TAGLN is an actin-binding protein family that comprises three isoforms with theorized roles in smooth muscle differentiation, tumour development, lymphocyte activation, and brain chemistry. However, ...their fundamental characteristics in regulation of the actin-based cytoskeleton are not fully understood. Here we show that TAGLN2 (including TAGLN1 and TAGLN3) extensively nucleates G-actin polymerization under low-salt conditions, where polymerization would be completely suppressed. The calponin homology domain and actin-binding loop are essential to mechanically connect two adjacent G-actins, thereby mediating multimeric interactions. However, TAGLN2 blocked the Arp2/3 complex binding to actin filaments under physiological salt conditions, thereby inhibiting branched actin nucleation. In HeLa and T cells, TAGLN2 enhanced filopodium-like membrane protrusion. Collectively, the dual functional nature of TAGLN2-G-actin polymerization and Arp2/3 complex inhibition-may account for the mechanisms of filopodia development at the edge of Arp2/3-rich lamellipodia in various cell types.
The process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are ...reported to result from and also be causal to cellular senescence. As a result, modifying any of them-senescence, metabolism, or the circadian clock-may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial burden of fatty acid oxidation. As a result, if senescence, metabolism, and circadian rhythm are all linked, anti-obesity treatments may improve metabolic regulation while also alleviating senescence and circadian rhythm. Vutiglabridin is a small molecule in clinical trials that improves obesity by enhancing mitochondrial function. We found that chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin alleviates all investigated markers of cellular senescence (SA-β-gal, CDKN1A, CDKN2A) and dysfunctional cellular circadian rhythm (BMAL1) while remarkably preventing the alterations of mitochondrial function and structure that occur during the process of cellular senescence. Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock.
The conventional (CH3NH3I (MAI)):PbI2:PbCl2 = 3 : 0: 1 abbreviated as (3:0:1) precursor solution is known to result in CH3NH3PbI3–xClx films with large grain sizes when processed in an inert ...atmosphere, but it gives non-uniform perovskite films containing lots of voids and cracks when processed in ambient air. Furthermore, a dramatically longer annealing time (usually 100 min) is required for these films (3:0:1) due to the slow formation of the MAPbI3 phase via MACl loss, which is not conducive to perovskite film formation under ambient conditions due to perovskite degradation upon long exposure to moisture. Pure MAPbI3 films can be formed very rapidly from (1:1:0) (MAI:PbI2:PbCl2 = 1 : 1: 0) solution within a short annealing time, but they show small grain sizes and poor film quality. This work demonstrated that a fractional substitution of PbI2 with PbCl2 in the (MAI:PbI2 = 1 : 1) precursor solution has a significant influence on film morphology and quality in terms of crystallization rate, grain size, crystallinity, and trap density of the formed perovskite film. Perovskite films can be formed with 5-min annealing at 100 °C from the precursor (MAI: PbI2:PbCl2 = 1: 0.8 : 0.2) processed in ambient air (humidity, 20% RH), exhibiting more uniform, increased grain size and higher film quality with reduced trap densities compared to film (1:1:0), thus leading to significantly improved power conversion efficiency (PCE), from 16.7% for perovskite solar cells (PrSCs) based on film (1:1:0) to 20.04% for the cell based on film (1:0.8:0.2). Further, the effects of R (R = MAI/PbI2+PbCl2) on morphology, hole mobility, carrier lifetime and efficiency of PrSCs were systematically and thoroughly investigated. This study found that MAPbI3–xClx at R = 1 can enable the highest hole mobility and longest carrier lifetime, thus giving the best performance at R = 1.
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•MAPbI3–xClx film prepared from 3MAI:1PbCl2 requires long annealing time and exhibited poor coverage under ambient air.•1MAI:0.8PbI2:0.2PbCl2 improves film coverage and significantly shortens the annealing time from 120 min to 5 min.•20% substitution of PbI2 with PbCl2 for 1MAI:1PbI2 produces films with enlarged grain size and reduced trap densities.•Effects of MAI/PbI2+PbCl2 on the performance of the perovskite solar cells were systematically investigated.•The optimal device processed under ambient air (20% RH) gives a power-conversion efficiency of > 20%.
Chondromas rarely occur in the nasal area and are usually found in the metaphyseal area of the phalanges and metacarpals of the hands, as well as the pelvis, sternum and scapula. The authors present ...an unusual case of dysphagia induced by histologically confirmed chondroma arising from the nasal septum. Treatment is to completely remove the mass with adequate margins of normal tissues to prevent recurrence and malignancy. Intranasal endoscopic removal of tumor with an adequate margin of normal tissue. After one year of treatment, there was no evidence of recurrence. We present a case of nasal septal chondroma in 18-year-old male. Keywords: chondroma; dysphagia; septum.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), characterized by the gut mucosal ulceration. Growing evidence indicates that dysregulation of immune response to the commensal ...microbiota involves the pathogenesis of IBD. Previous studies have demonstrated the favorable probiotic effects of fermented rice extracts through triple fermentation with Saccharomyces cerevisiae and Weissella cibaria (FRe). Thus, the therapeutic potential of FRe for UC was examined. Dextran sodium sulfate UC mice model was orally administered distilled water as a control, sulfasalazine, or FRe at 300, 200, and 100 mg/kg, once a day for a week. The UC control exhibited body weight loss, bloody stools, and colonic shortening. However, the FRe, especially at 300 mg/kg, led to a reduction in weight loss, disease activity index scores, and colon weight, and an increase in colorectal length. The histopathological analyses revealed mild changes involved in the colonic crypt and mucosal damages in the FRe groups, along with inhibited inflammation. Indeed, the FRe reduced neutrophil infiltration and production of proinflammatory cytokines (i.e., tumor necrosis factor‐α, interleukin‐6/‐8). This was accompanied by the down‐regulation of nuclear factor‐kappa B. The gene expression responsible for the intestinal barrier integrity (i.e., Zonna occludens‐1/‐2, Claudin‐1, Occludin, Mucin‐1/‐2) was up‐regulated in the FRe groups. In addition, the FRe reduced lipid peroxidation and enhanced antioxidant activity. Interestingly, the microbiota dysbiosis was attenuated in the FRe groups, and the number of beneficial bacteria, Lactobacilli and Bifidobacteria, was increased. It suggests that the FRe potently ameliorate UC as a functional food.
Oral treat of FRe ameliorated the UC symptoms by (a) improved dysbiosis as prebiotics, (b) NF‐κB‐mediated anti‐inflammation, (c) enhanced antioxidant activity, (d) restored mucus layer and the tight junction, (e) reduced immunity of CD4+ and CD8+ T cell, and (f) increased serum IgG but decreased IgA.
Metastasis and multiple myeloma are common malignant bone marrow lesions which may be difficult to distinguish because of similar imaging findings. The purpose of this study was to determine the ...value of adding diffusion-weighted imaging (DWI) to standard MR imaging to differentiate multiple myeloma from metastasis.
25 patients with metastasis and 18 patients with multiple myeloma underwent 3T MR imaging with DWI (b = 0, 800 s/mm2) were enrolled. They all had pathologically confirmed bone lesions and were in a treatment naïve state. Two readers who were blind of final diagnosis measured the average ADC (ADCav) and minimum ADC (ADCmin) on the DWI. They then estimated the diagnosis, based on the standard MR imaging and measured ADC values. Another reader performed histogram analysis on the whole tumor volume and obtained mean ADC (ADCvol), standard deviation (SDvol), skewness, and kurtosis. Comparison of the obtained values from DWI was performed by the t-test or Mann-Whitney U test. The receiver operating characteristic (ROC) curve with areas under the curve (AUC) was used to obtain the cut off values and to evaluate the diagnostic performance of the two readers.
ADCav, ADCmin, and ADCvol of multiple myeloma were significantly lower than those of metastasis: ADCav, 752 μm2/sec versus 1081 μm2/sec; ADCmin, 704 μm2/sec vs 835 μm2/sec; ADCvol 761 μm2/sec vs 1184 μm2/sec (p < .001). In histogram analysis, ADC values of multiple myeloma showed narrow distribution than metastasis: SDvol, 144 vs 257 (p < .001). Areas under the receiver operating characteristic curve was significantly higher with additive DWI than standard MR alone: 0.762 vs 0.953; 0.706 vs 0.950 (p < .05) for two readers.
This study suggested that the addition of axial DWI to standard MR imaging can be helpful to diagnose multiple myeloma from metastasis at 3T.
The KVSSII is widely used to evaluate olfactory function in the Korean population. We evaluated the usefulness of the first recognized
n
-butanol concentration, which is obtained at the beginning ...part of KVSS II, in predicting olfactory dysfunction. Three hundred seventy two subjects were enrolled in our study. The results of KVSS II and the demographic characteristics were statistically analyzed. The first recognized
n
-butanol concentration was positively correlated with the result of KVSS II. The mean value of first recognized
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-butanol concentration was 5.59 ± 1.42 in normosmia, 4.10 ± 1.40 in hyposmia, and 0.84 ± 1.68 in the anosmia group. By ROC curve, cut-off value of 2.5 showed sensitivity of 85.9% and specificity of 90.6% for anosmia, and cut-off value of 4.5 showed sensitivity of 77.6% and specificity of 69.8% for hyposmia. Consequently, we suggest that it may be useful in assessing olfactory function, in geriatric patients who are not able to tolerate conventional KVSS II.
Previously, we introduced a noninvasive prenatal testing (NIPT) protocol for diagnosing compound heterozygous autosomal recessive point mutations via maternal plasma DNA and simulated control genomic ...DNA sampling based on fetal DNA fraction. In our present study, we have improved our NIPT protocol to make it possible to diagnose homozygous autosomal recessive point mutations without the need to acquire fetal DNA fraction. Moreover, chi-squared test and empirical statistical range based on the proportion of mutant allele reads among the total reads served as the gatekeeping method. If this method yielded inconclusive results, then the Bayesian method was performed; final conclusion was drawn from the results of both methods. This protocol was applied to three families co-segregating congenital sensorineural hearing loss with monogenic homozygous mutations in prevalent deafness genes. This protocol successfully predicted the fetal genotypes from all families without the information about fetal DNA fraction using one-step dPCR reactions at least for these three families. Furthermore, we suspect that confirmatory diagnosis under this protocol is possible, not only by using picodroplet dPCR, but also by using the more readily available chip-based dPCR, making our NIPT protocol more useful in the diagnosis of autosomal recessive point mutations in the future.
MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear ...implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness.
Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants.
In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants.
Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation.
To report the nationwide prevalence of dizziness and vestibular dysfunction in the Korean population and determine the associated factors.
Cross-sectional analysis of a nationwide health survey.
We ...obtained data from the 2009 to 2010 Korea National Health and Nutrition Examination Surveys, which were cross-sectional surveys of the South Korean civilian, non-institutionalised population aged 40 years and older (N=3267). A field survey team performed interviews and physical examinations. Structured questionnaires were handed out and balance function tests using the modified Romberg test of standing balance on firm and compliant support surfaces were performed on participants. Failure on the modified Romberg test was regarded to indicate vestibular dysfunction.
The prevalence of dizziness during the past year was 16.70% (95% CI 14.65% to 18.76%). The presence of vestibular dysfunction was noted in 1.84% (95% CI 1.18% to 2.51%). In addition, the prevalence of experiencing falls and positional dizziness were 1.46% (95% CI 0.87% to 2.06%) and 1.73% (95% CI 1.17% to 2.29%), respectively. Multivariable analysis revealed that dizziness was associated with increased age, female gender, hearing loss and stress. Vestibular dysfunction was associated with increased age, history of dizziness and hearing loss.
Vertigo and dizziness are the greatest contributors to the burden of disability in the aged population. Screening for dizziness and vestibular dysfunction, and management of associated factors might be important for improving compromised quality of life due to postural imbalance caused by vestibular problems.
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