A Fast Markovian Method For Modeling Channel Noise In Neurons

Channel noise results from rapid transitions of protein channels from closed to open state and is generally considered as the most dominant source of electrical noise causing membrane-potential fluctuations even in the absence of synaptic inputs. The simulation of a realistic channel noise remains a source of possible error. Although the Markovian method is considered as the golden standard for appropriate description of channel noise, its computation time increasing exponentially with numbers of channels, it is poorly suitable to simulate realistic features. We describe here a novel algorithm for simulating ion channel noise based on Markov chains (MC). Although this new algorithm refers to a Monte-Carlo process, it only needs few random numbers whatever the number of channels involved. Our fast MC (FMC) model does not exhibit the drawbacks due to approximations based on stochastic differential equations. In fact, we show here, that these drawbacks can be highlighted even for a high number of channels.

Downregulation of RyR and NCX in the neonatal rat ventricular myocyte modulates cytosolic [Ca2+]

Calcium (Ca2+) is necessary for cardiac muscle contraction. RyR, NCX, and SERCA are key regulatory protein channels for cytosolic Ca2+ in the cardiomyocyte. Expression levels of these proteins are a function of development and disease. We investigated how downregulation by siRNAs of RyR and NCX affected expression levels of complimentary proteins their corresponding intracellular Ca2+ transients. We compared the experimentally observed Ca2+ transients to those predicted by mathematical models. Experimental results show RyR downregulation decreased SERCA and increased NCX protein levels. The associated Ca2+ transient had decreased amplitude, increased time-to-peak (TTP), time-to-50% (T50), and time-to-90% (T90) Ca2+ removal with respect to the control population. NCX downregulation increased SERCA production without significant changes in RyR expression levels. The corresponding Ca2+ transient increased amplitude, no change in TTP and T50 Ca2+ removal, but increased T90 Ca2+ removal with respect to the control population. Computational models that accurately predict the observed experimental data suggest compensatory changes occurring in the expression levels as well as biochemical activity of the regulatory proteins.

IMCellXMBD: A statistical approach for robust cell identification and quantification from imaging mass cytometry images

ImagingMass Cytometry (IMC) has become a useful tool in biomedical research due to its capability to measure over 100 markers simultaneously. Unfortunately, some protein channels in IMC images can be very noisy, whichmay significantly affect the phenotyping results without proper data processing. We developed IMCellXMBD, a highly effective and generalizable cell identification and quantification method for IMC images. IMCell performs denoising by subtracting an estimated background noise value from pixel values for each individual protein channel, identifies positive cells from negative cells by comparing the distribution between segmented cells and decoy cells, and normalize the protein expression levels of the identified positive cells for downstream data analysis. Experimental results demonstrate that our method significantly improves the reliability of cell phenotyping which is essential for using IMC in biomedical studies.

The Role of Space Weather and Geophysical Processes in Behavioral Studies

Living organisms with developed endocrine systems react in a complex way to environmental changes. Changing atmospheric pressure causes different blood pressures or hormone levels; carcinogenic radiation modifies the structure of DNA. Charged particles and ions act as neurotransmitters and block certain types of protein channels and receptors. A high concentration of carbon dioxide has an indirect effect on both blood pressure and neuron activity. The bioelectric nature of living tissues highlights the complexity of the connection between the dynamic physical environment and biological systems. Recent results from studies on the interactions and connections mentioned above are reviewed in this paper.

Aquaporins in Immune Cells and Inflammation: New Targets for Drug Development

The mammalian immune system senses foreign antigens by mechanisms that involve the interplay of various kinds of immune cells, culminating in inflammation resolution and tissue clearance. The ability of the immune cells to communicate (via chemokines) and to shift shape for migration, phagocytosis or antigen uptake is mainly supported by critical proteins such as aquaporins (AQPs) that regulate water fluid homeostasis and volume changes. AQPs are protein channels that facilitate water and small uncharged molecules’ (such as glycerol or hydrogen peroxide) diffusion through membranes. A number of AQP isoforms were found upregulated in inflammatory conditions and are considered essential for the migration and survival of immune cells. The present review updates information on AQPs’ involvement in immunity and inflammatory processes, highlighting their role as crucial players and promising targets for drug discovery.

Membrane protein channels equipped with a cleavable linker for inducing catalysis inside nanocompartments

Precisely timed initiation of catalysis and stability of the catalytic enzymes provided by stimuli-responsive compartments.

Porous organic cages as synthetic water channels

Nature has protein channels (e.g., aquaporins) that preferentially transport water molecules while rejecting even the smallest hydrated ions. Aspirations to create robust synthetic counterparts have led to the development of a few one-dimensional channels. However, replicating the performance of the protein channels in these synthetic water channels remains a challenge. In addition, the dimensionality of the synthetic water channels also imposes engineering difficulties to align them in membranes. Here we show that zero-dimensional porous organic cages (POCs) with nanoscale pores can effectively reject small cations and anions while allowing fast water permeation (ca. 109 water molecules per second) on the same magnitude as that of aquaporins. Water molecules are found to preferentially flow in single-file, branched chains within the POCs. This work widens the choice of water channel morphologies for water desalination applications.

Role of channels in the oxygen permeability of red blood cells

Many have believed that oxygen (O2) crosses red blood cell (RBC) membranes by dissolving in lipids that offer no resistance to diffusion. However, using stopped-flow (SF) analyses of hemoglobin (Hb) absorbance spectra during O2 off-loading from mouse RBCs, we now report that most O2 traverses membrane-protein channels. Two agents excluded from the RBC interior markedly slow O2 off-loading: p-chloromercuribenzenesulfonate (pCMBS) reduces inferred membrane O2 permeability (PMembrane) by ∼82%, and 4,4’-diisothiocyanatostilbene-2,2’-disulfonate (DIDS), by ∼56%. Because neither likely produces these effects via membrane lipids, we examined RBCs from mice genetically deficient in aquaporin-1 (AQP1), the Rh complex (i.e., rhesus proteins RhAG + mRh), or both. The double knockout (dKO) reduces PMembrane by ∼55%, and pCMBS+dKO, by ∼91%. Proteomic analyses of RBC membranes, flow cytometry, hematology, and mathematical simulations rule out explanations involving other membrane proteins, RBC geometry, or extracellular unconvected fluid (EUF). By identifying the first two O2 channels and pointing to the existence of other O2 channel(s), all of which could be subject to physiological regulation and pharmacological intervention, our work represents a paradigm shift for O2 handling.

Light as a Life Tool

Visual light, and radiation of other frequencies, are highly important for scientific research. The first light microscopes made it possible for the first time to see that organisms from plants to humans are composed of cells. Electron microscopes have allowed scientists to study the structural components of cells in great detail, and even determine the shapes of individual proteins. Many lifeforms also use light to attract a mate or prey, or deter an attacker. Following the identification of the gene coding for the fluorescent protein that makes certain jellyfish glow green it has become possible to use this to genetically label proteins in a living cell, or even a live animal. This means that now the location of proteins in a cell can be determined exactly. A major recent step forward in neuroscience came with the discovery of protein channels in algae that conduct ions in response to light. By creating transgenic mice that have these proteins in their brain neurons, it is now possible to modulate the activity of these neurons by shining light into the brain though microscopic fibre optic cables. This new science of optogenetics allows neurons to be switched on or off experimentally. The optogenetic approach has been used to uncover the neural circuits involved in memory, pain and pleasure. In the future this technique might be used to treat physical pain or depression in people. Controversially, it might be also be misused, to supress memories, or even create completely false ones in people’s heads.

Study on the association SLC2A9 RS12510549 with uric acid and gout in Vietnamese population

Gout is the most common form of arthritis in Vietnam and around the world, caused by an excess of blood uric acid levels. The occurrence of gout is influenced by many risk factors such as diet, living and genetic factors. Studies showed gout is associated with polymorphisms located on genes that encode transport protein channels, including SLC2A9 rs12510549. To evaluate the association of polymorphism SLC2A9 rs12510549 to uric acid levels and gout in the Vietnamese population, we genotyped rs12510549 of 519 subjects (168 gout patients and 351 healthy people) by the PCR–RFLP method. The relationship between genotype distribution, the allele frequency of polymorphism with uric acid levels and gout was assessed through statistical methods. The results show that SLC2A9rs12510549 was in accordance with HWE (p> 0.05) and the genotype frequencies of TT, TC and CC were 0.73, 0.25 and 0.02, respectively, confirming the randomness and representation of the study population. The genotype distribution and frequency of the rs12510549 allele were determined unrelated to uric acid levels and gout in the Vietnamese population (p>0.05). Further study with a larger sample size should be implemented to confirm our results on the association of SLC2A9rs12510549 and gout in the Vietnamese population.