Physiological Regulation Research Articles

Long Non-Coding RNA LOC113219358 Regulates Immune Responses in Apis mellifera Through Protein Interactions.

Long non-coding RNAs (lncRNAs) are emerging as critical regulators in honeybee physiology, influencing development, behavior, and stress responses. This study investigates the role of lncRNA LOC113219358 in the immune response and neurophysiological regulation of Apis mellifera brains. Using RNA interference (RNAi) and RNA sequencing (RNA-seq), we demonstrate that silencing lncLOC113219358 significantly alters the expression of 162 mRNA transcripts, including genes associated with detoxification, energy metabolism, and neuronal signaling. Functional enrichment analysis revealed involvement in neuropeptide signaling, ATP synthesis, and oxidative phosphorylation pathways. Acetylcholinesterase (AChE), Glutathione-S-transferase (GST) and cytochrome P450 (CYP450) activities were significantly downregulated with 48 h of RNAi treatment. Additionally, RNA pull-down assays identified 113 proteins interacting with lncLOC113219358, including ATP synthase subunits, heat shock proteins, and major royal jelly proteins, suggesting its role in cellular stress responses and neural activity modulation. These findings provide mechanistic insights into how lncLOC113219358 mediates honeybee responses to environmental stressors, contributing to our understanding of lncRNA-regulated neural and immune functions in pollinators.

Kisspeptin and Neurokinin B: roles in reproductive health.

Kisspeptin and neurokinin B (NKB) play a key role in several physiological processes including in puberty, adult reproductive function including the menstrual cycle, as well as mediating the symptoms of menopause. Infundibular kisspeptin neurons, which co-express NKB, regulate the activity of gonadotropin releasing hormone (GnRH) neurons, and thus the physiological pulsatile secretion of GnRH from the hypothalamus. Outside of their hypothalamic reproductive roles, these peptides are implicated in several physiological functions including sexual behavior and attraction, placental function, and bone health. Over the last two decades, research findings have considerably enhanced our understanding of the physiological regulation of the hypothalamic-pituitary-gonadal (HPG) axis and identified potential therapeutic applications. For example, recognition of the role of kisspeptin as the natural inductor of ovulation has led to research investigating its use as a safer, more physiological trigger of oocyte maturation in <em>in vitro</em> fertilization (IVF) treatment. Moreover, the key role of NKB in the pathophysiology of menopausal hot flashes has led to the development of pharmacological antagonism of this pathway. Indeed, Fezolinetant, a neurokinin 3 receptor antagonist, has recently received Food and Drug Administration (FDA) approval for clinical use to treat menopausal vasomotor symptoms. Herein, we discuss the roles of kisspeptin and NKB in human physiology, including in the regulation of puberty, menstrual cyclicity, reproductive behavior, pregnancy, menopause, and bone homeostasis. We describe how perturbations of these key physiological processes can result in disease states and consider how kisspeptin and NKB could be exploited diagnostically, as well as therapeutically to treat reproductive disorders.

A high-throughput platform for single-molecule tracking identifies drug interaction and cellular mechanisms.

The regulation of cell physiology depends largely upon interactions of functionally distinct proteins and cellular components. These interactions may be transient or long-lived, but often affect protein motion. Measurement of protein dynamics within a cellular environment, particularly while perturbing protein function with small molecules, may enable dissection of key interactions and facilitate drug discovery; however, current approaches are limited by throughput with respect to data acquisition and analysis. As a result, studies using super-resolution imaging are typically drawing conclusions from tens of cells and a few experimental conditions tested. We addressed these limitations by developing a high-throughput single-molecule tracking (htSMT) platform for pharmacologic dissection of protein dynamics in living cells at an unprecedented scale (capable of imaging >106 cells/day and screening >104 compounds). We applied htSMT to measure the cellular dynamics of fluorescently tagged estrogen receptor (ER) and screened a diverse library to identify small molecules that perturbed ER function in real time. With this one experimental modality, we determined the potency, pathway selectivity, target engagement, and mechanism of action for identified hits. Kinetic htSMT experiments were capable of distinguishing between on-target and on-pathway modulators of ER signaling. Integrated pathway analysis recapitulated the network of known ER interaction partners and suggested potentially novel, kinase-mediated regulatory mechanisms. The sensitivity of htSMT revealed a new correlation between ER dynamics and the ability of ER antagonists to suppress cancer cell growth. Therefore, measuring protein motion at scale is a powerful method to investigate dynamic interactions among proteins and may facilitate the identification and characterization of novel therapeutics.

Epibrassinolide Regulates Lhcb5 Expression Though the Transcription Factor of MYBR17 in Maize.

Photosynthesis, which is the foundation of crop growth and development, is accompanied by complex transcriptional regulatory mechanisms. Research has established that brassinosteroids (BRs) play a role in regulating plant photosynthesis, with the majority of research focusing on the physiological level and regulation of rate-limiting enzymes in the dark reactions of photosynthesis. However, studies on their effects on maize photosynthesis, specifically on light-harvesting antenna proteins, have yet to be conducted. The peripheral light-harvesting antenna protein Lhcb5 is crucial for capturing and dissipating light energy. Herein, by analyzing the transcriptomic data of maize seedling leaves treated with 24-epibrassinolide (EBR) and verifying them using qPCR experiments, we found that the MYBR17 transcription factor may regulate the expression of the photosynthetic light-harvesting antenna protein gene. Further experiments using protoplast transient expression and yeast one-hybrid tests showed that the maize transcription factor MYBR17 responds to EBR signals and binds to the promoter of the light-harvesting antenna protein Lhcb5, thereby upregulating its expression. These results were validated using an Arabidopsis mybr17 mutant. Our results offer a theoretical foundation for the application of BRs to enhance the photosynthetic efficiency of maize.

Discrimination, sleep, and physical health: Moderation by respiratory sinus arrythmia reactivity

Discrimination (unfair treatment due to group membership) is relatively common among adolescents and has been linked to poor sleep and physical health. Individual differences in physiological functioning may moderate these associations. A sample of 323 youth (48% boys, 52% girls; 58.5% White, 40.9% Black, Mage = 17.38 years, SD = 10.18 months) participated. Adolescents reported on discrimination and health, wore actigraphs to measure sleep, and came to the laboratory to assess respiratory sinus arrythmia reactivity (RSA-R) to two stressful tasks. Results indicate that discrimination was directly associated with health. Furthermore, discrimination interacted with RSA-R to predict sleep and health. Discrimination was related to more sleep activity and poorer health when RSA increased relative to baseline (augmentation), and better sleep quality (higher efficiency, fewer long wake episodes), when RSA decreased relative to baseline (suppression). Findings support the importance of examining physiological regulation as a protective/vulnerability factor when attempting to explicate relations between discrimination and health.

Mechanisms of the Effect of Starvation Duration on the Regulation of Feeding Rhythm and Metabolic Physiology of Cultured Large Yellow Croaker (Larimichthys crocea)

In recent years, significant progress has been made in China in the field of deep-sea large yellow croaker (Larimichthys crocea) farming. Compared with the traditional inshore aquaculture model, deep-sea culture of large yellow croaker enjoys a wider growing space with better water quality, thus enhancing fish quality. However, deep-sea aquaculture also faces challenges such as typhoons and strong currents, which often lead to prolonged starvation in fish. Therefore, in order to further promote the technological advancement of large yellow croaker in the field of deep-sea aquaculture, this experiment aimed to investigate the effects of varying starvation durations on the feeding rhythm and physiological state of large yellow croaker. With an initial body mass of 122.62 ± 11.08 g and a body length of (17.9 ± 1.04) cm as the samples, the experiment was divided into five groups, which were starved for 0 d (S0), 2 d (S2), 4 d (S4), 8 d (S8), and 16 d (S16) before resumption of feeding. The results were as follows: under starvation stress for 8 consecutive days, the total duration of feeding gradually decreased in large yellow croaker, but increased at starvation up to 16 days. Each replicate group had 50 large yellow croakers as test subjects, for a total of 750 large yellow croakers. Analyzing the linear regression equations of S0 with S2, S4, S8, and S16 groups, it was found that the trend of rate of change in feeding duration was consistent with the total duration of feeding, i.e., it decreased during 8 days and increased at 16 days. It indicated that the rate of feeding of large yellow croaker was accelerated within 8 days of starvation, while the rate of feeding was slowed down at 16 days of starvation. Furthermore, the blood glucose concentration of large yellow croaker decreased significantly after 8 days of starvation, while it rebounded significantly in the S16 group. Meanwhile, large areas of fatty degeneration were observed in the liver on the 8th day of starvation, followed by extensive hepatocyte necrosis on the 16th day. After resumption of feeding, there was some recovery within 4 days, but hepatocytes were still extensively edematous in the S8 and S16 groups. Meanwhile, the expression of inflammatory factor genes such as IL-1β, IL-10 and TNF-α in the liver increased with the prolongation of starvation time, in which both S8 and S16 groups in the liver were significantly different from the S0 group, and after resumption of feeding, the IL-1β and TNF-α genes of the S8 and S16 groups were significantly different from those of the normal feeding group (p &lt; 0.05), while there was no differentiation for the IL-10 gene. Therefore, based on the results of this study, it is recommended to limit the duration of starvation in the large yellow croaker to no more than 8 days.

Effect of air temperature in indoor transition spaces on the thermal response of occupant during summer

During the hot summer months, the significant temperature disparity between outdoor and indoor air-conditioned spaces can lead to thermal discomfort and pose a potential health risk. Transition areas such as corridors and elevator lobbies, serving as intermediary zones connecting indoors and outdoors, have been found effective in mitigating this thermal discomfort. In this study, three different temperatures (25 °C-case 1, 27 °C-case 2, and 29 °C-case 3) were employed to investigate the dynamic physiological regulation and thermal perception response of individuals when transitioning from an outdoor environment into an indoor neutral room through a transition space. The findings revealed that mTsk decreased by 0.31 °C, 0.13 °C, and 0.07 °C; TSV decreased by 1.63, 1.56, and 0.9 units; while TCV increased by 1.9, 2.16 ,and 0.81units for cases1-3 respectively indicating that an air temperature of around 27 °C is most suitable for achieving optimal comfort levels in these transition spaces. The correlation between UTCI index with MTSV was stronger compared to PET or SET* throughout the entire process; moreover, a better linear relationship was observed between ΔTSV and ΔT than ΔTCV. Furthermore, a second-order polynomial function model was established using dissatisfaction rate at initial entry moment into new environment along with operative temperature difference, resulting in acceptable temperatures ranging from 25.3 °C to 27.93 °C within current experimental conditions.

Protective effects of small RNAs encapsulated in Artemisia Capillaris-derived exosomes against non-alcoholic fatty liver disease.

Artemisia capillaris, a traditional medicinal plant, is renowned for its therapeutic properties, including the promotion of anti-inflammatory and bile secretion. Notably, it has demonstrated efficacy in the treatment of jaundice. This study aimed to evaluate the potential of Artemisia capillaris-derived exosomes (ACDEs) as a novel therapeutic approach in non-alcoholic fatty liver disease (NAFLD). The physicochemical properties of ACDEs were isolated and characterized using differential centrifugation, and the therapeutic efficacy was evaluated in an in vivo methionine-choline-deficient (MCD) diet induced NAFLD mouse model. In vitro, mouse hepatocytes were treated with palmitic acid (PA) to simulate a high fat environment. Intracellular triglycerides (TG) and total cholesterol (TC) levels were quantified, and Oil Red O staining was assessed. Additionally, the expression levels of proteins and RNAs associated with lipogenesis and inflammation were analyzed. The NAFLD mouse model exhibited notable liver damage, including lipid deposition and inflammatory responses. However, treatment with ACDEs exhibited broad pharmacological activities, effectively reversing hepatic lipid accumulation and inflammatory damage. In vitro experiments revealed that ACDEs were internalized by AML12 cells via macropinocytosis and caveolin-mediated endocytosis. This treatment ameliorated dysregulated lipid metabolism and inhibited inflammatory responses. High throughput sequencing further identified a distinct small RNA profile in ACDEs, indicating the potential involvement in interspecies physiological regulation. In conclusion, this study provides evidence for the therapeutic potential of ACDEs in NAFLD and offers a novel perspective for the development of Artemisia capillaris-based therapies for NAFLD, related metabolic disorders, and hepatitis.

Regulation of physiological and pathological condensates by molecular chaperones.

Biomolecular condensates are dynamic membraneless compartments that regulate a myriad of cellular functions. A particular type of physiological condensate called stress granules (SGs) has gained increasing interest due to its role in the cellular stress response and various diseases. SGs, composed of several hundred RNA-binding proteins, form transiently in response to stress to protect mRNAs from translation and disassemble when the stress subsides. Interestingly, SGs contain several aggregation-prone proteins, such as TDP-43, FUS, hnRNPA1, and others, which are typically found in pathological inclusions seen in autopsy tissues from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. Moreover, mutations in these genes lead to the familial form of ALS and FTD. This has led researchers to propose that pathological aggregation is seeded by aberrant SGs: SGs that fail to properly disassemble, lose their dynamic properties, and become pathological condensates which finally 'mature' into aggregates. Here, we discuss the evidence supporting this model for various ALS/FTD-associated proteins. We further continue to focus on molecular chaperone-mediated regulation of ALS/FTD-associated physiological condensates on one hand, and pathological condensates on the other. In addition to SGs, we review ALS/FTD-relevant nuclear condensates, namely paraspeckles, anisosomes, and nucleolar amyloid bodies, and discuss their emerging regulation by chaperones. As the majority of chaperoning mechanisms regulate physiological condensate disassembly, we highlight parallel themes of physiological and pathological condensation regulation across different chaperone families, underscoring the potential for early disease intervention.

Pumpkin Rootstocks Improve the Low-temperature Resistance of Bitter Gourd through Physiological Regulation

Bitter gourd (Momordica charantia L.) is one of the Cucurbitaceae species that is sensitive to low temperatures. Grafting onto pumpkin rootstock is an effective technique to increase the chilling tolerance of the Cucurbitaceae species upon exposure to low-temperature stress. However, research on the mechanism by which pumpkin rootstock increases chilling tolerance of bitter gourd remains limited. In this study, bitter gourd ‘Baoyu No.2’ was used as the scion, and pumpkin ‘Dongfang Changsheng’ served as the rootstock; self-rooted seedlings are used as a control. The grafted and self-rooted bitter gourd seedlings were exposed to low-temperature stress (10 °C) for 10 days and allowed to recover for 1 day at 25 °C/20 °C (D/N). Changes in chilling damage index, osmotic regulatory substance contents, antioxidant enzyme activity, and chlorophyll fluorescence induction kinetics were determined. We found that the malondialdehyde (MDA) and proline (PRO) levels in the leaves of both self-rooted and grafted bitter gourd seedlings, as well as the activity of antioxidant enzymes, including superoxide dismutase (SOD) and peroxidase (POD), tended to increase overall with increasing duration of low-temperature stress. After 10 days of low-temperature stress, the PRO content of grafted seedlings increased by 312.77% compared with the self-rooted seedlings. The SOD activity increased by 46.19%, and the POD activity increased by 4.66%. Under low-temperature stress, the chlorophyll fluorescence induction kinetics (OJIP) curves of both self-rooted and grafted seedlings clearly changed. As the low-temperature stress duration increased, the maximum fluorescence intensity (P) decreased compared with 0 day, and the J-I-P curve tended to flatten. However, the decline and flattening for grafted seedlings were weaker than those for self-rooted seedlings. After 3 days of low-temperature stress, the Fv/Fm of the self-rooted seedlings reached its lowest point of 0.63, which was 24.10% lower and 18.18% lower than that noted at 0 day and for the grafted seedlings, respectively. The PIABS of the self-rooted seedlings reached its lowest point of 0.61, which was 86.76% lower than that noted at 0 day and 68.88% lower than the grafted seedlings. Furthermore, after 3 days of low-temperature stress, the absorption per active reaction center (ABS/RC) of the self-rooted seedlings increased by 25.19% compared with 0 day and 26.54% compared with the grafted seedlings. Moreover, the dissipation energy per active reaction center (DIo/RC) of the self-rooted seedlings was 179.43% of that noted at 0 day and 108.45% greater than that of the grafted seedlings.

Developmental expression patterns of gonadal hormone receptors in arcuate kisspeptin and GABA neurons of the postnatal female mouse.

The arcuate nucleus of the hypothalamus (ARC) is central in the neuronal regulation of fertility and reproduction through translating gonadal steroid hormone cues into the GnRH signaling pathway in the brain. Evidence suggests that circulating gonadal steroids play an important role in modulating female reproduction via kisspeptin and γ-aminobutyric acid (GABA) neurons in the ARC in both development and adulthood. However, the temporal onset of these ARC neurons' sensitivity to gonadal steroids is unknown. Using RNAscope® in situ hybridization, we localized androgen receptor (Ar), estrogen receptor alpha (Esr1), and progesterone receptor (Pgr) expression in ARC kisspeptin or GABA neurons of female mice at postnatal day (P)4, P8, P12, P20, and P60. A probe that binds to kiss1 mRNA or vGat mRNA was used to produce signal in kisspeptin or GABA neurons, respectively. In adult, we identified that the vast majority of kisspeptin neurons coexpressed Esr1 (95%) and Pgr (93%), while a smaller proportion coexpressed Ar (66%). Similar proportions of Ar- or Esr1-positive kisspeptin neurons were seen from P4, suggesting that kisspeptin neurons develop adult-like sensitivity to androgen and estrogen in early postnatal life. In contrast, the proportion of Pgr-positive kisspeptin cells in early life was significantly lower than in adulthood, suggesting that progesterone sensitivity develops over time in the ARC kisspeptin population. ARC GABA neurons also colocalized with Ar (70%), Esr1 (64%), or Pgr (85%) in adulthood. GABA neurons continuously expressed Esr1 or Pgr from the postnatal stages to adulthood, while the proportion of Ar-positive GABA neurons gradually increased from P4 (24%) to P20 (59%). These results suggest that while ARC GABA neurons can respond to circulating estrogen and progesterone from early postnatal ages, this same population may become more sensitive to androgens during later postnatal life. Our findings identified the expression patterns of Ar, Esr1, and Pgr by ARC kisspeptin and GABA neurons during early postnatal life. These data provide the understanding for the hormone sensitivity of these populations during early postnatal life, the critical time for the formation and regulation of female reproductive physiology.Esr1 (95%) and Pgr (93%), while a smaller proportion coexpressed Ar (66%). Similar proportions of Ar- or Esr1-positive kisspeptin neurons were seen from P4, suggesting that kisspeptin neurons develop adult-like sensitivity to androgen and estrogen in early postnatal life. In contrast, the proportion of Pgr-positive kisspeptin cells in early life was significantly lower than in adulthood, suggesting that progesterone sensitivity develops over time in the ARC kisspeptin population. ARC GABA neurons also colocalized with Ar (70%), Esr1 (64%), or Pgr (85%) in adulthood. GABA neurons continuously expressed Esr1 or Pgr from the postnatal stages to adulthood, while the proportion of Ar-positive GABA neurons gradually increased from P4 (24%) to P20 (59%). These results suggest that while ARC GABA neurons can respond to circulating estrogen and progesterone from early postnatal ages, this same population may become more sensitive to androgens during later postnatal life. Our findings identified the expression patterns of Ar, Esr1, and Pgr by ARC kisspeptin and GABA neurons during early postnatal life. These data provide the understanding for the hormone sensitivity of these populations during early postnatal life, the critical time for the formation and regulation of female reproductive physiology.

Mammalian Mitochondrial Inorganic Polyphosphate (polyP) and Cell Signaling: Crosstalk Between PolyP and the Activity of AMPK.

In this manuscript, we explored the intriguing possibility that the effects of polyP on signal transduction could be mechanistically linked to those exerted on bioenergetics. To conduct our studies, we used a combination of cellular and animal models. Our findings demonstrate for the first time the intimate crosstalk between the levels of polyP and the activation status of the AMPK signaling pathway, via a mechanism involving free phosphate homeostasis. AMPK is a key player in mammalian cell signaling, and a crucial regulator of cellular and mitochondrial homeostasis. Our results show that the depletion of mitochondrial polyP in mammalian cells downregulates the activity of AMPK. Moreover, increased levels of polyP activate AMPK. Accordingly, the genetic downregulation of AMPKF0611 impairs polyP levels in both SH-SY5Y cells and in the brains of female mice. This manuscript sheds new light on the regulation of AMPK and positions polyP as a potent regulator of mammalian cell physiology beyond mere bioenergetics, paving the road for using its metabolism as an innovative pharmacological target in pathologies characterized by dysregulated bioenergetics.

Transcriptional profile of the rat cardiovascular system at single cell resolution

We sought to characterize cellular composition across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We performed single-nucleus RNA sequencing (snRNA-seq) in 78 samples in 10 distinct regions, including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins, which produced 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, with different cellular composition across cardiac regions and tissue-specific transcription for each cell type. Several cell subtypes were region specific, including a subtype of vascular smooth muscle cells enriched in the large vasculature. We observed tissue-enriched cellular communication networks, including heightened Nppa-Npr1/2/3 signaling in the sinoatrial node. The existence of tissue-restricted cell types suggests regional regulation of cardiovascular physiology. Our detailed transcriptional characterization of each cell type offers the potential to identify novel therapeutic targets and improve preclinical models of cardiovascular disease.

Neurosteroids and Translocator Protein (TSPO) in neuroinflammation.

Neurosteroids have a crucial role in physiological intrinsic regulations of the Central Nervous System functions. They are derived from peripheral steroidogenic sources and from the de novo neurosteroidogenic capacity of brain cells. Significant alterations of neurosteroid levels have been frequently observed in neuroinflammation and neurodegenerative diseases. Such level fluctuations may be useful for both diagnosis and treatment of these pathological conditions. Beyond steroid administration, enhancing the endogenous production by Translocator Protein (TSPO) targeting has been proposed to restore these altered pathological levels. However, the neurosteroid quantification and the prediction of their final effects are often troublesome, sometimes controversial and context dependent, due to the complexity of neurosteroid biosynthetic pathway and to the low produced amounts. The aim of this review is to report recent advances, and technical limitations, in neurosteroid-related strategies against neuroinflammation.

The antimicrobial effects of nitric oxide: A narrative review.

Nitric oxide (NO) is a versatile endogenous molecule with multiple physiological roles, including neurotransmission, vasodilation, and immune regulation. As part of the immune response, NO exerts antimicrobial effects by producing reactive nitrogen species (RNS). These RNS combat pathogens via mechanisms such as DNA deamination, S-nitrosylation of thiol groups, and lipid peroxidation, leading to disruptions in microbial cell membranes and vital protein functions. Due to these broad actions, NO targets many pathogens, including bacteria, fungi, and viruses, with minimal risk of resistance development. Given its potent antimicrobial properties, the therapeutic potential of exogenous NO has been recently studied. Various preparations, such as NO donors, inhaled gaseous NO, and topical preparations, have shown promising results in preclinical and clinical settings. This literature review examines the antimicrobial effects of exogenous NO reported in in vitro studies, animal models, and human clinical trials. We provide an overview of the mechanisms by which NO exerts its antimicrobial activity, highlighting its efficacy against diverse pathogens. By presenting the current findings, we aim to contribute to the growing body of evidence supporting the use of NO as a versatile antimicrobial agent in clinical practice.

Autoimmune Thyroid Disease and Pregnancy: The Interaction Between Genetics, Epigenetics and Environmental Factors

Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly pronounced risk during the reproductive years. Pregnancy exerts profound effects on thyroid physiology and immune regulation due to hormonal fluctuations and immune adaptations aimed at fostering maternal–fetal tolerance, potentially triggering or exacerbating AITD. The impact of AITD on pregnancy outcomes is multifaceted. Both HT and GD have been associated with adverse obstetric and neonatal outcomes, including miscarriage, preterm delivery, preeclampsia and fetal growth restriction. Inadequately managed AITD can also affect fetal neurodevelopment due to disrupted maternal thyroid hormone availability during critical periods of brain maturation. This review explores the complex interplay between the genetic, epigenetic and environmental factors that drive AITD during pregnancy, highlighting their roles in disease development and impacts on pregnancy outcomes. Gaining a deeper understanding of these mechanisms is crucial for improving diagnostic tools, treatment options and preventive measures to enhance the health and well-being of both the mother and the newborn.

Dimensions of childhood adversity differentially affect autonomic nervous system coordination in response to stress

It is well-established that disrupted autonomic nervous system (ANS) reactivity exacerbates risk for long-term maladjustment following childhood adversity (CA). However, few studies have integrated measures of both the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS, resulting in a unidimensional understanding of ANS functioning as a mechanism of risk. Further, past work has primarily measured CA only at the aggregate level (e.g. “total CA”), necessitating further research to accurately characterize this risk pathway. The present study examines how CA, measured cumulatively and dimensionally (i.e. CA characterized by threat versus deprivation), moderates the association between the SNS and PNS at rest and in response to acute social and nonsocial stressors. Participants included 97 adolescents ages 10-15 (Mage = 12.22, SD age = 1.68) experiencing a range of CA and one accompanying caregiver. Participants completed questionnaires assessing prior CA exposure. SNS and PNS responses were then continuously measured during rest and two stress tasks. First, results indicate a blunting effect of cumulative CA and CA characterized by threat (e.g. physical abuse) on resting SNS activity. Second, in moderation analyses assessing ANS coordination, threat exposure emerged as a significant moderator of the association between SNS and PNS reactivity to social stress. Results suggest that CA characterized by threat may specifically impact physiologic regulation by disrupting the coordination of the two branches of the ANS. Disentangling the independent and concurrent engagement of biological stress response systems following CA remains an important target for research to identify the etiology of aberrant stress reactivity patterns.

CHANGES IN PERSONALITY TRAITS PREDICT ALLOSTATIC LOAD

Abstract Understanding the influences personality change has on physical health has been identified as a key direction for personality research (Leszko et al., 2016). One key indicator of health and aging process is allostatic load, an objective index capturing physiological regulation (or dysregulation) across a variety of biological systems (e.g., inflammation, cardiovascular health). While some evidence suggests cross sectional associations between personality traits and allostatic load in older adult populations (Yoneda et al., 2023), little research at present has assessed if changes in personality are also associated with allostatic load. The present study utilizes the Midlife Development in the United States (MIDUS) data set (N = 998; Mean age = 46.14; range = 25-74), to analyze change scores in personality traits at two time points (1994-1995 to 2004-2005) as predictors of allostatic load at a subsequent time point (2004-2009). Age, race, gender, education level (at 1994-1995) and baseline level of personality traits were used as covariates. Regression analyses revealed that increases in openness (b = -.20, p =.034) and decreases in agreeableness (b =.27, p =.004) were associated with a lower allostatic load. These findings have implications for considering the role personality development has on healthy aging. Given that naturalistic change in personality does associate with important markers of physical health and physiological processes, future studies could attempt to intervene at the level of personality (e.g., attempt to increase openness) in order to promote more optimal physical health and aging processes.

Engineered tRNAs efficiently suppress CDKL5 premature termination codons

The CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disorder characterized by early-onset epilepsy, intellectual disability, motor and visual dysfunctions. The causative gene is CDKL5, which codes for a kinase required for brain development. There is no cure for CDD patients; treatments are symptomatic and focus mainly on seizure control. Several pathogenic variants are loss-of-function, but recent studies suggest that the CDD phenotype is sensitive to the CDKL5 gene dosage. Therefore, mRNA-targeted correction strategies that respect the physiological regulation of CDKL5 could be a valid alternative to augmentative gene therapy. Nonsense mutations cause ~ 11% of CDD cases, and these patients might benefit from readthrough therapies. We proved that drug-mediated readthrough efficiently suppresses premature CDKL5 nonsense codons, but the recoded kinase remained highly hypomorphic, curtailing the translational value of this pharmacological approach. In this study we explored if the recently developed Anticodon-edited tRNAs (ACE-tRNAs) offer an alternative readthrough strategy for CDD. Transfecting cells expressing different CDKL5 nonsense variants, we demonstrated that ACE-tRNAs efficiently restore full-length kinase synthesis. The recoded CDKL5 is correctly localized and catalytically active, thereby bringing tRNA-based therapy back into the spotlight for future investigations to assess the efficacy of this approach in correcting the pathological phenotype of CDD.

Emotion, attention and stress regulation as markers of resilience in male and female Israeli soldiers during the Israel-Hamas war.

Psychological resilience is a key factor for societal and military stability when faced with terror attacks and/or war. The research presents physiological findings-obtained with the electrodermal activity (EDA) and Auditory Sustained Attention Test (ASAT)-on stress responses, attentional and emotion regulation abilities in 57 Israel Defense Force male and female combat soldiers during the ongoing Israel-Hamas war. In addition, it shows self-reported resilience scores and post traumatic symptomatology measured by questionnaires and explores the relationship between the subjective and objective data. Compared to male soldiers, female soldiers showed significantly higher hyperarousal symptoms yet showed a tendency to a significantly lower specific skin conductance response (on the EDA) to the first startle sound. Furthermore, the self-reported acute stress symptoms positively and significantly correlated with the physiological emotion regulation measured by startle responses, and negatively correlated with attentional regulation measured by the ASAT. The lack of gender differences in stress level, resilience and self-regulation abilities emphasizes the high capabilities of women combat soldiers, especially due to gender-related risks in combat. Relatively high scores of acute stress symptomology in the population of combat soldiers invite later screening and assessment for the prevention of post traumatic disorders in vulnerable individuals. The combination of physiological measures and questionnaires highlights possible report biases, and thus underscores the importance of combining these objective/subjective measures for adequate assessment of resilience and post traumatic symptomology.