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The process of end-joining during nonhomologous repair of DNA double-strand breaks (DSBs) after radiation damage is considered. Experimental evidence has revealed that the dynamics of DSB ends exhibit subdiffusive motion rather than simple diffusion with rare directional movement. Traditional models often overlook the rare long-range directed motion. To address this limitation, we present a heterogeneous anomalous diffusion model consisting of subdiffusive fractional Brownian motion interchanged with short periods of long-range movement. Our model sheds light on the underlying mechanisms of heterogeneous diffusion in DSB repair and could be used to quantify the DSB dynamics on a time scale inaccessible to single particle tracking analysis. The model predicts that the long-range movement of DSB ends is responsible for the misrepair of DSBs in the form of dicentric chromosome lesions. [ABSTRACT FROM AUTHOR]

Transport of vesicles and organelles inside cells consists of constant-speed bidirectional movement along cytoskeletal filaments interspersed by periods of idling. This transport shows many features of anomalous diffusion. In this paper, we develop a non-Markovian persistent random walk model for intracellular transport that incorporates the removal rate of organelles. The model consists of two active states with different speeds and one resting state. The organelle transitions between states with switching rates that depend on the residence time the organelle spends in each state. The mesoscopic master equations that describe the average densities of intracellular transport in each of the three states are the main results of the paper. We also derive ordinary differential equations for the dynamics for the first and second moments of the organelles' position along the cell. Furthermore, we analyse models with power-law distributed random times, which reveal the prevalence of the Mittag-Leffler resting state and its contribution to subdiffusive and superdiffusive behaviour. Finally, we demonstrate a non-Markovian non-additivity effect when the switching rates and transport characteristics depend on the rate of organelles removal. The analytical calculations are in good agreement with numerical Monte Carlo simulations. Our results shed light on the dynamics of intracellular transport and emphasise the effects of rest times on the persistence of random walks in complex biological systems. [ABSTRACT FROM AUTHOR]

This paper is devoted to the current status of the novel fully active 3D (three-dimensional) fine-grained scintillator detector SuperFGD as a main part of the near off-axis detector upgrade program for the T2K experiment. The following important components related to the SuperFGD such as SuperFGD electronics and mechanics, wavelength shifting (WLS) fibers, and light emitting diode (LED) calibration system are also discussed here as well as the detector's near future. [ABSTRACT FROM AUTHOR]

Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses, the disease is related to increased levels and/or abnormal synthesis of certain proteins in the organism due to pathological processes, e.g., monoclonal gammopathy and chronic inflammation in rheumatic arthritis. Treatment of amyloidoses is focused on reducing amyloidogenic protein production and inhibition of its aggregation. Therapeutic approaches critically depend on the type of amyloidosis, which underlines the importance of early differential diagnostics. In fact, the most accurate diagnostics of amyloidosis and its type requires analysis of a biopsy specimen from the disease-affected organ. However, absence of specific symptoms of amyloidosis and the invasive nature of biomaterial sampling causes the late diagnostics of these diseases, which leads to a delayed treatment, and significantly reduces its efficacy and patient survival. The establishment of noninvasive diagnostic methods and discovery of specific amyloidosis markers are essential for disease detection and identification of its type at earlier stages, which enables timely and targeted treatment. This review focuses on current approaches to the diagnostics of amyloidoses, primarily with renal involvement, and research perspectives in order to design new specific tests for early diagnosis. [ABSTRACT FROM AUTHOR]

RAD51 is a central protein of homologous recombination and DNA repair processes that maintains genome stability and ensures the accurate repair of double-stranded breaks (DSBs). In this work, we assessed amyloid properties of RAD51 in vitro and in the bacterial curli-dependent amyloid generator (C-DAG) system. Resistance to ionic detergents, staining with amyloid-specific dyes, polarized microscopy, transmission electron microscopy (TEM), X-ray diffraction and other methods were used to evaluate the properties and structure of RAD51 aggregates. The purified human RAD51 protein formed detergent-resistant aggregates in vitro that had an unbranched cross-β fibrillar structure, which is typical for amyloids, and were stained with amyloid-specific dyes. Congo-red-stained RAD51 aggregates demonstrated birefringence under polarized light. RAD51 fibrils produced sharp circular X-ray reflections at 4.7 Å and 10 Å, demonstrating that they had a cross-β structure. Cytoplasmic aggregates of RAD51 were observed in cell cultures overexpressing RAD51. We demonstrated that a key protein that maintains genome stability, RAD51, has amyloid properties in vitro and in the C-DAG system and discussed the possible biological relevance of this observation. [ABSTRACT FROM AUTHOR]

The stationary solution of Smoluchowski's coagulation equation with injection is found analytically with different exponentially decaying source terms. The latter involve a factor in the form of a power law function that plays a decisive role in forming the steady-state particle distribution shape. An unsteady analytical solution to the coagulation equation is obtained for the exponentially decaying initial distribution without injection. An approximate unsteady solution is constructed by stitching the initial and final (steady-state) distributions. The obtained solutions are in good agreement with experimental data for the distributions of endocytosed low-density lipoproteins. [ABSTRACT FROM AUTHOR]

In this paper, we set up a stochastic model for the dynamics of active Rab5 and Rab7 proteins on the surface of endosomes and the acidification process that govern the virus–endosome fusion and endosomal escape of pH-responsive nanoparticles. We employ a well-known cut-off switch model for Rab5 to Rab7 conversion dynamics and consider two random terms: white Gaussian and Poisson noises with zero mean. We derive the governing equations for the joint probability density function for the endosomal pH, Rab5 and Rab7 proteins. We obtain numerically the marginal density describing random fluctuations of endosomal pH. We calculate the probability of having a pH level inside the endosome below a critical threshold and therefore the percentage of viruses and pH-responsive nanoparticles escaping endosomes. Our results are in good qualitative agreement with experimental data on viral escape. [ABSTRACT FROM AUTHOR]

We introduce a persistent random walk model for the stochastic transport of particles involving self-reinforcement and a rest state with Mittag–Leffler distributed residence times. The model involves a system of hyperbolic partial differential equations with a non-local switching term described by the Riemann–Liouville derivative. From Monte Carlo simulations, we found that this model generates superdiffusion at intermediate times but reverts to subdiffusion in the long time asymptotic limit. To confirm this result, we derived the equation for the second moment and find that it is subdiffusive in the long time limit. Analyses of two simpler models are also included, which demonstrate the dominance of the Mittag–Leffler rest state leading to subdiffusion. The observation that transient superdiffusion occurs in an eventually subdiffusive system is a useful feature for applications in stochastic biological transport. [ABSTRACT FROM AUTHOR]

Trajectories of endosomes inside living eukaryotic cells are highly heterogeneous in space and time and diffuse anomalously due to a combination of viscoelasticity, caging, aggregation and active transport. Some of the trajectories display switching between persistent and anti-persistent motion, while others jiggle around in one position for the whole measurement time. By splitting the ensemble of endosome trajectories into slow moving subdiffusive and fast moving superdiffusive endosomes, we analyzed them separately. The mean squared displacements and velocity auto-correlation functions confirm the effectiveness of the splitting methods. Applying the local analysis, we show that both ensembles are characterized by a spectrum of local anomalous exponents and local generalized diffusion coefficients. Slow and fast endosomes have exponential distributions of local anomalous exponents and power law distributions of generalized diffusion coefficients. This suggests that heterogeneous fractional Brownian motion is an appropriate model for both fast and slow moving endosomes. This article is part of a Special Issue entitled: "Recent Advances In Single-Particle Tracking: Experiment and Analysis" edited by Janusz Szwabiński and Aleksander Weron. [ABSTRACT FROM AUTHOR]