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[Display omitted] • Regulated cell death (RCD) is associated with Parkinson's disease. • HSP90 participates in various RCDs by modulating clients' stability and function. • HSP90 in Parkinson's disease: Trick or treat? • HSP90 modulates proteostasis and protein quality control. • HSP90 inhibitors may be as potential therapeutic approaches of neurodegenerative disorders. Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by abnormal α-synuclein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, as well as progressive death of dopaminergic neurons in the substantia nigra. Molecular chaperones play a role in stabilizing proteins and helping them achieve their proper structure. Previous studies have shown that overexpression of heat shock protein 90 (HSP90) can lead to the death of dopaminergic neurons associated with PD. Inhibiting HSP90 is considered a potential treatment approach for neurodegenerative disorders, as it may reduce protein aggregation and related toxicity, as well as suppress various forms of regulated cell death (RCD). This review provides an overview of HSP90 and its role in PD, focusing on its modulation of proteostasis and quality control of LRRK2. The review also explores the effects of HSP90 on different types of RCD, such as apoptosis, chaperone-mediated autophagy (CMA), necroptosis, and ferroptosis. Additionally, it discusses HSP90 inhibitors that have been tested in PD models. We will highlight the under-investigated neuroprotective effects of HSP90 inhibition, including modulation of oxidative stress, mitochondrial dysfunction, PINK/PARKIN, heat shock factor 1 (HSF1), histone deacetylase 6 (HDAC6), and the PHD2-HSP90 complex-mediated mitochondrial stress pathway. By examining previous literature, this review uncovers overlooked neuroprotective mechanisms and emphasizes the need for further research on HSP90 inhibitors as potential therapeutic strategies for PD. Finally, the review discusses the potential limitations and possibilities of using HSP90 inhibitors in PD therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] Rice (Oryza sativa L.) production is threatened by global warming associated with extreme high temperatures, and rice heat sensitivity is differed when stress occurs between daytime and nighttime. However, the underlying molecular mechanism are largely unknown. We show here that two glycine-rich RNA binding proteins, OsGRP3 and OsGRP162, are required for thermotolerance in rice, especially at nighttime. The rhythmic expression of OsGRP3 / OsGRP162 peaks at midnight, and at these coincident times, is increased by heat stress. This is largely dependent on the evening complex component OsELF3-2. We next found that the double mutant of OsGRP3 /Os GRP162 is strikingly more sensitive to heat stress in terms of survival rate and seed setting rate when comparing to the wild-type plants. Interestingly, the defect in thermotolerance is more evident when heat stress occurred in nighttime than that in daytime. Upon heat stress, the double mutant of OsGRP3 / OsGRP162 displays globally reduced expression of heat-stress responsive genes, and increases of mRNA alternative splicing dominated by exon-skipping. This study thus reveals the important role of OsGRP3/OsGRP162 in thermotolerance in rice, and unravels the mechanism on how OsGRP3/OsGRP162 regulate thermotolerance in a diurnal manner. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is an essential element for maintaining normal metabolism in vertebrates. Mn dioxide nanoparticles (MnO 2 NPs), a novel Mn source, have shown great potentials in biological and biomedical applications due to their distinct physical and chemical properties. However, little is known about potential adverse effects on animal or cellular metabolism. Here, we investigated whether and how dietary MnO 2 NPs affect hepatic lipid metabolism in vertebrates. We found that, excessive MnO 2 NPs intake increased hepatic and mitochondrial Mn content, promoted hepatic lipotoxic disease and lipogenesis, and inhibited hepatic lipolysis and fatty acid β-oxidation. Moreover, excessive MnO 2 NPs intake induced hepatic mitochondrial oxidative stress, damaged mitochondrial function, disrupted mitochondrial dynamics and activated mitophagy. Importantly, we uncovered that mtROS-activated phosphorylation of heat shock factor 1 (Hsf1) at Ser326 residue mediated MnO 2 NPs-induced hepatic lipotoxic disease and mitophagy. Mechanistically, MnO 2 NPs-induced lipotoxicity and mitophagy were via mtROS-induced phosphorylation and nucleus translocation of Hsf1 and its DNA binding capacity to plin2 / dgat1 and bnip3 promoters, respectively. Overall, our findings uncover novel mechanisms by which mtROS-mediated mitochondrial dysfunction and phosphorylation of Hsf1S326 contribute to MnO 2 NPs-induced hepatic lipotoxicity and mitophagy, which provide new insights into the effects of metal oxides nanoparticles on hepatotoxicity in vertebrates. [Display omitted] • MnO 2 NPs increased Mn and lipid contents, promoted lipogenesis, and inhibited lipolysis and fatty acid β-oxidation. • MnO 2 NPs induced mitochondrial oxidative stress, damaged mitochondrial structure and function, and activated mitophagy. • mtROS-activated phosphorylation of Hsf1Ser326 residue mediated MnO 2 NPs-induced hepatic lipotoxicity and mitophagy. • MnO 2 NPs-induced lipotoxicity and mitophagy were via mtROS-induced Hsf1 phosphorylation and bnip3 activation. • Hsf1 mediated MnO 2 NPs-induced lipotoxicity through transcriptional activation of plin2 and dgat1. [ABSTRACT FROM AUTHOR]

Reactive sulfur species (RSS) have emerged as key regulators of protein quality control. However, the mechanisms by which RSS contribute to cellular processes are not fully understood. In this study, we identified a novel function of RSS in preventing parthanatos, a nonapoptotic form of cell death that is induced by poly (ADP-ribose) polymerase-1 and mediated by the aggresome-like induced structures (ALIS) composed of SQSTM1/p62. We found that sodium tetrasulfide (Na2S4), a donor of RSS, strongly suppressed oxidative stress-dependent ALIS formation and subsequent parthanatos. On the other hand, the inhibitors of the RSS-producing enzymes, such as 3-mercaptopyruvate sulfurtransferase and cystathionine ?-lyase, clearly enhanced ALIS formation and parthanatos. Interestingly, we found that Na2S4 activated heat shock factor 1 by promoting its dissociation from heat shock protein 90, leading to accelerated transcription of HSP70. Considering that the genetic deletion of HSP70 allowed the enhanced ALIS formation, these findings suggest that RSS prevent parthanatos by specifically suppressing ALIS formation through induction of HSP70. Taken together, our results demonstrate a novel mechanism by which RSS prevent cell death, as well as a novel physiological role of RSS in contributing to protein quality control through HSP70 induction, which may lead to better understanding of the bioactivity of RSS. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) has multifaceted roles in plants. He et al. report that NO produced in the shoot apex causes S -nitrosation of transcription factor GT-1. This mediator of NO signal perception subsequently regulates the expression of the HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2) gene, thus leading to thermotolerance in Arabidopsis thaliana. [ABSTRACT FROM AUTHOR]

During winter hibernation, a diverse range of small mammals can enter prolonged torpor. They spend the nonhibernation season as a homeotherm but the hibernation season as a heterotherm. In the hibernation season, chipmunks (Tamias asiaticus) cycle regularly between 5 and 6 days-long deep torpor with a body temperature (Tb) of 5 to 7 °C and interbout arousal of -20 h, during which, their Tb returns to the normothermic level. Here, we investigated Per2 expression in the liver to elucidate the regulation of the peripheral circadian clock in a mammalian hibernator. In the nonhibernation season, as in mice, heat shock factor 1, activated by elevated Tb during the wake period, activated Per2 transcription in the liver, which contributed to synchronizing the peripheral circadian clock to the Tb rhythm. In the hibernation season, we determined that the Per2 mRNA was at low levels during deep torpor, but Per2 transcription was transiently activated by heat shock factor 1, which was activated by elevated Tb during interbout arousal. Nevertheless, we found that the mRNA from the core clock gene Bmal1 exhibited arrhythmic expression during interbout arousal. Since circadian rhythmicity is dependent on negative feedback loops involving the clock genes, these results suggest that the peripheral circadian clock in the liver is nonfunctional in the hibernation season. [ABSTRACT FROM AUTHOR]

Cells respond to multiple signals from the environment simultaneously, which often creates crosstalk between pathways affecting the capacity to adapt to the changing environment. Chaperones are an important component in the cellular integration of multiple responses to environmental signals, often implicated in negative feedback and inactivation mechanisms. These mechanisms include the stabilization of steroid hormone nuclear receptors in the cytoplasm in the absence of their ligand. Here, we show using immunofluorescence, chromatin immunoprecipitation, and nascent transcripts production that the heat shock protein 70 (HSP70) chaperone plays a central role in a new crosstalk mechanism between the steroid and heat shock response pathways. HSP70-dependent feedback mechanisms are required to inactivate the heat shock factor 1 (HSF1) after activation. Interestingly, a steroid stimulation leads to faster accumulation of HSF1 in inactive foci following heat shock. Our results further show that in the presence of estrogen, HSP70 accumulates at HSF1-regulated noncoding regions, leading to deactivation of HSF1 and the abrogation of the heat shock transcriptional response. Using an HSP70 inhibitor, we demonstrate that the crosstalk between both pathways is dependent on the chaperone activity. These results suggest that HSP70 availability is a key determinant in the transcriptional integration of multiple external signals. Overall, these results offer a better understanding of the crosstalk between the heat shock and steroid responses, which are salient in neurodegenerative disorders and cancers. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases affect millions of Americans every year. One factor linked to the formation of aggregates associated with these diseases is damage sustained to proteins by oxidative stress. Management of protein misfolding by the ubiquitous Hsp70 chaperone family can be modulated by modification of two key cysteines in the ATPase domain by oxidizing or thiol-modifying compounds. To investigate the biological consequences of cysteine modification on the Hsp70 Ssa1 in budding yeast, we generated cysteine null (cysteine to serine) and oxidomimetic (cysteine to aspartic acid) mutant variants of both C264 and C303 and demonstrate reduced ATP binding, hydrolysis, and protein folding properties in both the oxidomimetic and hydrogen peroxide-treated Ssa1. In contrast, cysteine nullification rendered Ssa1 insensitive to oxidative inhibition. Additionally, we determined the oxidomimetic ssa1-2CD (C264D, C303D) allele was unable to function as the sole Ssa1 isoform in yeast cells and also exhibited dominant negative effects on cell growth and viability. Ssa1 binds to and represses Hsf1, the major transcription factor controlling the heat shock response, and we found the oxidomimetic Ssa1 failed to stably interact with Hsf1, resulting in constitutive activation of the heat shock response. Consistent with our in vitro findings, ssa1-2CD cells were compromised for de novo folding, post-stress protein refolding, and in regulated degradation of a model terminally misfolded protein. Together, these findings pinpoint Hsp70 as a key link between oxidative stress and proteostasis, information critical to understanding cytoprotective systems that prevent and manage cellular insults underlying complex disease states. [ABSTRACT FROM AUTHOR]

Biomolecular condensates are self-organized membraneless bodies involved in many critical cellular activities, including ribosome biogenesis, protein synthesis, and gene transcription. Aliphatic alcohols are commonly used to study biomolecular condensates, but their effects on transcription are unclear. Here, we explore the impact of the aliphatic dialcohol, 1,6-hexanediol (1,6-HD), on Pol II transcription and nucleosome occupancy in budding yeast. As expected, 1,6-HD, a reagent effective in disrupting biomolecular condensates, strongly suppressed the thermal stress-induced transcription of Heat Shock Factor 1-regulated genes that have previously been shown to physically interact and coalesce into intranuclear condensates. Surprisingly, the isomeric dialcohol, 2,5-HD, typically used as a negative control, abrogated Heat Shock Factor 1-target gene transcription under the same conditions. Each reagent also abolished the transcription of genes that do not detectably coalesce, including Msn2/Msn4-regulated heat-inducible genes and constitutively expressed housekeeping genes. Thus, at elevated temperature (39 °C), HDs potently inhibit the transcription of disparate genes and as demonstrated by chromatin immunoprecipitation do so by abolishing occupancy of RNA polymerase in chromatin. Concurrently, histone H3 density increased at least twofold within all gene coding and regulatory regions examined, including quiescent euchromatic loci, silent heterochromatic loci, and Pol III-transcribed loci. Our results offer a caveat for the use of HDs in studying the role of condensates in transcriptional control and provide evidence that exposure to these reagents elicits a widespread increase in nucleosome density and a concomitant loss of both Pol II and Pol III transcription. [ABSTRACT FROM AUTHOR]

Phosphate (Pi) availability has become a major constraint limiting crop growth and production. Heat shock factors (Hsfs) play important roles in mediating plant resistance to various environmental stresses, including heat, drought and salinity. However, whether members of the Hsf family are involved in the transcriptional regulation of plant responses to Pi insufficiency has not been reported. Here, we identified that TaHsfA2d , a member of the heat shock factor family, was strongly repressed by Pi deficiency. Overexpressing TaHsfA2d-4A in Arabidopsis results in significantly enhanced sensitivity to Pi deficiency, evidenced by increased anthocyanin content, decreased proliferation and elongation of lateral roots, and reduced Pi uptake. Furthermore, RNA-seq analyses showed that TaHsfA2d-4A functions through up-regulation of a number of genes involved in stress responses and flavonoid biosynthesis. Collectively, these results provide evidence that TaHsfA2d participates in the regulation of Pi deficiency stress, and that TaHsfA2d could serve as a valuable gene for genetic modification of crop tolerance to Pi starvation. • Heat shock factor (Hsf) genes are reported to be involved in plant responses to phosphate deficiency for the first time. • The expression of wheat TaHsfA2d was repressed by phosphate deficiency. • Overexpression of the TaHsfA2d-4A gene in Arabidopsis results in significantly enhanced sensitivity to phosphate deficiency. • TaHsfA2d-4A functions through regulating the expression of flavonoid biosynthesis and stress-related genes. [ABSTRACT FROM AUTHOR]

• A multifunctional exothermic bioactive nanoglass was reported for therapy-regeneration. • The bioactive nanoglass showed antimicrobial, antioxidant, photothermal, angiogenic activity. • The bioactive nanoglass exerts oxidative stress alleviation in vivo by activating the Nrf2 pathway. • The exothermic bioactive nanoglass system could efficiently promote tissue regeneration in MRSA-infected wounds repair. • The tissue repair mechanism was attributed to the thermo-ions coordination pathway. The efficient repair and tissue regeneration of chronic infected wounds is still a major challenge, among which the bacterial infection, inflammation and oxidative stress induced poor angiogenesis are the key obstacles. The nanosystem with single repair pathway could not meet the requirement of regenerating complicated wound tissue. Herein, we construct an photothermal multifunctional bioactive nanoglass (BGN) with the metal polyphenol coordination surface to treat methicillin-resistant Staphylococcus aureus （MRSA）infected wound. The BGN was coated with copper (Cu) coordinated polydopamine (PDA-Cu) to bioactive BGN@PDA-Cu nanoparticles, which release bioactive ions (Ca2+, SiO 4 4- and Cu2+) and show the robust antibacterial/antioxidant/mild photothermal activities. BGN@PDA-Cu possesses the strong MRSA inhibition, reactive oxygen species scavenging, mild photothermal stimulation (41℃) and hemostatic ability. The antioxidant activity, thermal stimulation and sustainable bioactive ions release could significantly reverse the inflammatory phenotype of macrophage and enhance the angiogenesis through the activation of hypoxia-inducible factor HIF-1α and heat shock protein HSP90 pathways. The in vivo MRSA infected wound model demonstrated that BGN@PDA-Cu could significantly inhibit the MRSA infection and accelerate the wound repair which has 2 times improvement on healing rate compared with commercial bioglass dressing. This work demonstrates that bioactive ions release combined with mild thermal stimulation is a promising strategy to design multifunctional bioactive biomaterials for angiogenetic tissue regeneration. [ABSTRACT FROM AUTHOR]

Zucchini squashes are cold-sensitive and vulnerable to chilling injury (CI) resulting from reactive oxygen species (ROS) and hot water (HW) immersing effectively reduce CI symptoms during cold storage. However, mechanism involved in reduced ROS due to HW treatment has not been characterized well. In this study, tender green zucchini fruit were treated with HW for 15 min at 45 ± 1 °C and stored for 15 d at 4 ± 1 °C and above 90 % relative humidity. Results showed substantial reduction in CI index, electrolyte leakage, malonaldehyde (MDA) contents and ROS accumulation along with increased activity of ROS-scavenging enzymes due to HW treatment. To gain insight into the molecular mechanism involved in antioxidant defense system, transcriptomic analysis revealed that heat shock factors (HSF) accumulated due to HW treatment regulated the ROS pathway during cold stress. CpHSFA4a was one of the highly expressed transcription factors (TF) due to HW treatment that regulated the transcription of ROS enzymes related genes. CpHSFA4a bind actively with heat shock element (HSE) in promoter regions of CpSOD , CpCAT , CpAPX1 , CpAPX2 , and CpAPX3 , activated and increased the expression of these genes. In conclusion, HW treatment alleviated the CI by maintaining ROS homeostasis through CpHSFA4a mediated ROS pathway in zucchini squashes during cold storage. • HW treatment alleviated CI and maintained post storage quality of zucchini squashes. • HW treatment induced the ROS signal transduction which in turn triggered the transcription of HSFs. • CpHSFA4a played a pivotal role in ROS homeostasis by transcriptional regulation of ROS related downstream genes. • HW treatment upregulated the enzymes related to ROS metabolism. [ABSTRACT FROM AUTHOR]

Chicken meat processing generates a substantial number of byproducts, which are either underutilized or improperly disposed. In this study, we employed in silico approaches to identify antioxidant peptides in chicken liver byproducts. Notably, the peptide WYR exhibited remarkable 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity with an IC 50 of 0.13 ± 0.01 mg/mL and demonstrated stability under various conditions, including thermal, pH, NaCl, and simulated gastrointestinal digestion. Molecular docking analysis revealed significant hydrogen bonding interactions, while molecular dynamics showed differential stability with ABTS and 2,2-Diphenyl-1-picrylhydrazyl (DPPH). WYR exhibited improved stress resistance, decreased levels of reactive oxygen species (ROS), elevated the activities of superoxide dismutase (SOD) and catalase (CAT), and modulated the expression of crucial genes through the insulin/insulin-like growth factor (IIS) signaling pathway, mitogen-activated protein kinase (MAPK), and heat shock transcription factor-1 (HSF-1) pathways. These effects collectively contributed to the extension of Caenorhabditis elegans ' lifespan. This study not only provides an effective method for antioxidant peptide analysis but also highlights the potential for enhancing the utilization of poultry byproducts. [ABSTRACT FROM AUTHOR]

Melatonin (MT) is an amine hormone secreted by the body that has antioxidant and anti-inflammatory properties. The aim of this study was to investigate pathophysiological protection of MT in heat-stressed chickens. By modelling heat-stressed chickens and treating them with MT. After 21 days of administration, serum antioxidant enzymes, biochemical indices, inflammatory cytokine and heat-stress indices were detected, along with cardiopulmonary function indices and histological observations in chickens. The results show heat-stress induced a decrease (P < 0.05) in body weight and an increase in body temperature, which was reversed after MT intervention. Treatment with MT inhibited (P < 0.05) the secretion of pro-inflammatory factors interleukin-1β, interleukin-6, tumor necrosis factor α, serum heat shock protein 70, corticosterone, and elevated (P < 0.05) the levels of biochemical factors total protein, albumin, globulin, and increased (P < 0.05) the activities of antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase in chicken serum caused by heat stress, and the best effect was observed with the medium dose of MT. The heat-stress caused cardiac atrophy and pulmonary congestion, decreased (P < 0.05) the cardiac function indices creatine kinase isoenzyme, cardiac troponin I, angiotensin receptor I, creatine kinase and lung function indices myeloperoxidase, angiotensin-II, heat shock factor I, and increased (P < 0.05) the lung vascular endothelial growth factor II. Sections of the heart and lungs after administration of MT were observed to be more complete with more normal tissue indices. At the same time, compared with heat stress, heart and lung function indices of grade chickens after MT administration were significantly (P < 0.05) reduced and tended to normal levels, and the best effect was observed in the medium-dose MT. In conclusion, heat stress can cause pathophysiological damage in chickens, and 1 mg/kg/d of exogenous melatonin can attenuate this adverse effect. • Heat stress (34 ± 2 °C) alters physiological functions in chickens. • Melatonin improves anti-inflammatory, antioxidant and immune functions in chickens. • Melatonin reduces heat stress-induced cardiopulmonary injury in chickens. [ABSTRACT FROM AUTHOR]

[Display omitted] Aurora kinase (AURK) and heat shock factor 1 (HSF1) are commonly overexpressed in non-small cell lung cancer (NSCLC), correlating with poor prognosis. This study aims to assess the therapeutic potential of combining the Danusertib (Danu, AURK inhibitor) and KRIBB11 (HSF1 inhibitor) for NSCLC treatment. The effects of this combination were investigated in A549 cells and a tumor xenograft mouse model. The findings demonstrate that concurrent administration of Danu and KRIBB11 effectively impedes cell proliferation, induces apoptosis, and triggers G2/M cell cycle arrest. Moreover, the combination treatment upregulates pro-apoptotic proteins (Cleaved-caspase3, Cleaved-PARP, and Bax) while downregulating anti-apoptotic proteins (Bcl-2), as well as G2/M−related proteins (CDC2 and cyclin B1). Additionally, the combination treatment elevates reactive oxygen species (ROS) levels, decreases mitochondrial membrane potential, and activates the DNA damage pathway. Interestingly, we discovered that the PI3K/AKT pathway is involved in mediating the effects of both Danu and KRIBB11. Furthermore, the combination treatment inhibits tumor growth and AKT signaling in the xenograft mouse model, increases levels of the tumor tissue oxidation product malondialdehyde (MDA), and induces DNA damage. To summarize, a potential therapeutic approach for NSCLC may involve dual inhibition of AURK and HSF1, resulting in the downregulation of the PI3K/AKT signaling pathway, and the activation of ROS-mediated mitochondrial and DNA damage pathways. [ABSTRACT FROM AUTHOR]

• The first example of exploiting photothermal preprotection to defend HIRI. • Wedelolactone can serve as a new and effective drug for the treatment of HIRI. • Hypoxia dynamics in HIRI was studied by photoacoustic imaging for the first time. • Hypoxia can serve as an indicator for monitoring the treatment outcome of HIRI. Hepatic ischemia reperfusion injury (HIRI) following transplantation or resection can lead to irreversible liver dysfunction and even failure, yet current therapeutic interventions are limited. Herein, we introduce a "defend–attack and capture flag" nanotheranostic strategy for the cascade management of HIRI. Firstly, the NIR-II photothermal pretreatment with the developed nanosystem provides preprotection for the liver, acting as "defend". Subsequently, the pharmacotherapy furnishes direct cure for HIRI via the delivery and controlled release of wedelolactone from the nanosystem, serving as "attack". Meanwhile, the photoacoustic (PA) imaging ability of the nanosystem enables the real-time monitoring of the inflammatory hypoxia, which is the "flag" to be captured in HIRI treatment. The photothermal preprotection can activate heat shock factor 1 (HSF-1), while the pharmaceutical therapy directly attacks NF-κB, both of which eventually inhibits NLRP3 inflammasome, thus reducing the activity of proinflammatory cytokine IL-1β, ending up with the alleviation of necrosis and apoptosis in HIRI. Such treatment effect can be reported by the real-time PA imaging. By the organic combination of the above three-step mechanism, significantly enhanced therapeutic efficacy was achieved in the animal model of HIRI, providing an effective solution for overcoming the challenge of HIRI. [ABSTRACT FROM AUTHOR]

Heat shock transcription factors (Hsfs) play multifaceted roles in plant growth, development, and responses to environmental factors. However, their involvement in seed dormancy and germination processes has remained elusive. In this study, we identified a wheat class B Hsf gene, TaHsf-7A , with higher expression in strong-dormancy varieties compared to weak-dormancy varieties during seed imbibition. Specifically, TaHsf-7A expression increased during seed dormancy establishment and subsequently declined during dormancy release. Through the identification of a 1-bp insertion (ins)/deletion (del) variation in the coding region of TaHsf-7A among wheat varieties with different dormancy levels, we developed a CAPS marker, Hsf-7A-1319, resulting in two allelic variations: Hsf-7A-1319-ins and Hsf-7A-1319-del. Notably, the allele Hsf-7A-1319-ins correlated with a reduced seed germination rate and elevated dormancy levels, while Hsf-7A-1319-del exhibited the opposite trend across 175 wheat varieties. The association of TaHsf-7A allelic status with seed dormancy and germination levels was confirmed in various genetically modified species, including Arabidopsis, rice, and wheat. Results from the dual luciferase assay demonstrated notable variations in transcriptional activity among transformants harboring distinct TaHsf-7A alleles. Furthermore, the levels of abscisic acid (ABA) and gibberellin (GA), along with the expression levels of ABA and GA biosynthesis genes, showed significant differences between transgenic rice lines carrying different alleles of TaHsf-7A. These findings represent a significant step towards a comprehensive understanding of TaHsf-7A 's involvement in the dormancy and germination processes of wheat seeds. • The class B Hsf gene TaHsf-7A is highly expressed in wheat grains. • Transgenic experiments confirmed TaHsf-7A's crucial role in seed dormancy regulation. • AtHsfB2b and TaHsf-7A have functional similarity in regulating seed dormancy. • TaHsf-7A is involved in the ABA and GA signaling pathways to regulate seed dormancy. [ABSTRACT FROM AUTHOR]

Heat shock transcription factors (Hsfs) are essential regulators of plant responses to abiotic stresses, growth, and development. However, all the Hsf family members have not been identified in Sorbus pohuashanensis. Therefore, the aim of this study was to identify the Hsf family members in S. pohuashanensis and examine their expression under abiotic stress conditions through the integration of gene structure, phylogenetic relationships, chromosome location, and expression patterns. Bioinformatics-based methods, identified 33 Hsfs in S. pohuashanensis. Phylogenetic analysis of Hsfs from S. pohuashanensis and other species revealed that they were more closely related to apples and white pears, followed by Populus trichocarpa , and most distantly related to Arabidopsis. Moreover, the Hsfs were clustered into three major groups: A, B, and C. Gene structure and conserved motif analysis revealed a high degree of conservation among members of the same class. Collinearity analysis revealed that segmental duplication played an essential role in increasing the size of the SpHsfs gene family in S. pohuashanensis. Additionally, several cis-acting elements associated with growth and development, hormone response, and stress were found in the promoter region of SpHsfs genes. Furthermore, expression analysis in various tissues of S. pohuashanensis showed that the genes were closely associated with heat, drought, salt stress, growth, and developmental processes. Overall, these results provide valuable information on the evolutionary relationships of the Hsf gene family. These genes stand as strong functional candidates for further studies on the resistance of S. pohuashanensis to abiotic stresses. • This is the first study that attempted to identify Hsfs genes in Sorbus pohuashanensis. • A total of 33 SpHsfs genes were identified in Sorbus pohuashanensis. • The genes stand as functional candidates for further studies on the resistance of S. pohuashanensis to abiotic stresses. [ABSTRACT FROM AUTHOR]

To thrive and to fulfill their functions, cells need to maintain proteome homeostasis even in the face of adverse environmental conditions or radical restructuring of the proteome during differentiation. At the center of the regulation of proteome homeostasis is an ancient transcriptional mechanism, the so-called heat shock response (HSR), orchestrated in all eukaryotic cells by heat shock transcription factor 1 (Hsf1). As Hsf1 is implicated in aging and several pathologies like cancer and neurodegenerative disorders, understanding the regulation of Hsf1 could open novel therapeutic opportunities. In this review, we discuss the regulation of Hsf1's transcriptional activity by multiple layers of control circuits involving Hsf1 synthesis and degradation, conformational rearrangements and post-translational modifications (PTMs), and molecular chaperones in negative feedback loops. Hsf1 is a thermosensor itself and directly senses elevated temperatures with conformational changes in the leucin zipper domains HR-A/B and HR-C. Hsp70, not Hsp90 as proposed in many studies, is the main chaperone regulating Hsf1 activity by monomerizing Hsf1 trimers and thereby dissociating Hsf1 from DNA. A complex network of post-translational modifications (PTMs) accompanies Hsf1 through its lifetime, providing fine-tuning of its activity to integrate many input signals and to meet the respective needs of the cell at any time. Hsf1 activity downregulation could be beneficial to treat cancer, whereas Hsf1 upregulation may help to counteract neurodegenerative diseases like Parkinson or Alzheimer, or could be a key to healthy aging by prolonging the optimal proteostasis capacity. [ABSTRACT FROM AUTHOR]

• A similar number of HSF genes was identified between Carica papaya and Arabidopsis thaliana (19 vs 21). • The CpHSF family presented two events associated with genome expansion: a pair of tandem duplicated genes (CpHSFA9.1.1 and CpHSFA9.2), a single segmental duplication event between the CpHSFA6b and CpHSFA7a genes. • 12 CpHSF genes were differentially expressed in response to 14 days of water deficit. • The wild genotype can express more CpHSFs in response to water deficit than the commercial Maradol genotype. Heat shock transcription factors (HSFs) are a family of genes that are involved in plant development and in the response to biotic and abiotic stresses, including drought stress. HSFs are involved in regulating the expression of heat shock proteins (HSPs) by binding to heat stress elements (HSEs). The recent resequencing of the genome of Carica papaya cv. SunUp enables a more detailed in silico HSF genetic and functional study in this important species. In the present study, 19 CpHSF genes were identified. Phylogenetic analysis of HSF in Carica papaya and Arabidopsis thaliana revealed that they are closely related; both species showed a similar number (19 vs 21). As a result, they shared a similar phylogenetic tree with 3 well-defined classes (A, B, and C). Collinearity and synteny analysis indicated that the HSF family presented two events associated with genome expansion: a pair of tandem duplicated genes (CpHSFA9.1 and CpHSFA9.2) was identified, a single segmental duplication event between the CpHSFA6b and CpHSFA7a genes. The presence of cis-acting elements in the promoter regions of CpHSFs highlighted the regulatory role in response to light, high temperatures, ABA and drought inducibility. To determine the possible role of this family in the response mechanism to drought, experiments were carried out by exposing plants of 3 papaya genotypes to a period of 21 d water deficit stress (WDS). Our transcriptome results showed that the majority of CpHSF increased their expression when plants were exposed to 14d of WDS. Most importantly, it was clear that the wild genotype showed higher expression of various CpHSFs in response to drought, than the commercial genotype Maradol. Those results were confirmed using qRT-PCR of selected CpHSFs from plants exposed during 21 days to WDS. Again, the wild genotype had consistently higher expression of both CpHSFA1 and CpHSFB3, than the commercial genotype. [ABSTRACT FROM AUTHOR]

High temperature is a major constrait limiting the yield and quality of wheat. Wheat heat shock transcription factor (Hsf) plays important roles in regulating plant response to heat shock. In previous study, we found there are 82 Hsfs in wheat and TaHsfA2–11 expression was obviously upregulated by heat stress. In this study, we aim to investigate TaHsfA2–11 function and regulating mechanism in response to heat shock through genetic transformation into wheat Fielder. Gene expression analyses results showed that TaHsfA2–11 was expressed in all detected tissues and the most highly expressed level was in wheat mature roots. The expression level of TaHsfA2–11 was strongly upregulated by heat shock in wheat leaves. Subcellular localization results represented that TaHsfA2–11 is located to the nucleus. Transgenic wheat seedlings overexpressing TaHsfA2–11 showed stronger thermotolerance than the control Fielder after treated under 50 °C for 12 h. After heat shock, the TaHsfA2–11 overexpressing lines showed increased survival rate, chlorophyll content, POD (Peroxidase) activity, SOD (Superoxide dismutase) activity and photosynthetic rate, and decreased relative electrolyte leakage and MDA (malondialdehyde) content compared with Fielder. The results of RNA-sequence data demonstrated that TaHsfA2–11 can regulate many heat response genes, such as Hsp genes TaHsp16.6 and TaHsp21 , ER (Endoplasmic reticulum) stress genes TaBiP2 and TaERDJ3A, photoprotectant for PSII gene TaELIPHV58 , flavone biosynthesis related genes TaUGT-2A and TaPMaT , etc after heat stress. These results showed that TaHsfA2–11 can impove thermotolerance perhaps through effecting signal pathway of heat, ER stress, photosynthesis and ROS (Reactive Oxygen Species). The findings will provide useful gene resource for performing genetic modification of wheat thermotolerance in heat-resistant breeding. • TaHsfA2-11 up-regulated in wheat response to HS, H 2 O 2 and SA treatment. • TaHsfA2-11 has transactivation transcriptional activity. • Overexpression of TaHsfA2-11 in wheat improves thermotolerance. [ABSTRACT FROM AUTHOR]

The molecular responses of plants to the important abiotic stress, heat stress (HS), have been extensively studied at the transcriptional level. Alternative splicing (AS) is a post-transcriptional regulatory process in which an intron-containing gene can generate more than one mRNA variant. The impact of HS on the pre-mRNA splicing process has been reported in various eukaryotes but seldom discussed in-depth, especially in plants. Here, we review AS regulation in response to HS in different plant species. We discuss potential molecular mechanisms controlling heat-inducible AS regulation in plants and hypothesize that AS regulation participates in heat-priming establishment and HS memory maintenance. We propose that the pre-mRNA splicing variation is an important regulator of plant HS responses (HSRs). Pre-mRNA splicing regulation is a universal heat HSR mechanism in plants. Genes encoding essential transcription factors in response to HS, such as heat stress transcription factor A1 (HFSA1), HFSA2 , dehydration-responsive element binding protein 2B (DREB2B) , and heat shock proteins (HSPs) undergo extensive AS regulations in a variety of plants. Heat-inducible AS regulation of heat-responsive genes has been found in different plants. However, there is considerable variation in AS regulation among genotypes and species. AS regulation is carried out in an HS-dependent manner in plants. A group of pre-mRNA splicing factors, belonging to the SR protein family, participates in HS-dependent AS regulation in plants through modulation of their own transcription, pre-mRNA splicing, and phosphorylation status. Heat priming triggers pre-mRNA splicing memory in primed plants. [ABSTRACT FROM AUTHOR]

Specialized mechanisms ensure proper expression of critically important genes such as those specifying cell identity or conferring protection from environmental stress. Investigations of the heat shock response have been critical in elucidating basic concepts of transcriptional control. Recent studies demonstrate that in response to thermal stress, heat shock-responsive genes associate with high levels of transcriptional activators and coactivators and those in yeast intensely interact across and between chromosomes, coalescing into condensates. In mammalian cells, cell identity genes that are regulated by super-enhancers (SEs) are also densely occupied by transcriptional machinery that form phase-separated condensates. We suggest that the stress-remodeled yeast nucleome bears functional and structural resemblance to mammalian SEs, and will reveal fundamental mechanisms of gene control by transcriptional condensates. The rapid dynamics, robust induction, and conserved components of the HSF1-driven heat shock response make it an ideal system to study eukaryotic gene regulation. Heat shock (acute thermal stress) induces both short- and long-range changes in the chromosomal topology of budding yeast Heat Shock Protein (HSP) genes, culminating in their physical coalescence. HSP gene coalescence shares several key attributes with mammalian super-enhancers and multi-enhancer olfactory receptor hubs, including exceptional concentration of transcription factors and coactivators, extensive DNA looping and clustering, and cooperative assembly into phase-separated condensates. Elucidating the molecular basis for HSP gene coalescence could reveal fundamental mechanisms of gene control during critical cellular processes such as differentiation and development. [ABSTRACT FROM AUTHOR]

Winter cold is one of the major environmental stresses for ectotherm species. Chilo suppressalis , a notorious lepidopteran pest of rice, has a wide geographic region that includes temperate zones with severe environmental conditions. Although C. suppressalis exhibits remarkable cold tolerance, its cold-adaptation mechanisms remain unclear. Here, we used bioinformatics approaches to evaluate transcript levels of genes comprising the C. suppressalis heat shock protein (HSP)/co-chaperone network in response to cold-induced stress. Using all such genes identified in the C. suppressalis genome, we experimentally examined the corresponding transcript levels under cold-acclimation or intermittent cold-shock stresses in diapause and non-diapausing larvae. In total, we identified 19 HSPs and 8 HSP co-chaperones in the C. suppressalis genome. Nine (hsp90 , hsp75 , hsp70 , hsp40 , small hsp , activator of 90 kDa heat shock protein ATPase-like , heat shock factor , heat shock factor binding protein 1-like and HSPB1-associated protein 1) were highly cold-inducible and likely comprise the principal cold-response HSP/co-chaperone network in C. suppressalis. We also found that transcriptional regulation of the HSP/co-chaperone networks response differs between cold-acclimation and short-term cold-shock. Moreover, activation of the HSP/co-chaperone network depends on the diapause state of overwintering larvae and cold acclimation may further increase larval cold tolerance. These results provide key new insights in the cold-adaptation mechanisms in C. suppressalis. • The HSP/co-chaperone gene network was activated by environmental cold stress. • The HSP/co-chaperone network response differs between acclimated and short-term cold. • The HSP/co-chaperone network response differs between diapause status. • Our results provide key new insights in the insect cold-adaptation mechanism. [ABSTRACT FROM AUTHOR]

γ-Aminobutyric acid (GABA) is a non-protein amino acid involved in regulating various environmental adaption in plants. Twenty-six-day-old creeping bentgrass plants were treated with or without GABA (0.5 mM) and then exposed to heat stress (35/30 °C, day/night) for 25 days. Results showed that exogenous GABA application significantly increased endogenous GABA accumulation and alleviated heat-caused growth inhibition and water loss during heat stress. GABA-treated creeping bentgrass maintained significantly lower carbonyl content, malondialdehyde content, and electrolyte leakage, but exhibited higher total antioxidant capacity and antioxidant enzyme activities (SOD, CAT, POD, APX, and DR) than untreated plants under heat stress. Heat stress significantly decreased chlorophyll content, stomatal conductance, transpiration rate, net photosynthesis, and water use efficiency. However, GABA application effectively alleviated these heat-induced negative effects in creeping bentgrass. In addition, exogenous GABA further increased the expression of heat-induced HSPs (HSP12, HSP1 7.8, HSP26.7, HSP70, HSP82, HSP90.1-A1, HSP90.1-B1 , and HSP90-5) and HSFs (HSFA-2c, HSFA-2d, HSFA-6a, HSFB-2b , and HSFC-2b) and also further increased the abundance of HSP70, HSP90-1, and HSP101 in leaves of creeping bentgrass under heat stress. These results indicated that GABA alleviated heat-induced oxidative damage and chlorophyll loss through enhancing antioxidant capacity. GABA-treated creeping bentgrass maintained higher photosynthesis in leaves contributing to higher accumulation of water soluble carbohydrates for osmotic balance and energy supply under heat stress. GABA-regulated thermotolerance could be involved in upregulating HSF pathways in creeping bentgrass. • GABA alleviates heat-induced damage and chlorophyll loss through enhancing antioxidant capacity in creeping bentgrass. • GABA regulates the accumulation of water soluble carbohydrates for osmotic balance and energy supply under heat stress. • GABA regulates heat shock pathways and the accumulation of heat shock proteins in creeping bentgrass under heat stress. [ABSTRACT FROM AUTHOR]

Calcium-dependent protein kinases (CDPKs) are Ca2+ decoders in plants. AtCPK1 is a positive regulator in the plant response to biotic and abiotic stress. Inactivation of the autoinhibitory domain of AtCPK1 in the mutated form KJM23 provides constitutive activity of the kinase. In the present study, we investigated the effect of overexpressed native and mutant KJM23 forms on salinity tolerance in Nicotiana tabacum. Overexpression of native AtCPK1 provided tobacco resistance to 120 mM NaCl during germination and 180 mM NaCl during long-term growth, while the resistance of plants increased to 240 mM NaCl during both phases of plant development when transformed with KJM23. Mutation in the junction KJM4, which disrupted Ca2+ induced activation, completely nullified the acquired salt tolerance up to levels of normal plants. Analysis by confocal microscopy showed that under high salinity conditions, overexpression of AtCPK1 and KJM23 inhibited reactive oxygen species (ROS) accumulation to levels observed in untreated plants. Quantitative real-time PCR analysis showed that overexpression of AtCPK1 and KJM23 was associated with changes in expression of genes encoding heat shock factors. In all cases, the KJM23 mutation enhanced the effect of AtCPK1, while the KJM4 mutation reduced it to the control level. We suggest that the autoinhibitory domains in CDPKs could be promising targets for manipulation in engineering salt-tolerant plants. • AtCPK1 provided tobacco resistance to 120 mM NaCl (germination) and 180 mM NaCl (long-term growth). • Mutated AtCPK1 , KJM23 increased the resistance of plants up to 240 mM NaCl. • Mutated AtCPK1 , KJM4 completely nullified the acquired salt tolerance up to levels of normal plants. • AtCPK1 and KJM23 inhibited early ROS accumulation under high salinity conditions. • AtCPK1 and KJM23 associated with changes in expression of genes encoding heat shock factors. [ABSTRACT FROM AUTHOR]

Heat shock transcription factors (HSF) have been demonstrated to play a significant transcriptional regulatory role in plants and considered as an integral part of signal transduction pathways against environmental stresses especially heat stress. Despite of their importance, HSFs have not yet been identified and characterized in all cotton species. In this study, we report the identification of 42, 39, 67, and 79 non-redundant HSF genes from diploid cottons G. arboreum (A2) and G. raimondii (D5), and tetraploid cottons G. barbadense (AD2) and G. hirsutum (AD1) respectively. The chromosome localization of identified HSFs revealed their random distribution on all the 13 chromosomes of A and D genomes of cotton with few regions containing HSFs in clusters. The genes structure and conserved domain analysis revealed the family-specific conservation of intron/exon organization and conserved domains in HSFs. Various abiotic stress-related cis-regulatory elements were identified from the putative promoter regions of cotton HSFs suggesting their possible role in mediating abiotic stress tolerance. The combined phylogenetic analysis of all the cotton HSFs grouped them into three subfamilies; with 145 HSFs belong to class A, 85 to class B, and 17 to class C subfamily. Moreover, a detailed analysis of HSF gene family in four species of cotton elucidated the role of allopolyploid and hybridization during evolutionary cascade of allotetraploid cotton. Comparatively, existence of more orthologous genes in cotton species than Arabidopsis, advocated that polyploidization produced new cotton specific orthologous gene clusters. Phylogenetic, collinearity and multiple synteny analyses exhibited dispersed, segmental, proximal, and tandem gene duplication events in HSF gene family. Duplication of gene events suggests that HSF gene family of cotton evolution was under strong purifying selection. Expression analysis revealed that GarHSF04 were found to be actively involved in PEG and salinity tolerance in G. arboreum. GhiHSF14 upregulated in heat and downregulated in salinity whilst almost illustrated similar behavior under cold and PEG treatments and GhiHSF21 exhibited down regulation almost across all the stresses in G. hirsutum. Overwhelmingly, present study paves the way to better understand the evolution of cotton HSF TFs and lays a foundation for future investigation of HSFs in improving abiotic stress tolerance in cotton. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1. This study aims to elucidate the role of the OrHSF1 in responding to anthropogenic noise. • 2. Silencing of OrHSF1 resulted in suppression of Hsp70 expression. • 3. The HSF1-Hsp70 axis plays a crucial role in mediating anthropogenic noise-induced stress responses. To investigate the regulatory role of heat shock transcription factor 1 of sea slug Onchidium reevesii (OrHSF1) on Hsp70 expression in the sea slug under stress , the OrHSF1 gene was cloned and bioinformatics analysis was performed, then the gene and protein expressions by RNA interference (RNAi) mediated knockdown of OrHSF1 expression were measured to clarify the regulatory relationship between OrHSF1 and Hsp70 under low-frequency noise (LFN) stress. Our study was the first to clone a 1572 bp sequence of the OrHSF1 gene, with the sequence coding for amino acids (CDS) being 729 bp, encoding 243 amino acids. O. reevesii shared a close evolutionary relationship with mollusks such as the Aplysia californica. OrHSF1 gene is widely expressed in different tissues of sea slugs, with the highest expression in the intestine and the lowest in the reproductive glands. Furthermore, we used RNA interference (RNAi) as a tool to silence the OrHSF1 gene in the central nervous system (CNS) and the results indicated that gene silencing was occurring systematically in the CNS and the suppression of OrHSF1 expression by RNAi-mediated gene silencing altered the expression of Hsp70 ; besides, the expression trends of OrHSF1 gene and Hsp70 were consistent in the 3 and 5-day RNAi experiment. Moreover, in sea slugs injected with siHSF1 and exposed to LFN, the mRNA expression and protein expression of Hsp70 in the CNS were significantly decreased compared to the low-frequency noise group (P < 0.05). This study demonstrated that OrHSF1 regulates Hsp70 expression in marine mollusks under low-frequency noise, and HSF1-Hsp70 axis plays a key role in stress response. [ABSTRACT FROM AUTHOR]

DNA N 6 -methyladenine (6 mA) is an evolutionarily conserved DNA modification in procaryotes and eukaryotes. The DNA 6 mA methylation is tightly controlled by 6 mA regulatory proteins. DNA N 6 -adenine methyltransferase 1 (DAMT-1) has been identified as a DNA 6 mA methyltransferase in animals. In plants, DNA 6 mA methylation has been found, however, the DNA 6 mA methyltransferases and their function in plants are largely unknown. In our study, we find METTL4 is a DNA 6 mA methyltransferase in Arabidopsis thaliana. Both in vitro and in vivo evidences support the DNA 6 mA methyltransferase activity of METTL4. mettl4 mutant is hypersensitive to heat stress, suggesting DNA 6 mA methylation plays important role in heat stress adaption. RNA-seq and 6 mA IP-qPCR analysis show that METTL4 participates in heat stress tolerance by regulating expression of heat responsive genes. Our study find METTL4 is a plant DNA 6 mA methyltransferase and illustrates its function in regulating heat stress response. ● METTL4 functions as a 6mA methyltransferase both in vitro and in vivo in Arabidopsis. ● Loss of function of METTL4 affects heat tolerance. ● METTL4 regulates transcription of heat responsive genes. [ABSTRACT FROM AUTHOR]

Heat waves associated with climate change seriously threaten crop productivity. Crop seed yield depends on the success of reproduction. However, reproductive development is most vulnerable to heat stress conditions. Perception of heat and its conversion into cellular signals is a complex process. The basic helix loop helix (bHLH) transcription factor, Phytochrome Interacting Factor 4 (PIF4) , plays a significant role in this process. However, studies on PIF4 - mediated impacts on crop grain yield at a higher temperature are lacking. We investigated the overexpression of Gm PIF4b in soybean to alleviate heat-induced damage and yield using a transgenic approach. Our results showed that under high-temperature conditions (38°C/28°C), overexpressing soybeans plants had higher chlorophyll a and b, and lower proline accumulation compared to WT. Further , overexpression of GmPIF4b improved pollen viability under heat stress and reduced heat-induced structural abnormalities in the male and female reproductive organs. Consequently, the transgenic plants produced higher pods and seeds per plant at high temperatures. Quantitative RT-PCR analysis showed that the overexpressing GmPIF4b soybeans had higher transcripts of heat shock factor, GmHSF-34, and heat-shock protein, GmHSP90A2. Collectively, our results suggest that GmPIF4b regulates multiple morpho-physiological traits for better yield under warmer climatic conditions. • Soybean GmPIF4b regulates multiple morpho-physiological traits for better yield under warmer climatic conditions. • Overexpression of GmPIF4b reduced heat-induced structural abnormalities in the male and female reproductive organs. • Overexpression of GmPIF4b improved pollen viability under heat stress. • Ectopic expression of GmPIF4b produced higher pods and seeds per plant at high temperatures. • Soybean PIF4 -mediated thermal signalling could be used to enhance crop yield under changing climate conditions. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether acute passive heat stress 1) decreases muscle Maximal Voluntary Contraction (MVC); 2) increases peripheral muscle fatigue; 3) increases spinal cord excitability, and 4) increases key skeletal muscle gene signaling pathways in skeletal muscle. Examining the biological and physiological markers underlying passive heat stress will assist us in understanding the potential therapeutic benefits. MVCs, muscle fatigue, spinal cord excitability, and gene signaling were examined after control or whole body heat stress in an environmental chamber (heat; 82 °C, 10% humidity for 30 min). Heart Rate (HR), an indicator of stress response, was correlated to muscle fatigue in the heat group (R = 0.59; p < 0.05) but was not correlated to MVC, twitch potentiation, and H reflex suppression. Sixty-one genes were differentially expressed after heat (41 genes >1.5-fold induced; 20 < 0.667 fold repressed). A strong correlation emerged between the session type (control or heat) and principal components (PC1) (R = 0.82; p < 0.005). Cell Signal Transduction, Metabolism, Gene Expression and Transcription, Immune System, DNA Repair, and Metabolism of Proteins were pathway domains with the largest number of genes regulated after acute whole body heat stress. Acute whole-body heat stress may offer a physiological stimulus for people with a limited capacity to exercise. • Acute whole body heat stress increases skeletal muscle fatigue. • Acute whole body heat stress induces Heat Shock Factor 1 gene expression. • Acute whole body heat stress induces skeletal muscle metabolism signaling. • Acute whole body heat stress may offer a "primer" prior to exercise. [ABSTRACT FROM AUTHOR]

Heat shock transcription factors (HSFs), play a crucial role in plant growth, development and defense processes. The functions of some HSFs have been well studied in response some stresses in model plants. At present, the genome of the medicinal plant Cannabis sativa L. has been fully sequenced. Nevertheless, there is little known about the HSF genes family in Cannabis sativa L, as well as a lack of understanding of its evolutionary history. Herein, 18 HSFs were identified in the cannabis genome and phylogenetically classified into three groups based on the structural characteristics and phylogenetic analysis, including classes A (9 genes), classes B (8 genes), and classes C (1 gene). They were distributed over 9 of 10 chromosomes without chromosome 8. Then, the motif composition and evolutionary relationship of CsHSF proteins are discussed in detail, along with gene structures, cis -acting elements in the promoter, and synchronization analysis. Furthermore, our results also revealed that CsHSF transcription levels varied significantly among tissues, suggesting that the functions of CsHSF may be different. Finally, we found that red and blue light treatments had a significant effect on HSF genes expression and cannabinoids accumulation in vegetative organs of hemp young seedlings, implying the expression of HSF genes may regulate the content of cannabinoids under different light conditions. Although cannabinoid biosynthesis and response to light in vegetative organs of hemp young seedlings may not represent the mature stage of hemp, these results provided an essential theoretical basis to elucidate the regulatory mechanism of HSF in cannabinoid biosynthesis in the future. • A total of 18 HSFs were identified in the cannabis genome. • CsHSF transcription levels varied significantly among tissues. • There were large numbers of light responsiveness elements in all 18 CsHSF promoters. • Light treatment affected the expression of several stress-responsive HSF genes and the accumulation of cannabinoid in vegetative organs of hemp seedlings. [ABSTRACT FROM AUTHOR]

The heat shock response is a transcriptional program of organisms to counteract an imbalance in protein homeostasis. It is orchestrated in all eukaryotic cells by heat shock transcription factor 1 (Hsf1). Despite very intensive research, the intricacies of the Hsf1 activation-attenuation cycle remain elusive at a molecular level. Post-translational modifications belong to one of the key mechanisms proposed to adapt the Hsf1 activity to the needs of individual cells, and phosphorylation of Hsf1 at multiple sites has attracted much attention. According to cell biological and proteomics data, Hsf1 is also modified by small ubiquitin-like modifier (SUMO) at several sites. How SUMOylation affects Hsf1 activity at a molecular level is still unclear. Here, we analyzed Hsf1 SUMOylation in vitro with purified components to address questions that could not be answered in cell culture models. In vitro Hsf1 is primarily conjugated at lysine 298 with a single SUMO, though we did detect low-level SUMOylation at other sites. Different SUMO E3 ligases such as protein inhibitor of activated STAT 4 enhanced the efficiency of in vitro modification but did not alter SUMO site preferences. We provide evidence that Hsf1 trimerization and phosphorylation at serines 303 and 307 increases SUMOylation efficiency, suggesting that Hsf1 is SUMOylated in its activated state. Hsf1 can be SUMOylated when DNA bound, and SUMOylation of Hsf1 does neither alter DNA-binding affinity nor affects heat shock cognate 71kDa protein (HSPA8)+DnaJ homolog subfamily B member 1-mediated monomerization of Hsf1 trimers and concomitant dislocation from DNA. We propose that SUMOylation acts at the transcription level of the heat shock response. [ABSTRACT FROM AUTHOR]

Over the last decade, the CMGC kinase DYRK2 has been reported as a tumor suppressor across various cancers triggering major antitumor and proapoptotic signals in breast, colon, liver, ovary, brain, and lung cancers, with lower DYRK2 expression correlated with poorer prognosis in patients. Contrary to this, various medicinal chemistry studies reported robust antiproliferative properties of DYRK2 inhibitors, whereas unbiased 'omics' and genome-wide association studybased studies identified DYRK2 as a highly overexpressed kinase in various patient tumor samples. A major paradigm shift occurred in the last 4 years when DYRK2 was found to regulate proteostasis in cancer via a two-pronged mechanism. DYRK2 phosphorylated and activated the 26S proteasome to enhance degradation of misfolded/tumor-suppressor proteins while also promoting the nuclear stability and transcriptional activity of its substrate, heat-shock factor 1 triggering protein folding. Together, DYRK2 regulates proteostasis and promotes protumorigenic survival for specific cancers. Indeed, potent and selective small-molecule inhibitors of DYRK2 exhibit in vitro and in vivo anti-tumor activity in triple-negative breast cancer and myeloma models. However, with conflicting and contradictory reports across different cancers, the overarching role of DYRK2 remains enigmatic. Specific cancer (sub)types coupled to spatiotemporal interactions with substrates could decide the procancer or anticancer role of DYRK2. The current review aims to provide a balanced and critical appreciation of the literature to date, highlighting top substrates such as p53, c-Myc, c-Jun, heat-shock factor 1, proteasome, or NOTCH1, to discuss DYRK2 inhibitors available to the scientific community and to shed light on this duality of protumorigenic and antitumorigenic roles of DYRK2. [ABSTRACT FROM AUTHOR]

Heat shock transcription factor 1 (HSF1) orchestrates cellular stress protection by activating or repressing gene transcription in response to protein misfolding, oncogenic cell proliferation, and other environmental stresses. HSF1 is tightly regulated via intramolecular repressive interactions, posttranslational modifications, and protein-protein interactions. How these HSF1 regulatory protein interactions are altered in response to acute and chronic stress is largely unknown. To elucidate the profile of HSF1 protein interactions under normal growth and chronic and acutely stressful conditions, quantitative proteomics studies identified interacting proteins in the response to heat shock or in the presence of a poly-glutamine aggregation protein cell-based model of Huntington's disease. These studies identified distinct protein interaction partners of HSF1 as well as changes in the magnitude of shared interactions as a function of each stressful condition. Several novel HSF1-interacting proteins were identified that encompass a wide variety of cellular functions, including roles in DNA repair, mRNA processing, and regulation of RNA polymerase II. One HSF1 partner, CTCF, interacted with HSF1 in a stressinducible manner and functions in repression of specific HSF1 target genes. Understanding how HSF1 regulates gene repression is a crucial question, given the dysregulation of HSF1 target genes in both cancer and neurodegeneration. These studies expand our understanding of HSF1-mediated gene repression and provide key insights into HSF1 regulation via protein-protein interactions. [ABSTRACT FROM AUTHOR]

Ultrasound (US) can modify the plant growth and development. Previous assessments of the transcriptome of in vitro potato (Solanum tuberosum L.) exposed to US transmitted through air (AB-US) or liquid (PE-US) revealed the up- or down-regulation of several stress-related differentially expressed genes (DEGs) related to abiotic stress. In a bid to better characterize stress-related elements over a four-week period, the transcriptome of AB-US was compared to that of PE-US. When comparing the controls of both treatments, DEGs related to hypoxia were not detected. Nevertheless, hypoxia-related DEGs were detected in the combination of liquid medium and ultrasonication. DEGs coding for chitinase, peroxidase, glutathione- S -transferase, transcription factors of ERF (ethylene responsive factor), DREB (dehydration-responsive element-binding), WRKY and MYB were also significantly highly expressed in PE-US, relative to AB-US. Up- and down-regulation of DEGs related to metabolic processes, and enzymes of the antioxidant system also confirm that PE-US is a more acute abiotic stress than AB-US. A transcriptomic analysis revealed that liquid-based ultrasonication was a stronger abiotic stressor than air-based ultrasonication. Of particular interest were the heat shock proteins and transcription factors in this comparison. Despite the ultrasound stress, explants survived and plantlets developed. [ABSTRACT FROM AUTHOR]

• Dysregulated transcripts of irradiated human skin keratinocytes were identified by Microarray-based expression profiling. • These dysregulated transcripts were implicated in multiple pathways including type I interferon-mediated pathways. • Interferon α inducible protein 6 (IFI6) is induced by radiation in human skin cells and confers radio protection. • IFI6 is translocated into nucleus and regulating the transcriptional activity of HSF1. 5. A certain amount of potential HSF1-targeted genes upregulated by IFI6 overexpression post radiation is involved. Radiation-induced skin injury is one of the main adverse effects and a dose-limiting factor of radiotherapy without feasible treatment. The underlying mechanism of this disease is still limited. To investigate the potential molecular pathways and mechanisms of radiation-induced skin injury. mRNA expression profiles were determined by Affymetrix Human HTA2.0 microarray. IFI6 overexpression and knockdown were mediated by lentivirus. The functional changes of skin cells were measured by flow cytometry, ROS probe and Edu probe. Protein distribution was detected by immunofluorescence experiment, and IFI6-interacting proteins were detected by immunoprecipitation (IP) combined with mass spectrometry. The global gene changes in IFI6-overexpressed skin cells after irradiation were detected by RNA-seq. mRNA expression profiling showed 50 upregulated and 13 down regulated genes and interferon alpha inducible protein 6 (IFI6) was top upregulated. Overexpression of IFI6 promoted cell proliferation and reduced cell apoptosis as well as ROS production following radiation, and conversely, increased the radiosensitivity of HaCaT and human skin fibroblast (WS1). IFI6 was translocated into nucleus in irradiated skin cells and the interacting relationship with mitochondrial single-stranded DNA-binding protein 1 (SSBP1), which could enhance the transcriptional activity of heat shock transcription factor 1 (HSF1). IFI6 augmented HSF1 activity following radiation in HaCaT and WS1 cells. RNA-seq analysis showed IFI6 modulated virus infection and cellular response to stress pathways, which may help to further explore how IFI6 regulate the transcriptional activity of HSF1. This study reveals that IFI6 is induced by ionizing radiation and confers radioprotection in skin cells. [ABSTRACT FROM AUTHOR]

This research was to determine effects of supplemental dietary microalgal astaxanthin (AST) on hepatic gene expression and protein production of redox enzymes, heat shock proteins (HSPs), cytokines, and lipid metabolism in broilers (BR) and laying hens (LH) under high ambient temperatures. A total of 240 (day old) Cornish male BR and 50 (19 wk old) White Leghorn Shavers LH were allotted in 5 dietary treatments with 6 and 10 cages/treatment (8 BR or 1 LH/cage), respectively. The birds were fed corn-soybean meal basal diets supplemented with microalgal (Haematococcus pluvialis) AST at 0, 10, 20, 40, and 80 mg/kg diet for 6 wk. Supplemental AST to the BR diet linearly decreased (P, 0.10, R2 5 0.18-0.36) hepatic mRNA levels of several redox status-controlling genes, heat shock protein 70 (HSP70), heat shock transcription factor 1 (HSTF1), c-Jun N-terminal kinase 1 (JNK1), tumor necrosis factor-a, and sterol regulatory element-binding protein 1 (SREBP1). The supplementation linearly elevated (P 5 0.04, R2 5 0.20) diacylglycerol acyltransferase 2 (DGAT2) mRNA level and produced quadratic changes (P, 0.10, R2 5 0.15-0.47) in mRNA levels of glutathione S-transferase (GST), serine/threonine kinase (AKT1), P38 mitogen-activated protein kinase (P38MAKP), lipid metabolism-controlling genes, and the protein production of HSP90 and P38MAPK in the liver. Supplementing AST to the LH diets linearly decreased (P, 0.10, R2 5 0.18-0.56) mRNA levels of GST, HSF1, JNK1, and interleukin 10; lipogenesis genes; and JNK1 protein production. However, supplemental dietary AST produced quadratic changes (P, 0.10, R2 5 0.26-0.72) in mRNA levels of most antioxidant-, stress-responsive, and lipid metabolism-related genes in the liver of LH. In conclusion, supplemental dietary AST affected the hepatic gene expression and protein production related to redox status, heat stress and inflammation, and lipid metabolism in both BR and LH. The impacts varied with the chicken type and demonstrated linear and quadratic regressions with the inclusion levels of AST. [ABSTRACT FROM AUTHOR]

Heat shock protein 70 (Hsp70) proteins are a family of ancient and conserved chaperones. Cysteine modifications have been widely detected among different Hsp70 family members in vivo, but their effects on Hsp70 structure and function are unclear. Here, we treated HeLa cells with diamide, which typically induces disulfide bond formation except in the presence of excess GSH, when glutathionylated cysteines predominate. We show that in these cells, HspA1A (hHsp70) undergoes reversible cysteine modifications, including glutathionylation, potentially at all five cysteine residues. In vitro experiments revealed that modification of cysteines in the nucleotide-binding domain of hHsp70 is prevented by nucleotide binding but that Cys-574 and Cys-603, located in the C-terminalα-helical lid of the substratebinding domain, can undergo glutathionylation in both the presence and absence of nucleotide. We found that glutathionylation of these cysteine residues results in unfolding of the α-helical lid structure. The unfolded region mimics substrate by binding to and blocking the substrate-binding site, thereby promoting intrinsic ATPase activity and competing with binding of external substrates, including heat shock transcription factor 1 (Hsf1). Thus, post-translational modification can alter the structure and regulate the function of hHsp70. [ABSTRACT FROM AUTHOR]

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at258 to250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues. [ABSTRACT FROM AUTHOR]

In this study, the aim was to investigate effects of chronic heat stress (CHS) on the mRNA levels of proinflammatory cytokines (interleukin [IL]-6, IL-8, IL-1β, and tumor necrosis factor alpha [TNF-α]), toll-like receptors (TLR2 and TLR4), heat shock proteins (Hsp70, heat shock transcription factor [HSF]-1, and HSF3) and antioxidant enzymes (catalase, glutathione peroxidase, NADPH oxidase, and superoxidedismutase) in the jejunal mucosae of broiler chickens subjected to thermal manipulation (TM) during embryogenesis. TM was carried out at 39C and 65% relative humidity (RH) for 18 h daily from embryonic days 10 to 18. Control group was incubated at 37.8C and 56% RH. CHS was induced by raising the temperature to 35C for 7 D throughout posthatch days 28 to 35. On post-hatch-day 28 (day zero of CHS) and after 1, 3, 5, and 7 D of CHS, the jejunal mucosae were collected from both groups to evaluate the mRNA levels by realtime reverse transcription-PCR analysis. On day zero of CHS, the mRNA levels of antioxidant enzymes, TLRs, HSF3, IL-1β, and TNF-α were not significantly different between TM and control groups, while the levels of IL-6, IL-8, and HSF1 were lower and the level of Hsp70 was higher in TM. However, during CHS, the mRNA levels of antioxidant enzymes, IL-1β, TNF-α, TLR4, and HSF1 were significantly lower in TM than in controls, while the levels of TLR2 and IL-8 were significantly higher in TM than in controls. In addition, TM led to significant increase of mRNA levels of IL-6 and HSF3 after 1 D and Hsp70 after 3 D of CHS and to significant decrease of mRNA levels of IL-6 after 3 and 5 D, HSF3 after 7 D, and Hsp70 after 5 D of CHS. Results of this study suggest that TM led to altered posthatch antioxidant, immunological, and Hsp response to CHS in the jejunal mucosae of broiler chickens, probably indicating that TM may mitigate the adverse effects of CHS. [ABSTRACT FROM AUTHOR]

Heat shock factors (HSFs) and heat shock proteins (HSPs) are crucial regulators and effectors of the heat shock response (HSR). In this study, the full-length cDNA sequences of MjHSP10 and MjHSF1 were cloned by rapid amplification of cDNA ends (RACE). The deduced MjHSP10 and MjHSF1 amino acid (aa) sequences exhibited conserved structures and the functional features of HSP10 and HSF1, respectively. The tissue distributions and mRNA expression profiles of the two genes in response to heat stress were analyzed by quantitative real-time PCR (qRT-PCR). MjHSP10 and MjHSF1 were ubiquitously expressed in various tissues. Heat stress induced a significant increase in MjHSP10 expression that tend to positively correlate with temperature. Additionally, MjHSF1 transcription was up-regulated less than MjHSP10 transcription under heat stress. MjHSF1 expression in the hepatopancreas was up-regulated under only long-term (48 h) heat stress, and MjHSF1 transcription in the gill increased under only acute (34 °C) heat stress. MjHSF1 knockdown by RNA interference (RNAi) down-regulated MjHSP10 expression. Glutathione-S-transferase (GST) pull-down assays showed an interaction between MjHSP10 and the DNA-binding domain (DBD) of MjHSF1. This study provided new insights into cross talk between HSP10 and HSF1 in Marsupenaeus japonicus. [ABSTRACT FROM AUTHOR]

Mitochondrial and cytosolic proteostasis are of central relevance for cellular stress resistance and organismal health. Recently, a number of individual cellular programs were described that counter the fatal consequences of mitochondrial dysfunction. These programs remove arrested import intermediates from mitochondrial protein translocases, stabilize protein homeostasis within mitochondria, and, in particular, increase the levels and activity of chaperones and the proteasome system in the cytosol. Here, we describe the different responses to mitochondrial perturbation and propose to unify the seemingly distinct mitochondrial-cytosolic quality control mechanisms into a single network, the mitoprotein-induced stress response. This holistic view places mitochondrial biogenesis at a central position of the cellular proteostasis network, emphasizing the importance of mitochondrial protein import processes for development, reproduction, and ageing. Owing to their post-translational mode of import, mitochondrial precursor proteins represent a significant challenge to the cells' ability to maintain cytosolic proteostasis, particularly when the amount of cytosolic precursors exceeds the import capacity of mitochondria. Mitoprotein-induced stress elicits a complex regulatory network that: (i) removes stalled precursors from the mitochondrial surface, (ii) slows down the synthesis of mitochondrial proteins, and (iii) increases the levels of chaperones and proteases and attenuates cytosolic translation. Seemingly disparate reactions to mitochondrial stress are integrated into a general mitoprotein-induced stress response that couples 'mitochondria-centric' adaptations with general stress programs such as the heat shock response. [ABSTRACT FROM AUTHOR]

• Interaction of SA and NO modulated physiological and biochemical defence response in HT stressed lablab plants. • Interactive SA and NO were effective in ameliorating HT induced oxidative stress compared to their individual application. • The results of in-silico analysis reconciled with in-vitro experiments and can be exploited for characterizing other HSPs. • Our study provided valuable insights that can be used in the generation of new/improved HT tolerant lines in other crops. Salicylic acid (SA) and nitric oxide (NO) are considered as putative plant growth regulators that are involved in the regulation of an array of plant's growth and developmental functions under environmental fluctuations when applied at lower concentrations. The possible involvement of NO in SA induced attenuation of high temperature (HT) induced oxidative stress in plants is however, still vague and need to be explored. Therefore, the present study aimed to investigates the biochemical and physiological changes induced by foliar spray of SA and NO combinations to ameliorate HT induced oxidative stress in Lablab purpureus L. Foliar application of combined SA and NO significantly improved relative water content (27.8 %), photosynthetic pigment content (67.2 %), membrane stability (45 %), proline content (1.0 %), expression of enzymatic antioxidants (7.1–18 %) along with pod yield (1.0 %). Heat Shock Factors (HSFs) play crucial roles in plants abiotic stress tolerance, however there structural and functional classifications in L. purpureus L. is still unknown. So, In-silico approach was also used for functional characterization and homology modelling of HSFs in L. purpureus. The experimental findings depicted that combine effect of SA and NO enhances tolerance in HT stressed L. purpureus L. plants by regulating physiological functions, antioxidants, expression and regulation of stress-responsive genes via transcriptional regulation of heat shock factor. [ABSTRACT FROM AUTHOR]

• Multiple myeloma cells activate Apg-1 expression and HSF1 translocation in response to bortezomib. • Apg-1 inhibition may increase chemosensitivity to bortezomib by enhancing cell apoptosis. • Targeting HSF1 with an HSF1 inhibitor or drugs can downregulate Apg-1 and sensitize cells to bortezomib treatment. • Combination triptolide/bortezomib therapy could overcome cell adhesion-mediated drug resistance, and triptolide rendered these cells more sensitive to the bortezomib treatment. • A potential mechanism for bortezomib-mediated cell death is proposed. Exposure of cells to bortezomib (BTZ) could activate heat shock protein (HSP) expression, which is regulated mainly by heat shock factor 1 (HSF1). We determined the role of Apg-1 (HSPA4L, a member of the HSP110 family) in HSF1 activation and bortezomib sensitivity by silencing HSF1 in multiple myeloma (MM) cells. We observed that the Apg-1 protein level was upregulated as BTZ concentration increased. To investigate the mechanism underlying Apg-1 induction, we evaluated the HSF1 translocation and found BTZ-inducible transposition to the nucleus of HSF1. In addition, cleaved caspase 3 and PARP might account for increased BTZ sensitivity on Apg-1 silencing. Furthermore, silencing HSF1 with shRNA or triptolide resulted in significant BTZ sensitivity. It had a more profound effect on cell death caused by BTZ when myeloma cells were adherent to bone marrow stromal cell lines (Hs-5). In summary, we found that Apg-1 knockdown sensitized myeloma cells to bortezomib treatment, which may provide a new approach in multiple myeloma treatment. [ABSTRACT FROM AUTHOR]

The ability of cancer cells to cope with stressful conditions is critical for their survival, proliferation, and metastasis. The heat shock transcription factor 1 (HSF1) protects cells from stresses such as chemicals, radiation, and temperature. These properties of HSF1 are exploited by a broad spectrum of cancers, which exhibit high levels of nuclear, active HSF1. Functions for HSF1 in malignancy extend well beyond its central role in protein quality control. While HSF1 has been validated as a powerful target in cancers by genetic knockdown studies, HSF1 inhibitors reported to date have lacked sufficient specificity and potency for clinical evaluation. We review the roles of HSF1 in cancer, its potential as a prognostic indicator for cancer treatment, evaluate current HSF1 inhibitors and provide guidelines for the identification of selective HSF1 inhibitors as chemical probes and for clinical development. Heat shock transcription factor 1 (HSF1) is a pivotal protein for cellular stress protection in response to a variety of environmental insults and physiological stresses. The prosurvival and other key functions of HSF1 have been exploited by a surprisingly broad spectrum of human malignancies to support cancer cell survival, proliferation, invasion, and metastasis. The functional importance of HSF1 in cancer extends far beyond its classical role in protein homeostasis, revealing unique opportunities for targeting HSF1 as a novel cancer therapy. Insights into the specificity and mechanism of action of current HSF1 inhibitors, and concepts for the identification and validation of bona fide HSF1 inhibitors, will be important to advance HSF1 as a therapeutic target. [ABSTRACT FROM AUTHOR]

Protein homeostasis and cellular fitness in the presence of proteotoxic stress is promoted by heat shock factor 1 (Hsf1), which controls basal and stress-induced expression of molecular chaperones and other targets. The major heat shock proteins and molecular chaperones Hsp70 and Hsp90, in turn, participate in a negative feedback loop that ensures appropriate coordination of the heat shock response with environmental conditions. Features of this regulatory circuit in the budding yeast Saccharomyces cerevisiae have been recently defined, most notably regarding direct interaction between Hsf1 and the constitutively expressed Hsp70 protein Ssa1. Here, we sought to further examine the Ssa1/Hsf1 regulation. We found that Ssa1 interacts independently with both the previously defined CE2 site in the Hsf1 C-terminal transcriptional activation domain and with an additional site that we identified within the N-terminal activation domain. Consistent with both sites bearing a recognition signature for Hsp70, we demonstrate that Ssa1 contacts Hsf1 via its substrate-binding domain and that abolishing either regulatory site results in loss of Ssa1 interaction. Removing Hsp70 regulation of Hsf1 globally dysregulated Hsf1 transcriptional activity, with synergistic effects on both gene expression and cellular fitness when both sites are disrupted together. Finally, we report that Hsp70 interacts with both transcriptional activation domains of Hsf1 in the related yeast Lachancea kluyveri. Our findings indicate that Hsf1 transcriptional activity is tightly regulated to ensure cellular fitness and that a general and conserved Hsp70-HSF1 feedback loop regulates cellular proteostasis in yeast. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify whether more and less adapted Angus and Simmental cattle differed in physiological responses and expression of the heat shock factor 1 (HSF1) and the heat shock 70 kDa protein 6 (HSPA6), when subjected to heat stress. Thirty bulls (n = 15 ANG; n = 15 SIM), extremes "more adapted" and "less adapted" within each breed were selected to the heat tolerance test. They were selected according to an index based on the average of the respiratory rate obtained on two hot summer days from one hundred bulls. Before the heat tolerance test day, animals were taken to a paddock with water, grass and shade until 7 a.m. of the following day for morning measurements. They were kept in the barn without access to water and shade until 1 p.m. for the afternoon measurements. Respiratory rate in the morning (MRR) and afternoon (ARR), hair coat surface temperature in the morning (MST) and afternoon (AST), rectal temperature in the morning (MRT) and afternoon (ART) were measured and blood samples were collected for expression analysis of the HSF1 and HSPA6 genes. The MIXED procedure of SAS was used for all statistical analysis. The more adapted Simmental group had lesser values of MRR (P = 0.023) and MRT (P = 0.095), but there was no difference within Angus breed. The ARR was greater (P = 0.004) in less adapted animals for both breeds. The ART was lower in the Simmental breed (P < 0.001). Less adapted had greater levels of mRNA of HSF1 (P = 0.06) and HSPA6 (P = 0.09). In conclusion, respiratory rate, rectal temperature and expression of the HSF1 and HSPA6 genes can be indicators of thermotolerance in taurine cattle. Both breeds show physiologically similar responses under heat stress conditions. • Simmental breed is more resistant than Angus breed under thermal comfort. • Breeds resemble each other in physiological characteristics in hotter conditions. • Respiratory rate and rectal temperature are good indicators of thermotolerance. • HSF1 and HSPA6 genes can be used as thermotolerance indicators in taurine cattle. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is a widespread environmental toxicant that severely impacts agricultural production and animal and human health. Nevertheless, DEHP-induced hepatotoxicity at the molecular level in quail remains unexplored. The heat shock response (HSR), involving heat shock proteins (HSPs) and heat shock transcription factors (HSFs), is a highly conserved molecular response that is triggered by stressors, especially exposure to toxicants. To explore the DEHP-induced hepatotoxicity that occurs via regulation of HSR in birds, female quail were dosed with DEHP by oral gavage (0, 250, 500 and 1000 mg/kg) for 45 days. Based on histopathological analysis, the livers of the DEHP-treated groups exhibited structural alterations of hepatocytes, including mitochondrial swelling, derangement of hepatic plates, inflammatory cell infiltration and adipose degeneration. Ultrastructural evaluation of the livers of DEHP-treated quail revealed swollen mitochondria, partial disappearance of mitochondrial membranes and cristae, nuclear chromatin margination and nuclear condensation. The expression of HSF1 and HSF3 significantly decreased after DEHP exposure. The levels of HSPs (HSP10, HSP25, HSP27, HSP40, HSP47, HSP60, HSP70 and HSP90) were significantly downregulated in the livers of DEHP-treated quail. In this study, we concluded that DEHP exposure resulted in liver function damage and hepatotoxicity by reducing the expression of HSFs and HSPs in quail liver, which inhibited the protective effect of the HSR signaling pathway. DEHP can be absorbed by quail via a trophic chain that eventually results in hepatotoxicity. The results of this study indicated that mitochondria are target organelles of DEHP hepatotoxicity. DEHP can activate the HSR signaling pathway and suppress HSP system homeostasis to alleviate mitochondrial dysfunction. The present study provides new insights and shows that DEHP-induced hepatotoxicity is associated with the HSR-mediated defense system. Image 1 • DEHP exposure induced hepatotoxicity. • DEHP triggered the HSR signaling pathway. • DEHP induced hepatotoxicity via suppressing of the HSR signaling pathway. • DEHP exposure resulted in hepatotoxicity via reducing HSPs and HSFs expression. [ABSTRACT FROM AUTHOR]