Subthreshold-level activities in neurons play a crucial role in neuronal oscillations. These small-amplitude oscillations have been suggested to be involved in synaptic plasticity and in determining the frequency of network oscillations. Subthreshold membrane oscillations (STOs) and subthreshold resonance oscillations (SROs) are the main constituents of subthreshold-level activities in neurons. In this study, a general theoretical framework for analyzing the mechanisms underlying STOs and SROs in neurons is presented. Results showed that the resting membrane potential and the hyperpolarization-activated potassium channel (h-channel) affect the subthreshold-level activities in stellate cells. The contribution of h-channel on resonance is attributed to its large time constant, which produces the time lag between Ih and the membrane potential. Conversely, the persistent sodium channels (Nap-channels) only play an amplifying role in these neurons.
Various types of neurons exhibit subthreshold resonance oscillation (preferred frequency response) to fluctuating sinusoidal input currents. This phenomenon is well known to influence the synaptic plasticity and frequency of neural network oscillation. This study evaluates the resonant properties of pacemaker pyloric dilator (PD) neurons in the central pattern generator network through mathematical modeling. From the pharmacological point of view, calcium currents cannot be blocked in PD neurons without removing the calcium-dependent potassium current. Thus, the effects of calcium (I(Ca)) and calcium-dependent potassium (I(KCa)) currents on resonant properties remain unclear. By taking advantage of Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine the effects of changing resting membrane potential and those ionic currents on the resonance. Results show that changing the resting membrane potential influences the amplitude and frequency of resonance so that the strength of resonance (Q-value) increases by both depolarization and hyperpolarization of the resting membrane potential. Moreover, hyperpolarization-activated inward current (I(h)) and I(Ca) (in association with I(KCa)) are dominant factors on resonant properties at hyperpolarized and depolarized potentials, respectively. Through mathematical analysis, results indicate that I h and I(KCa) affect the resonant properties of PD neurons. However, I(Ca) only has an amplifying effect on the resonance amplitude of these neurons.
Fibroblast-mediated compaction of collagen gels attracts extensive attention in studies of wound healing, cellular fate processes, and regenerative medicine. However, the underlying mechanism and the cellular mechanical niche still remain obscure. This study examines the mechanical behaviour of collagen fibrils during the process of compaction from an alternative perspective on the primary mechanical interaction, providing a new viewpoint on the behaviour of populated fibroblasts. We classify the collagen fibrils into three types - bent, stretched, and adherent - and deduce the respective equations governing the mechanical behaviour of each type; in particular, from a putative principle based on the stationary state of the instantaneous Hamiltonian of the mechanotransduction system, we originally quantify the stretching force exerted on each stretched fibrils. Via careful verification of a structural elementary model based on this classification, we demonstrate a clear physical picture of the compaction process, quantitatively elucidate the panorama of the micro mechanical niche and reveal an intrinsic biphasic relationship between cellular traction force and matrix elasticity. Our results also infer the underlying mechanism of tensional homoeostasis and stress shielding of fibroblasts. With this study, and sequel investigations on the putative principle proposed herein, we anticipate a refocus of the research on cellular mechanobiology, in vitro and in vivo.
In this paper, we present a general, fibril-based structural constitutive theory which accounts for three material aspects of crosslinked filamentous materials: the single fibrillar force response, the fibrillar network model, and the effects of alterations to the fibrillar network. In the case of the single fibrillar response, we develop a formula that covers the entropic and enthalpic deformation regions, and introduce the relaxation phase to explain the observed force decay after crosslink breakage. For the filamentous network model, we characterize the constituent element of the fibrillar network in terms its end-to-end distance vector and its contour length, then decompose the vector orientation into an isotropic random term and a specific alignment, paving the way for an expanded formalism from principal deformation to general 3D deformation; and, more important, we define a critical core quantity over which macroscale mechanical characteristics can be integrated: the ratio of the initial end-to-end distance to the contour length (and its probability function). For network alterations, we quantitatively treat changes in constituent elements and relate these changes to the alteration of network characteristics. Singular in its physical rigor and clarity, this constitutive theory can reproduce and predict a wide range of nonlinear mechanical behavior in materials composed of a crosslinked filamentous network, including: stress relaxation (with dual relaxation coefficients as typically observed in soft tissues); hysteresis with decreasing maximum stress under serial cyclic loading; strain-stiffening under uniaxial tension; the rupture point of the structure as a whole; various effects of biaxial tensile loading; strain-stiffening under simple shearing; the so-called "negative normal stress" phenomenon; and enthalpic elastic behaviors of the constituent element. Applied to compacted collagen gels, the theory demonstrates that collagen fibrils behave as enthalpic elasticas with linear elasticity within the gels, and that the macroscale nonlinearity of the gels originates from the curved fibrillar network. Meanwhile, the underlying factors that determine the mechanical properties of the gels are clarified. Finally, the implications of this study on the enhancement of the mechanical properties of compacted collagen gels and on the cellular mechanics with this model tissue are discussed.
miR-1 and miR-133 are clustered on the same chromosomal loci and are transcribed together as a single transcript that is positively regulated by ecotropic virus integration site-1 (EVI1). Previously, we described how miR-133 has anti-tumorigenic potential through repression of EVI1 expression. It has also been reported that miR-1 is oncogenic in the case of acute myeloid leukemia (AML). Here, we show that expression of miR-1 and miR-133, which have distinct functions, is differentially regulated between AML cell lines. Interestingly, the expression of miR-1 and EVI1, which binds to the promoter of the miR-1/miR-133 cluster, is correlative. The expression levels of TDP-43, an RNA-binding protein that has been reported to increase the expression, but inhibits the activity, of miR-1, were not correlated with expression levels of miR-1 in AML cells. Taken together, our observations raise the possibility that the balance of polycistronic miRNAs is regulated post-transcriptionally in a hierarchical manner possibly involving EVI1, suggesting that the deregulation of this balance may play some role in AML cells with high EVI1 expression.