Percolation transition determines protein size limit for passive transport through the nuclear pore complex

Nuclear pore complexes (NPCs) control biomolecular transport in and out of the nucleus. Disordered nucleoporins in the complex's central pore form a permeation barrier, preventing unassisted transport of large biomolecules. Here, we combine coarse-grained simulations of an experimentally-derived NPC structure with a theoretical model to determine the microscopic mechanism of passive transport. Brute-force simulations of protein diffusion through the NPC reveal telegraph-like behavior, where prolonged diffusion on one side of the NPC is interrupted by rapid crossings to the other. We rationalize this behavior using a theoretical model that reproduces the energetics and kinetics of permeation solely from statistical analysis of transient voids within the disordered mesh. As the protein size increases, the mesh transforms from a soft to a hard barrier, enabling orders-of-magnitude reduction in permeation rate for proteins beyond the percolation size threshold. Our model enables exploration of alternative NPC architectures and sets the stage for uncovering molecular mechanisms of facilitated nuclear transport.

Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis

This review focuses on the consequences of GAPDH S-nitrosylation at the catalytic cysteine residue. The widespread hypothesis according to which S-nitrosylation causes a change in GAPDH structure and its subsequent binding to the Siah1 protein is considered in detail. It is assumed that the GAPDH complex with Siah1 is transported to the nucleus by carrier proteins, interacts with nuclear proteins, and induces apoptosis. However, there are several conflicting and unproven elements in this hypothesis. In particular, there is no direct confirmation of the interaction between the tetrameric GAPDH and Siah1 caused by S-nitrosylation of GAPDH. The question remains as to whether the translocation of GAPDH into the nucleus is caused by S-nitrosylation or by some other modification of the catalytic cysteine residue. The hypothesis of the induction of apoptosis by oxidation of GAPDH is considered. This oxidation leads to a release of the coenzyme NAD+ from the active center of GAPDH, followed by the dissociation of the tetramer into subunits, which move to the nucleus due to passive transport and induce apoptosis. In conclusion, the main tasks are summarized, the solutions to which will make it possible to more definitively establish the role of nitric oxide in the induction of apoptosis.

An update on passive transport in and out of plant cells

Transport across membranes is critical for plant survival. Membranes are the interfaces at which plants interact with their environment. The transmission of energy and molecules into cells provides plants with the source material and power to grow, develop, defend, and move. An appreciation of the physical forces that drive transport processes is thus important for understanding plant growth and development. We focus on the passive transport of molecules, describing the fundamental concepts and demonstrating how different levels of abstraction can lead to different interpretations of the driving forces. We summarise recent developments on quantitative frameworks for describing diffusive and bulk flow transport processes in and out of cells, with a more detailed focus on plasmodesmata, and outline open questions and challenges.

A parsimonious model of longitudinal stream DOC patterns based on groundwater inputs and in-stream uptake

The supply of terrestrial dissolved organic carbon (DOC) to aquatic ecosystems affects local in-stream processes and downstream transport of DOC in the fluvial network. However, we have an incomplete understanding on how terrestrial DOC inputs alter longitudinal variations of DOC concentration along headwater stream reaches because groundwater discharge, groundwater DOC concentration and in-stream DOC uptake vary at relatively short spatial and temporal scales. In the riparian zone, the convergence of subsurface flow paths can facilitate the inflow of terrestrial DOC from large upslope contributing areas to narrow sections of the stream. We refer to these areas of flow path convergence as discrete riparian inflow points (DRIPs). In this study, we ask how longitudinal patterns of stream DOC concentrations are affected by DRIPs, as they are major inputs of terrestrial DOC and important locations for in-stream processes. We used a mixing model to simulate stream DOC concentrations along a 1.5 km headwater reach for fifteen sampling campaigns with flow conditions ranging from droughts to floods. Four sets of model scenarios were used to compare different representations of hydrology (distributed inputs of DRIPs vs diffuse groundwater inflow), and in-stream processes (passive transport vs in-stream biological uptake). Results showed that under medium (10–50 l/s) and high flow conditions (> 50 l/s), accounting for lateral groundwater inputs from DRIPs improved simulations of stream DOC concentrations along the reach. Moreover, in-stream biological uptake improved simulations across low to medium flow conditions (< 50 l/s). Only during an experimental drought, longitudinal patterns of stream DOC concentration were simulated best using diffuse groundwater inflow and passive transport scenarios. These results show that the role of hydrology and in-stream processes on modulating downstream DOC exports varies over time. Importantly, we demonstrate that accounting for preferential groundwater inputs to the stream is needed to capture longitudinal dynamics in mobilization and in-stream uptake of terrestrial DOC. The dominant role of DRIPs in these transport and reaction mechanisms suggests that consideration of DRIPs can improve stream biogeochemistry frameworks and help inform management of near-stream areas that exert a large influence on stream conditions.

Transport Characteristics of Plasma Membranes of PK-15 Passaged Cells

The values of permeability coefficients to water molecules and cryoprotectants are demanded to select the optimal duration of exposure of cells in cryoprotective media at the stage of their preparation for cryopreservation, as well as to find optimal cooling and warming rates during the freeze-thawing of cell suspensions. The necessary numerical values of such cell parameters as the osmotically inactive volume α and the surface-area-to-volume ratio γ were obtained for the analytical evaluation of the permeability coefficients of the PK-15 cells’ plasma membranes using physico-mathematical modelling. The permeability coefficients kp of the plasma membranes of PK-15 cells to 1,2-PD, EG, DMSO and glycerol cryoprotectants molecules, as well as the filtration coefficients Lp to water molecules at temperatures of 25, 15 and 5°C were determined by approximating the experimental data of the change in relative volume of cells on exposure time in the studied solutions by theoretical curves calculated on the basis of physical and mathematical model of passive transport of water and permeable substances under the condition of their maximum coincidence. The value of the activation energy of the transmembrane transfer of molecules of these substances is calculated

Transmembrane penetration mechanism of Cyclic Pollutants Inspected by Molecular Dynamics and Metadynamics. Case of Morpholine, Phenol, 1,4-Dioxane and Oxane.

The presence of industrially produced chemicals in water is often not monitored while their passive transport and accumulation can cause serious damage in living cells. Molecular dynamics simulations make an...

Methods of feeding colostrum and their effect on the passive immunity

Passive transport of colostral immunoglobulins is essential for calves to maintain optimal health. There are many factors that influence the absorption of immunoglobulins such as colostrum density, timing of ingestion, volume of colostrum but also the method of feeding. This study compares two manners of feeding calves – the esophageal tube feeder (n = 97) and the nipple bottle (n = 97), and their effect on the number of all absorbed immunoglobulins (IgG, IgM, IgA, IgD, and IgE). It was statistically proven that absorption of immunoglobulins is better with the nipple bottle (P < 0.0001). The feeding of calves through a nipple bottle is more beneficial because the content of total protein is the higher than by the feeding through an esophageal tube feeder.