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Abstract Among contributors to diffusible signaling are portal systems which join two capillary beds through connecting veins. Portal systems allow diffusible signals to be transported in high concentrations directly from one capillary bed to the other without dilution in the systemic circulation. Two portal systems have been identified in the brain. The first was discovered almost a century ago and connects the median eminence to the anterior pituitary gland. The second was discovered a few years ago and links the suprachiasmatic nucleus to the organum vasculosum of the lamina terminalis, a sensory circumventricular organ (CVO). Sensory CVOs bear neuronal receptors for sensing signals in the fluid milieu. They line the surface of brain ventricles and bear fenestrated capillaries thereby lacking blood–brain barriers. It is not known whether the other sensory CVOs, namely the subfornical organ (SFO), and area postrema (AP) form portal neurovascular connections with nearby parenchymal tissue. To preserve the integrity of the vasculature of CVOs and their adjacent neuropil, we combined iDISCO clearing and light‐sheet microscopy to acquire volumetric images of blood vessels and traced the vasculature in two experiments. In the first, the whole brain vasculature was registered to the Allen Brain Atlas in order to identify the nuclei to which the SFO and AP are attached. In the second study, regionally specified immunolabeling was used to identify the attachment sites and vascular connections between the AP, and the SFO to their respective parenchymal attachment sites. There are venous portal pathways linking the capillary vessels of the SFO and the posterior septal nuclei, namely the septofimbrial nucleus and the triangular nucleus of the septum. Unlike the arrangement of portal vessels, the AP and the nucleus of the solitary tract share a common capillary bed. Taken together, the results reveal that all three sensory CVOs bear direct capillary connections to adjacent neuropil, providing a direct route for diffusible signals to travel from their source to their targets.more » « lessFree, publicly-accessible full text available January 7, 2026
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Sourjik, Victor (Ed.)Cells must access resources to survive, and the anatomy of multicellular structures influences this access. In diverse multicellular eukaryotes, resources are provided by internal conduits that allow substances to travel more readily through tissue than they would via diffusion. Microbes growing in multicellular structures, called biofilms, are also affected by differential access to resources and we hypothesized that this is influenced by the physical arrangement of the cells. In this study, we examined the microanatomy of biofilms formed by the pathogenic bacteriumPseudomonas aeruginosaand discovered that clonal cells form striations that are packed lengthwise across most of a mature biofilm’s depth. We identified mutants, including those defective in pilus function and in O-antigen attachment, that show alterations to this lengthwise packing phenotype. Consistent with the notion that cellular arrangement affects access to resources within the biofilm, we found that while the wild type shows even distribution of tested substrates across depth, the mutants show accumulation of substrates at the biofilm boundaries. Furthermore, we found that altered cellular arrangement within biofilms affects the localization of metabolic activity, the survival of resident cells, and the susceptibility of subpopulations to antibiotic treatment. Our observations provide insight into cellular features that determine biofilm microanatomy, with consequences for physiological differentiation and drug sensitivity.more » « less
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