Following the dominant firm-competitive fringe model, this paper analyses the response of Japan’s nonrenewable electricity utilities to the renewable portfolio standards (RPS) and feed-in tariff ...(FIT) scheme. The output of electricity from renewable energy sources (RES-E) is primarily correlated with the magnitude of the RPS requirement and the fixed tariff. Nonrenewable firms suffer a reduction in revenue due to increased RES-E production under both schemes. The RPS requirement has direct impact on the renewable energy certificate (NEC) price. If the incumbent nonrenewable electricity utilities gain market power in both electricity and NEC markets, they can suppress the RPS quota to preserve their vested benefits. In the FIT scheme, the above-market RES-E generation cost is passed on to consumers via a surcharge. Since grid-connected RES-E accelerated rapidly under FIT, nonrenewable electricity utilities would face a substantial increase in costs to maintain network reliability due to the intermittent and variable nature of RES-E technologies. The Japanese government should therefore take measures to ensure variable renewable power occupies a higher share of the electricity system, and to do so in a cost-effective manner.
•This paper analyzes firms’ response to subsidy schemes of renewable energy in Japan.•The dominant firm-competitive fringe model was followed.•The renewable generators behave competitively and act as price takers.•Japan needs to integrate more viable renewable energy in a cost-effective manner.
Abstract
Voltage-gated sodium (Na
V
) channels play fundamental roles in initiating and propagating action potentials. Na
V
1.3 is involved in numerous physiological processes including neuronal ...development, hormone secretion and pain perception. Here we report structures of human Na
V
1.3/β1/β2 in complex with clinically-used drug bulleyaconitine A and selective antagonist ICA121431. Bulleyaconitine A is located around domain I-II fenestration, providing the detailed view of the site-2 neurotoxin binding site. It partially blocks ion path and expands the pore-lining helices, elucidating how the bulleyaconitine A reduces peak amplitude but improves channel open probability. In contrast, ICA121431 preferentially binds to activated domain IV voltage-sensor, consequently strengthens the Ile-Phe-Met motif binding to its receptor site, stabilizes the channel in inactivated state, revealing an allosterically inhibitory mechanism of Na
V
channels. Our results provide structural details of distinct small-molecular modulators binding sites, elucidate molecular mechanisms of their action on Na
V
channels and pave a way for subtype-selective therapeutic development.
Sodium/proton exchanger 1 (NHE1) is an electroneutral secondary active transporter present on the plasma membrane of most mammalian cells and plays critical roles in regulating intracellular pH and ...volume homeostasis. Calcineurin B-homologous protein 1 (CHP1) is an obligate binding partner that promotes NHE1 biosynthetic maturation, cell surface expression and pH-sensitivity. Dysfunctions of either protein are associated with neurological disorders. Here, we elucidate structures of the human NHE1-CHP1 complex in both inward- and inhibitor (cariporide)-bound outward-facing conformations. We find that NHE1 assembles as a symmetrical homodimer, with each subunit undergoing an elevator-like conformational change during cation exchange. The cryo-EM map reveals the binding site for the NHE1 inhibitor cariporide, illustrating how inhibitors block transport activity. The CHP1 molecule differentially associates with these two conformational states of each NHE1 monomer, and this association difference probably underlies the regulation of NHE1 pH-sensitivity by CHP1.
Abstract
The low-voltage activated T-type calcium channels regulate cellular excitability and oscillatory behavior of resting membrane potential which trigger many physiological events and have been ...implicated with many diseases. Here, we determine structures of the human T-type Ca
V
3.3 channel, in the absence and presence of antihypertensive drug mibefradil, antispasmodic drug otilonium bromide and antipsychotic drug pimozide. Ca
V
3.3 contains a long bended S6 helix from domain III, with a positive charged region protruding into the cytosol, which is critical for T-type Ca
V
channel activation at low voltage. The drug-bound structures clearly illustrate how these structurally different compounds bind to the same central cavity inside the Ca
V
3.3 channel, but are mediated by significantly distinct interactions between drugs and their surrounding residues. Phospholipid molecules penetrate into the central cavity in various extent to shape the binding pocket and play important roles in stabilizing the inhibitor. These structures elucidate mechanisms of channel gating, drug recognition, and actions, thus pointing the way to developing potent and subtype-specific drug for therapeutic treatments of related disorders.
It is widely believed that the dehydrogenation of organic compounds is a thermodynamically unfavorable process, and thus requires stoichiometric oxidants such as dioxygen and metal oxides or ...sacrificial hydrogen acceptors to remove the hydrogen from the reaction mixture to drive the equilibrium towards the products. Here we report a previously unappreciated combination of common commercial Pd/C and H2 which dehydrogenates a wide range of substituted cyclohexanones and 2-cyclohexenones to their corresponding phenols with high isolated yields, with H2 as the only byproduct. The reaction requires no oxidants or hydrogen acceptors because instead of removing the generated hydrogen with oxidants or hydrogen acceptors, we demonstrated it can be used as a cocatalyst to help power the reaction. This method for phenol synthesis manifests a high atom economy, and is inherently devoid of the complications normally associated with oxidative dehydrogenations.
Glycosylphosphatidylinositol (GPI) molecules are complex glycophospholipids and serve as membrane anchors for tethering many proteins to the cell surface. Attaching GPI to the protein in the ...endoplasmic reticulum (ER) is catalyzed by the transmembrane GPI transamidase (GPIT) complex, which is essential for maturation of the GPI-anchored proteins. The GPIT complex is known to be composed of five subunits: PIGK, PIGU, PIGT, PIGS and GPAA1. Here, we determined the structure of the human GPIT complex at a resolution of 3.1 Å using single-particle cryo-EM, elucidating its overall assembly. The PIGK subunit functions as the catalytic component, in which we identified a C206-H164-N58 triad that is critical for the transamination reaction. Transmembrane helices constitute a widely opened cleft, which is located underneath PIGK, serving as a GPI substrate-binding site. The ubiquitin E3 ligase RNF121 is visualized at the back of the complex and probably serves as a quality control factor for the GPIT complex.
Salt-overly-sensitive 1 (SOS1) is a unique electroneutral Na
/H
antiporter at the plasma membrane of higher plants and plays a central role in resisting salt stress. SOS1 is kept in a resting state ...with basal activity and activated upon phosphorylation. Here, we report the structures of SOS1. SOS1 forms a homodimer, with each monomer composed of transmembrane and intracellular domains. We find that SOS1 is locked in an occluded state by shifting of the lateral-gate TM5b toward the dimerization domain, thus shielding the Na
/H
binding site. We speculate that the dimerization of the intracellular domain is crucial to stabilize the transporter in this specific conformation. Moreover, two discrete fragments and a residue W1013 are important to prevent the transition of SOS1 to an alternative conformational state, as validated by functional complementation assays. Our study enriches understanding of the alternate access model of eukaryotic Na
/H
exchangers.
By using the latest China-Japan input-output data sets and the index decomposition analysis (IDA) approach, this article analyzes the driving forces of CO2 emissions embodied in trade between the two ...countries during 1990-2000. We found that the growth of trade volume had a large influence on the increase of CO2 emissions embodiments in bilateral trade. The dramatic decline in carbon intensity of the Chinese economy is a primary cause in offsetting CO2 emissions exported from China to Japan over 1995-2000. We argue that a better understanding of the factors affecting CO2 emissions embodied in international trade will assist in seeking more effective climate policies with wider participation in the post-Kyoto regime.
In the central nervous system (CNS), excitatory amino acid transporters (EAATs) mediate the uptake of excitatory neurotransmitter glutamate and maintain its low concentrations in the synaptic cleft ...for avoiding neuronal cytotoxicity. Dysfunction of EAATs can lead to many psychiatric diseases. Here we report cryo-EM structures of human EAAT2 in an inward-facing conformation, in the presence of substrate glutamate or selective inhibitor WAY-213613. The glutamate is coordinated by extensive hydrogen bonds and further stabilized by HP2. The inhibitor WAY-213613 occupies a similar binding pocket to that of the substrate glutamate. Upon association with the WAY-213613, the HP2 undergoes a substantial conformational change, and in turn stabilizes the inhibitor binding by forming hydrophobic interactions. Electrophysiological experiments elucidate that the unique S441 plays pivotal roles in the binding of hEAAT2 with glutamate or WAY-213613, and the I464-L467-V468 cluster acts as a key structural determinant for the selective inhibition of this transporter by WAY-213613.
Background Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and ...mechanistic underpinnings of ursolic acid’s effect on busulfan-induced oligospermia in mouse models. Methods A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis. Results The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.
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