Circadian rhythms in glucocorticoids are the product of interactions between hypothalamic-pituitary-adrenal (HPA) axis and mammalian clock gene system. The adrenal can generate glucocorticoid rhythm that turn synchronizes other peripheral clocks to maintain homeostasis. Stress acutely activates chronically upregulates HPA axis, suggesting could be modulated by stress. However, there is no direct evidence stress affects rhythm. We tested hypothesis a model chronic subordination (CSS) has...

Cryptococcus neoformans is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little known about immunological conditions establishing latent granuloma lungs. To investigate this, we performed an analysis cell populations, cytokine changes, during with disease-causing clinical isolate C3HeB/FeJ mice over 360 days. We found...

The development of small-animal models is necessary to understand host responses and immunity emerging infectious diseases potential bioterrorism agents. In this report we have characterized a murine model intestinal ricin intoxication. Ricin administered intragastrically (i.g.) BALB/c mice at doses ranging from 1 10 mg/kg body weight induced dose-dependent morphological changes in the proximal small intestine (i.e., duodenum), including widespread villus atrophy epithelial damage....

The pathogenic yeast Cryptococcus neoformans produces polyploid titan cells in response to the host lung environment that are critical for adaptation and subsequent disease. We analyzed vivo vitro cell cycles identify key aspects of C. cycle important formation cells. identified unbudded 2C cells, referred as a G2 arrest, produced both various stresses. Deletion nonessential cyclin Cln1 resulted overproduction transient morphology defects upon release from stationary phase vitro. Using...

The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoids, yet how the is synchronized to external environment unknown. Using mPER2::Luciferase (mPER2Luc) knockin mice, which luciferase rhythmically expressed under control of mouse Per2 gene, we hypothesized ACTH transmits entrainment signals adrenal. Adrenal explants were administered at different phases mPER2Luc rhythm. Treatment with 1-39 produced phase delay was phase-dependent, maximum time (CT)18; did...

The glucocorticoid (GC) rhythm is entrained to light-dark (LD) cycles via a molecular clock in the suprachiasmatic nucleus (SCN) and maintained by an adrenal synchronized SCN-dependent signals. Targeted deletion of core gene Bmal1 can disrupt function. requirement stabilize circadian GC during exposure aberrant LD was determined using novel aldosterone synthase (AS)Cre/+::Bmal1Fl/Fl mice which occurred postnatal transdifferentiation. To examine whether results loss clock, were crossed with...

Half maximal inhibitory concentrations (IC50) to the experimental drug ATI-2307 and complete inhibition (IC90) of common clinically used antifungal amphotericin B were determined by microbroth dilution assay for a collection 69 clinical isolates Cryptococcus neoformans from Uganda that had high fluconazole IC50 values. The majority tested at or above 8 µg/mL, but susceptible both (IC90 ≤1 μg/mL) (IC50 ≤0.0312 µg/mL). No correlation between increased minimum concentration (MIC) MIC was...

The role adenosine plays in evoking the exercise pressor reflex humans remains controversial. We hypothesized that localized forearm receptor blockade would attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing handgrip humans. Blood pressure (Finometer), heart rate, and MSNA from peroneal were assessed 11 healthy young volunteers during isometric handgrip, postexercise circulatory occlusion (PECO), passive stretch PECO. protocol was performed before after by local...

The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoid production, yet it is unclear how the responds to acute stress. We hypothesized stress-induced ACTH provides signal phase shifts clock. To assess whether stress vivo phase-dependent manner, mPER2:LUC mice on 12:12-h light:dark cycle underwent restraint for 15 min or no at zeitgeber time (ZT) 2 (early subjective day) ZT16 night). Adrenal explants from stressed ZT2 showed were phase-advanced by ~2 h,...

Dehydrated rats exhibit a rapid inhibition of the hypothalamic-pituitary-adrenal axis after rehydration. Drinking activates vagal afferents that project to neurons in nucleus tractus solitarius (NTS). We hypothesized when dehydrated drink, stimulate NTS initiating activity. Experiments assessed activity by measuring Fos expression. Rats were water restricted for 1 or 6 d, limiting access 30 min/d morning. single repeated restriction increased Fos, demonstrating next examined contribution...

is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little known about immunological conditions establishing latent granuloma lungs. To investigate this, we performed an analysis cell populations, cytokine changes, during with disease-causing clinical isolate C3HeB/FeJ mice over 360 days. We found latently infected progress...

Abstract The pathogenic yeast Cryptococcus neoformans produces polyploid titan cells in response to the host lung environment that are critical for adaptation and subsequent disease. We analyzed vivo vitro cell cycles identify key aspects of C. cycle important formation cells. identified unbudded 2C cells, referred as a G2 arrest, produced both various stresses. Deletion non-essential cyclin Cln1 resulted over-production , transient morphology defects upon release from stationary phase ....

Prior studies suggest that adenosine, nitric oxide and prostaglandins contribute to skeletal muscle vasodilation induced by systemic hypoxia in humans. However, pharmacological blocking other vasodilator systems such as for example endothelium‐derived hyperpolarizing factor (EDHF) may be involved. Fluconazole, an antifungal agent with cytochrome P450 2C9 inhibitor properties can used block EDHF. We exposed healthy humans (n=8) (inspired O 2 fraction 0.1 10 min; arterial pO ~38 mmHg) measured...

The role adenosine plays in evoking the exercise pressor reflex humans remain controversial. Interestingly, animal studies suggest that can inhibit type 1 vanilloid receptors activity. Thus, we hypothesized receptor blockade would accentuate muscle sympathetic nerves activity (MSNA) response to fatiguing humans. Blood pressure (Finometer), heart rate, and MSNA from peroneal nerve were assessed 11 healthy young volunteers during isometric handgrip, post ischemia (PEMI), passive stretch PEMI....