A DUAL FUNCTION OF PRDM14 IN HUMAN EMBRYONIC STEM CELLS AND REPROGRAMMING

Ph.DDOCTOR OF PHILOSOPH

Dynamic Transcription of Distinct Classes of Endogenous Retroviral Elements Marks Specific Populations of Early Human Embryonic Cells

SummaryAbout half of the human genome consists of highly repetitive elements, most of which are considered dispensable for human life. Here, we report that repetitive elements originating from endogenous retroviruses (ERVs) are systematically transcribed during human early embryogenesis in a stage-specific manner. Our analysis highlights that the long terminal repeats (LTRs) of ERVs provide the template for stage-specific transcription initiation, thereby generating hundreds of co-expressed, ERV-derived RNAs. Conversion of human embryonic stem cells (hESCs) to an epiblast-like state activates blastocyst-specific ERV elements, indicating that their activity dynamically reacts to changes in regulatory networks. In addition to initiating stage-specific transcription, many ERV families contain preserved splice sites that join the ERV segment with non-ERV exons in their genomic vicinity. In summary, we find that ERV expression is a hallmark of cellular identity and cell potency that characterizes the cell populations in early human embryos

Brief Communication Ophthalmic plastic and orbital surgery in Taiwan

Abstract We describe in this paper the current status of ophthalmic plastic and orbital surgery in Taiwan. Data were collected from the Bureau of National Health Insurance of Taiwan, the Bulletin of the Taiwan Ophthalmic Plastic and Reconstructive Society, and the Statistics Yearbook of Practicing Physicians and Health Care Organizations in Taiwan by the Taiwan Medical Association. We ascertained that 94 ophthalmologists were oculoplastic surgeons and accounted for 5.8% of 1621 ophthalmologists in Taiwan. They had their fellowship training abroad (most ophthalmologists trained in the United States of America) or in Taiwan. All ophthalmologists were well trained and capable of performing major oculoplastic surgeries. The payment rates by our National Health Insurance for oculoplastic and orbital surgeries are relatively low, compared to Medicare payments in the United States. Ophthalmologists should promote the concept that oculoplastic surgeons specialize in periorbital plastic and aesthetic surgeries. However, general ophthalmologists should receive more educational courses on oculoplastic and cosmetic surgery

Assessing the role of the cadherin/catenin complex at the Schwann cell-axon interface and in the initiation of myelination

Myelination is dependent on complex reciprocal interactions between the Schwann cell (SC) and axon. Recent evidence suggests that the SC–axon interface represents a membrane specialization essential for myelination; however, the manner in which this polarized-apical domain is generated remains a mystery. The cell adhesion molecule N-cadherin is enriched at the SC–axon interface and colocalizes with the polarity protein Par-3. The asymmetric localization is induced on SC–SC and SC–axon contact. Knockdown of N-cadherin in SCs cocultured with DRG neurons disrupts Par-3 localization and delays the initiation of myelination. However, knockdown or overexpression of neuronal N-cadherin does not influence the distribution of Par-3 or myelination, suggesting that homotypic interactions between SC and axonal N-cadherin are not essential for the events surrounding myelination. To further investigate the role of N-cadherin, mice displaying SC-specific gene ablation of N-cadherin were generated and characterized. Surprisingly, myelination is only slightly delayed, and mice are viable without any detectable myelination defects. β-Catenin, a downstream effector of N-cadherin, colocalizes and coimmunoprecipitates with N-cadherin on the initiation of myelination. To determine whether β-catenin mediates compensation on N-cadherin deletion, SC-specific gene ablation of β-catenin was generated and characterized. Consistent with our hypothesis, myelination is more severely delayed than when manipulating N-cadherin alone, but without any defect to the myelin sheath. Together, our results suggest that N-cadherin interacts with β-catenin in establishing SC polarity and the timely initiation of myelination, but they are nonessential components for the formation and maturation of the myelin sheath

Somatodendritic Expression of JAM2 Inhibits Oligodendrocyte Myelination

Myelination occurs selectively around neuronal axons to increase the efficiency and velocity of action potentials. While oligodendrocytes are capable of myelinating permissive structures in the absence of molecular cues, structurally permissive neuronal somata and dendrites remain unmyelinated. Utilizing a purified spinal cord neuron-oligodendrocyte myelinating coculture system, we demonstrate that disruption of dynamic neuron-oligodendrocyte signaling by chemical crosslinking results in aberrant myelination of the somatodendritic compartment of neurons. We hypothesize that an inhibitory somatodendritic cue is necessary to prevent non-axonal myelination. Using next-generation sequencing and candidate profiling, we identify neuronal Junction Adhesion Molecule 2 (JAM2) as an inhibitory myelin-guidance molecule. Taken together, our results demonstrate that the somatodendritic compartment directly inhibits myelination, and suggest a model in which broadly indiscriminate myelination is tailored by inhibitory signaling to meet local myelination requirements

Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis

Perception of Stigma and Its Associated Factors Among Patients With Major Depressive Disorder: A Multicenter Survey From an Asian Population

Stigma of major depressive disorder (MDD) is an important public health problem. This study aimed to examine the level of perceived stigma and its associated factors in MDD patients in five Asian countries, including China, Korea, Malaysia, Singapore, and Thailand. A total of 547 outpatients with MDD were included from Asian countries. We used the stigma scale of the Explanatory Model Interview Catalogue (EMIC) to assess stigma. The Montgomery–Asberg Depression Rating Scale (MADRS), Symptoms Checklist 90-Revised (SCL-90-R), Fatigue Severity Scale (FSS), Sheehan Disability Scale (SDS), 36-Item Short-Form Health Survey (SF-36), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to assess symptoms, clinical features, functional impairment, health status, and social support. The stigma scores of patients under 55 years old were significantly higher than those equal to or greater than 55 years old (P < 0.001). The stigma scores exhibited significant negative correlation with age; MSPSS scores of family, friends, and others; and SF-36 subscale of mental health, but significant positive correlation with MADRS, FSS, SDS, and SCL-90-R subscale scores of depression, interpersonal sensitivity, obsession–compulsion, psychoticism, and somatization. Multivariate regression analysis revealed that age, SCL-90-R interpersonal sensitivity, obsession–compulsion, psychoticism, MSPSS scores of friends and others, and SF-36 of mental health were significantly associated with the level of perceived stigma. These findings suggest that MDD patients who are young, have a high degree of interpersonal sensitivity and psychoticism, have low health-related quality of life, and have low social support are the target population for stigma interventions in Asia

Executive cash compensation and tax aggressiveness of Chinese firms

We examine the influence of corporate compensation policies on firms’ tax aggressiveness in an emerging market where executive compensation is primarily in cash form. Based on a hand-collected dataset of 958 firm-year observations of Chinese listed firms for the 2006-2012 period, we find that firms paying higher executive cash compensation are associated with lower tax aggressiveness. This relationship also holds for the excess cash compensation measures which control for executive shareholding, firm profitability, size, growth opportunity, and board independence. We further document that mutual funds ownership pressure firms paying higher compensation to reduce their tax aggressiveness, suggesting adverse selection by mutual funds on firms exhibiting risky tax avoidance activities. High leverage offsets the negative link between cash compensation and tax aggressiveness, indicating a complementary effect between debt and tax avoidance, and, hence, suggesting that creditor monitoring is weak. These results are robust to the system-GMM estimation, which simultaneously account for the endogeneity of executive compensation, tax aggressiveness, ownership and control, leverage, and corporate governance. Our findings on Chinese firms have important policy implications for developing countries around the world with concentrated ownership structure, weak institutional environment, widespread corruption, ineffective rule of law, and ongoing significant social and political transformation

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres