ETS transcription factor Etsrp / Etv2 is required for lymphangiogenesis and directly regulates <i>vegfr3 / flt4</i> expression

Davis, Jennifer A.,Koenig, Andrew L.,Lubert, Allison,Chestnut, Brendan,Liu, Fang,Palencia Desai, Sharina,Winkler, Tamara,Pociute, Karolina,Choi, Kyunghee,Sumanas, Saulius Elsevier 2018 Developmental Biology Vol.440 No.1

<P><B>Abstract</B></P> <P>The molecular mechanisms initiating the formation of the lymphatic system, lymphangiogenesis, are still poorly understood. Here we have identified a novel role in lymphangiogenesis for an ETS transcription factor, Etv2/Etsrp, a known regulator of embryonic vascular development. Through the use of fully validated photoactivatable morpholinos we show that inducible Etv2 inhibition in zebrafish embryos at 1 day post-fertilization (dpf) results in significant inhibition of lymphangiogenesis, while development of blood vessels is unaffected. In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including <I>lyve1b</I>, <I>prox1a</I>, and <I>vegfr3/flt4</I>, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor <I>Vegfr3/Flt4</I> and lymphatic marker <I>Lyve1</I>, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of <I>flt4</I> within the posterior cardinal vein.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Etv2 expression is enriched in the vein during zebrafish lymphangiogenesis. </LI> <LI> Inducible Etv2 knockdown inhibits lymphangiogenesis. </LI> <LI> Blood vessels are not affected by Etv2 knockdown at 24 hpf. </LI> <LI> Vegfc fails to induce lymphangiogenesis in Etv2 knockdown embryos. </LI> <LI> Etv2 directly binds to Flt4 promoter and promotes its expression. </LI> </UL> </P>

TFOS DEWS II Definition and Classification Report

Craig, Jennifer P.,Nichols, Kelly K.,Akpek, Esen K.,Caffery, Barbara,Dua, Harminder S.,Joo, Choun-Ki,Liu, Zuguo,Nelson, J. Daniel,Nichols, Jason J.,Tsubota, Kazuo,Stapleton, Fiona Elsevier 2017 The ocular surface Vol.15 No.3

<P><B>Abstract</B></P> <P>The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Central to the scheme is a positive diagnosis of DED with signs and symptoms, and this is directed towards management to restore homeostasis. The scheme also allows consideration of various related manifestations, such as non-obvious disease involving ocular surface signs without related symptoms, including neurotrophic conditions where dysfunctional sensation exists, and cases where symptoms exist without demonstrable ocular surface signs, including neuropathic pain. This approach is not intended to override clinical assessment and judgment but should prove helpful in guiding clinical management and research.</P>

Follow the Leader: Cross-Industry Herding in Earnings Management

Lin xiao Liu,Michael R Williams,Jennifer Yin 사람과세계경영학회 2014 Global Business and Finance Review Vol.19 No.1

We employ Vector Autoregressions and quarterly financial statement data to explicitly test for both own- and cross-industry earnings management "spillovers". We find that earnings management behavior can transmit from one industry to another, similar industry. Further, we find an indirect, information-based channel whereby earnings management information may reach less-related industries with a lag of about six months. These results provide initial evidence that managers within similar industries "herd" in their discretionary accrual strategies. That is, earnings management in one sub-industry classification provides an informative signal to other industries. Others, then, follow suit by adopting like strategies either for competitive parity or purely wealth-maximizing purposes. In addition, we find that earnings management is persistent and does not mean-revert. Thus, earnings management can have long-term permanent impacts on a firm and its financial statements. This paper presents both methodological and policy implications for the academic accounting literature.

Improvement of OMI ozone profile retrievals in the troposphere and lower stratosphere by use of a tropopause-based ozone profile climatology

Juseon Bak,Xiong Liu,Jennifer C. Wei,Laura L. Pan,Jae H. Kim,Kelly Chance,Christopher D. Barnet 한국기상학회 2011 한국기상학회 학술대회 논문집 Vol.2011 No.10-2

A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases

Zhao, Jian,Ma, Jianyang,Deng, Yun,Kelly, Jennifer A,Kim, Kwangwoo,Bang, So-Young,Lee, Hye-Soon,Li, Quan-Zhen,Wakeland, Edward K,Qiu, Rong,Liu, Mengru,Guo, Jianping,Li, Zhanguo,Tan, Wenfeng,Rasmussen, Nature Pub. Co 2017 Nature genetics Vol.49 No.3

<P>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type 1 interferon signatures. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the lmmunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production(2), predisposes to SLE (odds ratio (OR) = 3.47 in Asians (P-meta = 3.1 x 10(-104)), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjogren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.</P>

Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes

Qing-Lin Lou,Xiao-Jun Ouyang,Liu-Bao Gu,Yong-Zhen Mo,Ronald Ma,Jennifer Nan,Alice Kong,Wing-Yee So,Gary Ko,Juliana Chan,Chun-Chung Chow,Rong-Wen Bian 대한당뇨병학회 2012 Diabetes and Metabolism Journal Vol.36 No.6

Background: To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009. Methods: Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g. Results: We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively. Conclusion: In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.

Validity of Glycated Hemoglobin in Screening and Diagnosing Type 2 Diabetes Mellitus in Chinese Subjects

( Yun Yu ),( Xiao Jun Ouyang ),( Qing-lin Lou ),( Liu Bao Gu ),( Yong Zhen Mo ),( Gary T. Ko ),( Chun Chung Chow ),( Wing Yee So ),( Ronald Ma ),( Alice Kong ),( Nicola Brown ),( Jennifer Nan ),( Juli 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.1

Background/Aims: The application of glycated hemoglobin (HbA1c) for the diagnosis of diabetes is currently under extensive discussion. In this study, we explored the validity of using HbA1c as a screening and diagnostic test in Chinese subjects recruited in Nanjing, China. Methods: In total, 497 subjects (361 men and 136 women) with fasting plasma glucose (PG) ≥ 5.6 mmol/L were recruited to undergo the oral glucose tolerance test (OGTT) and HbA1c test. Plasma lipid, uric acid, and blood pressure were also measured. Results: Using a receiver operating characteristic curve, the optimal cutoff point of HbA1c related to diabetes diagnosed by the OGTT was 6.3%, with a sensitivity and specificity of 79.6% and 82.2%, respectively, and the area under the curve was 0.87 (95% confidence interval, 0.83 to 0.92). A HbA1c level of 6.5% had a sensitivity and specificity of 62.7% and 93.5%, respectively. When comparing the HbA1c ≥ 6.5% or OGTT methods for diagnosing diabetes, the former group had significantly higher HbA1c levels and lower levels of fasting and 2-hour PG than the latter group. No significant difference was observed in the other metabolism indexes between the two groups. Conclusions: Our results suggest that HbA1c ≥ 6.5% has reasonably good specificity for diagnosing diabetes in Chinese subjects, which is in concordance with the American Diabetes Association recommendations.

The catalytic core of DEMETER guides active DNA demethylation in <i>Arabidopsis</i>

Zhang, Changqing,Hung, Yu-Hung,Rim, Hyun Jung,Zhang, Dapeng,Frost, Jennifer M.,Shin, Hosub,Jang, Hosung,Liu, Fang,Xiao, Wenyan,Iyer, Lakshminarayan M.,Aravind, L.,Zhang, Xiang-Qian,Fischer, Robert L. National Academy of Sciences 2019 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.116 No.35

<P><B>Significance</B></P><P>Flowering plants reproduce via a unique double-fertilization event, producing the zygote and the nutritive endosperm. The genome of the central cell, the precursor of the endosperm, undergoes extensive demethylation prior to fertilization. This epigenetic reconfiguration, directed by the DEMETER (DME) glycosylase at thousands of loci in <I>Arabidopsis</I>, differentiates the epigenetic landscapes of parental genomes and establishes parent of origin-specific expression of many imprinted genes in endosperm essential for seed development. However, how DME is targeted to various locations remains unknown. Here we show that the multidomain DME is organized into 2 functional regions: the C-terminal region, which guides localization and catalysis, and the N-terminal region, which likely recruits chromatin remodelers to facilitate demethylation within heterochromatin.</P><P>The <I>Arabidopsis</I> DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it is recruited to these differing chromatin landscapes is unknown. The C-terminal half of DME consists of 3 conserved regions required for catalysis in vitro. We show that this catalytic core guides active demethylation at endogenous targets, rescuing <I>dme</I> developmental and genomic hypermethylation phenotypes. However, without the N terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. Comparative analysis revealed that the conserved DME N-terminal domains are present only in flowering plants, whereas the domain architecture of DME-like proteins in nonvascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets.</P>

The Safety and Efficacy of a Dietary Herbal Supplement and Gallic Acid for Weight Loss

Frank L. Greenway,Andrew T. Roberts,Corby K. Martin,Zhijun Liu,Ronald J. Amen,Eugene A. Woltering,Jennifer C. Rood,Mary K. Caruso,Ying Yu,Hui Xie 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.1

The objective of this study was to test the safety and efficacy of NT, a dietary herbal supplement made fromrhubarb, ginger, astragulus, red sage, and turmeric, combined with gallic acid (GA) to reduce food intake and cause weightloss. A total of 105 healthy subjects, 1860 years old with a body mass index of 2535 kg/m2 and on no chronic medication,were randomized to a 300 mg/1.2 g NT-GA combination, a 600 mg/2.4 g NT-GA combination, or placebo in three divideddoses daily for 24 weeks. Food intake was measured at baseline and 2 weeks, and safety parameters were followed regularly.Pharmacokinetic studies of a 200 mg/800 mg NT-GA combination and 800 g GA alone were performed with and withoutfood. There was no dose-related weight loss or reduction in food intake at the 8-week analysis, and the study was terminatedearly. Pharmacokinetic studies showed plasma levels of GA did not increase above 10 .M and were not dose-related. TheNT-GA at all concentrations was well tolerated, but was ineffective in causing weight loss or in suppressing food intake. Phar-macokinetics suggested that GA plasma levels were limited by oral absorption, and may be the reason for lack of efficacy.

The 14-3-3 Gene Function of Cryptococcus neoformans Is Required for its Growth and Virulence

( Jingbo Li ),( Yun C. Chang ),( Chun Hua Wu ),( Jennifer Liu ),( Kyung J. Kwon Chung ),( Sheng He Huang ),( Hiro Shimada ),( Rob Fante ),( Xiaowei Fu ),( Ambrose Jong ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.5

Cryptococcus neoformans is a life-threatening pathogenic yeast that causes devastating meningoencephalitis. The mechanism of cryptococcal brain invasion is largely unknown, and recent studies suggest that its extracellular microvesicles may be involved in the invasion process. The 14-3-3 protein is abundant in the extracellular microvesicles of C. neoformans, and the 14-3-3-GFP fusion has been used as the microvesicle’s marker. However, the physiological role of 14-3-3 has not been explored. In this report, we have found that C. neoformans contains a single 14-3-3 gene that apparently is an essential gene. To explore the functions of 14-3-3, we substituted the promoter region of the 14-3-3 with the copper-controllable promoter CTR4. The CTR4 regulatory strain showed an enlarged cell size, drastic changes in morphology, and a decrease in the thickness of the capsule under copper-enriched conditions. Furthermore, the mutant cells produced a lower amount of total proteins in their extracellular microvesicles and reduced adhesion to human brain microvascular endothelial cells in vitro. Proteomic analyses of the protein components under 14-3-3-overexpressed and -suppressed conditions revealed that the 14-3-3 function(s) might be associated with the microvesicle biogenesis. Our results support that 14-3-3 has diverse pertinent roles in both physiology and pathogenesis in C. neoformans. Its gene functions are closely relevant to the pathogenesis of this fungus.