Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein

AbstractSelenoprotein W (SelW) is expressed in various tissues, particularly in skeletal muscle. We have previously reported that SelW is up-regulated during C2C12 skeletal muscle differentiation and inhibits binding of 14-3-3 to its target proteins. 14-3-3 reduces myogenic differentiation by inhibiting nuclear translocation of transcriptional co-activator with PDZ-binding motif (TAZ). Phosphorylation of TAZ at Ser89 is required for binding to 14-3-3, leading to cytoplasmic retention of TAZ and a delay in myogenic differentiation. Here, we show that myogenic differentiation was delayed in SelW-knockdown C2C12 cells. Down-regulation of SelW also increased TAZ binding to 14-3-3, which eventually resulted in decreasing translocation of TAZ to the nucleus. However, phosphorylation of TAZ at Ser89 was not affected. Although phosphorylation of TAZ at Ser89 was sustained by the phosphatase inhibitor okadaic acid, nuclear translocation of TAZ was increased by ectopic expression of SelW. This result was due to decreased binding of TAZ to 14-3-3. We also found that the interaction between TAZ and MyoD was increased by ectopic expression of SelW. Taken together, these findings strongly demonstrate that SelW enhances C2C12 cell differentiation by inhibiting TAZ binding to 14-3-3

EFFECTS OF WALKING SPEED AND AGE ON THE DIRECTIONAL STRIDE REGULARJRY AND GAIT VARIABILITY IN TREADMILL WALKING

The purpose of this study was to assess the directional stride regularity (SR) and gait variability (GV) of data from shoe-type inertial measurement unit (IMU) sensors during levelled treadmill walking. The DynaStabtm (IMU based gait analysis system) including Smart Balance' (shoe-type data logger) was used to collect normal gait data from forty-four subjects in their 20s (n=20), 40s (n=13), and 60s (n=ll). Four different walking speeds (3, 4, 5, and 6 km/h, respectively) on a treadmill were applied for one-minute of continuous levelled walking. Only lateral kinematics (mediolateral acceleration and yawing and rolling angular velocities) revealed significant interactions from walking speed and age, demonstrating lower stride regularity and higher gait variability than the anteroposterior and vertical kinematics

Modelling Surround-aware Contrast Sensitivity for HDR Displays

Despite advances in display technology, many existing applications rely on psychophysical datasets of human perception gathered using older, sometimes outdated displays. As a result, there exists the underlying assumption that such measurements can be carried over to the new viewing conditions of more modern technology. We have conducted a series of psychophysical experiments to explore contrast sensitivity using a state-of-the-art HDR display, taking into account not only the spatial frequency and luminance of the stimuli but also their surrounding luminance levels. From our data, we have derived a novel surroundaware contrast sensitivity function (CSF), which predicts human contrast sensitivity more accurately. We additionally provide a practical version that retains the benefits of our full model, while enabling easy backward compatibility and consistently producing good results across many existing applications that make use of CSF models. We show examples of effective HDR video compression using a transfer function derived from our CSF, tone-mapping, and improved accuracy in visual difference prediction

High-intensity Focused Ultrasound Ablation of Soft-tissue Tumors and Assessment of Treatment Response with Multiparametric Magnetic Resonance Imaging: Preliminary Study Using Rabbit VX2 Tumor Model

BackgroundHigh-intensity focused ultrasound (HIFU) is an emerging technique for noninvasive ablative treatment. However, HIFU has rarely been performed for the treatment of soft-tissue tumors. Thus, we aimed to assess the feasibility and safety of performing extracorporeal HIFU for the treatment of soft-tissue tumor. The treatment response was assessed using functional magnetic resonance imaging (MRI) techniques.Materials and methodsIn the rabbit VX2 intramuscular tumor model, HIFU was performed using an extracorporeal HIFU device (YDME FEP-BY02) by varying the electric power from 50 to 400 W, with the other parameters being fixed. The HIFU beam was insonated to one layer of focal spots having a depth of 8 mm. The degree of ablation was evaluated by histological examination and functional MRI techniques including dynamic contrast-enhanced MRI (DCE-MRI) and apparent diffusion coefficient (ADC) map. The presence of skin burn was also evaluated.ResultsApplying HIFU with an electric power of 200 W discretely produced the ablation zone without skin burn as planned before treatment (maximal depth: 8–9 mm), which shows the suitability of using HIFU (with 200 W electric power) for the treatment of soft-tissue tumors. By contrast, HIFU with an electric power of 100 W produced an ill-marginated ablation zone with internal residual tumor foci, and HIFU with 300–400 W produced ablation zones with a maximum depth of 13–24 mm, which far exceeded the planned depth and caused skin burn. Perfusion maps of DCE-MRI demonstrated the devascularized ablation zone more conspicuously than conventional contrast-enhanced T1-weighted images, and ADC map demonstrated the surrounding edema or granulation tissue better than conventional T2-weighted images.ConclusionExtracorporeal HIFU treatment for soft-tissue tumor may be a feasible approach with adjustment of input energy level. For post-treatment assessment, functional MRI techniques including DCE-MRI and ADC map may be useful and complementary to conventional MRI

SPON1 Can Reduce Amyloid Beta and Reverse Cognitive Impairment and Memory Dysfunction in Alzheimer's Disease Mouse Model

Alzheimer's disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (A beta) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of A beta, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in A beta reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of A beta when co-cultured with A beta -secreting Neuro 2a cells. The human SPON1 gene itself also reduced A beta in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of A beta and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations

Copy number variations (CNVs) identified in Korean individuals

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) are deletions, insertions, duplications, and more complex variations ranging from 1 kb to sub-microscopic sizes. Recent advances in array technologies have enabled researchers to identify a number of CNVs from normal individuals. However, the identification of new CNVs has not yet reached saturation, and more CNVs from diverse populations remain to be discovered.</p> <p>Results</p> <p>We identified 65 copy number variation regions (CNVRs) in 116 normal Korean individuals by analyzing Affymetrix 250 K Nsp whole-genome SNP data. Ten of these CNVRs were novel and not present in the Database of Genomic Variants (DGV). To increase the specificity of CNV detection, three algorithms, CNAG, dChip and GEMCA, were applied to the data set, and only those regions recognized at least by two algorithms were identified as CNVs. Most CNVRs identified in the Korean population were rare (<1%), occurring just once among the 116 individuals. When CNVs from the Korean population were compared with CNVs from the three HapMap ethnic groups, African, European, and Asian; our Korean population showed the highest degree of overlap with the Asian population, as expected. However, the overlap was less than 40%, implying that more CNVs remain to be discovered from the Asian population as well as from other populations. Genes in the novel CNVRs from the Korean population were enriched for genes involved in regulation and development processes.</p> <p>Conclusion</p> <p>CNVs are recently-recognized structural variations among individuals, and more CNVs need to be identified from diverse populations. Until now, CNVs from Asian populations have been studied less than those from European or American populations. In this regard, our study of CNVs from the Korean population will contribute to the full cataloguing of structural variation among diverse human populations.</p

Incidence and Predictive Factors of Benign Renal Lesions in Korean Patients with Preoperative Imaging Diagnoses of Renal Cell Carcinoma

The present study was performed to determine the incidence and predictive factors of benign renal lesions in Korean patients undergoing nephrectomy for presumed renal cell carcinoma on preoperative imaging. We analyzed the pathologic reports and medical records of 1,598 eligible patients with unilateral, nonmetastatic, and nonfamilial renal masses. Of the 1,598 renal masses, 114 (7.1%) were benign lesions, including angiomyolipoma in 47 (2.9%), oncocytoma in 23 (1.4%), and complicated cysts in 18 (1.1%) patients. On univariate analysis, the proportion of benign lesions was significantly higher in female patients, and in patients with smaller tumors, cystic renal masses, and without gross hematuria as a presenting symptom. When renal lesions were stratified by tumor size, the proportion of benign as opposed to malignant lesions decreased significantly as tumor size increased. On multivariate analysis, female gender, smaller tumor size, and cystic lesions were significantly associated with benign histological features. The findings in this large cohort of Korean patients show a lower incidence (7.1%) of benign renal lesions than those of previous Western reports. Female gender, cystic renal lesions, and smaller tumor size are independent predictors of benign histological features

Molecular Identification of Taenia Tapeworms by Cox1 Gene in Koh Kong, Cambodia

We collected fecal samples from 21 individuals infected with Taenia tapeworms in Koh Kong Province, Cambodia, and performed nucleotide sequencing of the cox1 gene and multiplex PCR on the eggs for DNA differential diagnosis of human Taenia tapeworms. Genomic DNA was extracted from the eggs of a minimum number of 10 isolated from fecal samples. Using oligonucleotide primers Ta7126F, Ts7313F, Tso7466F, and Rev7915, the multiplex PCR assay proved useful for differentially diagnosing Taenia solium, Taenia saginata, and Taenia asiatica based on 706, 629, and 474 bp bands, respectively. All of the Taenia specimens from Kho Kong, Cambodia, were identified as either T. saginata (n=19) or T. solium (n=2) by cox1 sequencing and multiplex PCR