Biology subjects

Oliveri, H.

Publications and source records attributed to Oliveri, H..

8 recordsLinked to original sources

bioRxiv2025

Heterogeneity in human brain clearance adds resilience against tauopathy -- a computational model informed by glymphatic MRI

Neurotoxic protein fragments such as amyloid-beta and tau accumulate in characteristic staging patterns in Alzheimers disease (AD). The brain clears such metabolic substances via multiple different systems, including via the glymphatic (extracellular/extravascular) pathway. Here, we ask how the distinct features that characterize human glymphatic function would affect the prion-like cascade of protein invasion associated with AD. To address this question, we extract and analyze individual clearance rates from human glymphatic MRI (gMRI) data sets. These clearance rates define subject-specific maps of glymphatic clearance that vary both across cortical lobes and Braak staging regions. We apply these clearance maps as initial states in a computational network model linking misfolded proteins, tissue damage, and local clearance to simulate a series of individual proteinopathy trajectories. Our results show that the spatial heterogeneity in initial clearance induces characteristic propagation patterns, delaying and redirecting the disease progression. Moreover, reducing this spatial heterogeneity accelerates disease progression and induces staging patterns typically associated with AD. A comparison between well-rested subjects and subjects who underwent a single night of sleep deprivation did not reveal differences in initial clearance maps nor in simulated disease progression. These findings suggest that spatial heterogeneity in brain clearance may be a key factor for neurodegenerative resilience.

neuroscience↗

bioRxiv2023

Mechanics reveals the role of peristome geometry in prey capture in carnivorous pitcher plants (Nepenthes)

Carnivorous pitcher plants (Nepenthes) are a striking example of a natural pitfall trap. The traps slippery rim, or peristome, plays a critical role in insect capture via an aquaplaning mechanism that is well documented. Whilst the peristome has received significant research attention, the conspicuous variation in peristome geometry across the genus remains unexplored. We examined the mechanics of prey capture using Nepenthes pitcher plants with divergent peristome geometries. Inspired by living materials, we developed a mathematical model that links the peristomes three-dimensional geometries to the physics of prey capture under the laws of Newtonian mechanics. Linking form and function enables us to test hypotheses related to the function of features such as shape and ornamentation, orientation in a gravitational field, and the presence of teeth, while analysis of the energetic costs and gains of a given geometry provides a means of inferring potential evolutionary pathways. In a separate modeling approach, we show how prey size may correlate with peristome dimensions for optimal capture. Our modeling framework provides a physical platform to understand how divergence in peristome morphology may have evolved in the genus Nepenthes in response to shifts in prey diversity, availability, and size. Significance StatementPitcher plants (Nepenthes) produce an astonishing array of leaf-derived traps into which preys (typically insects) slide from a rim (the peristome). How prey capture varies across this varied genus is a mystery. We hypothesized that insects behave differently depending on peristome size and geometry. We examined the physics of prey capture under the laws of Newtonian mechanics to show that prey size and behavior correlate with peristome shape. We conclude that a diversity of peristomes in Nepenthes evolved in response to variation in prey capture.

plant biology↗

bioRxiv2022

Rheology of growing axons

The growth of axons is a key process in neural system development, which relies upon a subtle balance between external mechanical forces and remodeling of cellular constituents. A key problem in the biophysics of axons is therefore to understand the overall response of the axon under stretch, which is often modeled phenomenologically using morphoelastic or viscoelastic models. Here, we develop a microscopic mixture model of growth and remodeling based on protein turnover and damage to obtain the macroscopic rheology of axonal shafts. First, we provide an estimate for the instantaneous elastic response of axons. Second, we demonstrate that under moderate traction velocities, axons behave like a viscoelastic Maxwell material. Third, for larger velocities, we show that failure takes place due to extensive damage.

developmental biology↗

bioRxiv2022

The role of clearance in neurodegenerative diseases

Alzheimers disease, the most common form of dementia, is a systemic neurological disorder associated with the formation of toxic, pathological aggregates of proteins within the brain that lead to severe cognitive decline, and eventually, death. In normal physiological conditions, the brain rids itself of toxic proteins using various clearance mechanisms. The efficacy of brain clearance can be adversely affected by the presence of toxic proteins and is also known to decline with age. Motivated by recent findings, such as the connection between brain cerebrospinal fluid clearance and sleep, we propose a mathematical model coupling the progression of toxic proteins over the brains structural network and protein clearance. The model is used to study the interplay between clearance in the brain, toxic seeding, brain network connectivity, aging, and progression in neurodegenerative diseases such as Alzheimers disease. Our findings provide a theoretical framework for the growing body of medical research showing that clearance plays an important role in the etiology, progression and treatment of Alzheimers disease.

neuroscience↗

bioRxiv2022

Front propagation and arrival times in networks with application to neurodegenerative diseases

Many physical, epidemiological, or physiological dynamical processes on networks support front-like propagation, where an initial localized perturbation grows and systematically invades all nodes in the network. A key question is then to extract estimates for the dynamics. In particular, if a single node is seeded at a small concentration, when will other nodes reach the same initial concentration? Here, motivated by the study of toxic protein propagation in neurodegenerative diseases, we present and compare three different estimates for the arrival time in order of increasing analytical complexity: the linear arrival time, obtained by linearizing the underlying system; the Lambert time, obtained by considering the interaction of two nodes; and the nonlinear arrival time, obtained by asymptotic techniques. We use the classic Fisher-Kolmogorov-Petrovsky-Piskunov equation as a paradigm for the dynamics and show that each method provides different insight and time estimates. Further, we show that the nonlinear asymptotic method also gives an approximate solution valid in the entire domain and the correct ordering of arrival regions over large regions of parameters and initial conditions.

biophysics↗

bioRxiv2020

An optic ray theory for durotactic axon guidance

During the development of the nervous system, neurons extend bundles of axons that grow and meet other neurons to form the neuronal network. Robust guidance mechanisms are needed for these bundles to migrate and reach their functional target. Directional information depends on external cues such as chemical or mechanical gradients. Unlike chemotaxis that has been extensively studied, the role and mechanism of durotaxis, the directed response to variations in substrate rigidity, remain unclear. We model bundle migration and guidance by rigidity gradients by using the theory of morphoelastic rods. We show that at a rigidity interface, the motion of axon bundles follows a simple behavior analogous to optic ray theory and obeys Snells law for refraction and reflection. We use this powerful analogy to demonstrate that axons can be guided by the equivalent of optical lenses and fibers created by regions of different stiffnesses.

neuroscience↗

bioRxiv2020

Multiscale integration of environmental stimuli in plant tropism produces complex behaviors

Plant tropism refers to the directed movement of an organ or organism in response to external stimuli. Typically, these stimuli induce hormone transport that triggers cell growth or deformation. In turn, these local cellular changes create mechanical forces on the plant tissue that are balanced by an overall deformation of the organ, hence changing its orientation with respect to the stimuli. This complex feedback mechanism takes place in a three-dimensional growing plant with varying stimuli depending on the environment. We model this multiscale process in filamentary organs for an arbitrary stimulus by linking explicitly hormone transport to local tissue deformation leading to the generation of mechanical forces and the deformation of the organ in three dimensions. We show, as examples, that the gravitropic, phototropic, nutational, and thigmotropic dynamic responses can be easily captured by this framework. Further, the integration of evolving stimuli and/or multiple contradictory stimuli can lead to complex behavior such as sun following, canopy escape, and plant twining. Significance StatementTo survive and to thrive, plants rely on their ability to sense multiple environmental signals, such as gravity or light, and respond to them by growing and changing their shape. To do so, the signals must be transduced down to the cellular level to create the physical deformations leading to shape changes. We propose a multiscale theory of tropism that takes multiple stimuli and transforms them into auxin transport that drives tissue-level growth and remodeling, thus modifying the plant shape and position with respect to the stimuli. This feedback loop can be dynamically updated to understand the response to individual stimuli or the complex behavior generated by multiple stimuli such as canopy escape or pole wrapping for climbing plants.

plant biology↗

bioRxiv2019

A microtubule-mediated mechanical feedback controls leaf blade development in three dimensions

Many plant species have thin leaf blades, which is an important adaptation that optimizes the exchanges with the environment. Here, we provide evidence that their three-dimensional geometry is governed by microtubule alignment along mechanical stress patterns in internal walls. Depending on the primary shape of the primordium, this process has the potential to amplify an initial degree of flatness, or promote the formation of nearly axisymmetric, mostly elongating organs, such as stems and roots. This mechanism may explain leaf evolution from branches, which is alternative to Zimmermanns influential, but widely questioned, telome theory.\n\nOne Sentence SummaryMechanical feedback controls leaf development in three dimensions

developmental biology↗