Grey matter structure within the visual networks in migraine with aura: multivariate and univariate analyses.

BACKGROUND: The visual cortex is involved in the generation of migraine aura. Voxel-based multivariate analyses applied to this region may provide complementary information about aura mechanisms relative to the commonly used mass-univariate analyses. METHODS: Structural images constrained within the functional resting-state visual networks were obtained in migraine patients with (n = 50) and without (n = 50) visual aura and healthy controls (n = 50). The masked images entered a multivariate analysis in which Gaussian process classification was used to generate pairwise models. Generalizability was assessed by five-fold cross-validation and non-parametric permutation tests were used to estimate significance levels. A univariate voxel-based morphometry analysis was also performed. RESULTS: A multivariate pattern of grey matter voxels within the ventral medial visual network contained significant information related to the diagnosis of migraine with visual aura (aura vs. healthy controls: classification accuracy = 78%, p < 0.001; area under the curve = 0.84, p < 0.001; migraine with aura vs. without aura: classification accuracy = 71%, p < 0.001; area under the curve = 0.73, p < 0.003). Furthermore, patients with visual aura exhibited increased grey matter volume in the medial occipital cortex compared to the two other groups. CONCLUSIONS: Migraine with visual aura is characterized by multivariate and univariate patterns of grey matter changes within the medial occipital cortex that have discriminative power and may reflect pathological mechanisms.

Responsiveness and minimal clinically important difference of TNO-AZL Preschool Children Quality of Life in children with cerebral palsy.

PURPOSE: To examine the responsiveness and minimal clinically important difference (MCID) of the TNO-AZL (Netherlands Organization for Applied Scientific Research Academic Medical Centre) Preschool Children Quality of Life (TAPQOL) in children with cerebral palsy (CP). METHODS: Ninety-seven children with CP (60 males, 37 females; aged 1-6 years) and their caregivers were recruited from the rehabilitation programs of Chang Gung Memorial Hospital in Taiwan for this 6-month longitudinal follow-up study. The Functional Independence Measure for Children (WeeFIM) and TAPQOL outcomes were measured at baseline and at a 6-month follow-up. Responsiveness was examined using the standardized response mean (SRM). The distribution-based and anchor-based MCID were determined. The TAPQOL outcomes include physical functioning (PF), social functioning (SF), cognitive functioning (CF), and emotional functioning (EF) domains. RESULTS: The responsiveness of the TAPQOL for all of TAPQOL domains was marked (SRM = 1.12-1.54). The anchor-based MCIDs of TAPQOL for PF, SF, CF, EF, and total domains were 1.25, 3.28, 2.93, 2.25, and 1.73, respectively, which were similar to the distribution-based MCID values of TAPQOL, except in the PF domain. The distribution-based MCIDs of TAPQOL in various domains were 2.85-3.73 when effect size (ES) was 0.2, 7.13-9.32 when ES was 0.5, and 11.40-14.91 when ES was 0.8. CONCLUSIONS: TAPQOL is markedly responsive to detect change in children with CP. The caregivers perceived the minimally important change in HRQOL of their children at a relatively low treatment efficacy. Researchers and clinicians can utilize TAPQOL data to determine whether changes in TAPQOL scores indicate clinically meaningful effects post-treatment and at the follow-up.

58-kDa microspherule protein (MSP58) is novel Brahma-related gene 1 (BRG1)-associated protein that modulates p53/p21 senescence pathway.

The nucleolar 58-kDa microspherule protein (MSP58) protein is a candidate oncogene implicated in modulating cellular proliferation and malignant transformation. In this study, we show that knocking down MSP58 expression caused aneuploidy and led to apoptosis, whereas ectopic expression of MSP58 regulated cell proliferation in a context-dependent manner. Specifically, ectopic expression of MSP58 in normal human IMR90 and Hs68 diploid fibroblasts, the H184B5F5/M10 mammary epithelial cell line, HT1080 fibrosarcoma cells, primary mouse embryonic fibroblasts, and immortalized NIH3T3 fibroblasts resulted in induction of premature senescence, an enlarged and flattened cellular morphology, and increased senescence-associated ß-galactosidase activity. MSP58-driven senescence was strictly dependent on the presence of functional p53 as revealed by the fact that normal cells with p53 knockdown by specific shRNA or cells with a mutated or functionally impaired p53 pathway were effective in bypassing MSP58-induced senescence. At least two senescence mechanisms are induced by MSP58. First, MSP58 activates the DNA damage response and p53/p21 signaling pathways. Second, MSP58, p53, and the SWI/SNF chromatin-remodeling subunit Brahma-related gene 1 (BRG1) form a ternary complex on the p21 promoter and collaborate to activate p21. Additionally, MSP58 protein levels increased in cells undergoing replicative senescence and stress-induced senescence. Notably, the results of analyzing expression levels of MSP58 between tumors and matched normal tissues showed significant changes (both up- and down-regulation) in its expression in various types of tumors. Our findings highlight new aspects of MSP58 in modulating cellular senescence and suggest that MSP58 has both oncogenic and tumor-suppressive properties.

Correction: Chung et al. Physiological and Psychological Effects of Treadmill Overtraining Implementation. Biology 2021, 10, 515.

In the original publication [...].

ATPase family AAA domain-containing 3A is a novel anti-apoptotic factor in lung adenocarcinoma cells.

AAA domain-containing 3A (ATAD3A) is a member of the AAA-ATPase family. Three forms of ATAD3 have been identified: ATAD3A, ATAD3B and ATAD3C. In this study, we examined the type and expression of ATAD3 in lung adenocarcinoma (LADC). Expression of ATAD3A was detected by reverse transcription-polymerase chain reaction, immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy. Our results show that ATAD3A is the major form expressed in LADC. Silencing of ATAD3A expression increased mitochondrial fragmentation and cisplatin sensitivity. Serum deprivation increased ATAD3A expression and drug resistance. These results suggest that ATAD3A could be an anti-apoptotic marker in LADC.

Rsf-1, a chromatin remodeling protein, induces DNA damage and promotes genomic instability.

Rsf-1 (HBXAP) has been reported as an amplified gene in human cancer, including the highly aggressive ovarian serous carcinoma. Rsf-1 protein interacts with SNF2H to form an ISWI chromatin remodeling complex, RSF. In this study, we investigated the functional role of Rsf-1 by observing phenotypes after expressing it in nontransformed cells. Acute expression of Rsf-1 resulted in DNA damage as evidenced by DNA strand breaks, nuclear γH2AX foci, and activation of the ATM-CHK2-p53-p21 pathway, leading to growth arrest and apoptosis. Deletion mutation and gene knockdown assays revealed that formation of a functional RSF complex with SNF2H was required for Rsf-1 to trigger DNA damage response (DDR). Gene knock-out of TP53 alleles, TP53 mutation, or treatment with an ATM inhibitor abolished up-regulation of p53 and p21 and prevented Rsf-1-induced growth arrest. Chronic induction of Rsf-1 expression resulted in chromosomal aberration and clonal selection for cells with c-myc amplification and CDKN2A/B deletion. Co-culture assays indicated Rsf-1-induced DDR as a selecting barrier that favored outgrowth of cell clones with a TP53 mutation. The above findings suggest that increased Rsf-1 expression and thus excessive RSF activity, which occurs in tumors harboring Rsf-1 amplification, can induce chromosomal instability likely through DDR.

Physiological and Psychological Effects of Treadmill Overtraining Implementation.

Overtraining in athletes usually causes profound and lasting deleterious effects on the maintenance of health and exercise capacity. Here, we established an overtraining animal model to investigate the physiological modulation for future strategic applications in vivo. We subjected C57BL/6 mice to exhaustive treadmill exercises daily for 8 weeks (the exhaustive exercise group). Next, the physiological and psychological outcomes were compared with the regular exercise and sedentary groups. Outcome measures included growth, glucose tolerance, exercise metabolism profiles, cytokine levels, intestinal tight junction gene expression, and psychological behavioral changes. Our results revealed that overtraining negatively affected the physiological and psychological changes in the current model. The exhaustive exercise group exhibited significantly lower endurance performance and imbalanced energy expenditure, causing a decrease in body fat mass and slowing down the growth curve. In addition, the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1ß) and immune cells (neutrophils and monocytes) were significantly elevated after successive exhaustive exercise interventions. Furthermore, overtraining-induced stress resulted in increased anxiety status and decreased food intake. Our findings reinforce the idea that an imbalance between exercise and recovery can impair health and performance maintenance after overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.

Hepatoprotective effect of piceatannol against carbon tetrachloride-induced liver fibrosis in mice.

Piceatannol (3,5,3',4'-trans-tetrahydroxystilbene) is a natural analog and a metabolite of resveratrol present in grapes and red wine. Previous studies have reported that piceatannol exerts a broad spectrum of health benefits including antioxidant, anti-inflammatory, chemopreventive, and neuroprotective effects. However, little is known about the hepatoprotective effect of piceatannol against toxin-induced liver fibrosis. Therefore, the objective of this study is to evaluate the protective effect of piceatannol in a mouse model of CCl4-induced hepatic fibrosis. Oral administration of piceatannol significantly improved the hepatic functions of CCl4-treated mice in both therapeutic and preventive models. Additionally, the immunohistochemical staining results revealed that collagen deposition in CCl4-injected mice was significantly reduced by treatment with piceatannol. Moreover, piceatannol remarkably suppressed the expressions of collagen I, α-smooth muscle protein (α-SMA), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) induced by CCl4. The anti-fibrotic mechanism of piceatannol was associated with the regulation of the transforming growth factor-ß (TGF-ß)/Smad signaling pathway. Finally, piceatannol also profoundly alleviated CCl4-induced hepatic oxidative damage by elevating the level of glutathione and catalase activity. Altogether, our current findings suggest that piceatannol may serve as a bioactive agent that inhibits or alleviates toxic-induced fibroproliferative diseases, especially in the prevention of liver fibrosis.

Correction: Hepatoprotective effect of piceatannol against carbon tetrachloride-induced liver fibrosis in mice.

Correction for 'Hepatoprotective effect of piceatannol against carbon tetrachloride-induced liver fibrosis in mice' by Wei-Lun Hung et al., Food Funct., 2021, DOI: 10.1039/D1FO02545G.

Nuclear expression of dynamin-related protein 1 in lung adenocarcinomas.

Dynamin-related protein 1 (DRP1), an 80 kDa GTPase, is involved in mitochondrial fission and anticancer drug-mediated cytotoxicity, which implicate an association with disease progression of cancer. In this study we investigated the prognostic value of DRP1 in lung adenocarcinomas. Using immunohistochemistry, we measured the expression of DRP1 in 227 patients with lung adenocarcinomas. Expression of DRP1 was confirmed by immunoblotting. The correlation between DRP1 expression and clinicopathological parameters was analyzed by statistical analysis. Difference of survivals between different groups was compared by a log-rank test. The results showed that DRP1 expression was detected in 202 patients with lung adenocarcinomas. Among these, nuclear DRP1 (DRP1(nuc)) was detected in 184 patients. A significant difference was found in cumulative survival between patients with high DRP1(nuc) levels and those with DRP1(cyt) levels (P<0.001). In vitro, hypoxia increased DRP1(nuc) levels and cisplatin resistance. Antibodies specific to DRP1 co-precipitated a human homologue of yeast Rad23 protein A (hHR23A) and silencing of hHR23A decreased the nuclear DRP1 level and cisplatin resistance. In conclusion, DRP1(nuc) is highly expressed in lung adenocarcinomas, and correlates with poor prognosis. Nuclear DRP1 may increase drug resistance during hypoxia, and hHR23A is essential for nuclear transportation of DRP1. Our results suggest that other than the protein level alone, intracellular distribution of the protein is critical for determining the protein function in cells.

Synthesis, Characterization, and Visible Light Curing Capacity of Polycaprolactone Acrylate.

Polycaprolactone (PCL) is drawing increasing attention in the field of medical 3D printing and tissue engineering because of its biodegradability. This study developed polycaprolactone prepolymers that can be cured using visible light. Three PCL acrylates were synthesized: polycaprolactone-530 diacrylate (PCL530DA), glycerol-3 caprolactone triacrylate (Glycerol-3CL-TA), and glycerol-6 caprolactone triacrylate (Glycerol-6CL-TA). PCL530DA has two acrylates, whereas Glycerol-3CL-TA and Glycerol-6CL-TA have three acrylates. The Fourier transform infrared and nuclear magnetic resonance spectra suggested successful synthesis of all PCL acrylates. All are liquid at room temperature and can be photopolymerized into a transparent solid after exposure to 470 nm blue LED light using 1% camphorquinone as photoinitiator and 2% dimethylaminoethyl methacrylate as coinitiator. The degree of conversion for all PCL acrylates can reach more than 80% after 1 min of curing. The compressive modulus of PCL530DA, Glycerol-3CL-TA, and Glycerol-6CL-TA is 65.7 ± 12.7, 80.9 ± 6.1, and 32.1 ± 4.1 MPa, respectively, and their compressive strength is 5.3 ± 0.29, 8.3 ± 0.18, and 3.0 ± 0.53 MPa, respectively. Thus, all PCL acrylates synthesized in this study can be photopolymerized and because of their solid structure and low viscosity, they are applicable to soft tissue engineering and medical 3D printing.

A trophic model for the Danshuei River Estuary, a hypoxic estuary in northern Taiwan.

The estuary of the Danshuei River, a hypoxic subtropical estuary, receives a high rate of untreated sewage effluent. The Ecopath with Ecosim software system was used to construct a mass-balanced trophic model for the estuary, and network analysis was used to characterize the structure and matter flow in the food web. The estuary model was comprised of 16 compartments, and the trophic levels varied from 1.0 for primary producers and detritus to 3.0 for carnivorous and piscivorous fishes. The large organic nutrient loading from the upper reaches has resulted in detritivory being more important than herbivory in the food web. The food-chain length of the estuary was relatively short when compared with other tropical/subtropical coastal systems. The shortness of food-chain length in the estuary could be attributed to the low biomass of the top predators. Consequently, the trophic efficiencies declined sharply for higher trophic levels due to low fractions of flows to the top predators and then high fractions to detritus. The low biomass of the top predators in the estuary was likely subject to over-exploitation and/or hypoxic water. Summation of individual rate measurements for primary production and respiration yielded an estimate of -1791 g WW m(-2) year(-1), or -95 g C m(-2) year(-1), suggesting a heterotrophic ecosystem, which implies that more organic matter was consumed than was produced in the estuary.

Differential vergence movements in reading Chinese and English: Greater fixation-initial binocular disparity is advantageous in reading the denser orthography.

We explore two aspects of exovergence: we test whether smaller binocular fixation disparities accompany the shorter saccades and longer fixations observed in reading Chinese; we test whether potentially advantageous psychophysical effects of exovergence (cf. Arnold & Schindel, 2010; Kersten & Murray, 2010) transfer to text reading. We report differential exovergence in reading Chinese and English: Chinese readers begin fixations with more binocular disparity, but end fixations with a disparity closely similar to that of the English readers. We conclude that greater fixation-initial binocular fixation disparity can be adaptive in the reading of visually and cognitively denser text.

Caspase-14 is an anti-apoptotic protein targeting apoptosis-inducing factor in lung adenocarcinomas.

Using apoptosis-inducing factor protein as bait in a yeast hybrid assay to screen protein libraries, we identified three proteins that interacted with apoptosis-inducing factor: human homolog of yeast Rad23 protein A (hHR23A), microsomal glutathione S-transferase and caspase-14 (casp-14). In this study, we investigated the expression and function of casp-14 in lung adenocarcinomas (LADC). Our results showed that monoclonal antibodies were specific to casp-14, and that casp-14 was highly expressed in LADC. Casp-14 overexpression correlated with tumor stage, cell differentiation and lymphovascular involvement, suggesting that casp-14 was associated with tumor cell growth and metastatic potential. In vitro, casp-14 interacted with apoptosis-inducing factor, and silencing of casp-14 expression reduced cisplatin resistance. Our data suggest that casp-14 is an anti-apoptotic protein targeting apoptosis-inducing factor and increases cisplatin resistance in LADC cells.