Statistical modeling of mRNP transport in dendrites: A comparative analysis of ß-actin and Arc mRNP dynamics.

Localization of messenger RNA (mRNA) in dendrites is crucial for regulating gene expression during long-term memory formation. mRNA binds to RNA-binding proteins (RBPs) to form messenger ribonucleoprotein (mRNP) complexes that are transported by motor proteins along microtubules to their target synapses. However, the dynamics by which mRNPs find their target locations in the dendrite have not been well understood. Here, we investigated the motion of endogenous ß-actin and Arc mRNPs in dissociated mouse hippocampal neurons using the MS2 and PP7 stem-loop systems, respectively. By evaluating the statistical properties of mRNP movement, we found that the aging Lévy walk model effectively describes both ß-actin and Arc mRNP transport in proximal dendrites. A critical difference between ß-actin and Arc mRNPs was the aging time, the time lag between transport initiation and measurement initiation. The longer mean aging time of ß-actin mRNP (~100 s) compared with that of Arc mRNP (~30 s) reflects the longer half-life of constitutively expressed ß-actin mRNP. Furthermore, our model also permitted us to estimate the ratio of newly generated and pre-existing ß-actin mRNPs in the dendrites. This study offers a robust theoretical framework for mRNP transport, which provides insight into how mRNPs locate their targets in neurons.

Anomalous diffusion of active Brownian particles cross-linked to a networked polymer: Langevin dynamics simulation and theory.

Quantitatively understanding the dynamics of an active Brownian particle (ABP) interacting with a viscoelastic polymer environment is a scientific challenge. It is intimately related to several interdisciplinary topics such as the microrheology of active colloids in a polymer matrix and the athermal dynamics of the in vivo chromosomes or cytoskeletal networks. Based on Langevin dynamics simulation and analytic theory, here we explore such a viscoelastic active system in depth using a star polymer of functionality f with the center cross-linker particle being ABP. We observe that the ABP cross-linker, despite its self-propelled movement, attains an active subdiffusion with the scaling ΔR2(t) ∼ tα with α ≤ 1/2, through the viscoelastic feedback from the polymer. Counter-intuitively, the apparent anomaly exponent α becomes smaller as the ABP is driven by a larger propulsion velocity, but is independent of functionality f or the boundary conditions of the polymer. We set forth an exact theory and show that the motion of the active cross-linker is a Gaussian non-Markovian process characterized by two distinct power-law displacement correlations. At a moderate Péclet number, it seemingly behaves as fractional Brownian motion with a Hurst exponent H = α/2, whereas, at a high Péclet number, the self-propelled noise in the polymer environment leads to a logarithmic growth of the mean squared displacement (∼ln t) and a velocity autocorrelation decaying as -t-2. We demonstrate that the anomalous diffusion of the active cross-linker is precisely described by a fractional Langevin equation with two distinct random noises.

[Strategic decisions in public psychiatric institutions: a proposed method for resource analysis and allocation]. / La décision stratégique en établissement public de psychiatrie : proposition de méthode pour l'analyse et l'allocation des moyens.

Because of its sector-based organization and extra-hospital care, public psychiatry has a unique position in healthcare. This paper describes the tools and procedures used to analyze and allocate the resources of the "Centre Hospitalier Alpes-Isère", a hospital serving a catchment population of 530,000 adults. A consensus-based approach was used to validate the selected indicators and included the participation of a geographer. Five levels of resource allocation were identified and classified using a decision tree. At each level, the relevant authorities and criteria were identified as key components of the decision-making process. This paper describes the first three levels of care provision. Focusing on adult care, a comparative assessment of the resources allocated to general psychiatric care and specialist care was conducted, in addition to a comparative assessment of the resources allocated to each of the hospital's four local centers. Geographical accessibility to extramural facilities was also assessed. A study of the characteristics of each general psychiatry clinic revealed significant disparities. The paper highlights several issues: the poor knowledge of psychiatric epidemiological data relating to the population within the catchment area, the difficulty of assessing non-consolidated data or indicators from multiple sources, and the limited and partial nature of geographical data for characterizing and evaluating health care in the hospital's peripheral clinics. Several studies are currently underway to assess the operational effectiveness of the tools and procedures used to analyze and allocate resources.

Mapping the spectrum of 3D communities in human chromosome conformation capture data.

Several experiments show that the three dimensional (3D) organization of chromosomes affects genetic processes such as transcription and gene regulation. To better understand this connection, researchers developed the Hi-C method that is able to detect the pairwise physical contacts of all chromosomal loci. The Hi-C data show that chromosomes are composed of 3D compartments that range over a variety of scales. However, it is challenging to systematically detect these cross-scale structures. Most studies have therefore designed methods for specific scales to study foremost topologically associated domains (TADs) and A/B compartments. To go beyond this limitation, we tailor a network community detection method that finds communities in compact fractal globule polymer systems. Our method allows us to continuously scan through all scales with a single resolution parameter. We found: (i) polymer segments belonging to the same 3D community do not have to be in consecutive order along the polymer chain. In other words, several TADs may belong to the same 3D community. (ii) CTCF proteins-a loop-stabilizing protein that is ascribed a big role in TAD formation-are well correlated with community borders only at one level of organization. (iii) TADs and A/B compartments are traditionally treated as two weakly related 3D structures and detected with different algorithms. With our method, we detect both by simply adjusting the resolution parameter. We therefore argue that they represent two specific levels of a continuous spectrum 3D communities, rather than seeing them as different structural entities.

Emergence of nonwhite noise in Langevin dynamics with magnetic Lorentz force.

We investigate the low mass limit of Langevin dynamics for a charged Brownian particle driven by a magnetic Lorentz force. In the low mass limit, velocity variables relaxing quickly are coarse-grained out to yield effective dynamics for position variables. Without the Lorentz force, the low mass limit is equivalent to the high friction limit. Both cases share the same Langevin equation that is obtained by setting the mass to zero. The equivalence breaks down in the presence of the Lorentz force. The low mass limit cannot be achieved by setting the mass to zero. The limit is also distinct from the large friction limit. We derive the effective equations of motion in the low mass limit. The resulting stochastic differential equation involves a nonwhite noise whose correlation matrix has antisymmetric components. We demonstrate the importance of the nonwhite noise by investigating the heat dissipation by a driven Brownian particle, where the emergent nonwhite noise has a physically measurable effect.

Overdamped limit and inverse-friction expansion for Brownian motion in an inhomogeneous medium.

We revisit the problem of the overdamped (large-friction) limit of the Brownian dynamics in an inhomogeneous medium characterized by a position-dependent friction coefficient and a multiplicative noise (local temperature) in one-dimensional space. Starting from the Kramers equation and analyzing it through the expansion in terms of eigenfunctions of a quantum harmonic oscillator, we derive analytically the corresponding Fokker-Planck equation in the overdamped limit. The result is fully consistent with the previous finding by Sancho, San Miguel, and Dürr [J. Stat. Phys. 28, 291 (1982)]. Our method allows us to generalize the Brinkman's hierarchy, and thus it would be straightforward to obtain higher-order corrections in a systematic inverse-friction expansion without any assumption. Our results are confirmed by numerical simulations for simple examples.

Faster is more different: mean-field dynamics of innovation diffusion.

Based on a recent model of paradigm shifts by Bornholdt et al., we studied mean-field opinion dynamics in an infinite population where an infinite number of ideas compete simultaneously with their values publicly known. We found that a highly innovative society is not characterized by heavy concentration in highly valued ideas: Rather, ideas are more broadly distributed in a more innovative society with faster progress, provided that the rate of adoption is constant, which suggests a positive correlation between innovation and technological disparity. Furthermore, the distribution is generally skewed in such a way that the fraction of innovators is substantially smaller than has been believed in conventional innovation-diffusion theory based on normality. Thus, the typical adoption pattern is predicted to be asymmetric with slow saturation in the ideal situation, which is compared with empirical data sets.