Depression is one of the most common neurologic diseases. It is associated with multiple factors such as inflammation, NMDAR, GABAR, and monoamine neurotransmitters. Ubiquitin and ubiquitination are responsible for protein degradation. The ubiquitin enzyme system plays an essential role in neuromodulation. At the same time, proteolysis-targeting chimeras (PROTACs), which selectively degrade target proteins based on the ubiquitin enzyme system, have been recognized as the most popular technology for drug development in recent years. Therefore, we reviewed the ubiquitin proteases that have been reported, which are associated with depression. Among them, nine ubiquitin ligase E3s are highlighted. Simultaneously, we summarized the pharmacological mechanism network of E3 ubiquitin ligases. In addition, the structural features of E3 ubiquitin-protein ligases were also reviewed. This review aims to discuss the possibility of developing drugs with ubiquitin and PROTAC technology. Additionally, the study reviews the regulation of the ubiquitin protease system within the mechanistic network of depression.

Small heat shock proteins (sHSPs) are molecular chaperones known for their role in maintaining cellular homeostasis and protecting cells from various environmental stresses. This study focuses on the silkworm small heat shock protein HSP19.5 and its potential functions in the context of Nosema bombycis infection, a microsporidian pathogen causing severe disease in the sericulture industry. We cloned and characterized HSP19.5 and revealed its expression patterns in different silkworm tissues and developmental stages. Our results indicate that HSP19.5 expression is significantly up-regulated in response to N. bombycis infection, suggesting a role in the host stress response. Through a series of experiments, including RNA interference and overexpression analyses, we demonstrated that HSP19.5 promotes N. bombycis proliferation, possibly by inhibiting host cell apoptosis and regulating intracellular ROS levels. The cytoplasmic localization of HSP19.5 in silkworm cells is consistent with its function as a molecular chaperone. The results enhance our understanding of the complex host-pathogen interactions between silkworms and N. bombycis, and provides insights that may inform the development of novel strategies to control the pebrine disease.

The small interfering RNA pathway is the primary antiviral defense mechanism in invertebrates and plants. This systemic mechanism relies on the recognition, transport, and internalization of double-stranded RNA (dsRNA). Our aim was to identify cell surface proteins that bind extracellular dsRNA and mediate its internalization in Drosophila cells. We used coimmunoprecipitation coupled with proteomics analysis and found that silencing heat shock cognate protein 70-4 (Hsc70-4), a constitutively expressed heat shock protein, impairs dsRNA internalization. Unexpectedly, despite lacking a predicted transmembrane domain, Hsc70-4 localizes to the cell membrane via lipid interactions. Antibody blocking experiments revealed an extracellular domain on Hsc70-4 that is essential for dsRNA internalization. Intriguingly, this dsRNA-specific binding capacity of Hsc70-4 functions independently of its chaperone activity. These findings not only highlight Hsc70-4 as a previously uncharacterized and essential component in the dsRNA internalization process but also offer promising insights for advancing RNA interference-based technologies to combat pests and vector-borne diseases.

The daily rise and fall in ambient temperature caused by Earth's 24-hour rotation may help regulate circadian rhythms in visually impaired individuals. In all mammals, circadian rhythms, the daily cycles of physiology and behavior, are time controlled by the suprachiasmatic nucleus (SCN), the brain's central clock. The SCN typically synchronizes circadian rhythms with the light/dark cycle through photoentrainment, a process in which specialized retinal cells capture ambient light and transmit this information to the SCN, allowing it to set its phase. Without light input, the rodent SCN's light-driven circuits can become desynchronized, potentially allowing alternative entrainment signals, such as ambient temperature, to influence central timing. Here, we consider whether a similar mechanism could benefit visually impaired humans who, due to retinal damage, have reduced or absent photic input to the central clock. Visually impaired individuals often experience circadian misalignment, whereby internal rhythms drift out of synchrony with the light-dark cycle, and we suggest that temperature information may mitigate some of this drift. Temperature entrainment could operate through heat shock pathways from the skin, via thermoregulatory brain regions with reciprocal connections to the SCN, or by shifting core body temperature through warm or cold baths, which can alter the phase of clocks in peripheral organs and potentially feedback to adjust central time. Given that temperature is a weaker cue than light, it remains unknown if, and to what extent, it may significantly impact central timing. However, if effective, temperature entrainment in the visually impaired could potentially improve circadian disorders, poor sleep, and adverse health outcomes associated with circadian dysfunction including depression, cognitive decline, and metabolic disorders, which are more prevalent in this population. Research is needed to confirm the long-term effectiveness of temperature as an entrainment cue in the visually impaired population, which may have broader implications for circadian timekeeping in mammals and the role of temperature in the absence of light.

The fall armyworm (Spodoptera frugiperda) is a major invasive pest. To explore its adaptive mechanisms under temperature stress, we conducted transcriptome analysis across six developmental stages and both sexes at 0, 26, and 46 °C. High-temperature stress induced more differentially expressed genes (DEGs, 8,703) than low-temperature stress (5,426), with fourth instar larvae showing the most DEGs at low temperatures. Sex-specific responses were also evident. Sixteen heat shock protein (HSP) genes and 31 apoptosis-related genes were identified as key stress-responsive factors. RNAi knockdown of SfDNAJA1 and SfHSP68 reduced survival under temperature stress, increased ROS and Cyt c levels, and upregulated apoptosis-related genes, while ATP levels decreased. Elevated caspase-3, G6PD, and GST activities further indicated oxidative and apoptotic responses. These results underscore the essential role of HSPs in maintaining cellular homeostasis and regulating apoptosis during thermal stress, offering insights into pest adaptation and potential control strategies.

As climate change causes marine heat waves to become more intense and frequent, marine species increasingly suffer from heat stress. This stress can result in reduced growth, disrupted breeding cycles, vulnerability to diseases and pathogens, and increased mortality rates. Abalone (genus Haliotis) are an ecologically significant group of marine gastropods and are among the most highly valued seafood products. However, heat stress events have had devastating impacts on both farmed and wild populations. Members of this genus are among the most susceptible marine species to climate change impacts, with over 40% of all abalone species listed as threatened with extinction. This has motivated researchers to explore the genetics linked to heat stress in abalone. A substantial portion of publicly available studies has employed transcriptomic approaches to investigate abalone genetic response to heat stress. However, to date, no meta-analysis has been conducted to determine the common response to heat stress (i.e. the core response) across the genus. This study uses a standardized bioinformatic pipeline to reanalyze and compare publicly available RNA-seq datasets from different heat stress studies on abalone.

Nine publicly available RNA-seq datasets from nine different heat-stress studies on abalone from seven different abalone species and three hybrids were included in the meta-analysis. We identified a core set of 74 differentially expressed genes (DEGs) in response to heat stress in at least seven out of nine studies. This core set of DEGs mainly included genes associated with alternative splicing, heat shock proteins (HSPs), Ubiquitin-Proteasome System (UPS), and other protein folding and protein processing pathways.

The detection of a consistent set of genes that respond to heat stress across various studies, despite differences in experimental design (e.g. stress intensity, species studied-geographical distribution, preferred temperature range, etc.), strengthens our proposal that these genes are key elements of the heat stress response in abalone. The identification of the core response to heat stress in abalone lays an important foundation for future research. Ultimately, this study will aid conservation efforts and aquaculture through the identification of resilient populations, genetic-based breeding programs, possible manipulations such as early exposure to stress, gene editing and the use of immunostimulants to enhance thermal tolerance.

Cells respond to many different types of stresses by overhauling gene expression patterns, both at the transcriptional and translational levels. Under heat stress, global transcription and translation are inhibited, while the expression of chaperone proteins is preferentially favored. As the direct link between mRNA transcription and protein translation, transfer RNA (tRNA) expression is intricately regulated during the stress response. Despite extensive research into the heat shock response (HSR), the regulation of tRNA expression by RNA polymerase III (Pol III) transcription has yet to be fully elucidated in mammalian cells. Here, we examine the regulation of Pol III transcription during different stages of heat shock stress in mouse embryonic stem cells. We observe that Pol III transcription is downregulated after 30 min of heat shock, followed by an overall increase in transcription after 60 min of heat shock. This effect is more evident in tRNAs, although other Pol III gene targets are also similarly affected. Notably, we show that the downregulation at 30 min of heat shock is independent of HSF1, the master transcription factor of the HSR, but that the subsequent increase in expression at 60 min requires HSF1. Taken together, these results demonstrate an adaptive RNA Pol III response to heat stress and an intricate relationship between the canonical HSR and tRNA expression.

High temperature (HT) is a major environmental factor that restrains eggplant growth and production. Heat shock factors (HSFs) play a vital role in the response of plants to high-temperature stress (HTS). However, the molecular mechanism by which HSFs regulate heat tolerance in eggplants remains unclear. Previously, we reported that SmEGY3 enhanced the heat tolerance of eggplant. Herein, SmHSFA8 activated SmEGY3 expression and interacted with SmEGY3 protein to enhance the activation function of SmEGY3 on SmCSD1. Virus-induced gene silencing (VIGS) and overexpression assays suggested that SmHSFA8 positively regulated heat tolerance in plants. SmHSFA8 enhanced the heat tolerance of tomato plants by promoting SlEGY3 expression, H2O2 production and H2O2-mediated retrograde signalling pathway. DNA affinity purification sequencing (DAP-seq) analysis revealed that SmHSPs (SmHSP70, SmHSP70B and SmHSP21) and SmF3H were candidate downstream target genes of SmHSFA8. SmHSFA8 regulated the expression of HSPs and F3H and flavonoid content in plants. The silencing of SmF3H by VIGS reduced the flavonoid content and heat tolerance of eggplant. In addition, exogenous flavonoid treatment alleviated the HTS damage to eggplants. These results indicated that SmHSFA8 enhanced the heat tolerance of eggplant by activating SmHSPs exprerssion, mediating the SmEGY3-SmCSD1 module, and promoting SmF3H-mediated flavonoid biosynthesis.

Under stress, cells orchestrate a complex regulatory response to maintain protein homeostasis, leveraging differential translational regulation for constitutively expressed mRNAs and the transcriptionally induced heat shock protein HSP70 transcripts. Constitutive mRNAs typically experience partial translational suppression, consistent with their partitioning into stress-induced phase-separated condensates and the global reduction in protein synthesis. In contrast, inducible HSP70 mRNAs bypass this repression to remain in the cytosol where they recruit the available components of the translational machinery to ensure the rapid synthesis of HSP70. Although the components involved in the preferential translation of HSP70 mRNA during heat stress have not been fully elucidated, differences in the mRNA and translation factors between yeast and mammals suggest organism-specific mechanisms of HSP70 mRNA translation. In this review, we consider these differences to discuss the current knowledge on heat shock regulation of translation. We extend the discussion to go beyond the cytosolic needs of HSP70 to ponder the important interplay between the cytosol and mitochondria in activating HSP70 accumulation, which becomes vital for preserving intercompartmental proteostasis and cell survival.

Gene family expansion underlies a host of biological innovations across the tree of life. Understanding why specific gene families expand or contract requires comparative genomic investigations clarifying further how species adapt in the wild. This study investigates the gene family change dynamics within several species of Daphnia, a group of freshwater microcrustaceans that are insightful model systems for evolutionary genetics' research. We employ comparative genomics approaches to understand the forces driving gene evolution and draw upon candidate gene families that change gene numbers across Daphnia. Our results suggest that genes related to stress responses and glycoproteins generally expand across taxa, and we investigate evolutionary hypotheses of adaptation that may underpin expansions. Through these analyses, we shed light on the interplay between gene expansions and selection within other ecologically relevant stress response gene families. While we show generalities in gene family turnover in genes related to stress response (i.e., DNA repair mechanisms), most gene family evolution is driven in a species-specific manner. Additionally, while we show general trends toward positive selection within some expanding gene families, many genes are not under selection, highlighting the complexity of diversification and evolution within Daphnia. Our research enhances the understanding of individual gene family evolution within Daphnia and provides a case study of ecologically relevant genes prone to change.

Heat shock proteins (HSPs) function as molecular chaperones to maintain protein homeostasis and repair denatured proteins, counteracting abiotic stresses. Despite their functional importance, a systematic bioinformatics analysis of the HSP gene family was lacking in Poaceae. In this study, we revealed that HSPs are widely distributed from algae to eudicots, with varying numbers in Poaceae including Oryza, Triticum, and Panicum. Gene duplication events, particularly dispersed duplication (DSD), tandem duplication (TD), and genome polyploidization, have probably driven the increased number of HSP genes and the expansion of HSP family proteins. Gene Ontology (GO) annotation analyses suggested their conserved functions. Promoter cis-acting element analyses indicated that their expression levels were tightly regulated by abiotic stresses. We validated that many collinear HSP genes are indeed regulated by the cold stress by analyzing the published RNA-seq data in rice, maize, and wheat, and performing RT-qPCR in rice. Our findings shed light on the role of HSPs in the abiotic stress response, laying the groundwork for further exploration of HSP functions in Poaceae.

Neurons deviate from a canonical heat shock response (HSR). Here, we revealed that neuronal adaptation to heat shock accompanies a brake on mRNA translation, slowed elongating ribosomes, phosphorylation of eukaryotic elongation factor-2 (p-eEF2), and suppressed the integrated stress response (ISR). Returning neurons to control temperature within 1 h of starting heat shock was necessary for survival and allowed for restored translation following dephosphorylation of eEF2. Subsequent to recovery, neurons briefly activated the ISR and were sensitive to the ISR inhibitor ISRIB, which enhanced protein synthesis and survival. Ribosome profiling and RNA sequencing (RNA-seq) identified newly synthesized and existing transcripts associated with ribosomes during heat shock. Preservation of these transcripts for translation during recovery was in part mediated by p-eEF2 and slowed ribosomes. Our work supports a neuronal heat shock model of a partially suspended state of translation poised for rapid reversal if recovery becomes an option and provides insight into regulation between the HSR and the ISR.

Heat-related mortality remains health challenges exacerbated by climate change, with sex-based differences in outcomes, yet underlying mechanisms remain poorly understood. This study examined transcriptomic responses to heat exposure in peripheral blood mononuclear cells from 19 patients with heat stroke (HS; 8 males, mean age 64.8 ± 6.6 yr; 11 females, mean age 49.7 ± 11 yr) and 19 controls (11 males, mean age 48.9 ± 9.6 yr; 8 females, mean age 44.9 ± 11.8 yr). At admission, gene expression revealed upregulation of heat shock protein genes, and pathway analysis demonstrated activation of heat shock and unfolded protein responses across both sexes consistent with proteotoxic stress. However, distinct metabolic, oxidative stress, cell cycle control, and immune responses were observed within each sex. Females displayed inhibition of protein synthesis, oxidative phosphorylation, and metabolic pathways, including glucose metabolism, indicative of a hypometabolic state. Males maintained metabolic activity precooling and enhanced adenosine triphosphate production postcooling. Females activated nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress responses and inhibited DNA replication and mitosis, potentially mitigating genomic instability, whereas these pathways showed limited regulation in males. Females promoted innate immunity via interleukin (IL)-6, inflammasome, and triggering receptor expressed on myeloid cells 1 (TREM1) signaling, whereas males showed suppression of both innate and adaptive immunity, including IL-12, Th1, and T-cell receptor pathways. Upstream analysis identified over 100 transcription factors in both sexes. Males primarily relied on transcriptional mechanisms, whereas females also exhibited translational regulation via La ribonucleoprotein 1 (LARP1), fragile X messenger ribonucleoprotein 1 (FMR1), insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), and eukaryotic translation initiation factor 6 (EIF6). These findings suggest distinct, sex-specific molecular adaptations to heat stroke, underscoring the need for targeted therapeutic strategies to mitigate heat-induced morbidity and mortality.NEW & NOTEWORTHY Heat-related mortality continues to rise with climate change. Our transcriptomic analysis reveals distinct sex-specific metabolic strategies to heat stroke: females enter a hypometabolic state, an evolutionary adaptation that conserves energy, whereas males sustain metabolic activity. Transcription factors and a subset of translation regulators in females modulate proteostasis and bioenergetics, driving these sex-specific pathways. These novel findings highlight the critical need to consider sex-specific differences in heat-related illnesses and inform carefully targeted interventions to improve patient outcomes.

Spinal muscular atrophy and amyotrophic lateral sclerosis are devastating neurodegenerative diseases characterized by motor neuron loss. Although these 2 disorders have distinct genetic origins, recent studies suggest that they share common etiological mechanisms rooted in proteostatic dysfunction. At the heart of this emerging understanding is the survival motor neuron (SMN) complex.

Heat hormesis describes the beneficial adaptations from transient exposure to mild heat stress, which enhances stress resilience and promotes healthy aging. It is thought to be the underlying basis of popular wellness practices like sauna therapy. Despite extensive documentation across species, the molecular basis of the long-term protective effects of heat hormesis remain poorly understood. This study bridges that critical gap through a comprehensive multiomic analysis, providing key insights into the transcriptomic and chromatin accessibility landscapes throughout a heat hormesis regimen adapted in C. elegans. We uncover highly dynamic dose-dependent molecular responses to heat stress and reveal that while most initial stress-induced changes revert to baseline, key differences in response to subsequent heat shock challenge are directly linked to physiological benefits. We identify new regulators of heat hormesis, including MARS-1/MARS1, SNPC-4/SNAPc, ELT-2/GATA4, FOS-1/c-Fos, and DPY-27/SMC4, which likely orchestrate gene expression programs that enhance stress resilience through distinct biological pathways. This study advances our understanding of stress resilience mechanisms, points to multiple new avenues of future investigations, and suggests potential strategies for promoting healthy aging through mid-life stress management.

Heat shock proteins are molecular chaperones that play crucial roles in the folding and unfolding of complex polypeptides within the cellular system. These molecules are involved in various processes, including vesicular transport, prevention of protein aggregation in the cytosol, and cell signaling. They are also linked to autoimmunity, infection immunity, and tumor immunology. Stressors like heat shock, exposure to heavy metals, cytokines, reactive oxygen species, inflammation, and viruses can influence the production of these molecules. In complex diseases such as cancer, malaria, and COVID-19, heat shock proteins are considered both biomarkers and drug targets. The upregulation of small heat shock proteins like hsp27 and major heat shock proteins 70/90 has been recognized as crucial biomarkers and therapeutic targets for cancer. Additionally, it has been reported that the invasion of Plasmodium falciparum, the causative agent of malaria, leads to the upregulation of heat shock proteins such as hsp40, hsp70, and hsp90. This sudden increase is a protective mechanism from the human host and enhances the parasite's growth, making these proteins significant as biomarkers and malarial drug targets. The presence of the SARS-CoV-2 virus in the human cellular system correlates with a substantial increase in heat shock protein 70 production from host cells. Furthermore, our research group has demonstrated that SARS-CoV-2 hijacks the host's heat shock proteins, and we are currently developing tools to prevent the virus from utilizing the host's protein folding system. This review aims to highlight the role of heat shock proteins as biomarkers and therapeutic targets for selected refractory diseases, focusing on cancer, malaria, and COVID-19. A fundamental molecular docking study was performed to investigate the interaction between a non-structural complex from SARS-CoV-2 and chosen small molecules, which is emphasized in this review.

HSPA1A, a major heat shock protein, is known to translocate to the plasma membrane (PM) in response to cellular stress and cancer, where it plays protective roles in membrane integrity and stress resistance. Although phosphatidylinositol 4-phosphate [PI(4)P] is essential in this translocation, the signals that trigger and facilitate HSPA1A's movement remain undefined.Given that membrane lipid composition dynamically shifts during stress, we hypothesized that heat shock-induced PI(4)P changes are crucial for HSPA1A's PM localization. To test this hypothesis, we investigated the mechanisms driving PI(4)P changes and HSPA1A PM localization under heat shock. Lipidomic analysis, enzyme-linked immunosorbent assay (ELISA), and confocal imaging revealed a rapid PI(4)P increase at the PM post-heat shock, with levels peaking at 0 hours and declining by 8 hours. RNA sequencing and protein quantification indicated no transcriptional increase in PI4KIII alpha, the kinase responsible for PI(4)P synthesis, suggesting an alternative regulatory mechanism. Hypothesizing that heat shock enhances PI4KIII alpha activity, we performed ELISA coupled with immunoprecipitation, confirming a significant rise in PI4KIII alpha activity following heat shock. Functional analyses further demonstrated that RNAi-mediated PI4KIII alpha depletion or pharmacological PI(4)P reduction, using GSK-A1, impairs HSPA1A's localization to the PM, confirming that HSPA1A translocation is PI(4)P-dependent. Our findings identify PI4KIII alpha activity as a key regulator of PI(4)P accumulation and subsequent HSPA1A recruitment to the PM in stressed and cancer cells. This lipid-mediated response offers new insights into stress adaptation and potentially modifiable pathways for therapeutic interventions to control HSPA1A function in cancer.

Photothermal therapy (PTT) has shown promise in the ablation of small, unresectable tumors by boosting the tumor's temperature above 50 °C. However, the high local temperature-induced cancer cell necrosis could create severe local inflammation, which may deteriorate normal tissues and increase tumor spreading. Although mild photothermal therapy (MPTT) at 42-45 °C could avoid the undesired side effect to some extent with minimal nonspecific heat diffusion, the self-protective behavior of tumors during MPTT results in an unsatisfactory therapeutic effect. Inspired by the widespread applications of traditional Chinese medicine (TCM) in various ailments, we also extensively explored the use of TCM in PTT and MPTT. In this Review, we summarize the application and function of TCM in PTT and MPTT, including the following: (1) TCM improves the performance of PTT and MPTT by elevating the photothermal conversion ability of photothermal agents (PTAs) and overcoming the self-protective effect of tumors, (2) PTT enhances TCM-based chemotherapy by improving the sensitivity and cellular uptake of TCM in tumors, and (3) natural TCM and metal-chelated TCM-based nanoparticles could directly act as PTAs for carrier-free combination therapy. We expect this Review will further illuminate TCM's utility and applicability in cancer treatment and create new combination strategies for theragnostic use.

Under tropical climate heat stress is a major challenge for livestock production. HSP70.1 is a ubiquitously expressed protein maintaining cellular machinery through proper folding of denatured proteins and prevents cellular apoptosis and protect cell from heat stress. Therefore, present investigation was undertaken to explore genetic variability in HSP70.1 gene in Gangatiri cattle, its comparison with buffalo sequences and differential expression in different season. The allelic variant was identified by sequencing amplified PCR product of HSP70.1 gene by primer walking. Season-wise total RNA samples was prepared for differential expression study. Brilliant SYBR Green QPCR technique was used to study the expression kinetics of this gene. DNA sequencing by primer walking identified four allelic variants in Gangatiri cattle. Sequence alignment study revealed four, six and one substitutions in the 5' untranslated region (5'UTR), coding and 3' untranslated region ((3'UTR) of HSP70.1 gene, respectively. Comparative analysis of HSP70.1 gene revealed that Cattle has shorter 5'UTR and 3' UTR than the buffalo. In Gangatiri cattle, summer season has significantly higher (P ≤ 0.05) expression of HSP70.1 than the spring and winter. The relative expression of HSP70.1 was increased by more than six folds in summer and nearly 1.5 folds higher in winter in comparison to the spring season. Therefore, HSP70.1 may be considered to have a critical role in the development of thermal tolerance in Gangatiri cattle.

Chaperonin containing tailless complex polypeptide 1 (CCT) functions as a molecular chaperone and is essential for ensuring proper protein folding. Glucose-regulated protein 78 (GRP78/Bip), also a type of chaperone, not only assists in folding of proteins, but also facilitates the transportation of proteins into the endoplasmic reticulum (ER) via the Sec protein complex. In this study, we identified the CCTη of N. bombycis (NbCCTη) for the first time. Immunoprecipitations and mass spectrometry (IP-MS) of NbCCTη analysis showed that NbBip may interact with CCT subunits. Yeast two-hybrid assays validated that NbBip interacts with NbCCTη, as well as NbCCTα and NbCCTε. Furthermore, RNA interference on NbBip brought about radical expression of NbCCTα, NbCCTε, and NbCCTη, while RNAi on NbCCT subunits resulted in abnormal expression of NbBip. Immunofluorescence assay results showed that NbBip colocalized with NbCCTα and NbCCTη, and CCTη colocalized with Nbβ-tubulin and Nbactin in the parasite. Collectively, these findings suggest that NbBip may act as a crucial factor in the subunit-folding and assembly of CCT complex in N. bombycis.

Understanding the molecular mechanisms underlying thermal acclimation and heat shock responses in marine ectotherms is critical for assessing their adaptive capacity in the context of climate change and climate extremes. This study examines the expression dynamics of heat shock proteins (HSPs) in the scallop Nodipecten subnodosus, shedding light on their role in thermal adaptation. Our analysis revealed the presence of several conserved functional signatures in N. subnodosus HSPs deduced amino acid sequences. Comparative gene expression profiling between two populations of N. subnodosus, maintained for 15 days under constant and oscillatory thermal regimes and then exposed to acute heat stress, revealed conserved adaptive traits. The heat-inducible nature of N. subnodosus HSP70 (HSPA8) gene expression highlights its potential as a stress marker, in contrast to its human homolog, which is constitutively expressed. Furthermore, the identification of HSP90 (HSPC3) and its overexpression during acute heat stress underscores its critical role in initiating a protective stress response. Population-specific responses in the magnitude of gene expression were observed; however, both populations exhibited similar overall patterns of HSP induction, suggesting a shared adaptive response mechanism. This study also elucidated the diversity and expansion of members of the HSP70 family members, specifically the HSPA12 subfamily, in N. subnodosus. This characteristic, previously observed in other bivalves, underscores the role of HSPA12 in environmental adaptation, providing molecular plasticity to withstand varying environmental pressures. These findings offer valuable insights into the molecular basis of thermal adaptation in N. subnodosus, highlighting the importance of HSPs in coping with environmental stochasticity under climate change scenarios.

Global transcription machinery engineering (gTME) is a strategy for optimizing complex phenotypes in microbes by manipulating transcription factors (TFs) and their downstream transcriptional regulatory networks (TRN). In principle, gTME leads to a focused but comprehensive optimization of a microbe, also enabling the engineering of nonpathway functionalities, like stress resistance, protein expression, or growth rate. A link between a TF and a desired phenotype is to be established for a rationally designed gTME. For use in a high-throughput format with extensive libraries of TRN-engineered clones tested under multiple conditions, well-developed culturing and analytical protocols are needed, to reveal the pleiotropic effects of the TFs. This mini-review summarizes the gTME strategies and TFs described under different contexts in Yarrowia lipolytica. The outcomes of the gTME strategy application are also addressed, demonstrating its effectiveness in engineering complex, industrially relevant traits in Y. lipolytica.

Heat shock proteins (HSPs) are crucial molecular chaperones that help organisms maintain protein stability under stress conditions. As a major stored-product pest, Rhyzopertha dominica (Fabricius) faces distinct stresses compared to field insects, primarily due to the specific pest control methods applied during grain storage. In this study, a total of 53 HSP genes from five gene families (HSP90, HSP70, HSP60, sHSP, and DnaJ) were identified and characterized using bioinformatics methods. Among them, DnaJ was the largest and the most diverse HSP family in R. dominica. Transcriptome sequencing and RT-qPCR were then used to evaluate HSP gene expression patterns under four storage-related stresses, following a series of bioassays. Extreme high temperature was the strongest inducer of HSP expression, with 12 genes showing over a 10-fold increase. Controlled nitrogen atmosphere also led to considerable upregulation of HSP genes, especially in the HSP70 family. In contrast, phosphine fumigation and K-Obiol grain protectant caused very limited induction of HSP genes, which might have been due to the less severe protein damage caused by chemical stresses compared to physical stresses. Our study provides a theoretical basis for further research on HSP functions in R. dominica.

The cellular stress response (CSR) is a conserved mechanism that protects cells from -environmental and physiological stressors. The heat shock response (HSR), a critical component of the CSR, utilizes molecular chaperones to mitigate proteotoxic stress caused by elevated temperatures. We hypothesized that while the canonical HSR pathways are conserved across cell types, specific cell lines may exhibit unique transcriptional responses to heat shock. To test this, we compared the transcriptomic responses of HEK293, HepG2, and HeLa cells under control conditions immediately following heat shock and after an 8-h recovery period. RNA sequencing revealed the conserved activation of canonical HSR pathways, including the unfolded protein response, alongside the -enrichment of the non-canonical "Receptor Ligand Activity" pathway across all cell lines. Cell-line-specific variations were observed, with HepG2 cells exhibiting significantly higher ex-pression levels of certain genes compared to other cell lines under stress conditions, as well as greater fold changes in gene expression relative to its control conditions. Validation by qPCR confirmed the activation of key genes within the "Receptor Ligand Activity" pathway across time points. These findings provide insights into conserved and context-specific aspects of the HSR, contributing to a more comprehensive understanding of stress response mechanisms across mammalian cells.

Heat shock proteins (HSPs) are essential molecular chaperones that protect cells by aiding in protein folding and preventing aggregation under stress conditions. Small heat shock proteins (sHSPs), which include members from HSPB1 to HSPB10, are particularly important for cellular stress responses. These proteins share a conserved α-crystallin domain (ACD) critical for their chaperone function, with flexible N- and C-terminal extensions that facilitate oligomer formation. Phosphorylation, a key post-translational modification (PTM), plays a dynamic role in regulating sHSP structure, oligomeric state, stability, and chaperone function. Unlike other PTMs such as deamidation, oxidation, and glycation-which are often linked to protein destabilization-phosphorylation generally induces structural transitions that enhance sHSP activity. Specifically, phosphorylation promotes the disaggregation of sHSP oligomers into smaller, more active complexes, thereby increasing their efficiency. This disaggregation mechanism is crucial for protecting cells from stress-induced damage, including apoptosis, inflammation, and other forms of cellular dysfunction. This review explores the role of phosphorylation in modulating the function of sHSPs, particularly HSPB1, HSPB4, and HSPB5, and discusses how these modifications influence their protective functions in cellular stress responses.

The ultrastructural organization of the nuclei of the tegmental region in juvenile chum salmon (Oncorhynchus keta) was examined using transmission electron microscopy (TEM). The dorsal tegmental nuclei (DTN), the nucleus of fasciculus longitudinalis medialis (NFLM), and the nucleus of the oculomotor nerve (NIII) were studied. The ultrastructural examination provided detailed ultrastructural characteristics of neurons forming the tegmental nuclei and showed neuro-glial relationships in them. Neurons of three size types with a high metabolic rate, characterized by the presence of numerous mitochondria, polyribosomes, Golgi apparatus, and cytoplasmic inclusions (vacuoles, lipid droplets, and dense bodies), were distinguished. It was found that large interneurons of the NFLM formed contacts with protoplasmic astrocytes. Excitatory synaptic structures were identified in the tegmentum and their detailed characteristic are provided for the first time. Microglia-like cells were found in the NIII. The ultrastructural characteristics of neurogenic zones of the tegmentum of juvenile chum salmon were also determined for the first time. In the neurogenic zones of the tegmentum, adult-type neural stem progenitor cells (aNSPCs) corresponding to cells of types III and IVa Danio rerio. In the neurogenic zones of the tegmentum, neuroepithelial-like cells (NECs) corresponding to cells previously described from the zebrafish cerebellum were found and characterized. In the tegmentum of juvenile chum salmon, patterns of paracrine neurosecretion were observed and their ultrastructural characteristics were recorded. Patterns of apoptosis in large neurons of the tegmentum were examined by TEM. Using immunohistochemical (IHC) labeling of the brain lipid-binding protein (BLBP) and aromatase B (AroB), patterns of their expression in the tegmentum of intact animals and in the post-traumatic period after acute injury to the medulla oblongata were characterized. The response to brainstem injury in chum salmon was found to activate multiple signaling pathways, which significantly increases the BLBP and AroB expression in various regions of the tegmentum and valvula cerebelli. However, post-traumatic patterns of BLBP and AroB localizations are not the same. In addition to a general increase in BLBP expression in the tegmental parenchyma, BLBP overexpression was observed in the rostro-lateral tegmental neurogenic zone (RLTNZ), while AroB expression in the RLTNZ was completely absent. Another difference was the peripheral overexpression of AroB and the formation of dense reactive clusters in the ventro-medial zone of the tegmentum. Thus, in the post-traumatic period, various pathways were activated whose components were putative candidates for inducers of the "astrocyte-like" response in the juvenile chum salmon brain that are similar to those present in the mammalian brain. In this case, BLBP acted as a factor enhancing the differentiation of both radial glia and neurons. Estradiol from AroB+ astrocytes exerted paracrine neuroprotective effects through the potential inhibition of inflammatory processes. These results indicate a new role for neuronal aromatization as a mechanism preventing the development of neuroinflammation. Moreover, our findings support the hypothesis that BLBP is a factor enhancing neuronal and glial differentiation in the post-traumatic period in the chum salmon brain.

Plant pathogenic bacteria are responsible for a substantial number of plant diseases worldwide, resulting in significant economic losses. Bacteria are exposed to numerous stress factors during their epiphytic life and within the host. Their ability to survive in the host and cause symptomatic infections depends on their capacity to overcome stressors. Bacteria have evolved a range of defensive and adaptive mechanisms to thrive under varying environmental conditions. One such mechanism involves the induction of chaperone proteins that belong to the heat shock protein (Hsp) family. Together with proteases, these proteins are integral components of the protein quality control system (PQCS), which is essential for maintaining cellular proteostasis. However, knowledge of their action is considerably less extensive than that of human and animal pathogens. This study discusses the modulation of Hsp levels by phytopathogenic bacteria in response to stress conditions, including elevated temperature, oxidative stress, changes in pH or osmolarity of the environment, and variable host conditions during infection. All these factors influence bacterial virulence. Finally, the secretion of GroEL and DnaK proteins outside the bacterial cell is considered a potentially important virulence trait.

PME12-mutated plants displayed altered stomatal characteristics and susceptibility to ABA-induced closure. Despite changes in PME activity, the mutant exhibited enhanced thermotolerance. These findings suggest a complex interplay between pectin methylesterification, ABA response, and stomatal function, contributing to plant adaptation to heat stress. Pectin, an essential component of plant cell walls, is synthesized in the Golgi apparatus and deposited into the cell wall in a highly methylesterified form. The degree and distribution of methylesterification within homogalacturonan (HGA) domains are crucial in determining its functional properties. Pectin methylesterase (PME) catalyzes the demethylesterification of HGA, which is pivotal for adjusting cell wall properties in response to environmental cues. Our investigation of PME12, a type-I pectin methylesterase in Arabidopsis, reveals its role in abscisic acid (ABA)-mediated stomatal regulation during heat stress, with the pme12 mutant showing increased stomatal density, reduced size, and heightened sensitivity to ABA-induced closure. Additionally, pme12 plants exhibited altered PME activities under heat stress but displayed enhanced thermotolerance. Moreover, our study identified SCRM as a transcriptional regulator positively influencing PME12 expression, linking stomatal development with PME12-mediated pectin methylesterification. These findings suggest that PME12-mediated pectin modification plays a role in coordinating ABA responses and influencing stomatal behavior under heat stress conditions.

The stress response following burns may be a crucial factor in keloid formation, yet the underlying pathological mechanisms remain to be elucidated. This study initially investigated how heat shock factor 1 (HSF1) and heat shock proteins (HSPs) within the heat shock pathway influence keloid fibrosis, providing insights into the role of the heat shock response in keloid development. This study aims to further elucidate the role of the heat shock pathway in keloid fibrosis and investigate the specific function of HSF1 within this pathway. This study focused on human keloid fibroblasts, examining the expression and regulatory role of HSF1 on HSPs under heat stress using immunohistochemistry, RNA interference, real-time fluorescent PCR, and Western blotting techniques. HSF1 was overexpressed in keloid fibroblasts and tissues compared to normal skin, and heat stress could further enhance HSF1 expression in both keloid tissues and fibroblasts. Functional inhibition of HSF1 significantly affected the expression of downstream HSPs in keloid fibroblasts, ultimately leading to the inhibition of keloid fibrosis. The heat shock pathway plays a crucial role in keloid fibrosis, with HSF1 as a key regulator influencing the expression of HSPs. Heat stress treatment of keloid fibroblasts offers an approach for investigating keloid formation.

Adaptation to environmental conditions occurs over diverse evolutionary timescales. In multi-cellular organisms, adaptive traits are often studied in tissues/organs relevant to the environmental challenge. We argue for the importance of an underappreciated layer of evolutionary adaptation manifesting at the cellular level. Cell-autonomous adaptations (CAAs) are inherited traits that boost organismal fitness by enhancing individual cell function. For instance, the cell-autonomous enhancement of mitochondrial oxygen utilization in hypoxic environments differs from an optimized erythropoiesis response, which involves multiple tissues. We explore the breadth of CAAs across challenges and highlight their counterparts in unicellular organisms. Applying these insights, we mine selection signals in Andean highlanders, revealing novel candidate CAAs. The conservation of CAAs across species may reveal valuable insights into multi-cellular evolution.

Climate change and growing population and their strain on animal production are the impending challenges that the developing countries, like India, need to tackle in the coming days. This study aimed to detect and analyze the uncharacterized variation in the gene expression patterns with the change of condition, from thermoneutral to chronic hot-humid, in the Sahiwal cattle, one of the best breeds of milk-producing cattle in India, known for being heat-tolerant. Using RNA-Seq analysis on peripheral blood mononuclear cells (PBMCs), 4021 differentially expressed mRNAs (2772 upregulated, 1249 downregulated) and 1303 differentially expressed long non-coding RNAs (769 upregulated, 534 downregulated) were identified, with the thresholds of false discovery rate < 0.05 and|log2(fold change)| > 2. Significantly (p-adjusted < 0.05) overrepresented Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathways were analyzed, revealing upregulation of processes like pyruvate metabolic process, gluconeogenesis, ion transmembrane transport, neuropeptide signaling pathway, and animal organ development, with genes like SHH, GRK1, CHRM3, CAMK2A, and HSPB7 were upregulated, while translation and immune responses, with genes like RPS3, EEF1A1, TNF, BoLA-DRB3, and UBB were downregulated. Analysis of cis-mRNAs of DE-lncRNAs showed presence of both up- and down-regulated cis-mRNAs for both up- and down-regulated lncRNAs indicating existence of positive and negative regulation of mRNA expression by lncRNAs. Managemental nudges that decrease metabolic heat generation, like betaine and chromium supplementation, and increase heat dissipation, like microenvironment cooling, should be utilized. This study highlights the role of pyruvate metabolism and gluconeogenesis in coping up with heat stress and offers an improved understanding of the heat stress response of Sahiwal cattle along with the genes and pathways responsible for it.

The cellular stress response (CSR) is a conserved mechanism that protects cells from environmental and physiological stressors. The heat shock response (HSR), a critical component of the CSR, utilizes molecular chaperones to mitigate proteotoxic stress caused by elevated temperatures. We hypothesized that while the canonical HSR pathways are conserved across cell types, specific cell lines may exhibit unique transcriptional responses to heat shock. To test this, we compared the transcriptomic responses of HEK293, HepG2, and HeLa cells under control conditions immediately following heat shock and after an 8-hour recovery period. RNA sequencing revealed conserved activation of canonical HSR pathways, including the unfolded protein response, alongside enrichment of the non-canonical "Receptor Ligand Activity" pathway across all cell lines. Cell line-specific variations were also observed, with HepG2 cells displaying more uniquely expressed genes and elevated expression levels (fold changes) of shared genes under stress conditions. Validation by qPCR confirmed the activation of key genes within the "Receptor Ligand Activity" pathway across time points. These findings provide insights into conserved and context-specific aspects of the HSR, contributing to a more comprehensive understanding of stress response mechanisms across mammalian cells.

Heat shock protein A1A (HSPA1A) is a molecular chaperone crucial in cell survival. In addition to its cytosolic functions, HSPA1A translocates to heat-shocked and cancer cells' plasma membrane (PM). In cancer, PM-localized HSPA1A (mHSPA1A) is associated with increased tumor aggressiveness and therapeutic resistance, suggesting that preventing its membrane localization could have therapeutic value. This translocation depends on HSPA1A's interaction with PM phospholipids, including phosphatidylserine (PS). Although PS binding regulates HSPA1A's membrane localization, the exact trigger for this movement remains unclear. Given that lipid modifications are a cancer hallmark, we hypothesized that PS is a crucial lipid driving HSPA1A translocation and that heat-induced changes in PS levels trigger HSPA1A's PM localization in response to heat stress. We tested this hypothesis using pharmacological inhibition and RNA interference (RNAi) targeting PS synthesis, combined with confocal microscopy, lipidomics, and western blotting. Lipidomic analysis and PS-specific biosensors confirmed a heat shock-induced PS increase, peaking immediately post-stress. Inhibition of PS synthesis with fendiline and RNAi significantly reduced HSPA1A's PM localization, while depletion of cholesterol or fatty acids had minimal effects, confirming specificity for PS. Further experiments showed that PS saturation and elongation changes did not significantly impact HSPA1A's PM localization, indicating that the total PS increase, rather than specific PS species, is the critical factor. These findings reshape current models of HSPA1A trafficking, demonstrating that PS is a crucial regulator of HSPA1A's membrane translocation during the heat shock response. This work offers new insights into lipid-regulated protein trafficking and highlights the importance of PS in controlling cellular responses to stress.

As many proteins prioritize functionality over constancy of structure, a proteome is the shortest stave in the Liebig's barrel of cell sustainability. In this regard, both prokaryotes and eukaryotes possess abundant machinery supporting the quality of the proteome in healthy and stressful conditions. This machinery, namely chaperones, assists in folding, refolding, and the utilization of client proteins. The functions of chaperones are especially important for brain cells, which are highly sophisticated in terms of structural and functional organization. Molecular chaperones are known to exert beneficial effects in many brain diseases including one of the most threatening and widespread brain pathologies, ischemic stroke. However, whether and how they exert the antioxidant defense in stroke remains unclear. Herein, we discuss the chaperones shown to fight oxidative stress and the mechanisms of their antioxidant action. In ischemic stroke, during intense production of free radicals, molecular chaperones preserve the proteome by interacting with oxidized proteins, regulating imbalanced mitochondrial function, and directly fighting oxidative stress. For instance, cells recruit Hsp60 and Hsp70 to provide proper folding of newly synthesized proteins-these factors are required for early ischemic response and to refold damaged polypeptides. Additionally, Hsp70 upregulates some dedicated antioxidant pathways such as FOXO3 signaling. Small HSPs decrease oxidative stress via attenuation of mitochondrial function through their involvement in the regulation of Nrf- (Hsp22), Akt and Hippo (Hsp27) signaling pathways as well as mitophagy (Hsp27, Hsp22). A similar function has also been proposed for the Sigma-1 receptor, contributing to the regulation of mitochondrial function. Some chaperones can prevent excessive formation of reactive oxygen species whereas Hsp90 is suggested to be responsible for pro-oxidant effects in ischemic stroke. Finally, heat-resistant obscure proteins (Hero) are able to shield client proteins, thus preventing their possible over oxidation.

In warm environments, thermoregulation in poultry is controlled by heat shock protein 70 (HSP70), whose expression is controlled by heat shock factor 3 (HSF3). Although the association between genetic polymorphisms in these genes and thermotolerance as well as reproductive traits has been extensively studied in mammals, the association has not yet been studied in poultry. This study aimed to explore the relationship between single-nucleotide polymorphisms (SNPs) in these genes and the egg production traits of Bangladeshi hilly chickens. Sequencing and allele-specific PCR (AS-PCR) were used to detect new SNPs and perform genotyping. We identified two novel SNPs (G-399A and A-68G) in the 5'-flanking regions of HSP70 that were significantly associated with egg numbers (ENs) at 161-190 days and increased egg weight (EW) at 40 weeks of age. Furthermore, three SNPs in HSP70 (A258G, C276G and C1431A) and one SNP in HSF3 (A-1388G) were associated with EN at different ages. The haplotype and combined genotypic effects of these two genes were found to be associated with age at sexual maturity (ASM), EN, EW, and body weight at ASM. The identified SNPs and their corresponding haplotypes may be useful in selective breeding to enhance the productivity of chickens in warm environments.

Climate warming is expected to substantially impact the global landscape of mosquito-borne disease, but these impacts will vary across disease systems and regions. Understanding which diseases, and where within their distributions, these impacts are most likely to occur is critical for preparing public health interventions. While research has centered on potential warming-driven expansions in vector transmission, less is known about the potential for vectors to experience warming-driven stress or even local extirpations. In conservation biology, species risk from climate warming is often quantified through vulnerability indices such as thermal safety margins-the difference between an organism's upper thermal limit and its habitat temperature. Here, we estimated thermal safety margins for 8 mosquito species that are the vectors of malaria, dengue, chikungunya, Zika, West Nile and other major arboviruses, across their known ranges to investigate which mosquitoes and regions are most and least vulnerable to climate warming. We find that several of the most medically important mosquito vector species, including Ae. aegypti and An. gambiae, have positive thermal safety margins across the majority of their ranges when realistic assumptions of mosquito behavioral thermoregulation are incorporated. On average, the lowest climate vulnerability, in terms of both the magnitude and duration of thermal safety, was just south of the equator and at northern temperate range edges, and the highest climate vulnerability was in the subtropics. Mosquitoes living in regions including the Middle East, the western Sahara, and southeastern Australia, which are largely comprised of desert and xeric shrubland biomes, have the highest climate vulnerability across vector species.

Genome-wide association studies (GWAS) have identified more than 200 breast cancer risk-associated genetic loci, yet the causal genes and biological mechanisms for most loci remain elusive. Proteins, as final gene products, are pivotal in cellular function. In this study, we conducted a proteome-wide association study (PWAS) to identify proteins in breast tissue related to breast cancer risk.

We profiled the proteome in fresh frozen breast tissue samples from 120 cancer-free European-ancestry women from the Susan G. Komen Tissue Bank (KTB). Protein expression levels were log2-transformed then normalized via quantile and inverse-rank transformations. GWAS data were also generated for these 120 samples. These data were used to build statistical models to predict protein expression levels via cis-genetic variants using the elastic net method. The prediction models were then applied to the GWAS summary statistics data of 133,384 breast cancer cases and 113,789 controls to assess the associations of genetically predicted protein expression levels with breast cancer risk overall and its subtypes using the S-PrediXcan method.

A total of 6388 proteins were detected in the normal breast tissue samples from 120 women with a high detection false discovery rate (FDR) p value < 0.01. Among the 5820 proteins detected in more than 80% of participants, prediction models were successfully built for 2060 proteins with R > 0.1 and P < 0.05. Among these 2060 proteins, five proteins were significantly associated with overall breast cancer risk at an FDR p value < 0.1. Among these five proteins, the corresponding genes for proteins COPG1, DCTN3, and DDX6 were located at least 1 Megabase away from the GWAS-identified breast cancer risk variants. COPG1 was associated with an increased risk of breast cancer with a p value of 8.54 × 10-4. Both DCTN3 and DDX6 were associated with a decreased risk of breast cancer with p values of 1.01 × 10-3 and 3.25 × 10-4, respectively. The corresponding genes for the remaining two proteins, LSP1 and DNAJA3, were located in previously GWAS-identified breast cancer risk loci. After adjusting for GWAS-identified risk variants, the association for DNAJA3 was still significant (p value of 9.15 × 10-5 and adjusted p value of 1.94 × 10-4). However, the significance for LSP1 became weaker with a p value of 0.62. Stratification analyses by breast cancer subtypes identified three proteins, SMARCC1, LSP1, and NCKAP1L, associated with luminal A, luminal B, and ER-positive breast cancer. NCKAP1L was located at least 1Mb away from the GWAS-identified breast cancer risk variants. After adjusting for GWAS-identified breast cancer risk variants, the association for protein LSP1 was still significant (adjusted p value of 6.43 × 10-3 for luminal B subtype).

We conducted the first breast-tissue-based PWAS and identified seven proteins associated with breast cancer, including five proteins not previously implicated. These findings help improve our understanding of the underlying genetic mechanism of breast cancer development.

Many essential conserved functions depend, paradoxically, on proteins that evolve rapidly under positive selection. How such adaptively evolving proteins promote biological innovation while preserving conserved, essential functions remains unclear. Here, we experimentally test the hypothesis that adaptive protein-protein coevolution within an essential multi-protein complex mitigates the deleterious incidental byproducts of innovation under pressure from selfish genetic elements. We swapped a single, adaptively evolving subunit of a telomere protection complex from Drosophila yakuba into its close relative, D. melanogaster. The heterologous subunit uncovered a catastrophic interspecies incompatibility that caused lethal telomere fusions. Restoring six adaptively evolving sites on the protein-protein interaction surface, or introducing the D. yakuba interaction partner, rescued telomere integrity and viability. Our in vivo, evolution-guided manipulations illuminate how adaptive protein-protein coevolution preserves essential functions threatened by an evolutionary pressure to innovate.

Developmental environmental stressors can have instructive effects on an organism's phenotype. This developmental plasticity can prepare organisms for potentially stressful future environments, circumventing detrimental effects on fitness. However, the physiological mechanisms underlying such adaptive plasticity are understudied, especially in vertebrates. We hypothesized that captive male zebra finches (Taeniopygia castanotis) exposed to a mild heat conditioning during development would acquire a persisting thermotolerance, and exhibit increased heat-shock protein (HSP) levels associated with a decrease in oxidative damage when exposed to a high-intensity stressor in adulthood. To test this, we exposed male finches to a prolonged mild heat conditioning (38°C) or control (22°C) treatment as juveniles. Then in a 2 × 2 factorial manner, these finches were exposed to a high heat stressor (42°C) or control (22°C) treatment as adults. Following the adult treatment, we collected testes and liver tissue and measured HSP70, HSP90, and HSP60 protein levels. In the testes, finches exhibited lower levels of HSP90 and HSP60 when exposed to the high heat stressor in adulthood if they were exposed to the mild heat conditioning as juveniles. In the liver, finches exposed to the high heat stressor in adulthood had reduced HSP90 and HSP60 levels, regardless of whether they were conditioned as juveniles. In some cases, elevated testes HSP60 levels were associated with increased liver oxidative damage and diminishment of a condition-dependent trait, indicating potential stress-induced tradeoffs. Our results indicate that a mild conditioning during development can have persisting effects on HSP expression and acquired thermotolerance.

The exposure of broiler chickens to high ambient temperatures causes heat stress (HS), negatively affecting their health and production performance. To mitigate heat stress in broilers, various strategies, including dietary, managerial, and genetic interventions, have been extensively tested with varying degrees of efficacy. For sustainable broiler production, it is imperative to develop an innovative approach that effectively mitigates the adverse effects of HS. Our previous studies have provided valuable insights into the effects of prehatch embryonic thermal manipulation (TM) and posthatch baicalein supplementation on embryonic thermotolerance, metabolism, and posthatch growth performance. This follow-up study investigated the effect of these interventions on gluconeogenesis and lipid metabolism in the liver, as well as muscle proliferation and regeneration capacity in heat-stressed broiler chickens. A total of six-hundred fertile Cobb 500 eggs were incubated for 21 d. After candling, 238 eggs were subjected to TM at 38.5°C with 55% relative humidity (RH) from embryonic day (ED) 12 to 18. These eggs were transferred to the hatcher and kept at a standard temperature (37.5°C) from ED 19 to 21, while 236 eggs were incubated at a controlled temperature (37.5°C) till hatch. After hatching, 180 day-old chicks from both groups were raised in 36 pens treatment (n = 10 birds/pen, 6 replicates per treatment). The treatments were: 1) Control, 2) TM, 3) Control heat stress (CHS), 4) Thermal manipulation heat stress (TMHS), 5) Control heat stress supplement (CHSS), and 6) Thermal manipulation heat stress supplement (TMHSS). Baicalein was added to the treatment group diets starting from d 1. All birds were raised under the standard environment for 21 d, followed by chronic heat stress from d 22 to 35 (32-33 ⁰C for 8 h) in the CHS, TMHS, CHSS, and TMHSS groups. A thermoneutral (22-24⁰C) environment was maintained in the Control and TM groups. RH was constant (50 ± 5%) throughout the trial. In the liver, TM significantly increased (P < 0.05) IGF2 expression. Baicalein supplementation significantly increased (P < 0.05) HSF3, HSP70, SOD1, SOD2, TXN, PRARα, and GHR expression. Moreover, the combination of TM and baicalein supplementation significantly increased (P < 0.05) the expression of HSPH1, HSPB1, HSP90, LPL, and GHR. In the muscle, TM significantly increased (P < 0.05) HSF3 and Myf5 gene expression. TM and baicalein supplementation significantly increased (P < 0.05) the expression of MyoG and significantly (P < 0.05) decreased mTOR and PAX7. In conclusion, the prehatch TM of embryos and posthatch baicalein supplementation mitigated the deleterious effects of HS on broiler chickens by upregulating genes related to liver gluconeogenesis, lipid metabolism, and muscle proliferation.

Mutations that impair a protein-folding chaperone can lead to brain malformations.

Environmental transitions, such as the salinity divide separating marine and fresh waters, shape biodiversity over both shallow and deep timescales, opening up new niches and creating opportunities for accelerated speciation and adaptive radiation. Understanding the genetics of environmental adaptation is central to understanding how organisms colonise and subsequently diversify in new habitats. We used time-resolved transcriptomics to contrast the hyposalinity stress responses of two diatoms. Skeletonema marinoi has deep marine ancestry but has recently invaded brackish waters. Cyclotella cryptica has deep freshwater ancestry and can withstand a much broader salinity range. Skeletonema marinoi is less adept at mitigating even mild salinity stress compared to Cyclotella cryptica, which has distinct mechanisms for rapid mitigation of hyposaline stress and long-term growth in low salinity. We show that the cellular mechanisms underlying low salinity tolerance, which has allowed diversification across freshwater habitats worldwide, includes elements that are both conserved and variable across the diatom lineage. The balance between ancestral and lineage-specific environmental responses in phytoplankton have shaped marine-freshwater transitions on evolutionary timescales and, on contemporary timescales, will affect which lineages survive and adapt to changing ocean conditions.

Translation initiation of most mammalian mRNAs is mediated by a 5' cap structure that binds eukaryotic initiation factor 4E (eIF4E). Notably, most mRNAs are still capped when eIF4E is inhibited, suggesting alternative mechanisms likely mediate cap-dependent mRNA translation without functional eIF4F. Here we found that, when eIF4E is inhibited, the ribosomal scaffold RACK1 recruits eIF3d on the 43S pre-initiation complex. Moreover, we found that it is just PKCBII in its active form that promotes the binding of RACK1 to eIF3d. These studies disclose a previously unknown role of ribosomal RACK1 for eIF3d specialized translation.