bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of Wind Farm Simulators for Wind Farm Control
Authors: Kim Minjeong , Lim Hyeyeong , Park Sungsu
Published: April 2023

This paper conducts a comparative analysis of three wind farm simulators, examining the influence of wake on the local wind speed and power output for downstream turbines using experimental data. The study features experiments in three distinct scenarios, evaluating differences among the simulators by calculating the local wind speed and power for each. Each simulator employs a unique wake model, which substantially affects the local wind speed experienced by downstream turbines. Furthermore, the experiment involves adjusting parameter values for each simulator to assess their respective impacts on wind farm performance. The findings of this research are expected to play an important role in investigations related to power optimization and wake effects in the wind farm control.
Why Agree to a Forest Easement? Perception of the Residents about the Adaptation of the Conservation Easement in Qianjiangyuan National Park
Authors: He Siyuan , Wei Yu
Published: April 2023

Conservation easements (CEs) were introduced in the Chinese context to resolve the conflict between rural land use and area-based conservation measures. As conservation easements are usually set on private lands, little is known about their adaptation to the collective land tenure. We introduced a social-psychological aspect to sustainable livelihoods (SL) for an integrated decision-making mechanism to assess rural residents’ motivations for granting CEs. We surveyed farmers in the Qianjiangyuan National Park pilot area in order to explore how tangible factors, i.e., the livelihood assets, and intangible factors, i.e., farmers’ perceptions of the livelihood environment, affected their true feeling of conservation easements. Results suggested that CEs that were adapted to the collectively-owned forestland followed a well-established grassroots democracy but sacrificed the CE’s diversity in restricted uses tailored to specific landowners and properties. Institutional capital and perception of the economic environment appeared most important to affect farmers’ acceptance of CEs. Furthermore, the livelihood assets affected farmers’ perception of the livelihood environment, and their acceptance of CEs affected the perception of policy outcomes. Overall, our findings demonstrate the acceptance of conservation easements as a livelihood strategic choice and strengthen the importance of securing economic rights in the changing institutional environment.
The Determinants of Forest Products Footprint: A New Fourier Cointegration Approach
Authors: Yilanci Veli
Published: April 2023

This study aims to determine the factors that affect the forest products footprint (FPF) in Brazil during the period 1965–2018 by proposing a new cointegration test which augments the Engle-Granger cointegration test with a Fourier function (Fourier Engle-Granger) and allows multiple structural breaks in the long-run relationship. Since the results of the unit root tests show that all variables are nonstationary, we applied the Fourier Engle-Granger cointegration test and revealed that there was a long-term relationship between the forest products’ footprint, energy consumption, gross domestic product, and trade openness. Although energy consumption was found to have a decreasing effect on FPF, the remaining variables were found to have a healing effect on FPF. Policymakers in Brazil should consider shifting energy consumption to clean energy sources and sustain international trade and economic growth in the current form to consider the FPF.
Community Abundance of Resprouting in Woody Plants Reflects Fire Return Time, Intensity, and Type
Authors: Shen Yicheng , Cai Wenjia , Prentice I. Colin , Harrison Sandy P.
Published: April 2023

Plants in fire-prone ecosystems have evolved a variety of mechanisms to resist or adapt to fire. Post-fire resprouting is a key adaptation that promotes rapid ecosystem recovery and hence has a major impact on the terrestrial carbon cycle. However, our understanding of how the incidence of resprouting varies in different fire regimes is largely qualitative. The increasing availability of plant trait data and plot-based species cover data provides an opportunity to quantify the relationships between fire-related traits and fire properties. We investigated the quantitative relationship between fire frequency (expressed as the fire return time) and the proportion of resprouters in woody plants using plot data on species cover from Australia and Europe. We also examined the relationship between the proportion of resprouters and gross primary production (GPP) and grass cover, where GPP was assumed to reflect fuel loads and hence fire intensity, while grass cover was considered to be an indicator of the likelihood of ground fire and the speed of fire spread, using generalised linear modelling. The proportion of resprouting species decreased significantly as the fire return time increased. When the fire return time was considered along with other aspects of the fire regime, the proportion of resprouters had significant negative relationships with the fire return time and grass cover and a significant positive relationship with GPP. These findings demonstrate that plants with the ability to resprout occur more often where fire regimes are characterised by high-frequency and high-intensity crown fires. Establishing quantitative relationships between the incidence of resprouting and the fire return time and fire type provides a basis for modelling resprouting as a consequence of the characteristics of the fire regime, which in turn makes it possible to model the consequences of changing fire regimes on ecosystem properties.
Every Fish Counts: Challenging Length–Weight Relationship Bias in Discards
Authors: Rodríguez-García Carlos , Castro-Gutiérrez Jairo , Domínguez-Bustos Ángel Rafael , García-González Alberto , Cabrera-Castro Remedios
Published: April 2023

Bycatch is a significant issue in global fisheries and understanding the length–weight relationships (LWR) of fish species can provide valuable insights for stock assessment and management efforts. In this study, we estimated the LWR of 74 fish species in trawl fleet discards from the Gulf of Cadiz, including 24 species for which LWR data had not been previously reported in this region. LWR was calculated from the formula W = aLb where parameter a is the intercept of the equation, related to body shape, and parameter b is the slope, which indicates the type of growth of the species. A total of 20,007 individuals from 40 families were measured and weighed. The most abundant species were Engraulis encrasicolus, Trachurus trachurus, Serranus hepatus, Sardina pilchardus, Capros aper, and Diplodus bellottii, and the Sparidae family was the most represented with ten species. The parameter b, which represents the type of growth, ranged from 2.1607 to 3.7040. A positive allometric growth trend was observed in 64% of the species. The inclusion of individuals with a low sample size proved useful, particularly for first reports in a new study area. However, caution should be taken when using these data, as the estimates of the length–weight relationship for these species may be less precise. Further studies with larger sample sizes are needed to confirm the results and improve the accuracy of the estimates. Overall, our findings contribute to the understanding of the LWR of fish species in the Gulf of Cadiz, informing future research and management efforts in the region.
Benefits, Facilitators and Barrier Reductions in Physical Activity Programmes for People with Severe Mental Disorder: A Systematic Review
Authors: Méndez-Aguado Cristina , Cangas Adolfo J. , Aguilar-Parra José M. , Lirola María J.
Published: April 2023

The current high prevalence of people with Severe Mental Disorder and the high impact the latter has on their quality of life is one of the main problems in terms of health, as it affects both physical and mental health. One of the lines of action to intervene in these factors is the practice of physical activity, as this usually has a low level of participation due to different barriers. However, there are several facilitators that improve adherence to these practices. The main objectives of this work were (1) to conduct a systematic review of the scientific literature on the possible benefits obtained by people with SMD from their participation in physical activity programmes; (2) to identify the characteristics of physical activity programmes and determine the barriers to their implementation that have been considered and (3) the facilitators incorporated. To meet these objectives, the SCOPUS, Web of Science, PubMed, Dialnet and Elsevier online databases were consulted and, following the PRISMA statement, 17 articles were finally selected. Their analysis has revealed various physical, psychological and social benefits, as well as the barriers that appear in the intervention programmes, mostly related to personal factors and the programme itself, and those factors that facilitate their adherence or development, the most common being the carrying out of the activities outdoors, the inclusion of social components and the possibility of adapting the activities. In this way, the results obtained have made it possible to highlight the characteristics that should be taken into account when planning this type of intervention.
Identification of Factors Affecting Self-Efficacy in Women with Spontaneous Pregnancy Loss
Authors: Mróz Mariola , Bień Agnieszka , Iwanowicz-Palus Grażyna , Krysa Justyna
Published: April 2023

Pregnancy loss is a difficult situation that can affect a woman’s physical and psychological health, and thus requires appropriate management and support. An individual’s sense of self-efficacy is an important factor in the process of coping with a problem. Therefore, an analysis of self-efficacy in women after spontaneous pregnancy loss is warranted, so as to establish its association with social support, socio-demographic variables, quality of care, and specific behaviors of the medical staff. The cross-sectional study was performed in a group of 610 patients hospitalized due to spontaneous pregnancy loss in hospitals in Lublin (Poland). The study used a diagnostic survey with questionnaires: Generalized Self-Efficacy Scale (GSES), the Berlin Social Support Scales (BSSS), and a standardized interview questionnaire. Post-pregnancy loss patients rated partner support highest (M = 9.25), while the best-rated category of social support was perceived available instrumental support (M = 3.78). In relation to medical personnel, the quality of care provided by midwives was rated the highest (M = 4.57). The study demonstrated a statistically significant (p < 0.05) association between the selected socio-demographic factors and the specific types and sources of support on the one hand, and generalized self-efficacy on the other, in the patients after pregnancy loss who were studied. Socio-demographic factors that affected self-efficacy in the respondents included their relationship status and socio-economic standing. Self-efficacy is positively correlated with social support in women after pregnancy loss.
Managing Predicted Post-Orthognathic Surgical Defects Using Combined Digital Software: A Case Report
Authors: Onică Neculai , Onică Cezara Andreea , Tatarciuc Monica , Baciu Elena-Raluca , Vlasie Georgiana-Lena , Ciofu Mihai , Balan Mihail , Gelețu Gabriela Luminița
Published: April 2023

For facial abnormalities, recent developments in virtual surgical planning (VSP) and the virtual design of surgical splints are accessible. Software companies have worked closely with surgical teams for accurate outcomes, but they are only as reliable as the data provided to them. The current case’s aim was to show a fully digitized workflow using a combination of three digital software to correct predicted post–upward sliding genioplasty defects. To reach our goal, we presented a 28-year-old man with long-face syndrome for orthodontic treatment. Before orthognathic surgery, a clinical and paraclinical examination was performed. For a virtual surgical plan, we used the dedicated surgical planning software NemoFab (Nemotec, Madrid, Spain) and Autodesk MeshMixer (Autodesk Inc., San Rafael, CA, USA). To create the design of the digital guides, DentalCAD 3.0 Galway (exocad GmbH, Darmstadt, Germany) and Autodesk MeshMixer (Autodesk Inc., San Rafael, CA, USA) were used. The patient had undergone bilateral sagittal split osteotomy in addition to Le Fort 1 osteotomy and genioplasty, followed by mandible base recontouring ostectomy. Stable fixation was used for each osteotomy. Based on our case, the current orthognathic surgery planning software was not able to perform all the necessary operations autonomously; therefore, future updates are eagerly awaited.
Genome-Wide Identification of ATP-Binding Cassette (ABC) Transporter Provides Insight to Genes Related to Anthocyanin Transportation in New Teinturier Grape Germplasm ‘ZhongShan-HongYu’
Authors: Li Hui , Yang Yaxin , Wang Qianlan , Li Haoran , Wang Wu , Zheng Huan , Tao Jianmin
Published: April 2023

ATP-binding cassette (ABC) transporters are a large class of superfamily involved in a variety of biological processes with multiple functions, including phytohormone transport, heavy metal ion detoxification, and so on. Anthocyanin pigmentation in grapes is a commercially important feature of this superfamily. To elucidate the mechanisms of the VvABC gene at different stages in grape berries, we analyzed and characterized the ABC family in ‘ZhongShan-HongYu’ (ZS-HY) berries using RNA-seq analysis. In this study, a total of 146 VvABC genes were identified by comprehensive bioinformatics analysis, which outlined their gene structure, chromosomal location, conserved domains, phylogenetic relationships, and collinearity analysis. The VvABC family could be divided into eight subfamilies based on the phylogenetic analysis. Fifty-eight VvABC genes were identified from the RNA-seq data, of which 31 belong to the ABCG subfamily, 15 belong to the ABCC subfamily, 8 belong to the ABCB subfamily, 2 belong to the ABCF subfamily, and only 1 belongs to each of the ABCA and ABCD subfamilies. We used qRT-PCR to detect the expression of VvABC genes in different organs and found that it changed significantly in different organs. Phylogenetic analysis showed that genes involved in anthocyanin transport in other species were closely related to members of the ABCC subfamily. Subsequently, analysis of the promoter elements and the protein interactions of the VvABCC genes using RNA-seq was performed. This study has improved our understanding of the functions of the ABC gene family and provided a basis for the role of ABC genes in grape anthocyanin transport.
Trends in the Epidemiology of Non-Typhoidal Salmonellosis in Israel between 2010 and 2021
Authors: Bassal Ravit , Davidovich-Cohen Maya , Yakunin Eugenia , Rokney Assaf , Ken-Dror Shifra , Strauss Merav , Wolf Tamar , Sagi Orli , Amit Sharon , Moran-Gilad Jacob , Treygerman Orit , Karyo Racheli , Keinan-Boker Lital , Cohen Dani
Published: April 2023

Non-typhoidal salmonellosis (NTS) is one of the most common foodborne diseases worldwide. In this study, we aimed to analyze trends in the epidemiology of NTS in the last decade in Israel. Laboratory-confirmed cases of NTS at eight sentinel laboratories were reported to the Israel Sentinel Laboratory-Based Surveillance Network, integrated with the serotype identification performed at the Salmonella National Reference Laboratory of the Ministry of Health. The decrease in NTS incidence since 1999 continued between 2010 and 2014 (16.1 per 100,000 in 2014) and was interrupted by a rise between 2015 and 2017 (39.1 per 100,000 in 2017) associated with outbreaks of Salmonella Enteritidis. The incidence of NTS dropped again thereafter (21.4 per 100,000 in 2021). The 0–4 age group was the most affected by NTS (55.5% of the cases) throughout the surveillance period. The age-adjusted incidence rates were consistently high in the summer months (June-September) and low in the winter months (December–February). The overall decrease in the incidence of NTS in Israel since 1999 was temporarily interrupted in the last decade by country-wide outbreaks involving emerging or re-emerging Salmonella serotypes. Control measures should be enhanced for all risk points of food chain transmission of Salmonella spp. to further reduce the NTS morbidity in Israel.
Overview of Activities in the Field of Occupational Health and Safety during the COVID-19 Period Taken by Polish SMEs
Authors: Olkiewicz Marcin
Published: April 2023

The safety of work, employees, and clients of micro, small, and medium-sized enterprises (SMEs) is important because it is significantly related to the proper functioning and development of the entity and determines the decision-making process. The purpose of this publication is to show what actions aimed at increasing the sense of occupational safety and health during the COVID-19 pandemic were undertaken by Polish SMEs from the central Pomeranian region. The analysis of the literature most often presents the effects of the COVID-19 pandemic and the actions of governments in the field of protecting the public but does not present analyses of activities strictly taken by entrepreneurs. A survey was addressed to 300 business entities, of which 195 took part, determining the effectiveness rate at the level of 65%. Unfortunately, research shows that as many as 56% of the surveyed entities were negatively affected by the COVID-19 pandemic. Organizations used a number of safeguards aimed at increasing the sense of occupational health and safety, e.g., by using gels or liquids for disinfecting hands and surfaces during working hours (77%); regular cleaning and disinfection of equipment and workstations (84%); and maintaining social distance (76%). The analysis of the collected data covering the year 2021 indicates that this study should be treated as a survey study. This provides an opportunity to expand the area and scope of research. The presented research results indicate that, depending on the type of activity, as well as legal epidemic restrictions, SMEs increased the safety of employees and customers in different ways and with different tools during the development of the COVID-19 pandemic.
Challenges and Burdens in the Coronary Artery Disease Care Pathway for Patients Undergoing Percutaneous Coronary Intervention: A Contemporary Narrative Review
Authors: Kodeboina Monika , Piayda Kerstin , Jenniskens Inge , Vyas Pearl , Chen Sara , Pesigan Ramon Julian , Ferko Nicole , Patel Barkha P. , Dobrin Annamaria , Habib Jayson , Franke Jennifer
Published: April 2023

Clinical and economic burdens exist within the coronary artery disease (CAD) care pathway despite advances in diagnosis and treatment and the increasing utilization of percutaneous coronary intervention (PCI). However, research presenting a comprehensive assessment of the challenges across this pathway is scarce. This contemporary review identifies relevant studies related to inefficiencies in the diagnosis, treatment, and management of CAD, including clinician, patient, and economic burdens. Studies demonstrating the benefits of integration and automation within the catheterization laboratory and across the CAD care pathway were also included. Most studies were published in the last 5–10 years and focused on North America and Europe. The review demonstrated multiple potentially avoidable inefficiencies, with a focus on access, appropriate use, conduct, and follow-up related to PCI. Inefficiencies included misdiagnosis, delays in emergency care, suboptimal testing, longer procedure times, risk of recurrent cardiac events, incomplete treatment, and challenges accessing and adhering to post-acute care. Across the CAD pathway, this review revealed that high clinician burnout, complex technologies, radiation, and contrast media exposure, amongst others, negatively impact workflow and patient care. Potential solutions include greater integration and interoperability between technologies and systems, improved standardization, and increased automation to reduce burdens in CAD and improve patient outcomes.
The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Non-Melanoma Skin Cancer
Authors: Iden Jennifer Ana , Raphael-Mizrahi Bitya , Naim Aaron , Kolomansky Albert , Liron Tamar , Neumann Drorit , Vered Marilena , Gabet Yankel
Published: April 2023

Five million non-melanoma skin cancers occur globally each year, and it is one of the most common malignant cancers. The dysregulation of the endocannabinoid system, particularly cannabinoid receptor 2 (CB2), is implicated in skin cancer development, progression, and metastasis. Comparing wildtype (WT) to systemic CB2 knockout (CB2-/-) mice, we performed a spontaneous cancer study in one-year old mice, and subsequently used the multi-stage chemical carcinogenesis model, wherein cancer is initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). We found that aging CB2-/- mice have an increased incidence of spontaneous cancerous and precancerous skin lesions compared to their WT counterparts. In the DMBA/TPA model, CB2-/- developed more and larger papillomas, had decreased spontaneous regression of papillomas, and displayed an altered systemic immune profile, including upregulated CD4+ T cells and dendritic cells, compared to WT mice. Immune cell infiltration in the tumor microenvironment was generally low for both genotypes, although a trend of higher myeloid-derived suppressor cells was observed in the CB2-/- mice. CB2 expression in carcinogen-exposed skin was significantly higher compared to naïve skin in WT mice, suggesting a role of CB2 on keratinocytes. Taken together, our data show that endogenous CB2 activation plays an anti-tumorigenic role in non-melanoma skin carcinogenesis, potentially via an immune-mediated response involving the alteration of T cells and myeloid cells coupled with the modulation of keratinocyte activity.
Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets
Authors: Zhang Pengyu , Solari Fiorella A. , Heemskerk Johan W. M. , Kuijpers Marijke J. E. , Sickmann Albert , Walter Ulrich , Jurk Kerstin
Published: April 2023

Bruton’s tyrosine kinase (Btk) and spleen tyrosine kinase (Syk) are major signaling proteins in human platelets that are implicated in atherothrombosis and thrombo-inflammation, but the mechanisms controlling their activities are not well understood. Previously, we showed that Syk becomes phosphorylated at S297 in glycoprotein VI (GPVI)-stimulated human platelets, which limits Syk activation. Here, we tested the hypothesis that protein kinases C (PKC) and A (PKA) and protein phosphatase 2A (PP2A) jointly regulate GPVI-induced Btk activation in platelets. The GPVI agonist convulxin caused rapid, transient Btk phosphorylation at S180 (pS180↑), Y223 and Y551, while direct PKC activation strongly increased Btk pS180 and pY551. This increase in Btk pY551 was also Src family kinase (SFK)-dependent, but surprisingly Syk-independent, pointing to an alternative mechanism of Btk phosphorylation and activation. PKC inhibition abolished convulxin-stimulated Btk pS180 and Syk pS297, but markedly increased the tyrosine phosphorylation of Syk, Btk and effector phospholipase Cγ2 (PLCγ2). PKA activation increased convulxin-induced Btk activation at Y551 but strongly suppressed Btk pS180 and Syk pS297. PP2A inhibition by okadaic acid only increased Syk pS297. Both platelet aggregation and PLCγ2 phosphorylation with convulxin stimulation were Btk-dependent, as shown by the selective Btk inhibitor acalabrutinib. Together, these results revealed in GPVI-stimulated platelets a transient Syk, Btk and PLCγ2 phosphorylation at multiple sites, which are differentially regulated by PKC, PKA or PP2A. Our work thereby demonstrated the GPVI–Syk–Btk signalosome as a tightly controlled protein kinase network, in agreement with its role in atherothrombosis.
Molecular and Cellular Mechanisms of Corneal Scarring and Advances in Therapy
Authors: Fuest Matthias , Jhanji Vishal , Yam Gary Hin-Fai
Published: April 2023

On the basis of WHO global blindness data, it may be stated that 23 million people globally suffer from unilateral corneal blindness, while 4 [...]
Preparation and Optical Study of 1-Formamido-5-Isocyanonaphthalene, the Hydrolysis Product of the Potent Antifungal 1,5-Diisocyanonaphthalene
Authors: Kopcsik Erika , Mucsi Zoltán , Kontra Bence , Vanyorek László , Váradi Csaba , Viskolcz Béla , Nagy Miklós
Published: April 2023

Aromatic isocyanides have gained a lot of attention lately as promising antifungal and anticancer drugs, as well as high-performance fluorescent analytical probes for the detection of toxic metals, such as mercury, even in vivo. Since this topic is relatively new and aromatic isocyanides possess unique photophysical properties, the understanding of structure–behavior relationships and the preparation of novel potentially biologically active derivatives are of paramount importance. Here, we report the photophysical characterization of 1,5-diisocyanonaphthalene (DIN) backed by quantum chemical calculations. It was discovered that DIN undergoes hydrolysis in certain solvents in the presence of oxonium ions. By the careful control of the reaction conditions for the first time, the nonsymmetric product 1-formamido-5-isocyanonaphthalene (ICNF) could be prepared. Contrary to expectations, the monoformamido derivative showed a significant solvatochromic behavior with a ~50 nm range from hexane to water. This behavior was explained by the enhanced H-bond-forming ability of the formamide group. The significance of the hydrolysis reaction is that the isocyano group is converted to formamide in living organisms. Therefore, ICNF could be a potential drug (for example, antifungal) and the reaction can be used as a model for the preparation of other nonsymmetric formamido–isocyanoarenes. In contrast to its relative 1-amino-5-iscyanonaphthalene (ICAN), ICNF is highly fluorescent in water, enabling the development of a fluorescent turnoff probe.
Improving the Modeling of Extracellular Ligand Binding Pockets in RosettaGPCR for Conformational Selection
Authors: Liessmann Fabian , Künze Georg , Meiler Jens
Published: April 2023

G protein-coupled receptors (GPCRs) are the largest class of drug targets and undergo substantial conformational changes in response to ligand binding. Despite recent progress in GPCR structure determination, static snapshots fail to reflect the conformational space of putative binding pocket geometries to which small molecule ligands can bind. In comparative modeling of GPCRs in the absence of a ligand, often a shrinking of the orthosteric binding pocket is observed. However, the exact prediction of the flexible orthosteric binding site is crucial for adequate structure-based drug discovery. In order to improve ligand docking and guide virtual screening experiments in computer-aided drug discovery, we developed RosettaGPCRPocketSize. The algorithm creates a conformational ensemble of biophysically realistic conformations of the GPCR binding pocket between the TM bundle, which is consistent with a knowledge base of expected pocket geometries. Specifically, tetrahedral volume restraints are defined based on information about critical residues in the orthosteric binding site and their experimentally observed range of Cα-Cα-distances. The output of RosettaGPCRPocketSize is an ensemble of binding pocket geometries that are filtered by energy to ensure biophysically probable arrangements, which can be used for docking simulations. In a benchmark set, pocket shrinkage observed in the default RosettaGPCR was reduced by up to 80% and the binding pocket volume range and geometric diversity were increased. Compared to models from four different GPCR homology model databases (RosettaGPCR, GPCR-Tasser, GPCR-SSFE, and GPCRdb), the here-created models showed more accurate volumes of the orthosteric pocket when evaluated with respect to the crystallographic reference structure. Furthermore, RosettaGPCRPocketSize was able to generate an improved realistic pocket distribution. However, while being superior to other homology models, the accuracy of generated model pockets was comparable to AlphaFold2 models. Furthermore, in a docking benchmark using small-molecule ligands with a higher molecular weight between 400 and 700 Da, a higher success rate in creating native-like binding poses was observed. In summary, RosettaGPCRPocketSize can generate GPCR models with realistic orthosteric pocket volumes, which are useful for structure-based drug discovery applications.
An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis
Authors: Balogh Dora Bianka , Wagner Laszlo Jozsef , Fekete Andrea
Published: April 2023

Metabolic diseases, particularly diabetes mellitus (DM), are significant global public health concerns. Despite the widespread use of standard-of-care therapies, cardiovascular disease (CVD) remains the leading cause of death among diabetic patients. Early and evidence-based interventions to reduce CVD are urgently needed. Large clinical trials have recently shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) ameliorate adverse cardiorenal outcomes in patients with type 2 DM. These quite unexpected positive results represent a paradigm shift in type 2 DM management, from the sole importance of glycemic control to the simultaneous improvement of cardiovascular outcomes. Moreover, SGLT2i is also found to be cardio- and nephroprotective in non-diabetic patients. Several mechanisms, which may be potentially independent or at least separate from the reduction in blood glucose levels, have already been identified behind the beneficial effect of these drugs. However, there is still much to be understood regarding the exact pathomechanisms. This review provides an overview of the current literature and sheds light on the modes of action of novel antidiabetic drugs, focusing on inflammation, oxidative stress, and fibrosis.
“Pathomorphogenic” Changes Caused by Citrus Bark Cracking Viroid and Transcription Factor TFIIIA-7ZF Variants Support Viroid Propagation in Tobacco
Authors: Matoušek Jaroslav , Wüsthoff Kevin P. , Steger Gerhard
Published: April 2023

Viroids are small, non-coding, pathogenic RNAs with the ability to disturb plant developmental processes. This dysregulation redirects the morphogenesis of plant organs, significantly impairing their functionality. Citrus bark cracking viroid (CBCVd) causes detrimental developmental distortions in infected hops (Humulus lupulus) and causes significant economic losses. CBCVd can infect cells and tissues of the model plant tobacco (Nicotiana tabacum), provided it is delivered via transgenesis. The levels of CBCVd in tobacco were enhanced in plant hybrids expressing CBCVd cDNAs and either the tobacco or hop variant of TFIIIA-7ZF, a viroid-mediated splicing derivative of transcription factor IIIA, which is important for viroid replication by DNA-dependent RNA polymerase II. The TFIIIA-7ZF variants can change the tobacco morphogenesis if expressed in leaves and shoots. In addition to the splitting of shoots, the “pathomorphogenic” network in hybrid plants expressing CBCVd and HlTFIIIA-7ZF induced leaf fusions and malformations. Moreover, CBCVd can dramatically change another morphogenesis into teratomic and petal-like tissues if propagated above some limit in young transgenic tobacco microspores and anthers. By comparative RNA profiling of transgenic tobacco shoots bearing TFIIIA-7ZFs and CBCVd-transformed/infected anthers, we found a differential expression of many genes at p < 0.05. As the main common factor showing the differential up-regulation in shoot and anther tissues, a LITTLE ZIPPER 2-like transcription factor was found. We propose that this factor, which can interact as a competitive inhibitor of the also dysregulated homeobox-leucin zipper family protein (HD-ZIPIII) in apical meristem, is essential for a network responsible for some morphological changes and modifications of plant degradome within shoot meristem regulation and secondary xylem differentiation.
Polymorphism of Saccharomyces cerevisiae Strains in DNA Metabolism Genes
Authors: Zhuk Anna S. , Lada Artem G. , Pavlov Youri I.
Published: April 2023

Baker’s yeast, S. cerevisiae, is an excellent model organism exploited for molecular genetic studies of the mechanisms of genome stability in eukaryotes. Genetic peculiarities of commonly used yeast strains impact the processes of DNA replication, repair, and recombination (RRR). We compared the genomic DNA sequence variation of the five strains that are intensively used for RRR studies. We used yeast next-generation sequencing data to detect the extent and significance of variation in 183 RRR genes. We present a detailed analysis of the differences that were found even in closely related strains. Polymorphisms of common yeast strains should be considered when interpreting the outcomes of genome stability studies, especially in cases of discrepancies between laboratories describing the same phenomena.
Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia
Authors: Ivanova Tatiana , Churnosova Maria , Abramova Maria , Plotnikov Denis , Ponomarenko Irina , Reshetnikov Evgeny , Aristova Inna , Sorokina Inna , Churnosov Mikhail
Published: April 2023

The aim of the study was directed at studying the sex-specific features of the correlation between genome-wide association studies (GWAS)-noticeable polymorphisms and hypertension (HTN). In two groups of European subjects of Russia (n = 1405 in total), such as men (n = 821 in total: n = 564 HTN, n = 257 control) and women (n = 584 in total: n = 375 HTN, n = 209 control), the distribution of ten specially selected polymorphisms (they have confirmed associations of GWAS level with blood pressure (BP) parameters and/or HTN in Europeans) has been considered. The list of studied loci was as follows: (PLCE1) rs932764 A > G, (AC026703.1) rs1173771 G > A, (CERS5) rs7302981 G > A, (HFE) rs1799945 C > G, (OBFC1) rs4387287 C > A, (BAG6) rs805303 G > A, (RGL3) rs167479 T > G, (ARHGAP42) rs633185 C > G, (TBX2) rs8068318 T > C, and (ATP2B1) rs2681472 A > G. The contribution of individual loci and their inter-locus interactions to the HTN susceptibility with bioinformatic interpretation of associative links was evaluated separately in men’s and women’s cohorts. The men–women differences in involvement in the disease of the BP/HTN-associated GWAS SNPs were detected. Among women, the HTN risk has been associated with HFE rs1799945 C > G (genotype GG was risky; ORGG = 11.15 ppermGG = 0.014) and inter-locus interactions of all 10 examined SNPs as part of 26 intergenic interactions models. In men, the polymorphism BAG6 rs805303 G > A (genotype AA was protective; ORAA = 0.30 ppermAA = 0.0008) and inter-SNPs interactions of eight loci in only seven models have been founded as HTN-correlated. HTN-linked loci and strongly linked SNPs were characterized by pronounced polyvector functionality in both men and women, but at the same time, signaling pathways of HTN-linked genes/SNPs in women and men were similar and were represented mainly by immune mechanisms. As a result, the present study has demonstrated a more pronounced contribution of BP/HTN-associated GWAS SNPs to the HTN susceptibility (due to weightier intergenic interactions) in European women than in men.
Differential Modulation of Dendritic Cell Biology by Endogenous and Exogenous Aryl Hydrocarbon Receptor Ligands
Authors: Sadeghi Shermeh Atefeh , Royzman Dmytro , Kuhnt Christine , Draßner Christina , Stich Lena , Steinkasserer Alexander , Knippertz Ilka , Wild Andreas B.
Published: April 2023

The aryl hydrocarbon receptor (AhR) is a decisive regulatory ligand-dependent transcription factor. It binds highly diverse ligands, which can be categorized as either endogenous or exogenous. Ligand binding activates AhR, which can adjust inflammatory responses by modulating immune cells such as dendritic cells (DCs). However, how different AhR ligand classes impact the phenotype and function of human monocyte-derived DCs (hMoDCs) has not been extensively studied in a comparative manner. We, therefore, tested the effect of the representative compounds Benzo(a)pyrene (BP), 6-formylindolo[3,2-b]carbazole (FICZ), and Indoxyl 3-sulfate (I3S) on DC biology. Thereby, we reveal that BP significantly induces a tolerogenic response in lipopolysaccharide-matured DCs, which is not apparent to the same extent when using FICZ or I3S. While all three ligand classes activate AhR-dependent pathways, BP especially induces the expression of negative immune regulators, and subsequently strongly subverts the T cell stimulatory capacity of DCs. Using the CRISPR/Cas9 strategy we also prove that the regulatory effect of BP is strictly AhR-dependent. These findings imply that AhR ligands contribute differently to DC responses and incite further studies to uncover the mechanisms and molecules which are involved in the induction of different phenotypes and functions in DCs upon AhR activation.
An Evaluation of the Cytotoxic and Genotoxic Effects of the Marine Toxin C17-SAMT in Human TK6 and HepaRG Cell Lines
Authors: Marzougui Zeineb , Le Hegarat Ludovic , Hogeveen Kevin , Huet Sylvie , Kharrat Riadh , Marrouchi Riadh , Fessard Valérie
Published: April 2023

This study investigates the genotoxicity and cytotoxicity of C17-sphinganine analog mycotoxin (C17-SAMT) using in vitro assays. C17-SAMT was previously identified as the cause of unusual toxicity in cultured mussels from the Bizerte Lagoon in northern Tunisia. While a previous in vivo genotoxicity study was inconclusive, in vitro results demonstrated that C17-SAMT induced an increase in micronucleus formation in human lymphoblastoid TK6 cells at concentrations of 0.87 µM and 1.74 µM. In addition, multiparametric cytotoxicity assays were performed in the human hepatoma HepaRG cell line, which showed that C17-SAMT induced mitochondrial dysfunction, decreased cellular ATP levels, and altered the expression of various proteins, including superoxide dismutase SOD2, heme oxygenase HO-1, and NF-κB. These results suggest that C17-SAMT is mutagenic in vitro and can induce mitochondrial dysfunction in HepaRG cells. However, the exact mode of action of this toxin requires further investigation. Overall, this study highlights the potential toxicity of C17-SAMT and the need for further research to better understand its effects.
Pharmacological Evidence Suggests That Slo3 Channel Is the Principal K+ Channel in Boar Spermatozoa
Authors: Cooray Akila , Kim Jeongsook , Nirujan Beno Ramesh , Jayathilake Nishani Jayanika , Lee Kyu Pil
Published: April 2023

Sperm ion channels are associated with the quality and type of flagellar movement, and their differential regulation is crucial for sperm function during specific phases. The principal potassium ion channel is responsible for the majority of K+ ion flux, resulting in membrane hyperpolarization, and is essential for sperm capacitation-related signaling pathways. The molecular identity of the principal K+ channel varies greatly between different species, and there is a lack of information about boar K+ channels. We aimed to determine the channel identity of boar sperm contributing to the primary K+ current using pharmacological dissection. A series of Slo1 and Slo3 channel modulators were used for treatment. Sperm motility and related kinematic parameters were monitored using a computer-assisted sperm analysis system under non-capacitated conditions. Time-lapse flow cytometry with fluorochromes was used to measure changes in different intracellular ionic concentrations, and conventional flow cytometry was used to determine the acrosome reaction. Membrane depolarization, reduction in acrosome reaction, and motility parameters were observed upon the inhibition of the Slo3 channel, suggesting that the Slo3 gene encodes the main K+ channel in boar spermatozoa. The Slo3 channel was localized on the sperm flagellum, and the inhibition of Slo3 did not reduce sperm viability. These results may aid potential animal-model-based extrapolations and help to ameliorate motility and related parameters, leading to improved assisted reproductive methods in industrial livestock production.
APP in the Neuromuscular Junction for the Development of Sarcopenia and Alzheimer’s Disease
Authors: Wu Min-Yi , Zou Wen-Jun , Lee Daehoon , Mei Lin , Xiong Wen-Cheng
Published: April 2023

Sarcopenia, an illness condition usually characterized by a loss of skeletal muscle mass and muscle strength or function, is often associated with neurodegenerative diseases, such as Alzheimer’s disease (AD), a common type of dementia, leading to memory loss and other cognitive impairment. However, the underlying mechanisms for their associations and relationships are less well understood. The App, a Mendelian gene for early-onset AD, encodes amyloid precursor protein (APP), a transmembrane protein enriched at both the neuromuscular junction (NMJ) and synapses in the central nervous system (CNS). Here, in this review, we highlight APP and its family members’ physiological functions and Swedish mutant APP (APPswe)’s pathological roles in muscles and NMJ. Understanding APP’s pathophysiological functions in muscles and NMJ is likely to uncover insights not only into neuromuscular diseases but also AD. We summarize key findings from the burgeoning literature, which may open new avenues to investigate the link between muscle cells and brain cells in the development and progression of AD and sarcopenia.
T-Cells Subsets in Castleman Disease: Analysis of 28 Cases Including Unicentric, Multicentric and HHV8-Related Clinical Forms
Authors: Fraticelli Sara , Lucioni Marco , Neri Giuseppe , Marchiori Deborah , Cristinelli Caterina , Merli Michele , Monaco Rodolfo , Borra Tiziana , Lazzaro Antonio , Uccella Silvia , Arcaini Luca , Paulli Marco
Published: April 2023

Castleman disease (CD) is a rare lymphoproliferative disorder that includes various clinico-pathological subtypes. According to clinical course, CD is divided into unicentric CD (UCD) and multicentric CD (MCD). MCD is further distinguished based on the etiological driver in herpes virus-8-related MCD (that can occur in the setting of HIV); in MCD associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes); and idiopathic MCD (iMCD). The latter can also be divided in iMCD-TAFRO (thrombocytopenia, anasarca, fever, myelofibrosis, organomegaly) and iMCD not otherwise specified. To date, CD pathogenesis is still uncertain, but CD may represent the histological and clinical result of heterogeneous pathomechanisms. Transcriptome investigations in CD lymph nodes have documented the expression and up-regulation of different cytokines; furthermore, few recent studies have shown alterations of different T-cell subsets in CD patients, suggesting a possible role of the nodal microenvironment in CD development. On this basis, our study aimed to investigate the distribution of T-cell subsets in the clinico-pathological spectrum of CD. We evaluated the CD4/CD8 ratio and the number of T-regulatory (T-reg) FOXP3+ cells in 28 CD cases. In total, 32% of cases showed a decreased CD4/CD8 ratio due to increased CD8+ T-cells, including both UCD, iMCD, and HHV8+ MCD cases. The T-reg subset analysis revealed a statistically significant (p < 0.0001) lower mean number of FOXP3+ T-reg cells in CD cases when compared with non-specific reactive lymph nodes. We did not find statistically significant differences in T-reg numbers between the different CD subtypes. These findings may suggest that alterations in T-cell subpopulations that can lead to disruption of immune system control may contribute to the numerous changes in different cellular compartments that characterize CD.
SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury
Authors: González-Soria Isaac , Soto-Valadez Axel D. , Martínez-Rojas Miguel Angel , Ortega-Trejo Juan Antonio , Pérez-Villalva Rosalba , Gamba Gerardo , Sánchez-Navarro Andrea , Bobadilla Norma A.
Published: April 2023

We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected, I/R increased serum creatinine and BUN, with a GFR reduction in both genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR group. Interestingly, the increase in UH2O2 induced by I/R was not equally seen in the KOSA3+IR group, an effect that was associated with the preservation of antioxidant enzymes’ mRNA levels. Additionally, FOXO3 expression was initially greater in the KOSA3 than in the WT group. Moreover, the increase in BAX protein level and the decrease in Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group, suggesting that these animals have better cellular responses to hypoxic injury. Our findings suggest that SerpinA3K is involved in the renal oxidant response, HIF1α/VEGF pathway, and cell apoptosis.
Preliminary Analysis of Transcriptome Response of Dioryctria sylvestrella (Lepidoptera: Pyralidae) Larvae Infected with Beauveria bassiana under Short-Term Starvation
Authors: Guo Hongru , Jia Niya , Chen Huanwen , Xie Dan , Chi Defu
Published: April 2023

The Dioryctria genus contains several destructive borer pests that are found in coniferous forests in the Northern Hemisphere. Beauveria bassiana spore powder was tested as a new method of pest control. In this study, Dioryctria sylvestrella (Lepidoptera: Pyralidae) was used as the object. A transcriptome analysis was performed on a freshly caught group, a fasting treatment control group, and a treatment group inoculated with a wild B. bassiana strain, SBM-03. Under the conditions of 72-h fasting and a low temperature of 16 ± 1 °C, (i) in the control group, 13,135 of 16,969 genes were downregulated. However, in the treatment group, 14,558 of 16,665 genes were upregulated. (ii) In the control group, the expression of most genes in the upstream and midstream of the Toll and IMD pathways was downregulated, but 13 of the 21 antimicrobial peptides were still upregulated. In the treatment group, the gene expression of almost all antimicrobial peptides was increased. Several AMPs, including cecropin, gloverin, and gallerimycin, may have a specific inhibitory effect on B. bassiana. (iii) In the treatment group, one gene in the glutathione S-transferase system and four genes in the cytochrome P450 enzyme family were upregulated, with a sharp rise in those that were upregulated significantly. In addition, most genes of the peroxidase and catalase families, but none of the superoxide dismutase family were upregulated significantly. Through innovative fasting and lower temperature control, we have a certain understanding of the specific defense mechanism by which D. sylvestrella larvae may resist B. bassiana in the pre-wintering period. This study paves the way for improving the toxicity of B. bassiana to Dioryctria spp.