Nandakumar P.,Michigan Science Center
Journal of Hypertension | Year: 2017
OBJECTIVES:: Hypertension is a major risk factor for all cardiovascular diseases, especially among African Americans. This study focuses on identifying specific blood pressure (BP) genes using 15?914 individuals of African ancestry from eight cohorts (Africa America Diabetes Mellitus, Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in young Adults, Genetics Network, Genetic Epidemiology Network of Arteriopathy, Howard University Family Study, Hypertension Genetic Epidemiology Network, and Loyola University Chicago Cohort) to further genetic findings in this population which has generally been underrepresented in BP studies. METHODS:: We genotyped and performed various single variant and gene-based exome-wide analyses on 15?914 individuals on the Illumina HumanExome Beadchip v1.0 or v1.1 to test association with SBP and DBP long-term average residuals that were adjusted for age, age-squared, sex, and BMI. RESULTS:: We identified rare variants affecting SBP and DBP in 10 genes: AFF1, GAPDHS, SLC28A3, COL6A1, CRYBA2, KRBA1, SEL1L3, YOD1, CCDC13, and QSOX1. Prior experimental evidence for six of these 10 candidate genes supports their involvement in cardiovascular mechanisms, corroborating their potential roles in BP regulation. CONCLUSION:: Although our results require replication or validation due to their low numbers of carriers, and an ethnicity-specific genotyping array may be more informative, this study, which has identified several candidate genes in this population most susceptible to hypertension, presents one of the largest African-ancestry BP studies to date and the largest including analysis of rare variants. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
News Article | May 22, 2017
The all-new TET is prominently featured on the lower level of MiSci. The exterior of the theater features an interactive wall that allows visitors to engage in unique STEM activities. Once inside, the TET delivers a unique four-dimensional experience that engages multiple senses. It houses a state-of-the-art HD projection system with 3D viewing capabilities and enhanced space and lighting for a more immersive experience. The TET is the only theater in Michigan to incorporate "spark" effects without heat, smoke or pyrotechnics. Additionally, advanced viewing technology enables MiSci to live stream video footage to and from virtually anywhere in the world bolstering the facility's distance learning programs. "We're focused on empowering and enriching all children and all communities with STEM," said Dr. Tonya Matthews, Michigan Science Center president and CEO. "Our partnership with Toyota, and the TET, with its new technology, will help reach communities across Michigan and build a legacy and inspiration of STEM education for students, schools, and families." Toyota has made Michigan its hub for North American automotive research and development. Through its Ann Arbor-based, state-of-art product development facility, the company has access to a talent pool of experienced engineers. "Because of places like the Michigan Science Center, there will be a good number of students who are inspired to go into science, inspired to think to the future and do great things," said Detroit native, Chris Reynolds, executive vice president of Corporate Resources, chief diversity officer & managing officer at Toyota Motor Corporation. The theater's public grand opening is Saturday, May 27 to celebrate, MiSci is offering free general admission and TET tickets for the entire weekend to the world debut of the National Geographic film "Extreme Weather 4D," exclusively produced for MiSci. The film is an interactive experience that transports visitors as they discover the dynamic and complex forces shaping our planet - and the surprising connections that help us understand and adapt to our ever-changing weather. Pre-registration is required and can be found at Mi-Sci.org "We are excited to open our doors and allow the community to experience this one-of-a-kind experience for free and want to thank Toyota for their continued support," added Matthews. About the Michigan Science Center The Michigan Science Center inspires nearly 300,000 curious minds of all ages every year through STEM (science, technology, engineering, and math) discovery, innovation and interactive education in Detroit and across the state of Michigan. As the STEM hub of the state, we focus on developing and introducing expanded education programs, exhibits, and initiatives that enable us to empower and enrich all children and all communities with STEM. Through our Traveling Science Program and distance learning initiative, we are expanding beyond our Detroit-based facility, with a goal of reaching all 83 counties of Michigan. With Toyota's 4D Engineering Theater, live stage shows, Michigan's only IMAX® Dome Theatre, a Planetarium, lab activities, 250+ hands-on exhibits, and more, there are dozens of ways to customize your MiSci visit. The Michigan Science Center is a 501(c)(3) nonprofit organization and does not receive support from the city of Detroit or the state of Michigan. For more information, please call 313.577.8400 or visit the website, Mi-Sci.org. About Toyota Toyota (NYSE: TM) has been a part of the cultural fabric in the U.S. and North America for 60 years, and is committed to advancing sustainable, next-generation mobility through our Toyota and Lexus brands. During that time, Toyota has created a tremendous value chain as our teams have contributed to world-class design, engineering, and assembly of more than 33 million cars and trucks in North America, where we operate 14 manufacturing plants (10 in the U.S.) and directly employ more than 46,000 people (more than 36,000 in the U.S.). Our 1,800 North American dealerships (nearly 1,500 in the U.S.) sold almost 2.7 million cars and trucks (2.45 million in the U.S.) in 2016 – and about 85 percent of all Toyota vehicles sold over the past 15 years are still on the road today. Toyota Motor North America Research & Development (TMNA R&D) aims to redefine next-generation cars as not simply a form of transportation, but as a fully connected vehicle. In fact, Toyota is the leader in automotive patents, including autonomous vehicle patents (over 2,000). Centered in Ann Arbor, Michigan, Toyota puts the brightest thinkers from all across America together to focus on letting people live more safely and comfortably. Globally, Toyota spends approximately $1 million per hour on R&D to ensure that Toyota rapidly and continuously develops cutting-edge, high-quality, and appealing vehicles. To date, Toyota has contributed more than $900 million to American nonprofit groups. For more information about Toyota's contributions in the U.S., visit http://www.toyota.com/about To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/michigan-science-center-unveils-new-144m-toyota-4d-engineering-theater-300461427.html
Pereira G.,German Cancer Research Center |
Yamashita Y.M.,Michigan Science Center
Trends in Cell Biology | Year: 2011
Cell division is generally thought to be a process that produces an exact copy of the mother cell by precisely replicating its genomic DNA, doubling organelles, and segregating them into two cells. Many cell types from bacteria to human cells divide asymmetrically, however, to generate daughter cells with distinct characteristics. Such asymmetric divisions are fundamental to the lifespan of a cell, to embryonic development, and to stem cell homeostasis. Asymmetric division requires coordination of cellular asymmetry and the cell division machinery. Accumulating evidence suggests that the basic molecular mechanisms that govern this process are conserved from yeast to humans. In this review we highlight similarities in the mechanisms of asymmetric cell division in yeast and Drosophila male germline stem cells (GSCs) in the hope of extracting common themes underlying several systems. © 2011 Elsevier Ltd.
Yamashita Y.M.,Michigan Science Center
Seminars in Cell and Developmental Biology | Year: 2013
The immortal strand hypothesis, which emerged four decades ago, proposes that certain cells retain a template copy of chromosomal DNA to protect against replication-induced mutations. As the interest in stem cells rose in recent years, researchers speculated that stem cells, which must maintain proliferative capacity throughout the life of the organism, may be the population that most needs the strong protection afforded by immortal strand segregation. Alternative hypotheses have also been proposed to explain observed non-random sister chromatid segregation. We recently found that Drosophila male germline stem cells segregate sister chromatids non-randomly, but such bias was limited to the sex chromosomes. Interestingly, the biased segregation does not lead to immortal strand segregation. We will discuss the implications of this observation and molecular mechanisms, which might be applicable to non-random sister chromatid segregation in other systems as well. © 2013 Elsevier Ltd.
Ma D.,Michigan Science Center |
Panda S.,Salk Institute for Biological Studies |
Lin J.D.,Michigan Science Center
EMBO Journal | Year: 2011
Temporal organization of tissue metabolism is important for maintaining nutrient and energy homeostasis in mammals. Autophagy is a conserved cellular pathway that is activated in response to nutrient limitation, resulting in the degradation of cytoplasmic components and the release of amino acids and other nutrients. Here, we show that autophagy exhibits robust circadian rhythm in mouse liver, which is accompanied by cyclic induction of genes involved in various steps of autophagy. Functional analyses of transcription factors and cofactors identified C/EBPβ as a potent activator of autophagy. C/EBPβ is rhythmically expressed in the liver and is regulated by both circadian and nutritional signals. In cultured primary hepatocytes, C/EBPβ stimulates the program of autophagy gene expression and is sufficient to activate autophagic protein degradation. Adenoviral-mediated RNAi knockdown of C/EBPβ in vivo abolishes diurnal autophagy rhythm in the liver. Further, circadian regulation of C/EBPβ and autophagy is disrupted in mice lacking a functional liver clock. We have thus identified C/EBPβ as a key factor that links autophagy to biological clock and maintains nutrient homeostasis throughout light/dark cycles. © 2011 European Molecular Biology Organization | All Rights Reserved.
Valley T.S.,Michigan Science Center
Critical Care Medicine | Year: 2016
OBJECTIVE:: Despite increasing use, evidence is mixed as to the appropriate use of noninvasive ventilation in patients with pneumonia. We aimed to determine the relationship between receipt of noninvasive ventilation and outcomes for patients with pneumonia in a real-world setting. DESIGN, SETTING, PATIENTS:: We performed a retrospective cohort study of Medicare beneficiaries (aged > 64 yr) admitted to 2,757 acute-care hospitals in the United States with pneumonia, who received mechanical ventilation from 2010 to 2011. EXPOSURES:: Noninvasive ventilation versus invasive mechanical ventilation. MEASUREMENT AND MAIN RESULTS:: The primary outcome was 30-day mortality with Medicare reimbursement as a secondary outcome. To account for unmeasured confounding associated with noninvasive ventilation use, an instrumental variable was used—the differential distance to a high noninvasive ventilation use hospital. All models were adjusted for patient and hospital characteristics to account for measured differences between groups. Among 65,747 Medicare beneficiaries with pneumonia who required mechanical ventilation, 12,480 (19%) received noninvasive ventilation. Patients receiving noninvasive ventilation were more likely to be older, male, white, rural-dwelling, have fewer comorbidities, and were less likely to be acutely ill as measured by organ failures. Results of the instrumental variable analysis suggested that, among marginal patients, receipt of noninvasive ventilation was not significantly associated with differences in 30-day mortality when compared with invasive mechanical ventilation (54% vs 55%; p = 0.92; 95% CI of absolute difference, –13.8 to 12.4) but was associated with significantly lower Medicare spending ($18,433 vs $27,051; p = 0.02). CONCLUSIONS:: Among Medicare beneficiaries hospitalized with pneumonia who received mechanical ventilation, noninvasive ventilation use was not associated with a real-world mortality benefit. Given the wide CIs, however, substantial harm associated with noninvasive ventilation could not be excluded. The use of noninvasive ventilation for patients with pneumonia should be cautioned, but targeted enrollment of marginal patients with pneumonia could enrich future randomized trials. Copyright © by 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Yang D.,Michigan Science Center
Journal of visualized experiments : JoVE | Year: 2013
Apolipoprotein (Apo) C-III (ApoCIII) resides on the surface of plasma chylomicron (CM), very low density lipoprotein (VLDL) and high density lipoproteins (HDL). It has been recognized that high levels of plasma ApoCIII constitutea risk factor for cardiovascular diseases (CVD). Elevated plasma ApoCIII level often correlates with insulin resistance, obesity, and hypertriglyceridemia. Invaluable knowledge on the roles of ApoCIIIin lipid metabolisms and CVD has been obtained from transgenic mouse models including ApoCIII knockout (KO) mice; however, it is noted that the metabolism of lipoprotein in mice is different from that of humans in many aspects. It is not known until now whether elevated plasma ApoCIII is directly atherogenic. We worked to develop ApoCIII KO rabbits in the present study based on the hypothesis that rabbits can serve as a reasonablemodelfor studying human lipid metabolism and atherosclerosis. Zinc finger nuclease (ZFN) sets targeting rabbit ApoCIIIgene were subjected to in vitro validation prior to embryo microinjection. The mRNA was injected to the cytoplasm of 35 rabbit pronuclear stage embryos, and evaluated the mutation rates at the blastocyst state. Of sixteen blastocysts that were assayed, a satisfactory 50% mutation rate (8/16) at the targeting site was achieved, supporting the use of Set 1 for in vivo experiments. Next, we microinjected 145 embryos with Set 1 mRNA, and transferred these embryos to 7 recipient rabbits. After 30 days gestation, 21 kits were born, out of which five were confirmed as ApoCIII KO rabbits after PCR sequencing assays. The KO animal rate (#KO kits/total born) was 23.8%. The overall production efficiency is 3.4% (5 kits/145 embryos transferred). The present work demonstrated that ZFN is a highly efficient method to produce KO rabbits. These ApoCIII KO rabbits are novel resources to study the roles of ApoCIII in lipid metabolisms.
Buchstaller J.,Michigan Science Center |
McKeever P.E.,University of Michigan |
Morrison S.J.,Michigan Science Center |
Morrison S.J.,Howard Hughes Medical Institute
Cancer Cell | Year: 2012
Tumor-initiating cells have been suggested to be rare in many cancers. We tested this in mouse malignant peripheral nerve sheath tumors (MPNSTs) and found that 18% of primary and 49% of passaged MPNST cells from Nf1 +/-; Ink4a/Arf -/- mice formed tumors upon transplantation, whereas only 1.8% to 2.6% of MPNST cells from Nf1 +/-; p53 +/- mice did. MPNST cells of both genotypes require laminin binding to β1-integrin for clonogenic growth. Most MPNST cells from Nf1 +/-; Ink4a/Arf -/- mice expressed laminin, whereas most MPNST cells from Nf1 +/-; p53 +/- mice did not. Exogenous laminin increased the percentage of MPNST cells from Nf1 +/-; p53 +/- but not Nf1 +/-; Ink4a/Arf -/- mice that formed tumorigenic colonies. Tumor-forming potential is common among MPNST cells, but the assay conditions required to detect it vary with tumor genotype. © 2012 Elsevier Inc.
Yamashita Y.M.,Michigan Science Center
Current Opinion in Cell Biology | Year: 2010
Adult stem cells inevitably communicate with their cellular neighbors within the tissues they sustain. Indeed, such communication, particularly with components of the stem cell niche, is essential for many aspects of stem cell behavior, including the maintenance of stem cell identity and asymmetric cell division. Cell adhesion mediates this communication by placing stem cells in proximity to the signaling source and by providing a polarity cue that orients stem cells. Here, I review the recent discovery that cell adhesion molecules govern the behavior of stem cells. © 2010 Elsevier Ltd.
Zhao X.-Y.,Michigan Science Center |
Li S.,Michigan Science Center |
Wang G.-X.,Michigan Science Center |
Yu Q.,Michigan Science Center |
Lin J.D.,Michigan Science Center
Molecular Cell | Year: 2014
Brown and beige/brite fats generate heat via uncoupled respiration to defend against cold. The total mass and activity of thermogenic adipose tissues are also tightly linked to systemic energy and nutrient homeostasis. Despite originating from distinct progenitors, brown and beige adipocytes acquire remarkably similar molecular and metabolic characteristics during differentiation through the action of a network of transcription factors and cofactors. How this regulatory network interfaces with long noncoding RNAs (lncRNAs), an emerging class of developmental regulators, remains largely unexplored. Here, we globally profiled lncRNA gene expression during thermogenic adipocyte formation and identified Brown fat lncRNA 1 (Blnc1) as a nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype. © 2014 Elsevier Inc.