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https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html The hypothalamus-pituitary-adrenal (HPA) axis is a key neuroendocrine system implicated in stress response, major depression disorder, and post-traumatic stress disorder. We present a new, compact dynamical systems model for the response of the HPA axis to external stimuli, representing stressors or therapeutic intervention, in the presence of a circadian input. Our work builds upon previous HPA axis models where hormonal dynamics are separated into slow and fast components. Several simplifications allow us to derive an effective model of two equations, similar to a multiplicative-input FitzHugh-Nagumo system, where two stable states, a healthy and a diseased one, arise. We analyze the effective model in the context of state transitions driven by external shocks to the hypothalamus, but also modulated by circadian rhythms. Our analyses provide mechanistic insight into the effects of the circadian cycle on input driven transitions of the HPA axis and suggest a circadian influence on exposure or cognitive behavioral therapy in depression, or post-traumatic stress disorder treatment.Candidiasis, aspergillosis, and mucormycosis cause the majority of nosocomial fungal infections in immunocompromised patients. Using an unbiased transcriptional profiling in PBMCs exposed to the fungal species causing these infections, we found a core host response in healthy individuals that may govern effective fungal clearance it consists of 156 transcripts, involving canonical and non-canonical immune pathways. Systematic investigation of key steps in antifungal host defense revealed fungal-specific signatures. As previously demonstrated, Candida albicans induced type I and Type II interferon-related pathways. In contrast, central pattern recognition receptor, reactive oxygen species production, and host glycolytic pathways were down-regulated in response to Rhizopus oryzae, which was associated with an ER-stress response.

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