Significance We tested the hypothesis that a form of mitochondrial dysfunction alters the homeostasis of the cytosolic Parkinson disease (PD)-associated protein α-synuclein (α-syn). Using yeast and ...worm models of PD, we show that low levels of phosphatidylethanolamine (PE), caused by the depletion of mitochondrial phosphatidylserine decarboxylase (psd), lead to decreased respiration, endoplasmic reticulum (ER) stress, high levels of α-syn and cytoplasmic α-syn foci, and slow growth. Ethanolamine, which replenishes PE through the Kennedy pathway, diminished ER stress, decreased the level of α-syn, eliminated foci, and restored growth of psd1 Δ cells to near wild-type levels. A low level of mitochondrial PE disrupts the homeostasis of α-syn and leads to the accumulation of cytoplasmic foci of this protein.
Phosphatidylserine decarboxylase, which is embedded in the inner mitochondrial membrane, synthesizes phosphatidylethanolamine (PE) and, in some cells, synthesizes the majority of this important phospholipid. Normal levels of PE can decline with age in the brain. Here we used yeast and worms to test the hypothesis that low levels of PE alter the homeostasis of the Parkinson disease-associated protein α-synuclein (α-syn). In yeast, low levels of PE in the phosphatidylserine decarboxylase deletion mutant ( psd1 Δ) cause decreased respiration, endoplasmic reticulum (ER) stress, a defect in the trafficking of the uracil permease, α-syn accumulation and foci, and a slow growth phenotype. Supplemental ethanolamine (ETA), which can be converted to PE via the Kennedy pathway enzymes in the ER, had no effect on respiration, whereas, in contrast, this metabolite partially eliminated ER stress, decreased α-syn foci formation, and restored growth close to that of wild-type cells. In Caenorhabditis elegans , RNAi depletion of phosphatidylserine decarboxylase in dopaminergic neurons expressing α-syn accelerates neurodegeneration, which supplemental ETA rescues. ETA fails to rescue this degeneration in worms that undergo double RNAi depletion of phosphatidylserine decarboxylase ( psd-1 ) and choline/ETA phosphotransferase ( c ept-1 ), which encodes the last enzyme in the CDP–ETA Kennedy pathway. This finding suggests that ETA exerts its protective effect by boosting PE through the Kennedy pathway. Overall, a low level of PE causes ER stress, disrupts vesicle trafficking, and causes α-syn to accumulate; such cells likely die from a combination of ER stress and excessive accumulation of α-syn.
Conjugated linoleic acid (CLA) has been reported to have anti-obesity and antidiabetic effects. However, the benefits of CLA combined with exercise remain unclear, and studies report conflicting ...results.
A systematic review and meta-analysis were performed to investigate the synergistic effect of CLA and exercise on body composition, exercise-related indices, insulin resistance, and lipid profiles; and of the safety of CLA supplements.
In October 2021, the PubMed, Embase, and Cochrane Library databases were searched for reports on clinical trials of the combined intervention of CLA and exercise.
A total of 18 randomized controlled trials and 2 crossover trials were included. The methodological quality assessment was performed using the revised Cochrane risk-of-bias tool. Pooled effect sizes were reported as standardized mean difference (SMD) for continuous data and risk ratio for dichotomous data with their corresponding 95% confidence intervals (CIs). Heterogeneity was tested using the I2 statistic.
The combination of CLA and exercise resulted in significantly decreased body fat (SMD, -0.42 95%CI, -0.70, -0.14; P = 0.003; I2 = 65) and insulin resistance (SMD, -0.25 95%CI, -0.44, -0.06; P = 0.01; I2 = 0) than did exercise alone. In subgroup analysis, the following factors were associated with significant outcomes: (1) body mass index ≥25 kg/m2; (2) female sex; (3) follow-up time >4 weeks; and (4) intervention duration >4 weeks. Nevertheless, supplementation with CLA during exercise programs was not effective for body-weight control, exercise performance enhancement, or lipid-profile improvement. CLA in combination with exercise did not result in a higher risk of adverse events (risk ratio, 1.32 95%CI, 0.94-1.84; P > 0.05; I2 = 0).
CLA combined with exercise is generally safe and can lower body fat and insulin resistance but does not reduce body weight, enhance exercise performance, or improve lipid profiles.
This paper presents an isolated bidirectional interleaved converter with minimum active switches to achieve high conversion ratio. The proposed converter has symmetric structure for easy control, and ...incorporates two coupled inductors for galvanic isolation and high voltage ratio achievement. A dual-inductor-capacitor-diode (LCD) snubber with common resonant inductor at low-voltage side is in charge of leakage energy recycling for efficiency improvement. In addition, the converter can obtain interleaved terminal current at low-voltage side for lowering current ripples, no matter in boost mode or buck mode. Finally, a 400-W prototype is built for validation, where the experimental results indicate that the highest efficiencies in boost and buck modes are 95.5% and 95.4%, respectively.
•Erector spinae plane block (ESPB) administration at varying distances from the incision (ES distance) does not significantly affect postoperative pain scores within the Enhanced Recovery After ...Surgery (ERAS) protocol for lumbar spine surgery.•Postoperative pain management with ESPB shows no significant difference in Numerical Rating Scale (NRS) pain scores between different ES distances immediately after surgery and up to 72 hours postoperatively within the ERAS group.•Patients in the ERAS group reported significantly lower pain scores and reduced morphine consumption compared to the non-ERAS group, indicating the effectiveness of the ERAS protocol.•ERAS protocols facilitated quicker resumption of diet and reduced the incidence of postoperative nausea and vomiting.•The study suggests that lumbar ESPB may be preferable due to difficulties with sonovisualization and to avoid the risk of pleural injury, establishing a safe and effective range for ESPB application.
Postoperative pain control following spine surgery can be difficult. The Enhanced Recovery After Surgery (ERAS) programs use multimodal approaches to manage postoperative pain. While an erector spinae plane block (ESPB) is commonly utilized, the ideal distance for injection from the incision, referred to as the ES (ESPB to mid-surgical level) distance, remains undetermined.
We evaluated the impact of varying ES distances for ESPB on Numerical Rating Scale (NRS) measures of postoperative pain within the ERAS protocol.
Retrospective observational study.
Adult patients who underwent elective lumbar spine fusion surgery.
Primary outcome measures include the comparative postoperative NRS scores across groups at immediate (T1), 24 (T2), 48 (T3), and 72 (T4) hours postsurgery. For secondary outcomes, a propensity matching analysis compared these outcomes between the ERAS and non-ERAS groups, with opioid-related recovery metrics also assessed.
All included patients were assigned to one of three ERAS groups according to the ES distance: Group 1 (G1, ES > 3 segments), Group 2 (G2, ES = 2–3 segments), and Group 3 (G3, ES<2 segments). Each patient underwent a bilateral ultrasound-guided ESPB with 60 mL of diluted ropivacaine or bupivacaine.
Patients within the ERAS cohort reported mild pain (NRS < 3), with no significant NRS variation across G1 to G3 at any time. Sixty-five patients were matched across ERAS and non-ERAS groups. The ERAS group exhibited significantly lower NRS scores from T1 to T3 than the non-ERAS group. Total morphine consumption during hospitalization was 26.7 mg for ERAS and 41.5 mg for non-ERAS patients. The ERAS group resumed water and food intake sooner and had less postoperative nausea and vomiting.
ESPBs can be effectively administered at or near the mid-surgical level to the low thoracic region for lumbar spine surgeries. Given challenges with sonovisualization, a lumbar ESPB may be preferred to minimize the risk of inadvertent pleural injury.
Abstract
Glutathione is an important antioxidant in most prokaryotes and eukaryotes. It detoxifies reactive oxygen species and is also involved in the modulation of gene expression, in redox ...signaling, and in the regulation of enzymatic activities. In this study, the subcellular distribution of glutathione was studied in Saccharomyces cerevisiae by quantitative immunoelectron microscopy. Highest glutathione contents were detected in mitochondria and subsequently in the cytosol, nuclei, cell walls, and vacuoles. The induction of oxidative stress by hydrogen peroxide (H2O2) led to changes in glutathione-specific labeling. Three cell types were identified. Cell types I and II contained more glutathione than control cells. Cell type II differed from cell type I in showing a decrease in glutathione-specific labeling solely in mitochondria. Cell type III contained much less glutathione contents than the control and showed the strongest decrease in mitochondria, suggesting that high and stable levels of glutathione in mitochondria are important for the protection and survival of the cells during oxidative stress. Additionally, large amounts of glutathione were relocated and stored in vacuoles in cell type III, suggesting the importance of the sequestration of glutathione in vacuoles under oxidative stress.
The mucosal microbiome plays a role in regulating host health. The research conducted in humans and mice has governed and detailed the information on microbiome-host immunity interactions. Teleost ...fish, different from humans and mice, lives in and relies on the aquatic environment and is subjected to environmental variation. The growth of teleost mucosal microbiome studies, the majority in the gastrointestinal tract, has emphasized the essential role of the teleost microbiome in growth and health. However, research in the teleost external surface microbiome, as the skin microbiome, has just started. In this review, we examine the general findings in the colonization of the skin microbiome, how the skin microbiome is subjected to environmental change and the reciprocal regulation with the host immune system, and the current challenges that potential study models can address. The information collected from teleost skin microbiome-host immunity research would help future teleost culturing from the potential parasitic infestation and bacterial infection as foreseeing growing threats.
Parkinson disease (PD) results from the slow, progressive loss of dopaminergic neurons in the substantia nigra. Alterations in α-synuclein (aSyn), such as mutations or multiplications of the gene, ...are thought to trigger this degeneration. Here, we show that aSyn disrupts mitogen-activated protein kinase (MAPK)-controlled stress signaling in yeast and human cells, which results in inefficient cell protective responses and cell death. aSyn is a substrate of the yeast (and human) polo-like kinase Cdc5 (Plk2), and elevated levels of aSyn prevent Cdc5 from maintaining a normal level of GTP-bound Rho1, which is an essential GTPase that regulates stress signaling. The nine N-terminal amino acids of aSyn are essential for the interaction with polo-like kinases. The results support a unique mechanism of PD pathology.
Saccharomyces cerevisiae Sro7 and Sro77 are homologues of the Drosophila tumour suppressor lethal giant larvae (Lgl), which regulates cell polarity in Drosophila epithelial cells. Here, we showed ...that double mutation of SRO7/SRO77 was defective in colony growth. The colony of the SRO7/SRO77 double deletion was much smaller than the WT and appeared to be round with a smooth surface, compared with the WT. Analysis using transmission electron microscopy revealed multiple defects of the colony cells, including multiple budding, multiple nuclei, cell lysis and dead cells, suggesting that the double deletion caused defects in cell polarity and cell wall integrity (CWI). Overexpression of RHO1, one of the central regulators of cell polarity and CWI, fully recovered the sro7Δ/sro77Δ phenotype. We further demonstrated that sro7Δ/sro77Δ caused a decrease of the GTP-bound, active Rho1, which in turn caused an upregulation of TOR1. Deletion of TOR1 in sro7Δ/sro77Δ (sro7Δ/sro77Δ/tor1Δ) recovered the cell growth and colony morphology, similar to WT. Our results suggested that the tumour suppressor homologue SRO7/SRO77 regulated cell proliferation and yeast colony development via the Rho1-Tor1 pathway.
Aeromonas hydrophila is the most common opportunistic pathogen that plagues freshwater and euryhaline fishponds. Here, we present the complete genome sequence of A. hydrophila strain LP0103, which ...was isolated from a bacterial septicemia outbreak among suckermouth catfish (Pterygoplichthys pardalis) at Lotus Pond in Kaohsiung City, Taiwan.
► In budding yeast, mitochondrial DNA protects against salt stress-induced cell death. ► Salt stress-induced apoptosis in rho0 cells is mediated by cytochrome c release. ► MIG1 regulates cytochrome c ...transcription during salt stress.
Here we report that budding yeast mitochondrial DNA protects against salt stress-induced apoptosis. Yeast cells lacking mitochondrial DNA (ρ0) are hypersensitive to salt stress-induced apoptosis, which is mediated by mitochondrial cytochrome c release. In addition, cytochrome c expression is downregulated upon salt stress, suggesting a transcriptionally regulated, homeostatic protection mechanism. The repression of cytochrome c transcription is mediated by transcription factor Mig1. Consistently, deletion of MIG1 induces cytochrome C transcription and yields ρ0 cells that are more sensitive to salt stress. In summary, deletion of mitochondrial function leads to salt stress-induced transcriptional deregulation of cytochrome C, causing apoptosis in yeast.
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