Callose homeostasis at plasmodesmata: molecular regulators and developmental relevance

Plasmodesmata are membrane-lined channels that are located in the plant cell wall and that physically interconnect the cytoplasm and the endoplasmic reticulum (ER) of adjacent cells. Operating as controllable gates, plasmodesmata regulate the symplastic trafficking of micro- and macromolecules, such as endogenous proteins [transcription factors (TFs)] and RNA-based signals (mRNA, siRNA, etc.), hence mediating direct cell-to-cell communication and long distance signaling. Besides this physiological role, plasmodesmata also form gateways through which viral genomes can pass, largely facilitating the pernicious spread of viral infections. Plasmodesmatal trafficking is either passive (e.g., diffusion) or active and responses both to developmental and environmental stimuli. In general, plasmodesmatal conductivity is regulated by the controlled build-up of callose at the plasmodesmatal neck, largely mediated by the antagonistic action of callose synthases (CalSs) and beta-1,3-glucanases. Here, in this theory and hypothesis paper, we outline the importance of callose metabolism in PD SEL control, and highlight the main molecular factors involved. In addition, we also review other proteins that regulate symplastic PD transport, both in a developmental and stress-responsive framework, and discuss on their putative role in the modulation of PD callose turn-over. Finally, we hypothesize on the role of structural sterols in the regulation of (PD) callose deposition and outline putative mechanisms by which this regulation may occur

Calcium in the initiation, progression and as an effector of Alzheimer's disease pathology.

The cause(s) of sporadic Alzheimer's disease (sAD) are complex and currently poorly understood. They likely result from a combination of genetic, environmental, proteomic and lipidomic factors that crucially occur only in the aged brain. Age-related changes in calcium levels and dynamics have the potential to increase the production and accumulation of both amyloid-beta peptide (Abeta) and tau pathologies in the AD brain, although these two pathologies themselves can induce calcium dyshomeostasis, particularly at synaptic membranes. This review discuses the evidence for a role for calcium dyshomeostasis in the initiation of pathology, as well as the evidence for these pathologies themselves disrupting normal calcium homeostasis, which lead to synaptic and neuronal dysfunction, synaptotoxicity and neuronal loss, underlying the dementia associated with the disease

The emergence of environmental homeostasis in complex ecosystems

The Earth, with its core-driven magnetic field, convective mantle, mobile lid tectonics, oceans of liquid water, dynamic climate and abundant life is arguably the most complex system in the known universe. This system has exhibited stability in the sense of, bar a number of notable exceptions, surface temperature remaining within the bounds required for liquid water and so a significant biosphere. Explanations for this range from anthropic principles in which the Earth was essentially lucky, to homeostatic Gaia in which the abiotic and biotic components of the Earth system self-organise into homeostatic states that are robust to a wide range of external perturbations. Here we present results from a conceptual model that demonstrates the emergence of homeostasis as a consequence of the feedback loop operating between life and its environment. Formulating the model in terms of Gaussian processes allows the development of novel computational methods in order to provide solutions. We find that the stability of this system will typically increase then remain constant with an increase in biological diversity and that the number of attractors within the phase space exponentially increases with the number of environmental variables while the probability of the system being in an attractor that lies within prescribed boundaries decreases approximately linearly. We argue that the cybernetic concept of rein control provides insights into how this model system, and potentially any system that is comprised of biological to environmental feedback loops, self-organises into homeostatic states

Modelling the evolution of cerebral aneurysms: biomechanics, mechanobiology and multiscale modelling

Intracranial aneurysms (IAs) are abnormal dilatations of the cerebral vasculature. Computational modelling may shed light on the aetiology of the disease and lead to improved criteria to assist diagnostic decisions. We briefly review models of aneurysm evolution to date and present a novel fluid-solid-growth (FSG) framework for patient-specific modelling of IA evolution. We illustrate its application to 4 clinical cases depicting an IA. The section of arterial geometry containing the IA is removed and replaced with a cylindrical section: this represents an idealised section of healthy artery upon which IA evolution is simulated. The utilisation of patient-specific geometries enables G&R to be explicitly linked to physiologically realistic spatial distributions and magnitudes of haemodynamic stimuli. In this study, we investigate the hypothesis that elastin degradation is driven by locally low wall shear stress (WSS). In 3 out of 4 cases, the evolved model IA geometry is qualitatively similar to the corresponding in vivo IA geometry. This suggests some tentative support for the hypothesis that low WSS plays a role in the mechanobiology of IA evolution

The Daisystat: A model to explore multidimensional homeostasis

The Homeostat was a physical device that demonstrated Ashby’s notion of ‘ultrastability’. The components interact in such a way as to maintain sets of essential variables to within critical ranges in the face of an externally imposed regime of perturbations. The Daisystat model is presented that bears a number of similarities to Ashby’s Homeostat but which can also be considered as a higher dimensional version of the Watson & Lovelock Daisyworld model that sought to explain how homeostasis operating at the planetary scale may arise in the absence of foresight or planning. The Daisystat model features a population of diverse individuals that affect and are affected by the environment in different ways. The Daisystat model extends Daisyworld in that homeostasis is observed with systems comprised of four environmental variables and beyond. It is shown that the behaviour of the population is analogous to the ‘uniselector’ in the Homeostat in that rapid changes in the population allows the system to ‘search’ for stable states. This allows the system to find and recover homeostatic states in the face of externally applied perturbations. It is proposed that the Daisystat may afford insights into the evolution of increasingly complex systems such as the Earth system