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Chen, Paula Renee,Shin, Sangsu,Choi, Young Min,Kim, Elizabeth,Han, Jae Yong,Lee, Kichoon MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.3
<P>In avians, yolk synthesis is regulated by incorporation of portomicrons from the diet, transport of lipoproteins from the liver, and release of lipids from adipose tissue; however, the extent to which lipolysis in adipose tissue contributes to yolk synthesis and egg production has yet to be elucidated. G0/G1 switch gene 2 (<I>G0S2</I>) is known to bind and inhibit adipose triglyceride lipase (ATGL), the rate-limiting enzyme in lipolysis. The objective of this study was to determine whether overexpression of the <I>G0S2</I> gene in adipose tissue could successfully inhibit endogenous ATGL activity associated with egg laying. Two independent lines of transgenic quail overexpressing <I>G0S2</I> had delayed onset of egg production and reduced number of eggs over a six-week period compared to non-transgenic quail. Although no differences in measured parameters were observed at the pre-laying stage (5 weeks of age), <I>G0S2</I> transgenic quail had significantly larger interclavicular fat pad weights and adipocyte sizes and lower NEFA concentrations in the serum at early (1 week after laying first egg) and active laying (5 weeks after laying first egg) stages. Overexpression of <I>G0S2</I> inhibited lipolysis during early and active laying, which drastically shifted the balance towards a net accumulation of triacylglycerols and increased adipose tissue mass. Thereby, egg production was negatively affected as less triacylglycerols were catabolized to produce lipids for the yolk.</P>
Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow
Brunk, Elizabeth,Chang, Roger L.,Xia, Jing,Hefzi, Hooman,Yurkovich, James T.,Kim, Donghyuk,Buckmiller, Evan,Wang, Harris H.,Cho, Byung-Kwan,Yang, Chen,Palsson, Bernhard O.,Church, George M.,Lewis, Nat National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.43
<P>Understanding the complex interactions of protein posttranslational modifications (PTMs) represents a major challenge in metabolic engineering, synthetic biology, and the biomedical sciences. Here, we present a workflow that integrates multiplex automated genome editing (MAGE), genome-scale metabolic modeling, and atomistic molecular dynamics to study the effects of PTMs on metabolic enzymes and microbial fitness. This workflow incorporates complementary approaches across scientific disciplines; provides molecular insight into how PTMs influence cellular fitness during nutrient shifts; and demonstrates how mechanistic details of PTMs can be explored at different biological scales. As a proof of concept, we present a global analysis of PTMs on enzymes in the metabolic network of Escherichia coll. Based on our workflow results, we conduct a more detailed, mechanistic analysis of the PTMs in three proteins: enolase, serine hydroxymethyltransferase, and transaldolase. Application of this workflow identified the roles of specific PTMs in observed experimental phenomena and demonstrated how individual PTMs regulate enzymes, pathways, and, ultimately, cell phenotypes.</P>
Perception of upper lip augmentation utilizing simulated photography
Gary Linkov,Elizabeth Wick,Dorina Kallogjeri,Collin L. Chen,Gregory H. Branham 대한성형외과학회 2019 Archives of Plastic Surgery Vol.46 No.3
Background No head to head comparison is available between surgical lip lifting and upper lip filler injections to decide which technique yields the best results in patients. Despite the growing popularity of upper lip augmentation, its effect on societal perceptions of attractiveness, successfulness and overall health in woman is unknown. Methods Blinded casual observers viewed three versions of independent images of 15 unique patient lower faces for a total of 45 images. Observers rated the attractiveness, perceived success, and perceived overall health for each patient image. Facial perception questions were answered on a visual analog scale from 0 to 100, where higher scores corresponded to more positive responses. Results Two hundred and seventeen random observers with an average age of 47 years (standard deviation, 15.9) rated the images. The majority of observers were females (n=183, 84%) of white race (n=174, 80%) and had at least some college education (n=202, 93%). The marginal mean score for perceived attractiveness from the natural condition was 1.5 points (95% confidence interval [CI], 0.9–2.18) higher than perceived attractiveness from the simulated upper lip filler injection condition, and 2.6 points higher (95% CI, 1.95–3.24) than the simulated upper lip lift condition. There was a moderate to strong correlation between the scores of the same observer. Conclusions Simulated upper lip augmentation is amenable to social perception analysis. Scores of the same observer for attractiveness, successfulness, and overall health are strongly correlated. Overall, the natural condition had the highest scores in all categories, followed by simulated upper lip filler, and lastly simulated upper lip lift.
Perception of upper lip augmentation utilizing simulated photography
Linkov, Gary,Wick, Elizabeth,Kallogjeri, Dorina,Chen, Collin L.,Branham, Gregory H. Korean Society of Plastic and Reconstructive Surge 2019 Archives of Plastic Surgery Vol.46 No.3
Background No head to head comparison is available between surgical lip lifting and upper lip filler injections to decide which technique yields the best results in patients. Despite the growing popularity of upper lip augmentation, its effect on societal perceptions of attractiveness, successfulness and overall health in woman is unknown. Methods Blinded casual observers viewed three versions of independent images of 15 unique patient lower faces for a total of 45 images. Observers rated the attractiveness, perceived success, and perceived overall health for each patient image. Facial perception questions were answered on a visual analog scale from 0 to 100, where higher scores corresponded to more positive responses. Results Two hundred and seventeen random observers with an average age of 47 years (standard deviation, 15.9) rated the images. The majority of observers were females (n=183, 84%) of white race (n=174, 80%) and had at least some college education (n=202, 93%). The marginal mean score for perceived attractiveness from the natural condition was 1.5 points (95% confidence interval [CI], 0.9-2.18) higher than perceived attractiveness from the simulated upper lip filler injection condition, and 2.6 points higher (95% CI, 1.95-3.24) than the simulated upper lip lift condition. There was a moderate to strong correlation between the scores of the same observer. Conclusions Simulated upper lip augmentation is amenable to social perception analysis. Scores of the same observer for attractiveness, successfulness, and overall health are strongly correlated. Overall, the natural condition had the highest scores in all categories, followed by simulated upper lip filler, and lastly simulated upper lip lift.
Chia-Lun Kuo,Pei-Chen Lee,Li-Jung Elizabeth Ku,Yu Sun,Tsung-Hsueh Lu,Muhammad Atoillah Isfandiari,Chung-Yi Li 한국역학회 2023 Epidemiology and Health Vol.45 No.-
OBJECTIVES: Information regarding the underlying causes of death (UCODs) and standardized mortality ratio (SMR) of dementia is instrumental in formulating medical strategies to prolong life in persons with dementia (PWD). We examined the leading UCODs among PWD and estimated the overall and cause-specific SMRs in relation to dementia in Taiwan. METHODS: Data were retrieved from 2 national datasets: the Taiwan Death Registry and the medical claim datasets of the National Health Insurance program. The observed person-years for each study participant were counted from the date of cohort enrollment to either the date of death or the final day of 2016. Sex-specific and age-specific SMRs were then calculated. RESULTS: The leading UCOD was circulatory disease, accounting for 26.0% of total deaths (n=3,505), followed by respiratory disease at 21.3% (n=2,875). PWD were at significantly increased risk of all-cause mortality (SMR, 2.01), with SMR decreasing with advancing age. A cause-specific analysis revealed that the highest SMRs were associated with nervous system diseases (SMR, 7.58) and mental, behavioral, and neurodevelopmental disorders (SMR, 4.80). Age appeared to modify SMR, suggesting that younger age at cohort enrollment was linked to higher SMRs for nearly all causes of mortality. CONCLUSIONS: Circulatory and respiratory diseases were the leading UCODs among PWD. The particularly elevated mortality due to nervous system diseases and mental disorders suggests that allocating more resources to neurological and psychiatric services is warranted. The elevated SMRs of various UCODs among younger PWD underscore the need for clinicians to pay particular attention to the medical care provided to these patients.
Ion-Mediated Electron Transfer in a Supramolecular Donor-Acceptor Ensemble
Park, Jung Su,Karnas, Elizabeth,Ohkubo, Kei,Chen, Ping,Kadish, Karl M.,Fukuzumi, Shunichi,Bielawski, Christopher W.,Hudnall, Todd W.,Lynch, Vincent M.,Sessler, Jonathan L. American Association for the Advancement of Scienc 2010 Science Vol.329 No.5997
<P>Ion binding often mediates electron transfer in biological systems as a cofactor strategy, either as a promoter or as an inhibitor. However, it has rarely, if ever, been exploited for that purpose in synthetic host-guest assemblies. We report here that strong binding of specific anions (chloride, bromide, and methylsulfate but not tetrafluoroborate or hexafluorophosphate) to a tetrathiafulvalene calix[4]pyrrole (TTF-C4P) donor enforces a host conformation that favors electron transfer to a bisimidazolium quinone (BIQ<SUP>2+</SUP>) guest acceptor. In contrast, the addition of a tetraethylammonium cation, which binds more effectively than the BIQ<SUP>2+</SUP> guest in the TTF-C4P cavity, leads to back electron transfer, restoring the initial oxidation states of the donor and acceptor pair. The products of these processes were characterized via spectroscopy and x-ray crystallography.</P>
Differential Sensitivity of Target Genes to Translational Repression by miR-17~92
Jin, Hyun Yong,Oda, Hiroyo,Chen, Pengda,Yang, Chao,Zhou, Xiaojuan,Kang, Seung Goo,Valentine, Elizabeth,Kefauver, Jennifer M.,Liao, Lujian,Zhang, Yaoyang,Gonzalez-Martin, Alicia,Shepherd, Jovan,Morgan, Public Library of Science 2017 PLoS genetics Vol.13 No.2
<▼1><P>MicroRNAs (miRNAs) are thought to exert their functions by modulating the expression of hundreds of target genes and each to a small degree, but it remains unclear how small changes in hundreds of target genes are translated into the specific function of a miRNA. Here, we conducted an integrated analysis of transcriptome and translatome of primary B cells from mutant mice expressing miR-17~92 at three different levels to address this issue. We found that target genes exhibit differential sensitivity to miRNA suppression and that only a small fraction of target genes are actually suppressed by a given concentration of miRNA under physiological conditions. Transgenic expression and deletion of the same miRNA gene regulate largely distinct sets of target genes. miR-17~92 controls target gene expression mainly through translational repression and 5’UTR plays an important role in regulating target gene sensitivity to miRNA suppression. These findings provide molecular insights into a model in which miRNAs exert their specific functions through a small number of key target genes.</P></▼1><▼2><P><B>Author summary</B></P><P>MicroRNAs (miRNAs) are small RNAs encoded by our genome. Each miRNA binds hundreds of target mRNAs and performs specific functions. It is thought that miRNAs exert their function by reducing the expression of all these target genes and each to a small degree. However, these target genes often have very diverse functions. It has been unclear how small changes in hundreds of target genes with diverse functions are translated into the specific function of a miRNA. Here we take advantage of recent technical advances to globally examine the mRNA and protein levels of 868 target genes regulated by miR-17~92, the first oncogenic miRNA, in mutant mice with transgenic overexpression or deletion of this miRNA gene. We show that miR-17~92 regulates target gene expression mainly at the protein level, with little effect on mRNA. Surprisingly, only a small fraction of target genes respond to miR-17~92 expression changes. Further studies show that the sensitivity of target genes to miR-17~92 is determined by a non-coding region of target mRNA. Our findings demonstrate that not every target gene is equal, and suggest that the function of a miRNA is mediated by a small number of key target genes.</P></▼2>
de Lorenzo, Ví,ctor,Prather, Kristala LJ,Chen, Guo‐,Qiang,O'Day, Elizabeth,von Kameke, Conrad,Oyarzú,n, Diego A,Hosta‐,Rigau, Leticia,Alsafar, Habiba,Cao, Cong,Ji, Weizhi,Okano John Wiley and Sons Inc. 2018 EMBO reports Vol.19 No.4
<P>The UN's Sustainable Development Goals present a challenge for biotechnology to develop new environmentally‐friendly and sustainable products and production processes. </P>
Yun, Eun-Jin,Lin, Chun-Jung,Dang, Andrew,Hernandez, Elizabeth,Guo, Jiaming,Chen, Wei-Min,Allison, Joyce,Kim, Nathan,Kapur, Payal,Brugarolas, James,Wu, Kaijie,He, Dalin,Lai, Chih-Ho,Lin, Ho,Saha, Debab American Association for Cancer Research 2019 Clinical Cancer Research Vol.25 No.14
<P><B>Purpose:</B></P><P>Renal cell carcinoma (RCC) is known to be highly radioresistant but the mechanisms associated with radioresistance have remained elusive. We found DOC-2/DAB2 interactive protein (DAB2IP) frequently downregulated in RCC, is associated with radioresistance. In this study, we investigated the underlying mechanism regulating radioresistance by DAB2IP and developed appropriate treatment.</P><P><B>Experimental Design:</B></P><P>Several RCC lines with or without DAB2IP expression were irradiated with ionizing radiation (IR) for determining their radiosensitivities based on colony formation assay. To investigate the underlying regulatory mechanism of DAB2IP, immunoprecipitation-mass spectrometry was performed to identify DAB2IP-interactive proteins. PARP-1 expression and enzymatic activity were determined using qRT-PCR, Western blot analysis, and ELISA. <I>In vivo</I> ubiquitination assay was used to test PARP-1 degradation. Furthermore, <I>in vivo</I> mice xenograft model and patient-derived xenograft (PDX) model were used to determine the effect of combination therapy to sensitizing tumors to IR.</P><P><B>Results:</B></P><P>We notice that DAB2IP-deficient RCC cells acquire IR-resistance. Mechanistically, DAB2IP can form a complex with PARP-1 and E3 ligases that is responsible for degrading PARP-1. Indeed, elevated PARP-1 levels are associated with the IR resistance in RCC cells. Furthermore, PARP-1 inhibitor can enhance the IR response of either RCC xenograft model or PDX model.</P><P><B>Conclusions:</B></P><P>In this study, we unveil that loss of DAB2IP resulted in elevated PARP-1 protein is associated with IR-resistance in RCC. These results provide a new targeting strategy to improve the efficacy of radiotherapy of RCC.</P>