Arginine-selective modulation of the lysosomal transporter PQLC2 through a gate-tuning mechanism

Lysosomes degrade excess or damaged cellular components and recycle their building blocks through membrane transporters. They also act as nutrient-sensing signaling hubs to coordinate cell responses. The membrane protein PQ-loop repeat-containing protein 2 (PQLC2; “picklock two”) is implicated in both functions, as it exports cationic amino acids from lysosomes and serves as a receptor and amino acid sensor to recruit the C9orf72/SMCR8/WDR41 complex to lysosomes upon nutrient starvation. Its transport activity is essential for drug treatment of the rare disease cystinosis. Here, we quantitatively studied PQLC2 transport activity using electrophysiological and biochemical methods. Charge/substrate ratio, intracellular pH, and reversal potential measurements showed that it operates in a uniporter mode. Thus, PQLC2 is uncoupled from the steep lysosomal proton gradient, unlike many lysosomal transporters, enabling bidirectional cationic amino acid transport across the organelle membrane. Surprisingly, the specific presence of arginine, but not other substrates (lysine, histidine), in the discharge (“trans”) compartment impaired PQLC2 transport. Kinetic modeling of the uniport cycle recapitulated the paradoxical substrate-yet-inhibitor behavior of arginine, assuming that bound arginine facilitates closing of the transporter’s cytosolic gate. Arginine binding may thus tune PQLC2 gating to control its conformation, suggesting a potential mechanism for nutrient signaling by PQLC2 to its interaction partners.

Peritoneal physicochemical transport mechanisms: Hypotheses, models and controversies

This study answers criticisms by Waniewski et al. of the recent paper by Wolf on peritoneal transport kinetic models. Their criticisms centre on the accuracy of the data used for model fits, the hypothesis presented, which involves changes in glucose membrane parameters at high peritoneal glucose concentration and on the necessary techniques required to achieve accurate model parameter estimation. In response, this article shows that (1) the mean values previously captured from graphical depictions of Heimburger et al. are not different than those captured from the recent Waniewski et al. graphs, (2) a much simpler hypothesis is proposed, which centres on intraperitoneal pressure-induced lymph flow during the dialysis dwell and (3) the finding that the new model predictions, with only two constant parameter values, as estimated by the Powell algorithm, give a closer fit than the Waniewski model, which uses many time-varying parameters. The current findings again bring into question of the validity of their vasodilation hypothesis, leading to transient changes in capillary surface area during the dwell.

Role of Atomic Transport Kinetic on Nano-Film Solid State Growth

Nanostructures used to build current technology devices are generally based on the stack of several thin films (from few nanometer-thick to micrometer-thick layers) having different physical properties (conductors, semiconductors, dielectrics, etc.). In order to build such devices, thin film fabrication processes compatible with the entire device fabrication need to be developed (each subsequent process step should not deteriorate the previous construction). Solid-state reactive diffusion allows thin film exhibiting good interfacial properties (mechanical, electrical…) to be produced. In this case, the film of interest is grown from the reaction of an initial layer with the substrate on which it has been deposited, during controlled thermal annealing. In the case of the reaction of a nano-layer (thickness < 100 nm) with a semi-infinite substrate, nanoscale effects can be observed: i) the phases appear sequentially, ii) not all the thermodynamic stable phases appear in the sequence (some phases are missing), and iii) some phases are transient (they disappear as fast as they appear). The understanding of the driving forces controlling such nanoscale effects is highly desired in order to control the phase formation sequence, and to stabilize the phase of interest (for the targeted application) among all the phases appearing in the sequence.This chapter presents recent investigations concerning the influence of atomic transport on the nanoscale phenomena observed during nano-film reactive diffusion. The results suggest that nano-film solid-state reaction could be controlled by modifying atomic transport kinetics, allowing current processes based on thin-film reactive diffusion to be improved.

Evaluation of Phenol Transport Using Polymer Inclusion Membrane (PIM) with Polyeugenol as a Carrier

A recovery study of phenol with Polymer Inclusion Membranes (PIMs) needs to be evaluated to determine values of transport kinetic parameter, level of stability, and selectivity of the membrane. This paper describes results of the evaluation of phenol transport using PIMs with polyeugenol as a carrier. PIMs were made by mixing polyeugenol, dibenzylether, and polyvinylchloride in a solvent (tetrahydrofuran) then printed in a container with diameter 4.5 cm and allowed to vaporize for 72 hours. Further evaluation studies are conducted at pH 4.5 with various parameters, among of them are various times that were taken to identify parameters of the transport kinetics of phenol, membrane stability, characterization, and testing of membrane selectivity by comparing transport of phenol with another compound, in this study chromium is used. This study results in calculation of values of transport kinetics of membrane permeability obtained at 8.8 x 10-5 m/s, flux value of 9.512 x 10-4 g/m2s, and diffusion coefficient of 3.826 x 10-11 m2/s. Repeating use over three times, 48 hours, indicates reduction in power of phenol transport by 70.81%. While selectivity test indicates that membrane is used more selectively against phenol than chromium metal. Based on study results, phenol transport effectiveness using PIM with polyeugenol as carrier is 91.4% in optimum condition.

Canonical Transfer and Multiscale Energetics for Primitive and Quasigeostrophic Atmospheres

The past years have seen the success of a novel and rigorous localized multiscale energetics formalism in a variety of ocean and engineering fluid applications. In a self-contained way, this study introduces it to the atmospheric dynamical diagnostics, with important theoretical updates and clarifications of some common misconceptions about multiscale energy. Multiscale equations are derived using a new analysis apparatus—namely, multiscale window transform—with respect to both the primitive equation and quasigeostrophic models. A reconstruction of the “atomic” energy fluxes on the multiple scale windows allows for a natural and unique separation of the in-scale transports and cross-scale transfers from the intertwined nonlinear processes. The resulting energy transfers bear a Lie bracket form, reminiscent of the Poisson bracket in Hamiltonian mechanics; hence, we would call them “canonical.” A canonical transfer process is a mere redistribution of energy among scale windows, without generating or destroying energy as a whole. By classification, a multiscale energetic cycle comprises available potential energy (APE) transport, kinetic energy (KE) transport, pressure work, buoyancy conversion, work done by external forcing and friction, and the cross-scale canonical transfers of APE and KE, which correspond respectively to the baroclinic and barotropic instabilities in geophysical fluid dynamics. A buoyancy conversion takes place in an individual window only, bridging the two types of energy, namely, KE and APE; it does not involve any processes among different scale windows and is hence basically not related to instabilities. This formalism is exemplified with a preliminary application to the study of the Madden–Julian oscillation.