TAZ Suppresses NFAT5 Activity through Tyrosine Phosphorylation

Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple renal cysts and urinary concentration defects; however, the molecular functions of TAZ in renal cells remain largely unknown. In this study, we examined the effects of osmotic stress on TAZ expression and activity in renal cells. We found that hyperosmotic stress selectively increased protein phosphorylation at tyrosine 316 of TAZ and that this was enhanced by c-Abl activation in response to hyperosmotic stress. Interestingly, phosphorylated TAZ physically interacted with nuclear factor of activated T cells 5 (NFAT5), a major osmoregulatory transcription factor, and subsequently suppressed DNA binding and transcriptional activity of NFAT5. Furthermore, TAZ deficiency elicited an increase in NFAT5 activity in vitro and in vivo, which then reverted to basal levels following restoration of wild-type TAZ but not mutant TAZ (Y316F). Collectively, the data suggest that TAZ modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation.open3

Birth and Death of One-dimensional Domains in Cylindrically Confined Liquid Crystals

Nematic liquid crystal (LC) is a partially ordered matter that has been a popular model system for studying a variety of topological behaviors in condensed matter. In this work, utilizing a spontaneously twisting achiral LC, we introduce a one-dimensional (1D) model system to investigate how domains and topological defects arise and annihilate, reminiscing the Kibble-Zurek mechanism. Because of the unusual elastic properties, lyotropic chromonic LCs form a double-twist structure in a cylindrical capillary with degenerate planar anchoring, exhibiting chiral symmetry breaking despite the absence of intrinsic chirality. Consequently, the domains of different handedness coexist with equal probabilities, forming the topological defects between them. We experimentally measure the domain-length distribution and its time evolution, best fitted by a three-parameter log-normal distribution. We propose that the coalescence within a train of 1D domains having the normal length distribution and randomly assigned handedness, may lead to the domains of the log-normal-like length distribution. Our cylindrically confined LC provides a practical model system to study the formation and annihilation of domains and defects in 1D

PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

A Novel Secretory Vesicle from Deer Antlerogenic Mesenchymal Stem Cell-Conditioned Media (DaMSC-CM) Promotes Tissue Regeneration

Multipotent stem cells have the capacity to generate terminally differentiated cell types of each lineage; thus, they have great therapeutic potential for a wide variety of diseases. The most widely available stem cells are derived from human tissues, and their use for therapeutic application is limited by their high cost and low productivity. Herein, we report that conditioned media of mesenchymal stem cells (MSCs) isolated from deer antlers enhanced tissue regeneration through paracrine action via a combination of secreted growth factors and cytokines. Notably, DaMSC-conditioned media (DaMSC-CM) enhanced hair regeneration by activating the Wnt signaling pathway. In addition, DaMSC-CM had regenerative potential in damaged skin tissue through induction of skin regeneration-related genes. Remarkably, we identified round vesicles derived from DaMSC-CM, with an average diameter of ~120 nm that were associated with hair follicle formation, suggesting that secretory vesicles may act as paracrine mediators for modulation of local cellular responses. In addition, these secretory vesicles could regulate the expression of Wnt-3a, Wnt-10b, and lymphoid enhancer-binding factor-1 (LEF-1), which are related to tissue renewal. Thus, our findings demonstrate that the use of DaMSC-CM as a unique natural model for rapid and complete tissue regeneration has possible application for therapeutic development

Lack of Mitochondrial DNA Sequence Divergence between Two Subspecies of the Siberian Weasel from Korea: Mustela sibirica coreanus from the Korean Peninsula and M. s. quelpartis from Jeju Island

The objective of this study was to determine the degree of mitochondrial DNA (mtDNA) divergence between two subspecies of Mustela sibirica from Korea (M. s. coreanus on the Korean Peninsula and M. s. quelpartis on Jeju Island) and to examine the taxonomic status of M. s. quelpartis. Thus, we obtained complete sequences of mtDNA cytochrome b gene (1,140 bp) from the two subspecies, and these sequences were compared to a corresponding haplotype of M. s. coreanus, downloaded from GenBank. From this analysis, it was observed that the sequences from monogenic M. s. quelpartis on Jeju Island were identical to the sequences of four M. s. coreanus from four locations across the Korean Peninsula, and that the two subspecies formed a single clade; the average nucleotide distance between the two subspecies was 0.26% (range, 0.00 to 0.53%). We found that the subspecies quelpartis is not genetically distinct from the subspecies coreanus, and that this cytochrome b sequencing result does not support the current classification, distinguishing these two subspecies by pelage color. Further systematic analyses using morphometric characters and other DNA markers are necessary to confirm the taxonomic status of M. s. quelpartis

MLN51 and GM-CSF involvement in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unclear etiology. This study was conducted to identify critical factors involved in the synovial hyperplasia in RA pathology. We applied cDNA microarray analysis to profile the gene expressions of RA fibroblast-like synoviocytes (FLSs) from patients with RA. We found that the MLN51 (metastatic lymph node 51) gene, identified in breast cancer, is remarkably upregulated in the hyperactive RA FLSs. However, growth-retarded RA FLSs passaged in vitro expressed small quantities of MLN51. MLN51 expression was significantly enhanced in the FLSs when the growth-retarded FLSs were treated with granulocyte – macrophage colony-stimulating factor (GM-CSF) or synovial fluid (SF). Anti-GM-CSF neutralizing antibody blocked the MLN51 expression even though the FLSs were cultured in the presence of SF. In contrast, GM-CSF in SFs existed at a significant level in the patients with RA (n = 6), in comparison with the other inflammatory cytokines, IL-1β and TNF-α. Most RA FLSs at passage 10 or more recovered from their growth retardation when cultured in the presence of SF. The SF-mediated growth recovery was markedly impaired by anti-GM-CSF antibody. Growth-retarded RA FLSs recovered their proliferative capacity after treatment with GM-CSF in a dose-dependent manner. However, MLN51 knock-down by siRNA completely blocked the GM-CSF/SF-mediated proliferation of RA FLSs. Taken together, our results imply that MLN51, induced by GM-CSF, is important in the proliferation of RA FLSs in the pathogenesis of RA

Crowned dens syndrome as a rare cause of anterior neck pain after transurethral resection of the prostate: a case report

We describe the case of a 79-year-old man who presented with progressive aggravation of severe axial neck pain and fever 3 days after transurethral resection of the prostate (TURP), despite maintaining neutral neck posture during surgery. Laboratory examination revealed markedly elevated C-reactive protein levels and erythrocyte sedimentation rates. Computed tomography revealed crown-like calcifications surrounding the odontoid process. We diagnosed crowned dens syndrome (CDS) as the cause of acute-onset neck pain after TURP. The patient was treated with nonsteroidal anti-inflammatory drugs for 5 days, and his symptoms resolved completely. CDS is a rare disease characterized by calcific deposits around the odontoid process with acute onset of severe neck pain and restricted motion. Evidence of inflammation on serological testing and fever are typical of CDS. However, the prevalence and pathophysiology of CDS remain unclear. We hypothesized that systemic inflammation after prostate surgery may have induced a local inflammatory response involving calcification around the odontoid process

Saccadic Palsy after Cardiac Surgery: Serial Neuroimaging Findings during a 6-Year Follow-Up

Background Patients who develop horizontal and vertical saccadic palsy after cardiac surgery have rarely been described. Although most such patients exhibit distinct neurological deficits, their brain MRI findings are almost normal. In addition, functional neuroimaging of such patients has never been reported.Case Report A 43-year-old woman with dysarthria, dysphagia, and horizontal and vertical saccadic palsy after cardiac surgery was followed up for about 6 years; serial brain MRIs has been performed during this period, including susceptibility-weighted imaging (SWI) and [[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Multiple microbleeds in the cerebral cortex, cerebellum, and brainstem, and glucose hypometabolism in the brainstem, cerebellum, and multiple cortical areas.Conclusions To the best of our knowledge, this is the first reported case of saccadic palsy after cardiac surgery with serial SWI and [F-18]-FDG-PET performed to explore the possible cerebral lesions.Background Patients who develop horizontal and vertical saccadic palsy after cardiac surgery have rarely been described. Although most such patients exhibit distinct neurological deficits, their brain MRI findings are almost normal. In addition, functional neuroimaging of such patients has never been reported. Case Report A 43-year-old woman with dysarthria, dysphagia, and horizontal and vertical saccadic palsy after cardiac surgery was followed up for about 6 years; serial brain MRIs has been performed during this period, including susceptibility-weighted imaging (SWI) and [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Multiple microbleeds in the cerebral cortex, cerebellum, and brainstem, and glucose hypometabolism in the brainstem, cerebellum, and multiple cortical areas. Conclusions To the best of our knowledge, this is the first reported case of saccadic palsy after cardiac surgery with serial SWI and [18F]-FDG-PET performed to explore the possible cerebral lesions.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000004487/28SEQ:28PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000004487ADJUST_YN:YEMP_ID:A075641DEPT_CD:801CITE_RATE:1.807FILENAME:kimej-saccadic palsy after cardiac surgery-j clin neurol-2014-10(4)367.pdfDEPT_NM:의학과SCOPUS_YN:YCONFIRM: