Search Results (1,479)

Neuroblastoma is a devastating disease accounting for ~15% of all childhood cancer deaths. Collagen content and fiber association within the tumor stroma influence tumor progression and metastasis. High expression levels of collagen receptor kinase, Discoidin domain receptor II (DDR2), are associated with the poor survival of neuroblastoma patients. Additionally, cancer cells generate and sustain mechanical forces within their environment as a part of their normal physiology. Despite this, evidence regarding whether collagen-activated DDR2 signaling dysregulates these migration forces is still elusive. To address these questions, a novel shRNA DDR2 knockdown neuroblastoma cell line (SH-SY5Y) was engineered to evaluate the consequence of DDR2 on cellular mechanics. Atomic force microscopy (AFM) and traction force microscopy (TFM) were utilized to unveil the biophysical altercations. DDR2 downregulation was found to significantly reduce proliferation, cell stiffness, and cellular elongation. Additionally, DDR2-downregulated cells had decreased traction forces when plated on collagen-coated elastic substrates. Together, these results highlight the important role that DDR2 has in reducing migration mechanics in neuroblastoma and suggest DDR2 may be a promising novel target for future therapies. Full article

Roots are usually underground plant organs, responsible for anchoring to the soil, absorbing water and nutrients, and interacting with the rhizosphere. During root development, roots respond to a variety of environmental signals, contributing to plant survival. Histone post-translational modifications play essential roles in gene expression regulation, contributing to plant responses to environmental cues. Histone acetylation is one of the most studied post-translational modifications, regulating numerous genes involved in various biological processes, including development and stress responses. Although the effect of histone acetylation on plant responses to biotic and abiotic stimuli has been extensively reviewed, no recent reviews exist focusing on root development regulation by histone acetylation. Therefore, this review brings together all the knowledge about the impact of histone acetylation on root development in several plant species, mainly focusing on Arabidopsis thaliana. Here, we summarize the role of histone acetylation and deacetylation in numerous aspects of root development, such as stem cell niche maintenance, cell division, expansion and differentiation, and developmental zone determination. We also emphasize the gaps in current knowledge and propose new perspectives for research toward deeply understanding the role of histone acetylation in root development. Full article

This study focuses on optimizing the storage capacity of an underground natural gas storage facility through numerical modeling and simulation techniques. The reservoir, characterized by an elongated dome structure, was discretized into approximately 16,000 cells. Simulations were conducted using key parameters such as permeability (10–70 mD) and porosity (12–26%) to assess the dynamics of gas injection and pressure distribution. The model incorporated core and petrophysical data to accurately represent the reservoir’s behavior. By integrating new wells in areas with storage deficits, the model demonstrated improvements in storage efficiency and pressure uniformity. The introduction of additional wells led to a significant increase in storage volume from 380 to 512 million Sm³ and optimized the injection process by reducing the storage period by 25%. The study concludes that reservoir performance can be enhanced with targeted well placement and customized flow rates, resulting in both increased storage capacity and economic benefits. Full article

Telomeres—special DNA–protein structures at the ends of linear eukaryotic chromosomes—define the proliferation potential of cells. Extremely short telomeres promote a DNA damage response and cell death to eliminate cells that may have accumulated mutations after multiple divisions. However, telomere elongation is associated with the increased proliferative potential of specific cell types, such as stem and germ cells. This elongation can be permanent in these cells and is activated temporally during immune response activation and regeneration processes. The activation of telomere lengthening mechanisms is coupled with increased proliferation and the cells’ need for energy and building resources. To obtain the necessary nutrients, cells are capable of finely regulating energy production and consumption, switching between catabolic and anabolic processes. In this review, we focused on the interconnection between metabolism programs and telomere lengthening mechanisms during programmed activation of proliferation, such as in germ cell maturation, early embryonic development, neoplastic lesion growth, and immune response activation. It is generally accepted that telomere disturbance influences biological processes and promotes dysfunctionality. Here, we propose that metabolic conditions within proliferating cells should be involved in regulating telomere lengthening mechanisms, and telomere length may serve as a marker of defects in cellular functionality. We propose that it is possible to reprogram metabolism in order to regulate the telomere length and proliferative activity of cells, which may be important for the development of approaches to regeneration, immune response modulation, and cancer therapy. However, further investigations in this area are necessary to improve the understanding and manipulation of the molecular mechanisms involved in the regulation of proliferation, metabolism, and aging. Full article

As a reader of tri-methylated lysine 36 on histone H3 (H3K36me3), Npac has been shown to have a significant role in gene transcription elongation. However, its potential implication in RNA splicing remains unknown. Here, we characterized the phenotypes of Npac knockout in mES cells. We discovered that loss of Npac disrupts pluripotency and identity in mESCs. We also found that Npac is associated with many cellular activities, including cell proliferation, differentiation, and transcription regulation. Notably, we uncovered that Npac is associated with RNA splicing machinery. Furthermore, we found that Npac regulates alternative splicing through its interaction with the splicing factors, including Srsf1. Our research thus highlights the important role of Npac in maintaining ESC identity through the regulation of pre-mRNA splicing. Full article

Background: Intermittent pneumatic compression is a non-invasive therapeutic technique that has been gaining popularity in recent years due to its potential use in many areas of medicine. It can be successfully used alone or in combination with other therapeutic methods. The aim of this study was to investigate whether and how a series of pressotherapy treatments on the lower limbs affects the rheological properties of blood (blood count, red blood cell deformability and aggregation, and blood viscosity), lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), and renal profile (urea, creatinine, and estimated glomerular filtration rate) in young, healthy women. Methods: The study group consisted of 15 healthy women aged 20–26 (22.5 ± 1.5), without chronic diseases and not practicing competitive sports. The participants underwent a series of 10 lower limb pressotherapy treatments. A single treatment lasted 30 min and each time the pressure used during the treatment was individually selected according to the participants’ preference. The first blood test was performed a week before the treatments; the second on the day of the start of treatment, but before the pneumatic massage; the third after the completed series of pressotherapy treatments; and the fourth a week after the completed series of treatments. Results: In the conducted study, the analysis of the values of the complete blood count showed the following: a significant decrease in red blood cell count, hemoglobin, average hemoglobin concentration in erythrocytes, average red blood cell volume, average hemoglobin mass in red blood cells; a significant increase in average red blood cell volume; and an average hemoglobin mass in red blood cells. The analysis of the values of rheological parameters showed the following: a significant decrease in elongation indices 0.58, 1.13, 4.24, 15.95, 30.94, and 60.00; blood viscosity; the aggregation index; the degree of complete aggregation; and a significant increase in elongation indices 0.30, 1.13, 8.23, 30.94, 60.00; blood viscosity; the degree of complete aggregation; and the half-time of complete aggregation. A decrease in the concentration of low-density lipoprotein and high-density lipoprotein fractions was also noted. No significant changes were found in the values of total cholesterol and triglycerides, as well as in renal profile elements. Conclusions: The application of a series of 10 lower limb pressotherapy treatments has a beneficial effect, with a decrease in blood viscosity and the aggregation index, and an increase in the elongation index at shear stress from 0.30 [Pa] to 8.23 [Pa] in young, healthy women. A series of 10 lower limb pressotherapy treatments may affect the decrease in the values at high shear stress forces of 30.95 [Pa] and from 60.00 [Pa] in young, healthy women. The use of a series of 10 lower limb pressotherapy treatments increases the values of hemoglobin, the average red blood cell volume, and the average hemoglobin concentration in erythrocytes, and also reduces the values of red blood cell count, average hemoglobin mass in red blood cells and low-density lipoproteins and high-density lipoproteins in young, healthy women (it also does not cause any adverse changes). The use of pressotherapy on the lower limbs seems to be an effective element of the multi-component prevention of circulatory system diseases. Full article

Seed dormancy and germination are critical factors affecting oil palm production efficiency. The typical dormancy-breaking process involves dry heat treatment (38–40 °C for 40–60 days) followed by germination at 30–32 °C. To understand the molecular mechanisms behind this process and improve germination rates and speed, we conducted transcriptome analysis at three stages: pre-incubation, 45-day incubation at 40 °C, and 14-day germination at 32 °C. Our findings, supported by qRT–PCR and DEGs analysis, identified four key stages: ABA degradation, energy mobilization, starch mobilization, and cell elongation and division. ABA pathway genes (SnRK2, PYR/PYL) were active during dormancy release, while GAE and GPI were upregulated after heat treatment, indicating increased energy metabolism and structural changes. During germination, genes involved in starch/sucrose metabolism (SPS, TPP, SS, MGAM) and cell wall biosynthesis (GAUT1, PE, GAE) supported embryo expansion, with BAM, PGM, GlgB fueling early growth. Auxin (TIR1, AUX/IAA, ARF), brassinosteroid (BRI1, BSK, BIN2, CYCD3), ethylene (ETR, CTR1), and jasmonic acid (JAR1, COI1) pathway genes regulated cell growth and stress response, promoting seedling development. Though gibberellins were not crucial for this oil palm variety, gene expression varied between varieties. This study provides information on oil palm seed germination that could be applied to other oil palm species, particularly in terms of incubation times and chemical treatments. Full article

Background. Cyclin-dependent kinase 8 (CDK8) is a multifaceted regulator and represents a catalytic component of the transcriptional Mediator complex. CDK8 activity, on the one hand, increases transcriptional elongation by the recruitment of Mediator/super elongation complexes, but, on the other hand, negatively regulates CDK7-controlled transcriptional initiation through inactivating cyclin H phosphorylation. Recently, these combined properties of CDK8 have also suggested its rate-limiting importance for herpesviral replication. Objectives. In this paper, we focused on human cytomegalovirus (HCMV) and addressed the question of whether the pharmacological inhibition or knock-down of CDK8 may affect viral replication efficiency in cell culture models. Methods. A number of human and animal herpesviruses, as well as non-herpesviruses, were used to analyze the importance of CDK8 for viral replication in cell culture models, and to assess the antiviral efficacy of CDK8 inhibitors. Results. Using clinically relevant CDK8 inhibitors (CCT-251921, MSC-2530818, and BI-1347), HCMV replication was found strongly reduced even at nanomolar drug concentrations. The EC₅₀ values were consistent for three different HCMV strains (i.e., AD169, TB40, and Merlin) analyzed in two human cell types (i.e., primary fibroblasts and astrocytoma cells), and the drugs comprised a low level of cytotoxicity. The findings highlighted the following: (i) the pronounced in vitro SI values of anti-HCMV activity obtained with CDK8 inhibitors; (ii) a confirmation of the anti-HCMV efficacy by CDK8–siRNA knock-down; (iii) a CDK8-dependent reduction in viral immediate early, early, and late protein levels; (iv) a main importance of CDK8 for viral late-stage replication; (v) several mechanistic aspects, which point to a strong impact on viral progeny production and release, but a lack of CDK8 relevance for viral entry or nuclear egress; (vi) a significant anti-HCMV drug synergy for combinations of inhibitors against host CDK8 and the viral kinase vCDK/pUL97 (maribavir); (vii) finally, a broad-spectrum antiviral activity, as seen for the comparison of selected α-, β-, γ-, and non-herpesviruses. Conclusions. In summary, these novel data provide evidence for the importance of CDK8 as a positive regulator of herpesviral replication efficiency, and moreover, suggest its exploitability as an antiviral target for novel strategies of host-directed drug development. Full article

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1. Full article

Begonia rex cv. DS-EYWA is an important plant for indoor and outdoor cultivation, and cv. DS-EYWA is a rare unique cultivar with curly, colorful leaves. Due to their importance, applying plant tissue culture techniques for mass and healthy production in a short period of time without seasonal limitation is of immense economic value. Applying several concentrations of silver nitrate (AgNO₃) in combination with varied concentrations of cytokinins including 6-benzylaminopurine (BAP), thidiazuron (TDZ) (0, 0.5, 1, 1.5 mgL⁻¹), and 1-naphthaleneacetic acid (NAA) auxin (0, 0.5, 1 mgL⁻¹) via focusing on transverse thin cell layer (tTCL) petiole explants for high-scale production was used to establish an efficient in vitro propagation protocol. Our results showed that even low concentrations (25 mgL⁻¹) can control internal bacterial infection and increase shoot direct regeneration efficiency. A combination of 1.5 mgL⁻¹ BAP, 0.5 mgL⁻¹ NAA, and 25 mgL⁻¹ AgNO₃ was the best treatment to increase the number of direct regenerated shoots, and a lower concentration of BAP (0.5 mgL⁻¹) can be suggested for shoot elongation. Elongated shoots were successfully rooted in MS basal medium and acclimatized in a 1:1 peat moss/perlite sterilized pot mixture. Full article

Lithium-ion batteries (LIBs) are well known for their energy efficiency and environmental benefits. However, increasing their energy density compromises their safety. This study introduces a novel ceramic-coated separator to enhance the performance and safety of LIBs. Electrospinning was used to apply a coating consisting of an alumina (Al₂O₃) ceramic and polyacrylic acid (PAA) binder to a polypropylene (PP) separator to significantly improve the mechanical properties of the PP separator and, ultimately, the electrochemical properties of the battery cell. Tests with 2032-coin cells showed that the efficiency of cells containing separators coated with 0.5 g PAA/Al₂O₃ was approximately 10.2% higher at high current rates (C-rates) compared to cells with the bare PP separator. Open circuit voltage (OCV) tests revealed superior thermal safety, with bare PP separators maintaining stability for 453 s, whereas the cells equipped with PP separators coated with 4 g PAA/Al₂O₃ remained stable for 937 s. The elongation increased from 88.3% (bare PP separator) to 129.1% (PP separator coated with 4 g PAA/Al₂O₃), and thermal shrinkage decreased from 58.2% to 34.9%. These findings suggest that ceramic/PAA-coated separators significantly contribute to enhancing the thermal safety and capacity retention of high-energy-density LIBs. Full article

Submergence stress challenges direct seeding in rice cultivation. In this study, we identified a heat shock protein, NAL11, with a DnaJ domain, which can regulate the length of rice coleoptiles under flooded conditions. Through bioinformatics analyses, we identified cis-regulatory elements in its promoter, making it responsive to abiotic stresses, such as hypoxia or anoxia. Expression of NAL11 was higher in the basal regions of shoots and coleoptiles during flooding. NAL11 knockout triggered the rapid accumulation of abscisic acid (ABA) and reduction of Gibberellin (GA), stimulating rice coleoptile elongation and contributes to flooding stress management. In addition, NAL11 mutants were found to be more sensitive to ABA treatments. Such knockout lines exhibited enhanced cell elongation for coleoptile extension. Quantitative RT-PCR analysis revealed that NAL11 mediated the gluconeogenic pathway, essential for the energy needed in cell expansion. Furthermore, NAL11 mutants reduced the accumulation of reactive oxygen species (ROS) and malondialdehyde under submerged stress, attributed to an improved antioxidant enzyme system compared to the wild-type. In conclusion, our findings underscore the pivotal role of NAL11 knockout in enhancing the tolerance of rice to submergence stress by elucidating its mechanisms. This insight offers a new strategy for improving resilience against flooding in rice cultivation. Full article

Plants from the Brassicales order are known for the presence of a glucosinolate–myrosinase link, which is an important protection strategy against multiple stressors. The main goal of this study was to investigate the presence of the myrosinase enzyme and reveal the myrosin cell ultrastructure in the vegetative organs of nasturtium. The presence, localisation and expression of the enzyme myrosinase type 1 (TGG1) at different developmental stages of Tropaeolum majus L. (nasturtium) were investigated using immunohistochemical and immunofluorescent techniques. The expression of myrosinase was detected in the vegetative organs of T. majus. During plant development, within four consecutive weeks, a decrease in myrosinase expression was noticed in all studied plant organs. The location of greater myrosinase accumulation and activity is shown to be the root, contrary to the nasturtium stem and leaf, where we found the lowest myrosinase expression. Transmission electron microscopy was used to reveal the ultrastructural features of the myrosin cells of nasturtium. Myrosin cells are usually scattered between parenchyma cells and S-cells. Mostly, they are rectangular or slightly elongated in shape and can be recognised by an electron-dense large central vacuole and an expanded rough endoplasmic reticulum. The results of this study provide new data on myrosin cell morphology and the expression pattern of myrosinase in T. majus. Full article

Lately, the inclusion of additional lactic acid bacteria (LAB) strains to cheeses is becoming more popular since they can affect cheese’s nutritional, technological, and sensory properties, as well as increase the product’s safety. This work studied the effect of Lactiplantibacillus pentosus L33 and Lactiplantibacillus plantarum L125 free cells and supernatants on feta cheese quality and Listeria monocytogenes fate. In addition, rapid and non-invasive techniques such as Fourier transform infrared (FTIR) and multispectral imaging (MSI) analysis were used to classify the cheese samples based on their sensory attributes. Slices of feta cheese were contaminated with 3 log CFU/g of L. monocytogenes, and then the cheese slices were sprayed with (i) free cells of the two strains of the lactic acid bacteria (LAB) in co-culture (F, ~5 log CFU/g), (ii) supernatant of the LAB co-culture (S) and control (C, UHT milk) or wrapped with Na-alginate edible films containing the pellet (cells, FF) or the supernatant (SF) of the LAB strains. Subsequently, samples were stored in air, in brine, or in vacuum at 4 and 10 °C. During storage, microbiological counts, pH, and water activity (a_w) were monitored while sensory assessment was conducted. Also, in every sampling point, spectral data were acquired by means of FTIR and MSI techniques. Results showed that the initial microbial population of Feta was ca. 7.6 log CFU/g and consisted of LAB (>7 log CFU/g) and yeast molds in lower levels, while no Enterobacteriaceae were detected. During aerobic, brine, and vacuum storage for both temperatures, pathogen population was slightly postponed for S and F samples and reached lower levels compared to the C ones. The yeast mold population was slightly delayed in brine and vacuum packaging. For aerobic storage at 4 °C, an elongation in the shelf life of F samples by 4 days was observed compared to C and S samples. At 10 °C, the shelf life of both F and S samples was extended by 13 days compared to C samples. FTIR and MSI analyses provided reliable estimations of feta quality using the PLS-DA method, with total accuracy (%) ranging from 65.26 to 84.31 and 60.43 to 89.12, respectively. In conclusion, the application of bioprotective LAB strains can result in the extension of feta’s shelf life and provide a mild antimicrobial action against L. monocytogenes and spoilage microbiota. Furthermore, the findings of this study validate the effectiveness of FTIR and MSI techniques, in tandem with data analytics, for the rapid assessment of the quality of feta samples. Full article

Pearl millet is a major cereal crop that feeds more than 90 million people worldwide in arid and semi-arid regions. The stalk phenotypes of Poaceous grasses are critical for their productivity and stress tolerance; however, the molecular mechanisms governing stalk development in pearl millet remain to be deciphered. In this study, we spatiotemporally measured 19 transcriptomes for stalk internodes of four different early developmental stages. Data analysis of the transcriptomes defined four developmental zones on the stalks and identified 12 specific gene sets with specific expression patterns across the zones. Using weighted gene co-expression network analysis (WGCNA), we found that two co-expression modules together with candidate genes were involved in stalk elongation and the thickening of pearl millet. Among the elongation-related candidate genes, we established by SELEX that a MYB-family transcription factor PMF7G02448 can bind to the promoters of three cell wall synthases genes (CesAs). In summary, these findings provide insights into stalk development and offer potential targets for future genetic improvement in pearl millet. Full article