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Frontiers in Plant Science 2021Small RNAs (sRNAs) are a class of non-coding RNAs that consist of 21-24 nucleotides. They have been extensively investigated as critical regulators in a variety of... (Review)
Review
Small RNAs (sRNAs) are a class of non-coding RNAs that consist of 21-24 nucleotides. They have been extensively investigated as critical regulators in a variety of biological processes in plants. sRNAs include two major classes: microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biogenesis and functional pathways. Due to global warming, high-temperature stress has become one of the primary causes for crop loss worldwide. Recent studies have shown that sRNAs are involved in heat stress responses in plants and play essential roles in high-temperature acclimation. Genome-wide studies for heat-responsive sRNAs have been conducted in many plant species using high-throughput sequencing. The roles for these sRNAs in heat stress response were also unraveled subsequently in model plants and crops. Exploring how sRNAs regulate gene expression and their regulatory mechanisms will broaden our understanding of sRNAs in thermal stress responses of plant. Here, we highlight the roles of currently known miRNAs and siRNAs in heat stress responses and acclimation of plants. We also discuss the regulatory mechanisms of sRNAs and their targets that are responsive to heat stress, which will provide powerful molecular biological resources for engineering crops with improved thermotolerance.
PubMed: 34603356
DOI: 10.3389/fpls.2021.726762 -
GigaScience May 2020Omics technologies have been widely applied in toxicology studies to investigate the effects of different substances on exposed biological systems. A classical...
BACKGROUND
Omics technologies have been widely applied in toxicology studies to investigate the effects of different substances on exposed biological systems. A classical toxicogenomic study consists in testing the effects of a compound at different dose levels and different time points. The main challenge consists in identifying the gene alteration patterns that are correlated to doses and time points. The majority of existing methods for toxicogenomics data analysis allow the study of the molecular alteration after the exposure (or treatment) at each time point individually. However, this kind of analysis cannot identify dynamic (time-dependent) events of dose responsiveness.
RESULTS
We propose TinderMIX, an approach that simultaneously models the effects of time and dose on the transcriptome to investigate the course of molecular alterations exerted in response to the exposure. Starting from gene log fold-change, TinderMIX fits different integrated time and dose models to each gene, selects the optimal one, and computes its time and dose effect map; then a user-selected threshold is applied to identify the responsive area on each map and verify whether the gene shows a dynamic (time-dependent) and dose-dependent response; eventually, responsive genes are labelled according to the integrated time and dose point of departure.
CONCLUSIONS
To showcase the TinderMIX method, we analysed 2 drugs from the Open TG-GATEs dataset, namely, cyclosporin A and thioacetamide. We first identified the dynamic dose-dependent mechanism of action of each drug and compared them. Our analysis highlights that different time- and dose-integrated point of departure recapitulates the toxicity potential of the compounds as well as their dynamic dose-dependent mechanism of action.
Topics: Algorithms; Computational Biology; Dose-Response Relationship, Drug; Gene Expression Profiling; Gene Expression Regulation; Humans; Pharmacogenomic Testing; Pharmacogenomic Variants; Software; Toxicogenetics
PubMed: 32449777
DOI: 10.1093/gigascience/giaa055 -
BMC Plant Biology Oct 2020The immobile nature of plants means that they can be frequently confronted by various biotic and abiotic stresses during their lifecycle. Among the various abiotic... (Review)
Review
BACKGROUND
The immobile nature of plants means that they can be frequently confronted by various biotic and abiotic stresses during their lifecycle. Among the various abiotic stresses, water stress, temperature extremities, salinity, and heavy metal toxicity are the major abiotic stresses challenging overall plant growth. Plants have evolved complex molecular mechanisms to adapt under the given abiotic stresses. Long non-coding RNAs (lncRNAs)-a diverse class of RNAs that contain > 200 nucleotides(nt)-play an essential role in plant adaptation to various abiotic stresses.
RESULTS
LncRNAs play a significant role as 'biological regulators' for various developmental processes and biotic and abiotic stress responses in animals and plants at the transcription, post-transcription, and epigenetic level, targeting various stress-responsive mRNAs, regulatory gene(s) encoding transcription factors, and numerous microRNAs (miRNAs) that regulate the expression of different genes. However, the mechanistic role of lncRNAs at the molecular level, and possible target gene(s) contributing to plant abiotic stress response and adaptation, remain largely unknown. Here, we review various types of lncRNAs found in different plant species, with a focus on understanding the complex molecular mechanisms that contribute to abiotic stress tolerance in plants. We start by discussing the biogenesis, type and function, phylogenetic relationships, and sequence conservation of lncRNAs. Next, we review the role of lncRNAs controlling various abiotic stresses, including drought, heat, cold, heavy metal toxicity, and nutrient deficiency, with relevant examples from various plant species. Lastly, we briefly discuss the various lncRNA databases and the role of bioinformatics for predicting the structural and functional annotation of novel lncRNAs.
CONCLUSIONS
Understanding the intricate molecular mechanisms of stress-responsive lncRNAs is in its infancy. The availability of a comprehensive atlas of lncRNAs across whole genomes in crop plants, coupled with a comprehensive understanding of the complex molecular mechanisms that regulate various abiotic stress responses, will enable us to use lncRNAs as potential biomarkers for tailoring abiotic stress-tolerant plants in the future.
Topics: Adaptation, Physiological; Gene Expression Regulation, Plant; RNA, Plant; RNA, Untranslated; Stress, Physiological
PubMed: 33046001
DOI: 10.1186/s12870-020-02595-x -
Plant Biotechnology Journal Dec 2022Plants inevitably encounter environmental adversities, including abiotic and biotic stresses, which significantly impede plant growth and reduce crop yield. Thus,... (Review)
Review
Plants inevitably encounter environmental adversities, including abiotic and biotic stresses, which significantly impede plant growth and reduce crop yield. Thus, fine-tuning the fate and function of stress-responsive RNAs is indispensable for plant survival under such adverse conditions. Recently, post-transcriptional RNA modifications have been studied as a potent route to regulate plant gene expression under stress. Among over 160 mRNA modifications identified to date, N -methyladenosine (m A) in mRNAs is notable because of its multifaceted roles in plant development and stress response. Recent transcriptome-wide mapping has revealed the distribution and patterns of m A in diverse stress-responsive mRNAs in plants, building a foundation for elucidating the molecular link between m A and stress response. Moreover, the identification and characterization of m A writers, readers and erasers in Arabidopsis and other model crops have offered insights into the biological roles of m A in plant abiotic stress responses. Here, we review the recent progress of research on mRNA modifications, particularly m A, and their dynamics, distribution, regulation and biological functions in plant stress responses. Further, we posit potential strategies for breeding stress-tolerant crops by engineering mRNA modifications and propose the future direction of research on RNA modifications to gain a much deeper understanding of plant stress biology.
Topics: Plant Breeding; Plant Development; Crops, Agricultural; Genes, Plant; Arabidopsis; RNA, Messenger
PubMed: 36002976
DOI: 10.1111/pbi.13913 -
Frontiers in Oncology 2023The activation of anti-tumor immunity is critical in treating cancers. Recent studies indicate that several chemotherapy agents can stimulate anti-tumor immunity by... (Review)
Review
The activation of anti-tumor immunity is critical in treating cancers. Recent studies indicate that several chemotherapy agents can stimulate anti-tumor immunity by inducing immunogenic cell death and durably eradicate tumors. This suggests that immunogenic chemotherapy holds great potential for improving response rates. However, chemotherapy in practice has only had limited success in inducing long-term survival or cure of cancers when used either alone or in combination with immunotherapy. We think that this is because the importance of dose, schedule, and tumor model dependence of chemotherapy-activated anti-tumor immunity is under-appreciated. Here, we review immune modulation function of representative chemotherapy agents and propose a model of immunogenic chemotherapy-induced long-lasting responses that rely on synergetic interaction between killing tumor cells and inducing anti-tumor immunity. We comb through several chemotherapy treatment schedules, and identify the needs for chemotherapy dose and schedule optimization and combination therapy with immunotherapy when chemotherapy dosage or immune responsiveness is too low. We further review tumor cell intrinsic factors that affect the optimal chemotherapy dose and schedule. Lastly, we review the biomarkers indicating responsiveness to chemotherapy and/or immunotherapy treatments. A deep understanding of how chemotherapy activates anti-tumor immunity and how to monitor its responsiveness can lead to the development of more effective chemotherapy or chemo-immunotherapy, thereby improving the efficacy of cancer treatment.
PubMed: 38125944
DOI: 10.3389/fonc.2023.1308681 -
PLoS Pathogens Feb 2019Successful host colonization by bacteria requires sensing and response to the local ionic milieu, and coordination of responses with the maintenance of ionic homeostasis...
Successful host colonization by bacteria requires sensing and response to the local ionic milieu, and coordination of responses with the maintenance of ionic homeostasis in the face of changing conditions. We previously discovered that Mycobacterium tuberculosis (Mtb) responds synergistically to chloride (Cl-) and pH, as cues to the immune status of its host. This raised the intriguing concept of abundant ions as important environmental signals, and we have now uncovered potassium (K+) as an ion that can significantly impact colonization by Mtb. The bacterium has a unique transcriptional response to changes in environmental K+ levels, with both distinct and shared regulatory mechanisms controlling Mtb response to the ionic signals of K+, Cl-, and pH. We demonstrate that intraphagosomal K+ levels increase during macrophage phagosome maturation, and find using a novel fluorescent K+-responsive reporter Mtb strain that K+ is not limiting during macrophage infection. Disruption of Mtb K+ homeostasis by deletion of the Trk K+ uptake system results in dampening of the bacterial response to pH and Cl-, and attenuation in host colonization, both in primary murine bone marrow-derived macrophages and in vivo in a murine model of Mtb infection. Our study reveals how bacterial ionic homeostasis can impact environmental ionic responses, and highlights the important role that abundant ions can play during host colonization by Mtb.
Topics: Adaptation, Biological; Animals; Bacterial Proteins; Homeostasis; Host Microbial Interactions; Host-Pathogen Interactions; Ions; Macrophages; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Phagosomes; Potassium
PubMed: 30716121
DOI: 10.1371/journal.ppat.1007591 -
Chemical Science Sep 2018The responsive behavior of an entity towards its immediate surrounding is referred to as an adaptive response. The adaptive responses of a noncovalent interaction at the... (Review)
Review
The responsive behavior of an entity towards its immediate surrounding is referred to as an adaptive response. The adaptive responses of a noncovalent interaction at the molecular scale are reflected from its structural and functional roles. Intramolecular chalcogen bonding (IChB), an attractive interaction between a heavy chalcogen E (E = Se or Te) centered sigma hole and an -heteroatom Lewis base donor D (D = O or N), plays an adaptive role in defining the structure and reactivity of arylchalcogen compounds. In this perspective, we describe the adaptive roles of a chalcogen centered Lewis acid sigma hole and a proximal Lewis base (O or N) in accommodating built-in steric stress in 2,6-disubstituted arylchalcogen compounds. From our perspective, the IChB components (a sigma hole and the proximal Lewis base) act in synergism to accommodate the overwhelming steric force. The adaptive responses of the IChB components are inferred from the observed molecular structures and reactivity. These include (a) adaptation of a conformation without IChBs, (b) adaptation of a conformation with weak IChBs, (c) twisting the skeletal aryl ring while maintaining IChBs, (d) ionization of the E-X bond (, X = Br) to relieve stress and (e) intramolecular cyclization to relieve steric stress. A comprehensive approach, involving X-ray data analysis, density functional theory (DFT) calculations, reaction pattern analysis and principal component analysis (PCA), has been employed to rationalize the adaptive behaviors of IChBs in arylchalcogen compounds. We believe that the perception of ChB as an adaptive/stimulus responsive interaction would profit the futuristic approaches that would utilise ChB as self-assembly and molecular recognition tools.
PubMed: 30310623
DOI: 10.1039/c8sc01943f -
Materials (Basel, Switzerland) Jul 2020Stimuli-responsive, "smart" polymeric materials used in the biomedical field function in a bio-mimicking manner by providing a non-linear response to triggers coming... (Review)
Review
Stimuli-responsive, "smart" polymeric materials used in the biomedical field function in a bio-mimicking manner by providing a non-linear response to triggers coming from a physiological microenvironment or other external source. They are built based on various chemical, physical, and biological tools that enable pH and/or temperature-stimulated changes in structural or physicochemical attributes, like shape, volume, solubility, supramolecular arrangement, and others. This review touches on some particular developments on the topic of stimuli-sensitive molecular tools for biomedical applications. Design and mechanistic details are provided concerning the smart synthetic instruments that are employed to prepare supra- and macro-molecular architectures with specific responses to external stimuli. Five major themes are approached: (i) temperature- and pH-responsive systems for controlled drug delivery; (ii) glycodynameric hydrogels for drug delivery; (iii) polymeric non-viral vectors for gene delivery; (iv) metallic nanoconjugates for biomedical applications; and, (v) smart organic tools for biomedical imaging.
PubMed: 32727155
DOI: 10.3390/ma13153343 -
Scandinavian Journal of Immunology Jun 2021Early airway responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are of interest since they could decide whether coronavirus disease-19... (Review)
Review
Early airway responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are of interest since they could decide whether coronavirus disease-19 (COVID-19) will proceed to life-threatening pulmonary disease stages. Here I discuss endothelial-epithelial co-operative in vivo responses producing first-line, humoral innate defence opportunities in human airways. The pseudostratified epithelium of human nasal and tracheobronchial airways are prime sites of exposure and infection by SARS-CoV-2. Just beneath the epithelium runs a profuse systemic microcirculation. Its post-capillary venules respond conspicuously to mucosal challenges with autacoids, allergens and microbes, and to mere loss of epithelium. By active venular endothelial gap formation, followed by transient yielding of epithelial junctions, non-sieved plasma macromolecules move from the microcirculation to the mucosal surface. Hence, plasma-derived protein cascade systems and antimicrobial peptides would have opportunity to operate jointly on an unperturbed mucosal lining. Similarly, a plasma-derived, dynamic gel protects sites of epithelial sloughing-regeneration. Precision for this indiscriminate humoral molecular response lies in restricted location and well-regulated duration of plasma exudation. Importantly, the endothelial responsiveness of the airway microcirculation differs distinctly from the relatively non-responsive, low-pressure pulmonary microcirculation that non-specifically, almost irreversibly, leaks plasma in life-threatening COVID-19. Observations in humans of infections with rhinovirus, coronavirus 229E, and influenza A and B support a general but individually variable early occurrence of plasma exudation in human infected nasal and tracheobronchial airways. Investigations are warranted to elucidate roles of host- and drug-induced airway plasma exudation in restriction of viral infection and, specifically, whether it contributes to variable disease responses following exposure to SARS-CoV-2.
Topics: Antibodies, Viral; Biomarkers; Blood Proteins; COVID-19; Capillary Permeability; Complement Activation; Complement System Proteins; Exudates and Transudates; Host-Pathogen Interactions; Humans; Immunity, Humoral; Immunity, Innate; Immunoglobulin M; Microvessels; Respiratory Mucosa; SARS-CoV-2
PubMed: 33523532
DOI: 10.1111/sji.13024 -
International Journal of Molecular... May 2018Owing to diverse abiotic stresses and global climate deterioration, the agricultural production worldwide is suffering serious losses. Breeding stress-resilient crops... (Review)
Review
Owing to diverse abiotic stresses and global climate deterioration, the agricultural production worldwide is suffering serious losses. Breeding stress-resilient crops with higher quality and yield against multiple environmental stresses via application of transgenic technologies is currently the most promising approach. Deciphering molecular principles and mining stress-associate genes that govern plant responses against abiotic stresses is one of the prerequisites to develop stress-resistant crop varieties. As molecular switches in controlling stress-responsive genes expression, transcription factors (TFs) play crucial roles in regulating various abiotic stress responses. Hence, functional analysis of TFs and their interaction partners during abiotic stresses is crucial to perceive their role in diverse signaling cascades that many researchers have continued to undertake. Here, we review current developments in understanding TFs, with particular emphasis on their functions in orchestrating plant abiotic stress responses. Further, we discuss novel molecular mechanisms of their action under abiotic stress conditions. This will provide valuable information for understanding regulatory mechanisms to engineer stress-tolerant crops.
Topics: Anaerobiosis; Energy Metabolism; Gene Expression Regulation, Plant; Plant Physiological Phenomena; Plants; Reactive Oxygen Species; Stress, Physiological; Transcription Factors
PubMed: 29857524
DOI: 10.3390/ijms19061634