bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pyrogeography of Methane Emissions from Seasonal Mosaic Burning Regimes in a West African Landscape
Authors: Laris Paul , Koné Moussa , Dembélé Fadiala , Rodrigue Christine M. , Yang Lilian , Jacobs Rebecca , Laris Quincy , Camara Facourou
Published: February 2023

People have set fire to the savannas of West Africa for millennia, creating a pyrogeography. Fires render the landscape useful for many productive activities, but there is also a long history of efforts to regulate indigenous burning practices. Today, savanna fires are under scrutiny because they contribute to greenhouse gas emissions, especially methane. Policy efforts aimed at reducing emissions by shifting fire regimes earlier are untested. Most emissions estimates contain high levels of uncertainty because they are based on generalizations of diverse landscapes burned by complex fire regimes. To examine the importance of seasonality and other factors on methane emissions, we used an approach grounded in the practices of people who set fires. We conducted 107 experimental fires, collecting data for methane emissions and a suite of environmental variables. We sampled emissions using a portable gas analyzer, recording values for CO, CO2, and CH4. The fires were set both as head and backfires for three fire periods—the early, middle, and late dry season. We also set fires randomly to test whether the emissions differed from those set according to traditional practices. We found that methane emission factors and densities did not increase over the dry season but rather peaked mid-season due to higher winds and fuel moisture as well as green leaves on small trees. The findings demonstrate the complexity of emissions from fires and cast doubt on efforts to reduce emissions based on simplified characterizations of fire regimes and landscapes.
Evolution of Water Wave Groups in the Forced Benney–Roskes System
Authors: Maleewong Montri , Grimshaw Roger H. J.
Published: February 2023

For weakly nonlinear waves in one space dimension, the nonlinear Schrödinger Equation is widely accepted as a canonical model for the evolution of wave groups described by modulation instability and its soliton and breather solutions. When there is forcing such as that due to wind blowing over the water surface, this can be supplemented with a linear growth term representing linear instability leading to the forced nonlinear Schrödinger Equation. For water waves in two horizontal space dimensions, this is replaced by a forced Benney–Roskes system. This is a two-dimensional nonlinear Schrödinger Equation with a nonlocal nonlinear term. In deep water, this becomes a local nonlinear term, and it reduces to a two-dimensional nonlinear Schrödinger Equation. In this paper, we numerically explore the evolution of wave groups in the forced Benney–Roskes system using four cases of initial conditions. In the one-dimensional unforced nonlinear Schrödinger equa tion, the first case would lead to a Peregrine breather and the second case to a line soliton; the third case is a long-wave perturbation, and the fourth case is designed to stimulate modulation instability. In deep water and for finite depth, when there is modulation instability in the one-dimensional nonlinear Schdrödinger Equation, the two-dimensional simulations show a similar pattern. However, in shallow water where there is no one-dimensional modulation instability, the extra horizontal dimension is significant in producing wave growth through modulation instability.
The Mathematics of ‘Natural Beauty’ in the Architecture of Andrea Palladio and Le Corbusier: An Analysis of Colin Rowe’s Theory of Formal Complexity Using Fractal Dimensions
Authors: Dawes Michael , Ostwald Michael , Lee Ju
Published: February 2023

In a famous architectural discussion, Colin Rowe links the geometric properties of two sixteenth century villas by Andrea Palladio and two twentieth century villas by the architect Le Corbusier. Rowe observed that different structural systems produced heightened geometric complexity in cross sections through Palladio’s villas and in Le Corbusier’s plans. Rowe also described a particular type of geometric scaling in portions of the four villas which he partially explains as a type of mathematical ‘natural beauty’ akin to the golden ratio and Fibonacci sequence. In his writings, Rowe refers to several geometric properties that encapsulate complex, scaled structures, but he lacked a mathematical system to rigorously describe and test his ideas. The present paper utilises the box-counting method for calculating fractal dimensions to analyse 100 images, consisting of architectural plans, sections, and elevations of the four villas and two Fibonacci sequences, to test Rowe’s ideas. Ultimately, the results of this research do not support the majority of Rowe’s claims about geometric complexity in the villas of Palladio and Le Corbusier, but they do provide insights into Rowe’s discussion of geometric scaling and the properties of four famous houses.
Plantae tinctoriae: The 1759 Dissertation on Dye Plants by Engelbert Jörlin
Authors: Hofmann-de Keijzer Regina , de Keijzer Matthijs
Published: February 2023

In the late 1750s, the Swedish botanist Engelbert Jörlin (1733–1810), one of Carl Linnaeus’ students wrote his dissertation Plantae tinctoriae on more than one hundred dye plants. The article presents a systematic study on these dyeing materials and reflects the knowledge in the mid-18th century. His dissertation focused on domestic plants that could be suitable instead of expensive imported trade goods and was published during the Age of Utility (1719–1771). The Latin text of Jörlin’s dissertation was first converted into a digital version by the ‘Noscemus General Model’ from Transkribus and then translated into English. The current scientific names were obtained from various biological websites. The dyestuffs were assigned to four groups: native and applied in Sweden (A); imported trade products (B); native to Sweden with potential use for dyeing (C); non-native and used abroad (D). They were mainly applied for dyeing textiles, less frequently for pharmaceuticals, cosmetics (make-up), inks and artists’ pigments. In his dissertation, Jörlin refers to scriptures from antiquity, Latin botanical literature from the 16th and 17th centuries but especially to the publications of Carl Linnaeus.
Preparation, Characterization, and Biological Properties of Hydroxyapatite from Bigeye Snapper (Priancanthus tayenus) Bone
Authors: Jindapon Nunnuth , Klinmalai Phatthranit , Surayot Utoomporn , Tanadchangsaeng Nuttapol , Pichaiaukrit Woradej , Phimolsiripol Yuthana , Vichasilp Chaluntorn , Wangtueai Sutee
Published: February 2023

The optimum condition of acid hydrolysis for hydroxyapatite extraction from bigeye snapper (Priancanthus tayenus) bone and the effects of extraction time (10–60 min) and HCl concentration (2.0–5.0% w/v) on yield and hydroxyapatite properties were determined. The optimum extracted condition was found using 5% HCl for 60 min, which was 13.4% yield; 19.8 g/100 g Ca content; 9.6 g/100 g P content; 2.1 Ca/P ratio; L*, a*, b*; and ΔE as 84.5, 2.8, 16.5, and 15.6, respectively. The using of 5% NaOH solution was optimum for hydroxyapatite precipitation from the extracted solution. The characteristic and biological properties of the obtained hydroxyapatite were studied. Fourier transform infrared spectroscopy and X-ray diffraction results showed a good comparison between the extracted and commercial hydroxyapatite. The microstructure of the extracted hydroxyapatite from a scanning electron microscope showed an irregular and flat-plate shape, large surface area, and roughness. The extracted hydroxyapatite was non- and low-cytotoxicity at a concentration of 50 and 100–400 µg/mL, respectively. Bovine serum albumin (BSA) adsorption and desorption of hydroxyapatite was studied. An increasing BSA concentration, hydroxyapatite amount, and adsorption time significantly increased protein adsorption on hydroxyapatite. Protein desorption from BSA-loaded hydroxyapatite showed an increase of release initially in the first 4 days and became a steady release rate until 14 days.
Mapping of QTLs and Screening Candidate Genes Associated with the Ability of Sugarcane Tillering and Ratooning
Authors: Wang Ting , Xu Fu , Wang Zhoutao , Wu Qibin , Cheng Wei , Que Youxiong , Xu Liping
Published: February 2023

The processes of sugarcane tillering and ratooning, which directly affect the yield of plant cane and ratoon, are of vital importance to the population establishment and the effective stalk number per unit area. In the present study, the phenotypic data of 285 F1 progenies from a cross of sugarcane varieties YT93-159 × ROC22 were collected in eight environments, which consisted of plant cane and ratoon cultivated in three different ecological sites. The broad sense heritability (H2) of the tillering and the ratoon sprouting was 0.64 and 0.63, respectively, indicating that they were middle to middle-high heritable traits, and there is a significantly positive correlation between the two traits. Furthermore, a total of 26 quantitative trait loci (QTLs) related to the tillering ability and 11 QTLs associated with the ratooning ability were mapped on two high-quality genetic maps derived from a 100K SNP chip, and their phenotypic variance explained (PVE) ranged from 4.27–25.70% and 6.20–13.54%, respectively. Among them, four consistent QTLs of qPCTR-R9, qPCTR-Y28, qPCTR-Y60/qRSR-Y60 and PCTR-Y8-1/qRSR-Y8 were mapped in two environments, of which, qPCTR-Y8-1/qRSR-Y8 had the PVEs of 11.90% in the plant cane and 7.88% in the ratoon. Furthermore, a total of 25 candidate genes were identified in the interval of the above four consistent QTLs and four major QTLs of qPCTR-Y8-1, qPCTR-Y8-2, qRSR-R51 and qRSR-Y43-2, with the PVEs from 11.73–25.70%. All these genes were associated with tillering, including eight transcription factors (TFs), while 15 of them were associated with ratooning, of which there were five TFs. These QTLs and genes can provide a scientific reference for genetic improvement of tillering and ratooning traits in sugarcane.
From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies
Authors: Alekseenko Irina , Kondratyeva Liya , Chernov Igor , Sverdlov Eugene
Published: February 2023

The unprecedented non-reproducibility of the results published in the field of cancer research has recently come under the spotlight. In this short review, we try to highlight some general principles in the organization and evolution of cancerous tumors, which objectively lead to their enormous variability and, consequently, the irreproducibility of the results of their investigation. This heterogeneity is also extremely unfavorable for the effective use of molecularly targeted medicine. Against the seemingly comprehensive background of this heterogeneity, we single out two supramolecular characteristics common to all tumors: the clustered nature of tumor interactions with their microenvironment and the formation of biomolecular condensates with tumor-specific distinctive features. We suggest that these features can form the basis of strategies for tumor-specific supramolecular targeted therapies.
Synthesis, Biological and In Silico Studies of Griseofulvin and Usnic Acid Sulfonamide Derivatives as Fungal, Bacterial and Human Carbonic Anhydrase Inhibitors
Authors: Angeli Andrea , Petrou Anthi , Kartsev Victor , Lichitsky Boris , Komogortsev Andrey , Capasso Clemente , Geronikaki Athina , Supuran Claudiu T.
Published: February 2023

Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the essential reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho-/physiological conditions. A series of griseofulvin and usnic acid sulfonamides were synthesized and tested as possible CA inhibitors. Since β- and γ- classes are expressed in microorganisms in addition to the α- class, showing substantial structural differences to the human isoforms they are also interesting as new antiinfective targets with a different mechanism of action for fighting the emerging problem of extensive drug resistance afflicting most countries worldwide. Griseofulvin and usnic acid sulfonamides were synthesized using methods of organic chemistry. Their inhibitory activity, assessed against the cytosolic human isoforms hCA I and hCA II, the transmembrane hCA IX as well as β- and γ-CAs from different bacterial and fungal strains, was evaluated by a stopped-flow CO2 hydrase assay. Several of the investigated derivatives showed interesting inhibition activity towards the cytosolic associate isoforms hCA I and hCA II, as well as the three γ-CAs and Malassezia globosa (MgCA) enzyme. Six compounds (1b–1d, 1h, 1i and 1j) were more potent than AAZ against hCA I while five (1d, 1h, 1i, 1j and 4a) showed better activity than AAZ against the hCA II isoform. Moreover, all compounds appeared to be very potent against MgCA with a Ki lower than that of the reference drug. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds within the active site of human CAs.
Identification of Novel Sphydrofuran-Derived Derivatives with Lipid-Lowering Activity from the Active Crude Extracts of Nocardiopsis sp. ZHD001
Authors: Tian Yuhong , Jiang Yongjun , Wen Zhengshun , Guan Liping , Ouyang Xiaokun , Ding Wanjing , Ma Zhongjun
Published: February 2023

Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe and effective novel lipid-lowering drugs. In the course of our project aimed at discovering the chemical novelty and bioactive natural products of marine-derived actinomycetes, we found that the organic crude extracts (OCEs) of Nocardiopsis sp. ZHD001 exhibited strong in vivo efficacies in reducing weight gain, lowering LDL-C, TC, and TG levels, and improving HDL-C levels in high-fat-diet-fed mice models. Chemical investigations of the active OCEs led to identifying two new sphydrofuran-derived compounds (1–2) and one known 2-methyl-4-(1-glycerol)-furan (3). Their structures were elucidated by the analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, compound 1 represents a novel rearranged sphydrofuran-derived derivative. Bioactivity evaluations of these pure compounds showed that all the compounds exhibited significant lipid-lowering activity with lower cytotoxicity in vitro compared to simvastatin. Our results demonstrate that sphydrofuran-derived derivatives might be promising candidates for lipid-lowering drugs.
Monocyte-Derived miRNA-1914-5p Attenuates IL-1β–Induced Monocyte Adhesion and Transmigration
Authors: Toriuchi Kohki , Kihara Toshie , Aoki Hiromasa , Kakita Hiroki , Takeshita Satoru , Ueda Hiroko , Inoue Yasumichi , Hayashi Hidetoshi , Shimono Yohei , Yamada Yasumasa , Aoyama Mineyoshi
Published: February 2023

Atherosclerosis can lead to cardiovascular and cerebrovascular diseases. Atherosclerotic plaque formation is promoted by the accumulation of inflammatory cells. Therefore, modulating monocyte recruitment represents a potential therapeutic strategy. In an inflammatory state, the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) is upregulated in endothelial cells. We previously reported that miR-1914-5p in endothelial cells suppresses interleukin (IL)-1β–induced ICAM-1 expression and monocyte adhesion to endothelial cells. However, whether monocyte miR-1914-5p affects monocyte recruitment is unclear. In this study, IL-1β decreased miR-1914-5p expression in a human monocyte cell line. Moreover, miR-1914-5p inhibition enhanced adhesion to endothelial cells with the upregulation of macrophage-1 antigen (Mac-1), a counter-ligand to ICAM-1. Transmigration through the endothelial layer was also promoted with the upregulation of monocyte chemotactic protein-1 (MCP-1). Furthermore, a miR-1914-5p mimic suppressed IL-1β–induced monocyte adhesion and transmigration in monocytes with Mac-1 and MCP-1 downregulation. Further investigation of miR-1914-5p in monocytes could lead to the development of novel diagnostic markers and therapeutic strategies for atherosclerosis.
Early Cell Cultures from Prostate Cancer Tissue Express Tissue Specific Epithelial and Cancer Markers
Authors: Ryabov Vladimir M. , Baryshev Mikhail M. , Voskresenskiy Mikhail A. , Popov Boris V.
Published: February 2023

Prostate cancer (PCa) is a widespread oncological disease that proceeds in the indolent form in most patients. However, in some cases, the indolent form can transform into aggressive metastatic incurable cancer. The most important task of PCa diagnostics is to search for early markers that can be used for predicting the transition of indolent cancer into its aggressive form. Currently, there are two effective preclinical models to study PCa pathogenesis: patients derived xenografts (PDXs) and patients derived organoids (PDOs). Both models have limitations that restrict their use in research. In this work, we investigated the ability of the primary 2D prostate cell cultures (PCCs) from PCa patients to express epithelial and cancer markers. Early PCCs were formed by epithelial cells that were progressively replaced with the fibroblast-like cells. Early PCCs contained tissue-specific stem cells that could grow in a 3D culture and form PDOs similar to those produced from the prostate tissue. Early PCCs and PDOs derived from the tissues of PCa patients expressed prostate basal and luminal epithelial markers, as well as cancer markers AMACR, TMPRSS2-ERG, and EZH2, the latter being a promising candidate to mark the transition from the indolent to aggressive PCa. We also identified various TMPRSS2-ERG fusion transcripts in PCCs and PDOs, including new chimeric variants resulting from the intra- and interchromosomal translocations. The results suggest that early PCCs derived from cancerous and normal prostate tissues sustain the phenotype of prostate cells and can be used as a preclinical model to study the pathogenesis of PCa.
Using CIVT-SELEX to Select Aptamers as Genetic Parts to Regulate Gene Circuits in a Cell-Free System
Authors: Guo Shaobin , Xu Zeqi , Lin Lujie , Guo Yan , Li Jingying , Lu Chunhua , Shi Xianai , Yang Huanghao
Published: February 2023

The complexity of genetic circuits has not seen a significant increase over the last decades, even with the rapid development of synthetic biology tools. One of the bottlenecks is the limited number of orthogonal transcription factor–operator pairs. Researchers have tried to use aptamer–ligand pairs as genetic parts to regulate transcription. However, most aptamers selected using traditional methods cannot be directly applied in gene circuits for transcriptional regulation. To that end, we report a new method called CIVT-SELEX to select DNA aptamers that can not only bind to macromolecule ligands but also undergo significant conformational changes, thus affecting transcription. The single-stranded DNA library with affinity to our example ligand human thrombin protein is first selected and enriched. Then, these ssDNAs are inserted into a genetic circuit and tested in the in vitro transcription screening to obtain the ones with significant inhibitory effects on downstream gene transcription when thrombins are present. These aptamer–thrombin pairs can inhibit the transcription of downstream genes, demonstrating the feasibility and robustness of their use as genetic parts in both linear DNAs and plasmids. We believe that this method can be applied to select aptamers of any target ligands and vastly expand the genetic part library for transcriptional regulation.
Investigation of the Key Genes Associated with Anthocyanin Accumulation during Inner Leaf Reddening in Ornamental Kale (Brassica oleracea L. var. acephala)
Authors: Zou Jiaqi , Gong Zhichao , Liu Zhiyong , Ren Jie , Feng Hui
Published: February 2023

Ornamental kale (Brassica oleracea L. var. acephala) is a popular decorative plant in late autumn and winter. However, only during low-temperature color-changed periods below rough 15 °C can the plant accumulate anthocyanins and exhibit a diverse array of foliar color patterns. In this study, we probed into the potential mechanism of inner leaf reddening in a red-leaf pure line of ornamental kale by physiological, metabolic, and transcriptomic analyses. Determination of anthocyanin contents in the uncolored new white leaves (S0), the light red leaves (S1) in the reddening period and the red leaves (S2) completing color change, and analysis of anthocyanin metabolites at stage S2, revealed that the coloring of red leaves was mainly attributed to the accumulation of cyanidins. We further used transcriptomic sequencing between the pairwise S0, S1, and S2 stages to identify 21 differentially expressed genes (DEGs) involved in anthocyanin biosynthesis, among which the expression level of 14 DEGs was positively correlated with anthocyanin accumulation, and 6 DEGs were negatively correlated with anthocyanin accumulation. A total of 89 co-expressed genes were screened out, from which three DEGs (BoCHI, Bo4CL3, and BoF3H) were identified as hub genes in co-expression DEGs network. BoDFR and BoCHI were the DEGs with the highest expressions at S2. Moreover, two co-expressed DEGs related to stress response (BoBBX17 and BoCOR47) also exhibited upregulated expressions and positive correlations with anthocyanin accumulation. A deep dive into the underlying regulatory network of anthocyanin accumulation comprising these six upregulated DEGs from S0 to S2 was performed via trend, correlation, and differentially co-expression analysis. This study uncovered the DEGs expression profiles associated with anthocyanin accumulation during ornamental kale inner leaf reddening, which provided a basis for further dissecting the molecular mechanisms of leaf color characteristic change in ornamental kale at low temperatures.
Feasibility of Co-Targeting HER3 and EpCAM Using Seribantumab and DARPin–Toxin Fusion in a Pancreatic Cancer Xenograft Model
Authors: Xu Tianqi , Schulga Alexey , Konovalova Elena , Rinne Sara S. , Zhang Hongchao , Vorontsova Olga , Orlova Anna , Deyev Sergey M. , Tolmachev Vladimir , Vorobyeva Anzhelika
Published: February 2023

Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1–LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled 99mTc(CO)3-Ec1–LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1–LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1–LoPE and MM-121 in vitro. An experimental therapy study using Ec1–LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified.
Plant Coumarins with Anti-HIV Activity: Isolation and Mechanisms of Action
Authors: Sharapov Ainur D. , Fatykhov Ramil F. , Khalymbadzha Igor A. , Zyryanov Grigory V. , Chupakhin Oleg N. , Tsurkan Mikhail V.
Published: February 2023

This review summarizes and systematizes the literature on the anti-HIV activity of plant coumarins with emphasis on isolation and the mechanism of their antiviral action. This review summarizes the information on the anti-HIV properties of simple coumarins as well as annulated furano- and pyranocoumarins and shows that coumarins of plant origin can act by several mechanisms: inhibition of HIV reverse transcriptase and integrase, inhibition of cellular factors that regulate HIV-1 replication, and transmission of viral particles from infected macrophages to healthy ones. It is important to note that some pyranocoumarins are able to act through several mechanisms or bind to several sites, which ensures the resistance of these compounds to HIV mutations. Here we review the last two decades of research on the anti-HIV activity of naturally occurring coumarins.
Baseline Gait and Motor Function Predict Long-Term Severity of Neurological Outcomes of Viral Infection
Authors: Karmakar Moumita , Pérez Gómez Aracely A. , Carroll Raymond J. , Lawley Koedi S. , Amstalden Katia A. Z. , Welsh C. Jane , Threadgill David W. , Brinkmeyer-Langford Candice
Published: February 2023

Neurological dysfunction following viral infection varies among individuals, largely due to differences in their genetic backgrounds. Gait patterns, which can be evaluated using measures of coordination, balance, posture, muscle function, step-to-step variability, and other factors, are also influenced by genetic background. Accordingly, to some extent gait can be characteristic of an individual, even prior to changes in neurological function. Because neuromuscular aspects of gait are under a certain degree of genetic control, the hypothesis tested was that gait parameters could be predictive of neuromuscular dysfunction following viral infection. The Collaborative Cross (CC) mouse resource was utilized to model genetically diverse populations and the DigiGait treadmill system used to provide quantitative and objective measurements of 131 gait parameters in 142 mice from 23 CC and SJL/J strains. DigiGait measurements were taken prior to infection with the neurotropic virus Theiler’s Murine Encephalomyelitis Virus (TMEV). Neurological phenotypes were recorded over 90 days post-infection (d.p.i.), and the cumulative frequency of the observation of these phenotypes was statistically associated with discrete baseline DigiGait measurements. These associations represented spatial and postural aspects of gait influenced by the 90 d.p.i. phenotype score. Furthermore, associations were found between these gait parameters with sex and outcomes considered to show resistance, resilience, or susceptibility to severe neurological symptoms after long-term infection. For example, higher pre-infection measurement values for the Paw Drag parameter corresponded with greater disease severity at 90 d.p.i. Quantitative trait loci significantly associated with these DigiGait parameters revealed potential relationships between 28 differentially expressed genes (DEGs) and different aspects of gait influenced by viral infection. Thus, these potential candidate genes and genetic variations may be predictive of long-term neurological dysfunction. Overall, these findings demonstrate the predictive/prognostic value of quantitative and objective pre-infection DigiGait measurements for viral-induced neuromuscular dysfunction.
Evaluation of In Vitro Distribution and Plasma Protein Binding of Selected Antiviral Drugs (Favipiravir, Molnupiravir and Imatinib) against SARS-CoV-2
Authors: Dömötör Orsolya , Enyedy Éva A.
Published: February 2023

There are a number of uncertainties regarding plasma protein binding and blood distribution of the active drugs favipiravir (FAVI), molnupiravir (MOLNU) and imatinib (IMA), which were recently proposed as therapeutics for the treatment of COVID-19 disease. Therefore, proton dissociation processes, solubility, lipophilicity, and serum protein binding of these three substances were investigated in detail. The drugs display various degrees of lipophilicity at gastric (pH 2.0) and blood pH (pH 7.4). The determined pKa values explain well the changes in lipophilic character of the respective compounds. The serum protein binding was studied by membrane ultrafiltration, frontal analysis capillary electrophoresis, steady-state fluorometry, and fluorescence anisotropy techniques. The studies revealed that the ester bond in MOLNU is hydrolyzed by protein constituents of blood serum. Molnupiravir and its hydrolyzed form do not bind considerably to blood proteins. Likewise, FAVI does not bind to human serum albumin (HSA) and α1-acid glycoprotein (AGP) and shows relatively weak binding to the protein fraction of whole blood serum. Imatinib binds to AGP with high affinity (logK′ = 5.8–6.0), while its binding to HSA is much weaker (logK′ ≤ 4.0). The computed constants were used to model the distribution of IMA in blood plasma under physiological and ‘acute-phase’ conditions as well.
Wilms Tumor 1-Driven Fibroblast Activation and Subpleural Thickening in Idiopathic Pulmonary Fibrosis
Authors: Gajjala Prathibha R. , Singh Priyanka , Odayar Varshini , Ediga Harshavardhana H. , McCormack Francis X. , Madala Satish K.
Published: February 2023

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that is often fatal due to the formation of irreversible scar tissue in the distal areas of the lung. Although the pathological and radiological features of IPF lungs are well defined, the lack of insight into the fibrogenic role of fibroblasts that accumulate in distinct anatomical regions of the lungs is a critical knowledge gap. Fibrotic lesions have been shown to originate in the subpleural areas and extend into the lung parenchyma through processes of dysregulated fibroproliferation, migration, fibroblast-to-myofibroblast transformation, and extracellular matrix production. Identifying the molecular targets underlying subpleural thickening at the early and late stages of fibrosis could facilitate the development of new therapies to attenuate fibroblast activation and improve the survival of patients with IPF. Here, we discuss the key cellular and molecular events that contribute to (myo)fibroblast activation and subpleural thickening in IPF. In particular, we highlight the transcriptional programs involved in mesothelial to mesenchymal transformation and fibroblast dysfunction that can be targeted to alter the course of the progressive expansion of fibrotic lesions in the distal areas of IPF lungs.
Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa
Authors: Cezard Adeline , Fouquenet Delphine , Vasseur Virginie , Jeannot Katy , Launay Fabien , Si-Tahar Mustapha , Hervé Virginie
Published: February 2023

Pseudomonas aeruginosa is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis (CF) or those hospitalized in intensive care units. Given its remarkable ability to resist antibiotics, P. aeruginosa eradication has grown more challenging. Therefore, there is an urgent need to discover and develop new strategies that can counteract P. aeruginosa-resistant strains. Here, we evaluated the efficacy of poly-L-lysine (pLK) in combination with commonly used antibiotics as an alternative treatment option against P. aeruginosa. First, we demonstrated by scanning electron microscopy that pLK alters the integrity of the surface membrane of P. aeruginosa. We also showed using a fluorometry test that this results in an enhanced permeability of the bacteria membrane. Based on these data, we further evaluated the effect of the combinations of pLK with imipenem, ceftazidime, or aztreonam using the broth microdilution method in vitro. We found synergies in terms of bactericidal effects against either sensitive or resistant P. aeruginosa strains, with a reduction in bacterial growth (up to 5-log10 compared to the control). Similarly, these synergistic and bactericidal effects were confirmed ex vivo using a 3D model of human primary bronchial epithelial cells maintained in an air–liquid interface. In conclusion, pLK could be an innovative antipseudomonal molecule, opening its application as an adjuvant antibiotherapy against drug-resistant P. aeruginosa strains.
Pulsed Electric Field Ablation of Esophageal Malignancies and Mitigating Damage to Smooth Muscle: An In Vitro Study
Authors: Gudvangen Emily , Mangalanathan Uma , Semenov Iurii , Kiester Allen S. , Keppler Mark A. , Ibey Bennett L. , Bixler Joel N. , Pakhomov Andrei G.
Published: February 2023

Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca2+ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them less vulnerable to electroporation. We infer that damage to SMC from nsPEF ablation of esophageal malignancies can be minimized by applying the electric field parallel to the predominant SMC orientation.
The Emerging Role of Cell Adhesion Molecules on Benign Prostatic Hyperplasia
Authors: Liu Jiang , Zhang Junchao , Fu Xun , Yang Shu , Li Yan , Liu Jianmin , DiSanto Michael E. , Chen Ping , Zhang Xinhua
Published: February 2023

Benign prostatic hyperplasia (BPH) is a common disease in elderly men. It is characterized by prostatic enlargement and urethral compression and often causes lower urinary tract symptoms (LUTs) such as urinary frequency, urgency, and nocturia. Existing studies have shown that the pathological process of prostate hyperplasia is mainly related to the imbalance of cell proliferation and apoptosis, inflammation, epithelial–mesenchymal transition (EMT), and growth factors. However, the exact molecular mechanisms remain incompletely elucidated. Cell adhesion molecules (CAMs) are a group of cell surface proteins that mediate cell–cell adhesion and cell migration. Modulating adhesion molecule expression can regulate cell proliferation, apoptosis, EMT, and fibrotic processes, engaged in the development of prostatic hyperplasia. In this review, we went over the important roles and molecular mechanisms of cell adhesion molecules (mainly integrins and cadherins) in both physiological and pathological processes. We also analyzed the mechanisms of CAMs in prostate hyperplasia and explored the potential value of targeting CAMs as a therapeutic strategy for BPH.
Effects of Salinomycin and Deferiprone on Lead-Induced Changes in the Mouse Brain
Authors: Petrova Emilia , Gluhcheva Yordanka , Pavlova Ekaterina , Vladov Ivelin , Dorkov Peter , Schaier Martin , Pashkunova-Martic Irena , Helbich Thomas H. , Keppler Bernhard , Ivanova Juliana
Published: February 2023

Lead (Pb) is a highly toxic heavy metal that has deleterious effects on the central nervous system. This study aimed to investigate the effects of salinomycin (Sal) and deferiprone (DFP) on brain morphology and on the content of some essential elements in Pb-exposed mice. Adult male Institute of Cancer Research (ICR) mice were exposed to a daily dose of 80 mg/kg body weight ( b.w.) Pb(II) nitrate for 14 days and subsequently treated with Sal (16 mg/kg b.w.) or DFP (19 mg/kg b.w.) for another 14 days. At the end of the experimental protocol, the brains were processed for histological and inductively coupled plasma mass spectrometry (ICP-MS) analyses. Pb exposure resulted in a 50-fold increase in Pb concentration, compared with controls. Magnesium (Mg) and phosphorus (P) were also significantly increased by 22.22% and 17.92%, respectively. The histological analysis of Pb-exposed mice revealed brain pathological changes with features of neuronal necrosis. Brain Pb level remained significantly elevated in Sal- and DFP-administered groups (37-fold and 50-fold, respectively), compared with untreated controls. Treatment with Sal significantly reduced Mg and P concentrations by 22.56% and 18.38%, respectively, compared with the Pb-exposed group. Administration of Sal and DFP ameliorated brain injury in Pb-exposed mice and improved histological features. The results suggest the potential application of Sal and DFP for treatment of Pb-induced neurotoxicity.
Regulatory Mechanism between Ferritin and Mitochondrial Reactive Oxygen Species in Spinal Ligament-Derived Cells from Ossification of Posterior Longitudinal Ligament Patient
Authors: Kim Jong Tae , Kim Yonggoo , Kim Ji Yeon , Lee Seungok , Kim Myungshin , Jekarl Dong Wook
Published: February 2023

Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.
Genome-Wide Identification of the SQUAMOSA Promoter-Binding Protein-like (SPL) Transcription Factor Family in Sweet Cherry Fruit
Authors: Sun Yueting , Wang Yanyan , Xiao Yuqin , Zhang Xiang , Du Bingyang , Turupu Maihemuti , Wang Chao , Yao Qisheng , Gai Shilin , Huang Jing , Tong Shi , Li Tianhong
Published: February 2023

Plant-specific SQUAMOSA promoter-binding protein-like (SPL) transcription factors play important regulatory roles during plant growth and development, fruit ripening, inflorescence branching, and biotic and abiotic stresses. However, there have been no identification or systematic studies of the SPL gene family in the sweet cherry. In this study, 12 SPL genes were identified in the sweet cherry reference genome, which were distributed over 6 chromosomes and classified into six groups according to phylogenetic relationships with other SPL gene families. Nine PavSPLs were highly expressed at green fruit stages and dramatically decreased at the onset of fruit ripening, which implied that they were important regulators during fruit development and ripening. The expression patterns of PavSPL genes under ABA, GA, and MeJA treatments showed that the PavSPLs were involved in the process of fruit ripening. A subcellular localization experiment proved that PavSPL4 and PavSPL7 proteins were localized in the nucleus. The genome-wide identification of the SPL gene family provided new insights while establishing an important foundation for sweet cherry studies.
Editorial: Special Issue on the “Molecular Biology of Disease Vectors”
Authors: Kotsyfakis Michail
Published: February 2023

Arthropod disease vectors not only transmit malaria but many other serious diseases, many of which are, to a greater or lesser degree, neglected [...]
Brain N-Glycosylation and Lipidomic Profile Changes Induced by a High-Fat Diet in Dyslipidemic Hamsters
Authors: Paton Beatrix , Foguet-Romero Elisabet , Suarez Manuel , Mayneris-Perxachs Jordi , Boqué Noemí , Caimari Antoni , Canela Núria , Herrero Pol
Published: February 2023

The consumption of diets rich in saturated fats is known to be associated with higher mortality. The adoption of healthy habits, for instance adhering to a Mediterranean diet, has proved to exert a preventive effect towards cardiovascular diseases and dyslipidemia. Little is known about how a suboptimal diet can affect brain function, structure, and the mechanisms involved. The aims of this study were to examine how a high-fat diet can alter the brain N-glycan and lipid profile in male Golden Syrian hamsters and to evaluate the potential of a Mediterranean-like diet to reverse this situation. During twelve weeks, hamsters were fed a normal fat diet (CTRL group), a high-fat diet (HFD group), and a high-fat diet followed by a Mediterranean-like diet (MED group). Out of seventy-two identified N-glycans, fourteen were significant (p < 0.05) between HFD and CTRL groups, nine between MED and CTRL groups, and one between MED and HFD groups. Moreover, forty-nine lipids were altered between HFD and CTRL groups, seven between MED and CTRL groups, and five between MED and HFD groups. Our results suggest that brain N-glycan composition in high-fat diet-fed hamsters can produce events comparable to those found in some neurodegenerative diseases, and may promote brain ageing.
Pro-Inflammatory Adipokine and Cytokine Profiles in the Saliva of Obese Patients with Non-Alcoholic Fatty Liver Disease (NAFLD)—A Pilot Study
Authors: Zyśk Beata , Ostrowska Lucyna , Smarkusz-Zarzecka Joanna , Witczak-Sawczuk Katarzyna , Gornowicz Agnieszka , Bielawska Anna
Published: February 2023

Undiagnosed and untreated non-alcoholic fatty liver disease (NAFLD) can lead to the development of many complications, such as cirrhosis, hepatocellular carcinoma, or cardiovascular diseases. Obese people are at increased risk of developing NAFLD. Due to the current lack of routine diagnostics, it is extremely important to look for new diagnostic methods and markers for this disease. The aim of this study was to assess the concentration of selected pro-inflammatory adipokines and cytokines in the unstimulated saliva of obese people with fatty liver disease in various stages (with or without slight fibrosis) and to analyze them for possible use as early markers of NAFLD diagnosis. The study involved 96 people who were divided into 5 groups based on the criterion of body mass index (BMI) and the degree of fatty liver (liver elastography). There were statistically significant differences between the groups in the concentrations of MMP-9 (matrix metalloproteinase 9), resistin, and IL-1β (interleukin 1β) in saliva. Statistically significant, positive correlations between hepatic steatosis and the concentration of MMP-2 (matrix metalloproteinase 2), resistin, and IL-1β in saliva were also found. Statistically significant positive correlations were also found between the concentration of resistin in saliva and the concentration of ALT (alanine aminotransferase) and GGTP (gamma-glutamyl transpeptidase) in serum. MMP-2, IL-1β, and resistin may be potential markers of NAFLD development, assessed in saliva. However, further research is needed because this is the first study to evaluate the concentrations of the selected pro-inflammatory parameters in the saliva of patients with NAFLD.
The Geomagnetic Field (GMF) Is Required for Lima Bean Photosynthesis and Reactive Oxygen Species Production
Authors: Parmagnani Ambra S. , Betterle Nico , Mannino Giuseppe , D’Alessandro Stefano , Nocito Fabio F. , Ljumovic Kristina , Vigani Gianpiero , Ballottari Matteo , Maffei Massimo E.
Published: February 2023

Plants evolved in the presence of the Earth’s magnetic field (or geomagnetic field, GMF). Variations in MF intensity and inclination are perceived by plants as an abiotic stress condition with responses at the genomic and metabolic level, with changes in growth and developmental processes. The reduction of GMF to near null magnetic field (NNMF) values by the use of a triaxial Helmholtz coils system was used to evaluate the requirement of the GMF for Lima bean (Phaseolus lunatus L.) photosynthesis and reactive oxygen species (ROS) production. The leaf area, stomatal density, chloroplast ultrastructure and some biochemical parameters including leaf carbohydrate, total carbon, protein content and δ13C were affected by NNMF conditions, as were the chlorophyll and carotenoid levels. RubisCO activity and content were also reduced in NNMF. The GMF was required for the reaction center’s efficiency and for the reduction of quinones. NNMF conditions downregulated the expression of the MagR homologs PlIScA2 and PlcpIScA, implying a connection between magnetoreception and photosynthetic efficiency. Finally, we showed that the GMF induced a higher expression of genes involved in ROS production, with increased contents of both H2O2 and other peroxides. Our results show that, in Lima bean, the GMF is required for photosynthesis and that PlIScA2 and PlcpIScA may play a role in the modulation of MF-dependent responses of photosynthesis and plant oxidative stress.
Compromised Vibration Isolator of Electric Power Generator Considering Self-Excitation and Basement Input
Authors: Park Young Whan , Kim Tae-Wan , Kim Chan-Jung
Published: February 2023

A previous study proposed an optimal vibration isolator for self-excitation, but the solution results showed a critical drawback for the basement input. Because the plant system is exposed to self-excitation and basement input, the vibration isolator characteristics must meet all the requirements of both excitation cases. Two performance indices of the vibration isolator were introduced to evaluate the vibration control capability over two excitation cases, self-excitation and basement input, using the theoretical linear model of the electric power generator. The compromise strategy was devoted to enhancing the vibration control capability over the basement input, owing to the acceptable margin for self-excitation. The modification of the mechanical properties of the vibration isolator focused on the isolator between the mass block and the surrounding building. Simulation results revealed that an increase in the spring coefficient and a decrease in the damping coefficient of the vibration isolator beneath the mass block could enhance the vibration reduction capability over the basement input.
Planning for Aging and Frailty: A Qualitative Study on Older Adults’ Perceptions, Facilitators, and Barriers
Authors: Frechman Erica , Buck Harleah , Dietrich Mary S. , Rhoten Bethany A. , Davis Amanda , Maxwell Cathy A.
Published: February 2023

Aging is often accompanied by health events that may disrupt older adults’ desires to age in place. Understanding older adults’ perceptions of planning for their aging process was a priority to identify how planning behaviors occur. Our study explored how people perceive the concept of planning for aging and frailty, and identified the facilitators and barriers involved in the planning process. Using conventional qualitative content analysis, we used the data from semi-structured interviews of twenty community-dwelling older adults aged 50–80 years old. Demographic information was obtained, followed by the participant interviews. Seventeen code categories surfaced including six categories in the perception domain (i.e., internal, external, and future-oriented), seven categories in the facilitators domain (i.e., internal, external, and systems), and four categories in the barriers domain (i.e., internal, and systems). The emergent categories included understanding one’s perception of planning through a holistic lens, the importance of experiences with self/others as facilitators, and the physical/cognitive/emotional factors that serve as barriers within a larger sphere of societal influence. Planning for aging and frailty is an innovative concept that normalizes the aging process and promotes planning through an awareness of aging across the life-course domains. Future research is warranted for intervention development to help older adults recognize and actively plan for aging and to address the barriers involved.