Biochimica et biophysica acta. General subjects最新文献

Background: Salinity stress affects plant growth, development, biomass, yield, as well as their survival. A series of signaling cascade is activated to cope the deleterious effect of salinity stress. Cytokinins are known for their regulatory roles from cell growth and expansion to abiotic stress signaling. Two component system (TCS) are important multistep phosphorelay signal transduction machinery converging cytokinin, ethylene and light signal transduction pathways together. Plant TCS comprises of histidine kinases, phosho-transfer proteins and response regulators. Histidine kinases perceive the signal and relay it to response regulator via histidine containing phosphor-transfer proteins.

Scope of review: Response regulators are one of the major and diverse component of TCS system which have been extensively studied for their role in plant growth, development and circadian rhythm. However, knowledge of their regulatory role in abiotic stress signaling is limited. This mini-review specifically focus on role of response regulators in salinity stress signaling.

Major conclusion: Response regulators is the divergent node of TCS machinery, where cross-talks with other stress-mediated, phytohormone-mediated, as well as, light-mediated signaling pathways ensues. Studies from past few years have established central role of response regulators in salinity stress, however, the detailed mechanism of their actions need to be studied further.

General significance: Response regulators act as both negative as well as positive regulator of salinity and cytokinin signaling, making it an excellent target to increase crop yield as well as stress tolerance capabilities.

Factors influencing variance of DNA methylation in vegetatively reproducing plants, both terrestrial plants and aquatic seagrasses, is just beginning to be understood. Improving our knowledge of these mechanisms will increase understanding of transgenerational epigenetics in plant clones, of the relationship between DNA methylation and seagrass development, and of the drivers of epigenetic variation, which may underly acclimation in clonally reproducing plants. Here, we sampled leaves, rhizomes and roots of three physically and spatially separated ramet sections from a clonally propagated field of the seagrass Zostera marina. Using reduced methylome sequencing, we studied variations in the methylome of seagrass Zostera marina between the sampled tissue types and across age groups. Our analysis of ramets of different ages showed variations in methylation between older and younger samples in both specific methylation patterns and global methylation levels. Our analysis of tissue types showed a marked differentiation of the roots from the rhizomes and leaves, which showed more similar methylation patterns. These findings are in agreement with the strong connection of DNA methylation and plant development and tissue differentiation. We also suggest an effect of differential environmental exposures on the methylome of the younger versus the older ramets due to the forming of molecular stress memories.

Recent emerging evidence demonstrates that some long non-coding RNAs (lncRNAs) can indeed be translated into functional polypeptides. These discoveries are pivotal for understanding de novo gene birth, the process by which new genes evolve from previously non-genic regions. In this review, we first introduce key methods, such as Ribo-seq and translation initiation site detection by translation complex analysis, for identifying coding sequences within lncRNAs and highlight examples of functional polypeptides derived from lncRNAs across species. These polypeptides play essential roles in maintaining cellular homeostasis and contribute to pathological processes, including cancer. However, because not all lncRNA-derived polypeptides appear to be functional, these lncRNAs may act as gene reservoirs. We also discuss how lncRNAs change their intracellular localization, how lncRNA-derived polypeptides evade immune surveillance, and how they gradually evolve into typical coding RNAs, providing evidence for the evolutionary model of de novo gene birth.

MicroRNAs (miRNAs), which are small non-coding RNAs, are recognized as important significant endogenous bio-molecules that regulate the post-transcriptional processes of target genes. However, predictive methods for significantly working miRNAs are poorly understood. The present study aimed to establish a novel method, miRNA protein analysis of integrative relationship (miR-PAIR), for the identification of effectively working miRNAs involved in physiological or pathological events. To establish the miR-PAIR, comprehensive expression data of miRNAs and proteins were obtained using small RNA-sequence and quantitative proteomics approach in the alveolar epithelial cell line, A549 treated with bleomycin (BLM) and methotrexate (MTX) as pulmonary toxic drugs. Differentially expressed miRNAs and proteins were integrated using TargetScan, a freely available web tool for predicting the target gene of miRNAs. Next, the enrichment of the integrated miRNA-protein pairs was analyzed, followed by the determination of significantly working miRNAs in BLM- and MTX-induced protein expression changes. The miR-PAIR method identified 22 downregulated and 9 upregulated miRNAs. Among them, miR-493-5p (p = 1.71E-05), an upregulated miRNA, suppressed approximately 70 % of the target proteins, and miR-598-3p (p = 1.1E-03), a downregulated miRNA, canceled 50 % of the target protein expression changes induced by BLM and MTX. Thus, a miR-PAIR could be an effective method to identify significantly working miRNAs associated with biological events such as drug-induced lung injury.

Understanding the folding and unfolding mechanism of the protein is not only crucial in applications like biomedical, pharmaceutical, tissue engineering but also to the food industry. In the present study, an electron beam with 6 MeV energy derived from the Microtron accelerator was utilized to irradiate the aqueous solution of bovine serum albumin (BSA) at fluences of 5 × 10¹⁴ and 10 × 10¹⁴ e^-/cm². The control and irradiated BSA solutions were analyzed using UV-visible and FTIR spectroscopy. UV-visible spectroscopy showed a hyperchromic red shift in 235 nm (π → π*) and a blue shift in 268 nm (n → π*) bands with increasing fluence. Changes in aromatic acid residues of the proteins tertiary structure were observed from the 2nd derivative of absorbance spectra. FTIR spectra revealed a decrease in peak area corresponding to β-turns (21.80 to 15.50 %), and random coil (41.30 to 28.80 %) and increase in peak area was observed for β-sheet (29.25 to 35.40 %). These findings reveal the conformal changes in the electron irradiated BSA. Further, a decrease in the interfacial tension at the air/water interface suggests increase in hydrophobicity of the aqueous solution with fluence.

Brownian dynamics (BD) simulations, a powerful computer simulation tool that has gained significant attraction in investigating the intricate dynamics of chemical and biological systems. By meticulously modeling the diffusive motion of molecules and their intricate interactions, BD simulations offer invaluable insights into a diverse array of phenomena, including reaction kinetics, molecular transport, and biomolecular association. This comprehensive review delves into the utility of BD simulations within the realms of chemistry and biology. We meticulously explore the theoretical underpinnings of the technique, critically analyze its strengths and limitations, and showcase its diverse applications across various scientific domains. By providing a comprehensive analysis of the existing literature, we aim to illuminate the potential of BD simulations to significantly advance our understanding of complex chemical and biological systems, ultimately contributing to the development of innovative therapeutic solutions serving a broad range of biomedical applications.

The study delves into the binding properties of acridine-9-amine and its selected, mainly N-substituted derivatives (A9As), with calf thymus deoxyribonucleic acid (CT-DNA). This investigation, conducted using UV-Vis spectrophotometry, steady-state fluorescence spectroscopy and isothermal titration calorimetry, provides insights into the relationship between their structure and activity. The absorption spectra of the A9As exhibited a slight red shift and significant hypochromic effects, while the fluorescence emission intensities decreased in the presence of CT-DNA. These results suggest that all fluorescent substrates intercalate into the double helix of native DNA to varying degrees. The binding constants for the A9As/CT-DNA complexes (log(K_A) were determined using various techniques in the range from 2.59 to 5.50). The thermodynamic parameters of A9As binding to DNA were obtained from ITC measurements (ΔG from - 7.51 to - 6.75 kcal·mol^-1, ΔH from - 11.58 to - 3.83 kcal·mol^-1, and TΔS from - 4.83 to 3.68 kcal·mol^-1) and indicated that the formation of all the investigated A9As-DNA complexes is an enthalpy-driven process. The study also discusses the influence of the emitters' structure and electronic properties of substituents on intercalation efficiency. This knowledge serves as a guide for further research and offers directions for functionalising new acridines as potential reagents. It also provides the latest information on the ability of intercalation to DNA, which can be instrumental in studies on the mechanism of binding small aromatic molecules to DNA and can potentially contribute to new anticancer drug designs.

Titanium oxide nanoparticles (TiO₂ NPs) are currently used as ingredients in medicines and sunscreens. Unfortunately, recent information about TiO₂ NPs indicates their undesirable biological effect on colon cells. Therefore, the aim of this work was to synthesize and evaluate the physicochemical characterization of spherical (TiO₂ NSs) and rods-like (TiO₂ NRs) NPs, followed by assessment their cytotoxicity. For this purpose, both normal colon epithelial cells (CRL-1790) and cancerous colon cells (SW480) were used. Scanning transmission electron microscopy (STEM) showed that TiO₂ NSs with a diameter of ≈10 nm and TiO₂ NRs with the size of the longer axis ≈25 nm and shorter axis ≈3 nm were obtained. Based on the selected area electron diffraction (SAED) patterns, it was found that crystalline phases were obtained for both TiO₂ NPs. The UV-Vis spectra showed no contamination of TiO₂ NPs. Zeta potential values were 9.7 mV and 3.1 mV for NSs and NRs, respectively. Cytotoxicity of TiO₂ NPs was assessed using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) test for various concentration of NPs. The cytotoxic effect for both TiO₂ NPs was visible for concentration of 75 μg/ml (for CRL-1790) and 50 μg/ml (for SW480) and higher, and it did not depend on the shape. Moreover, both types of TiO₂ NPs (in higher concentration) induce the generation of reactive oxygen species (ROS) in cells cultured with these NPs. Holotomographic microscopy studies showed increased cellular uptake of TiO₂ NPs by SW480. The obtained results for the synthesized TiO₂ NPs are a promising prospect for their use in biomedical application.

Atherosclerosis, the major underlying cause of cardiovascular disease, is believed to arise from the accumulation of low-density lipoprotein (LDL) in the arterial subendothelial space, ultimately leading to plaque formation. It is proposed that the accumulation of LDL is linked to its intrinsic aggregation propensity. Although the native LDL is not prone to aggregation, LDL(-), an electronegative LDL characterized in the plasma, has been shown to prime LDL aggregation in a domino-like behavior similar to amyloidogenic proteins. LDL(-) has also been observed to have a misfolded apolipoprotein B-100 (apo B-100), a huge protein consisting of 4563 amino acid residues. As misfolding of proteins is commonly associated with amyloid formation, apo B-100 is therefore being considered as the possible triggering factor in LDL aggregation. Previous computational studies have implicated the α2 domain to be the aggregation-prone region of apo B-100. In this study, the amyloidogenic properties of the α2 domain of apo B-100 were interrogated using both in silico and in vitro techniques. Since the crystal structure of the 570-amino acid α2 domain of apo B-100 is yet to be solved, we used several secondary structure prediction tools to model putative helical regions that make up the α2 domain. The stability of each of the 17 helices thus identified was further probed using molecular dynamics (MD), with the least stable of the helices considered as potentially amyloidogenic. In a 100 ns simulation window, helices k (YFEKLVGFIDDAVK), m (YHQFVDETNDKIREVTQRLNGEIQA), and p (QQELQRYLSLVGQVYS) were the least stable and appeared to transition to β-structures, the hallmark of amyloidogenesis. When the simulation was extended to longer times, only helices k and p formed stable β-sheets that persisted. Analysis of the data indicates that the final β-sheet conformation was stabilized by the π-π stacking interactions between the aromatic rings of Tyr-1 and Phe-8 for helix k and likely π-π stacking contacts between Arg-6 guanidino group and Tyr-15 ring for helix p. Based on the in silico work, we proceeded to synthesize and spectroscopically characterize helices k, m_17-25 (QRLNGEIQA), and p. As expected, k and p formed detectable amyloids, with the latter appearing to be substantially more amyloidogenic based on kinetic aggregation assays. Amyloid fibrils formed by p were confirmed using circular dichroism spectroscopy and transmission electron microscopy. Data obtained could be exploited to further investigate the roles of peptides derived from the α2 domain helices of apo B-100 in triggering LDL aggregation. Based on preliminary data, one of the peptides designed based on this work reduced the aggregation of LDL.

Endothelial cell-sourced exosomes are potential participants in the process of atherosclerosis, and their function is mainly affected by concentration. By studying the effects of exosome concentrations on vascular cells, atherosclerosis can be better intervened. In this study, exosomes with concentrations of 0, 0.07, 0.35, 1.75 and 8.75 μg/mL were set to interact with endothelial cells, macrophages and smooth muscle cells respectively. The results suggested that EC-Exo altered vascular cells' proliferation, migration and nitric oxide release abilities, increasing with EC-Exo concentrate from 0 to 1.75 μg/mL and varing with cell types at 8.75 μg/mL. The effects of exosome on cells is dose-responsive，and endothelial cells-sourced exosome favors vascular repair within the concentration of 0.35-1.75 μg/mL，showing potential for atherosclerosis regulation.