathing and many other critical physiological processes depend on this enzymatic activity. The CA superfamily function and inhibition in pathogenic bacteria has recently been the object of significant advances, being demonstrated to affect microbial survival/virulence. Targeting bacterial CAs may thus be a valid alternative to expand the pharmacological arsenal against the emergence of widespread antibiotic resistance. Here, we report an extensive study on the inhibition profile of the recently discovered ι-CA class present in some bacteria, including Burkholderia territorii, namely BteCAι, using substituted benzene-sulfonamides and clinically licensed sulfonamide-, sulfamate- and sulfamide-type drugs. The BteCAι inhibition profile showed: (i) several benzene-sulfonamides with an inhibition constant lower than 100 nM; (ii) a different behavior with respect to other α, β and γ-CAs; (iii) clinically used drugs having a micromolar affinity. This prototype study contributes to the initial recognition of compounds which efficiently and selectively inhibit a bacterial member of the ι-CA class, for which such a selective inhibition with respect to other protein isoforms present in the host is highly desired and may contribute to the development of novel antimicrobials.
Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review
Authors: Lavorato Andrea , Raimondo Stefania , Boido Marina , Muratori Luisa , Durante Giorgia , Cofano Fabio , Vincitorio Francesca , Petrone Salvatore , Titolo Paolo , Tartara Fulvio , Vercelli Alessandro , Garbossa Diego
Published: January 2021

Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords “nerve regeneration”, “stem cells”, “peripheral nerve injury”, “rat”, and “human” were used. Additionally, a “MeSH” research was performed in PubMed using the terms “stem cells” and “nerve regeneration”. The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.
The Resistance of Narrow-Leafed Lupin to Diaporthe toxica Is Based on the Rapid Activation of Defense Response Genes
Authors: Książkiewicz Michał , Rychel-Bielska Sandra , Plewiński Piotr , Nuc Maria , Irzykowski Witold , Jędryczka Małgorzata , Krajewski Paweł
Published: January 2021

Narrow-leafed lupin (Lupinus angustifolius L.) is a grain legume crop that is advantageous in animal nutrition due to its high protein content; however, livestock grazing on stubble may develop a lupinosis disease that is related to toxins produced by a pathogenic fungus, Diaporthe toxica. Two major unlinked alleles, Phr1 and PhtjR, confer L. angustifolius resistance to this fungus. Besides the introduction of these alleles into modern cultivars, the molecular mechanisms underlying resistance remained unsolved. In this study, resistant and susceptible lines were subjected to differential gene expression profiling in response to D. toxica inoculation, spanning the progress of the infection from the early to latent phases. High-throughput sequencing of stem transcriptome and PCR quantification of selected genes were performed. Gene Ontology term analysis revealed that an early (24 h) response in the resistant germplasm encompassed activation of genes controlling reactive oxygen species and oxylipin biosynthesis, whereas in the susceptible germplasm, it comprised induction of xyloglucan endotransglucosylases/hydrolases. During the first five days of the infection, the number of genes with significantly altered expressions was about 2.6 times higher in resistant lines than in the susceptible line. Global transcriptome reprogramming involving the activation of defense response genes occurred in lines conferring Phr1 and PhtjR resistance alleles about 4–8 days earlier than in the susceptible germplasm.
Colistin Dependence in Extensively Drug-Resistant Acinetobacter baumannii Strain Is Associated with ISAjo2 and ISAba13 Insertions and Multiple Cellular Responses
Authors: Chamoun Sherley , Welander Jenny , Martis-Thiele Mihaela-Maria , Ntzouni Maria , Claesson Carina , Vikström Elena , Turkina Maria V.
Published: January 2021

The nosocomial opportunistic Gram-negative bacterial pathogen Acinetobacter baumannii is resistant to multiple antimicrobial agents and an emerging global health problem. The polymyxin antibiotic colistin, targeting the negatively charged lipid A component of the lipopolysaccharide on the bacterial cell surface, is often considered as the last-resort treatment, but resistance to colistin is unfortunately increasing worldwide. Notably, colistin-susceptible A. baumannii can also develop a colistin dependence after exposure to this drug in vitro. Colistin dependence might represent a stepping stone to resistance also in vivo. However, the mechanisms are far from clear. To address this issue, we combined proteogenomics, high-resolution microscopy, and lipid profiling to characterize and compare A. baumannii colistin-susceptible clinical isolate (Ab-S) of to its colistin-dependent subpopulation (Ab-D) obtained after subsequent passages in moderate colistin concentrations. Incidentally, in the colistin-dependent subpopulation the lpxA gene was disrupted by insertion of ISAjo2, the lipid A biosynthesis terminated, and Ab-D cells displayed a lipooligosaccharide (LOS)-deficient phenotype. Moreover, both mlaD and pldA genes were perturbed by insertions of ISAjo2 and ISAba13, and LOS-deficient bacteria displayed a capsule with decreased thickness as well as other surface imperfections. The major changes in relative protein abundance levels were detected in type 6 secretion system (T6SS) components, the resistance-nodulation-division (RND)-type efflux pumps, and in proteins involved in maintenance of outer membrane asymmetry. These findings suggest that colistin dependence in A. baumannii involves an ensemble of mechanisms seen in resistance development and accompanied by complex cellular events related to insertional sequences (ISs)-triggered LOS-deficiency. To our knowledge, this is the first study demonstrating the involvement of ISAjo2 and ISAba13 IS elements in the modulation of the lipid A biosynthesis and associated development of dependence on colistin.
Marine Collagen Hydrolysates Downregulate the Synthesis of Pro-Catabolic and Pro-Inflammatory Markers of Osteoarthritis and Favor Collagen Production and Metabolic Activity in Equine Articular Chondrocyte Organoids
Authors: Bourdon Bastien , Contentin Romain , Cassé Frédéric , Maspimby Chloé , Oddoux Sarah , Noël Antoine , Legendre Florence , Gruchy Nicolas , Galéra Philippe
Published: January 2021

Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen® hydrolyzed fish collagens from skin (Promerim®30 and Promerim®60) and cartilage (Promerim®40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cytotoxicity and the beneficial effect of Promerim® hydrolysates on eAC metabolic activity under physioxia; further, Promerim®30 also delayed eAC senescence. To assess the effect of Promerim® in a cartilage-like tissue, eACs were cultured as organoids under hypoxia with or without BMP-2 and/or IL-1β. In some instances, alone or in the presence of IL-1β, Promerim®30 and Promerim®40 increased protein synthesis of collagen types I and II, while decreasing transcript levels of proteases involved in OA pathogenesis, namely Htra1, and the metalloproteinases Mmp1-3, Adamts5, and Cox2. Both Promerim® hydrolysates also decreased Htra1 protein amounts, particularly in inflammatory conditions. The effect of Promerim® was enhanced under inflammatory conditions, possibly due to a decrease in the synthesis of inflammation-associated molecules. Finally, Promerim® favored in vitro repair in a scratch wound assay through an increase in cell proliferation or migration. Altogether, these data show that Promerim®30 and 40 hold promise as dietary supplements to relieve OA symptoms in patients and to delay OA progression.
Extracellular Vesicles from Airway Secretions: New Insights in Lung Diseases
Authors: Pastor Laura , Vera Elisabeth , Marin Jose M. , Sanz-Rubio David
Published: January 2021

Lung diseases (LD) are one of the most common causes of death worldwide. Although it is known that chronic airway inflammation and excessive tissue repair are processes associated with LD such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), their specific pathways remain unclear. Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles with an important role in cell-to-cell communication. EVs are present in general biofluids as plasma or urine but also in secretions of the airway as bronchoalveolar lavage fluid (BALF), induced sputum (IS), nasal lavage (NL) or pharyngeal lavage. Alterations of airway EV cargo could be crucial for understanding LD. Airway EVs have shown a role in the pathogenesis of some LD such as eosinophil increase in asthma, the promotion of lung cancer in vitro models in COPD and as biomarkers to distinguishing IPF in patients with diffuse lung diseases. In addition, they also have a promising future as therapeutics for LD. In this review, we focus on the importance of airway secretions in LD, the pivotal role of EVs from those secretions on their pathophysiology and their potential for biomarker discovery.
Differential Interactions of Chiral Nanocapsules with DNA
Authors: Zoabi Amani , Margulis Katherine
Published: January 2021

(1) Background: Chiral nanoparticular systems have recently emerged as a compelling platform for investigating stereospecific behavior at the nanoscopic level. We describe chiroselective supramolecular interactions that occur between DNA oligonucleotides and chiral polyurea nanocapsules. (2) Methods: We employ interfacial polyaddition reactions between toluene 2,4-diisocyanate and lysine enantiomers that occur in volatile oil-in-water nanoemulsions to synthesize hollow, solvent-free capsules with average sizes of approximately 300 nm and neutral surface potential. (3) Results: The resultant nanocapsules exhibit chiroptical activity and interact differentially with single stranded DNA oligonucleotides despite the lack of surface charge and, thus, the absence of significant electrostatic interactions. Preferential binding of DNA on d-polyurea nanocapsules compared to their l-counterparts is demonstrated by a fourfold increase in capsule size, a 50% higher rise in the absolute value of negative zeta potential (ζ-potential), and a three times lower free DNA concentration after equilibration with the excess of DNA. (4) Conclusions: We infer that the chirality of the novel polymeric nanocapsules affects their supramolecular interactions with DNA, possibly through modification of the surface morphology. These interactions can be exploited when developing carriers for gene therapy and theranostics. The resultant constructs are expected to be highly biocompatible due to their neutral potential and biodegradability of polyurea shells.
CHD2-Related CNS Pathologies
Authors: Wilson Marc-Michel , Henshall David C. , Byrne Susan M. , Brennan Gary P.
Published: January 2021

Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. This class of disorders are increasingly being identified as resulting from de novo genetic mutations including many identified mutations in the family of chromodomain helicase DNA binding (CHD) proteins. In particular, several de novo pathogenic mutations have been identified in the gene encoding chromodomain helicase DNA binding protein 2 (CHD2), a member of the sucrose nonfermenting (SNF-2) protein family of epigenetic regulators. These mutations in the CHD2 gene are causative of early onset epileptic encephalopathy, abnormal brain function, and intellectual disability. Our understanding of the mechanisms by which modification or loss of CHD2 cause this condition remains poorly understood. Here, we review what is known and still to be elucidated as regards the structure and function of CHD2 and how its dysregulation leads to a highly variable range of phenotypic presentations.
Gliadin Sequestration as a Novel Therapy for Celiac Disease: A Prospective Application for Polyphenols
Authors: Van Buiten Charlene B. , Elias Ryan J.
Published: January 2021

Celiac disease is an autoimmune disorder characterized by a heightened immune response to gluten proteins in the diet, leading to gastrointestinal symptoms and mucosal damage localized to the small intestine. Despite its prevalence, the only treatment currently available for celiac disease is complete avoidance of gluten proteins in the diet. Ongoing clinical trials have focused on targeting the immune response or gluten proteins through methods such as immunosuppression, enhanced protein degradation and protein sequestration. Recent studies suggest that polyphenols may elicit protective effects within the celiac disease milieu by disrupting the enzymatic hydrolysis of gluten proteins, sequestering gluten proteins from recognition by critical receptors in pathogenesis and exerting anti-inflammatory effects on the system as a whole. This review highlights mechanisms by which polyphenols can protect against celiac disease, takes a critical look at recent works and outlines future applications for this potential treatment method.
Transposable Elements and Teleost Migratory Behaviour
Authors: Carotti Elisa , Carducci Federica , Canapa Adriana , Barucca Marco , Greco Samuele , Gerdol Marco , Biscotti Maria Assunta
Published: January 2021

Transposable elements (TEs) represent a considerable fraction of eukaryotic genomes, thereby contributing to genome size, chromosomal rearrangements, and to the generation of new coding genes or regulatory elements. An increasing number of works have reported a link between the genomic abundance of TEs and the adaptation to specific environmental conditions. Diadromy represents a fascinating feature of fish, protagonists of migratory routes between marine and freshwater for reproduction. In this work, we investigated the genomes of 24 fish species, including 15 teleosts with a migratory behaviour. The expected higher relative abundance of DNA transposons in ray-finned fish compared with the other fish groups was not confirmed by the analysis of the dataset considered. The relative contribution of different TE types in migratory ray-finned species did not show clear differences between oceanodromous and potamodromous fish. On the contrary, a remarkable relationship between migratory behaviour and the quantitative difference reported for short interspersed nuclear (retro)elements (SINEs) emerged from the comparison between anadromous and catadromous species, independently from their phylogenetic position. This aspect is likely due to the substantial environmental changes faced by diadromous species during their migratory routes.
Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material
Authors: Roosterman Dirk , Cottrell Graeme Stuart
Published: January 2021

In 1937, Sir H. A Krebs first published the Citric Acid Cycle, a unidirectional cycle with carboxylic acids. The original concept of the Citric Acid Cycle from Krebs’ 1953 Nobel Prize lecture illustrates the unidirectional degradation of lactic acid to water, carbon dioxide and hydrogen. Here, we add the heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex, connecting the original Citric Acid Cycle to the flow of energy and material. The heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex catalyses the first reaction of the Citric Acid Cycle, the oxidation of lactate to pyruvate, and thus secures the provision of pyruvic acid. In addition, we modify Krebs’ original concept by feeding the cycle with oxaloacetic acid. Our concept enables the integration of anabolic processes and allows adaption of the organism to recover ATP faster.