This allows for fast, in silico modeling – and manipulation – of epidemics and is especially powerful if complemented with adequate empirical data for parameterization.”
“Excess

tumor necrosis factor (TNF) plays a pivotal role in the pathogenesis of Alzheimer’s disease(AD). Clinical improvement following perispinal administration of etanercept in patients with Alzheimer’s disease and other forms of dementia and brain dysfunction is characteristically Repotrectinib concentration evident within minutes. The rapidity and constellation of the clinical effects across multiple domains (cognition, mood, memory, motor function, and attention) suggest they are mediated by non-synaptic signaling mechanisms previously unrecognized for etanercept. These mechanisms likely extend beyond the known

roles of TNF as a gliotransmitter that modulates synaptic strength, synaptic scaling, and AMPA receptor trafficking. Preliminary basic science and clinical investigation suggests that perispinal administration of etanercept may lead to its rapid penetration into the cerebrospinal fluid AZD6738 nmr (CSF) within the cerebral ventricles. Diffusion of large molecules into the periventricular brain parenchyma is known to occur, but this process may not be sufficient to explain the rapidity of the clinical effects. There exist populations of cells, including CSF-contacting neurons and modified ependymal cells called tanycytes, that have receptive surfaces in direct contact with the CSF. It is hypothesized that the rapid clinical effects of perispinal etanercept involve non-synaptic signal transduction across the ependymal barrier and into neuronal networks via these CSF-contacting cells. This hypothesis challenges the dogma that penetration of a therapeutic into the cerebral parenchyma through the endothelium of

the cerebral vasculature (the so-called blood-brain barrier) is necessary to produce rapid clinical effects in AD. CSF-contacting selleck inhibitor cells may constitute a therapeutic target for a diverse group of brain, psychiatric and spinal disorders.”
“The establishment of organ boundaries is a fundamental process for proper morphogenesis in multicellular organisms. In plants, the shoot meristem repetitively forms organ primordia from its periphery, and boundary cells are generated between them to separate their cellular fates. The genes CUP-SHAPED COTYLEDON1 (CUC1) and CUC2, which encode plant-specific NAC transcription factors, play central roles in establishment of the shoot organ boundaries in Arabidopsis thaliana. Here we show that CUC1 protein activates expression of LIGHT-DEPENDENT SHORT HYPOCOTYLS 4 (LSH4) and its homolog LSH3 in shoot organ boundary cells. Both genes encode nuclear proteins of the Arabidopsis LSH1 and Oryza G1 (ALOG) family, the members of which are widely conserved in land plants. Expression of LSH4 and LSH3 is detected in the boundary cells of various shoot organs, such as cotyledons, leaves and floral organs, and requires the activity of CUC1 and CUC2.