Modulation Of Stress Response Research Articles

Hawaiian coral holobionts reveal algal and prokaryotic host specificity, intraspecific variability in bleaching resistance, and common interspecific microbial consortia modulating thermal stress responses

Historically, Hawai‘i had few massive coral bleaching events, until two consecutive heatwaves in 2014–2015. Consequent mortality and thermal stress were observed in Kāne‘ohe Bay (O‘ahu). The two most dominant local species exhibited a phenotypic dichotomy of either bleaching resistance or susceptibility (Montipora capitata and Porites compressa), while the third predominant species (Pocillopora acuta) was broadly susceptible to bleaching. In order to survey shifts in coral microbiomes during bleaching and recovery, 50 colonies were tagged and periodically monitored. Metabarcoding of three genetic markers (16S rRNA gene ITS1 and ITS2) followed by compositional approaches for community structure analysis, differential abundance and correlations for longitudinal data were used to temporally compare Bacteria/Archaea, Fungi and Symbiodiniaceae dynamics. P. compressa corals recovered faster than P. acuta and Montipora capitata. Prokaryotic and algal communities were majorly shaped by host species, and had no apparent pattern of temporal acclimatization. Symbiodiniaceae signatures were identified at the colony scale, and were often related to bleaching susceptibility. Bacterial compositions were practically constant between bleaching phenotypes, and more diverse in P. acuta and M. capitata. P. compressa's prokaryotic community was dominated by a single bacterium. Compositional approaches (via microbial balances) allowed the identification of fine-scale differences in the abundance of a consortium of microbes, driving changes by bleaching susceptibility and time across all hosts. The three major coral reef founder-species in Kāne‘ohe Bay revealed different phenotypic and microbiome responses after 2014–2015 heatwaves. It is difficult to forecast, a more successful strategy towards future scenarios of global warming. Differentially abundant microbial taxa across time and/or bleaching susceptibility were broadly shared among all hosts, suggesting that locally, the same microbes may modulate stress responses in sympatric coral species. Our study highlights the potential of investigating microbial balances to identify fine-scale microbiome changes, serving as local diagnostic tools of coral reef fitness.

Stress-related biomolecular condensates in plants.

Biomolecular condensates are membraneless organelle-like structures that can concentrate molecules and often form through liquid-liquid phase separation. Biomolecular condensate assembly is tightly regulated by developmental and environmental cues. Although research on biomolecular condensates has intensified in the past 10 years, our current understanding of the molecular mechanisms and components underlying their formation remains in its infancy, especially in plants. However, recent studies have shown that the formation of biomolecular condensates may be central to plant acclimation to stress conditions. Here, we describe the mechanism, regulation, and properties of stress-related condensates in plants, focusing on stress granules and processing bodies, 2 of the most well-characterized biomolecular condensates. In this regard, we showcase the proteomes of stress granules and processing bodies in an attempt to suggest methods for elucidating the composition and function of biomolecular condensates. Finally, we discuss how biomolecular condensates modulate stress responses and how they might be used as targets for biotechnological efforts to improve stress tolerance.

Comprehensive analysis of AP2/ERF gene members in Acer truncatum B. and the positive regulator role of AtruDREB28 in drought tolerance

APETALA2/Ethylene Responsive Factor (AP2/ERF) play pivotal roles in resisting diverse stresses and in regulating growth and development in plant, but the information and function of the AP2/ERF genes are not well elucidated in Acer truncatum B. As an important woody tree producing oil with high economic values, A. truncatum has strong tolerance to drought. AP2/ERF may implicate in drought stress tolerance and growth of A. truncatum. In the current research, the AtruAP2/ERF family members were identified and comprehensive bioinformatics analysis were performed, including phylogenetic relationship, gene/protein structure, expression pattern, cis-acting element, protein interaction network, and functional characterization of AtruDREB28. Total of 117 AtruAP2/ERF members were identified in A. truncatum genome and were divided into five subfamilies, AP2 (17 genes), ERF (61 genes), DREB (35 genes), RAV (3 genes), and Soloist (one gene). The members from same clade exhibited relatively similar gene structure and motif compositions. Fifty-seven duplication events were identified in AtruAP2/ERF family, containing eight pairs generated from fragmental duplication, and 49 pairs generated from tandem duplication. Subsequently, a variety of cis-acting elements associated with development, hormone, and stress were identified in the promoter regions of AtruAP2/ERF, such as ARE, MBS, ABRE, TCA, etc. A potential interaction network of AtruAP2/ERFs was conducted to predict the interaction relationships. In addition, tissue expression analysis showed that majority of AtruAP2/ERFs exhibited tissue specific modes. The expression profiles of the majority of AtruAP2/ERFs were induced in response to drought stress, suggesting that AtruAP2/ERFs were involved in the modulation of drought stress response. Furthermore, overexpression of AtruDREB28 increased the tolerance to drought stress by enhancing the reactive oxygen species-scavenging capability. Together, these results give insights into the characteristics and functional analysis of AtruAP2/ERF genes in A. truncatum.

The transcription factor MYB43 antagonizes with ICE1 to regulate freezing tolerance in Arabidopsis.

Previous discovering meticulously illustrates the post-translational modifications and protein stability regulation of ICE1 and their role in cold stress. However, the studies on the interaction of ICE1 with other transcription factors, and their function in modulation cold stress tolerance, as well as in the transition between cold stress and growth are largely insufficient. In this work, we found that maltose binding protein (MBP) 43 directly binds to the promoters of CBF genes to repress their expression, thereby negatively regulating freezing tolerance. Biochemical and genetic analyses showed that MYB43 interacts and antagonizes with ICE1 to regulate the expression of CBF genes and plant's freezing stress tolerance. PLEIOTROPIC REGULATORY LOCUS 1 (PRL1) accumulates under cold stress and promotes MYB43 protein degradation; however, when cold stress disappears, PRL1 restores normal protein levels, causing MYB43 protein to re-accumulate to normal levels. Furthermore, PRL1 positively regulates freezing tolerance by promoting degradation of MYB43 to attenuate its repression of CBF genes and antagonism with ICE1. Thus, our study reveals that MYB43 inhibits CBF genes expression under normal growth condition, while PRL1 promotes MYB43 protein degradation to attenuate its repression of CBF genes and antagonism with ICE1, and thereby to the precise modulation of plant cold stress responses.

Perspectives on environmental heterogeneity and seasonal modulation of stress response in neotropical birds

Corticosterone (CORT), the main glucocorticoid in birds, regulates physiological and behavioral traits linked to predictable and unpredictable environmental fluctuations (i.e., stressors). Baseline and stress-induced CORT concentrations are known to fluctuate seasonally, linked to life history stages (LHS) such as breeding, molt, and wintering stage. These variations have been relatively well described in North American birds, but poorly addressed in neotropical species. To fill this gap, we explored how baseline and stress-induced CORT variation by LHS was affected by seasonality and environmental heterogeneity (i.e., frequency of unpredictable events such as droughts, flashfloods, etc) within the Neotropics using two approaches. First, we reviewed all currently available data about CORT concentrations for neotropical bird species. Second, we performed an in-depth analysis comparing the CORT responses of the two most common species of the Zonotrichia genus from North and South America (Z. leucophrys and Z. capensis, respectively) and their subspecies to seasonality and environmental heterogeneity. These species have been analyzed with the same methodology, allowing for an in-depth comparison of CORT variations. Despite scant data on neotropical bird species, we observed overlap between molt and breeding, and lower fluctuations of CORT among LHS. These patterns would be considered atypical compared to those described for North temperate species. Further, we found no significant associations between environmental heterogeneity and the stress-responses. In Zonotrichia we observed a positive association between baseline and stress-induced concentrations of CORT and latitude. We also observed differences by LHS. Both baseline and stress-induced CORT concentrations were higher during breeding and lower during molt. In addition, for both species, the overall pattern of seasonal modulation of stress response was heavily influenced by the migration strategy, with long-distance migrants showing significantly higher stress-induced CORT levels. Our results highlight the need for more data collection in the Neotropics. Comparative data would shed further light on the sensitivity of the adrenocortical response to stress under different scenarios of environmental seasonality and unpredictability.

IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.

Transcriptomic Modulation Reveals the Specific Cellular Response in Chinese Sea Bass (Lateolabrax maculatus) Gills under Salinity Change and Alkalinity Stress.

Salinity and alkalinity are among the important factors affecting the distribution, survival, growth and physiology of aquatic animals. Chinese sea bass (Lateolabrax maculatus) is an important aquaculture fish species in China that can widely adapt to diverse salinities from freshwater (FW) to seawater (SW) but moderately adapt to highly alkaline water (AW). In this study, juvenile L. maculatus were exposed to salinity change (SW to FW) and alkalinity stress (FW to AW). Coordinated transcriptomic responses in L. maculatus gills were investigated and based on the weighted gene co-expression network analysis (WGCNA), 8 and 11 stress-responsive modules (SRMs) were identified for salinity change and alkalinity stress, respectively, which revealed a cascade of cellular responses to oxidative and osmotic stress in L. maculatus gills. Specifically, four upregulated SRMs were enriched with induced differentially expressed genes (DEGs) for alkalinity stress, mainly corresponding to the functions of "extracellular matrix" and "anatomical structure", indicating a strong cellular response to alkaline water. Both "antioxidative activity" and "immune response" functions were enriched in the downregulated alkaline SRMs, which comprised inhibited alkaline specific DEGs, revealing the severely disrupted immune and antioxidative functions under alkalinity stress. These alkaline-specific responses were not revealed in the salinity change groups with only moderately inhibited osmoregulation and induced antioxidative response in L. maculatus gills. Therefore, the results revealed the diverse and correlated regulation of the cellular process and stress response in saline-alkaline water, which may have arisen through the functional divergence and adaptive recruitment of the co-expression genes and will provide vital insights for the development of L. maculatus cultivation in alkaline water.

Optical neuroimaging and neurostimulation in surgical training and assessment: A state-of-the-art review.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical neuroimaging technique used to assess surgeons' brain function. The aim of this narrative review is to outline the effect of expertise, stress, surgical technology, and neurostimulation on surgeons' neural activation patterns, and highlight key progress areas required in surgical neuroergonomics to modulate training and performance. A literature search of PubMed and Embase was conducted to identify neuroimaging studies using fNIRS and neurostimulation in surgeons performing simulated tasks. Novice surgeons exhibit greater haemodynamic responses across the pre-frontal cortex than experts during simple surgical tasks, whilst expert surgical performance is characterized by relative prefrontal attenuation and upregulation of activation foci across other regions such as the supplementary motor area. The association between PFC activation and mental workload follows an inverted-U shaped curve, activation increasing then attenuating past a critical inflection point at which demands outstrip cognitive capacity Neuroimages are sensitive to the impact of laparoscopic and robotic tools on cognitive workload, helping inform the development of training programs which target neural learning curves. FNIRS differs in comparison to current tools to assess proficiency by depicting a cognitive state during surgery, enabling the development of cognitive benchmarks of expertise. Finally, neurostimulation using transcranial direct-current-stimulation may accelerate skill acquisition and enhance technical performance. FNIRS can inform the development of surgical training programs which modulate stress responses, cognitive learning curves, and motor skill performance. Improved data processing with machine learning offers the possibility of live feedback regarding surgeons' cognitive states during operative procedures.

Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses.

The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

Abstract P6-05-16: Social isolation induces gut dysbiosis, mitochondrial metabolic dysfunction, and infiltration of tumor immunosuppressive cells: do they explain enhanced mammary tumorigenesis?

Abstract Inadequate social contacts and loneliness, often referred to as social isolation (SI), are associated with increased mortality from many diseases, including breast cancer. Up to 41% of breast cancer patients have been identified as feeling socially isolated. Moreover, socially isolated breast cancer survivors have a 43% higher risk of recurrence than socially integrated survivors. To prevent increased mortality, biological mechanisms which mediate the effects of SI on cancer need to be identified. One unexplored, but possible mechanism is through the gut microbiota. Through bidirectional interactions, the gut is affected by stress and the gut microbiota in turn can modulate stress response, host immunity and metabolism. Here we tested the hypothesis that SI induces gut dysbiosis. In our study, repeated in four separate experiments, adult female mice were divided into two groups – those kept group housed (GH, 4 mice per cage) and those housed singly in SI for 4 weeks. Several differences in the gut microbial family, genus and species levels were seen, but the differences were mostly unique to each of the four experiment. Beta-diversity was increased in three of the four studies in SI mice. Since beta-diversity is increased by aging, SI may accelerate the aging process. At the genus level, SI significantly suppressed the abundance of Akkermansia in all four studies and increased Acetatifactor in three studies. These two bacterial changes are expected to disrupt mitochondrial oxidative phosphorylation (OXPHOS), most likely by suppressing the short-chain fatty acid production. Further, low Akkermansia and high Acetatifactor are expected to increase inflammation. In a separate study, we discovered that SI impaired OXPHOS and activated inflammatory pathways in the mammary gland. We also have assessed immune cells in the spleen. SI increased the frequency of pro-inflammatory CD4+RORy+ cells, and the immunosuppressive Treg (CD4+Foxp3+) and PMN-MDSCs cells. In addition, SI increased PD1 expression in Foxp3+ cells, suggesting that anti-PD1 therapy might adversely affect socially isolated breast cancer patients by invigorating Treg cells. We are currently studying if the changes in the gut microbiota in SI mice are causally linked to their impaired mitochondrial metabolism, immunosuppression and increased mammary cancer mortality. We also plan to investigate if dietary modifications can reverse gut dysbiosis in SI mice and prevent their increased mortality from mammary cancer. Citation Format: Fabia de Oliveira Andrade, Lu Jin, Vivek Verma, Maddie McDermott, Chris Staley, Leena Hilakivi-Clarke. Social isolation induces gut dysbiosis, mitochondrial metabolic dysfunction, and infiltration of tumor immunosuppressive cells: do they explain enhanced mammary tumorigenesis? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-16.

Modulation of the endoplasmic reticulum stress and unfolded protein response mitigates the behavioral effects of early-life stress

BackgroundEarly-life stress (ELS) affects brain development and increases the risk of mental disorders associated with the dysfunction of the medial prefrontal cortex (mPFC). The mechanisms of ELS action are not well understood. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are cellular processes involved in brain maturation through the regulation of pro-survival or proapoptotic processes. We hypothesized that ER stress and the UPR in the mPFC are involved in the neurobiology of ELS.MethodsWe performed a maternal separation (MS) procedure from postnatal days 1 to 14 in rats. Before each MS, pups were injected with an inhibitor of ER stress, salubrinal or a vehicle. The mRNA and protein expression of UPR and apoptotic markers were evaluated in the mPFC using RT-qPCR and Western blot methods, respectively. We also estimated the numbers of neurons and glial cells using stereological methods. Additionally, we assessed behavioral phenotypes related to fear, anhedonia and response to psychostimulants.ResultsMS slightly enhanced the activation of the UPR in juveniles and modulated the expression of apoptotic markers in juveniles and preadolescents but not in adults. Additionally, MS did not affect the numbers of neurons and glial cells at any age. Both salubrinal and vehicle blunted the expression of UPR markers in juvenile and preadolescent MS rats, often in a treatment-specific manner. Moreover, salubrinal and vehicle generally alleviated the behavioral effects of MS in preadolescent and adult rats.ConclusionsModulation of ER stress and UPR processes may potentially underlie susceptibility or resilience to ELS.

Pepper clade A PP2C, CaSIP1, negatively modulates drought resistance by suppressing CaSnRK2.6 kinase activity

The phytohormone abscisic acid (ABA) plays a key role in plant response and adaptation to various environmental stimuli, including drought and salinity. As an ABA signaling core component, the serine/threonine kinase SnRK2.6/OST1 is known to undergo post-translational modifications in the modulation of ABA and drought stress responses. However, which proteins are involved in the process remains largely unclear in pepper plants. Here, we tried to isolate CaSnRK2.6-interacting partners through yeast two-hybrid screening and identified the type 2 C protein phosphatase CaSIP1 (Capsicum annuumSnRK2.6-interacting protein phosphatase 1), which belongs to the PP2CA branch. CaSIP1 transcript levels were enhanced by abiotic stress and ABA treatments. Our kinase assays showed that the CaSIP1 protein significantly suppressed the phosphorylation activity of CaSnRK2.6, but its amino acid–substitution mutant did not. Due to PP2C gene redundancy in pepper plants, we alternatively generated CaSIP1-overexpressing (OX) transgenic Arabidopsis plants to understand how CaSIP1 functionally contributes to plant responses to ABA and drought stress. Phenotypic analysis revealed that, compared to wild-type plants, CaSIP1-OX plants were hypersensitive to drought stress and hyposensitive to ABA. Collectively, our findings indicate that CaSIP1 negatively modulates the drought stress response via inhibiting CaSnRK2.6 kinase activity.

The transcription factor MYC1 interacts with FIT to negatively regulate iron homeostasis in Arabidopsis thaliana.

Iron (Fe) is an indispensable trace mineral element for the normal growth of plants, and it is involved in different biological processes; Fe shortage in plants can induce chlorosis and yield loss. The objective of this research is to identify novel genes that participated in the regulation of Fe-deficiency stress in Arabidopsis thaliana. A basic helix-loop-helix (bHLH) transcription factor (MYC1) was identified to be interacting with the FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) using a yeast-two-hybrid assay. Transcript-level analysis showed that there was a decrease in MYC1 expression in Arabidopsis to cope with Fe-deficiency stress. Functional deficiency of MYC1 in Arabidopsis leads to an increase in Fe-deficiency tolerance and Fe-accumulation, whereas MYC1-overexpressing plants have an enhanced sensitivity to Fe-deficiency stress. Additionally, MYC1 inhibited the formation of FIT and bHLH38/39 heterodimers, which suppressed the expressed level for Fe acquisition genes FRO2 and IRT1 during Fe-deficiency stress. These results showed that MYC1 functions as a negative modulator of the Fe-deficiency stress response by inhibiting the formation of FIT and bHLH38/39 heterodimers, thereby suppressing the binding of FIT and bHLH38/39 heterodimers to the promoters of FRO2 and IRT1 to modulate Fe intake during Fe-deficiency stress. Overall, the findings of this study elucidated the role of MYC1 in coping with Fe-deficiency stress, and provided potential targets for the developing of crop varieties resistant to Fe-deficiency stress.

The Involvement of Prolactin in Stress-Related Disorders.

The most important and widely studied role of prolactin (PRL) is its modulation of stress responses during pregnancy and lactation. PRL acts as a neuropeptide to support physiological reproductive responses. The effects of PRL on the nervous system contribute to a wide range of changes in the female brain during pregnancy and the inhibition of the hypothalamic-pituitary axis. All these changes contribute to the behavioral and physiological adaptations of a young mother to enable reproductive success. PRL-driven brain adaptations are also crucial for regulating maternal emotionality and well-being. Hyperprolactinemia (elevated PRL levels) is a natural and beneficial phenomenon during pregnancy and lactation. However, in other situations, it is often associated with serious endocrine disorders, such as ovulation suppression, which results in a lack of offspring. This introductory example shows how complex this hormone is. In this review, we focus on the different roles of PRL in the body and emphasize the results obtained from animal models of neuropsychiatric disorders.

The Endogenous Cannabinoid and the Nitricoxidergic Systems in the Modulation of Stress Responses.

The effects on stress-induced analgesia (SIA) from endogenous cannabinoid system (ECS) and nitric oxide (NO) interaction after 1 h of restraint stress were evaluated in male Wistar rats. The animals were subjected to 1 h of restraint and then injected with different combinations of cannabinoid receptor type 1 agonist anandamide (AEA) or antagonist AM251 along with an NO donor, NO precursor, or inhibitor of NO synthase. Nociception was evaluated using paw pressure (PP) or hot plate (HP) tests. AEA was administered immediately after the end of restraint-SIA (r-SIA). Administration of NO precursor reversed the pronociceptive effect of the CB1 agonist on r-SIA. Both the CB1 antagonist and the NOS inhibitor neutralized the pro-analgesic effect of L-arginine (L-arg). Administration of an NO donor, instead, increased r-SIA. Our experiments confirmed that the endogenous cannabinoid and the NO-ergic systems interact in the modulation of r-SIA. This interaction probably implies NO as a second messenger of the ECS.

Abstract TMP29: Elevated Levels Of Palmitic Acid Mediate Early Disruption Of Endothelial Barrier Integrity And Promote Behavioral Dysfunction Relevance To Vascular Cognitive Impairment And Dementia (VCID)

Increased consumption of a high-fat diet (HFD) is believed to increase the risk for the development and progression of VCID, but the underlying mechanisms of how HFD leads to cognitive impairment are unclear, partly due to the use of different HFD models in preclinical studies. Palmitic acid (PA), the most common form of saturated fatty acid, found in the human cerebrospinal fluid in obesity, promotes disruption of BBB integrity. We hypothesized that a PA-rich diet mediates early disruption of blood brain barrier (BBB) integrity which leads to progressive neurovascular pathologies and cognitive impairment in VCID. Methods: Experimental design for in vivo studies is depicted in Fig 1. In vitro studies included assessment of endothelial integrity by trans-endothelial electrical resistance (TEER) and FITC measurements, cell viability, and expression levels of tight junction proteins and cell stress markers (Hsp70, Occludin1, Claudin 5, and Carnitine Palmitoyl transferase 1A -CTP1A) in male BMVECs cultured in normal and high PA conditions. Results (Table): Animals that were on the PA-rich diet exhibited risk-taking behavior. BMVECs showed significantly increased permeability of FITC-dextran and decreased TEER measurements. While Hsp70 and CTP1A increased with PA treatment, tight junction protein levels did not change. Conclusion: A special PA-rich diet mediates an anxiety-like behavior as early as 8 weeks without any metabolic effects. Assessments at 22 and 24W will determine whether behavioral dysfunction worsens and progresses to cognitive deficits. In vitro results suggest that initiation of the stress response may be the underlying mechanism of early BBB impairment. Modulation of the endothelial stress response may prevent/attenuate the development/progression of cognitive deficits induced by a PA-rich diet.

RALF peptides modulate immune response in the moss Physcomitrium patens.

RAPID ALKALINIZATION FACTOR (RALFs) are cysteine-rich peptides that regulate multiple physiological processes in plants. This peptide family has considerably expanded during land plant evolution, but the role of ancient RALFs in modulating stress responses is unknown.Results: Here, we used the moss Physcomitrium patens as a model to gain insight into the role of RALF peptides in the coordination of plant growth and stress response in non-vascular plants. The quantitative proteomic analysis revealed concerted downregulation of M6 metalloprotease and some membrane proteins, including those involved in stress response, in PpRALF1, 2 and 3 knockout (KO) lines. The subsequent analysis revealed the role of PpRALF3 in growth regulation under abiotic and biotic stress conditions, implying the importance of RALFs in responding to various adverse conditions in bryophytes. We found that knockout of the PpRALF2 and PpRALF3 genes resulted in increased resistance to bacterial and fungal phytopathogens, Pectobacterium carotovorum and Fusarium solani, suggesting the role of these peptides in negative regulation of the immune response in P. patens. Comparing the transcriptomes of PpRALF3 KO and wild-type plants infected by F. solani showed that the regulation of genes in the phenylpropanoid pathway and those involved in cell wall modification and biogenesis was different in these two genotypes. Thus, our study sheds light on the function of the previously uncharacterized PpRALF3 peptide and gives a clue to the ancestral functions of RALF peptides in plant stress response.

Effect of the method of anesthetic aid on cellular immunity in periprosthetic infection of the hip joint: : a prospective open randomized study

BACKGROUND: Periprosthetic infection after primary hip replacement is a serious complication. For the anesthetic support of revision operations, both general and neuroaxial anesthesia methods can be used. The question of choosing an anesthetic aid that, with adequate modulation of the operational stress response, would have a minimal immunosuppressive effect is relevant.
 AIM: To examine the effect of general and combined spinalepidural anesthesia during revision operations in patients with periprosthetic hip joint infection on the parameters of cellular immunity.
 MATERIALS AND METHODS: An open prospective randomized study was performed on 25 patients (11 women and 14 men). The patients underwent surgical interventions of revision prosthetics with the replacement of all components of the prosthesis. Group 1 (n=10) underwent general anesthesia (GA), and group 2 (n=15) underwent surgery under combined spinalepidural anesthesia (CSEA). The indices of cellular immunity, namely, CD4+, CD8+, CD4+/CD8+, and B-lymphocytes, were evaluated. Blood sampling was performed in the morning on the day of surgery and then on days 1, 3, 5, and 7 after surgery.
 RESULTS: The CD4+ (%) level in the CSEA group was significantly higher than in the GA group on days 3 and 7 after surgery (p 0.05). Changes in the percentage of CD8+ lymphocytes, the immunoregulatory index, and the percentage of B-lymphocytes between the groups had no statistically significant differences.
 CONCLUSION: The CD4+ (%) level in the CSEA group was significantly higher than that in the GA group on days 3 and 7 after surgery (p 0.05). Statistically significant differences in the dynamics of CD8+, immunoregulatory index, and B-lymphocytes were not found, which may indicate a lesser effect of the type of anesthesia on these indicators.

Nepeta binaludensis Jamzad Attenuates Neuronal Injury Induced by Oxygen-Glucose-Serum Deprivation/Reperfusion in PC12 Cells

Background: Nepeta binaludensis Jamzad is a perennial medicinal plant with various pharmacological effects. However, the neuroprotective effects of Nepeta binaludensis extracts have not yet been investigated. This study aimed to examine the effects of N. binaludensis hydro-alcoholic extract (NBE) on oxidative stress markers and apoptosis-related proteins in PC12 cells exposed to oxygen-glucose deprivation/ reperfusion (OGD/R). Methods: PC12 cells were pretreated with NBE (at a concentration range of 10-200 μg/ml) before exposure to the OGD condition for 6 h, followed by a 24 h reoxygenation. Cell viability, the production of the reactive oxygen species (ROS), lipid peroxidation (LPO), and the levels of apoptosis-related proteins were evaluated using MTT, fluorimetry, and western blot analysis, respectively. Results: Survival of the cells preincubated for 6 h with NBE increased to 90.20 ± 15.62% compared with those subjected to OGD/R alone (51.26 ± 7.77 %, p < 0.001). ROS formation was also decreased following incubation with 200 μg/ml of NBE to 125.3 ± 18.38% compared to OGD/R group (356.9 ± 70.48%, p < 0.001). LPO was also suppressed after incubation with NBE to 155.5 ± 21.21% compared to the OGD/R group (260.5 ± 9.727%, p<0.001). NBE restored Bax/Bcl-2 ratio (1.3-fold of control), and cleaved caspase-3 (1.58-fold of control, p < 0.001). Conclusion: These results suggest that NBE may offer neuroprotection properties against OGD/Rinduced toxicity through modulation of oxidative stress and apoptotic responses.

Sex-based modulation of endoplasmic reticulum stress and antidepressant response in a mouse model of α-synucleinopathy

Sex-based modulation of endoplasmic reticulum stress and antidepressant response in a mouse model of α-synucleinopathy