Inhibition of the Aquaporin-1 Cation Conductance by Selected Furan Compounds Reduces Red Blood Cell Sickling

In sickle cell disease (SCD), the pathological shift of red blood cells (RBCs) into distorted morphologies under hypoxic conditions follows activation of a cationic leak current (Psickle) and cell dehydration. Prior work showed sickling was reduced by 5-hydroxylmethyl-2-furfural (5-HMF), which stabilized mutant hemoglobin and also blocked the Psickle current in RBCs, though the molecular basis of this 5-HMF-sensitive cation current remained a mystery. Work here is the first to test the hypothesis that Aquaporin-1 (AQP1) cation channels contribute to the monovalent component of Psickle. Human AQP1 channels expressed in Xenopus oocytes were evaluated for sensitivity to 5-HMF and four derivatives known to have differential efficacies in preventing RBC sickling. Ion conductances were measured by two-electrode voltage clamp, and osmotic water permeability by optical swelling assays. Compounds tested were: 5-HMF; 5-PMFC (5-(phenoxymethyl)furan-2-carbaldehyde); 5-CMFC (5-(4-chlorophenoxymethyl)furan-2-carbaldehyde); 5-NMFC (5-(2-nitrophenoxymethyl)-furan-2-carbaldehyde); and VZHE006 (tert-butyl (5-formylfuran-2-yl)methyl carbonate). The most effective anti-sickling agent, 5-PMFC, was the most potent inhibitor of the AQP1 ion conductance (98% block at 100 µM). The order of sensitivity of the AQP1 conductance to inhibition was 5-PMFC > VZHE006 > 5-CMFC ≥ 5-NMFC, which corresponded with effectiveness in protecting RBCs from sickling. None of the compounds altered AQP1 water channel activity. Combined application of a selective AQP1 ion channel blocker AqB011 (80 µM) with a selective hemoglobin modifying agent 5-NMFC (2.5 mM) increased anti-sickling effectiveness in red blood cells from human SCD patients. Another non-selective cation channel known to be expressed in RBCs, Piezo1, was unaffected by 2 mM 5-HMF. Results suggest that inhibition of AQP1 ion channels and capacity to modify hemoglobin are combined features of the most effective anti-sickling agents. Future therapeutics aimed at both targets could hold promise for improved treatments for SCD.

Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated With Lung Adenocarcinoma: A Case Report

Neuromyelitis Optica spectrum disorder is an inflammatory demyelinating disease affecting the central nervous system (CNS), characterized by triad optic neuritis, transverse myelitis, and area postrema syndrome. Antibodies directed against aquaporin-4 (AQP-4), a water channel expressed on the astrocytic membrane, are supposed to play a pathogenic role and are detected in ~80% of cases. Clinical signs of Neuromyelitis Optica spectrum disorder (NMOSD) in elderly patients should arouse the suspicion of paraneoplastic etiology. In this article, we discussed a case of a 76-year-old woman with a 2-month history of confusion, dysarthria, and progressive bilateral leg weakness. A whole-body CT scan showed a neoformation of 5 cm in diameter in the median lobe infiltrating the mediastinal pleura. The tumor had already spread to both the upper and lower right lobes, parietal pleura, and multiple lymph nodes. Pleural cytology revealed adenocarcinoma cells. The brain MRI documented hyperintense alteration in fluid-attenuated inversion recovery (FLAIR) images, involving the anterior portion of the corpus callosum and the periependymal white matter surrounding the lateral ventricles, with mild contrast enhancement on the same areas and meningeal tissue. T2-weighted spinal cord MRI sequences showed extended signal hyperintensity from bulbo-cervical junction to D7 metamer, mainly interesting the central component and the gray matter. Cerebrospinal fluid analysis revealed no neoplastic cells. Serum AQP-4 immunoglobulin (IgG) antibodies were found. Meanwhile, the patient rapidly developed progressive paraparesis and decreased level of consciousness. High-dose intravenous methylprednisolone therapy was started but her conditions rapidly deteriorated. No other treatment was possible.

Apelin-13 Decreases Epithelial Sodium Channel (ENaC) Expression and Activity in Kidney Collecting Duct Cells

BACKGROUND/AIMS: Apelin and its G protein-coupled receptor APLNR (also known as APJ) are widely expressed within the central nervous system and peripheral organs including heart, lung and kidney. Several studies have shown that the apelin/APJ system is involved in various important physiological processes such as energy metabolism, cardiovascular functions and fluid homeostasis. In the kidney, the apelin/APJ system performs a wide range of activities. We recently demonstrated that apelin antagonises the hydro-osmotic effect of vasopressin on aquaporin-2 water channel (AQP-2) expression by reducing its mRNA and protein levels in collecting duct principal cells. The central role of these cells in water and sodium transport is governed by AQP-2 and the epithelial sodium channel (ENaC). The coordination of these channels is essential for the control of extracellular fluid volume, sodium homeostasis and blood pressure. This study aimed at investigating the role of apelin in the regulation of sodium balance in the distal nephron, and more specifically its involvement in modulating the expression and activity of ENaC in collecting duct principal cells. METHODS: mpkCCD cells were incubated in the presence of aldosterone and treated with or without apelin-13. Transepithelial Na+ current was measured and the changes in ENaC expression determined by RT-PCR and immunoblotting. RESULTS: Our data show that apelin-13 reduces the transepithelial sodium amiloride-sensitive current in collecting duct principal cells after 8h and 24h treatment. This effect was associated with a decrease in αENaC subunit expression and mediated through the ERK pathway as well as SGK1 and Nedd4-2. CONCLUSION: Our findings indicate that apelin is involved in the fine regulation of sodium balance in the renal collecting duct by opposing the effects of aldosterone, likely by activation of ENaC ubiquitination.

A Novel Tool to Enhance The Lubricant Efficiency On Induction Heat-Assisted Incremental Sheet Forming of Ti-6Al-4V Sheets

For heat-assisted single point incremental sheet forming (SPIF) works of Ti-6Al-4V sheets, the use of lubricant has shown significant effects on surface quality and geometric accuracy at higher temperatures. Molybdenum disulphide (MoS2) is a common lubricant widely used in SPIF works, however, it usually indicates ineffective performance at high temperatures. This article has studied different lubricants of MoS2 lubricants and proposed a novel mixture of MoS2 to provide better surface quality and improve geometric accuracy. A forming tool with a ball-roller and water channel was designed to enable the MoS2 mixture to pass through the tool tip, allowing easy application of the lubricant on the localised area and reduce the thermal expansion on the ball-roller. Surface roughness analysis has revealed that the water-cooling MoS2 mixture performed well in reducing friction effects and achieved better geometric accuracy. Forming forces measurements, scanning electron microscope (SEM), energy dispersive X-ray Analysis (EDX) and micro-hardness tests also indicated that a higher strain hardening behaviour was detected for the water-cooling MoS2 mixture.

Real-­time parametric estimation of periodic wake-­foil interactions using bioinspired pressure sensing and machine learning

Periodic wake-­foil interactions occur in the collective swimming of bio­inspired robots. Wake interaction pattern estimation (and control) is crucial to thrust enhancement and propulsive efficiency optimization. In this paper, we study the wake interaction pattern estimation of two flapping foils in tandem configurations. The experiments are conducted at a Reynolds number of 1.41×10^4 in a water channel. A modified wake-­foil phase parameter Φ, which unifies the influences of inter­foil distance Lx, motion phase difference ∆φ and wake convection velocity Uv, is introduced to describe the wake interaction patterns parametrically. We use a differential pressure sensor on the downstream foil to capture wake interaction characteristics. Data sets at different tandem configurations are collected. The wake-­foil phase Φ is used to label the pressure signals. A one ­dimensional convolutional neural networks (1D-CNN) model is used to learn an end­to­end mapping between the raw pressure measurements and the wake-­foil phase Φ. The trained 1D-­CNN model shows accurate estimations (average error 3.5%) on random wake interaction patterns and is fast enough (within 40 ms). Then the trained 1D ­CNN model is applied to online thrust enhancement control of a downstream foil swimming in a periodic wake. Synchronous force monitoring and flow visualization demonstrate the effectiveness of the 1D-­CNN model. The limitations of the model are discussed. The proposed approach can be applied to the online estimation and control of wake interactions in the collective swimming and flying of biomimetic robots.

Flow Physics of Profile Control Fluids in Porous Media and Implications for Enhanced Oil Recovery: A Microfluidic Study

Novel profile control agents are constantly emerging in the field of enhanced oil recovery, contributing to the extension of a stable production period. However, evaluation performed through conventional core flow experiments is usually inadequate to reveal the in-depth mechanism of profile control agents. Besides, due to different operation and production modes, there is an urgent need for a specific experimental method applicable to horizontal wells in bottom water reservoirs. In this context, this paper describes two models tailored to bottom water reservoirs and investigates the flow characteristics and mechanisms of three water-shutoff agent types. At the pore scale, further study was carried out on the water-shutoff synergism between a gel and an emulsifier. The results show that the gel is present at the edge of the pore body, while the emulsion is blocked in the center of the pore body. Hence, gel that enters a water channel (main flow and accumulation area of emulsion) can cooperate with an emulsion to achieve high-strength water shutoff, making the bottom water that re-invades mainly break through at oil-rich areas. Compared with water shutoff with gel alone (randomly distributed in the breakthrough area), the synergism improves the gel’s ability to select flow channels, inhibits emulsifier channeling, and achieves a remarkable EOR effect.

Vortex- and Wake-Induced Vibrations of a Circular Cylinder Placed in the Proximity of Two Fixed Cylinders

Purpose This study aims to understand the vibratory response of a circular cylinder placed in proximity to other fixed bodies. Methods A circular cylinder model was placed in a circulating water channel and was supported elastically to vibrate in the water. Another two circular cylinders were fixed upstream of the vibrating cylinder. The temporal displacement variations of the vibrating cylinder were measured and processed by a frequency analysis. Results When the inline spacings were small, two amplitude peaks appeared in the reduced velocity range 3.0–13.0. When the inline spacings were large, the amplitude response showed a single peak. Conclusion For small inline spacings, the first peak was attributed to high-amplitude vibrations forced by Karman vortex streets shed from the upstream cylinders. The second peak arose from interactions of the wakes of the upstream cylinder with the vibrating cylinder. When the inline spacing increased, the vortex-induced vibrations resembled those of an isolated cylinder.

High-resolution cryo-electron microscopy structure of photosystem II from the mesophilic cyanobacterium, Synechocystis sp. PCC 6803

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a high-resolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the D1 subunit is flexible, some waters near the active site are partially occupied, and differences in the PsbV subunit block the Large (O1) water channel. These features strongly influence the structural picture of PSII, especially as it pertains to the mechanism of water oxidation.

Jejak Manajemen Air di Masa Hindia-Belanda; Identifikasi Saluran Air di kawasan Stasiun Bogor

This article describes the identification of the trace of the water management system during the Dutch East Indies era, in the form of a water channel found in the Bogor Station area. The analysis will be viewed from the spatial context; the significance of the water channel with the nearest river, the significance of the water channel to the nearest public facility, and its relevance to the racial urban space in Bogor. This research used a historical method that consists of four stages; heuristics, critics, interpretation, and historiography. Observations were made to explain the physical form and the estimated period of water channel construction. The results showed that the water channel near the Bogor Station was made with modern technology. In the past, the channel may have functioned as drainage that connected to the Ci Pakancilan. The location of the waters channel adjacent to public facilities and government administrative centers showed the accuracy of the Department of Public Works in anticipating floods and puddles in the area of European activity.