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The security of animal habitats, such as burrows and nests, is vital for their survival and essential activities, including eating, mating, and raising offspring. Animals instinctively exhibit defensive behaviors to protect themselves from imminent and potential threats. In 1963, researchers reported wild rats sealing the entrances to their burrows from the inside using materials such as mud, sand, and vegetation. This behavior, known as "entrance sealing (ES)," involves repetitive movements of their nose/mouth and forepaws and is likely a proactive measure against potential intruders, which enhances burrow security. These observations provide important insights into the animals' ability to anticipate potential threats that have not yet occurred and take proactive actions. However, this behavior lacks comprehensive investigation, and the neural mechanisms underpinning it remain unclear. Hypothalamic perifornical neurons expressing urocortin-3 respond to novel objects/potential threats and modulate defensive responses to the objects in mice, including risk assessment and burying. In this study, we further revealed that chemogenetic activation of these neurons elicited ES-like behavior in the home-cage. Furthermore, behavioral changes caused by activating these neurons, including manifestations of ESlike behavior, marble-burying, and risk assessment/burying of a novel object, were effectively suppressed by selective serotonin-reuptake inhibitors. The c-Fos analysis indicated that ES-like behavior was potentially mediated through GABAergic neurons in the lateral septum. These findings underscore the involvement of hypothalamic neurons in the anticipation of potential threats and proactive defense against them. The links of this security system with the manifestation of repetitive/stereotypic behaviors and the serotonergic system provide valuable insights into the mechanisms underlying the symptoms of obsessive-compulsive disorder. [ABSTRACT FROM AUTHOR]

Immune cells infiltrate adipose tissues and provide a framework to regulate energy homeostasis. However, the precise underlying mechanisms and signaling by which the immune system regulates energy homeostasis in metabolic tissues remain poorly understood. Here, we show that the AT-rich interactive domain 5A (Arid5a), a cytokine-induced nucleic acid binding protein, is important for the maintenance of adipose tissue homeostasis. Long-term deficiency of Arid5a in mice results in adult-onset severe obesity. In contrast, transgenic mice overexpressing Arid5a are highly resistant to high-fat diet-induced obesity. Inhibition of Arid5a facilitates the in vitro differentiation of 3T3-L1 cells and fibroblasts to adipocytes, whereas its induction substantially inhibits their differentiation. Molecular studies reveal that Arid5a represses the transcription of peroxisome proliferator activated receptor gamma 2 (Ppar-γ2) due to which, in the absence of Arid5a, Ppar-γ2 is persistently expressed in fibroblasts. This phenomenon is accompanied by enhanced fatty acid uptake in Arid5a-deficient cells, which shifts metabolic homeostasis toward prolipid metabolism. Furthermore, we show that Arid5a and Ppar-γ2 are dynamically counterregulated by each other, hence maintaining adipogenic homeostasis. Thus, we show that Arid5a is an important negative regulator of energy metabolism and can be a potential target for metabolic disorders. [ABSTRACT FROM AUTHOR]

Adenine-thymine (AT)-rich interactive domain 5a (Arid5a) is an RNA-binding protein found in the cytoplasm and nucleus of normally growing cells. Although Arid5a is known to play an important role in immune regulation, whether and how Arid5a subcellular localization impacts immune regulation has remained unclear. In this study, we generated Arid5a transgenic (TG) mice to address this question. While ectopic Arid5a overexpression did not affect expression of inflammatory cytokines under unstimulated conditions, significantly higher levels of inflammatory cytokines, such as IL-6, were produced in response to lipopolysaccharide (LPS) stimulation. Consistent with this, TG mice were more sensitive to LPS treatment than wild-type mice. We also found that Arid5a is imported into the nucleus via a classical importin-α/β1--mediated pathway. On stimulation, nuclear Arid5a levels were decreased, while there was a concomitant increase in cytoplasmic Arid5a. Arid5a is associated with up-frameshift protein 1 and its nuclear export is regulated by a nuclear export receptor, chromosomal region maintenance 1. Taken together, these data indicate that Arid5a is a dynamic protein that translocates to the cytoplasm from the nucleus so as to properly exert its dual function in mRNA stabilization and transcriptional regulation during inflammatory conditions. [ABSTRACT FROM AUTHOR]

Background: Most lactic acid bacteria are non-motile but some of them are flagellated and exhibit motility. So far, motile lactobacilli have rarely been studied, and characteristics of their flagellins are poorly understood. In this study, a highly motile strain of Lactobacillus agilis was recruited for transcriptional analysis and characterization of its flagellins. Results: Unlike another motile lactic acid bacteria of intestinal isolate, Lactobacillus ruminis, flagellar filaments of the L. agilis strain probably consist of two homologous but distinct flagellins. Glycosylation of the flagellar filaments and their resistance to heat, acid and SDS were also observed. The immunological activity of the flagellins was evaluated through the stimulation of Caco-2 cells. The results show that TLR5-stimulating activity of the protein is attenuated, likely due to an incomplete TLR5-recognition site. Conclusions: The flagella filaments of L. agilis BKN88 consist of two homologous glycosylated flagellins, which likely have an incomplete TLR5-recognition site. The characteristics of the flagellin are presumably a consequence of adaptation as a commensal microbe in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]