Perspectives of Molecular Therapy-Targeted Mitochondrial Fission in Hepatocellular Carcinoma

Current advances of molecular-targeting therapies for hepatocellular carcinoma (HCC) have improved the overall survival significantly, whereas the results still remain unsatisfied. Recently, much attention has been focused on organelles, such as the mitochondria, to reveal novel strategies to control the cancers. The mitochondria are vital organelles which supply energy and maintain metabolism in most of the eukaryotic cells. They not only execute critical bioenergetic and biosynthetic functions but also regulate ROS homeostasis and apoptosis. Existing in a dynamic equilibrium state, mitochondria constantly undergo the fission and fusion processes in normal situation. Increasing evidences have showed that mitochondrial fission is highly related to the diseases and cancers. Distinctive works have proved the significant effects of mitochondrial fission on HCC behaviors and the crosstalks with other molecular pathways. Here, we provide an overview of the mitochondrial fission and the link with HCC, emphasizing on the underlying molecular pathways and several novel materials that modulate HCC behaviors.

The Kinetics of Manganese Sorption on Ukrainian Tuff and Basalt—Order and Diffusion Models Analysis

The study aimed to determine the nature of the kinetics of the manganese sorption process on Ukrainian tuff and basalt at different temperatures characteristic of the natural water environment. The scope of the research included manganese sorption kinetic test on natural mineral sorbents at temperatures of 10, 17.5 and 25 °C in slightly acidic conditions. Sorption (pseudo-first order, pseudo-second order and Elovich models) and diffusion kinetic models (liquid film diffusion and intraparticle diffusion) were used in the analysis of test results. The manganese sorption process on both tuff and basalt proceeded quickly. The dynamic equilibrium state of manganese sorption settled after 35 and 45 min on tuff and basalt respectively. Although the process took place in a slightly acidic environment and below pHPZC of the sorbents, possible electrostatic repulsion did not inhibit the removal of Mn. The Mn sorption on both materials followed the PSO kinetics model. Based on the diffusion kinetic models, it was determined that Mn sorption process on both materials was influenced by diffusion through the boundary layer and intraparticle diffusion. The differences in removal efficiency and rate of Mn sorption in the temperature range of 10–25 °C were not found.

Morphodynamic equilibrium of lowland river systems during autoretreat

Lowland river systems (with channel slopes of 10−5 to 10−4) inevitably shift away (retreat upstream) from the receiving basin under a sustained rate of base-level rise, even if the system can maintain a period of advance at the onset of rise. This autogenic pattern of transition from progradation to retrogradation through steady base-level rise and sediment supply is termed “autoretreat.” Using a morphodynamic model of autoretreat, this study explored the varying channel hydrodynamics of lowland fluvial systems and associated stratigraphic record under sustained base-level rise and constant sediment supply. Results from the numerical simulations show that a fluvial system will reach a state of dynamic equilibrium during autoretreat where both the backwater length and the morphodynamic adjustment of the downdip channel profile become steady. Moreover, when this dynamic equilibrium state is realized, simulated systems display a persistent twofold downstream deepening of flow depth across the backwater zone, a pattern that is also present in many natural systems. In general, backwater effects play a key role in the morphodynamics of a lowland fluvial-deltaic system during autoretreat, and this hydrodynamic condition is therefore critical for predicting river responses to sea-level change.

Dynamics of the Bacillus subtilis Min system

SummaryDivision site selection is a vital process to ensure generation of viable offspring. In many rod-shaped bacteria a dynamic protein system, termed the Min system, acts as a central regulator of division site placement. The Min system is best studied in Escherichia coli where it shows a remarkable oscillation from pole to pole with a time-averaged density minimum at midcell. Several components of the Min system are conserved in the Gram-positive model organism Bacillus subtilis. However, in B. subtilis it is believed that the system forms a stationary bipolar gradient from the cell poles to midcell. Here, we show that the Min system of B. subtilis localizes dynamically to active sites of division, often organized in clusters. We provide physical modelling using measured diffusion constants that describe the observed enrichment of the Min system at the septum. Modelling suggests that the observed localization pattern of Min proteins corresponds to a dynamic equilibrium state. Our data provide evidence for the importance of ongoing septation for the Min dynamics, consistent with a major role of the Min system to control active division sites, but not cell pole areas.

A unique internal ribosome entry site representing a dynamic equilibrium state of RNA tertiary structure in the 5′-UTR of Wheat yellow mosaic virus RNA1

Internal ribosome entry sites (IRESes) were first reported in RNA viruses and subsequently identified in cellular mRNAs. In this study, IRES activity of the 5′-UTR in Wheat yellow mosaic virus (WYMV) RNA1 was identified, and the 3′-UTR synergistically enhanced this IRES activity via long-distance RNA–RNA interaction between C80U81and A7574G7575. Within the 5′-UTR, the hairpin 1(H1), flexible hairpin 2 (H2) and linker region (LR1) between H1 and H2 played an essential role in cap-independent translation, which is associated with the structural stability of H1, length of discontinuous stems and nucleotide specificity of the H2 upper loop and the long-distance RNA–RNA interaction sites in LR1. The H2 upper loop is a target region of the eIF4E. Cytosines (C55, C66, C105 and C108) in H1 and H2 and guanines (G73, G79 and G85) in LR1 form discontinuous and alternative base pairing to maintain the dynamic equilibrium state, which is used to elaborately regulate translation at a suitable level. The WYMV RNA1 5′-UTR contains a novel IRES, which is different from reported IRESes because of the dynamic equilibrium state. It is also suggested that robustness not at the maximum level of translation is the selection target during evolution of WYMV RNA1.

Geosystems‘ Pathways to the Future of Sustainability

The world’s future development depends on effective human-computer linkages. From local to global, the virtual illustrations of a geographical place have to emphasize in an integrative approach peoples‘ key position in the Geosystem. Human values and social networks are now empowered by the unlimited creativity of smartphone applications. Our Geosystem grounded theory envisions that the sustainable management of natural resources is a lifelong learning environment where the poor communities have access to the new technological advances. This paper will attempt to show the effectiveness of Geomedia techniques in the Geosystems identification, evaluation, and valorization processes for the benefit of local inhabitants. This present research methodology uses smartphone apps, Google Earth environmental datasets, Global Positioning Systems, and WebGIS for a geographical investigation and objective assessment of regions throughout the world. The results demonstrate that self-sustainable Geosystems will always be capable to regulate, control and assess progress towards their dynamic equilibrium state, continuously adapting to environmental and societal changes.

Reconstitution of the equilibrium state of dynamic actin networks

Principles of regulation of actin network dimensions, fundamentally important for cell functions, remain unclear. We studied in vitro and in silico the effect of key parameters, actin density, ADF/Cofilin concentration and network width on the network length. In the presence of ADF/Cofilin, networks reached equilibrium and became globally treadmilling. At the trailing edge, the network disintegrated into large fragments. A mathematical model predicts the network length as a function of width, actin and ADF/Cofilin concentrations. Local depletion of ADF/Cofilin by binding to actin is significant, leading to wider networks growing longer. A single rate of breaking network nodes, proportional to ADF/Cofilin density and inversely proportional to the square of the actin density, can account for the disassembly dynamics. Selective disassembly of heterogeneous networks by ADF/Cofilin controls steering during motility. Our results establish general principles on how the dynamic equilibrium state of actin network emerges from biochemical and structural feedbacks.

Limiting the development of riparian vegetation in the Isère River: A physical modelling study

Physical modelling experiments are conducted to investigate if a modification of the Isère River (French Alps) hydrology by changing dams management is able to foster riverbed morphodynamic and, thus limiting riparian plant development. The experimental setup is a 1:35 scale, undistorted movable bed designed to ensure the Froude number similarity and initial conditions for sediment particle motion. The physical model is 35 m long, 2.6 m wide, with a sand mixture composed of three grain size classes. Two runs with different flow and bed load conditions are simulated. Preliminary results show an intense riverbed activity when the system reaches a dynamic equilibrium state. Under these conditions, bar mobility is strong enough to limit vegetation encroachment only when water discharges are higher than the discharge of a 5-years flood during more than 10 days. These results indicate that the hydrological characteristics of the Isère River and the actual configuration of the hydropower structures could be not able to release annually the flow conditions needed to control riparian plant development.

Dynamic preservation of Texel Inlet, the Netherlands: understanding the interaction of an ebb-tidal delta with its adjacent coast

Tidal inlets and the associated ebb-tidal deltas can significantly impact the coastal sediment budget due to their ability to store or release large quantities of sand. Nearly 300 million m3(mcm) of sediments were eroded from Texel Inlet's ebb-tidal delta and the adjacent coasts following the closure of the Zuiderzee in 1932. This erosion continues even today as a net loss of 77 mcm was observed between 1986 and 2015. To compensate, over 30 mcm of sand has been placed on the adjacent coastlines since 1990, making maintenance of these beaches the most intensive of the entire Dutch coastal system.Highly frequent and detailed observations of both the hydrodynamics and morphodynamics of Texel Inlet have resulted in a unique dataset of this largest inlet of the Wadden Sea, providing an opportunity to investigate inlet sediment dynamics under the influence of anthropogenic pressure. By linking detailed measurements of bathymetric change to direct observations of processes we were able to unravel the various components that have contributed to the supply of sediment to the basin, and develop a four-stage conceptual model describing the multi-decadal adaptation of the ebb-tidal delta.Prior to closure of the Zuiderzee a dynamic equilibrium state (stage 1) existed with a stable ebb-tidal delta. The largest morphological changes occurred in roughly the first 40 years since the closure, and were dominated by the rotation and scouring of large tidal channels and landward retreat of the Noorderhaaks ebb shoal (stage 2; adaptation). Between 1975 and 2001 the general layout of main channels and shoals was stable, but large sediment losses continued to occur (stage 3; equilibrium erosional state). Since 2001, the erosion rates have significantly reduced to 2 mcm a−1(stage 4; stabilisation).Twenty-five years of data on ‘Dynamic Preservation’ prove that sand nourishments are well capable of keeping the coastlines adjacent to the Texel Inlet in place. Moreover, the abundant supply of sediment may also have compensated for the sediment losses on the larger scale of the southern part of the ebb-tidal delta, resulting in a recent stabilisation of its volume. This response illustrates the potential benefits of Dynamic Preservation not only for coastline resilience but also on the larger scale of the inlet system. Such knowledge is essential for future preservation, management and maintenance of inlet systems in the scope of climate change and accelerated sea-level rise.

Public administration and cyclical mechanisms socio-economic development

The article discusses the cyclical mechanisms of socio-economic development as one of kinds of natural cycles. The author notes that in all cases the basis of the self-oscillations are cyclical. And they are only possible with the constant influx of three resources - en-ergy, matter and information. On this basis, it is noted that the self-organization of co-herent structures, regardless of their Genesis, is due to intrinsically contradictory unity of two interacting types of resource flows - energy, matter and information – And-stream forming system, and the In-flow that will disrupt her. The cycle of development of sys-tems consists of two components: one that describes the development of a system with positive saturation, according to a logistic law (A>B); and another describing the devel-opment of the system with negative saturation (<A), which also occurs according to the logistic law. In all cases, the process is directed to A=B. Any development of social sys-tems can be divided into several types, among which are the following: 1) the conformal cycle (self-similar) development is dynamic - equilibrium state; 2) the evolutionary cycle of revolutions; 3) the evolutionary cycle of disasters. The author also considers the peculiarities of external influence on state control of economies by the countries-leaders who have the ability to regulate access to resources - energy, matter and information.