Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular organisms is hypothesized. While mARS complexes in lower eukaryotes may enhance efficiency of aminoacylation, little evidence exists to support a similar role in chordates or other higher eukaryotes. Rather, mARS complexes are reported to regulate multiple and variegated cellular processes that include angiogenesis, apoptosis, inflammation, anaphylaxis, and metabolism. Because all such processes are critical components of immune homeostasis, it is important to understand the role of mARS complexes in immune regulation. Here we provide a conceptual analysis of the current understanding of mARS complex dynamics and emerging mARS complex roles in immune regulation, the increased understanding of which should reveal therapeutic targets in immunity and immune-mediated disease.

Symbiogenesis has been systematically exploited to understand consciousness as the aggregate of our physiology. The Symbiogenic mechanism for assimilation of factors in the environment formulates the continuum from inside the cell to the Cosmos, both consciousness and cosmology complying with the Laws of Nature. Since Symbiogenesis is \'constructive\', whereas eliminating what threatens us is \'destructive\', why do we largely practice Symbiogenesis? Hypothetically, Symbiogenesis recursively simulates the monism of our origin, recognizing \'something bigger than ourselves\'. That perspective explains many heretofore unexplained aspects of consciousness, such as mind, epigenetic inheritance, physiology, behaviors, social systems, mathematics, the Arts, from an a priori perspective. Moreover, there is an energetic continuum from Newtonian to Quantum Mechanics, opening up to a novel way of understanding the \'true nature of our being\', not as \'materialism\', but instead being the serial homeostatic control of energy. The latter is consistent with the spirit of Claude Bernard and Walter B. Cannon\'s perspectives on physiology. Such a paradigm shift is overdue, given that materialism is causing the destruction of the Earth and ourselves.

The ectoderm is the outermost of the three germ layers of the early embryo that arise during gastrulation. Once the germ layers are established, the complex interplay of cellular proliferation, differentiation, and migration results in organogenesis. The ectoderm is the progenitor of both the surface ectoderm and the neural ectoderm. Notably, the surface ectoderm develops into the epidermis and its associated appendages, nails, external exocrine glands, olfactory epithelium, and the anterior pituitary. Specification, development, and homeostasis of these organs demand a tightly orchestrated gene expression program that is often dictated by epigenetic regulation. In this review, we discuss the recent discoveries that have highlighted the importance of chromatin regulatory mechanisms mediated by transcription factors, histone and DNA modifications that aid in the development of surface ectodermal organs and maintain their homeostasis post-development.

Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRβ, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRβ as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases.

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress.
RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage.
CONCLUSIONS: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

The triglyceride-glucose (TyG) index is a simple and inexpensive new marker of insulin resistance that is being increasingly used for the clinical prediction of metabolic syndrome (MetS). Nevertheless, there are only a few comparative studies on its predictive capacity for MetS versus those using the traditional homeostasis model assessment (HOMA). We conducted a cross-sectional study using a database from the National Health and Nutrition Examination Survey (1999 March to 2020 pre-pandemic period). Using statistical methods, we compared the predictive abilities of the TyG index and HOMA (including HOMA of insulin resistance [HOMA-IR] and HOMA of beta-cell function [HOMA-β]) for MetS. A total of 34,195 participants were enrolled and divided into the MetS group (23.1%) or no MetS group (76.9%) according to the International Diabetes Federation (IDF) diagnostic criteria. After applying weighted data, the baseline characteristics of the population were described. Following the exclusion of medication influences, the final count was 31,304 participants. Receiver operating characteristic curve analysis revealed that while distinguishing between MetS and no MetS, the TyG index had an area under the curve (AUC) of 0.827 (sensitivity = 71.9%, specificity = 80.5%), and the cutoff was 8.75, slightly outperforming HOMA-IR (AUC = 0.784) and HOMA-β (AUC = 0.614) with a significance of P < 0.01. The prevalence of MetS in the total population calculated using the TyG index cutoff value was 30.9%, which was higher than that reported in the IDF diagnostic criteria. Weighted data analysis using univariate and multivariate logistic regression displayed an independent association between elevated TyG and HOMA-IR with the risk of MetS. Subgroup analysis further revealed differences in the predictive ability of the TyG index among adult populations across various genders and ethnicities, whereas such differences were not observed for children and adolescents. The TyG index is slightly better than HOMA in predicting MetS and may identify more patients with MetS; thus, its applications in a clinical setting can be appropriately increased.

The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its role in regulating lipid homeostasis remains not fully understood. Here, we report that the activation of canonical Wnt/Wg signaling promotes lipolysis while concurrently inhibiting lipogenesis and fatty acid β-oxidation in both larval and adult adipocytes, as well as cultured S2R+ cells, in Drosophila. Using RNA-sequencing and CUT&RUN (Cleavage Under Targets & Release Using Nuclease) assays, we identified a set of Wnt target genes responsible for intracellular lipid homeostasis. Notably, active Wnt signaling directly represses the transcription of these genes, resulting in decreased de novo lipogenesis and fatty acid β-oxidation, but increased lipolysis. These changes lead to elevated free fatty acids and reduced triglyceride (TG) accumulation in adipocytes with active Wnt signaling. Conversely, downregulation of Wnt signaling in the fat body promotes TG accumulation in both larval and adult adipocytes. The attenuation of Wnt signaling also increases the expression of specific lipid metabolism-related genes in larval adipocytes, wing discs, and adult intestines. Taken together, these findings suggest that Wnt signaling-induced transcriptional repression plays an important role in regulating lipid homeostasis by enhancing lipolysis while simultaneously suppressing lipogenesis and fatty acid β-oxidation.

The liver is a vital organ that continuously adapts to a wide and dynamic diversity of self-antigens and xenobiotics. This involves the active contribution of immune cells, particularly by the liver-resident macrophages, the Kupffer cells (KCs), which exert a variety of central functions in liver homeostasis and disease. As such, KCs interact with their microenvironment to shape the hepatic cellular landscape, control gut-derived signal integration, and modulate metabolism. On injury, the rapid recruitment of bone marrow monocyte-derived macrophages alters this status quo and, when unrestrained, drastically compromises liver homeostasis, immune surveillance, and tissue organization. Several factors determine the functional roles of liver macrophages in these processes, such as their ontogeny, activation/polarization profile and, importantly, spatial distribution within the liver. Loss of tolerance and adaptability of the hepatic immune environment may result in persistent inflammation, hepatic fibrosis, cirrhosis, and a tumorigenic niche promoting liver cancer. In this review, we aim at providing the most recent breakthroughs in our understanding of liver macrophage biology, particularly their diversity and adaptability in the hepatic spatiotemporal context, as well as on potential therapeutic interventions that may hold the key to tackling remaining clinical challenges of varying etiologies in hepatology.

Mutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome. In contrast, prostate tumors with high pSHP2 and pACK1 activity exhibited progressive downregulation of pY54-H3 levels and higher AR expression that correlated with disease severity. Overall, pSHP2/pY54-H3 signaling acts as a sentinel of AR homeostasis, explaining not only growth retardation, genital abnormalities and infertility among NSML patients, but also significant AR upregulation in prostate cancer patients.

Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease.