Effect of Sodium Chloride Concentration on Saturated Permeability of Remolded Loess

Loess contains many sodium and chloride ions that can easily be leached when seepage occurs, thus affecting the mechanical properties of loess. This study investigated a series of sodium chloride solution concentrations to explore their influence on the permeability of remolded loess, as well as the underlying mechanism of such. The results indicated that the saturated hydraulic conductivity of remolded loess increases with time in response to different sodium chloride concentrations, and the sample was more permeable with increasing concentration. Moreover, the salt effect promoted the dissolution of calcite and dolomite, and the cation exchange stimulated the leaching of other cations, thus leading to further structural loosening. Furthermore, the aggregation of clay particles increased, thus forming a larger pore space among aggregates and providing effective channels for permeation. These findings provide a theoretical basis for an improved understanding of channel degradation in the loess area of Northwest China.

Protein kinase Cε activation induces EHD-dependent degradation and downregulation of KATP channels: Implications for glucose stimulated insulin secretion

Pancreatic β-cells have the unique ability to couple glucose metabolism to insulin secretion. This capacity is generally attributed to the ability of ATP to inhibit KATP channels, and the consequent β-cell membrane depolarization and excitation. This notion has recently been challenged by a study which demonstrated that high glucose (HG) downregulates the cell surface KATP channels, and thereby leads to β-cell depolarisation and excitation. The authors attributed the downregulation to HG-induced protein kinase C (PKC) activation and the consequent increase in channel endocytosis. This interpretation, however, is inconsistent with our previous findings that PKC activation does not affect endocytosis. To address this controversy, we revisited the problem: we have used cell biological and electrophysiological approaches combined with the pharmacological activator of PKC, PMA (phorbol 12-myristate 13-acetate). We first confirm that PKC does not play a role in KATP channel endocytosis; instead, it downregulates the channel by promoting lysosomal degradation coupled with reduced recycling. We then show that (i) mutation of the dileucine motif (355LL356) in the C-terminal domain of the Kir6.2 subunit of the KATP channel complex prevents lysosomal degradation; (ii) lysosomal targeting is mediated by the EHD (Eps15 homology domain– containing) proteins; and (iii) the PKC isoform responsible for channel degradation is PKCε. Taken together with the published data, we suggest that HG promotes β-cell excitability via two mechanisms: ATP-dependent channel inhibition and ATP-independent, PKCε-dependent channel degradation. The results likely have implications for glucose induced biphasic insulin secretion.

Clenbuterol Attenuates hERG Channel by Promoting the Mature Channel Degradation

Clenbuterol, a β2-selective adrenergic receptor agonist, is illicitly used in weight loss and performance enhancement and animal production. Increasing evidence demonstrates that clenbuterol induces various kinds of arrhythmias and QTc interval prolongation. However, little is known about the underlying mechanism. Most drugs are associated with QTc prolongation through interfering with human ether-a-go-go-related gene (hERG) K+ channels. The present study aims to investigate the effects and underlying mechanisms of clenbuterol on the hERG channel. HEK 293 cells were transfected with wild type and Y652A or F656A mutants of the hERG channel and treated with clenbuterol. The hERG current was recorded using whole-cell patch-clamp technique, and protein level was evaluated by Western blot. We found that clenbuterol decreases the mature form of the hERG protein at the cell membrane in a concentration- and time-dependent manner, without affecting the immature form. Correspondingly, clenbuterol chronic treatment reduced hERG current to a greater extent compared to acute treatment. In the presence of Brefeldin A (BFA), which was used to block hERG channel trafficking to cell membrane, clenbuterol reduced hERG on plasma membrane to a greater extent than BFA alone. In addition, the hERG channel’s drug binding sites mutant Y652A and F656A abolished clenbuterol-mediated hERG reduction and current blockade. In conclusion, clenbuterol reduces hERG channel expression and current by promoting the channel degradation. The effect of clenbuterol on the hERG channel is related to the drug-binding sites, Tyr-652 and Phe-656, located on the S6 domain. This biophysical mechanism may underlie clenbuterol-induced QTc prolongation or arrhythmia.

Practical Applications of Bed Scour Calculations: Two Case Studies

Pipelines can be exposed at water crossings where rivers lower the channel bed. Channel bed scour may cause damage to linear infrastructure such as pipelines by exposing the pipe to the flow of water and sediment. Accurate estimation of depth of scour is therefore critical in limiting damage to infrastructure. Channel bed scour has three main components: (1) general scour, (2) bed degradation, and (3) pool depth. General scour is the temporary lowering of the channel bed during a flood event. Channel bed degradation is the systematic lowering of a channel bed over time. Pool depth is depth of pools below the general bed elevation and includes the relocation of pools that result from river dynamics. Channel degradation is assessed in the field using indicators of channel incision such as channel bed armoring and bank characteristics, through the analysis of long profiles and sediment transport modelling. Pool depth is assessed using long profiles and channel movement over time. The catastrophic nature of bed lowering due to general scour requires a different assessment. A design depth of cover is based on analysis of depth of scour for a given return period (eg. 100-years). There are three main steps to predict general scour: (1) regional flood frequency analysis, (2) estimation of hydraulic variables, and (3) scour depth modelling. Typically, four scour models are employed: Lacey (1930), Blench (1969), Neill (1973), and Zeller (1981), with the average or maximum value used for design depth. We provide herein case studies for potential scour for pipeline water crossings at the Little Smoky River and Joachim Creek, AB. Using the four models above, and an analysis of channel degradation and pool depth, the recommended minimum depth of cover of 0.75 m and 0.142 m, respectively, were prescribed. Variability between scour models is large. The general scour model results varied from 0.45 m and 0.75 m for the Little Smoky River and 0.16 m to 0.51 m for Joachim Creek. While these models are more than 30 years old and do not adequately account for factors such as sediment mobility, they nevertheless do provide usable answers and should form part of the usual toolbox in water crossing scour calculations.