Confer Stress Resistance Research Articles

Integrated Metabolomic and Transcriptomic Analysis Reveals the Molecular Regulatory Mechanism of Gamma-Aminobutyric Acid Accumulation in White Quinoa (Chenopodium quinoa Willd.) in Response to Dark and Ultrasound Stress.

Gamma-aminobutyric acid (GABA) is a nonprotein amino acid, which confers stress resistance to plants. Precise mechanisms underlying GABA accumulation in quinoa (Chenopodium quinoa) subjected to dark and ultrasonic stresses have not been elucidated. We conducted transcriptome and metabolome analyses of quinoa samples exposed to various stress treatments to reveal molecular pathways leading to GABA accumulation. Through the comprehensive integration of metabolome and transcriptome data, an association was revealed between GABA accumulation, 9 differentially expressed metabolites, and 27 differentially expressed genes. Two pathways responsible for GABA synthesis were identified, involving glutamate decarboxylase and aldehyde dehydrogenases, respectively. These enzymes regulate the enrichment of GABA in quinoa under dark and ultrasonic stress conditions. We demonstrated that under ultrasonic stress, proline and alanine increased, whereas glutamate and arginine declined. Phenolic acid, flavonoids, and alkaloid metabolites increased. These findings provide novel insights into the mechanism by which darkness and ultrasound stress enhance GABA, supporting the development of targeted synthetic biology techniques.

FMO-4 SLOWS AGING DOWNSTREAM OF MTOR AND DR THROUGH ER TO MITOCHONDRIA CALCIUM SIGNALING

Abstract The geroscience field has identified several pathways that regulate aging across species. Of these pathways, dietary restriction and the reduced mechanistic target of rapamycin (mTOR) signaling are among the best studied but still not fully understood interventions. Recent work from our lab and others established the flavin containing monooxygenase family of enzymes as regulators of longevity across species. While others found that Fmos are induced by longevity interventions in mice, we found that Cefmo-2 promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. These results suggest that the FMO family could regulate longevity in multiple species, including humans. Our new work focuses on the role of C. elegans FMO-4, which is structurally similar to FMO-2 but expressed in a different tissue. Our data show that fmo-4 confers stress resistance and is required for DR- and mTOR-mediated longevity. We also find that fmo-4 does not act similar to fmo-2 but downstream of it, and interacts with calcium signaling and stress response to promote healthy aging. Under the hypothesis that modified calcium signaling is crucial for ER and mitochondrial homeostasis, we find evidence of 1) the metabolic, stress, and aging processes in which FMO-4 activity plays a role, and 2) the likely mechanisms for these roles. Overall, our data highlight the importance of FMOs in longevity, and reveal a novel mechanism for FMO regulation of longevity and metabolism.

Enhanced Multi-Stress Tolerance in Escherichia coli via the Heterologous Expression of Zymomonas mobilis recA: Implications for Industrial Strain Engineering

This study investigated the role of the Zymomonas mobilis recA gene in conferring stress resistance when expressed in Escherichia coli. The recA gene was cloned and expressed in E. coli BL21(DE3), producing a 39 kDa polypeptide. The results of comparative analyses demonstrated that the recombinant strain significantly enhanced survival rates under various stress conditions. In oxidative stress tests, the recombinant E. coli pET-22b(+)-recA exhibited superior survival at 3 mM and 5 mM H2O2 concentrations. Heat stress experiments at 50 °C and 55 °C revealed increased survival for the recombinant strain. Under ethanol stress, particularly at 20% (v/v), E. coli pET-22b(+)-recA displayed higher viability than controls. UV-C exposure tests further highlighted the protective effect of recA expression, with the recombinant strain maintaining viability after 60 min of exposure, while control strains showed no survival. These results indicate that the Z. mobilis recA gene product enhances resistance to oxidative, heat, ethanol, and UV-C stresses when expressed in E. coli. This study elucidates the broad stress-protective functions of the RecA protein across bacterial species and suggests potential applications in developing stress-tolerant bacterial strains for biotechnological purposes.

Genome-wide identification and expression analysis of CmoADHs in Cucurbita moschata—Critical role of CmoADH9 in drought tolerance

Genome-wide identification and expression analysis of CmoADHs in Cucurbita moschata—Critical role of CmoADH9 in drought tolerance

Transiently restricting individual amino acids protects Drosophila melanogaster against multiple stressors.

Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can protect Drosophila melanogaster against nicotine poisoning. Here, we sought to characterize the nature of this dietary-mediated protection and determine whether it was sex, amino acid and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. To understand whether these beneficial effects of diet were specific to nicotine or were generalizable across stressors, we pre-treated flies with amino acid restriction diets and exposed them to other types of stress. We found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.

Potentiality of Melatonin for Reinforcing Salinity Tolerance in Sorghum Seedlings via Boosting Photosynthetic Pigments, Ionic and Osmotic Homeostasis and Reducing the Carbonyl/Oxidative Stress Markers

Salinity stress has become a major threat to worldwide crop production. Exogenous melatonin (MT) has appeared as a promising treatment against salt stress in several plant species. However, MT effect on the tolerance of sorghum plants under different saline conditions (moderate and severe) remains ambiguous. This study was carried out to explore the impact of MT (0, 50, 100 and 200 µM) as a foliar application on sorghum seedlings grown under moderate and severe saline conditions using sodium chloride, NaCl (75 and 150 µM NaCl). Salinity treatments were applied as solution in sand medium in pots. The results demonstrated that rising salinity level negatively affected plant growth, photosynthetic pigments (chlorophylls and carotenoids), leaf water status and ionic homeostasis (sodium, potassium, and calcium ions). Applied-MT specifically at 100 or 200 µM enhanced the osmotic balance, cell membrane stabilizing and leaf relative water content. These effects were associated with an obvious restriction to the level of hydrogen peroxide, lipid peroxidation (malondialdehyde content) and methylglyoxal. Moreover, antioxidant activities of peroxidase, catalase, superoxide dismutase, and ascorbate peroxidase enzymes were modulated by MT treatments. Molecular docking modeling assessment illustrated top-ranked confirmations between MT and the target antioxidant enzymes. MT forms multiple hydrogen bonds with key amino acid residues for glycine (A: 162), tryptophan (A: 41), leucine (A: 165), tyrosine (A: 235) in the active site of ascorbate peroxidase. The alkyl interactions with leucine (A: 37), arginine (A: 38) and cysteine (A: 168) also contribute to its high affinity. Despite sorghum plant is commonly moderately tolerant to salinity stress, the results of this study confirmed its high sensitivity to a wide range of saline conditions at early growth stages. Melatonin spraying led to improvements in various morphological, physiological and biochemical mechanisms that harmonized together to confer stress resistance to salt-stressed sorghum seedlings.

Plant-Derived Extracts Plus Vitamin E and/or Aloe Vera Protect Against Intrinsic/Extrinsic Stressor in Human Skin: In Vitro and Clinical Evidence.

Humans are exposed to physical, biological, chemical, and psychological stressor throughout their life span. In recent years many medicinal plants have been shown to induce stress adapting and protective functions. Plant-derived extracts and vitamin E exhibit stress protection or resistance by normalizing cellular homeostasis and enhancing resistance to toxic stimuli to overcome cellular damage. Here we report the evaluation of a topical preparation (product test materials; PTM) containing an ingredient blend of Rhodiola Rosea, Eleutherococcus Senticosus (Siberian Ginseng), Rhaponticum Carthamoides, Inonotus Obliqus, and Slegainella Lepidophylla as the base formula and tested the addition of Lespedeza Capitata (leaf/stem) extract plus vitamin E and/or Aloe Vera to determine the induced protective functions in human skin when challenged with intrinsic and extrinsic stressors. The base topical preparation plus Lespedeza Capitata extract plus vitamin E or the base topical preparation plus vitamin E and Aloe Vera were assayed in vitro on (a) intrinsically stressed excised abdominoplasty skin, (b) full thickness (FT) skin equivalent models post-treated with a combination of ultra-violet (UV) B light (250 mJ/cm2) and diesel particular matter (DPM) (75 µg/mL) skin, for their effect on antioxidant, inflammation, and stress biomarker geners. Additionally, the bioadaptive activity of the PTMs was confirmed in providing resilience and protection against UV-induced erythema. For example, in a clinical study, daily topical application of the PTMs on the buttocks of 20 woman (18-78 years old), average age of 51.1 years, median body mass index (BMI) of 26.5 for 8 weeks followed by 2 minimal erythema dose (MED) of UVB exposure was accessed 24 hours after irradiation. Statistical analysis was performed by t-test and ANOVA, repectively. Pretreatment with the topical PTMs on intrsinically stressed skin significantly reduced the expression of the stress gene biomarkers, p53, pro-inflammatory cytokines Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNFα) and the pro-apoptotic BCL2 associated X, apoptosis regulator (BAX) values compared to controls. Topical application of the PTMs on Full Thickness (FT) human skin treated with UVB light and DPM significantly enhanced the stress response by activating heat shock transcription factor 4 (HSF4) and heat shock protein family B (small) member 1 (HSPB1) gene levels belonging to the heat shock protein (HSP) family by significantly increasing the expression of heme oxygenase 1 (HMOX1). At the same time, significantly reducing IL-1β levels were observed plus protection of skin cells from toxicity ocurred by significantly increasing the expression of B-cell lymphoma 2 (BCL2) (anti-apoptotic gene). In the clinical study, daily topical applications of the PTMs for 8 weeks followed by 2MED of UVB irradiation with clinical assessment 24 hours later revealed a significantly reduced intensity of erythema when compared to the buttock region treated with UVB alone. The PTMs containing adaptogen ingredients may confer stress resistance and induce stress protective responses against intrinsic as well as extrinsic stressors as demonstrated by the obtained in vitro and clinical evidence.

Fission Yeast Autophagy Machinery.

Autophagy is a conserved process that delivers cytoplasmic components to the vacuole/lysosome. It plays important roles in maintaining cellular homeostasis and conferring stress resistance. In the fission yeast Schizosaccharomyces pombe, autophagy is important for cell survival under nutrient depletion and ER stress conditions. Experimental analyses of fission yeast autophagy machinery in the last 10 years have unveiled both similarities and differences in autophagosome biogenesis mechanisms between fission yeast and other model eukaryotes for autophagy research, in particular, the budding yeast Saccharomyces cerevisiae. More recently, selective autophagy pathways that deliver hydrolytic enzymes, the ER, and mitochondria to the vacuole have been discovered in fission yeast, yielding novel insights into how cargo selectivity can be achieved in autophagy. Here, we review the progress made in understanding the autophagy machinery in fission yeast.

Recent Trends in Nano-Fertilizers for Sustainable Agriculture under Climate Change for Global Food Security.

Nano-fertilizers (NFs) significantly improve soil quality and plant growth performance and enhance crop production with quality fruits/grains. The management of macro-micronutrients is a big task globally, as it relies predominantly on synthetic chemical fertilizers which may not be environmentally friendly for human beings and may be expensive for farmers. NFs may enhance nutrient uptake and plant production by regulating the availability of fertilizers in the rhizosphere; extend stress resistance by improving nutritional capacity; and increase plant defense mechanisms. They may also substitute for synthetic fertilizers for sustainable agriculture, being found more suitable for stimulation of plant development. They are associated with mitigating environmental stresses and enhancing tolerance abilities under adverse atmospheric eco-variables. Recent trends in NFs explored relevant agri-technology to fill the gaps and assure long-term beneficial agriculture strategies to safeguard food security globally. Accordingly, nanoparticles are emerging as a cutting-edge agri-technology for agri-improvement in the near future. Interestingly, they do confer stress resistance capabilities to crop plants. The effective and appropriate mechanisms are revealed in this article to update researchers widely.

Fasting confers stress resistance to skeletal muscle stem cells through non-metabolic actions of β- hydroxybutyrate: implications in cardioprotection and aging

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A KBase case study on genome-wide transcriptomics and plant primary metabolism in response to drought stress in Sorghum.

A better understanding of the genetic and metabolic mechanisms that confer stress resistance and tolerance in plants is key to engineering new crops through advanced breeding technologies. This requires a systems biology approach that builds on a genome-wide understanding of the regulation of gene expression, plant metabolism, physiology and growth. In this study, we examine the response to drought stress in Sorghum, as we leverage the tools for transcriptomics and plant metabolic modeling we have implemented at the U.S. Department of Energy Systems Biology Knowledgebase (KBase). KBase enables researchers worldwide to collaborate and advance research by uploading private or public data into the KBase Narrative Interface, analyzing it using a rich, extensible array of computational and data-analytics tools, and securely sharing scientific workflows and conclusions. We demonstrate how to use the current RNA-seq tools in KBase, applicable to both plants and microbes, to assemble and quantify long transcripts and identify differentially expressed genes effectively. More specifically, we demonstrate the utility of the platform by identifying key genes differentially expressed during drought-stress in Sorghum bicolor, an important sustainable production crop plant. We then show how we can use KBase tools to predict the membership of genes in metabolic pathways and examine expression data in the context of metabolic subsystems. We demonstrate the power of the platform by making the data, analysis and interpretation available to the biologists in the reproducible, re-usable, point-and-click format of a KBase Narrative thus promoting FAIR (Findable, Accessible, Interoperable and Reusable) guiding principles for scientific data management and stewardship.

A standardized extract of Asparagus officinalis stem improves HSP70-mediated redox balance and cell functions in bovine cumulus-granulosa cells

Heat shock (HS) protein 70 (HSP70), a well-known HS-induced protein, acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to confer stress resistance to cells, HS causes cell toxicity by increasing reactive oxygen species (ROS) levels. Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the byproduct of asparagus, has been shown to induce HSP70 expression without HS and regulate cellular redox balance in pheochromocytoma cells. However, the effects of EAS on reproductive cell function remain unknown. Here, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa (CG) cells. EAS significantly increased HSP70 expression; however, no effect was observed on HSP27 and HSP90 under non-HS conditions. EAS decreased ROS generation and DNA damage and increased glutathione (GSH) synthesis under both non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression and increased progesterone levels in CG cells. Treatment with an HSP70 inhibitor significantly decreased GSH level, increased ROS level, and decreased HSF1, Nrf2, and Keap1 expression in the presence of EAS. Furthermore, EAS significantly increased progesterone synthesis. Thus, EAS improves HSP70-mediated redox balance and cell function in bovine CG cells.

Facing Adversity: Dormant Embryos in Rotifers.

An in-depth look at the basic aspects of dormancy in cyclic parthenogenetic organisms is now possible thanks to research efforts conducted over the past two decades with rotifer dormant embryos. In this review, we assemble and compose the current knowledge on four central themes: (1) distribution of dormancy in animals, with an overview on the phylogenetic distribution of embryo dormancy in metazoans, and (2) physiological and cellular processes involved in dormancy, with a strong emphasis on the dormant embryos of cyclically parthenogenetic monogonont rotifers; and discussions of (3) the selective pressures and (4) the evolutionary and population implications of dormancy in these animals. Dormancy in metazoans is a widespread phenomenon with taxon-specific features, and rotifers are among the animals in which dormancy is an intrinsic feature of their life cycle. Our review shows that embryo dormancy in rotifers shares common functional pathways with other taxa at the molecular and cellular level, despite the independent evolution of dormancy across phyla. These pathways include the arrest of similar metabolic routes and the usage of common metabolites for the stabilization of cellular structures and to confer stress resistance. We conclude that specific features of recurrent harsh environmental conditions are a powerful selective pressure for the fine-tuning of dormancy patterns in rotifers. We hypothesize that similar mechanisms at the organism level will lead to similar adaptive consequences at the population level across taxa, among which the formation of egg banks, the coexistence of species, and the possibility of differentiation among populations and local adaptation stand out. Our review shows how studies of rotifers have contributed to improved knowledge of all of these aspects.

Reversible Regulation of Polyubiquitin Gene UBC via Modified Inducible CRISPR/Cas9 System.

Ubiquitin is required under both normal and stress conditions. Under stress conditions, upregulation of the polyubiquitin gene UBC is essential to meet the requirement of increased ubiquitin levels to confer stress resistance. However, UBC upregulation is usually observed only under stress conditions and not under normal conditions. Therefore, it has not been possible to upregulate UBC under normal conditions to study the effect of excess ubiquitin on cellular machinery. Recently, the CRISPR/Cas9 system has been widely used in biological research as a useful tool to study gene disruption effects. In this study, using an inducible CRISPR/Cas9 variant, a dCas9–VP64 fusion protein, combined with a single guide RNA (sgRNA) containing MS2 aptamer loops and MS2-p65-HSF1, we developed a system to increase the ubiquitin pool via upregulation of UBC. Although it is challenging to upregulate the expression of a gene that is already expressed at high levels, the significance of our system is that UBC upregulation can be induced in an efficient, reversible manner that is compatible with cellular processes, even under normal conditions. This system can be used to study ubiquitin pool dynamics and it will be a useful tool in identifying the role of ubiquitin under normal and stress conditions.

NCAM1 (CD56) promotes leukemogenesis and confers drug resistance in AML

NCAM1 (CD56) promotes leukemogenesis and confers drug resistance in AML

Differential transcriptomic profiling of filamentous fungus during solid-state and submerged fermentation and identification of an essential regulatory gene PoxMBF1 that directly regulated cellulase and xylanase gene expression

BackgroundSolid-state fermentation (SSF) mimics the natural decay environment of soil fungi and can be employed to investigate the production of plant biomass-degrading enzymes. However, knowledge on the transcriptional regulation of fungal genes during SSF remains limited. Herein, transcriptional profiling was performed on the filamentous fungus Penicillium oxalicum strain HP7-1 cultivated in medium containing wheat bran plus rice straw (WR) under SSF (WR_SSF) and submerged fermentation (WR_SmF; control) conditions. Novel key transcription factors (TFs) regulating fungal cellulase and xylanase gene expression during SSF were identified via comparative transcriptomic and genetic analyses.ResultsExpression of major cellulase genes was higher under WR_SSF condition than that under WR_SmF, but the expression of genes involved in the citric acid cycle was repressed under WR_SSF condition. Fifty-six candidate regulatory genes for cellulase production were screened out from transcriptomic profiling of P. oxalicum HP7-1 for knockout experiments in the parental strain ∆PoxKu70, resulting in 43 deletion mutants including 18 constructed in the previous studies. Enzyme activity assays revealed 14 novel regulatory genes involved in cellulase production in P. oxalicum during SSF. Remarkably, deletion of the essential regulatory gene PoxMBF1, encoding Multiprotein Bridging Factor 1, resulted in doubled cellulase and xylanase production at 2 days after induction during both SSF and SmF. PoxMBF1 dynamically and differentially regulated transcription of a subset of cellulase and xylanase genes during SSF and SmF, and conferred stress resistance. Importantly, PoxMBF1 bound specifically to the putative promoters of major cellulase and xylanase genes in vitro.ConclusionsWe revealed differential transcriptional regulation of P. oxalicum during SSF and SmF, and identified PoxMBF1, a novel TF that directly regulates cellulase and xylanase gene expression during SSF and SmF. These findings expand our understanding of regulatory mechanisms of cellulase and xylanase gene expression during fungal fermentation.

Organoruthenium(II) complexes attenuate stress in Caenorhabditis elegans through regulating antioxidant machinery

Organoruthenium(II) complexes attenuate stress in Caenorhabditis elegans through regulating antioxidant machinery

Selective Pressure from Chemotherapy Drives Convergent Evolution in Relapsing and Refractory AML across Age Groups

Selective Pressure from Chemotherapy Drives Convergent Evolution in Relapsing and Refractory AML across Age Groups

A Major Facilitator Superfamily Transporter Regulated by the Stress-Responsive Transcription Factor Yap1 Is Required for Resistance to Fungicides, Xenobiotics, and Oxidants and Full Virulence in Alternaria alternata.

Alternaria alternata relies on the ability to produce a host-selective toxin and to detoxify reactive oxygen species to successfully colonize the host. An A. alternata major facilitator superfamily transporter designated AaMFS54 was functionally characterized by analysis of loss- and gain-of-function mutations to better understand the factors required for fungal pathogenesis. AaMFS54 was originally identified from a wild-type expression library after being subtracted with that of a mutant impaired for the oxidative stress-responsive transcription regulator Yap1. AaMFS54 contains 14 transmembrane helixes. Fungal mutant lacking AaMFS54 produced fewer conidia and increased sensitivity to many potent oxidants (potassium superoxide and singlet-oxygen generating compounds), xenobiotics (2,3,5-triiodobenzoic acid and 2-chloro-5-hydroxypyridine), and fungicides (clotrimazole, fludioxonil, vinclozolin, and iprodione). AaMFS54 mutant induced necrotic lesion sizes similar to those induced by wild-type on leaves of susceptible citrus cultivars after point inoculation with spore suspensions. However, the mutant produced smaller colonies and less fluffy hyphae on the affected leaves. Virulence assays on citrus leaves inoculated by spraying with spores revealed that AaMFS54 mutant induced less severe lesions than wild-type, indicating the requirement of AaMFS54 in pathogenesis. All defective phenotypes were restored in a strain re-acquiring a functional copy of AaMFS54. Northern blotting analysis revealed that the expression of AaMFS54 was suppressed by xenobiotics. The current studies indicate that the Yap1-mediated transporter plays a role in resistance to toxic oxidants and fungicides in A. alternata. The relationships of MFS transporters with other regulatory components conferring stress resistance and A. alternata pathogenesis are also discussed.

Regulation of Age-related Decline by Transcription Factors and Their Crosstalk with the Epigenome.

Aging is a complex phenomenon, where damage accumulation, increasing deregulation of biological pathways, and loss of cellular homeostasis lead to the decline of organismal functions over time. Interestingly, aging is not entirely a stochastic process and progressing at a constant rate, but it is subject to extensive regulation, in the hands of an elaborate and highly interconnected signaling network. This network can integrate a variety of aging-regulatory stimuli, i.e. fertility, nutrient availability, or diverse stresses, and relay them via signaling cascades into gene regulatory events - mostly of genes that confer stress resistance and thus help protect from damage accumulation and homeostasis loss. Transcription factors have long been perceived as the pivotal nodes in this network. Yet, it is well known that the epigenome substantially influences eukaryotic gene regulation, too. A growing body of work has recently underscored the importance of the epigenome also during aging, where it not only undergoes drastic age-dependent changes but also actively influences the aging process. In this review, we introduce the major signaling pathways that regulate age-related decline and discuss the synergy between transcriptional regulation and the epigenetic landscape.