Structural Basis for the Function of the C-Terminal Proton Release Pathway in the Calcium Pump

The calcium pump (sarco/endoplasmic reticulum Ca²⁺-ATPase, SERCA) plays a major role in calcium homeostasis in muscle cells by clearing cytosolic Ca²⁺ during muscle relaxation. Active Ca²⁺ transport by SERCA involves the structural transition from a low-Ca²⁺ affinity E2 state toward a high-Ca²⁺ affinity E1 state of the pump. This structural transition is accompanied by the countertransport of protons to stabilize the negative charge and maintain the structural integrity of the transport sites and partially compensate for the positive charges of the two Ca²⁺ ions passing through the membrane. X-ray crystallography studies have suggested that a hydrated pore located at the C-terminal domain of SERCA serves as a conduit for proton countertransport, but the existence and function of this pathway have not yet been fully characterized. We used atomistic simulations to demonstrate that in the protonated E2 state and the absence of initially bound water molecules, the C-terminal pore becomes hydrated in the nanosecond timescale. Hydration of the C-terminal pore is accompanied by the formation of water wires that connect the transport sites with the cytosol. Water wires are known as ubiquitous proton-transport devices in biological systems, thus supporting the notion that the C-terminal domain serves as a conduit for proton release. Additional simulations showed that the release of a single proton from the transport sites induces bending of transmembrane helix M5 and the interaction between residues Arg762 and Ser915. These structural changes create a physical barrier against full hydration of the pore and prevent the formation of hydrogen-bonded water wires once proton transport has occurred through this pore. Together, these findings support the notion that the C-terminal proton release pathway is a functional element of SERCA and also provide a mechanistic model for its operation in the catalytic cycle of the pump.     

Leucokinin and Associated Neuropeptides Regulate Multiple Aspects of Physiology and Behavior in Drosophila

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. LKs act on G-protein-coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep–metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (abdominal LK neurons, ABLKs) of the abdominal neuromeres co-express LK and a diuretic hormone (DH44), and together, these regulate water and ion homeostasis and associated stress as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs (anterior LK neurons), in the brain express LK in larvae, but inconsistently so in adults. These ALKs co-express three other neuropeptides and regulate water and ion homeostasis, feeding, and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.     

Biodegradable Polymeric Nanoparticles Containing an Immune Checkpoint Inhibitor (aPDL1) to Locally Induce Immune Responses in the Central Nervous System

Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.     

Analysis of ZTE MRI application to sandstone and carbonate

Microtomography (μCT) and nuclear magnetic resonance (NMR) have been used to characterize porous media for decades. Magnetic resonance imaging (MRI) enables direct visualization of pore architecture and many pulse sequences exist. In this work, we tested the MRI pulse sequence Zero Echo Time (ZTE) to study sandstone and carbonate for its ability to address short relaxation times. We aimed at resolving two fluid conduit scales, that is, pores and fractures. In this research, we study tighter porous systems than those previously reported using ZTE. Additionally, pore cluster analysis (PCA), combined with ZTE, can be used to analyze pore-fracture connectivity of relatively large core plugs. We show that ZTE can resolve two-scale pore systems simultaneously, that is, fractures and pores. By combining time-domain NMR pore-size analysis and PCA, we show that careful selection of resolution is necessary to understand transport in porous media.     

Hydrophobizing polyether sulfone membrane by sol-gel for water desalination using air gap membrane distillation

ABSTRACT

The hydrophobic polyether sulfone membranes were prepared by the sol-gel method to be applied in an air gap membrane distillation setup for desalination. The surface modifications were carried out using Trimethylsilyl chloride (TMSCl) and Methyltrimethoxysilane (MTMS) solutions. The membranes were characterized using Attenuated Total Reflection Infrared (ATR-IR) spectroscopy, Scanning Electron Microscopy (SEM), and Optical Contact Angle (OCA) methods. The effects of membrane preparation as well as operating conditions such as temperature difference, salt concentration, feed rotation speed, and cold-side temperature on membrane performance were investigated using central composite design method. It was found that feed temperature has the largest effect among the parameters on the permeation flux. The flow rate and salt rejection of the membrane in the optimum conditions were 4.47 Kg m^?2 h^?1 and 99.37%, respectively.     

Thermal transport and chemical conversion in single reacting sorbent particles

The effects of particle size and carbon dioxide concentration on chemical conversion in engineered spherical particles undergoing calcium oxide looping are investigated. Particles are thermochemically cycled in a furnace under different carbon dioxide concentrations. Changes in composition due to chemical reactions are measured using thermogravimetric analysis. Gas composition at the furnace exit is evaluated with mass spectroscopy. A numerical model of thermal transport phenomena developed previously is adapted to match the physical system investigated in the present study. The model is used to elucidate effects of reacting medium characteristics on particle temperature and reaction extent. Experimental and numerical results show that (1) an increase in particle size results in a decrease in carbonation extent, and (2) the carbonation step consists of fast and slow reaction regimes. The reaction rates in the fast and slow carbonation regimes increase with increasing carbon dioxide concentration. The effect of carbon dioxide concentration and the distinction between the fast and slow regimes become more pronounced with increasing particle size.     

Stem Photosynthesis—A Key Element of Grass Pea (Lathyrus sativus L.) Acclimatisation to Salinity

Grass pea (Lathyrus sativus) is a leguminous plant of outstanding tolerance to abiotic stress. The aim of the presented study was to describe the mechanism of grass pea (Lathyrus sativus L.) photosynthetic apparatus acclimatisation strategies to salinity stress. The seedlings were cultivated in a hydroponic system in media containing various concentrations of NaCl (0, 50, and 100 mM), imitating none, moderate, and severe salinity, respectively, for three weeks. In order to characterise the function and structure of the photosynthetic apparatus, Chl a fluorescence, gas exchange measurements, proteome analysis, and Fourier-transform infrared spectroscopy (FT-IR) analysis were done inter alia. Significant differences in the response of the leaf and stem photosynthetic apparatus to severe salt stress were observed. Leaves became the place of harmful ion (Na⁺) accumulation, and the efficiency of their carboxylation decreased sharply. In turn, in stems, the reconstruction of the photosynthetic apparatus (antenna and photosystem complexes) activated alternative electron transport pathways, leading to effective ATP synthesis, which is required for the efficient translocation of Na⁺ to leaves. These changes enabled efficient stem carboxylation and made them the main source of assimilates. The observed changes indicate the high plasticity of grass pea photosynthetic apparatus, providing an effective mechanism of tolerance to salinity stress.     

Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway

Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity.     

Direct View on the Origin of High Li+ Transfer Impedance in All-Solid-State Battery

Large interfacial resistance plays a dominant role in the performance of all-solid-state lithium-ion batteries. However, the mechanism of interfacial resistance has been under debate. Here, the Li⁺ transport at the interfacial region is investigated to reveal the origin of the high Li⁺ transfer impedance in a LiCoO₂(LCO)/LiPON/Pt all-solid-state battery. Both an unexpected nanocrystalline layer and a structurally disordered transition layer are discovered to be inherent to the LCO/LiPON interface. Under electrochemical conditions, the nanocrystalline layer with insufficient electrochemical stability leads to the introduction of voids during electrochemical cycles, which is the origin of the high Li⁺ transfer impedance at solid electrolyte-electrode interfaces. In addition, at relatively low temperatures, the oxygen vacancies migration in the transition layer results in the formation of Co₃O₄ nanocrystalline layer with nanovoids, which contributes to the high Li⁺ transfer impedance. This work sheds light on the mechanism for the high interfacial resistance and promotes overcoming the interfacial issues in all-solid-state batteries.