We have previously estimated the evolutionary rate (number of substitutions/site/million years) of mitochondrial cytochrome b gene (Cytb) sequences in rodents and moles to be about 0.11 at more ...recent divergence times of tens of thousands of years, and to decrease rapidly to about 0.03 at more distant divergence times. Because this time dependency is thought to be caused by the removal of mildly deleterious substitutions in later generations, we focused in this study on the abundance of nonsynonymous substitutions. We collected 23 haplogroups of Cytb with signals of late Quaternary population expansion events from rodents and moles and categorized them into three groups for comparison based on predicted expansion start time: 5,000–15,000 years ago (Group I), ca. 53,000 years ago (Group II) and 130,000–230,000 years ago (Group III). We counted the numbers of nonsynonymous and synonymous substitutions in all haplogroups. The rates of nonsynonymous substitutions were lowest in Groups II and III (0.08–0.22), whereas those in Group I varied markedly. We further classified Group I into two subgroups based on high (0.29–0.43) and low (0.09–0.20) nonsynonymous substitution rates, which were likely to be associated with the start of the expansion within 10,000 years and at around 15,000 years ago, respectively. The Group II and III networks had two- or three-step star-shaped structures and tended to exhibit frequent and less frequent nonsynonymous substitutions on exterior and interior branches, respectively. Based on temporal dynamics, nonsynonymous mitochondrial DNA (mtDNA) substitutions in small mammals accounted for at most 40% of all substitutions during the early evolutionary stage and then rapidly declined, dropping to approximately 15%. The results of this study provide a good explanation of the time-dependent trend in the mtDNA evolution rate predicted in previous work.
This paper develops a revealed preference analysis for limited consideration models. A revealed preference test is given for the decision model obeying two well-established hypotheses on a decision ...maker’s consideration: the
attention filter
property and
competition filter
property. We also provide a test for the two-step decision model called the
(transitive) rational shortlist method
. We conduct simulations to compare the relative strength of observable restrictions across leading models, where we find drastic differences in Bronars’ indices of models.
There is growing evidence that vasculopathy-induced hypoxia and oxidative stress enhance the process of fibrosis in systemic sclerosis (SSc). Kaempferol is a natural flavonoid widely found in various ...vegetables and fruits, and has been reported to have excellent antioxidant activity.
Objective was to elucidate the effect of kaempferol on skin fibrosis and the mechanism of the inhibitory regulation of fibrosis by kaempferol.
We assessed the effect of intraperitoneally administered kaempferol on bleomycin-induced dermal fibrosis in mice. The effect of kaempferol on oxidative stress in bleomycin-treated mice and SSc fibroblasts was assessed in vivo and in vitro.
We identified that kaempferol injection significantly inhibited bleomycin-induced dermal fibrosis in mice. The number of αSMA
myofibroblasts, CD3
T-cells, and CD68
macrophages in lesional skin was significantly decreased by kaempferol injections. Kaempferol administration also significantly suppressed the bleomycin-induced oxidative stress signal in OKD48 mice. Additionally, mRNA levels of oxidative stress-associated factors, such as HO-1 and NOX2, as well as inflammatory and pro-fibrotic cytokines, including IL-6, TGF-β and TNFα in sclerotic skin were significantly decreased by kaempferol. Kaempferol also reduced bleomycin-induced TUNEL
apoptotic cells in the lesional skin of bleomycin-treated mice. Furthermore, the oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in SSc fibroblasts was inhibited by kaempferol treatment. In addition, the oxidant-induced apoptosis of SSc fibroblasts was decreased by kaempferol in vitro.
Kaempferol might improve bleomycin-induced fibrosis by reducing oxidative stress, inflammation, and oxidative cellular damage. Administration of kaempferol might be an alternative treatment for skin fibrosis in SSc.
The unit commitment problem (UCP) is the problem of deciding up/down and generation-level patterns of energy production units. Due to the expansion of distributed energy resources and the ...liberalization of energy trading in recent years, solving the distributed UCP (DUCP) is attracting the attention of researchers. Once an up/down pattern is determined, the generation-level pattern can be decided distributively using the alternating direction method of multipliers (ADMM). However, ADMM does not guarantee convergence when deciding both up/down and generation-level patterns. In this paper, we propose a method to solve the DUCP using ADMM and constraint optimization programming. Numerical experiments show the efficacy of the proposed method.
Knowledge of variations in morphophysiological leaf traits with forest height is essential for quantifying carbon and water fluxes from forest ecosystems. Here, we examined changes in leaf traits ...with forest height in diverse tree species and their role in environmental acclimation in a tropical rain forest in Borneo that does not experience dry spells. Height-related changes in leaf physiological and morphological traits e.g., maximum photosynthetic rate (Amax), stomatal conductance (gs), dark respiration rate (Rd), carbon isotope ratio (δ¹³C), nitrogen (N) content, and leaf mass per area (LMA) from understory to emergent trees were investigated in 104 species in 29 families. We found that many leaf area-based physiological traits (e.g., Amax-area, Rd, gs), N, δ¹³C, and LMA increased linearly with tree height, while leaf mass-based physiological traits (e.g., Amax-mass) only increased slightly. These patterns differed from other biomes such as temperate and tropical dry forests, where trees usually show decreased photosynthetic capacity (e.g., Amax-area, Amax-mass) with height. Increases in photosynthetic capacity, LMA, and δ¹³C are favored under bright and dry upper canopy conditions with higher photosynthetic productivity and drought tolerance, whereas lower Rd and LMA may improve shade tolerance in lower canopy trees. Rapid recovery of leaf midday water potential to theoretical gravity potential during the night supports the idea that the majority of trees do not suffer from strong drought stress. Overall, leaf area-based photosynthetic traits were associated with tree height and the degree of leaf drought stress, even in diverse tropical rain forest trees.
•MSCs-derived exosomes suppressed bleomycin-induced dermal fibrosis in mice.•MSCs-derived exosome treatment decreased Type I Collagen expression in fibroblasts.•miR-196b-5p was most highly expressed ...in miRNA in MSCs-derived exosomes.•miR-196b-5p attenuated TGF-β-induced increased expression of COL1A2 in fibroblasts.
Systemic sclerosis (SSc) is a connective tissue disorder characterized by the development of fibrosis in the skin and internal organs. Increasing evidence suggests that mesenchymal stem cells (MSCs) can be used to a treatment for fibrotic diseases. Recent studies have demonstrated that some of the biological effects of MSCs are due to the secretion of exosomes. However, the precise mechanisms underlying MSCs-derived exosomes in skin fibrosis are not well understood.
We aimed to elucidate the effect of MSCs-derived exosomes on skin fibrosis in SSc and the mechanism underlying their inhibitory action on fibrosis.
Exosome was collected from MSCs by ultracentrifugation method. We examined the suppressive effect of MSCs-derived exosome on skin fibrosis in bleomycin-induced SSc mouse model. Skin samples from the injected site were collected for further examination, and micro-RNA analysis of MSCs-derived exosome was performed.
Injection of MSCs-derived exosomes significantly inhibited bleomycin-induced dermal fibrosis in mice. MSCs-derived exosomes significantly reduced the amount of collagen and the number of α-SMA+ myofibroblasts and CD68+ macrophages in lesional skin. They also reduced the expression of type I collagen and TGF-β receptor 1 in fibroblasts in vitro. Moreover, micro-RNA analysis revealed that several microRNAs in MSCs-derived exosomes have antifibrotic potential. We confirmed that overexpression of miR-196b-5p in fibroblasts significantly suppressed collagen type I alpha 2 expression.
This study demonstrated that inhibition of collagen type I expression by miR-196b-5p in exosomes might be one of the mechanisms by which MSCs suppress skin fibrosis in an SSc mouse model.
► Solvent extraction was used to separate Al, Cu, Co, and Li from acidic sulfate media. ► Copper was selectively extracted by Acorga M5640 at pH 1.5–2.0. ► Aluminum was selectively extracted by ...PC-88A at pH 2.5–3.0. ► Cobalt was selectively extracted by PC-88A/TOA mixed extractant at pH 5.5–6.0.
Acid leach liquors from spent lithium-ion batteries that use lithium cobalt dioxide (LiCoO2) as a cathode active material contain valuable metals such as cobalt and lithium, as well as common metals such as aluminum and copper. The objective of this study was to develop a hydrometallurgical process that provides a degree of high selectivity between aluminum, cobalt, copper, and lithium from acidic sulfate media.
The results from batch experiments showed that a selective hydroxide precipitation approach was not suitable because a significant amount of cobalt was coprecipitated with aluminum and/or copper hydroxides. In contrast, batch experiments and the subsequent data analysis indicated that the sequence of solvent extraction circuits using PC-88A, Acorga M5640, and tri-n-octylamine (TOA) extractants effectively separates four metals of interest. In the first circuit of the proposed process, copper was selectively extracted by Acorga M5640 at pH 1.5–2.0. Aluminum, cobalt, and lithium remained in the aqueous phase. In the second circuit, aluminum was selectively extracted by PC-88A at pH 2.5–3.0. For separation of the remaining cobalt and lithium, Acorga M5640 provided higher cobalt selectivity (separation factor could not be accurately obtained due to negligible lithium extraction) compared to PC-88A (βCo, 90%/Li=350 at pH 4.5) and PC-88A/TOA (βCo, 90%/Li=1,170 at pH 5.4). However, the stripping efficiency of cobalt from the Acorga M5640 organic phase was found to be low (less than 10%). Therefore, the PC-88A/TOA mixed extractant rather than Acorga M5640 is a suitable choice for the separation of cobalt and lithium.
Nursing students have limited opportunities to experience end-of-life care, so it is difficult for them to learn how to deliver it empirically. The use of simulations with standardized patients may ...be a way to provide realistic experience of end-of-life care for nursing students.
The aim of this study was to evaluate the effectiveness of end-of-life care simulations with standardized patients in improving the knowledge, skill performance and self-confidence of undergraduate nursing students.
Randomized controlled study.
Japanese university nursing school.
Thirty-eight students in the third year of the Bachelor's degree in nursing (simulation group = 20, control group = 18).
After randomization to a simulation or control group, participants in the simulation group participated in an end-of-life care simulation with standardized patients. The primary outcome of a change in the knowledge score was assessed using a knowledge questionnaire, skill performance by completing Objective Structured Clinical Evaluations, and self-confidence related to end-of-life care by self-reported questionnaires.
The simulation group improved significantly in knowledge, skill performance in physical assessment and psychological care, and self-confidence related to end-of-life care. The results of the two-way analysis of variance showed a significant interaction between groups and time (p = 0.000). Analysis of the simple main effect showed a significant difference (p = 0.000) between groups after the end-of-life care simulation and a significant difference (p = 0.000) over time in the simulation group. There were large effects on knowledge improvement (η2 = 0.372), physical assessment (η2 = 0.619), psychological care skill performance (η2 = 0.588), and self-confidence in both physical assessment (η2 = 0.410) and psychological care (η2 = 0.722).
End-of-life care simulation with standardized patients would be an effective strategy to train nursing students, who have limited opportunities to experience end-of-life care.
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-β (TGF-β) is thought to be involved in the ...pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-β inhibitor significantly ameliorated IC/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC/PBS has not been comprehensively analyzed. TGF-β has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H₂O₂) and examined the effects of three TGF-β inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-β inhibitor treatment improved urinary function and histological changes in the IC/PBS mouse model, and SB431542 was most effective among the TGF-β inhibitors. In our present study, TGF-β inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-β inhibitor.
Several studies have demonstrated potential roles for apelin/APJ signaling in the regulation of oxidative stress associated with ischemia-reperfusion (I/R) injury in several organs. Objective was to ...assess the role of apelin/APJ signaling in the development of pressure ulcers (PUs) formation after cutaneous I/R injury in mice. We identified that cutaneous I/R injury increased the expression of apelin in the skin at I/R site. Administration of apelin significantly inhibited the formation of PUs. The reductions of blood vessels, hypoxic area and apoptosis in I/R site were inhibited by apelin injection. Oxidative stress signals in OKD48 mice and the expressions of oxidative stress related genes in the skin were suppressed by apelin injection. H
O
-induced intracellular ROS and apoptosis in endothelial cells and fibroblasts were suppressed by apelin in vitro. Furthermore, MM07, biased agonist of APJ, also significantly suppressed the development of PUs after cutaneous I/R, and the inhibitory effect of MM07 on PUs formation was higher than that in apelin. We conclude that apelin/APJ signaling may inhibit cutaneous I/R injury-induced PUs formation by protecting the reduction of vascularity and tissue damage via suppression of oxidative stress. Exogenous application of apelin or MM07 might have therapeutic potentials against the development of PUs.
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