Reversible binding and rapid diffusion of proteins in complex with inositol lipids serves to coordinate free movement with spatial information

Polyphosphoinositol lipids convey spatial information partly by their interactions with cellular proteins within defined domains. However, these interactions are prevented when the lipids' head groups are masked by the recruitment of cytosolic effector proteins, whereas these effectors must also have sufficient mobility to maximize functional interactions. To investigate quantitatively how these conflicting functional needs are optimized, we used different fluorescence recovery after photobleaching techniques to investigate inositol lipid–effector protein kinetics in terms of the real-time dissociation from, and diffusion within, the plasma membrane. We find that the protein–lipid complexes retain a relatively rapid (∼0.1–1 µm2/s) diffusion coefficient in the membrane, likely dominated by protein–protein interactions, but the limited time scale (seconds) of these complexes, dictated principally by lipid–protein interactions, limits their range of action to a few microns. Moreover, our data reveal that GAP1IP4BP, a protein that binds PtdIns(4,5)P2 and PtdIns(3,4,5)P3 in vitro with similar affinity, is able to “read” PtdIns(3,4,5)P3 signals in terms of an elongated residence time at the membrane

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Electrochemical degradation of Reactive Blue 19 dye by combining boron doped diamond and reticulated vitreous carbon electrodes

Reactive Blue 19 (RB-19) dye has low fixation efficiency, a long half-life and high toxicity. It is easily loss during the cleaning of textiles and can remain in the environment for long time causing serious environmental problems if not removed. This study reports the degradation of RB-19 by: 1) the electrochemical direct degradation with Boron-Doped Diamond (BDD) electrodes and 2) a combined processes using BDD and Reticulated Vitreous Carbon (RVC) electrodes that generates H2O2. The direct degradation uses different current densities and concentrations. High currents densities, longer electrolysis time and low volumetric flow rates, favour RB-19 degradation removing total colour and 100 % TOC at 5 and 60 min respectively. At 41 mA cm-2 current density and 20 dm3 h-1 volumetric flow rate, the energy consumption to degrade 20 mg dm-3 of RB-19 was 279 kWh kg-1. The TOC removal of RB-19 dye combining BDD and RVC at a current density of 41 mA cm-2 was below 72% during 90 min and the energy consumption increased to 612 kWh kg-1. The higher energy consumption obtained during the combined process suggested that the direct degradation process at low volumetric flow rates is more efficient than the combined process

Electrochemical degradation of RB-5 dye by anodic oxidation, electro-Fenton and by combining anodic oxidation–electro-Fenton in a filter-press flow cell

This paper reports the removal of a recalcitrant and toxic dye, Reactive Black 5 (RB-5) by threemethods; 1) anodic oxidation (AO) on Boron-Doped Diamond (BDD), 2) by electro-Fenton (EF) process where hydrogen peroxide was produced by oxygen reduction on reticulated vitreous carbon (RVC) electrodes and 3) by the combination of AO–EF. The BDD and RVC electrodes were fitted in a filter-press flow cell in recycle batch mode of operation. The experimental set-up for the AO and EF processes consisted of two electrolyte compartments separated by a Nafion membrane with the dye contained in the anolyte and the catholyte, respectively. The combined AO–EF process used only one electrolyte compartment. The colour and total organic carbon (TOC) removal were more efficientwhen the AO and EF processes were used separately than the combined process, AO–EF. The influence of current density and initial concentration of ferrous ions were examined. The lowest energy efficiency (208 kWh kg?1) with the EF process was found when ?0.4 V vs. Ag/AgCl was applied to a RVC electrode and the concentration of Fe2+ was 1.0 × 10?4 mol dm?3 achieving total colour and 74% of TOC removals in less than 90 min electrolysis. All proposed processeswere able to promote high percentages of TOC removal following a pseudo-first order kinetic oxidation. The BDD electrode was the most effective material to remove RB-5 dye within 7.5 min and presented the highest apparent rate constant (0.835 min?1) with 82% TOC removal within 30 min at an energy consumption of 291 kWh kg?1 and 41.1 mA cm?2 current density. In the case of the combined process AO–EF the electrodegradation rate of RB-5 was at least three times lower, apparent rate constant (0.269 min?1), and 32% of TOC was removed with a high EC (682 kWh kg?1). Therefore oxidation process applied separately was more efficien

The Alpha Risk of Taguchi Method for LTB Type Quality Characteristic with L 8

Taguchi method, signal-to-noise ratio, alpha risk, simulation,