16,035 research outputs found

    Extended amygdala CRH circuits trigger aversive responses

    Get PDF
    Corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release and has a key role in stress-related behaviours. In addition, the corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioural adaptation to stress and is causally linked to stress-related emotional disorders. However, there are still unanswered questions. In this study, single-nucleus sequencing was conducted to resolve the heterogeneity of midbrain CRHR1 neurons encompassing dopaminergic, GABAergic and glutamatergic neurons, which was further substantiated by immunostaining. Anterograde and retrograde tracings revealed strong projections of extended amygdala CRH neurons into the VTA and SN. Chemogenetic and optogenetic manipulation demonstrated that activation of CRH neurons in the interstitial nucleus of the posterior limb of the anterior commissure (IPACL), resulted in maladaptive behaviour, arousal and place aversion. Systemic injection of the CRHR1 antagonist R121919 was sufficient to reverses these behaviours indicating a direct role of CRH and CRHR1 in these circuits contributing to the behavioural outcomes. Overall, this study uncovered a novel CRH circuit originating from the IPACL, which is a part of extended amygdala innervating the SN. This circuit is modulated by the CRH/CRHR1-system and is involved in the regulation of arousal and place aversion behaviour

    On the fate of vacuum bubbles on matter backgrounds

    Full text link
    In this letter we discuss cosmological first order phase transitions with de Sitter bubbles nucleating on (inhomogeneous) matter backgrounds. The de Sitter bubble can be a toy model for an inflationary phase of universes like our own. Using the thin wall approximation and the Israel junction method we trace the classical evolution of the formed bubbles within a compound model. We first address homogeneous ambient space (FRW model) and already find that bubbles nucleated in a dust dominated background cannot expand. For an inhomogeneous dust background (LTB model) we describe cases with at least initially expanding bubbles. Yet, an ensuing passage of the bubble wall through ambient curvature inhomogeneities remains unnoticed for observers inside the bubble. Notable effects also for interior observers are found in the case of a rapid background phase transition in a FRW model.Comment: 4 pages, 2 figures, proceedings (Annalen der Physik) of the Grassmannian Conference in Fundamental Cosmology (Grasscosmofun'09) Szczecin, Poland, 14-19 September 200

    Long-term Effects of Early Childhood Malaria Exposure on Education and Health: Evidence from Colonial Taiwan

    Get PDF
    We estimate the effects of early childhood malaria exposure on education and health at older ages by exploiting variations in malaria exposure risk around birth that resulted from a universal malaria eradication campaign in colonial Taiwan in the early 20th century. We find that malaria exposure around birth leads to lower life-time educational attainment and to worse mental and physical health outcomes in old age as reflected in particular in worse cognitive function, a higher likelihood of cardiovascular diseases and a higher mortality hazard, compared to those who were not exposed.malaria, early childhood, education, health, Taiwan

    Radiolabeling human peripheral blood stem cells for positron emission tomography (PET) imaging in young rhesus monkeys.

    Get PDF
    These studies focused on a new radiolabeling technique with copper ((64)Cu) and zirconium ((89)Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of (64)Cu-CD45 and (89)Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of (64)Cu-TETA-CD45 increased from 0 (92%) to 160 µCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of (64)Cu-TETA-CD45 >20 µCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p<0.05). For (89)Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of (89)Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0-40 µCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of (89)Zr-Df-CD45 labeling efficiency was observed when compared to (64)Cu-TETA-CD45. Similar to (64)Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05) (growth, colony formation). Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10(6) hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of (89)Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that (89)Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high
    corecore