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Molecular biology of the cell (4th ed.): Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P.
... Adenosine triphosphate-hydrolyzing enzymes (ATPases) are transmembrane proteins that play a key role in a varied array of cellular functions across all kingdoms of life [24]. These dynamic proteins transport solutes across membranes and act as molecular motors that use the energy of ATP hydrolysis to conduct such mechanical works as ion pumping, cellular metabolism, muscle movement, protein trafficking, unfolding, replication, and transcription [25]. ...
... The effects of LC 20 and LC 70 of the EOs on carboxylesterase and GST activities in the A. ipsilon 2nd instar larvae at different time intervals (24,48,72, and 96 h) post-treatments are presented in Figure 3. Two-way ANOVA and Tukey's test were used to compare the treatments with the control. Additionally, both tested EOs were compared with each other at different time intervals (Table 3). ...
... Ca 2+ -ATPase, or the Ca 2+ pump, exists in the sarcoplasmic reticulum membrane of skeletal muscle cells and is responsible for about 90% of the organelle membrane protein. This pump serves as an intracellular store of Ca 2+ and accounts for moving Ca 2+ from the cytosol to the sarcoplasmic reticulum [24]. As reported by [94], the regulation of Ca 2+ inner or outer nerve membranes is chiefly performed by Mg 2+ /Ca 2+ -ATPase and Ca 2+ -ATPase. ...
In this study, in vitro and in silico approaches were employed to assess the toxicity of marjoram (Origanum majorana) and rosemary (Rosmarinus officinalis) essential oils (EOs) to A. ipsilon larvae. The study determined the activities of ATPases in the larvae after treatment with the LC20 and LC70 of each EO. α-esterase and glutathione-S-transferase (GST) activities were also determined after treatment with LC10 and LC30 of each EO. Furthermore, molecular docking was employed to determine the binding affinity of terpinene-4-ol and α-pinene, the major constituents of O. majorana, and R. officinalis EOs, respectively, compared to the co-crystallized ligand of α-esterase, diethyl hydrogen phosphate (DPF). Toxicity assays revealed that O. majorana EO was more toxic than R. officinalis EO to the A. ipsilon larvae at 96 h post-treatment. However, the LC20 and LC70 of the latter significantly inhibited the activity of the Na+-K+ pump at almost all intervals. The same concentrations significantly inhibited the Mg2+/Ca2+-ATPase and Ca2+ pump at 96 h post-treatment. In contrast, O. majorana EO showed a variable effect on the Na+-K+ pump across different time intervals. On the other hand, LC10 and LC30 of both EOs showed varied effects on α-esterase and GST over time. Molecular docking revealed energy scores of −4.51 and −4.29 kcal/mol for terpinene-4-ol and α-pinene, respectively, compared to a score of −4.67 for PDF. Our study demonstrated the toxicity of the tested EOs to A. ipsilon, suggesting their potential efficacy as insecticides.
... As a major cell death pathway, apoptosis plays an important role in the biological maintenance of homeostasis and has been widely studied. 34 Aberrant apoptosis of cells would give rise to cardiovascular disease, immune disease, neurodegenerative diseases and osteoporosis. 35−37 Apoptosis could be visualized through multiple characteristics, including shrinkage of the cytoplasm, condensation of nuclei, detachment from the surrounding tissue, and convolution of outlines. ...
... One important pathway is mitogenactivated protein kinase (MAPK) induced by inflammation and ROS generation. 34 For instance, many studies have found that FPM could sensitize lung epithelial cells to apoptosis via nuclear factor kappa-B (NF-κB), TNF-α, and signal transducer and activator of transcription 1 (STAT1) signaling pathways, leading to the inflammation in the respiratory system. 43 This pathway has also been validated after silica nanoparticle (one typical model FPM) exposure to the lung epithelial cells, that the cells would be primed to undergo apoptosis. ...
Recently, the advent of health risks due to the cytotoxicity of fine particulate matter (FPM) is concerning. Numerous studies have reported abundant data elucidating the FPM-induced cell death pathways. However, several challenges and knowledge gaps are still confronted nowadays. On one hand, the undefined components of FPM (such as heavy metals, polycyclic aromatic hydrocarbons, and pathogens) are all responsible for detrimental effects, thus rendering it difficult to delineate the specific roles of these copollutants. On the other hand, owing to the crosstalk and interplay among different cell death signaling pathways, precisely determining the threats and risks posed by FPM is difficult. Herein, we recapitulate the current knowledge gaps present in the recent studies regarding FPM-induced cell death, and propose future research directions for policy-making to prevent FPM-induced diseases and improve knowledge concerning the adverse outcome pathways and public health risks of FPM.
... Cell membranes have a thickness ranging between 4 nm and 10 nm and are constituted by a molecular assembly resulting from low-energy interactions occurring among a wide range of lipids and proteins. 8 Phospholipids account for about half the mass of the cell membrane and are insoluble in water. In addition, due to their amphiphilic nature, lipids self-assemble into a double layer, with the non-polar hydrophobic tails facing each other in the bilayer core and the hydrophilic, polar phosphate heads in contact with water. ...
... Depending on their structure, proteins can be embedded into the membrane (integral proteins) or loosely attached to its inside or outside face (peripheral membrane proteins and lipidanchored proteins). 8 The protein and lipid composition is specific to each cell type, even though it can change during cell replication as a strategy to avoid excessive defect replication and to enhance species survivability. 4,6,7 The accepted model that describes the membrane structure and dynamics is known as the fluid mosaic model and was first proposed by Singer and Nicolson in 1972. ...
Cell membrane perturbation is a common way to stimulate cells by using external actuators. Recently, nanotechnology has added a number of new strategies for doing this, enlarging the scope and the range of mechanisms involved. Here, we describe a number of possible perturbation actions that are driven by light, and we try to capture the underlying phenomena. The discussion is based on the simple equivalent circuit model for the cell membrane.
... Moreover, the portion of 14-methyl-pentadecanoic acid (iso-C16:0), octadecanoic acid (C18:0), and eicosanoic acid (C20:0) in the cytoplasmic membrane were increased in the mutant strain. Long chain saturated fatty acids might have increased the survival rate of the mutant strain to β-lactam antibiotics by decreasing the membrane permeability and increasing the stability of the cytoplasmic membrane (Fig. 3c) (Hashimoto and Hossain 2018;Uzman 2003). ...
... Maintaining lower amount of extracellular fatty acids can block the possible anti-bacterial effect from free fatty acids which interfere with electron transfer chain, protein assembly and increase membrane permeability and leakage (García-Fernández et al. 2017;Yoon et al. 2018). On the other hand, accumulation of long chain fatty acids decrease membrane permeability and increase membrane stability (Uzman 2003). These changes might have affected the antibiotic resistance of Δagr mutant strain since physiology of phospholipid affect the antibiotic resistance (Rosado et al. 2015). ...
Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts resistance to β-lactam antibiotics remains unclear. In the present study, we found the Δagr mutant strain having higher resistance to high concentrations of β-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membrane. To target membrane, we applied several surfactants and found that sorbitan monolaurate (Span20) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr deletion allows for MRSA to resist antibiotics via several changes including constant expression of mecA, fatty acid metabolism, and biofilm thickening.
... In the presence of 50 μg/mL of oxacillin and ampicillin the disk diffusion method was carried out. The error bars represent the standard deviation of three replicates have increased the survival rate of the mutant strain to β-lactam antibiotics by decreasing the membrane permeability and increasing the stability of the cytoplasmic membrane (Fig. 3c) (Hashimoto and Hossain 2018;Uzman 2003). ...
... Maintaining lower amount of extracellular fatty acids can block the possible anti-bacterial effect from free fatty acids which interfere with electron transfer chain, protein assembly and increase membrane permeability and leakage (García-Fernández et al. 2017;Yoon et al. 2018). On the other hand, accumulation of long chain fatty acids decrease membrane permeability and increase membrane stability (Uzman 2003). These changes might have affected the antibiotic resistance of Δagr mutant strain since physiology of phospholipid affect the antibiotic resistance (Rosado et al. 2015). ...
Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and is therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts factors affecting resistance to β-lactam antibiotics remains unclear. In the present study, we found an Δagr mutant strain with higher resistance to high concentrations of b-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membranes. To target these differences in fatty acid distribution and membrane composition, we applied several surfactants and found that sorbitan trioleate (Span85) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr suppression allows for MRSA to antagonize antibiotics via several changes, including constant expression of mecA, fatty acid metabolism and distribution, and biofilm thickening, resulting in a strain with higher resistance to β-lactam antibiotics.
... The plasma membrane consists of a bilayer of amphipathic phospholipids made up of hydrophilic phosphate head groups as well as hydrophobic acyl chains, creating a barrier between the cytosol and extracellular space [62]. Most biological membranes vary in width between 3 and 10 nm depending on the lipid content and membrane protein composition [63,64]. ...
ABC toxin complexes are a class of protein toxin translocases comprised of a multimeric assembly of protein subunits. Each subunit displays a unique composition, contributing to the formation of a syringe-like nano-machine with natural cargo carrying, targeting, and translocation capabilities. Many of these toxins are insecticidal, drawing increasing interest in agriculture for use as biological pesticides. The A subunit (TcA) is the largest subunit of the complex and contains domains associated with membrane permeation and targeting. The B and C subunits, TcB and TcC, respectively, package into a cocoon-like structure that contains a toxic peptide and are coupled to TcA to form a continuous channel upon final assembly. In this review, we outline the current understanding and gaps in the knowledge pertaining to ABC toxins, highlighting seven published structures of TcAs and how these structures have led to a better understanding of the mechanism of host tropism and toxin translocation. We also highlight similarities and differences between homologues that contribute to variations in host specificity and conformational change. Lastly, we review the biotechnological potential of ABC toxins as both pesticides and cargo-carrying shuttles that enable the transport of peptides into cells.
... Proteins are the building units of skeletal muscles; therefore, dietary amino acid uptake through proteins is essential in maintaining the growth and repair of muscle mass and function [14,15]. Previous studies have shown that protein restriction during lactation inhibited the development of mammary glands, ultimately causing a decrease in the quantity and quality of breast milk produced [16][17][18]. ...
Sarcopenia is characterised by the loss of skeletal muscle mass and function, which leads to a high risk of increased morbidity and mortality. Maternal malnutrition has been linked to impaired development of skeletal muscle of the offspring; however, there are limited studies that report the long-term effect of a maternal low-protein diet during lactation on the ageing of skeletal muscles. This study aimed to examine how a maternal low-protein diet (LPD) during lactation affects skeletal muscle ageing in the offspring. Pups born from control mothers were lactated by mothers fed with an LPD. Post-weaning, mice were either maintained on an LPD or switched to a control, normal-protein diet (NPD). In males, an LPD mainly affected the size of the myofibres without a major effect on fibre number and led to reduced grip strength in ageing mice (24 months). Female mice from mothers on an LPD had a lower body and muscle weight at weaning but caught up with control mice at 3 months. During ageing, the muscle weight, myofibre number and survival rate of female pups were significantly affected. These findings highlight the effect of an LPD during lactation on skeletal muscle ageing, the lifespan of offspring and the importance of sexual dimorphism in response to dietary challenges.
... However, the actual number of B cell clones within a human is estimated to be around 10 9 . 1 Antibodies are secreted by activated plasma cells, and the sequence of the antigen-binding site in the released antibodies corre-sponds to the B cell receptor (BCR) sequence of the precursor cell. 2 Nonetheless, as only a fraction of all B cells are activated by antigens and subsequently produce antibodies, the immune repertoire of membrane-bound BCR does not completely and sufficiently represent that of the soluble antibodies circulating in the bloodstream. 3 As a result, BCR sequencing alone falls short in providing quantities of circulating antibodies. ...
The polyclonal repertoire of circulating antibodies potentially holds valuable information about an individual’s humoral immune state. While bottom-up proteomics is well suited for serum proteomics, the vast number of antibodies and dynamic range of serum challenge this analysis. To acquire the serum proteome more comprehensively, we incorporated high-field asymmetric waveform ion-mobility spectrometry (FAIMS) or two-dimensional chromatography into standard trypsin-based bottom-up proteomics. Thereby, the number of variable region (VR)-related spectra increased 1.7-fold with FAIMS and 10-fold with chromatography fractionation. To match antibody VRs to spectra, we combined de novo searching and BLAST alignment. Validation of this approach showed that, as peptide length increased, the de novo accuracy decreased and BLAST performance increased. Through in silico calculations on antibody repository sequences, we determined the uniqueness of tryptic VR peptides and their suitability as antibody surrogate. Approximately one-third of these peptides were unique, and about one-third of all antibodies contained at least one unique peptide.
... .intron (situated 20-50 nucleotides upstream of the acceptor site), and intron. . .Y rich -N-C-A-G-[cut]-G [6][7][8]. In some rare events, certain pre-mRNA introns undergo self-splicing, obviating Table 1. ...
The current investigation endeavors to identify differentially expressed alternatively spliced (DAS) genes that exhibit concordant expression with splicing factors (SFs) under diverse multifactorial abiotic stress combinations in Arabidopsis seedlings. SFs serve as the post-transcriptional mechanism governing the spatiotemporal dynamics of gene expression. The different stresses encompass variations in salt concentration, heat, intensive light, and their combinations. Clusters demonstrating consistent expression profiles were surveyed to pinpoint DAS/SF gene pairs exhibiting concordant expression. Through rigorous selection criteria, which incorporate alignment with documented gene functionalities and expression patterns observed in this study, four members of the serine/arginine-rich (SR) gene family were delineated as SFs concordantly expressed with six DAS genes. These regulated SF genes encompass cactin, SR1-like, SR30, and SC35-like. The identified concordantly expressed DAS genes encode diverse proteins such as the 26.5 kDa heat shock protein, chaperone protein DnaJ, potassium channel GORK, calcium-binding EF hand family protein, DEAD-box RNA helicase, and 1-aminocyclopropane-1-carboxylate synthase 6. Among the concordantly expressed DAS/SF gene pairs, SR30/DEAD-box RNA helicase, and SC35-like/1-aminocyclopropane-1-carboxylate synthase 6 emerge as promising candidates, necessitating further examinations to ascertain whether these SFs orchestrate splicing of the respective DAS genes. This study contributes to a deeper comprehension of the varied responses of the splicing machinery to abiotic stresses. Leveraging these DAS/SF associations shows promise for elucidating avenues for augmenting breeding programs aimed at fortifying cultivated plants against heat and intensive light stresses.
... Enzymes are crucial in converting substrates into products, releasing energy the cell can use for various cellular processes. 130 This involvement extends to various biochemical processes, including substrate oxidation−reduction reactions, glycolysis, the Krebs cycle, photosynthesis, and chemiosmosis. 131 The energy generated or consumed in an enzymatic reaction can serve as an indicator of the enzyme activity. ...
Enzymes serve as pivotal biological catalysts that accelerate essential chemical reactions, thereby influencing a variety of physiological processes. Consequently, the monitoring of enzyme activity and inhibition not only yields crucial insights into health and disease conditions but also forms the basis of research in drug discovery, toxicology, and the understanding of disease mechanisms. In this context, near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) have emerged as effective tools for tracking enzyme activity and inhibition through diverse strategies. This perspective explores the physicochemical attributes of SWCNTs that render them well-suited for such monitoring. Additionally, we delve into the various strategies developed so far for successfully monitoring enzyme activity and inhibition, emphasizing the distinctive features of each principle. Furthermore, we contrast the benefits of SWCNT-based NIR probes with conventional gold standards in monitoring enzyme activity. Lastly, we highlight the current challenges faced in this field and suggest potential solutions to propel it forward. This perspective aims to contribute to the ongoing progress in biodiagnostics and seeks to engage the wider community in developing and applying enzymatic assays using SWCNTs.
... [3a,5] These nano-/micro-compartments are perfectly designed to orchestrate cascades of chemical reactions within the confined space, significantly augmenting the reaction rates of both hydrophilic and oleophilic reactions in the phase-separated compartments. [6] Mimicking such biological compartments as nanoreactors with diverse catalytic properties encompassing both aqueous and non-aqueous reactions remains a significant challenge in the emerging pursuit of artificial, temporally controlled macromolecular systems. Besides, it is one of the most important aspects for the design of nextgeneration adaptive and self-repairing functional material systems with cell-like properties. ...
Dissipative supramolecular assemblies are hallmarks of living systems, contributing to their complex, dynamic structures and emerging functions. Living cells can spatiotemporally control diverse biochemical reactions in membrane compartments and condensates, regulating metabolite levels, signal transduction or remodeling of the cytoskeleton. Herein, we constructed membranous compartments using self‐assembly of lipid‐like amphiphiles (lipidoid) in aqueous medium. The new double‐tailed lipidoid features Cu(II) coordinated with a tetravalent chelator that dictates the binding of two amphiphilic ligands in cis‐orientation. Hydrophobic interactions between the lipidoids coupled with intermolecular hydrogen bonding led to a well‐defined bilayer vesicle structure. Oil‐soluble SNAr reaction is efficiently upregulated in the hydrophobic cavity, acting as a catalytic crucible. The modular system allows easy incorporation of exposed primary amine groups, which augments the catalysis of retro aldol and C−N bond formation reactions. Moreover, a higher‐affinity chelator enables consumption of the Cu(II) template leveraging the differential thermodynamic stability, which allows a controllable lifetime of the vesicular assemblies. Concomitant temporal upregulation of the catalytic reactions could be tuned by the metal ion concentration. This work offers new possibilities for metal ion‐mediated dynamic supramolecular systems, opening up a massive repertoire of functionally active dynamic “life‐like” materials.
... The transport mechanism of monosaccharide can be divided to two main pathways, one is facilitated passive diffusion from the apical to the basolateral side of enterocytes, another is carrier-mediated active uptake and passive diffusion from the intestine lumen to lamina propria. Due to its polar nature, the transportation of D-allulose across lipid-rich cell membrane necessitates associated carrier proteins on the epithelial cells (Alberts et al., 2002). Previous study used GLUT5 gene inducer to investigate the effect of promoting GLUT5 expression on the permeability of D-allulose, this finding indicated a 3.2-fold increase in D-allulose permeability, indicating that its transportation in the small intestine occurs through GLUT5-facilitated passive diffusion (Hishiike et al., 2013). ...
... Breaks of the polynucleotide chains, loss of DNA bases and failures during the processes of DNA replication occur frequently, caused by metabolic events such as oxidative stress. The continuity of the genomic information is only preserved by very efficient DNA repair pathways [25]. However, DNA repair is not always complete and not always perfect. ...
DNA damage is one of the foremost mechanisms of irradiation at the biological level. After the first isolation of DNA by Friedrich Miescher in the 19th century, the structure of DNA was described by Watson and Crick. Several Nobel Prizes have been awarded for DNA-related discoveries. This review aims to describe the historical perspective of DNA in radiation biology. Over the decades, DNA damage has been identified and quantified after irradiation. Depending on the type of sensing, different proteins are involved in sensing DNA damage and repairing the damage, if possible. For double-strand breaks, the main repair mechanisms are non-homologous end joining and homologous recombination. Additional mechanisms are the Fanconi anaemia pathway and base excision repair. Different methods have been developed for the detection of DNA double-strand breaks. Several drugs have been developed that interfere with different DNA repair mechanisms, e.g., PARP inhibitors. These drugs have been established in the standard treatment of different tumour entities and are being applied in several clinical trials in combination with radiotherapy. Over the past decades, it has become apparent that DNA damage mechanisms are also directly linked to the immune response in tumours. For example, cytosolic DNA fragments activate the innate immune system via the cGAS STING pathway.
... Gene expression is the process by which information encoded in DNA is transformed into functional products: either proteins or non-coding RNA (ncRNA) molecules. Gene expression is finely and dynamically controlled through the tightly coordinated and interconnected activity of multiple factors at different levels [1][2][3]. The first level of regulation is chromatin accessibility, which is determined by epigenetic marks: reversible modifications that, without altering gene sequence, determine chromatin structure and accessibility, leading to the activation or repression of transcription [4]. ...
SLU7 (Splicing factor synergistic lethal with U5 snRNA 7) was first identified as a splicing factor necessary for the correct selection of 3′ splice sites, strongly impacting on the diversity of gene transcripts in a cell. More recent studies have uncovered new and non-redundant roles of SLU7 as an integrative hub of different levels of gene expression regulation, including epigenetic DNA remodeling, modulation of transcription and protein stability. Here we review those findings, the multiple factors and mechanisms implicated as well as the cellular functions affected. For instance, SLU7 is essential to secure liver differentiation, genome integrity acting at different levels and a correct cell cycle progression. Accordingly, the aberrant expression of SLU7 could be associated with human diseases including cancer, although strikingly, it is an essential survival factor for cancer cells. Finally, we discuss the implications of SLU7 in pathophysiology, with particular emphasis on the progression of liver disease and its possible role as a therapeutic target in human cancer.
... Thus, in contrast to traditional vaccines, mRNA vaccines do not contain any viral proteins themselves, but only the information our own cells need to produce the viral signature that triggers the desired immune response [15]. Each of the three COVID-19 vaccines described above induces an immune response against SARS-CoV-2, and after our first encounter with a particular bacterium or virus, in the years or decades that follow, adaptation cells can remember them -this is what we call immune memory [16], if you come into contact with a real virus or bacteria in the future, the immune system will remember it, produce antibodies against it, and quickly activate the right immune cells, thereby killing viruses or bacteria and protecting us from disease. ...
In order to solve COVID-19 pandemic, the entire world has invested considerable manpower to develop various new vaccines to temporarily alleviate the disaster caused by the epidemic. In addition to the development of vaccines, we need to also develop effective assessment methods to confirm vaccines’ efficacy and maximize the benefits that vaccines can bring. In addition to common evaluation methods, vaccine-specific and temporal expression of microRNAs have been shown to be related to vaccine efficacy or vaccine-associated diseases. In this article, we have introduced a microRNA-array-based approach, which could be potentially used for evaluating COVID-19 vaccine efficacy, specifically for pregnant women. As the mRNA in mRNA vaccines is decomposed by host cells within a few days, it is considered more suitable for pregnant women to utilize the method of vaccination during pregnancy. Moreover, pregnant women belong to a high-risk group for COVID-19, and there is currently no appropriate vaccine to newborns. Therefore, it’s important to find improved tools for evaluation of vaccine efficacy in response to the current situation caused by COVID-19.
... While in arteries, all the layers are present with an abundance of smooth muscle cells(91), capillary vessel walls only have the intima with its endothelial cell layer and basal lamina(92). ...
... Cells attach to this structure by using some receptors, e.g., integrins. These receptors are involved in cell migration through the ECM (Uzman et al., 2003;Bonnans et al., 2014). ...
Metastasis is the process by which cancer cells acquire the capability to leave the primary tumor and travel to distant sites. Recent experiments have suggested that the epithelial–mesenchymal transition can regulate invasion and metastasis. Another possible scenario is the collective motion of cells. Recent studies have also proposed a jamming–unjamming transition for epithelial cells based on physical forces. Here, we assume that there exists a short-range chemical attraction between cancer cells and employ the Brownian dynamics to simulate tumor growth. Applying the network analysis, we suggest three possible phases for a given tumor and study the transition between these phases by adjusting the attraction strength.
... Meanwhile, cells are constantly remodeling the ECM in order to regulate their own behavior. 212,213 An ideal ECM-mimicking biomaterial scaffold for tissueengineering applications should provide proper mechanical and biochemical properties for the encapsulated cells in order to regulate relevant cell behavior and promote tissue regeneration. 214,215 As one key form of natural ECM component, carbohydrate-based macromolecules are particularly attractive for tissue-engineering scaffolds. ...
... Among the most popular drugs in the market, nearly half of them work through GPCRs directly or indirectly (Alexander et al., 2011). Therefore, it is of much significance to find GPCRs that interact with drugs in the process of drug development (Alberts et al., 2003;Alexander et al., 2011). ...
Background: As a class of membrane protein receptors, G protein-coupled receptors (GPCRs) are very important for cells to complete normal life function and have been proven to be a major drug target for widespread clinical application. Hence, it is of great significance to find GPCR targets that interact with drugs in the process of drug development. However, identifying the interaction of the GPCR–drug pairs by experimental methods is very expensive and time-consuming on a large scale. As more and more database about GPCR–drug pairs are opened, it is viable to develop machine learning models to accurately predict whether there is an interaction existing in a GPCR–drug pair.
Methods: In this paper, the proposed model aims to improve the accuracy of predicting the interactions of GPCR–drug pairs. For GPCRs, the work extracts protein sequence features based on a novel bag-of-words (BOW) model improved with weighted Silhouette Coefficient and has been confirmed that it can extract more pattern information and limit the dimension of feature. For drug molecules, discrete wavelet transform (DWT) is used to extract features from the original molecular fingerprints. Subsequently, the above-mentioned two types of features are contacted, and SMOTE algorithm is selected to balance the training dataset. Then, artificial neural network is used to extract features further. Finally, a gradient boosting decision tree (GBDT) model is trained with the selected features. In this paper, the proposed model is named as BOW-GBDT.
Results: D92M and Check390 are selected for testing BOW-GBDT. D92M is used for a cross-validation dataset which contains 635 interactive GPCR–drug pairs and 1,225 non-interactive pairs. Check390 is used for an independent test dataset which consists of 130 interactive GPCR–drug pairs and 260 non-interactive GPCR–drug pairs, and each element in Check390 cannot be found in D92M. According to the results, the proposed model has a better performance in generation ability compared with the existing machine learning models.
Conclusion: The proposed predictor improves the accuracy of the interactions of GPCR–drug pairs. In order to facilitate more researchers to use the BOW-GBDT, the predictor has been settled into a brand-new server, which is available at http://www.jci-bioinfo.cn/bowgbdt.
... Nucleoside triphosphates play crucial roles in several biological processes including energy transduction, cellular respiration, enzyme catalysis, and signaling [35][36][37][38]. They are the most targeted anionic species because of their ubiquitous presence in biological systems. ...
To understand the molecular interactions, present in living organisms and their environments, chemists are trying to create novel chemical tools. In this regard, peptide-based fluorescence techniques have attracted immense interest. Synthetic peptide-based fluorescent probes are advantageous over protein-based sensors, since they are synthetically accessible, more stable, and can be easily modified in a site-specific manner for selective biological applications. Peptide receptors labeled with environmentally sensitive/FRET fluorophores have allowed direct detection/monitoring of biomolecules in aqueous media and in live cells. In this review, key peptide-based approaches for different biological applications are presented.
... Antibodies are secreted through the body and inactivate the pathogens by binding to them, which also makes the pathogens visible so that they can be destroyed by phagocytic cells. On the other hand, T-cells are involved in the recognition of infected cells and they eliminate them [7]. ...
The macromolecular complex known as “inflammasome” is defined as an intracellular multi-protein complex composed of a sensor receptor (PRR), an adaptor protein and an effector enzyme (caspase-1) which oligomerize when they sense danger, such as how the NLR family, AIM-2 and RIG-1 receptors protect the body against danger via cytokines secretion. Within the NLR members, NLRP3 is the most widely known and studied inflammasome and has been linked to many diseases. Nowadays, people's interest in their lifestyles and nutritional habits is increasing, mainly due to the large number of diseases that seem to be related to both. The term “nutraceutical” has recently emerged as a hybrid term between “nutrition” and “pharmacological” and it refers to a wide range of bioactive compounds contained in food with relevant effects on human health. The relationship between these compounds and diseases based on inflammatory processes has been widely exposed and the compounds stand out as an alternative to the pathological consequences that inflammatory processes may have, beyond their defense and repair action. Against this backdrop, here we review the results of studies using several nutraceutical compounds in common diseases associated with the inflammation and activation of the NLRP3 inflammasomes complex. In general, it was found that there is a wide range of nutraceuticals with effects through different molecular pathways that affect the activation of the inflammasome complex, with positive effects mainly in cardiovascular, neurological diseases, cancer and type 2 diabetes.
... In living organisms, their functional units are often stabilized in am atrix. [8] We propose to integrate DNAzymes into an artificial host matrix, namely metal-organic frameworks (MOFs). [9] MOFs have been demonstrated as hosts for various guest species, including inorganic,o rganic, and biological guests, [10] and these guests are often stabilized after encapsulation. ...
DNAzymes are a promising class of bioinspired catalyst; however, their structural instability limits their potential. Herein, a method to stabilize DNAzymes by encapsulating them in a metal–organic framework (MOF) host is reported. This biomimetic mineralization process makes DNAzymes active under a wider range of conditions. The concept is demonstrated by encapsulating hemin‐G‐quadruplex (Hemin‐G4) into zeolitic imidazolate framework‐90 (ZIF‐90), which indeed increases the DNAzyme's structural stability. The stabilized DNAzymes show activities in the presence of Exonuclease I, organic solvents, or high temperature. Owing to its elevated stability and heterogeneous nature, it is possible to perform catalysis under continuous‐flow conditions, and the DNAzyme can be reactivated in situ by introducing K⁺. Moreover, it is found that the encapsulated DNAzyme maintains its high enantiomer selectivity, demonstrated by the sulfoxidation of thioanisole to (S)‐methyl phenyl sulfoxide. This concept of stabilizing DNAzymes expands their potential application in chemical industry.
... These findings indicated that the innate immune parameters of catfish remain at the same level before and after the challenge. This result could be due to the power of the fish immune system to rapidly recover from pathogen infection with early activation of the innate immune system soon after infection (Medzhitov & Janeway, 2000;Mogensen, 2009;Uzman, 2003). The ability of the immune system to recover from infection was found in Nile tilapia (Van Doan et al., 2016), Sparus aurata (Reyes-Becerril, Lopez-Medina, Ascencio-Valle, & Esteban, 2011), Oncorhynchus mykiss (Raida & Buchmann, 2009) and Piaractus mesopotamicus (Gimbo, Favero, Franco Montoya, & Urbinati"?>, ...
A few studies have illustrated the effects of sodium salt derived from alginic acid on different fish species. However, little is known about the effect of sodium alginate on catfish (Clarias gariepinus). Therefore, this study was performed to assess the use of low molecular weight sodium alginate (LMWSA) in C. gariepinus. A total of 180 apparently healthy C. gariepinus with a mean body weight of 45 g were randomly divided into three equal groups (D1, D2 and D3). D1 the control group received a control diet, while D2 and D3 received 1% and 3% LMWSA, respectively, for 8 weeks. A challenge test against Aeromonas hydrophila was performed on 15 randomly selected catfish for 15 days. At the end of the experiment, catfish in D3 that received a diet of 3% LMWSA showed significant increases in the final body weight, weight gain and thermal‐unit growth coefficient compared with those in D2 and D1. There was a significant decrease in the erythrogram in D1 after the 4‐day pathogen challenge. A leucogram revealed leucocytosis, heterophilia and lymphocytosis in catfish in D2 and D3 compared with those in D1. After the 4‐day challenge, the following changes took place: lysozyme, nitric oxide, phagocytic activity and the respiratory burst were significantly elevated in catfish that received LMWSA and were more pronounced in D3 than in D1. The mortalities of catfish have been stopped after pathogen challenge from 8‐day in D1 and D2 where at 6‐day in D3. Thus, administration of 1% and 3% LMWSA enhances the growth, immune response and resistance of C. gariepinus against A. hydrophila.
Computer-assisted analysis of proteomics and genomics is a method that uses computational tools and algorithms to analyze and interpret vast amounts of data generated by these investigations. This process aids in identifying patterns, predicting protein functions, understanding gene expression patterns, and identifying potential biomarkers or therapeutic targets. It also allows for the integration of various data sources, such as gene ontologies, pathway databases, and protein-protein interaction networks, providing a comprehensive understanding of cellular functions and diseases. Recent technological advancements have transformed proteomics and genomics, enabling faster and more precise data analysis, which could significantly enhance our understanding of diseases, metabolic processes, and biomolecular interactions. This paper explores how computer-assisted analysis is revolutionizing biological research, reshaping genomics and proteomics, and improving our understanding of diseases and the development of tailored medicines. Combining proteomics and genomes can enhance biomarker identification, expedite drug development, produce personalized treatments, and deepen our understanding of disease causes. The future of biomedical research relies on the successful integration of proteomic and genomic data, necessitating interdisciplinary collaboration and innovation in bioinformatics and analytical techniques.
Living tissues experience various external forces on cells, influencing their behaviour, physiology, shape, gene expression, and destiny through interactions with their environment. Despite much research done in this area, challenges remain in our better understanding of the behaviour of the cell in response to external stimuli, including the arrangement, quantity, and shape of organelles within the cell. This study explores the electromechanical behaviour of biological cells, including organelles like microtubules, mitochondria, nuclei, and cell membranes. A two-dimensional bio-electromechanical model for two distinct cell structures has been developed to analyze the behavior of the biological cell to the external electrical and mechanical responses. The piezoelectric and flexoelectric effects have been included via multiphysics coupling for the biological cell. All the governing equations have been discretized and solved by the finite element method. It is found that the longitudinal stress is absent and only the transverse stress plays a crucial role when the mechanical load is imposed on the top side of the cell through compressive displacement. The impact of flexoelectricity is elucidated by introducing a new parameter called the maximum electric potential ratio (VR,max). It has been found that VR,max depends upon the orientation angle and shape of the microtubules. The magnitude of VR,max exhibit huge change when we change the shape and orientation of the organelles, which in some cases (boundary condition (BC)-3) can reach to three times of regular shape organelles. Further, the study reveals that the number of microtubules significantly impacts effective elastic and piezoelectric coefficients, affecting cell behavior based on structure, microtubule orientation, and mechanical stress direction. The insight obtained from the current study can assist in advancements in medical therapies such as tissue engineering and regenerative medicine.
Multicellular organisms are composed of diverse cell types that must coordinate their behaviors through communication. Cell–cell communication (CCC) is essential for growth, development, differentiation, tissue and organ formation, maintenance, and physiological regulation. Cells communicate through direct contact or at a distance using ligand–receptor interactions. So cellular communication encompasses two essential processes: cell signal conduction for generation and intercellular transmission of signals, and cell signal transduction for reception and procession of signals. Deciphering intercellular communication networks is critical for understanding cell differentiation, development, and metabolism. First, we comprehensively review the historical milestones in CCC studies, followed by a detailed description of the mechanisms of signal molecule transmission and the importance of the main signaling pathways they mediate in maintaining biological functions. Then we systematically introduce a series of human diseases caused by abnormalities in cell communication and their progress in clinical applications. Finally, we summarize various methods for monitoring cell interactions, including cell imaging, proximity-based chemical labeling, mechanical force analysis, downstream analysis strategies, and single-cell technologies. These methods aim to illustrate how biological functions depend on these interactions and the complexity of their regulatory signaling pathways to regulate crucial physiological processes, including tissue homeostasis, cell development, and immune responses in diseases. In addition, this review enhances our understanding of the biological processes that occur after cell–cell binding, highlighting its application in discovering new therapeutic targets and biomarkers related to precision medicine. This collective understanding provides a foundation for developing new targeted drugs and personalized treatments.
Dissipative supramolecular assemblies are hallmarks of living systems, contributing to their complex, dynamic structures and emerging functions. Living cells can spatiotemporally control diverse biochemical reactions in membrane compartments and condensates, regulating metabolite levels, signal transduction or remodeling of the cytoskeleton. Herein, we constructed membranous compartments using self‐assembly of lipid‐like amphiphiles (lipidoid) in aqueous medium. The new double‐tailed lipidoid features Cu(II) coordinated with a tetravalent chelator that dictates the binding of two amphiphilic ligands in cis‐orientation. Hydrophobic interactions between the lipidoids coupled with intermolecular hydrogen bonding led to a well‐defined bilayer vesicle structure. Oil‐soluble SNAr reaction is efficiently upregulated in the hydrophobic cavity, acting as a catalytic crucible. The modular system allows easy incorporation of exposed primary amine groups, which augments the catalysis of retro aldol and C–N bond formation reactions. Moreover, a higher‐affinity chelator enables consumption of the Cu(II) template leveraging the differential thermodynamic stability, which allows a controllable lifetime of the vesicular assemblies. Concomitant temporal upregulation of the catalytic reactions could be tuned by the metal ion concentration. This work offers new possibilities for metal ion‐mediated dynamic supramolecular systems, opening up a massive repertoire of functionally active dynamic “life‐like” materials.
Understanding the genetic composition and regional adaptation of marine species under environmental heterogeneity and fishing pressure is crucial for responsible management. In order to understand the genetic diversity and adaptability of yellowfin seabream (Acanthopagrus latus) along southern China coast, this study was conducted a seascape genome analysis on yellowfin seabream from the ecologically diverse coast, spanning over 1600 km. A total of 92 yellowfin seabream individuals from 15 sites were performed whole-genome resequencing, and 4,383,564 high-quality single nucleotide polymorphisms (SNPs) were called. By conducting a genotype-environment association analysis, 29,951 adaptive and 4,328,299 neutral SNPs were identified. The yellowfin seabream exhibited two distinct population structures, despite high gene flow between sites. The seascape genome analysis revealed that genetic structure was influenced by a variety of factors including salinity gradients, habitat distance, and ocean currents. The frequency of allelic variation at the candidate loci changed with the salinity gradient. Annotation of these loci revealed that most of the genes are associated with osmoregulation, such as kcnab2a, kcnk5a, and slc47a1. These genes are significantly enriched in pathways associated with ion transport including G protein-coupled receptor activity, transmembrane signaling receptor activity, and transporter activity. Overall, our findings provide insights into how seascape heterogeneity affects adaptive evolution, while providing important information for regional management in yellowfin seabream populations.
A new copper( ii ) complex containing guanidine derivatives and gallic acid (1-HGA) interacted with CT-DNA via non-intercalation mode. 1-HGA was most active against MCF-7 cancer cells and had greater antibacterial activity than the starting compound.
Background
The indiscriminate use of antibiotics brings an alarming reality: in 2050, bacterial resistance could be the main cause of death in the world, resulting in the death of 10 million people, according to the World Health Organization (WHO). In this sense, to combat bacterial resistance, several natural substances, including chalcones, have been described in relation to antibacterial, representing a potential tool for the discovery of new antibacterial drugs.
Objective
The objective of this study is to perform a bibliographic survey and discuss the main contributions in the literature about the antibacterial potential of chalcones in the last 5 years.
Methods
A search was carried out in the main repositories, for which the publications of the last 5 years were investigated and discussed. Unprecedented in this review, in addition to the bibliographic survey, molecular docking studies were carried out to exemplify the applicability of using one of the molecular targets for the design of new entities with antibacterial activity.
Results
In the last 5 years, antibacterial activities were reported for several types of chalcones, for which activities were observed for both gram-positive and gram-negative bacteria with high potency, including MIC values in the nanomolar range. Molecular docking simulations demonstrated important intermolecular interactions between chalcones and residues from the enzymatic cavity of the enzyme DNA gyrase, one of the validated molecular targets in the development of new antibacterial agents.
Conclusion
The data presented demonstrate the potential of using chalcones in drug development programs with antibacterial properties, which may be useful to combat resistance, a worldwide public health problem.
Adjuvants are often included in vaccine formulations to enhance and modulate immune responses against pathogenic antigens. Aluminum-based adjuvants are prepared as hydrated colloids and are widely used due to their high efficacy and strong safety record. Previous studies have shown that freezing and thawing of aluminum adjuvants can lead to the aggregation of adjuvant particles, resulting in reduced vaccine potency. In this study, we demonstrated the use of contrast-matching small-angle neutron scattering (SANS) as a tool to directly probe hydration states of aluminum adjuvants in solution. Our study shows that aluminum hydroxide and aluminum phosphate adjuvants could be represented with the hydrated forms of Al(OH)3•2H2O and AlPO4•1.5H2O respectively. Moreover, our results demonstrate that freeze-thaw stress could lead to the dehydration of aluminum adjuvants, followed by aggregation of dehydrated adjuvant particles. Including sucrose in samples reduced freeze-thaw-induced dehydration of aluminum adjuvants, which in turn, inhibited the formation of large aggregates. The relationship between freeze-thaw-induced dehydration and aggregation of aluminum adjuvants could be used to explain the loss of adjuvanticity upon accidental freezing and thawing, and thus enable the more efficient development of thermostable vaccine products.
Obesity is a significant risk factor for arrhythmic cardiovascular death. Interactions between epicardial adipose tissue (EAT) and myocytes are thought to play a key role in the development of arrhythmias. In this review, the authors investigate the influence of EAT on arrhythmogenesis. First, they summarize electrocardiographic evidence showing the association between increased EAT volume and atrial and ventricular conduction delay. Second, they detail the structural cross talk between EAT and the heart and its arrhythmogenicity. Adipose tissue infiltration within the myocardium constitutes an anatomical obstacle to cardiac excitation. It causes activation delay and increases the risk of arrhythmias. Intercellular electrical coupling between cardiomyocytes and EAT can further slow conduction and increase the risk of block, favoring re-entry and arrhythmias. Finally, EAT secretes multiple substances that influence cardiomyocyte electrophysiology either by modulating ion currents and electrical coupling or by stimulating fibrosis. Thus, structural and paracrine cross talk between EAT and cardiomyocytes facilitates arrhythmias.
It is confusing: many common colds are caused by coronaviruses, but not all coronaviruses cause colds. Some, like SARS-CoV-2, the coronavirus responsible for COVID-19, can cause serious health complications and death. To reduce the risk of the public innocently (and understandably) conflating COVID-19 with the mild sicknesses associated with a common cold, one job of public health would need to be to “make the familiar strange and the strange familiar.” But wait, that is the work of anthropology. I argue that what is missing from many public discussions of COVID-19 is a straight answer to a simple question central to the public’s uptake of science, health guidelines, mandates, and even vaccines: “How do viruses work, that is, infect our cells and make us sick?” The essay that follows attempts to answer this question, contributing to public health by making a critical anthropological distinction between “sickness” and “infection.”
La membrane plasmique forme une barrière sélective pour la cellule, mais son rôle va bien au-delà d'une simple frontière. En effet, elle joue un rôle crucial dans les fonctions biologiques telles que l'endo et l'exocytose, la communication cellulaire ou l'adhésion. Il est actuellement largement admis que la répartition spatiale des lipides et des protéines membranaires n'est pas homogène mais que ces composants sont organisés en nanodomaines, qui se sont avérés être des acteurs clés des fonctions biologiques susmentionnées. Combinant des outils analytiques de physique statistique et des simulations numériques, nous proposons dans ce travail un mécanisme physique pour cette organisation membranaire dans un modèle simple de vésicule biphasique. À l'échelle mésoscopique, nous décrivons la membrane avec un mécanisme de couplage composition-courbure. Nous réalisons des simulations Monte Carlo extensives pour différents paramètres de la membrane (concentration, courbure spontanée, affinité du mélange, tension de surface) et étudions ses états d'équilibre. Nous caractérisons la gamme de paramètres conduisant à des modulations de phases en dressant des diagrammes de phases à partir des résultats numériques et les comparons à ceux obtenus précédemment par les techniques analytiques de la théorie des champs. Différentes observables sont mesurées telles que les fonctions de corrélation et les distributions de taille de domaines pour extraire des informations sur les structures membranaires émergentes, telles que leur forme, leur taille ou leur espacement typique. En ce qui concerne la forme des domaines, nous analysons les trajectoires expérimentales de protéines membranaires (récepteurs au VIH) pour quantifier la forme des domaines et la comparer à nos simulations. Afin de proposer un mécanisme pour la structuration de la membrane pertinent à différents échelles, nous effectuons également des simulations de dynamique moléculaire gros-grains (MARTINI) de bicouches lipidiques, incluant des composants générateurs de courbure, à partir desquelles nous extrayons les paramètres physiques membranaires qui peuvent être injectés dans le modèle mésoscopique. Nous étendons notre modèle mésoscopique en étudiant l'effet de forces appliquées à la vésicule, inspirés par le processus de division cellulaire au cours duquel les composants de la membrane se réorganisent et de telles forces sont en jeu.
Plasma membrane forms a selective barrier for the cell, yet its role goes far beyond a simple frontier. Indeed, it plays a crucial role in biological functions such as endo and exocytosis, cell communication or adhesion. It is now widely agreed that membrane lipid and protein spatial repartition is not homogeneous but that these components are organized into nanodomains, which have proven to be key players in the above-mentioned biological functions. Combining statistical physics analytical tools and numerical simulations, we propose in this work a physical mechanism for this membrane organization in a simple model bicomponent vesicle. At the mesoscale, we describe the membrane with a composition- curvature coupling mechanism. We perform extensive Monte Carlo simulations for different membrane parameters (concentration, spontaneous curvature, mixture affinity, surface tension) and study its equilibrium states. We characterize the range of parameters leading to phase modulations by drawing phase diagrams from the simulation results and compare them to the ones previously obtained by analytical field-theoretic techniques. Different observables are computed such as correlation functions and domain size distributions to extract information about the emerging membrane patterns, such as their typical shape, size or spacing. With respect to domain shape, we analyse experimental membrane protein (HIV receptors) trajectories to quantify domain shape and compare it to our simulations. In order to propose a valid rationale for membrane structuring at different scales, we also perform coarse-grained molecular dynamics simulations (MARTINI) of lipid bilayers including curvature-generating components from which we extract the physical membrane parameters that can be plugged into the mesoscale model. We extend our mesoscale model by studying the effect of applied forces to the vesicle, inspired by cell division process during which membrane components reorganize and such forces are at play.
Sequential infections with different dengue serotypes (DENV-1, 4) significantly increase the risk of a severe disease outcome (fever, shock, and hemorrhagic disorders). Two hypotheses have been proposed to explain the severity of the disease: (1) antibody-dependent enhancement (ADE) and (2) original T cell antigenic sin. In this work, we explored the first hypothesis through mathematical modeling. The proposed model reproduces the dynamic of susceptible and infected target cells and dengue virus in scenarios of infection-neutralizing and infection-enhancing antibody competition induced by two distinct serotypes of the dengue virus during secondary infection. The enhancement and neutralization functions are derived from basic concepts of chemical reactions and used to mimic binding to the virus by two distinct populations of antibodies. The analytic study of the model showed the existence of two equilibriums: a disease-free equilibrium and an endemic one. Using the concept of the basic reproduction number , we performed the asymptotic stability analysis for the two equilibriums. To measure the severity of the disease, we considered the maximum value of infected cells as well as the time when this maximum is reached. We observed that it corresponds to the time when the maximum enhancing activity for the infection occurs. This critical time was calculated from the model to be a few days after the occurrence of the infection, which corresponds to what is observed in the literature. Finally, using as output , we were able to rank the contribution of each parameter of the model. In particular, we highlighted that the cross-reactive antibody responses may be responsible for the disease enhancement during secondary heterologous dengue infection.
The metabolic disorders are the edge points for the initiation of various diseases. These disorders comprised of several diseases including diabetes, obesity, and cardiovascular complications. Worldwide, the prevalence of these disorders is increasing day by day. The world’s population is at higher threat of developing metabolic disease, especially diabetes. Therefore, there is an impregnable necessity of searching for a newer therapeutic target to reduce the burden of these disorders. Diabetes mellitus (DM) is marked with the dysregulated insulin secretion and resistance. The lipid and glucose transporters portray a pivotal role in the metabolism and transport of both of these. The excess production of lipid and glucose and decreased clearance of these leads to the emergence of DM. The ATP-binding cassette transporters (ABCT) are important for the metabolism of glucose and lipid. Various studies suggest the key involvement of ABCT in the pathologic process of different diseases. In addition, the involvement of other pathways, including IGF signaling, P13-Akt/PKC/MAPK signaling, and GLP-1 via regulation of ABCT, may help develop new treatment strategies to cope with insulin resistance dysregulated glucose metabolism, key features in DM.
Graphical abstract
Cadmium (Cd), a heavy metal with cytotoxicity, can activate autophagy. This study aimed to explore the effects and mechanisms of Potentilla anserine L. polysaccharide (PAP) on autophagy in N2a cells, primary neurons, and the brain of BALB/c mice exposed to Cd. The CCK-8 assay results showed that the cell viability decreased and the number of acidic vesicular organelles, autophagic vacuoles, lysosomes, and dysfunctional mitochondria increased in the cytoplasm of Cd-exposed N2a cells and primary neurons, as revealed by acridine orange staining, monodansylcadaverine staining, and transmission electron microscopy. PAP mitigated Cd-induced neuronal death and characteristic changes in autophagy. The expression of LC3 IILC3 II, Bcl-2, p62, Beclin-1, and PI3K class III was examined by Western blot analysis. Furthermore, the PI3K inhibitor (LY294002 or 3-MA) and/or PAP reversed the Cd-induced upregulated expression of LC3 II, Beclin-1, and PI3K class III, with a synergy between PI3K inhibitor and PAP against Cd-induced autophagy. The findings suggested that PAP partially prevented Cd-induced autophagic cell death in neurons by inhibiting the PI3K class III/Beclin-1 signaling pathway in vitro and in vivo.
Biomolecular interactions, which were studied earlier using only experimental techniques, became a vital resource of information after the introduction of computational approaches such as molecular modeling, docking, simulations, etc. In fact, the static picture of structural biology emerged to render the time-dependent structural and functional dynamics of biomolecules at the atomic scale. The introduction of molecular docking approach even simplified the understanding of biomolecular sensing mechanism with special emphasis on the types of interactions governing the complex formation. Today, molecular docking has evolved as a prime technique in structural molecular biology and computer-aided drug design. Its application in drug design has been of great importance in developing promising drug candidates. This chapter highlights the importance of molecular docking in understanding biomolecular interactions and the theoretical approaches implanted in docking techniques.
A utilização da biomassa vem crescendo mundialmente como fonte renovável para a produção de energia elétrica e de biocombustíveis (etanol, biodiesel, biogás etc.). Ademais, a biomassa se destaca como uma fonte de material de partida na produção de diversas substâncias orgânicas que servirão como insumos nos mais variados processos industriais. Neste livro são abordados os diversos aspectos da biomassa, desde a sua estrutura até sua valorização e emprego em biorrefinarias. Devido ao seu papel fundamental, os processos catalíticos para a produção de commodities e outros produtos de maior valor agregado a partir da biomassa são discutidos em detalhes, com exemplos recentes da literatura.
Precision medicine is a topical subject that attracts tremendous attention from scientific and medical communities, being set to transform health care in the future. This book will be among the first to cover the detection methods for precision medicine. The first section provides an overview of the biomarkers used for precision medicine, such as proteins, nucleic acids, and metabolites. The coverage then turns to sequencing techniques and their applications, and other bioanalytical techniques, including mass spectrometry for proteome and phosphoproteome analysis, immunological methods and droplet technologies. The final sections include biosensors applied to precision medicine and clinical applications.
This book provides a reference for researchers and students interested and working in the development of bioanalytical techniques for clinical applications. It provides a useful introduction for physicians and medical laboratory technologists to the recent advances in detection methods for precision medicine.
The present study considers a possible role of enzymatic reactions in the adaptive response of cells to the beta-emitting radionuclide tritium under conditions of low-dose exposures. Effects of tritiated water (HTO) on the reactions of bacterial luciferase and NAD(P)H:FMN-oxidoreductase, as well as a coupled system of these two reactions, were studied at radioactivity concentrations ≤ 200 MBq/L. Additionally, one of the simplest enzymatic reactions, photobiochemical proton transfer in Coelenteramide-containing Fluorescent Protein (CLM-FP), was also investigated. We found that HTO increased the activity of NAD(P)H:FMN-oxidoreductase at the initial stage of its reaction (by up to 230%); however, a rise of luciferase activity was moderate (<20%). The CLM-FP samples did not show any increase in the rate of the photobiochemical proton transfer under the exposure to HTO. The responses of the enzyme systems were compared to the ‘hormetic’ response of luminous marine bacterial cells studied earlier. We conclude that (1) the oxidoreductase reaction contributes significantly to the activation of the coupled enzyme system and bacterial cells by tritium, and (2) an increase in the organization level of biological systems promotes the hormesis phenomenon.
To explore the effect of direct cell-to-cell transmission on viral infection dynamics under the exposure of the non-cytolytic cure mechanism, a mathematical model integrating both the virus-to-cell and cell-to-cell transmissions with a non-cytolytic cure rate of infected cells in the presence of humoral immunity has been considered. Parameter variation experimentation suggests that a high cell-to-cell infection rate induces the chronic infection state in the host, whereas a high non-cytolytic cure rate positively contributes to the reduction of the viral load. We observe that a moderate cure rate under the exposure of a weak cell-to-cell transmission can effectively reduce the level of infection. Further, we examine the effect of cell-free transmission on the infection dynamics under the influence of cell-to-cell transmission. To substantiate our hypothesis, we present a case study of five HIV-1 infected patients to depict the primary HIV-1 infection dynamics in a real life scenario through model prediction.
Organic electrochemical transistors (OECTs) comprised of organic mixed conductors can operate in aqueous, biological media and translate low magnitude ionic fluctuations of biological origin into measurable electrical signals. The growing technological interest in these bio-transducers makes the fundamental understanding of ion-to-electron coupling extremely important for the design of new materials and devices. One crucial aspect in this process that has been so far disregarded is the water taken up by the film during device operation and its effects on device performance. Here, using a series of the same electrolyte with varying ion concentrations, we quantify the amount of water that is incorporated into a hydrophilic p-type organic semiconductor film alongside the dopant anions and investigate structural and morphological changes occurring in the film upon electrochemical doping. We show that infiltration of the hydrated dopant ions into the film irreversibly changes the polymer structure and negatively impacts the efficiency, reversibility and speed of charge generation. When less water is injected into the channel, OECTs exhibit higher transconductance and faster switching speeds. Although swelling is commonly suggested to be a necessity for efficient ion-to-electron transduction, this work uncovers the negative impact of a swollen channel material on the performance of accumulation mode OECTs and lays the foundation for future materials design.
Oscillation force has been demonstrated in theoretical studies as a critical role in unraveling the comprehensive enzymatic dynamics and address its regulation on enzyme activity. Utilizing the imposed external mechanical oscillation force by our newly developed magnetic tweezers coupled single-molecule photon-stamping imaging spectroscopic microscope, we experimentally studied a millisecond scale oscillation force manipulation on single Horseradish Peroxidase (HRP) enzymatic conformational and reaction dynamics. We have studied the enzymatic reaction dynamics and found that the enzyme activity changes under the real-time oscillatory force manipulation. Moreover, the oscillation force shows the capability of manipulating the enzyme active-site conformational state as well as the nascent-formed product’s interaction with the active site of the enzyme, which impacts on the product release pathways. Specifically, we have identified there are two product releasing pathways, the solvation-mediated diffusion releasing pathway and the spilling-out releasing pathway. We have observed that the spilling-out pathway can be significantly perturbed by the oscillatory force manipulation. Our correlated interpretation of enzymatic conformational and reaction dynamics provides a new insight into the comprehensive understanding of the complex conformational dynamics evolved in an enzymatic reaction. Technically, we have also demonstrated a novel approach capable of unfolding an enzyme under an enzymatic reaction condition in real time, and furthermore, by using an oscillatory mechanical weak pN force to manipulate enzyme conformations, and the enzyme thermal fluctuation is fully maintained. The real-time in situ fluorescence probe at the enzymatic active site reports the active site conformational dynamics through each enzymatic reaction turnovers.
The primary function of the cell membrane is to protect cells from their surroundings. This entails a strict regulation on controlling the exchange of matter between the cell and its environment. A key factor when considering potential biological applications of a particular chemical structure has to do with its ability to internalize into cells. Molecules that can readily cross cell membranes are frequently needed in biological research and medicine, since most therapeutic entities are designed to modulate intracellular components. However, the design of molecules that do not penetrate cells is also relevant toward, for example, extracellular contrast agents, which are most widely used in clinical diagnosis.
Simbiotics is a spatially explicit multi-scale modeling platform for the design, simulation and analysis of bacterial populations. Systems ranging from planktonic cells and colonies, to biofilm formation and development may be modeled. Representation of biological systems in Simbiotics is flexible, user-defined processes may be in a variety of forms depending on desired model abstraction. Simbiotics provides a library of modules such as cell geometries, physical force dynamics, genetic circuits, metabolic pathways, chemical diffusion and cell interactions. Model defined processes are integrated and scheduled for parallel multi-thead and multi-CPU execution. A virtual lab provides the modeler with analysis modules and some simulated lab equipment, enabling automation of sample interaction and data collection. An extendable and modular framework allows for the platform to be updated as novel models of bacteria are developed, coupled with an intuitive user interface to allow for model definitions with minimal programming experience. Simbiotics can integrate existing standards such as SBML, and process microscopy images to initialise the 3D spatial configuration of bacteria consortia. Two case studies, used to illustrate the platform flexibility, focus on the physical properties of the biosystems modeled. These pilot case studies demonstrate Simbiotics versatility in modeling and analysis of natural systems and as a CAD tool for synthetic biology.
This chapter mainly focuses on the musculoskeletal muscle. It presents a brief explanation on the main techniques to engineer synthetic scaffolds with particular attention on their relevance in the field of tendon/ligament and skeletal muscle engineering. The strategy to repair tendon, ligaments, and skeletal muscles using synthetic materials are generally based on the fabrication of structures that mimic the native tissue organization and its functional properties. To achieve this goal, several methods have been proposed so far, including electrospinning, knitting or braiding, and micropatterning. Cell-based therapies with or without the presence of a scaffold represent an alternative strategy for tendon and ligament repair as well for skeletal muscle regeneration. Stem cells in tendon/ligament and skeletal muscle tissue engineering can be divided into three main classes: embryonic stem cells (ESCs), induced pluripotent stem cells (IPSs), and mesenchymal stem cells (MSCs).
Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation. Since inflammatory cytokines are normally involved in anorexigenic responses, reduced inflammation has been independently shown to mediate changes in feeding behaviours and other metabolic parameters, resulting in obesity. Genetic variation in pro-inflammatory cytokines is also associated with both general obesity and weight change during AP treatment, and thus, may be implicated in the pharmacogenetics of AIWG. At this time, preliminary data support a cytokine-mediated model of AIWG which may have clinical utility in developing more effective metabolic monitoring guidelines and prevention measures. However, further research is still needed to clearly elucidate the validity of this immune model. This article reviews the evidence implicating inflammatory cytokines in AIWG and its potential clinical relevance.
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